1482 Questions
What is traditionally included in the myeloid tissues according to the text?
Granulocytes and spleen
Where do neoplastic disorders of myeloid progenitor cells originate?
Bone marrow
Which of the following is true about the lymphoid tissues?
Home of long-lived plasma cells
What is indicated by the formation of autoantibodies in red cell disorders?
Primary disorder of lymphocytes
Where do immunohemolytic anemia disorders originate from according to the text?
Bone marrow
Why is it not possible to draw neat lines between diseases involving myeloid and lymphoid tissues?
Because of the interconnectedness and overlap in physiological functions and disease origins
Which component of the hematopoietic system is the source of all lymphoid progenitors according to the text?
Bone marrow
From where do neoplastic disorders of myeloid progenitor cells primarily originate?
Bone marrow
What does the bone marrow serve as the source of in the hematopoietic system?
All lymphoid progenitors
Which of the following is derived from myeloid tissues according to the text?
Monocytes
In red cell disorders like immunohemolytic anemia, what indicates a primary disorder of lymphocytes?
Formation of autoantibodies
Why is the traditional division of hematopoietic cells into myeloid and lymphoid tissues considered artificial?
Because it does not consider the normal physiology of the cells
Which hematopoietic component houses long-lived plasma cells and memory lymphocytes?
Bone marrow
Where do neoplastic disorders of myeloid progenitor cells secondarily involve according to the text?
(To a lesser degree) Spleen
Where do hematopoietic stem cells (HSCs) migrate during the third month of embryogenesis?
Liver
What happens to hepatic hematopoiesis shortly after birth?
It ceases completely
When does hematopoiesis cease in distal bones in normal adults?
During puberty
What is the chief site of blood cell formation until shortly before birth?
Liver
Where are hematopoietic stem cells (HSCs) harvested from at birth for therapeutic transplantation?
Umbilical cord blood
By birth, where do hematopoietic stem cells (HSCs) shift in location to?
Bone marrow
What is the source of long-lived tissue macrophages such as microglial cells in the brain?
Yolk sac
Where do definitive hematopoietic stem cells (HSCs) arise several weeks later during embryonic development?
Mesoderm of intraembryonic aorta/gonad/mesonephros region
Where does hematopoiesis mainly occur in normal adults after puberty?
Axial skeleton
What essential properties are required for the maintenance of hematopoiesis according to the text?
Pluripotency and unlimited division capacity
What are HSCs the apex of in the hierarchy of bone marrow progenitors?
Progenitor cells
What do colony-forming units produce when grown in culture?
Mature myeloid cells
Which cells are the immediate progenitors of mature granulocytes, red cells, and platelets?
Myeloblasts
What is the differentiation potential of early progenitor cells derived from HSCs?
Multipotent
Which type of cells ultimately produce mainly myeloid cells or lymphoid cells?
Early progenitor cells
What do tumors derived from lymphoid cells prompt a revisitation of?
Differentiation potential
What property of HSCs allows for continual production of blood elements?
Self-renewal capacity
What is the primary source of formed elements in blood according to the text?
HSCs
What happens to HSCs that differentiate past a certain threshold?
They lose the capacity for self-renewal
What is the main function of hematopoietic growth factors on committed progenitors?
Regulating the response to short-term physiological needs
What is the current source of hematopoietic stem cells (HSCs) used in transplantation?
Peripheral blood of donors treated with G-CSF
What causes HSCs to give rise to cells more proliferative than themselves but with lesser self-renewal capacity?
Division of multipotent progenitors
What is a key characteristic of terminally differentiated cells supported by hematopoietic growth factors?
Constant need for replenishment
What is the role of hematopoietic growth factors in vitro?
Supporting colony growth of mature blood elements
What happens when newly committed progenitor cells pass a certain threshold?
They lose self-renewal capacity
What triggers rapid proliferation in newly committed progenitor cells?
Interaction with hematopoietic growth factors
Which growth factors act through receptors expressed only on committed progenitors with more restricted differentiation potentials?
GM-CSF and G-CSF
Which lineage-specific growth factors tune the marrow output according to the text?
GM-CSF and G-CSF
Which cells respond to infectious or inflammatory challenges by increasing their output of granulocytes under the direction of specific growth factors?
Committed progenitors
What are the ultimate source of most cells of the innate and adaptive immune system according to the text?
Stem cells
Which blood cell type is NOT listed in Table 13.1 Adult Reference Ranges for Blood Cells?
Granulocytes
Which growth factor acts through receptors expressed on very early committed progenitors?
FLT3 ligand
In response to infectious or inflammatory challenges, what type of blood cell output increases under the direction of specific growth factors?
Granulocytes
"Late Precursors and Mature Forms" category in Table 13.1 refers to which types of cells?
[[NK-cell]] and Late precursors
What effect do mutations in tumors of hematopoietic origin have on hematopoiesis?
Cause a decrease in blood cell production
What contributes to unregulated clonal expansion of hematopoietic elements in certain tumors?
Mutations blocking progenitor cell maturation or growth factor dependence
What may cause deficiencies in one or more types of blood cells, as mentioned in the text?
Disorders associated with defects in hematopoiesis
In which instances do some tumors of hematopoietic origin originate from transformed HSCs?
In limited cases
What is a potential outcome of mutations that block progenitor cell maturation?
Unregulated clonal expansion of hematopoietic elements
What contributes to the replacement of normal marrow progenitors by tumor cells?
Unregulated clonal expansion
Why are certain genetic diseases, infections, and toxins mentioned in the text?
To provide examples of factors that inhibit blood cell production
What is the primary consequence of defects in hematopoiesis mentioned in the text?
Deficiency of one or more types of blood cells
What is the term used to describe the abnormal release of immature precursors into the peripheral blood?
Leukoerythroblastosis
Where do normal megakaryocytes lie in proximity to, according to the text?
Sinusoids
What distinguishes proliferative disorders of white cells from leukopenias?
Expansion of leukocytes
What does marrow aspirate smears provide the best assessment of?
Hematopoietic cell morphology
What can distort the marrow architecture, leading to the abnormal release of immature precursors into the peripheral blood?
Metastatic cancer
What is the term for a deficiency of leukocytes?
Leukopenia
Where do differentiated blood cells enter the circulation through?
Transcellular migration through endothelial cells
What is the primary method used to assess hematopoietic cell morphology?
Marrow aspirate smears
What is the most common cause of leukopenia according to the text?
Acute viral infections
What primarily contributes to lymphopenia in the context of acute viral infections?
Decreased production of type I interferons
What is the main cause of granulocytopenia as discussed in the text?
Diminished granulocyte production
In what conditions do glucocorticoids and cytotoxic drugs contribute to leukopenia?
Neutropenia
What distinguishes lymphopenia in acute viral infections from other causes?
Changes in T-cell migration
Which factor plays a significant role in the development of granulocytopenia?
Reduced granulocyte production
What is the primary effect of autoimmune disorders on white cell counts?
Neutropenia
Which condition is least likely to cause leukopenia based on the text?
Diminished granulocyte function
What is the primary cause of neutropenia according to the text?
Inadequate granulopoiesis
What is a common feature of hypoplastic states, as mentioned in the text?
Decreased fat cell proportion
In what type of diseases do fat cells often disappear from the marrow according to the text?
Leukemias
What is a significant consequence of local marrow fibrosis induced by bacterial and fungal infections?
Susceptibility to Agranulocytosis
Which statement is true regarding marrow activity in normal adults based on the text?
Proportion of fat cells equals that of hematopoietic elements
What is a characteristic feature of mature precursors that helps differentiate them from immature "blast" forms?
"Blast" forms must be identified definitively using specific markers
What is a common cause of agranulocytosis as mentioned in the text?
Drug toxicity
Which condition can lead to ineffective hematopoiesis and defective precursors' death in the bone marrow?
Megaloblastic anemia
What can splenomegaly cause, leading to destruction of neutrophils in the spleen?
Modest neutropenia
Which scenario leads to locytic differentiation issues according to the text?
Drug toxicity
What could be a consequence of suppression of committed granulocytic precursors in the bone marrow?
Granulocytopenia
In what condition might ineffective hematopoiesis accompany anemia and thrombocytopenia?
Megaloblastic anemia
What might be a result of accelerated destruction or sequestration of neutrophils?
Neutropenia
What is a common consequence of agranulocytosis as mentioned in the text?
Infections
Where are ulcerating necrotizing lesions typically observed in the context of neutropenia?
Oral cavity
Which type of infections are particularly high risk for neutropenic patients due to the lack of granulocytes?
Fungal infections
What kind of bacterial growth pattern is seen in some severe cases of neutropenic infections?
Massive growth in colonies
Which term is used to describe the deep fungal infections that may occur in neutropenic patients?
Botryomycosis
What are the symptoms and signs related to infections in neutropenia that can include malaise, chills, and fever?
Marked weakness and fatigability
What can severe infections caused by neutropenia lead to within hours to days according to the text?
Death
'__ ___ __ lesions are quite characteristic' as described in the text regarding neutropenic angina.
'Ulcerating necrotizing'
What is the most likely consequence when neutrophil count falls below 500/mm³?
Onset of serious infections
What is the primary treatment for neutropenia following myelosuppressive chemotherapy?
Broad-spectrum antibiotics
Which growth factor stimulates the production of granulocytes from marrow precursors?
Granulocyte-Colony Stimulating Factor (G-CSF)
What is the main influence on the peripheral blood leukocyte count, as mentioned in the text?
Proportion of cells adhering to vessel walls
Which factor plays a significant role in maintaining leukocyte homeostasis?
Cytokines
What is the major mechanism of neutrophilic leukocytosis according to the text?
Infection
Which scenario leads to the most important cause of neutrophilic leukocytosis as per the text?
Bacterial infections
What is the primary source of neutrophilic leukocytosis according to the text?
Inflammatory states
What is the main mechanism of agranulocytosis induced by certain antibiotics and antipsychotic drugs?
Toxic effect on granulocytic precursors
What is considered the most likely mechanism for severe neutropenia occurring with monoclonal proliferations of large granular lymphocytes?
Suppression of granulocytic progenitors by neoplastic cell products
What is the primary cause of neutropenia in some cases of acquired idiopathic neutropenia?
Autoantibodies against neutrophil-specific antigens
What is the impact on bone marrow morphology when there is excessive destruction of neutrophils in the periphery?
Hypercellular marrow due to increased granulocytic precursors
What does suppression of committed granulocytic precursors in the bone marrow potentially lead to?
Aplastic anemia
What is the suspected mechanism behind agranulocytosis following the administration of certain drugs like sulfonamides?
Antibody-mediated destruction of granulocytic precursors
In cases of agranulocytosis due to certain medications, what primarily leads to the lack of red cells and platelets production as mentioned in the text?
Toxic impact on granulocytic precursors
What is the suspected cause of neutropenia induced by antipsychotic drugs according to the text?
Inhibition of white cell maturation
What is the primary effect of TNF and IL-1 on the bone marrow during acute infection?
Enhance the egress of mature granulocytes
Which types of cells are preferentially stimulated by IL-5?
Eosinophils
In which scenario might G-CSF play a significant role based on the text?
Increasing neutrophil production
What effect does decreased extravasation into tissues due to glucocorticoids have on leukocytes?
Reduces their movement into tissues
How do hematopoietic growth factors affect committed granulocytic progenitors?
Enhance their differentiation and proliferation
What is a characteristic effect of IL-1 and TNF on macrophages, stromal cells, and T cells?
Stimulating increased hematopoietic growth factor production
What leads to a sustained increase in neutrophil production over several days?
"Table 13.2 Mechanisms and Causes of Leukocytosis"
"Table 13.2 Mechanisms and Causes of Leukocytosis" mentions which factor as a cause of growth factor-independent leukocytosis?
"Myeloproliferative neoplasms"
What morphologic changes in neutrophils are often observed in sepsis or severe inflammatory disorders?
Increased Döhle bodies
What do Döhle bodies represent in neutrophils?
Dilated endoplasmic reticulum patches
In what scenario might immature granulocytes appear in the blood, mimicking myeloid leukemia?
Severe infections
Which feature distinguishes activated lymphocytes in acute viral infections from neoplastic lymphoid cells?
Morphologic abnormalities
What helps in distinguishing between reactive and neoplastic leukocytoses?
Special laboratory studies
What are the two characteristic structures seen in neutrophils on the peripheral blood smear of a patient with bacterial sepsis?
Coarse purple cytoplasmic granules and blue cytoplasmic patches
Which organs are considered central (primary) lymphoid organs in the process of lymphocyte development?
Bone marrow and thymus
What encapsulated structures contain separate B-cell and T-cell zones, richly invested with phagocytes and antigen-presenting cells?
Lymph nodes
In lymph nodes, what dynamic structures develop within pale-staining germinal centers?
B cells
What leads to mor- antigenic stimulation and enlargement of primary follicles in lymph nodes?
Activation of resident immune cells
Which structures in the lymph nodes may undergo hyperplasia under specific stimuli?
Paracortical T-cell zones
What influences the homeostasis of lymphocytes in peripheral (secondary) lymphoid tissues?
Cytokines and chemokines in circulation
What is the primary reason lymph nodes in adults are almost never 'normal' or 'resting'?
To distinguish past experiences from present diseases
What type of lymphadenitis is most often due to drainage of microbes or microbial products from infections of the teeth or tonsils?
Acute Nonspecific Lymphadenitis
In which regions does acute lymphadenitis occur most often due to infections in the extremities?
Axillary region
What is a common differential diagnosis for acute lymphadenitis in mesenteric lymph nodes?
Acute appendicitis
Which type of infections are particularly high risk for neutropenic patients due to the lack of granulocytes?
Bacterial infections
What mainly leads to the lack of red cells and platelets production in cases of agranulocytosis due to certain medications?
Bone marrow suppression
Where does hematopoiesis mainly occur in normal adults after puberty?
Bone marrow
What is a key characteristic of terminally differentiated cells supported by hematopoietic growth factors?
Long life-span
What is the main function of TNF and IL-1 on macrophages, stromal cells, and T cells during acute infection?
Induce cytokine release
What is the most common cause of eosinophilic leukocytosis (eosinophilia) based on the text?
Parasitic infestations
Which condition is often associated with basophilic leukocytosis (basophilia) according to the text?
Transient atheroembolic disease
In which scenario might neutrophilia be a predominant feature as per the text?
Endocarditis
What type of leukocytosis is typically indicative of chronic myeloid leukemia?
Neutrophilic leukocytosis
Which leukocytosis is commonly observed in disorders with chronic immunologic stimulation based on the text?
Lymphocytosis
What is a hallmark of eosinophilia according to the text?
Allergic disorders
What cell type containing the nuclear debris of B cells is found interspersed among germinal center B cells?
Follicular dendritic cells
Which type of hyperplasia is morphologically similar to follicular lymphoma?
Follicular hyperplasia
What type of cells undergo apoptosis if they fail to produce antibodies with high affinity for antigens in germinal centers?
Centroblasts
Which feature tends to be absent from neoplastic follicles, favoring a reactive (nonneoplastic) hyperplasia?
Phagocytic macrophages
Which condition is caused by stimuli that trigger T-cell-mediated immune responses?
Paracortical hyperplasia
What type of cells are found in the light zone of germinal centers?
Centrocytes
What happens to the nuclear debris of B cells that are phagocytosed by tingible-body macrophages in germinal centers?
Undergo apoptosis
What differentiates centroblasts from centrocytes within germinal centers?
Nuclear morphology
What type of cells are often prominent when pyogenic organisms cause lymphadenitis?
Neutrophils
In chronic nonspecific lymphadenitis, what defines follicular hyperplasia?
Presence of large oblong germinal centers
What is a characteristic of nodes involved in acute lymphadenitis?
Swollen and painful
What happens when suppurative infections penetrate through the capsule of lymph nodes?
They become fluctuant
What is associated with healing of abscesses in lymph nodes?
Scarring
What cell type is defined by a collar of small resting naive B cells surrounding large oblong germinal centers?
Mantle zone B cells
What effect do less severe reactions to pyogenic organisms have on the centers of lymphoid follicles?
Necrosis
What occurs when nodes involved by acute lymphadenitis produce draining sinuses to the skin?
Abscess formation
What are the key characteristics of immunoblasts found in T-cell regions?
Large size, round nuclei, open chromatin, several nucleoli, and moderate cytoplasm
In reactive follicles with mantle zones, what is characteristic of the dark zone?
High mitotic activity and numerous macrophages containing phagocytosed apoptotic cells
What is a prominent feature of sinus histiocytosis (reticular hyperplasia) in lymph nodes?
Increase in endothelial cell size and number in lymphatic sinusoids
What might be necessary when the number of immunoblasts in T-cell regions is so abundant that it raises suspicion of a neoplasm?
Performing immunohistochemistry studies to differentiate reactive from neoplastic processes
What is a common accompaniment to the proliferation of immunoblasts in T-cell zones that may lead to effacement of B-cell follicles?
Hypertrophy of sinusoidal and vascular endothelial cells
What is a distinguishing feature of sinusoidal endothelial cells in response to hyperplastic reactions?
Increase in the number and size of endothelial cells
What additional cell types may infiltrate sinusoidal and vascular spaces along with macrophages and eosinophils during hyperplastic reactions?
Mast cells
What contributes to effacement of B-cell follicles by expanded T-cell zones?
Increased number of immunoblasts
What may be required in particularly exuberant reactions to exclude a lymphoid neoplasm?
Immunohistochemistry studies on lymphocytes
What condition is often associated with Epstein-Barr virus infection as a common trigger?
Hemophagocytic lymphohistiocytosis (HLH)
Which cells' inability to properly form or deploy cytotoxic granules is a key aspect of familial forms of HLH?
Cytotoxic T cells (CTLs) and natural killer (NK) cells
What triggers excessive macrophage activation in Hemophagocytic lymphohistiocytosis (HLH)?
Persistent infection and cytokine production by CTLs
What is a common complication associated with peripheral T-cell lymphoma?
Hemophagocytic lymphohistiocytosis (HLH)
What is uniformly associated with extremely high levels in Hemophagocytic lymphohistiocytosis (HLH)?
Interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-α)
What is usually seen on bone marrow examination in patients with Hemophagocytic lymphohistiocytosis (HLH)?
Hemophagocytosis
What is the common feature of all forms of Hemophagocytic Lymphohistiocytosis (HLH) according to the text?
Systemic activation of macrophages and CD8+ cytotoxic T cells
What cytokine is probably involved in the establishment of 'extranodal' inflammation-induced collections of lymphoid cells?
Lymphotoxin
What term is sometimes used interchangeably with Hemophagocytic Lymphohistiocytosis (HLH) indicating signs and symptoms of systemic inflammation related to macrophage activation?
Macrophage activation syndrome
In HLH, what do the 'activated macrophages' do in the body?
Phagocytose blood cell progenitors in the marrow
What is the role of released mediators from macrophages and lymphocytes in Hemophagocytic Lymphohistiocytosis?
Suppress hematopoiesis
What are the typical laboratory findings in patients with HLH?
Elevated ferritin, soluble IL-2 receptor, liver function tests, and triglyceride levels
What complication can occur in untreated HLH patients?
Renal damage
What is the treatment approach for patients with resistant HLH?
Immunosuppressive drug therapy
What is the prognosis for HLH patients without treatment?
Grim, with death typically within 2 months
Which type of neoplasms do lymphoid neoplasms encompass?
Diverse group of B-cell, T-cell, and NK-cell origin
What happens if proliferative disorders of white cells are left untreated?
Progression to multiorgan failure and shock
What is the role of HSC transplantation in treating certain diseases?
Essential for favorable outcomes in some diseases
What is the term for a rare group of proliferative lesions involving macrophages and dendritic cells?
Histiocytoses
Which type of neoplastic disorders originate from early hematopoietic progenitor cells?
Myeloproliferative neoplasms
What is the consequence of increased production of terminally differentiated myeloid elements?
Elevated peripheral blood counts
Which cells give rise to a spectrum of neoplastic disorders known as Langerhans cell histiocytoses?
Dendritic cells
What is primarily responsible for the accumulation of immature progenitor cells in the bone marrow in AMLs?
Ineffective hematopoiesis
In white blood cell neoplasms, what factors are involved in the development of tumors according to the text?
Genetic alterations, infections, and chronic inflammation
What is the term used to describe the characteristic development of granulocytes in myeloid neoplasia?
Granulocytopoiesis
Which component of hematopoiesis mainly leads to elevated peripheral blood counts?
Granulocyte-macrophage colony-stimulating factor (GM-CSF)
Langerhans cell histiocytoses are attributed to which cell type's spectrum of neoplastic disorders?
Dendritic cells
What is a common characteristic of oncogenic mutations in acute leukemias?
Interfere with early cell differentiation
Which signaling pathways are often activated by mutations enhancing self-renewal of tumor cells?
PI3K/AKT and MAPK pathways
Which DNA-modifying enzyme is essential for immunoglobulin gene modifications in B cells after antigen stimulation?
AID
What is the common origin of potentially oncogenic mutations in lymphoid cells?
Germinal center B cells
Which type of gene modification replaces the IgM heavy-chain constant gene segment in B cells after activation?
Class switching
What is a prevalent mutation in certain hematologic malignancies according to the text?
Activating RAS signaling
Which type of mutations are often found to collaborate with those activating tyrosine kinases in driving cell growth?
Self-renewal-enhancing mutations
What is the role of activation-induced cytosine deaminase (AID) in B cells after antigen stimulation?
Facilitates Ig gene modifications
What is the main consequence of mutations in transcription factors that influence self-renewal, as mentioned in the text?
Increased self-renewal
Which process is NOT influenced by oncoproteins created by genomic aberrations, as stated in the text?
Cellular differentiation
What is the primary effect of pro-survival mutations such as the BCL2 translocation mentioned in the text?
Cellular protection from apoptotic cell death
What is the characteristic consequence of oncoproteins causing an arrest in differentiation, according to the text?
Inhibiting normal maturation
Which effect is associated with mutations that drive growth in white cell neoplasms, based on the text?
Turn on pro-growth signaling pathways
What do some mutations produce that interfere with normal functions, as mentioned in the text?
Dominant-negative proteins
What is a common outcome of oncogenic mutations that block normal maturation, according to the text?
Inhibition of normal maturation
What is the primary role of certain driver mutations in white cell neoplasms, based on the text?
Drive growth and prevent apoptosis
What is the primary function of somatic hypermutation within Ig genes?
Increasing antibody affinity for antigen
What is the mechanism through which AID expression induces MYC/Ig translocations in germinal center B cells?
Creating DNA lesions
Which of the following is a unique source of regulated genomic instability in precursor B and T cells?
V(D)J recombinase
What is the primary outcome of the joining of proto-oncogenes to antigen receptor gene regulatory elements?
Conversion of proto-oncogenes to oncogenes
Which type of tumors are particularly prone to the joining of proto-oncogenes to antigen receptor gene regulatory elements?
Tumors of precursor T cells
What role does AID play in the development of normal germinal center B cells?
Promoting somatic hypermutation
Which process is essential for generating diversity in assembled antigen receptor genes but can lead to genomic instability?
V(D)J recombinase activity
What distinguishes tumors of precursor T cells from other lymphoid neoplasms based on their pathogenesis?
"Mistargeting" of V(D)J recombinase
Which genetic diseases are mentioned in the text as promoting genomic instability and increasing the risk of acute leukemia?
Bloom syndrome, Fanconi anemia, ataxia telangiectasia
Which virus is implicated as a causative agent in adult T-cell leukemia/lymphoma?
Human T-cell leukemia virus-1 (HTLV-1)
What lymphomas is EBV found in according to the text?
Burkitt lymphoma, Hodgkin lymphoma, many B-cell lymphomas arising in the setting of T-cell immunodeficiency
Which virus is associated with an unusual B-cell lymphoma that presents as a malignant effusion, often in the pleural cavity?
Human herpesvirus-8 (HHV-8)
Which agents that cause localized chronic inflammation predispose to lymphoid neoplasia based on the text?
H.pylori infection, gluten-sensitive enteropathy, breast implants
What neoplasm does H.pylori infection associate with according to the text?
Gastric B-cell lymphomas
Which condition does gluten-sensitive enteropathy predispose to based on the text?
Intestinal T-cell lymphomas
What subtype of T-cell lymphoma are breast implants associated with according to the text?
'Anaplastic large cell' lymphoma
What type of leukemia/lymphoma is HHV-8 associated with that presents as a malignant effusion?
'Kaposi sarcoma-associated' lymphoma
Which genetic disorder is linked to an increased incidence of childhood leukemia?
Down syndrome (trisomy 21)
Why does smoking increase the incidence of Acute Myeloid Leukemia (AML) according to the text?
Presumably because of exposure to carcinogens in tobacco smoke
How do severe T-cell immunodeficiency and acquired immunodeficiency syndrome (AIDS) impact the risk of B-cell lymphomas according to the text?
They further increase the risk of B-cell lymphomas
What is one of the risks associated with radiation therapy and certain chemotherapy used in cancer treatment according to the text?
Elevated risk of myeloid and lymphoid neoplasms
What is a characteristic related to the pathophysiology of Hodgkin lymphoma as mentioned in the text?
Release of pro-inflammatory cytokines
How does ionizing radiation contribute to the increased risk of subsequent neoplasms in cancer patients according to the text?
Through its mutagenic effects on hematolymphoid progenitor cells
What is one factor associated with an increased incidence of lymphoid neoplasms in AIDS patients according to the text?
Association with EBV and KSHV/HHV-8
Why do smoking habits potentially influence the development of certain cancers?
Due to exposure to mutagenic effects present in tobacco smoke
What is one significant impact of iatrogenic factors on cancer treatment outcomes?
Elevating the risk of subsequent neoplasms
What is the most common presentation of NHLS and Hodgkin lymphomas?
Enlarged nontender lymph nodes
What symptom typically brings attention to lymphocytic leukemias?
Suppression of normal hematopoiesis
What differentiates the clinical presentation of NHLS from that of Hodgkin lymphomas?
Involvement of extranodal sites
What is the primary cause of pain in multiple myeloma?
Pathologic fractures
Which category do precursor T-cell neoplasms fall into according to the text?
Neoplasms of immature T cells
How are NHLS and Hodgkin lymphomas anatomically differentiated in terms of presentation?
>2 cm lymph nodes
What term is used to describe neoplasms presenting with widespread involvement of the bone marrow and sometimes peripheral blood?
Leukemias
Which group of tumors is specifically segregated from other forms within the category of lymphomas?
Hodgkin lymphoma
What is the primary characteristic feature that distinguishes Hodgkin lymphoma from other forms of lymphomas?
Distinctive pathologic features
What are neoplasms identical to leukemias that sometimes arise as soft tissue masses without detectable bone marrow disease?
Lymphomas
What terms merely reflect the usual tissue distribution of each disease at presentation in the context of lymphoid neoplasms?
Leukemia and lymphoma
In what scenario do some entities called 'lymphoma' occasionally have leukemic presentations?
'Lymphomas' that present with widespread bone marrow involvement
'Plasma cell neoplasms' are grouped under what special classification in the context of lymphoid neoplasms?
'Hodgkin lymphomas'
'Granulomas' are typically associated with which type of neoplastic disorders according to the text?
'Myeloid progenitor cells'
Which neoplasm is characterized by small mature lymphocytes with a slight increase in the blood and marrow, as well as variable lymphadenopathy and splenomegaly?
Hairy cell leukemia
Which T-cell neoplasm is a rare form of cutaneous T-cell lymphoma characterized by the presence of cerebriform nuclei?
Mycosis fungoides
Which Hodgkin lymphoma subtype is characterized by normal to increased numbers of lymphocytes in a background of collagen bands?
Lymphocyte-rich
Which condition includes characteristic skin lesions known as plaques or nodules, as well as circulating Sézary cells?
Sézary syndrome
Which B-cell neoplasm often arises from the marginal zone of lymphoid tissue and is commonly associated with chronic autoimmune disorders?
Marginal zone lymphoma
Which neoplasm is characterized by a mature B-cell population with varying degrees of differentiation, where <5% are prolymphocytes with prominent nucleoli?
B-cell prolymphocytic leukemia
'Enteropathy-associated' and 'Panniculitis-like' are associated with neoplasms of which cell type?
T-cells
'Large granular lymphocytes' are characteristic of which type of leukemia?
Large granular lymphocytic leukemia
Which neoplasm is associated with an overexpression of cyclin D1 due to t(11;14) translocation?
Mantle cell lymphoma
Where do cutaneous T-cell lymphomas primarily home to?
Skin
What is a characteristic pattern of involvement seen in follicular lymphomas?
Homing to germinal centers in lymph nodes
What do most lymphoid tumors exhibit at the time of diagnosis?
Widespread dissemination
Which type of lymphoid tumor may sometimes be restricted to one group of lymph nodes?
Hodgkin lymphomas
What is the common behavior of neoplastic B and T lymphoid cells in terms of recirculation?
Recirculation through the lymphatics and peripheral blood to distant sites
Where do marginal zone B-cell lymphomas tend to be often restricted to?
Sites of chronic inflammation
Which characteristic is associated with cutaneous T-cell lymphomas?
'Panniculitis-like' lesions
What type of examination is required for the diagnosis of lymphoid neoplasms?
Histologic examination
What distinguishes antigen receptor gene rearrangement in malignant proliferations from normal immune responses?
Monoclonal vs polyclonal populations of lymphocytes
What is an important complement to morphologic studies in the characterization of lymphomas and leukemias?
Genetic alterations analysis
What is shared by all daughter cells derived from a malignant progenitor concerning antigen receptor proteins?
Identical antigen receptor protein sequence and configuration
How can antigen receptor gene analysis be used to distinguish reactive and malignant lymphoid proliferations?
By comparing monoclonal and polyclonal populations
What is the role of lineage-specific protein expression analysis in the context of lymphoid neoplasms?
Characterizing tumors
What is the significance of analyzing genetic alterations in the diagnosis of lymphomas and leukemias?
'Genetic alterations' complement morphologic studies in diagnosis
What feature of lymphoid neoplasms is used in their classification?
Clonal markers
Which cell type forms the vast majority (85% to 90%) of lymphoid neoplasms?
B cells
What immune abnormalities are often associated with lymphoid neoplasms?
Protective immunity loss and tolerance breakdown
In which patients are individuals at high risk of developing certain lymphoid neoplasms?
Individuals with immunodeficiency
What is a characteristic behavior of neoplastic B and T cells according to the text?
They recapitulate the behavior of normal counterparts
Which component of lymphoid neoplasms is rare according to the text?
NK-cell tumors
'Resemble some recognizable stage of B- or T-cell differentiation' is a feature used in the classification of which type of neoplasms?
'Lymphoid' neoplasms
Which cellular component is associated with EBV receptor and mature B cells?
Activated mature B cells
Which group of cells is primarily associated with CD15?
Granulocytes; Reed-Sternberg cells and variants
What is the primary association of CD34 in terms of cell types?
Pluripotent hematopoietic stem cells and progenitor cells of many lineages
Which type of cells express CD56 primarily?
NK cells and granulocytes
Which cell type lacks the expression of CD30?
Granulocytes, monocytes, and macrophages
Which cell type group expresses primarily CD64?
Mature myeloid cells
In which demographic group is T-ALL less common compared to B-ALL?
Adolescent females
At what age does B-ALL peak in incidence according to the text?
3 years old
Which ethnic group has the highest incidence of ALL according to the text?
Hispanics
What cell type group is most affected by chromosomal aberrations in ALL pathogenesis?
B and T-cells
What is the primary age group affected by ALL?
Under 5 years old
What characteristic distinguishes T-ALL from B-ALL regarding presentation?
Thymic lymphomas
Which type of ALL peaks in incidence during adolescence?
T-ALL
Why is T-ALL less common in adult populations according to the text?
Thymus size decrease with age
Which population group has a slightly higher frequency of ALL?
Boys
What type of cells make up approximately 85% of acute lymphoblastic leukemia/lymphomas?
Pre-B cells
Which cell type is NOT mentioned as a component of B cell neoplasms in the text?
Peripheral T cells
Which characteristic is associated with Chronic lymphocytic leukemia according to the text?
Development from Common lymphoid precursor
What is the origin of Mature B cell neoplasms that include Follicular lymphoma and Hairy cell leukemia?
Mantle B cells
Which type of neoplasm is NOT classified under Mature B cell neoplasms?
Peripheral T cell lymphomas
What is the primary differentiation stage of cells in Acute Lymphoblastic Leukemia/Lymphomas?
Common lymphoid precursor
Which neoplasm is characterized by diverse chromosomal translocations and is associated with RUNX1 and ETV6 genes?
Burkitt lymphoma
Which neoplasm is mainly associated with NOTCH1 mutations?
Adult T-cell leukemia/lymphoma
Which neoplasm commonly exhibits translocations involving MYC and Ig genes?
Follicular lymphoma
Which neoplasm is characterized by EBV-associated loci and often involves the t(8;14) translocation?
Burkitt lymphoma
Which neoplasm is primarily associated with a diverse range of chromosomal rearrangements?
Multiple myeloma/solitary plasmacytoma
'Extranodal NK/T-cell lymphoma' is most likely to be of which origin?
Thymic
'Mycosis fungoides/Sézary syndrome' primarily involves which type of T cell?
'Large granular Helper T cell'
'Naive B cell' origin is typically seen in which neoplasm?
'Small lymphocytic lymphoma/chronic lymphocytic leukemia'
'Peripheral T-cell lymphoma, unspecified' is most likely to involve which type of T cell?
'Cytotoxic T cell'
Which neoplasm primarily originates from post-germinal center bone marrow homing plasma cells?
Multiple myeloma/solitary plasmacytoma
What chromosomal changes are most commonly seen in ALL?
Hyperploidy
Which mutations are suggested to be sufficient to produce full-blown ALL according to deep sequencing data?
Fewer than 10 mutations
What is the significance of hyperdiploidy and hypodiploidy in ALL?
Hyperdiploidy is associated with better prognosis and hypodiploidy with worse prognosis
Which ALL subtype is better characterized by numerical or structural chromosomal changes?
B-ALL
Which factor frequently correlates with immunophenotype and sometimes prognosis in ALL?
Chromosomal changes
What type of neoplasm is associated with hyperdiploidy in ALL?
B-ALL
Which statement is true about the genetic complexity of ALL compared to solid tumors?
Solid tumors are genetically simpler than ALL
What is the most common chromosomal change seen in ALL?
>50 chromosomes (hyperploidy)
"Changes in chromosome numbers are of uncertain pathogenic significance but are important because they frequently correlate with immunophenotype and sometimes prognosis." What does this statement imply about the role of chromosomal changes in ALL?
"Changes in chromosome numbers" may provide valuable clinical information despite their exact role being unclear
"B-ALL and T-ALL are associated with completely..." What information can be inferred about B-ALL and T-ALL based on this statement?
"B-ALL and T-ALL" have different immunophenotypes and prognoses
Which genetic abnormality leads to the creation of BCL6-IGH fusion gene?
t(14;18)
What is the characteristic genetic feature of adult T-cell leukemia/lymphoma?
HTLV-1 provirus presence
Which mutation leads to the formation of cyclin D1-IGH fusion gene?
Activating BRAF mutations
What type of mutation is most commonly associated with Trisomy 12 in certain lymphomas?
Splicing factor mutations
Which chromosomal abnormality is linked to the creation of MALT I-IAP2 fusion gene?
t(11;18)
What is the characteristic genetic alteration seen in primary cutaneous T-cell lymphomas?
ALK rearrangements
Which gene modification results in the formation of BCL2-IGH fusion gene?
t(14;18)
What are the symptoms related to depression of marrow function mentioned in the text?
Fatigue, fever, and bleeding
What type of symptoms are caused by mass effects due to neoplastic infiltration in ALL?
Bone pain and splenomegaly
Which manifestation is more common in T-ALL cases according to the text?
Complications related to compression of large vessels
What is one of the central nervous system manifestations mentioned in the text?
Vomiting
Which treatment approach has resulted in about 95% of children with ALL obtaining a complete remission?
Chemotherapy
What percentage of adults are cured of ALL according to the text?
35% to 40%
Despite significant achievements in treating pediatric ALL, what percentage of adults are not cured?
<50%
'Treatment of pediatric ALL is one of the great success stories of oncology' - What success rate is mentioned for children with ALL?
~95%
What is a specialized DNA polymerase expressed only in pre-B and pre-T lymphoblasts?
Terminal deoxynucleotidyl transferase (TdT)
Which marker is typically expressed by very immature B-ALLs but not by more mature 'late pre-B' ALLs?
CD10
Which transcription factor is expressed both by lymphoblasts and helps distinguish B-ALLs?
PAX5
In most T-ALL cases, which marker is positive while other markers are usually negative in more immature tumors?
CD3
What feature helps differentiate B-ALLs and T-ALLs based on the expression of specific proteins?
CD19 positivity
Which protein is expressed by pre-T-cell tumors but not by the more immature T-ALLs?
CD1
What are the common features of Acute Lymphoblastic Leukemia (ALL) as mentioned in the text?
Sudden onset of symptoms over days to weeks
What is the characteristic phenotype of B-ALL (B-cell Acute Lymphoblastic Leukemia) based on the information in the text?
CD22 positive, CD19 positive, CD10 negative
What is the significance of TdT expression in Acute Lymphoblastic Leukemia (ALL) according to the text?
An indicator of a B-cell leukemia
In ALL, what does a high blood blast count generally reflect based on the details provided?
Poor prognosis
What is a key function of the fusion gene involving the tyrosine kinase Myeloid Leukemia gene in hematologic malignancies?
Enhancing tyrosine kinase activity
How is molecular detection currently being used in Acute Lymphoblastic Leukemia (ALL)?
For prognostic evaluation
How does the activity level of Myeloid Leukemia gene differ between myeloid and lymphoblastic leukemias?
Higher activity in lymphoblastic leukemias
What is a key morphological feature that distinguishes lymphoblasts in B-ALL and T-ALL from myeloblasts?
Large nuclei with delicate chromatin
What characteristic appearance might be observed in rapidly growing lymphoid tumors due to interspersed macrophages?
Starry sky appearance
In leukemic presentations, what is the typical cellular composition of the bone marrow?
Hypercellular and packed with lymphoblasts
What is a distinguishing feature between ALL and AML in terms of cellular characteristics?
Presence of granules in lymphoblast cytoplasm
What is a common feature associated with thymic masses in T-ALL?
Lymphadenopathy
How does the nuclear appearance of lymphoblasts in ALL differ from that of myeloblasts in AML?
Finely stippled chromatin
What is the typical nuclear membrane appearance seen in tumor cells of ALL?
Deeply subdivided
'Starry sky' appearance in lymphoid tumors is due to macrophages ingesting:
Viable tumor cells
What is the protein size of the BCR-ABL protein found in B-ALL?
Usually 190 kDa
Which genetic anomalies are commonly found in CLL/SLL?
Deletions of 13q14.3, 11q, and 17p
What is the favorable prognostic marker for ALL related to blood blast counts?
Greater than 100,000
Which microRNAs are implicated as tumor suppressor genes in chromosomal deletions of CLL/SLL?
miR-15a and miR-16-1
Which chromosomal translocation is found in B-ALL that creates a constitutively active BCR-ABL fusion gene?
(9;22)
What is the primary function of the t(9;22) chromosomal translocation in B-ALL?
Creates a constitutively active BCR-ABL fusion gene
What is the most common prognostic marker related to ALL based on the text?
(3) hyperdiploidy
Why is the BCR-ABL protein in B-ALL more active than in chronic myeloid leukemia?
Size difference - usually 190 kDa in B-ALL vs. 210 kDa in CML
What is believed to cause the overexpression of the anti-apoptotic protein BCL2 in CLL/SLL?
Somatic hypermutation of Ig genes
Which characteristic is associated with tumors of unmutated Ig segments in CLL/SLL?
More aggressive course
What mutation is frequently observed in CLL genomes that involves genes regulating RNA splicing?
Mutations in genes regulating RNA splicing
Which treatment approach has shown high effectiveness in t(9;22)-positive ALLs?
BCR-ABL kinase inhibitors combined with conventional chemotherapy
Cryptic rearrangements involving genes encoding tyrosine kinases other than ABL are therapeutic targets in which subtype of B-ALL?
Molecular subtype of B-ALL
Why is the outlook for older adults with ALL guarded?
Differences in molecular pathogenesis from childhood ALL
What is a characteristic feature of deep sequencing of CLL genomes?
Revealing gain-of-function mutations and frequent RNA splicing mutations
Why do tumors with unmutated Ig segments pursue a more aggressive course?
Naive B-cell origin which leads to aggressive behavior
What is a significant drawback associated with dramatic responses achieved with chimeric antigen receptor T cells directed against CD19 in B-ALL treatment?
High cost and associated toxicities
What genetic lesions in tumor cells of highly aggressive B-ALL tumors lead to the accumulation of immature, nonfunctional blasts?
Genetic lesions that block differentiation
Which signaling pathway is triggered by the B-cell receptor in Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) to promote cell survival?
Activation of Bruton tyrosine kinase (BTK)
What type of cells express a variety of factors in proliferation centers that stimulate NF-kB activity and MYC activity in CLL/SLL?
Stromal cells
In which neoplasm do CLL/SLL cells largely grow within proliferation centers receiving critical cues from the microenvironment?
Chronic lymphocytic leukemia
What is a subset of B-ALL tumors containing activating mutations in tyrosine kinases like BCR-ABL considered as?
High-risk tumors
What important targets of therapy are tumors with activating mutations in tyrosine kinases, like BCR-ABL, considered as?
High-risk targets
What is the primary cause of fatal outcomes sometimes associated with achieving dramatic responses in B-ALL using chimeric antigen receptor T cells directed against CD19?
'On-target, off-tumor' toxicities
What is the diagnostic requirement for chronic lymphocytic leukemia (CLL)?
Absolute lymphocyte count >5000/mm³
What is the male-to-female ratio in chronic lymphocytic leukemia (CLL)?
2:1
What distinguishes chronic lymphocytic leukemia (CLL) from small lymphocytic lymphoma (SLL)?
Level of peripheral blood lymphocytosis
What gene is implicated in X-linked agammaglobulinemia, emphasizing its importance in B cells?
BTK gene
Which cells depend on B-cell receptor signaling and BTK activity for their growth and survival?
CLL cells
Where are proliferation centers commonly found in cases of chronic lymphocytic leukemia (CLL)?
Lymph nodes
What variables correlate with a worse outcome in chronic lymphocytic leukemia (CLL)?
Deletions of 11q and 17p, lack of somatic hypermutation, expression of ZAP-70, and NOTCH1 mutations
What is a common treatment approach for symptomatic patients with chronic lymphocytic leukemia (CLL)?
Chemotherapy and immunotherapy with CD20 antibodies
Which proteins are targeted by immunotherapy in chronic lymphocytic leukemia (CLL)?
CD20 and BTK inhibitors
What is the impact of newly available BTK inhibitors and BCL2 inhibitors on chronic lymphocytic leukemia (CLL) treatment?
Their impact on the disease course is still being determined.
Which genetic mutation is specifically mentioned in relation to a worse outcome in chronic lymphocytic leukemia (CLL)?
NOTCH1 mutations
What is the typical median survival range for individuals with chronic lymphocytic leukemia (CLL)?
4 to 6 years
Which protein, when expressed, augments signals produced by the Ig receptor in chronic lymphocytic leukemia (CLL)?
ZAP-80
What type of therapy is generally recommended for individuals with minimal tumor burden at chronic lymphocytic leukemia (CLL) diagnosis?
Watchful waiting
What is a distinguishing histological feature seen in chronic lymphocytic leukemia (CLL)?
Disrupted tumor cells known as smudge cells
Which syndrome often involves enlargement of the liver in patients with small lymphocytic lymphoma/chronic lymphocytic leukemia?
Articular Manifestations Syndrome
What is a notable characteristic finding in the peripheral blood smear of chronic lymphocytic leukemia?
Nucleated erythroid cell presence
Which factor contributes to the presence of effacement of nodal architecture in small lymphocytic lymphoma/chronic lymphocytic leukemia?
Diffuse effacement of nodal architecture
What is a key difference between small lymphocytic lymphoma and chronic lymphocytic leukemia based on the text?
Size of round lymphocytes
In chronic lymphocytic leukemia, what characteristic hematological feature distinguishes it from other neoplastic disorders?
'Smudge cells' in peripheral blood smears
What is a common accompanying condition seen in chronic lymphocytic leukemia along with disrupted tumor cells?
'Smudge cells' in peripheral blood smears
Which hematologic malignancy presents with a 'flooded' peripheral blood smear full of small round lymphocytes?
'Flooded' peripheral blood with small round lymphocytes
What is a common feature in asymptomatic patients with monoclonal B cells that differentiates them from symptomatic CLL patients?
Monoclonal Ig spike in the blood
Which of the following contributes to an increased susceptibility to infection in patients with CLL/SLL?
Hypogammaglobulinemia
What is considered a precursor lesion to symptomatic CLL and progresses at a rate of 1% per year?
Monoclonal lymphocytosis of uncertain significance
Which condition can disrupt normal immune function through uncertain mechanisms in patients with CLL/SLL?
Hypogammaglobulinemia
What chromosomal translocation is strongly associated with follicular lymphoma?
t(14;18)
Which gene overexpression is a hallmark of follicular lymphoma due to the t(14;18) translocation?
BCL2
In Richter transformation, what genetic abnormalities are often acquired that lead to poor prognosis?
TP53 or MYC
Which lymphoma type is the most common form of indolent lymphoma in the United States?
Follicular lymphoma
What event is often heralded by the development of a rapidly enlarging mass within a lymph node or the spleen in Richter transformation?
Richter syndrome
Which of the following is associated with an ominous event in Richter transformation?
Survival less than 1 year
What is the typical gender distribution in patients afflicted with follicular lymphoma?
Males and females equally
What is the main trigger for transformation of CLL/SLL to diffuse large B-cell lymphoma (DLBCL)?
'Richter syndrome'
What type of cells are most abundant in most follicular lymphomas?
Centrocytes
Which gene mutation is identified in about 90% of cases of follicular lymphoma?
KMT2D
What cell type is responsible for encoding a histone methyltransferase in follicular lymphoma?
KMT2D
What is the typical growth pattern observed in involved lymph nodes in most follicular lymphomas?
Nodular
Which feature distinguishes centrocytes from centroblasts in follicular lymphoma?
Cell size
What surrounds follicular lymphoma cells growing in lymph nodes early in the disease?
Reactive follicular dendritic cells
Which cells are predictive of the outcome of follicular lymphoma cells to therapy?
Stromal cells
'Small cleaved cells' refer to which cell type observed in nodular growth patterns of follicular lymphomas?
Centrocytes
'Large cells with open nuclear chromatin, several nucleoli, and modest amounts of cytoplasm' are characteristic of which cell type found in follicular lymphomas?
'Centroblasts'
Which genetic aberration is most commonly associated with the overexpression of the antiapoptotic protein BCL2 in diffuse large B-cell lymphoma (DLBCL)?
t(14:18)
What is the distinctive feature of tumors with follicular lymphoma that frequently transform into DLBCL?
Presence of somatic hypermutation
Which protein, involved in gene expression regulation, is frequently mutated in diffuse large B-cell lymphoma (DLBCL)?
p300
In DLBCL genomes, what gene encoding histone acetyltransferases is commonly mutated, impacting gene expression?
p300
What characteristic chromosomal translocation is associated with approximately 5% of DLBCLs and often involves MYC?
t(8:14)
Diffuse large B-cell lymphoma (DLBCL) is characterized by which common genetic feature?
Ig gene rearrangement
DLBCL is associated with a slight male predominance. What is the median age range for this condition?
60-70 years
DLBCL can also affect young adults and children. What is a distinguishing feature of DLBCL in young individuals?
Unique molecular signatures
DLBCL accounts for a significant number of non-Hodgkin lymphoma cases. What is the approximate annual incidence of new DLBCL cases in the United States?
10,000 cases
What is the primary approach to managing symptomatic patients with Follicular lymphoma?
Low-dose chemotherapy or immunotherapy
Which transcriptional repressor is overexpressed in Follicular lymphoma, contributing to its development?
BCL6
Which extranodal site involvement is relatively uncommon in Follicular lymphoma?
Bone marrow
What is the median survival range for individuals with Follicular lymphoma?
7 to 9 years
Which oncogene, when overexpressed, can contribute to histologic transformation of follicular lymphoma to DLBCL?
MYC
What is a characteristic consequence of mutations similar to those found in BCL6?
Contribution to DLBCL development
What is a common outcome of histologic transformation in follicular lymphomas?
Increased MYC expression
Which type of therapy does not improve the survival of individuals with Follicular lymphoma?
Radiation therapy
What is the primary function of BCL2 in follicular lymphoma cells?
Promoting follicular-center B cell survival
Which protein is NOT expressed in follicular center B cells, as highlighted in the text?
BCL6
What is the main difference between neoplastic cells in follicular lymphoma and normal germinal center B cells?
Presence of BCL2
Which of the following transcription factors is commonly associated with follicular lymphoma?
NF-kB
What is the genetic anomaly found in a significant percentage of DLBCL cases according to the text?
Mutations in BCL6 promoter sequences
Which feature distinguishes reactive follicles from neoplastic follicles based on the text?
Staining intensity of BCL2
What differentiates CD5 expression between follicular lymphoma and other lymphoid neoplasms according to the text?
"Unlike CLL/SLL and mantle cell lymphoma, CD5 is not expressed" in follicular lymphoma cases
What type of nucleoli are found in the nucleus of cells in diffuse large B-cell lymphomas (DLBCLs) according to the text?
Two to three large nucleoli centrally placed
What feature is observed in more anaplastic tumors that can help identify them?
Basophilic cytoplasm
Where are the multi-nucleated oroplasmic cells with inclusion-like nucleoli typically found?
Hodgkin lymphoma
What is a distinguishing characteristic of germinal center B cells compared to activated post-germinal center B cells?
Different molecular subtypes
In diffuse large B-cell lymphomas, what type of disease course is associated with individuals having limited disease?
Improved outcome
What is the main effect of intensive combination chemotherapy on diffuse large B-cell lymphoma (DLBCL) patients?
40% to 50% cure rate
'Adjuvant therapy with anti-CD20 antibody' has what impact on diffuse large B-cell lymphoma (DLBCL) treatment outcomes?
Improves response and outcome
'Expression profiling' in diffuse large B-cell lymphoma (DLBCL) has identified which distinct molecular subtypes?
'Germinal center B cells' and 'Activated post-germinal center B cells'
What is the primary mechanism by which MYC contributes to Burkitt lymphoma growth?
Enhancing Warburg metabolism for biosynthesis
Which chromosomal translocation is most commonly associated with MYC in Burkitt lymphoma?
t(8;14)
What distinguishes Waldeyer ring in the context of DLBCL development?
Common presentation site for DLBCL masses
Which feature is characteristic of HHV-8 infection in DLBCL?
Presence of clonal IGH gene rearrangements
How do Burkitt lymphoma cells differ in metabolism compared to normal cells?
Heightened Warburg metabolism activity
What is a significant characteristic of DLBCL cells regarding gene rearrangements?
Limited involvement of IGH gene alterations
Which site is commonly noted for primary or secondary involvement in DLBCL?
Liver and spleen
What role does IGH gene rearrangement play in DLBCL pathology?
Identification of clonal tumor cell population
What effect do the translocations in sporadic Burkitt lymphoma and endemic Burkitt lymphoma have on the MYC coding sequence?
Position it adjacent to strong Ig enhancer elements
What is the specialized DNA-modifying enzyme required for both Ig class switching and somatic hypermutation in germinal center B cells?
AID
What is the main effect of TCF3 mutations in Burkitt lymphoma cells?
Increase MYC expression
What is the role of point mutations in the translocated MYC allele in Burkitt lymphoma?
Stabilize MYC protein and decrease its activity
Which region of the IGH locus do breakpoints in sporadic Burkitt lymphoma usually occur?
'5 class switch regions
What drives increased MYC expression in Burkitt lymphoma?
Strong Ig enhancer elements
In which type of B cells can translocations similar to those in Burkitt lymphoma be induced by AID?
Germinal center B cells
What is the DNA-modifying enzyme required for Ig class switching and somatic hypermutation in germinal center B cells?
AID
Where do breakpoints tend to lie within the IGH locus in endemic Burkitt lymphoma?
'5 V(D)J sequences
What is a potential treatment option for DLBCLs with MYC translocations?
Chemotherapy regimens used for Burkitt lymphoma
Which cell surface antigen is targeted by CAR T cells for the treatment of DLBCL?
CD19
What is a characteristic marker expressed by mature B-cell tumors, including DLBCLs?
CD10
What protein's high-level expression can predict aggressive behavior in DLBCLs?
MYC
In what setting are DLBCLs associated with T-cell immunodeficiency usually seen?
In individuals infected with HIV
What pathogen is usually found infecting neoplastic B cells in DLBCLs occurring in T-cell immunodeficiency?
Epstein-Barr virus (EBV)
'African (endemic) Burkitt lymphoma' is a subtype of Burkitt lymphoma that is characterized by what factor?
Geographic distribution
What is the role of TCF3 in Burkitt lymphoma?
Drives the expression of genes promoting rapid growth
What is the relationship between EBV infection and Burkitt lymphoma development?
EBV plays a speculative role in Burkitt lymphoma genesis
What is the characteristic morphology of lymphoid cells in Burkitt lymphoma?
Intermediate-sized cells with round or oval nuclei, coarse chromatin, and moderate cytoplasm
What contributes to the 'starry sky' appearance seen in Burkitt lymphoma?
High number of apoptotic cells
In Burkitt lymphoma, which gene collaborates with MYC to enable rapid growth?
Cyclin E
What percentage of HIV-associated tumors have EBV infection according to the text?
~25%
What is the primary feature of the effaced tissues in Burkitt lymphoma?
Small cell size with scant cytoplasm
What is the primary role of EBV in Burkitt lymphoma?
Precise role remains speculative but significant
What characteristic feature is seen in the tumor cells of Burkitt lymphoma?
Round or oval nuclei with coarse chromatin and several nucleoli
What is a typical histological feature of Burkitt lymphoma at high power?
Multiple small nucleoli and high mitotic index
Which protein is almost always not expressed in Burkitt lymphoma, unlike most other tumors of germinal center origin?
BCL2
Where do most Burkitt lymphomas manifest?
Extranodal sites
What is a characteristic feature of endemic Burkitt lymphoma?
Involvement of mandible
Which immunophenotype is consistent with a germinal center B-cell origin in Burkitt lymphoma?
IgM, CD20, BCL6
What is the characteristic genetic alteration seen in Burkitt lymphoma?
t(8;14)
Which age group is most commonly affected by Burkitt lymphoma?
Children or young adults
What is the unusual predilection for involvement in endemic Burkitt lymphoma?
Kidneys and adrenal glands
What is the unique expression status of BCL2 in Burkitt lymphoma compared to other germinal center origin tumors?
No expression of BCL2
What is the primary genetic abnormality seen in mantle cell lymphoma?
Translocation involving the IGH locus on chromosome 11
What is the age range when mantle cell lymphoma usually presents?
Fifth to sixth decades of life
Which lymphoma is most likely to spread through mucosal involvement producing polyp-like lesions in the small bowel or colon?
Mantle cell lymphoma
What is the key promoting factor in mantle cell lymphoma that leads to G₁- to S-phase progression?
Cyclin D1
Where do tumor cells in mantle cell lymphoma closely resemble normal B cells?
Germinal centers
What percentage of NHL in Europe is constituted by mantle cell lymphoma?
~9%
What is the typical gender distribution observed in patients with mantle cell lymphoma?
Male predominance
Where does mantle cell lymphoma primarily involve extranodally, aside from generalized lymphadenopathy?
Bone marrow
What is a distinguishing feature of mantle cell lymphoma in involved lymph nodes?
Reactive germinal centers surrounding nodal tumor cells
What is a distinguishing feature of marginal zone lymphomas that arise at extranodal sites?
Origination in tissues with chronic inflammatory disorders
Which gene mutation is primarily associated with shorter survival in blastoid variant lymphomas?
TP53
Where are mucosa-associated lymphoid tumors (MALTomas) more likely to be found?
Stomach
What is the median survival time for individuals with white cell median survival disorders?
8 to 10 years
What is the key characteristic of Burkitt lymphoma cells in terms of metabolism?
Increased glycolysis
Which lymphoma category is recognized for its unusual pathogenesis and exceptional characteristics?
Marginal Zone Lymphomas
In which organ may marginal zone lymphomas arise within tissues involved by chronic inflammatory disorders?
Stomach
What type of lymphoma often regresses with the eradication of H.pylori?
Gastric MALToma
At what stage does withdrawal of the responsible antigen cause tumor involution in lymphomas?
When a B-cell clone emerges
Which lymphoid neoplasm lies on a continuum between reactive lymphoid hyperplasia and full-blown lymphoma?
Extranodal marginal zone lymphoma
In which type of neoplasms does the disease likely begin as a polyclonal immune reaction?
Extranodal marginal zone lymphoma
What kind of cells are suggested to drive growth and survival in B-cell clones at an early stage of certain lymphomas?
T-helper cells
Which characteristic distinguishes gastric MALToma among the given options?
Regression with H.pylori eradication
What is a distinguishing feature of IGH genes in Hairy Cell Leukemia?
Presence of somatic hypermutation
Which demographic group is predominantly affected by Hairy Cell Leukemia?
Middle-aged white males
What is the most common initial presentation of Hairy Cell Leukemia?
Painless lymphadenopathy
Which lymphoid neoplasm is moderately aggressive and incurable?
Mantle Cell Lymphoma
In Hairy Cell Leukemia, what is the male-to-female ratio?
5:1
What is a common symptom seen in Hairy Cell Leukemia patients related to the spleen?
Splenomegaly
Which is a distinguishing feature that helps differentiate Hairy Cell Leukemia from CLL/SLL?
Expression of CD23
What is the most common gender affected by Mantle Cell Lymphoma?
'Male predominant'
'Naive B cell origin' in Hairy Cell Leukemia is supported by which characteristic regarding IGH genes?
'CD5+ and CD23- expression'
What is the consequence of (11;18) chromosomal translocation in tumors?
Activation of NF-κB
How do mantle cell lymphomas differ from follicular lymphomas?
Absence of proliferation centers
Which protein components are up-regulated by (1;14) chromosomal translocation in tumors?
BCL10 and MALT1
What is a distinguishing feature of mantle cell lymphomas?
High levels of cyclin D1 and CD20 expression
Which cell feature helps differentiate 'blastoid' variants from Acute Lymphoblastic Leukemia (ALL)?
Scant cytoplasm and condensed chromatin
What is a characteristic immunophenotype of mantle cell lymphomas?
IgM and IgD expression with κ light chain
What distinguishes mantle cell lymphomas from follicular lymphoma and CLL/SLL?
Absence of centroblast-like large cells
What is a key characteristic of extranodal marginal zone lymphomas according to the text?
Dependence on antigen-stimulated T-helper cells for growth and survival signals
In the context of lymphoma genesis, what is the significance of the acquisition of unknown initiating mutations?
It results in the emergence of a B-cell clone
How do extranodal marginal zone lymphomas primarily differ from reactive lymphoid hyperplasia?
Acquisition of mutations rendering growth antigen-independent
What event triggers tumor involution in gastric MALToma according to the text?
Antibiotic therapy directed against H.pylori
What is the consequence of tumors acquiring mutations that render growth antigen-independent?
Growth and survival independent of the responsible antigen
Which chromosomal translocations are relatively specific for extranodal marginal zone lymphomas?
(11;18), (14;18), and (1;14)
What is the role of H.pylori eradication in tumors like gastric MALToma?
Causes tumor involution
What characteristic distinguishes marginal zone lymphomas arising at extranodal sites?
Originating from chronic inflammatory disorders
What term is used to describe the mantle cell lymphoma pattern shown in Figure 13.16?
Mantle zone pattern
Which lymphoma is often found in tissues affected by Sjögren disease?
Marginal zone lymphoma
What is a common characteristic of marginal zone lymphomas occurring at extranodal sites?
"MALTomas"
What is a notable clinical feature associated with marginal zone lymphomas arising at extranodal sites?
Shorter median survival
What is a key distinguishing factor of marginal zone lymphomas from other B-cell tumors?
"Tumor cell evidence of somatic hypermutation"
Which inflammatory disorder can lead to the development of marginal zone lymphoma in the stomach?
"Helicobacter gastritis"
What sets apart marginal zone lymphomas at extranodal sites for special attention?
"Exceptional characteristics"
What is a distinguishing feature of mantle cell lymphoma compared to follicular lymphoma and CLL/SLL?
Expression of CD5 and CD23
Which protein components are up-regulated by (11;14) chromosomal translocation in tumors?
Cyclin D1 and CD19
What is a characteristic immunophenotype of mantle cell lymphomas?
CD5+ and CD23-
Which type of B-cell is likely to lack somatic hypermutation in the IGH genes?
Naive B cell
What is the main function of the signaling complex involving BCL10 or MALT1?
Activate NF-kB
In mantle cell lymphoma, which immunophenotype is inconsistent with CLL/SLL?
Surface Ig-
Which factor helps distinguish blastoid variants from ALL in mantle cell lymphoma?
$\text{Brisk mitotic rate}$
What is the key feature of mantle cell lymphoma nuclei in most cases?
$\text{Condensed chromatin and inconspicuous nucleoli}$
'Blastoid' variants in mantle cell lymphoma are distinguished from ALL by:
$\text{Brisk mitotic rate}$
'Hairy Cell Leukemia' is known for presenting with:
$\text{Painless lymphadenopathy}$
What is the most common abnormal physical finding in hairy cell leukemia?
Splenomegaly
What is a common manifestation resulting from marrow involvement and sequestration of cells in the enlarged spleen in hairy cell leukemia?
Pancytopenia
Approximately what percentage of individuals affected by hairy cell leukemia present with infections?
50%
What type of infections have an increased incidence among individuals with hairy cell leukemia?
Atypical mycobacterial infections
What is a distinctive feature of the activity of BRAF inhibitors in tumors that have failed conventional chemotherapy in hairy cell leukemia?
Excellent responses
What is a unique characteristic of tumor relapse after 5 or more years in hairy cell leukemia?
Generally respond well to retreatment with the same agents
What is the prognosis typically like for individuals with hairy cell leukemia?
Excellent prognosis
Which type of therapy is particularly effective for hairy cell leukemia due to its sensitivity?
"Gentle" chemotherapeutic regimens
What morphological feature distinguishes hairy cell leukemia cells when viewed under a phase-contrast microscope?
Round or reniform nuclei with pale blue cytoplasm
Why is obtaining a bone marrow sample from hairy cell leukemia patients often challenging?
Cells are enmeshed in an extracellular matrix
What characteristic splenic appearance is associated with hairy cell leukemia?
White pulp obliteration with a beefy red gross appearance
Which markers are commonly expressed on hairy cell leukemia cells?
CD11c, CD25, CD103, annexin A1
What distinguishes the morphological appearance of hairy cell leukemia cells in the bone marrow?
Oblong or reniform nuclei with pale cytoplasm
Which hematologic malignancy is known for its involvement of hepatic portal triads?
Langerhans cell histiocytosis
What feature characterizes hairy cell leukemia cells' appearance under a phase-contrast microscope?
Fine hair-like projections
What makes hairy cells in leukemia different from other leukemic cells under a phase-contrast microscope?
Thread-like or bleb-like cytoplasmic extensions
What is the key morphological feature of cells found in Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia?
Round or folded nuclei and modest amounts of pale blue, agranular cytoplasm
Which lymphoma is associated with a (14;18) translocation resulting in overexpression of BCL2?
Follicular Lymphoma
Which mutation or rearrangement is recognized to be associated with about one-third of Diffuse Large B-Cell Lymphomas?
Mutations in BCL6 gene
What is a distinguishing feature of Burkitt Lymphoma?
Very aggressive tumor that arises at extranodal sites
Which lymphoma shares a growth pattern similar to normal germinal center B cells?
Follicular Lymphoma
What characteristic sets Diffuse Large B-Cell Lymphoma apart among adult lymphomas?
Heterogeneous group with mature B-cell tumors
What is the defining characteristic of Small Lymphocytic Lymphoma/Chronic Lymphocytic Leukemia?
Most common leukemia of adults
Which lymphoma is specifically associated with rearrangements or mutations of the BCL6 gene?
Diffuse Large B-Cell Lymphoma
What makes Follicular Lymphoma stand out as the most common indolent lymphoma among adults?
(14;18) translocation that results in overexpression of BCL2
Which neoplasm is characterized by indolent tumors of antigen-primed B cells that arise at sites of chronic immune stimulation?
Marginal Zone Lymphoma
What is the distinguishing feature of Hairy Cell Leukemia among the listed neoplasms?
Involvement of spleen and marrow
Which aspect differentiates Mantle Cell Lymphoma from other neoplasms?
Translocations involving the cyclin D1 gene
What distinguishes Peripheral T-Cell Lymphomas from other neoplasms in terms of phenotype?
Resemblance to mature T cells or NK cells
Which region shows a higher incidence of T- and NK-cell tumors compared to the United States and Europe?
Far East
What differentiates Marginal Zone Lymphoma from other neoplasms?
Localization for long periods of time
What characteristic cells are typically seen in Anaplastic Large-Cell Lymphoma (ALK Positive)?
Horseshoe-shaped nuclei
Which gene rearrangement leads to the formation of chimeric genes encoding ALK fusion proteins in Anaplastic Large-Cell Lymphoma (ALK Positive)?
ALK
What is a reliable indicator of an ALK gene rearrangement in T-cell lymphomas?
Detection of ALK protein
Which age group tends to be associated with T-cell lymphomas having ALK rearrangements?
Children or young adults
Which type of lymphomas carry a very good prognosis when they involve soft tissues?
ALK- Anaplastic Large Cell Lymphoma
What is the cure rate with chemotherapy for Anaplastic Large-Cell Lymphoma (ALK Positive)?
$75%$ to $80%
What is a common feature seen in peripheral T-cell lymphomas derived from mature T cells?
Infiltrate of reactive cells like eosinophils
What is the significance of DNA analysis in diagnosing difficult cases between lymphoma and reactive processes?
Confirming the presence of clonal T-cell receptor gene rearrangements
Which receptors are expressed by peripheral T-cell lymphomas according to the text?
CD2, CD3, CD5, and either aẞ or yo T-cell receptors
What is a characteristic marker expressed by peripheral T-cell lymphomas derived from mature T cells?
CD2
How do peripheral T-cell lymphomas typically differ from mature B-cell neoplasms in terms of prognosis?
Mature B-cell neoplasms have a worse prognosis
What is the key role of DNA analysis in confirming a diagnosis of peripheral T-cell lymphoma?
Confirming the presence of clonal T-cell receptor gene rearrangements
Which syndrome is characterized by Microphthalma, Polydactyly, Microcephaly, and mental retardation?
Patau syndrome
Which syndrome is associated with Rocker-bottom feet?
Edwards syndrome
Which infection may lead to a demyelinating disease of the central nervous system and spinal cord?
HTLV-1
Which neoplastic disorder is associated with cells containing clonal HTLV-1 proviruses?
Adult T-cell leukemia/lymphoma
Which chromosomal translocation leads to the formation of chimeric genes encoding ALK fusion proteins in Anaplastic Large-Cell Lymphoma?
(8;14)
What distinguishing feature is observed in Hairy Cell Leukemia regarding IGH genes?
Inversion
Which lymphoma type is most likely to spread through mucosal involvement producing polyp-like lesions in the small bowel or colon?
MALT Lymphoma
What is the primary function of the signaling complex involving BCL10 or MALT1?
NF-κB activation
What is a key difference between T-cell variants and NK-cell variants based on the text?
Surface expression of CD3
In the context of the text, what dominates the clinical picture despite the relative paucity of marrow infiltration?
Neutropenia and anemia
What is a rare manifestation that may be seen in the context of the text?
Pure red cell aplasia
Which disorder includes a triad of rheumatoid arthritis, splenomegaly, and neutropenia as an underlying cause according to the text?
Felty syndrome
What is suggested to likely cause the varied clinical abnormalities mentioned in the text?
Autoimmunity triggered by tumors
What may autoimmunity be provoked by according to the text?
Tumor
What clinical feature is more prevalent in Felty syndrome according to the text?
Splenomegaly as a predominant feature
What factor remains unknown despite certain clinical abnormalities in patients mentioned in the text?
Basis for varied clinical abnormalities
What is the most common site for the occurrence of Large Granular Lymphocytic Leukemia?
Lymph nodes
Which transcription factor is constitutively activated in approximately 30% to 40% of Large Granular Lymphocytic Leukemias?
STAT3
What is a typical morphological feature of the tumor cells in Large Granular Lymphocytic Leukemia?
Abundant blue cytoplasm
In what form of Large Granular Lymphocytic Leukemia do acquired mutations in STAT3 occur?
Both T-cell and NK-cell
Which organ is usually free from lymphadenopathy in individuals with T-cell disease?
Spleen
What is the main role of STAT3 in the pathogenesis of Large Granular Lymphocytic Leukemias?
Regulating cell proliferation
Which type of leukemia/lymphoma presents with skin lesions that rarely proceed to tumefaction?
Mycosis Fungoides
What is the variant of mycosis fungoides characterized by skin involvement manifested as a generalized exfoliative erythroderma?
Szary Syndrome
Which molecule, expressed by tumor cells, contributes to the homing of CD4+ T cells to the skin in mycosis fungoides?
CCR10
Late disease progression in mycosis fungoides is characterized by extracutaneous spread, most commonly to which locations?
Lymph Nodes and Bone Marrow
In mycosis fungoides, which phase involves neoplastic T cells with a cerebriform appearance due to marked infolding of the nuclear membrane?
Plaque Phase
Which lymphoma variant is a rare form of cutaneous T-cell lymphoma characterized by the presence of cerebriform nuclei?
Szary Syndrome
Which molecule expressed by tumor cells contributes to the homing of CD4+ T cells to the skin in Szary Syndrome?
CCR4
What is the main consequence of mutations in transcription factors that influence self-renewal?
Increase in genomic instability
What is a distinguishing feature of marginal zone lymphomas that arise at extranodal sites?
Involvement of only the skin
What do clonal HTLV-1 proviruses in tumor cells suggest about the role of the virus?
Direct pathogenic role
Why does the transformation process leading to adult T-cell leukemia/lymphoma remain poorly understood?
Complexity and limited clarity
What leads to a sustained increase in neutrophil production over several days?
Specific growth factors
What triggers rapid proliferation in newly committed progenitor cells?
Inflammatory challenges
Which characteristic is associated with tumors of unmutated Ig segments in CLL/SLL?
'Horseshoe-like' nuclei appearance
Which adhesion molecule is expressed by tumor cells in both mycosis fungoides and Sézary syndrome?
Cutaneous leukocyte antigen
What is the characteristic nuclear appearance of 'Sézary' cells in Sézary syndrome?
Cerebriform
Which chemokine receptors are expressed by tumor cells in both mycosis fungoides and Sézary syndrome?
CCR4 and CCR10
What is the median survival of indolent tumors, such as mycosis fungoides and Sézary syndrome?
10 years
In which phase do cutaneous lesions in mycosis fungoides typically progress through three somewhat distinct stages?
Tumor phase
What is the main difference between mycosis fungoides and Sézary syndrome regarding skin involvement?
Erythroderma
Which structures are characterized by a marked infolding of the nuclear membrane in neoplastic T cells of mycosis fungoides?
'Cerebriform' appearance
What characterizes late disease progression in mycosis fungoides and Sézary syndrome?
'Extracutaneous' spread
'Sézary' syndrome is distinguished by the presence of which cells with characteristic nuclei?
'Cerebriform'
What is a common clinical presentation of NK-cell disease in Large Granular Lymphocytic Leukemia?
Subtle symptoms with little or no splenomegaly
What is the predominant clinical feature in T-cell variants of Large Granular Lymphocytic Leukemia?
Neutropenia
What is the genetic mutation found in approximately 30% to 40% of Large Granular Lymphocytic Leukemias?
STAT3
Which cell surface marker is characteristic of T-cell variants of Large Granular Lymphocytic Leukemia?
CD3
What is the primary role of STAT3 mutations in Large Granular Lymphocytic Leukemia pathogenesis?
Lead to cytokine-independent activation of STAT3
How do NK-cell variants of Large Granular Lymphocytic Leukemia differ from T-cell variants?
Expression of CD56
Which cellular characteristic distinguishes neoplastic cells in Large Granular Lymphocytic Leukemias according to peripheral blood smears?
Presence of large azurophilic granules
What is the characteristic marrow infiltrate observed in Large Granular Lymphocytic Leukemias?
Sparse interstitial lymphocytic infiltrate
What is a distinguishing feature of NK-cell variants compared to T-cell variants in Large Granular Lymphocytic Leukemias?
Expression of CD56
Which transcription factor mutation is associated with Large Granular Lymphocytic Leukemias?
STAT3
What is the hallmark of Adult T cell leukemia/lymphoma?
CD4+ T cell association
Which protein is commonly secreted by neoplastic plasma cells in plasma cell neoplasms?
Monoclonal Ig
Which tumor is strongly associated with EBV infection?
Extranodal NK/T cell lymphoma
What does ALK tyrosine kinase activation result from in Anaplastic large cell lymphoma?
Chromosomal translocations involving ALK gene
What is the primary marker of plasma cell neoplasms used for diagnosis?
Monoclonal Ig
'Monoclonal gammopathy' and 'paraproteinemia' are terms associated with which group of neoplasms?
'Plasma cell neoplasms'
'Large granular lymphocytic leukemia' is most commonly derived from which type of cells?
'Natural Killer (NK) cells'
What is a characteristic feature of Extranodal NK/T-cell lymphoma in terms of response to chemotherapy?
Resistant
What is the common response of extranodal NK/T-cell lymphoma to radiation therapy?
Strong response
Which type of treatment has shown positive results in extranodal NK/T-cell lymphoma akin to other virus-driven cancers?
Immune checkpoint inhibitors
What is a distinctive feature of the tumor cells in Extranodal NK/T-cell lymphoma regarding EBV episomes?
All contain identical EBV episomes
Which surface protein is notably absent on tumor cells in Extranodal NK/T-cell lymphoma despite being the B-cell EBV receptor?
CD21
What is a significant difference between extranodal NK/T-cell lymphomas and mature B-cell neoplasms regarding chromosome abnormalities?
Neither exhibit consistent chromosome abnormalities
How do extranodal NK/T-cell lymphomas generally respond to immune checkpoint inhibitors?
Positive response
What is a distinguishing feature of Extranodal NK/T-cell lymphomas compared to other neoplasms regarding CD3 expression and T-cell receptor rearrangements?
Do not express CD3 and lack T-cell receptor rearrangements
Plasma cell tumors often synthesize excess light chains along with complete Igs. In most patients, the level of free light chains is elevated and skewed toward one light chain at the expense of the second. What are these light chains referred to when excreted in the urine?
Bence Jones proteins
Which type of lymphoma is rare in the United States and Europe but constitutes as many as 3% of NHLS in Asia, often presenting as a destructive nasopharyngeal mass?
Extranodal NK/T-Cell Lymphoma
Which neoplasm is identified by the presence of a monoclonal Ig in the blood known as an M component?
Multiple Myeloma
In multiple myeloma, what is excluded from the urine in the absence of glomerular damage?
Complete M components
Which presentation is most common for Extranodal NK/T-Cell Lymphoma?
Nasopharyngeal mass
What is the most frequent site of presentation for Extranodal NK/T-Cell Lymphoma aside from the nasopharynx?
Testis
'Monoclonal Ig' identified in multiple myeloma patients has a molecular weight of:
> 160,000
'Bence Jones proteins' are excreted in the urine due to plasma cell tumors. What is a defining characteristic of these proteins?
Small size
What is a defining feature of solitary myeloma (plasmacytoma)?
Characterized by a single mass in bone or soft tissue
Which variant is defined by a lack of symptoms and a high plasma M component?
Smoldering myeloma
What distinguishes Waldenström macroglobulinemia from other variants mentioned?
High levels of IgM leading to hyper-viscosity symptoms
What is a common feature of heavy-chain disease as mentioned in the text?
Synthesis and secretion of free heavy-chain fragments
What characterizes primary or immunocyte-associated amyloidosis?
Deposition of light chains as amyloid
Which condition results from monoclonal proliferation of plasma cells secreting light chains?
Monoclonal gammopathy of undetermined significance
What is a defining characteristic of Monoclonal gammopathy of undetermined significance (MGUS)?
Patients without signs or symptoms but have M components in blood
What is the distinguishing feature of MGUS compared to other symptomatic plasma cell neoplasms?
Moderately large M components in blood without signs or symptoms
Which variant is very common in older adults and may transform to multiple myeloma or other symptomatic plasma cell neoplasms?
Monoclonal gammopathy of undetermined significance (MGUS)
Which cytokine is highlighted in the text as a crucial growth factor for plasma cells in multiple myeloma?
IL-6
What is a common genetic aberration associated with late-stage, highly aggressive forms of multiple myeloma?
Mutation in the TP53 gene
Which proto-oncogene is frequently involved in rearrangements associated with multiple myeloma?
MYC
What chromosome locus is mainly implicated in the genetic rearrangements seen in multiple myeloma?
14q32
Which signaling pathway mutations are commonly identified in deep sequencing of myeloma genomes?
NF-κB pathway
What is the peak age of incidence for multiple myeloma as stated in the text?
60-65 years
What is the predominant gender affected by multiple myeloma according to the text?
Men
Which specific gene rearrangement is NOT mentioned in association with late-stage, highly aggressive forms of multiple myeloma?
BCL2 rearrangement
What is a significant outcome linked to deletions of chromosome 17p involving the TP53 tumor suppressor locus?
Resistance to chemotherapy
What is the primary characteristic of bone lesions in multiple myeloma?
Punched-out defects
What is the main cellular component that replaces normal elements in the bone marrow of patients with multiple myeloma?
Plasma cells
Which feature is characteristic of malignant plasma cells in multiple myeloma?
Prominent Golgi apparatus
What type of plasma cell can predominate in multiple myeloma based on the text?
Plasmablasts
Which cytologic variant is a result of dysregulated synthesis and secretion of immunoglobulin in multiple myeloma?
Cells with cytoplasmic droplets containing fat
What type of cells predominantly make up the marrow in multiple myeloma?
(Plasma cells)
Which feature is commonly seen in plasma cells in multiple myeloma?
(Perinuclear clearing due to a prominent Golgi apparatus)
What type of inclusions can be found in cells affected by the dysregulated synthesis and secretion of immunoglobulin in multiple myeloma?
(Fibrils)
'Fiery red cytoplasm' is a characteristic of which type of cell seen in multiple myeloma?
(Plasma cells)
What is the major pathologic feature of multiple myeloma as described in the text?
Bone destruction
Which factor released from tumor cells is mentioned as a potent inhibitor of osteoblast function in multiple myeloma?
Wnt pathway modulators
Where are sharply punched-out bone lesions most obvious in multiple myeloma?
Calvaria
In multiple myeloma, what bones are most commonly affected in descending order of frequency?
Vertebral column, ribs, skull, pelvis
What is the primary presentation pattern of multiple myeloma tumors as described in the text?
Destructive plasma cell tumors
What characteristic differentiates lesions caused by multiple myeloma from normal bone tissue?
Formation of pathologic fractures
Which of the following is an important factor that appears to augment osteoclast formation in multiple myeloma?
(CCL3) Chemokine
What is the net effect of the factors released from tumor cells like modulators of the Wnt pathway on bone resorption in multiple myeloma?
Marked increase in bone resorption
What is one characteristic feature of multiple myeloma lesions that distinguishes them from normal bone tissue?
Pathologic fractures
What is a common characteristic of multiple myeloma?
Decreased production of normal Igs
What is a typical clinical feature of plasma cell tumors?
Formation in tissues other than bones
What is a consequence of hypercalcemia in multiple myeloma?
Renal dysfunction symptoms
Which cell marker is often expressed in plasma cell tumors?
CD56
What clinical manifestation can arise from tumor cells flooding the peripheral blood?
Central nervous system effects
What is a distinctive feature of plasma cell leukemia?
Presence of CD56 marker on cells
Which condition is associated with rouleaux formation?
Chronic lymphocytic leukemia
What adhesion molecule is CD138 also known as?
'Syndecan-1'
What is the single most important factor contributing to renal failure in patients?
Bence Jones proteinuria
Which type of light chains are prone to cause amyloidosis of the AL type?
16 and 13 families
What is the main purpose of serum protein electrophoresis (SP) in multiple myeloma screening?
To detect monoclonal immunoglobulin (M protein)
How is the suspected monoclonal immunoglobulin (Ig) confirmed and characterized?
By immunofixation
Which specific proteins are used to visualize the sharp band indicative of IgGк M protein in serum electrophoresis?
Antibodies specific for IgG heavy chain and kappa light chain
What characteristic feature distinguishes polytypic IgG bands in normal serum from monoclonal Ig bands in patients with multiple myeloma?
Broad bands versus single sharp band
How does immunofixation help in identifying monoclonal immunoglobulins in multiple myeloma?
By trapping proteins with specific antibodies
'Serum from a patient with multiple myeloma contains a single sharp protein band' - What method would be best used to confirm this finding?
'Immunofixation'
What is the most common monoclonal Ig found in multiple myeloma patients?
IgA
In about 20% of multiple myeloma patients, what is observed in terms of M proteins?
Presence of only free light chains
Which Ig subtype is usually associated with hyper-viscosity symptoms in multiple myeloma patients?
IgA
What percentage of patients with multiple myeloma have a nonsecretory form where no M proteins are observed?
1%
What is the typical range of serum Ig levels seen in most patients with myelomas?
>3 g/dL
Which type of IgM is rare in multiple myeloma cases?
$IgM^{+}$
In what percentage of multiple myeloma patients are both free light chains and a serum M protein observed together?
>75%
What percentage of multiple myelomas express IgG as the monoclonal Ig?
~55%
What is a key component of the clinicopathologic diagnosis of multiple myeloma?
Identification of clonal plasma cells in the marrow
Which criteria are used to confirm the diagnosis of multiple myeloma?
CRAB criteria
Which genetic translocation in multiple myeloma is associated with a more aggressive disease course?
Translocation t(4;14)
What organelle's inhibition is effective in treating myeloma cells?
Proteasome
What might trigger apoptosis in myeloma cells if not degraded by proteasomes?
Misfolded Ig heavy and light chains
What genetic translocation is associated with a good outcome in multiple myeloma?
Translocation t(4;14)
What is the median survival range for patients with multiple myeloma?
4 to 7 years
Which type of myeloma patients may be asymptomatic for many years?
Patients with 'smoldering Transloca-myeloma'
What is the primary outcome achieved over the past decade regarding multiple myeloma?
Improvement in outcomes with advances in therapy
What might happen if misfolded proteins in myeloma cells are not degraded by proteasomes?
They trigger apoptosis
What is the main consequence of high levels of M protein in the blood according to the text?
Impaired humoral immunity
What is the characteristic feature of plasma cell tumors that helps in identifying neoplastic cells?
Expression of CD138
What contributes to the clinical features of multiple myeloma related to the bones?
Pathologic fractures
Which factor can give rise to neurologic manifestations in multiple myeloma patients?
Hypercalcemia
In multiple myeloma, what contributes to the suppression of normal humoral immunity?
Excessive Igs production
What is a key feature of myeloma kidney, a renal disease associated with multiple myeloma?
Renal failure
Which molecule is CD138 also known as, playing a role in plasma cell tumor immunophenotype?
'Syndecan-1'
What does CD56 expression in plasma cell tumors help in identifying?
'Neoplastic cells'
What is the single most important factor contributing to renal failure in patients?
Presence of Bence Jones proteinuria
What percentage of patients with myelomas are associated with more than 3 g/dL of serum Ig?
99%
Which type of monoclonal Ig is the most common in patients with myelomas?
IgA
What percentage of patients with myelomas experience symptoms related to hyperviscosity?
7%
In how many patients are both free light chains and a serum M protein observed together?
50-60%
What is the most common subtype of M protein observed in myeloma patients experiencing hyper-viscosity symptoms?
IgA
What characteristic protein spikes are usually first detected in serum or urine electrophoresis in myeloma patients?
Globulins
What renal condition results from the toxic effect of excreted light chains on renal tubular epithelial cells in myeloma patients?
'Myeloma kidney'
What is the most common genetic feature associated with a good outcome in myeloma patients?
Translocations involving cyclin D1
Which of the following is NOT included in the CRAB criteria for diagnosing myeloma?
Thrombocytopenia
What is the median survival range for myeloma patients?
4 to 7 years
Which organelle is targeted by inhibitors due to its sensitivity in myeloma cells?
Proteasome
What characteristic distinguishes 'smoldering Translocation-myeloma' patients from those with multiple bony lesions?
Survival duration
Which genetic anomaly is associated with a more aggressive course in myeloma patients?
Deletion of 17p
What is the primary factor contributing to the improved outcomes seen in myeloma over the past decade?
Proteasome inhibitors
Which treatment approach triggers apoptosis in myeloma cells by preventing the degradation of misfolded proteins?
"Proteasome inhibitors"
What percentage of multiple myelomas are nonsecretory?
1%
Which diagnostic method is used to screen for a monoclonal immunoglobulin in multiple myeloma?
Serum protein electrophoresis
In multiple myeloma, what confirms and characterizes the suspected monoclonal Ig?
Immunofixation
What is the characteristic feature of the serum protein electrophoresis in a patient with multiple myeloma?
A broad band
How are suspected monoclonal Ig proteins visualized in immunofixation?
By trapping in gel with specific antibodies
What contributes to the 'sharp band' appearance in serum protein electrophoresis of a patient with multiple myeloma?
Cross-linking by specific antibodies
What is decreased in the serum of a patient with multiple myeloma relative to normal, according to the text?
Polyclonal IgG levels
Which syndrome is known to be caused by the secretion of monoclonal IgM in Waldenström macroglobulinemia?
Hyperviscosity syndrome
Which protein plays a role in signaling events activating NF-κB in lymphoplasmacytic lymphoma?
MYD88
What type of cells are typically present in the infiltrate found in the marrow of lymphoplasmacytic lymphoma?
Mast cells
What is a frequent location of tumor dissemination at the time of lymphoplasmacytic lymphoma diagnosis?
Spleen
Which type of inclusion bodies containing Ig are commonly seen in some plasma cells of lymphoplasmacytic lymphoma?
Dutcher bodies
What is one of the rare complications in Waldenström macroglobulinemia compared to multiple myeloma?
Bone destruction
Which condition is associated with acquired mutations in MYD88 in lymphoplasmacytic lymphoma?
Hodgkin lymphoma
What is a distinguishing feature of large lymphoid cells found in some tumors associated with Waldenström macroglobulinemia?
'Vesicular nuclear chromatin' and 'prominent nucleoli'
What is the approximate percentage of individuals older than 70 years of age who may have Monoclonal Gammopathy of Undetermined Significance (MGUS)?
5%
Which plasma cell disorder is characterized by patients being asymptomatic and having a serum M protein level less than 3 g/dL?
Monoclonal Gammopathy of Undetermined Significance (MGUS)
Which type of plasmacytoma is more likely to be cured by local resection?
Extramedullary plasmacytoma
What fraction of patients with Monoclonal Gammopathy of Undetermined Significance (MGUS) develop a symptomatic plasma cell neoplasm annually?
1%
Which condition almost inevitably progresses to multiple myeloma but can take a decade or longer to do so?
Solitary osseous plasmacytoma
'Clonal plasma cells in MGUS contain many of the same chromosomal translocations and deletions' found in which condition indicating an early stage of myeloma development?
Multiple myeloma
'Lymphoplasmacytic lymphoma is a B-cell neoplasm' that typically presents in which decade of life?
Sixth or seventh decade
'Solitary osseous plasmacytoma almost inevitably progresses to multiple myeloma' over a span of how many years?
10 to 20 years
What is a characteristic of cold agglutinins mentioned in the text?
They cause autoimmune hemolysis
What is the primary characteristic feature of bone marrow biopsy in lymphoplasmacytic lymphoma?
Mixture of small lymphoid cells with plasma cell differentiation
Which symptom is NOT a common presenting complaint in patients with lymphoplasmacytic lymphoma?
Fever
What is the role of CD20 in lymphoid cells as discussed in the text?
B-cell marker expression
What is a common feature found in patients with IgM-secreting tumors?
Autoimmune hemolysis caused by warm agglutinins
Which organ is LEAST likely to be affected in patients with lymphoplasmacytic lymphoma?
Kidneys
What is the mechanism by which lenalidomide affects myeloma growth?
Redirects and activates certain ubiquitin ligases
What is a distinguishing feature between smoldering myeloma and multiple myeloma?
75% of patients progress to multiple myeloma
Which drug class is known to reduce pathologic fractures and limit hypercalcemia in myeloma treatment?
Bisphosphonates
In what percentage of plasma cell neoplasms do solitary osseous plasmacytomas typically present?
3% to 5%
What is the characteristic of plasma cells in solitary osseous plasmacytomas when compared to multiple myeloma?
Solitary lesion of bone or soft tissue
Which cells make up 10% to 30% of the marrow cellularity in cases of smoldering myeloma?
Plasma cells
What is the primary effect of HSC transplantation in myeloma cases?
Prolonging life
What role do thalidomide and lenalidomide play in myeloma treatment?
Retard bone resorption through effects on stromal cells
What is one of the visual impairments associated with the hyperviscosity syndrome caused by high IgM concentrations?
Retinal hemorrhages
Which symptom can be alleviated by plasmapheresis in individuals with high IgM levels?
Hemolysis
What is a neurological problem associated with the hyperviscosity syndrome from high IgM concentrations?
Stupor
Which treatment approach is effective for controlling tumor growth in lymphoplasmacytic lymphoma?
Low doses of chemotherapeutic drugs and anti-CD20 antibody immunotherapy
What is a characteristic of lymphoplasmacytic lymphoma in response to BTK inhibitors?
Decreased tumor growth
What symptom can result from the formation of complexes between macroglobulins and clotting factors in hyperviscosity syndrome?
Raynaud phenomenon
What is a characteristic of transformation to large-cell lymphoma in lymphoplasmacytic lymphoma?
Rare event
What clinical feature is most commonly seen in plasma cell neoplasms?
Hyperviscosity due to high levels of tumor-derived IgM
Which translocation is frequently associated with multiple myeloma?
t(11;14)
What differentiates smoldering myeloma from multiple myeloma?
Absence of lytic bone lesions
Which neoplasm commonly progresses to multiple myeloma within 7 to 10 years?
Solitary osseous plasmacytoma
What is the characteristic feature of AL amyloidosis associated with multiple myeloma?
Amyloid deposits mainly composed of intact Ig light chains
Which neoplastic plasma cells secrete nephrotoxic antibodies in plasma cell neoplasms?
Dysregulated plasma cells
What distinguishes MGUS from multiple myeloma?
'CRAB' features (hypercalcemia, renal insufficiency, anemia, bone lesions)
What is a key morphological feature of Hodgkin lymphoma?
Presence of Reed-Sternberg cells
Which lymphoma type arises in a single node or chain of nodes and spreads contiguously?
Hodgkin lymphoma
What is the average age at diagnosis for Hodgkin lymphoma?
32 years
What distinguishes the spread pattern of Non-Hodgkin Lymphoma (NHL) from Hodgkin Lymphoma?
Noncontiguous spread
Which nodes are rarely involved in Hodgkin lymphoma?
Mesenteric nodes
In Hodgkin lymphoma, what is the primary source of neoplastic Reed-Sternberg cells?
Germinal center or post-germinal center B cells
What is a distinguishing histological feature of Hodgkin lymphoma?
'Tombstone' pattern
'Reactive lymphocytes, macrophages, and granulocytes typically make up greater than 90% of the tumor cellularity' describes which feature of Hodgkin lymphoma?
'Mixed cellularity' type
What is the primary source of formed elements in blood?
Bone marrow
What distinguishes Mantle Cell Lymphoma from other neoplasms?
Cytogenetic abnormality t(9;22)
What plays a significant role in the overexpression of the anti-apoptotic protein BCL2 in CLL/SLL?
MicroRNA downregulation
Which organ may marginal zone lymphomas arise within?
Stomach
What is one of the risks associated with radiation therapy and chemotherapy?
Secondary malignancies
Which signaling pathway mutations are commonly identified in deep sequencing of myeloma genomes?
PI3K/Akt/mTOR pathway mutations
What is one characteristic feature of multiple myeloma lesions that distinguishes them from normal bone tissue?
Lytic bone lesions
What is a common feature of hypoplastic states?
Leukopenia
What triggers rapid proliferation in newly committed progenitor cells?
Stimulation by erythropoietin
What are the factors produced by Reed-Sternberg cells that antagonize cytotoxic T-cell responses?
PD-L1 and PD-L2
Which of the following is not a characteristic of diagnostic Reed-Sternberg cells?
Small size (less than 20 μm in diameter)
What is a distinguishing feature of Lacunar cells seen in the nodular sclerosis subtype of Reed-Sternberg cells?
Nucleus sitting in an empty space (lacuna)
What is the average diameter of a diagnostic Reed-Sternberg cell's nucleus?
5 to 7 μm
Which type of Reed-Sternberg cell variant contains a single nucleus with a large inclusion-like nucleolus?
Mononuclear variants
What is a key morphological feature that helps in identifying Reed-Sternberg cells?
'Inclusion-like' nucleolus about the size of a small lymphocyte
Which subtype of Hodgkin lymphoma is associated with Lacunar cells?
'Nodular sclerosis' subtype
What is the primary factor responsible for inducing an ineffective host response by Reed-Sternberg cells?
'Cross-talk' with surrounding reactive cells
What is the peculiar form of cell death that Reed-Sternberg cells undergo known as in classic forms of Hodgkin lymphoma?
Mummification
Which variant of Hodgkin lymphoma is characterized by the presence of lacunar variant Reed-Sternberg cells and collagen deposition in bands that divide involved lymph nodes into circumscribed nodules?
Nodular Sclerosis Type Hodgkin Lymphoma
Which cell characteristic is characteristic of the lymphocyte predominance subtype of classic Hodgkin lymphoma?
Polypoid nuclei and prominent nucleoli
What is a key feature used for the identification of Reed-Sternberg cells in classic Hodgkin lymphoma?
Immunohistochemical profile
Which condition must be distinguished from Hodgkin lymphoma as it may show cells resembling Reed-Sternberg cells?
Infectious mononucleosis
What are the salient morphologic features present in Nodular Sclerosis Type Hodgkin Lymphoma?
"Lacunar" variant Reed-Sternberg cells
What is the primary diagnostic factor for identifying Hodgkin lymphoma?
"Neoplastic inflammatory cells"
Which variant of Hodgkin lymphoma constitutes 65% to 70% of cases?
"Nodular Sclerosis" type
What genetic mutation is particularly common in Reed-Sternberg cells and may contribute to increased NF-kB activity?
Copy number gains in the REL proto-oncogene on chromosome 2p
Which immune checkpoint proteins, when amplified due to copy number gains, inhibit antitumor T-cell responses in Hodgkin lymphoma?
PD-L1 and PD-L2
In Hodgkin lymphoma, what factors secreted by Reed-Sternberg cells attract reactive cells to tissues involved by the tumor?
Eotaxin and Vascular Endothelial Growth Factor (VEGF)
Which ligands activate CD30 and CD40 receptors on Reed-Sternberg cells, leading to up-regulation of NF-κB?
PD-L1 and PD-L2
What is the impact of copy number gains in genes encoding PD-L1 and PD-L2 on antitumor T-cell responses?
Inhibit antitumor T-cell responses
Which feature contributes to the remarkable metamorphosis of B cells into Reed-Sternberg cells in individuals with infectious mononucleosis?
Presence of EBV-encoded proteins
What type of clonal chromosomal aberrations are present in Reed-Sternberg cells?
'Aneuploidy' with diverse clonal chromosomal aberrations
'Florid accumulation of reactive cells' in classic Hodgkin lymphoma is primarily in response to which factor secreted by Reed-Sternberg cells?
'Monocyte Chemoattractant Protein-1' (MCP-1)
What is the proposed mechanism by which activation of NF-κB rescues 'crippled' germinal center B cells in classic Hodgkin lymphoma?
Up-regulation of unknown mutations
What is the role of latent membrane protein-1 (LMP-1) in the activation of NF-κB in classic Hodgkin lymphoma?
Transmits signals that up-regulate NF-κB
Which negative regulators of NF-κB are often mutated leading to its activation in EBV- tumors associated with classic Hodgkin lymphoma?
IкB and TNF-a-induced protein 3
What is the main function of activated NF-κB in classic Hodgkin lymphoma?
Promoting the growth and survival of Reed-Sternberg cells
What is the proposed role of NF-κB in preventing apoptosis in 'crippled' germinal center B cells?
Rescuing cells from apoptosis
Which cell surface protein expressed by EBV+ tumor cells transmits signals that lead to NF-κB up-regulation in classic Hodgkin lymphoma?
CD30
Which genetic factor is believed to be responsible for reprogramming gene expression in classic Hodgkin lymphoma?
'Unknown' widespread epigenetic changes
What is the primary reason for the failure of classic Hodgkin lymphoma Reed-Sternberg cells to express most B-cell-specific genes?
'Crippling' effects on germinal center B cells
What is the immunophenotype of Reed-Sternberg cells in classic Hodgkin lymphoma subtypes?
Positive for PAX5, CD15, and CD30; negative for other B-cell markers, T-cell markers, and CD45
What is the characteristic of Reed-Sternberg cells in the mixed-cellularity type of Hodgkin lymphoma?
Plentiful diagnostic Reed-Sternberg cells
Which type of Hodgkin lymphoma has a propensity to involve lower cervical, supraclavicular, and mediastinal lymph nodes of adolescents or young adults?
Nodular sclerosis type
What is the percentage of cases of mixed-cellularity type Hodgkin lymphoma that Reed-Sternberg cells are infected with EBV?
70%
Which of the following is true about the prognosis of nodular sclerosis type Hodgkin lymphoma?
Prognosis is excellent
In nodular sclerosis type Hodgkin lymphoma, which lymph nodes have a propensity to be involved?
Mediastinal and lower cervical lymph nodes
Which marker is NOT positive in Reed-Sternberg cells of classic Hodgkin lymphoma subtypes?
CD45
What is the characteristic infiltrate in involved lymph nodes in the mixed-cellularity type of Hodgkin lymphoma?
Eosinophils, plasma cells, and macrophages admixed with Reed-Sternberg cells
What is the term that describes the artifact created by the disruption of cytoplasm during chromatin in Reed-Sternberg cells?
Open space
Which of the following is characteristic of nodular sclerosis type Hodgkin lymphoma based on the provided text?
Fibrous bands dividing cellular areas into nodules
What is the main feature that distinguishes multiple myeloma lesions from normal bone tissue?
Suppression of normal humoral immunity
Which type of genetic disorder is associated with an increased incidence of childhood leukemia?
Chromosomal translocation creating ALK fusion proteins
What is the primary role of immunotherapy in chronic lymphocytic leukemia (CLL) according to the text?
Augmenting signals produced by the Ig receptor
In mantle cell lymphoma, which immunophenotype is inconsistent with CLL/SLL?
Abundant cytoplasm
Which characteristic feature of the RS cells is most commonly observed in Classic Hodgkin Lymphoma?
Presence of CD15+
In Burkitt Lymphoma, which variant has a paucity of background reactive cells?
Reticular variant
Which clinical feature is characteristic of the subtype of Burkitt Lymphoma that is more common in older adults?
Tends to be associated with advanced disease
What is a common site of lymphadenopathy in the uncommon subtype of Burkitt Lymphoma that occurs in young males?
Cervical
Which cellular type is prominently present in the background infiltrate of Classic Hodgkin Lymphoma?
Eosinophils
What is a distinguishing feature of the RS cells in the uncommon subtype of Burkitt Lymphoma found in older men and HIV-infected individuals?
CD15- and CD30-
Which type of Hodgkin lymphoma is characterized by the presence of 'popcorn cells'?
Nodular Lymphocyte Predominance Type
Which surface markers are typically expressed by the L&H variants in Hodgkin lymphoma?
CD20 and BCL6
What percentage of cases of Hodgkin lymphoma transform into a tumor resembling diffuse large B-cell lymphoma?
3% to 5%
Which subtype of Hodgkin lymphoma is commonly associated with EBV infection?
Mixed Cellularity Type
What is the defining characteristic of Lymphocyte-Rich Type of Hodgkin lymphoma?
Diffuse effacement by reactive lymphocytes
Which type of cells are usually scant or absent in the 'nondas cells' subtype of Hodgkin lymphoma?
Eosinophils
What type of mutation marks the L&H variants as transformed germinal center B cells in Hodgkin lymphoma?
Somatic hypermutation in IGH genes
Which Hodgkin lymphoma subtype is characterized by a diffuse effacement but sometimes shows vague nodularity?
'Lymphocyte-Rich' subtype
What is a distinguishing feature of the lymphocyte depletion type of Hodgkin lymphoma?
Paucity of lymphocytes and abundant Reed-Sternberg cells
What is the characteristic feature of lymphocyte depletion Hodgkin lymphoma?
Advanced stage and poor prognosis
What characterizes the classic subtypes of Hodgkin lymphoma in terms of prognosis?
Excellent prognosis
What is a distinguishing feature of Hodgkin lymphoma, mixed-cellularity type?
Contains a binucleate Reed-Sternberg cell
In what percentage of cases is Hodgkin lymphoma associated with EBV?
Approximately 40%
Which characteristic is associated with Hodgkin lymphoma, nodular sclerosis type?
Distinct bands of acellular collagen dividing the tumor
In which scenario does lymphocyte predominance Hodgkin lymphoma commonly occur?
Preferentially in young adults
Which age group is most likely to be affected by the lymphocyte depletion type of Hodgkin lymphoma?
Males usually younger than 35 years of age
What distinguishes large-cell NHLs infected with EBV from other subtypes?
High prevalence of EBV infection
Which is a common demographic that predominantly experiences lymphocyte depletion Hodgkin lymphoma?
Elderly individuals
Which cellular receptor is targeted by hepatocyte growth factor (HGF)?
C-MET
Which molecule is responsible for the suppression of Th1 and cytotoxic T-cell responses in Hodgkin lymphoma?
IL-10
What is the primary ligand for CD30 in the context of Hodgkin lymphoma?
CD30L
Which factor is responsible for enhancing the Treg response in Hodgkin lymphoma?
IL-5
Which molecule plays a role in promoting tissue eosinophilia in Hodgkin lymphoma?
Eotaxin
Which chemokine is associated with enhanced Th2 responses in Hodgkin lymphoma?
bFGF
Which cytokine receptor is linked to the activation-induced crosstalk between Reed-Sternberg cells and normal cells?
IL-13R
What is a potential long-term benefit of using immune checkpoint inhibitors for patients with classic Hodgkin lymphoma?
Decreased incidence of secondary tumors
In Hodgkin and Non-Hodgkin Lymphomas, which stage involves diffuse involvement of one or more extralymphatic organs or sites without lymphatic involvement?
Stage IV
What characteristic symptoms help further divide all stages of Hodgkin and Non-Hodgkin Lymphomas?
Unexplained fever and night sweats
For patients with classic Hodgkin lymphoma who fail conventional therapy, what type of inhibitors have proven to be highly effective?
PD-1 inhibitors
What is the primary purpose of current treatment regimens for Hodgkin and Non-Hodgkin Lymphomas?
Minimize the use of radiotherapy and genotoxic chemotherapeutic agents
What is the most important prognostic variable in current treatment protocols for lymphoma?
Stage of the tumor
What is the cure rate for patients with stages I and IIA of lymphoma?
90%
What is the disease-free survival rate at 5 years for patients with advanced lymphoma (stages IVA and IVB)?
60% to 70%
What was a recognized consequence for long-term survivors of localized Hodgkin lymphoma treated with radiotherapy?
All of the above
What were the significant adverse outcomes observed in long-term survivors treated with radiotherapy for Hodgkin lymphoma?
Elevated likelihood of secondary malignancies like lung cancer and melanoma
What is a distinguishing feature of Hodgkin lymphoma based on the text?
Presence of Reed-Sternberg cells
Which genetic abnormality is specifically associated with Burkitt lymphoma according to the text?
MYC translocations
What is a key feature that distinguishes nodular lymphocyte predominant Hodgkin lymphoma from classic Hodgkin lymphoma?
Presence of Reed-Sternberg cells
Which cancer hallmark is exemplified by BCL2 translocations in the context of Follicular lymphoma?
Evading growth suppressors
What is the primary characteristic genetic feature of mantle cell lymphoma according to the provided information?
Cyclin D1 translocations
Which key cancer hallmark is associated with ALL based on the text?
Deregulating cellular energetics
What major feature distinguishes mantle cell lymphoma from Burkitt lymphoma?
Expression of CDKN2A loss
What is the primary function of immune checkpoint inhibitors in treating classic Hodgkin lymphoma?
Stimulate host immune response
What distinguishes the EBV Lymphocyte predominance type from classic Hodgkin lymphoma?
Expression of B-cell markers
Which factor influences the host response in classic Hodgkin lymphoma?
Chemokines
What is the impact of Marginal zone lymphoma on antigen-dependency?
Reduces antigen stimulation
Which characteristic is not associated with EBV Lymphocyte predominance type?
Association with EBV
What makes classic forms of Hodgkin lymphoma frequently associated with acquired mutations?
NF-κB activation
What is the mechanism by which immune checkpoint inhibitors affect Reed-Sternberg cells in classic Hodgkin lymphoma?
Block PD-L1 and PD-L2 activity
Which gene dysregulation in Burkitt lymphoma leads to Warburg metabolism and rapid cell growth?
MYC
What gene amplification in Hodgkin lymphoma leads to evasion of host immunity?
PD-1 ligand
What is the common feature of neoplasms originating from hematopoietic progenitor cells?
Origin from hematopoietic progenitor cells
Which alteration leads to resistance to apoptosis in follicular lymphoma?
Dysregulation of BCL2
What mutations are linked to loss of cell cycle control in mantle cell lymphoma and acute lymphoblastic leukemia?
Mutations in transcription factors
What is the target of antibodies used in Hodgkin lymphoma therapy?
PD-1 ligand
What is a distinguishing factor between lymphoid and myeloid neoplasms mentioned in the text?
'Hematopoietic progenitor cell' origin in lymphoid neoplasms
'Leukemia stem cell' self-renewal enhancement is associated with mutations in which neoplasm mentioned in the text?
ALL
What therapeutic strategy is used for antagonizing BCL2 in follicular lymphoma and other B-cell tumors?
Antibodies
What is the primary impact of the genetic aberrations associated with some forms of AML?
Improving prognosis
What characterizes AMLs lacking specific genetic features according to the text?
Being grouped based on degree of differentiation and lineage of leukemic blasts
What is the likely direction of the classification of AML, according to the text?
A shift towards genetic classification
How do AMLs arising from myelodysplastic syndrome (MDS) respond to therapy?
They respond poorly
What symptoms are often seen in individuals with AML arising from secondary hematopoietic organs?
Symptoms related to altered hematopoiesis
What is the role of cytogenetic and molecular features in AML therapy according to the text?
Primary role in directing therapy
How do AMLs in the 'wastebasket' category get classified?
Based on absence of specific genetic features
What is the main characteristic feature of myeloproliferative neoplasms?
Increased production of one or more types of blood cells
Which component of normal hematopoiesis is crucial for understanding the pathogenesis of myeloid neoplasms?
HSCs
What is the main cause of myelodysplastic syndromes according to the text?
Defective maturation of myeloid progenitors
In the context of normal hematopoiesis, what is responsible for modulating the production of blood cells by the marrow?
Cytokines and growth factors
What distinguishes myeloid neoplasms from normal hematopoiesis?
Accumulation of immature myeloid forms
Which aspect is crucial for understanding the pathogenesis of myeloid neoplasms?
Normal hematopoiesis hierarchy
What role do homeostatic feedback mechanisms play in normal hematopoiesis?
Fine-tune marrow output
What is the primary genetic alteration associated with acute promyelocytic leukemia?
t(15;17)
Which gene fusion is responsible for creating a chimeric protein in acute promyelocytic leukemia?
RAR and PML
What is the main function of the RUNX1/CBFB transcription factor in normal hematopoiesis?
Promoting cellular differentiation
Which chromosomal rearrangement leads to the disruption of the CBFB gene?
inv(16)
What is the distinctive feature of AML associated with the t(8;21) chromosomal rearrangement?
Creation of a chimeric gene
What type of mutations interfere with normal myeloid differentiation in AML?
RUNX1 mutations
Which hematopoietic neoplasms are most commonly associated with driver mutations in older adults with clonal hematopoiesis?
Myelodysplastic syndromes
What is the main reason for the sometimes blurred divisions between myeloid neoplasms according to the text?
Transformed hematopoietic progenitors
What is a common characteristic of myelodysplastic syndromes and myeloproliferative neoplasms based on the information provided?
Evolution to more aggressive forms of disease
In chronic myeloid leukemia, what transformation is also observed, indicating its origin from a transformed pluripotent HSC?
Transformation to acute lymphoblastic leukemia
Which functional categories do driver mutations in AML tend to fall into according to the text?
Transformed hematopoietic progenitors
What effect do transforming events have on differentiation based on the information provided?
All of the above
What is a common outcome for both myelodysplastic syndromes and myeloproliferative neoplasms according to the text?
'Transformation' to more aggressive forms
What is the significance of understanding divisions between myeloid neoplasms according to the text?
To guide treatment decisions
What effect can be overcome by treatment with all-trans-retinoic acid and arsenic trioxide in the context discussed?
Granulocyte terminal differentiation interference
Which mutation is frequently associated with AML cases that also harbor the t(15;17) chromosomal translocation?
FLT3
What type of mutations may lead to abnormal DNA methylation patterns or involve proteins regulating chromatin organization?
Epigenetic mutations
Which feature distinguishes the leukemogenic potential of PML-RARO alone from the combination of PML-RARO and activated FLT3 in mice?
Increased cellular proliferation
What genetic characteristic is commonly seen in AML cases involving an accumulation of immature myeloid blasts?
Constitutive activation of pro-growth/survival pathways
Which mutations are commonly found in subsets of AML cases besides those with the t(15;17) chromosomal translocation?
FLT3 and RAS
What is a common consequence of marrow replacement by blasts in AML cases?
Anemia
What is the primary characteristic of AML with myelomonocytic maturation?
Presence of monoblasts in the blood
Which subtype of AML is defined by >80% erythroid precursors without myeloblasts?
Intermediate AML with erythroid maturation
Which cell lineage predominates in AML with megakaryocytic maturation?
Megakaryocytes
What type of markers are detected in the most common AML in Down syndrome?
Megakaryocyte-specific markers
What contributes to the development of AML according to the provided text?
Chromosomal translocations
Which condition is often associated with marrow AML and DIC?
MDS
What leads to alterations in gene expression contributing to the acquisition of cancer hallmarks in AML?
Epigenomic disturbances
Which gene mutation is mentioned in the provided text as being associated with AML?
TP53
Which type of AML is associated with the RUNX1-RUNX1T1 fusion gene?
AML with t(8;21)(q22:q22); RUNX1-RUNX1T1 fusion gene
Which feature distinguishes AML with multilineage dysplasia from other types of AML?
Abnormal myelocytic and monocytic differentiation
What is a characteristic feature of AML associated with t(11q23,v) and diverse KMT2A fusion genes?
High incidence of DIC
What distinguishes AML with maturing cells typical of MDS from other types of AML?
Presence of dysplastic features typical of MDS
Which genetic aberration is commonly associated with AML following alkylator or radiation therapy, leading to a latency period?
Translocations involving KMT2A
What is a key characteristic feature of AML classified as having 'MDS-Like Features'?
Presence of diagnostic Auer rods in immature granulocytes
What distinguishes AML with normal cytogenetics and mutated NPM1 from other types of AML?
'Full range of myelocytic maturation' with easily found Auer rods
'Myelocytic and monocytic differentiation; abnormal eosinophilic precursors with abnormal basophilic granules' is a characteristic feature of which subtype of AML?
'Maturing cells' typical of MDS detected by DNA sequencing
'Usually some degree of monocytic differentiation' is a characteristic feature associated with which subtype of AML?
'Myelocytic and monocytic differentiation; abnormal eosinophilic precursors with abnormal basophilic granules'
What distinctive clinicopathologic features are associated with AMLs having mutations impairing p53 function?
Resistance to standard therapies
In the diagnosis of AML, the presence of at least how many myeloid blasts in the bone marrow is required?
At least 20%
What is a distinguishing feature of monoblasts in AML compared to myeloblasts?
Folded or lobulated nuclei
Which type of differentiation in AML is often accompanied by marrow fibrosis?
Megakaryocytic differentiation
What distinguishes acute promyelocytic leukemia (AML with t(15;17)) from other types of AML?
Distinctive needle-like azurophilic granules (Auer rods)
What is a common range for the number of leukemic cells in the blood in patients with AML?
Over 100,000/mm³
Which cytogenetic aberration is associated with AML following etoposide therapy?
11q23-
What is a defining characteristic of AML with megakaryocytic maturation?
Detection with antibodies against fibrosis
Which AML subtype is defined by >50% dysplastic maturing erythroid precursors and >20% myeloblasts?
AML with erythroid maturation
What is the common presenting site for an unusual B-cell lymphoma associated with a malignant effusion?
Pleural cavity
Which AML subtype is typically associated with Down syndrome?
AML with monocytic maturation
What is the latency period typically seen after alkylator therapy or radiation therapy for MDS-like etoposide treatment?
8-10 years
What distinguishes AML with monocytic maturation from other subtypes?
>3% blasts positive for myeloperoxidase
'Maturing cells with dysplastic features typical of MDS' are typically found in which type of AML?
Intermediate AML without maturation
What distinctive clinicopathologic features are associated with AMLs that have mutations impairing p53 function?
Marked dysplasia and resistance to standard therapies
What is the key morphological feature that distinguishes monoblasts from myeloblasts in AML?
Folded or lobulated nuclei
In AML, what cellular feature is often observed with megakaryocytic differentiation and leads to marrow fibrosis?
Release of fibrogenic cytokines
What is a distinguishing feature of AML with t(15;17) compared to other types of AML?
Numerous Auer rods
What is a common characteristic of myeloid blasts in AML compared to lymphoblasts?
Larger cytoplasm
What is the morphological feature that distinguishes myeloid blasts from lymphoblasts in AML?
Delicate nuclear chromatin
In AML, what is a common feature of blasts associated with megakaryocytic differentiation?
Marrow fibrosis due to cytokines
What is the purpose of the Wing formula in correcting the reticulocyte count?
To account for anemia severity
In the World Health Organization Classification, which AML subtype is associated with a poor prognosis?
AML with t(15;17)(q22;11-12); RARA/PML fusion gene
Which AML subtype classifies as having favorable prognosis based on the World Health Organization Classification?
AML with inv(16)(p13;q22); CBFB/MYH!!fusion gene
What is a distinguishing feature of AML With MDS-Like Features in the World Health Organization Classification?
Abnormal eosinophilic precursors
Which subtype of AML listed in the classification shows abnormal granules and monocytic differentiation?
AML with t(15;17)(q22;11-12); RARA/PML fusion gene
What cytogenetic aberration is associated with AML With MDS-Like Features according to the World Health Organization Classification?
With prior MDS Poor AML with multilineage dysplasia
What kind of differentiation does AML With Genetic Aberrations typically exhibit in terms of myelocytic maturation?
Full range of myelocytic maturation
'Abnormal eosinophilic precursors with abnormal basophilic granules' are characteristic of which AML subtype?
'AML with t(15;17)(q22;11-12); RARA/PML fusion gene'
Why is a bone marrow examination essential for pancytopenic patients according to the text?
To exclude acute leukemia
How is the diagnosis of Acute Myeloid Leukemia (AML) confirmed?
By testing for myeloid-specific antigens
What is the marker of multipotent stem cells shown in the analysis mentioned in the text?
CD34
What is a characteristic feature used to differentiate myeloblasts and lymphoblasts in AML diagnosis?
Immunophenotype
What's the primary method used to confirm the diagnosis of AML?
Flow cytometry analysis
What do stains for myeloid-specific antigens assist in identifying?
Myeloblasts
In AML diagnosis, what is used to characterize immature myeloid maturation?
$CD34$ staining
'Aleukemic leukemia' refers to a condition where:
No leukemia cells are present in the blood
What is a common clinical manifestation seen in patients with thrombocytopenia?
Abnormal bleeding
In AML, what exacerbates the bleeding tendency?
Procoagulants and fibrinolytic factors released by leukemic cells
Which opportunistic organisms are mentioned to cause infections in AML patients?
Fungi, Pseudomonas, and commensals
What is the role of cytogenetic analysis in diagnosing AML?
Identifying specific chromosomal abnormalities
Which chromosomal abnormality is commonly associated with AML arising de novo in younger adults?
inv(16)
What is a characteristic feature of AML with t(15;17)?
Presence of promonocytes
Which type of cells are commonly detected in peripheral smear examination of patients with AML?
Monoblasts
What do cutaneous petechiae, ecchymoses, and mucosal hemorrhages indicate in AML patients?
Thrombocytopenia
What marker is expressed by neoplastic promyelocytes in Acute Promyelocytic Leukemia, as shown in Figure 13.31?
CD33
In Acute Myeloid Leukemia without maturation, what is a distinguishing feature of myeloblasts?
Delicate nuclear chromatin
Which factor helps differentiate myeloid blasts from mature myeloid cells in the context of acute myeloid leukemia?
Expression of CD64
What molecular abnormality characterizes Acute Promyelocytic Leukemia based on the provided information?
t(15:17) translocation
Which subtype of AML is characterized by abnormally coarse and numerous azurophilic granules in neoplastic promyelocytes?
M3
What is a distinguishing feature of AML with monocytic differentiation?
Expression of CD15
Which marker is NOT expressed by myeloid blasts in Acute Myeloid Leukemia without maturation?
CD64
In the context of AML subtypes, what is a key indicator of the FAB M5b subtype?
'monocytic differentiation'
What is the exception to the rule of AML involving deletions or monosomies in chromosomes 5 and 7?
Translocations involving the KTM2A gene on chromosome 11q23
What is a common feature associated with AML in older adults?
Deletions in chromosomes 5q and 7q
What is a distinguishing clinical presentation of AML from ALL in terms of tissue involvement?
Leukemia cutis and gingival infiltration
Which gene is involved in translocations associated with AML occurring after topoisomerase II inhibitors treatment?
KTM2A on chromosome 11q23
What is more commonly observed in AML in older adults compared to younger patients?
Deletions of chromosomes 5q and 7q
What is a unique feature of AML cases associated with the t(8;21) chromosomal rearrangement?
'Good' chromosomal aberrations
Which chromosomal abnormalities are more likely to be seen in AML occurring after topoisomerase II inhibitors treatment?
'Good' translocations involving KTM2A gene
What distinguishes AML in older adults from younger patients regarding karyotypic abnormalities?
'Bad' aberrations like del(17p)
'Leukemia cutis' and 'gingival infiltration' are clinical signs more commonly associated with which type of leukemia?
Acute Myeloid Leukemia (AML)
What is the primary cause of the severe pathophysiology seen in HbSS compared to HbSC and H&S diseases?
Enhanced tendency for polymerization
Which molecular subtype of AML has the best prognosis with targeted therapy using all-trans-retinoic acid and arsenic salts?
t(15;17)
What is the inevitable progression of a localized soft tissue mass known as myeloblastoma, myeloid sarcoma, or chloroma without systemic treatment?
Progression to full-blown AML
In HbC disease, what substitution occurs in red cells that contributes to the pathophysiology?
Lysine for glutamate
Which age group has a much worse prognosis in AML, partly due to the rarity of 'good' genetic subtypes in this setting?
Over 60 years
What distinguishes the prognostic outcome among different molecular subtypes of AML?
'Good' genetic subtypes
Which mutation is often associated with poor prognosis in AML patients who develop the disease following genotoxic therapy?
TP53 mutations
'Hemoglobin haves reshaped into a sickling disorder' refers to which pathophysiological phenomenon?
'Sickling crisis'
Which functional category of affected proteins in MDS involves factors that regulate DNA methylation, histone modifications, and chromatin looping?
Epigenetic factors
Which subset of tumors associated with MDS has mutations involving components of the 3' end of the RNA processing machinery?
RNA splicing factors
Which major functional category of affected proteins in MDS includes mutations affecting transcription factors required for normal myelopoiesis?
Transcription factors
What is a common characteristic shared by classic chromosomal rearrangements seen in de novo AML and the dysregulation of the epigenome in MDS?
Deranged differentiation
Which feature characterizes MDS regarding AML and their shared driver mutations?
Evolution to AML
What remains undetermined regarding mutations involving RNA splicing factors and their contribution to MDS development?
Precise mechanism of contribution
Which mutations in MDS contribute to deranged differentiation and may resemble those observed in classic chromosomal rearrangements seen in de novo AML?
Epigenetic factors dysregulation
What primary similarity exists between driver mutations associated with MDS and AML?
'Driver gene' overlap
What is a potential explanation provided in the text for how aneuploidy contributes to myelodysplastic syndromes?
Aneuploidy alters gene dosage, providing growth advantages to cells in MDS
Which genetic alteration, common in MDS, is associated with a complex karyotype and poor clinical outcomes similar to AML?
Loss-of-function mutations in TP53
What is one proposed way through which cells gain a growth advantage in MDS according to the text?
Altered gene dosage from aneuploidy
Which chromosomal aberration is specifically mentioned to contribute to ineffective erythropoiesis in MDS?
Deletion of chromosome 5q
What hallmark characteristic does loss of one copy of RPS14 produce, according to experimental systems mentioned in the text?
Ineffective erythropoiesis
In what state do cells frequently arise from before developing into myelodysplastic syndromes (MDS), as mentioned in the text?
Clonal hematopoiesis of indeterminate potential (CHIP)
What is the characteristic feature of patients with myelodysplastic syndrome (MDS) that distinguishes them from others?
Peripheral blood cytopenias
What is one of the risk factors that can lead to development of therapy-related myelodysplastic syndrome (t-MDS)?
Radiation therapy
Which treatment approach is effective for patients with IDH-mutated AML?
HSC transplantation
What is the term used to describe the group of clonal stem cell disorders characterized by maturation defects and high risk of transformation to AML?
Myelodysplastic Syndrome
What is the primary diagnostic challenge in identifying Myelodysplastic Syndrome (MDS)?
Laboratory test correlation requirement
What is a potential cause of MDS-associated inflammation, as mentioned in the text?
Activation of the inflammasome in neoplastic myeloid cells
Which characteristic finding is commonly observed within the erythroid series in MDS patients?
Ring sideroblasts with iron-laden mitochondria
What is a characteristic nuclear abnormality seen in MDS erythroblasts?
Polyploid nuclei with misshapen outlines
What is a common feature found in neutrophils of MDS patients?
Presence of Döhle bodies
Which term describes the characteristic morphology of MDS bone marrow at diagnosis?
Hypercellular
In MDS, what does the presence of megaloblastoid maturation in erythroid cells resemble?
Folate deficiency
Which cytologic abnormality is typically found in the neutrophils of MDS patients?
Pelger-Huët anomaly
What is a distinct morphological feature observed in neutrophils in patients with pseudo-Pelger-Hüet anomaly?
Two nuclear lobes
Which of the following cells can be found with single nuclear lobes or multiple separate nuclei in myelodysplastic syndromes?
Megakaryocytes
In myelodysplastic syndromes, what is the typical percentage of myeloid blasts in the overall marrow cellularity?
20%
Which type of cells are commonly seen in the blood of patients with myelodysplastic syndromes?
Giant platelets
What is a common cause of death in patients with myelodysplastic syndromes?
Bleeding due to thrombocytopenia
In therapy-related myelodysplastic syndromes, how quickly does progression to AML often occur after diagnosis?
Within 2 to 3 months
What is the median survival of patients with t-MDS (therapy-related MDS)?
4 to 8 months
'Pawn ball megakaryocytes' are characteristic of which condition?
'Therapy-Related Myelodysplastic Syndromes'
What treatment option holds promise for reconstituting normal hematopoiesis in younger patients with MDS?
Allogeneic HSC transplantation
Which characteristic is correlated with a hematologic response to thalidomide-like drugs in MDS patients?
Isolated 5q deletion
What type of deletion is associated with an unpredictable response to DNA methylation inhibitors in MDS?
Isolated 17p deletion
What is the mean age of onset for primary MDS?
70 years
How many categories is primary MDS divided into based on morphologic and cytogenetic features in the WHO classification?
Six
In primary MDS, what predicts worse outcomes in the developed prognostic scoring systems?
Higher blast counts and severe cytopenias
What is the common pathogenic feature in myeloproliferative neoplasms?
Mutated JAK2 kinase gene
How many categories does the WHO classification divide primary MDS into based on morphologic and cytogenetic features?
Six
What feature distinguishes the effectiveness of hematopoiesis and peripheral blood counts among MDS patients when treated with Thalidomide-like drugs and DNA methylation inhibitors?
The type of chromosomal abnormalities present
Which condition is most commonly associated with microangiopathic hemolytic anemia?
Thrombotic thrombocytopenic purpura (TTP)
What is the common pathogenic feature shared among disorders like malignant hypertension, hemolytic-uremic syndrome (HUS), and disseminated cancer?
Deposition of fibrin and glas in luminal narrowing
Which factor contributes to the mechanical shear stresses observed in microangiopathic hemolytic anemia?
Vascular changes producing shear stresses
Which feature is characteristic of nucleated red cell progenitors in myelodysplasia?
Multiple nuclei
What is the iron-laden structure seen as blue perinuclear granules in erythroid progenitors?
Mitochondria with iron deposits
Which tyrosine kinase mutation is associated with a high frequency of neutrophils and basophils in myeloproliferative neoplasms?
JAK2 mutations
What is the main consequence of constitutive ABL kinase activation due to the BCR-ABL fusion gene?
Scattered cytoplasm in reticulocytes
Which mutation leads to constitutive MPL kinase activation in myeloproliferative neoplasms?
MPL mutations
What is the characteristic of the BCR-ABL fusion gene?
Encodes a protein that activates multiple genes independently
In which myeloproliferative neoplasm is systemic mastocytosis commonly found?
Primary myelofibrosis
What is the primary consequence of CALR mutations in myeloproliferative neoplasms?
Constitutive JAK2 kinase activation
Which fusion gene is NOT typically associated with myeloproliferative neoplasms?
Various fusion genes involving FGFRI
What type of acquired aberrations in signaling pathways lead to growth factor independence in myeloproliferative neoplasms?
Activation of tyrosine kinases
What distinguishes Chronic Myeloid Leukemia from other myeloproliferative neoplasms?
Synthesis of a constitutively active BCR-ABL tyrosine kinase
What has increased the importance of molecular tests for tyrosine kinase mutations in myeloproliferative neoplasms?
Availability of kinase inhibitors
What is the primary origin of most myeloproliferative neoplasms?
Multipotent stem cells
Which neoplasm is associated with mutations in the KIT tyrosine kinase?
Systemic mastocytosis
What is the most common consequence of tyrosine kinase mutations in myeloproliferative neoplasms?
Increase in mature blood elements
What is a distinguishing feature of certain myeloproliferative neoplasms?
Association with activating mutations in specific tyrosine kinases
In which cell population do most myeloproliferative neoplasms originate?
Multipotent myeloid progenitors
What is the role of tyrosine kinase mutations in myeloproliferative neoplasms?
Selection of therapy
What is a key characteristic of tyrosine kinase mutations in myeloproliferative neoplasms?
Enhancement of cell proliferation
What distinguishes the effect of mutated tyrosine kinases in myeloproliferative neoplasms from normal signaling pathways?
Growth factor independence
What distinguishes Systemic mastocytosis from other neoplasms?
Associated mutations in the KIT tyrosine kinase
What is the distinguishing factor between CML and other myeloproliferative neoplasms at the molecular level?
'Chimeric BCR-ABL' gene presence
Which signaling component is primarily targeted by the mutated tyrosine kinases in myeloproliferative neoplasms?
Tyrosine kinases
What type of hematopoietic growth factors act on normal progenitors by activating tyrosine kinases to promote growth and survival?
Multiple types of hematopoietic growth factors
What is the primary method used to detect BCR-ABL fusion gene in cases where cytogenetically complex or cryptic rearrangements occur?
Fluorescence in situ hybridization
What domain in the BCR moiety of BCR-ABL facilitates self-association and activation of the ABL tyrosine kinase moiety?
Dimerization domain
Which signaling pathways are turned on by abnormal release of immature granulocytic and megakaryocytic forms from the marrow into the blood in response to BCR-ABL activation?
RAS and JAK/STAT pathways
What cellular characteristic is observed due to the markedly hypercellular marrow in response to BCR-ABL activation?
Increased numbers of maturing granulocytic precursors
Which protein domain in the BCR moiety of BCR-ABL is responsible for creating dimers and subsequently activating the ABL tyrosine kinase moiety?
SH3 domain
What type of translocation leads to the creation of BCR-ABL in most cases?
(9:22) translocation
Which hematopoietic cell type serves as the cell of origin for BCR-ABL?
Hematopoietic stem cell
What does the ABL tyrosine kinase moiety phosphorylate in response to dimerization and autophosphorylation caused by BCR-ABL activation?
Proteins inducing signaling through growth factor pathways
What is the primary consequence of the chimeric BCR-ABL fusion gene mentioned in chronic myeloid leukemia?
Growth factor-dependent proliferation of white blood cells
What is the main role of the BCR-ABL fusion protein in chronic myeloid leukemia?
Activating multiple downstream pathways for cell survival
How does the BCR-ABL fusion gene affect the differentiation of bone marrow progenitors in chronic myeloid leukemia?
Prevents differentiation into mature elements
What drives the growth factor-independent proliferation and survival of bone marrow progenitors in chronic myeloid leukemia?
Activation of multiple downstream pathways by BCR-ABL
What is the net result of BCR-ABL activation on bone marrow progenitors in chronic myeloid leukemia?
Increase in mature granulocytes and platelets
What is the role of the chimeric BCR-ABL fusion mRNA in chronic myeloid leukemia?
Encoding a constitutively active tyrosine kinase
Which downstream pathways are activated by the BCR-ABL fusion gene in chronic myeloid leukemia?
- STAT and AKT pathways
What genetic event leads to the activation of multiple downstream pathways in chronic myeloid leukemia?
- BCR-ABL fusion gene creation
What is a characteristic finding in Chronic Myeloid Leukemia (CML) regarding the spleen?
Moderately enlarged spleen with red pulp stemming from neoplastic hematopoiesis
Which cell type is typically predominant in the leukocytosis seen in Chronic Myeloid Leukemia (CML)?
Myelocytes
What symptom can be a presenting feature of Chronic Myeloid Leukemia (CML) due to splenomegaly?
Anorexia
How do blasts generally contribute to the leukocytosis observed in Chronic Myeloid Leukemia (CML)?
Predominantly make up the circulating cells
Which term describes the finding of numerous macrophages with abundant wrinkled green-blue cytoplasm in Chronic Myeloid Leukemia (CML)?
Sea-blue histiocytes
What differentiates Chronic Myeloid Leukemia (CML) from other myeloproliferative neoplasms at the molecular level?
Absence of BCR-ABL fusion gene
How does extramedullary hematopoiesis in Chronic Myeloid Leukemia (CML) typically manifest?
Mild hepatomegaly and splenic infarcts
What is the approximate median survival for patients with chronic myeloid leukemia (CML) without any treatment?
3 years
What percentage of patients with chronic myeloid leukemia (CML) enter an accelerated phase marked by increasing anemia and thrombocytopenia?
50%
What additional clonal cytogenetic abnormalities often appear in patients with chronic myeloid leukemia (CML) during the accelerated phase?
Trisomy 8
What is the most common origin of blasts in blast crises in chronic myeloid leukemia (CML)?
Myeloid
Which stem cell potential is suggested by the fact that chronic myeloid leukemia (CML) blasts can be of both myeloid and lymphoid origin?
Pluripotent stem cell
What are the characteristic blasts in lymphoid blast crises found in approximately 30% of chronic myeloid leukemia (CML) cases?
Pre-B cells
What is the name of the phase characterized by acute leukemia-like symptoms that terminates the accelerated phase in some patients with chronic myeloid leukemia (CML)?
Blast crisis
What cytogenetic abnormality is often seen in patients with chronic myeloid leukemia (CML) during the accelerated phase that indicates duplication of genetic material?
Trisomy 8
What type of stem cell potential suggests that chronic myeloid leukemia (CML) originates from a cell capable of giving rise to multiple blood cell types?
Multipotent stem cell
What is the primary reason why HSC transplantation is less effective in patients with accelerated phase or blast crisis?
Reduced bone marrow function
Which tyrosine kinase is implicated in Polycythemia Vera due to activating mutations in the JAK2 gene?
JAK2
What is the main distinguishing feature between Polycythemia Vera and relative polycythemia?
Increase in red cells
Which pathway downstream of hematopoietic growth factor receptors is affected by mutations in the JAK2 gene?
JAK/STAT pathway
What cellular characteristic do transformed progenitor cells in Polycythemia Vera exhibit?
Increased requirements for erythropoietin
Why is stable phase HSC transplantation curative in about 75% of relatively young patients?
Restores bone marrow function
What is the primary cause of most clinical symptoms in Polycythemia Vera?
Increase in red cells
What differentiates Polycythemia Vera from other causes of absolute polycythemia?
'Panmyelosis' phenomenon
What is the molecular target of BCR-ABL inhibitors in the treatment of CML?
BCR-ABL
What is the effect of BCR-ABL inhibitors on the BCR-ABL-positive cells in CML patients?
Sustained hematologic remissions
What is the potential limitation of BCR-ABL inhibitors in treating CML?
Curative potential uncertainty
How do BCR-ABL inhibitors affect the risk of transformation to blast crisis in CML?
Substantially decrease transformation risk
What is the proposed mechanism by which BCR-ABL inhibitors decrease disease progression in CML?
Lower proliferative drive of progenitors
What is the primary impact of BCR-ABL inhibitors on blood counts in CML patients?
Normalization of blood counts
Which cell population persists at low levels despite treatment with BCR-ABL inhibitors?
"CNIL 'Stemcell'"
What is the main benefit of using BCR-ABL inhibitors in CML treatment besides sustained remissions?
Decreased risk of transformation
What is the characteristic serum erythropoietin levels in Primary Polycythemia (PCV) as mentioned in the text?
Low levels
What is the impact of the elevated hematocrit in PCV on blood viscosity as described in the text?
Leads to increased blood viscosity
What distinguishes the red cell progenitors and megakaryocytes in PCV according to the text?
Increased numbers
What is a common morphological feature seen in bone marrows of patients with PCV?
Marked increase in reticulin fibers
What type of progression is often observed late in the course of PCV as mentioned in the text?
'Spent phase' progression
What distinguishes the proliferative drive in PCV from that in chronic myeloid leukemia (CML) according to the text?
'Promo marrow percellularity' in PCV
What characteristic is often observed late in the course of PCV according to the text?
'Extensive hematopoiesis in the spleen and liver'
What is a common feature of JAK2 signaling in PCV patients based on the provided text?
Quantitatively weak signals
What is a common characteristic of organomegaly in PCV patients according to the text?
Congestion-related
What distinguishes Essential Thrombocytosis (ET) from Polycythemia Vera (PCV) and primary myelofibrosis?
Presence of elevated platelet counts
What is the characteristic feature of the mutated forms of CALR seen in Essential Thrombocytosis (ET)?
Activation of thrombopoietin receptor
Which mutations are commonly associated with Essential Thrombocytosis (ET) according to the text?
Activating mutations in JAK2, MPL, and CALR
What clinical manifestation primarily separates Essential Thrombocytosis (ET) from Polycythemia Vera (PCV)?
Elevated platelet counts
How does Essential Thrombocytosis (ET) differ from Primary Myelofibrosis?
Absence of marrow fibrosis
What distinguishes the mutated forms of CALR seen in Essential Thrombocytosis (ET)?
Secretion and activation of thrombopoietin receptor
What is the primary clinical presentation of Essential Thrombocytosis (ET) compared to Primary Myelofibrosis?
Elevated platelet counts
What is a possible reason why some patients with JAK2 mutations present with Polycythemia Vera (PCV) and others with Essential Thrombocythemia (ET)?
Presence of iron deficiency
What distinguishes the transformation of Polycythemia Vera (PCV) to Acute Myeloid Leukemia (AML) from Chronic Myeloid Leukemia (CML) transformation to Acute Lymphoblastic Leukemia (ALL)?
Presence of specific gene mutations
Which mutation is commonly found in cases without JAK2 or MPL mutations in Polycythemia Vera?
CALR mutations
What is a characteristic feature of bone marrow cellularity in patients with Polycythemia Vera?
Mild increase in cellularity
What is the primary consequence of Constitutive JAK2 or MPL signaling in Polycythemia Vera?
Hyperproliferation of progenitors
In what way does the AML clone arising from Polycythemia Vera differ from the majority of cases of PCV?
Lack of JAK2 mutations
What percentage of patients with Polycythemia Vera have mild organomegaly due to extramedullary hematopoiesis?
~50%
What distinguishes the megakaryocytes observed in patients with Polycythemia Vera?
Increased size and number
What is a characteristic symptom associated with essential thrombocytosis (ET)?
Erythromelalgia
Which type of thrombotic event is NOT commonly observed in essential thrombocytosis (ET)?
Pulmonary embolism
What can platelet dysfunction in essential thrombocytosis (ET) lead to?
Thrombosis
What is the incidence rate of essential thrombocytosis (ET) per year?
1 per 100,000
What kind of sensation is erythromelalgia, a characteristic symptom of essential thrombocytosis (ET)?
Throbbing and burning
Which age group typically experiences essential thrombocytosis (ET)?
Over 60 years old
What is the primary clinical manifestation resulting from platelet abnormalities in essential thrombocytosis (ET)?
Thrombosis and hemorrhage
Which symptom is NOT typically associated with reactive thrombocytosis?
Intense pruritus
Which of the following is a common qualitative abnormality seen in platelets due to essential thrombocytosis (ET)?
'Giant platelets'
What is the likely hematocrit level in patients with Polycythemia Vera?
55% or more
Which condition is a common complication of Polycythemia Vera?
Deep venous thrombosis
What is a significant risk associated with thromboses in Polycythemia Vera?
Thrombotic episodes
Which symptom may indicate the involvement of hepatic veins in Polycythemia Vera?
Budd-Chiari syndrome
What percentage of Polycythemia Vera patients may initially present with deep venous thrombosis?
25% or more
'Life-threatening' hemorrhages occur in what percentage of Polycythemia Vera cases?
5% to 10%
'Minor hemorrhages' such as epistaxis and bleeding gums are common in what percentage of Polycythemia Vera cases?
~10%
What prolongs median survival to about 10 years in patients with Polycythemia Vera?
Phlebotomy
In Polycythemia Vera, what is mainly responsible for the transition to a 'spent phase' with features of myelofibrosis?
Bone marrow fibrosis
How does untreated Polycythemia Vera lead to death?
Bleeding or thrombosis
What distinguishes the platelets in patients with Polycythemia Vera?
Giant forms and functional defects
What leads to iron deficiency in chronic bleeding, ultimately suppressing erythropoiesis?
Hemoglobin concentration
What is the expected white cell count range in patients with the discussed condition?
< 12,000 cells/mm³
What extends median survival in Polycythemia Vera patients to about 10 years?
Bone marrow transplant
What primarily contributes to the lower hematocrit range in some patients with chronic bleeding?
> than hemoglobin concentration
What is the characteristic feature of primary myelofibrosis?
Development of obliterative marrow fibrosis
Which gene mutations are commonly found in primary myelofibrosis?
Activating mutations of JAK2, CALR, or MPL
What is the median survival time in essential thrombocytosis (ET)?
12 to 15 years
What type of complications are most likely in patients with very high platelet counts in essential thrombocytosis (ET)?
Thrombotic complications
What is the therapy approach for essential thrombocytosis (ET)?
'Gentle' chemotherapeutic agents that suppress thrombopoiesis
What is the primary pathologic feature in primary myelofibrosis?
Extensive deposition of collagen in the marrow
What is the hallmark feature that leads to cytopenias in primary myelofibrosis?
Obliterative marrow fibrosis reducing bone marrow hemato-poiesis
What causes marrow failure in primary myelofibrosis?
Extensive deposition of collagen displacing hematopoietic elements
What is the term used to describe the change when fibrose marige is converted into bone in the context of myelofibrosis?
Ossification
Which organ is usually markedly enlarged due to extramedullary hematopoiesis in the context of the provided text?
Spleen
What is the term for fibrotic obliteration of the marrow space leading to extensive extramedullary hematopoiesis often seen in myelofibrosis?
Myelosclerosis
In myelofibrosis, where does extramedullary hematopoiesis initially occur before expanding into the cords?
Spleen sinuses
What is a common feature seen in the liver of patients with myelofibrosis due to extramedullary hematopoiesis?
Sinusoidal foci of extramedullary hematopoiesis
Which cell type may exhibit hematopoietic elements within dilated sinusoids in the context of myelofibrosis?
Megakaryocytes
What does the firm, diffusely red spleen weighing up to 4000 g indicate in a patient with advanced myelofibrosis?
'Cloud-like' megakaryocytes
What category of clinical features are typically observed in primary myelofibrosis?
'Cloud-like' hematologic abnormalities
What is the term used to describe the release of nucleated erythroid and early granulocyte progenitors due to marrow distortion?
Leukoerythroblastosis
What characteristic shape do red cells (dacryocytes) exhibit in fibrotic marrows?
Teardrop-shaped
Apart from primary myelofibrosis, where else can teardrop red cells be observed?
Granulomatous diseases
In addition to teardrop red cells, what other blood finding is commonly associated with conditions causing marrow distortion?
Abnormally large platelets
What is a common feature of nucleated erythroid precursors in diseases associated with marrow distortion and fibrosis?
Immature appearance
Which term describes the condition of immature cells entering circulation from sites of extramedullary hematopoiesis?
Myeloid blast crisis
What is a notable observation in the peripheral blood smear of primary myelofibrosis patients?
Teardrop-shaped red cells
Apart from primary myelofibrosis, which other condition presents with leukoerythroblastosis on blood examination?
Metastatic cancers
What is the likely cause of moderate to severe anemia in patients with myelofibrosis?
Disordered red cell production at extramedullary sites
What effect does TGF-B have on collagen deposition and angiogenesis in myelofibrosis?
Promotes collagen deposition and angiogenesis
What happens as marrow fibrosis progresses in patients with myelofibrosis?
Marrow becomes more hypocellular and fibrotic
What is a distinguishing feature of megakaryocytes in the early stage of myelofibrosis?
Large size and abnormal clustering
How do circulating HSCs contribute to the progression of myelofibrosis?
They reside in niches in secondary hematopoietic organs
What is the consequence of red cell production disorder at extramedullary sites?
Moderate to severe anemia in affected patients
What factor contributes to the appearance of extramedullary hematopoiesis in myelofibrosis?
Increased residence of HSCs in niches outside the bone marrow
Which of the following is a characteristic feature of Langerhans Cell Histiocytosis?
Innate immune system involvement
In primary myelofibrosis, what contributes to the median survival range of 3 to 5 years?
Presence of thrombotic episodes
Which type of neoplasm is considered an unusual myeloid neoplasm due to its involvement with the innate immune system?
Langerhans Cell Histiocytosis
What distinguishes myeloid tumors characterized by disordered and ineffective hematopoiesis from primary myelofibrosis?
Mutations in splicing factors
Which factor significantly contributes to the mortality risk of primary myelofibrosis?
Intercurrent infections
What differentiates Langerhans cell histiocytoses from 'histiocytic' sarcomas?
'Histiocytic' sarcomas are clearly malignant
What is a key feature that makes Langerhans cells part of the innate immune system?
Phagocytic activity
What is a distinct characteristic of clonal histiocytoses like Langerhans Cell Histiocytosis that sets them apart from other disorders?
'Clonal proliferations of a special type of immature dendritic cell'
What is the most common mutation found in Langerhans cell histiocytosis?
Valine-to-glutamate substitution at residue 600 in JAK2
In myelofibrosis, what treatment option offers hope for cure in young and fit patients?
Stem cell transplantation
Which signaling pathway components are often mutated in aggressive tumors comprised of immature myeloid lineage blasts?
Genes encoding growth factor receptor signaling pathway components
What is the primary characteristic of AML tumors in adults compared to other groups based on the text?
Presence of driver mutations
Which gene mutation is less common but also detected in Langerhans cell histiocytosis cases?
TP53 mutation
What is the main feature associated with hairy cell leukemia cells' appearance under a phase-contrast microscope?
'Ground-glass' appearance of the nuclei
Which chromosome translocation leads to overexpression of cyclin D1 in mantle cell lymphoma?
(8;14)
What type of cells do cutaneous T-cell lymphomas primarily involve?
'Mature T cells'
What is a characteristic feature of MDS showing a lacunar variant of Reed-Sternberg cells?
Normocytic normochromic anemia
Which symptom commonly results from an increase in metabolism associated with the expanding mass of hematopoietic cells in MDS?
Night sweats
What is a common complication that can arise due to the high rate of cell turnover in MDS?
Hyperuricemia
Which laboratory finding is typically seen in MDS accompanying normocytic normochromic anemia?
Hypochromic microcytic red cells
What blood finding may supervene as myelodysplastic syndrome progresses, according to the provided information?
Thrombocytopenia
Which symptom arises due to splenomegaly in individuals with MDS?
"Fullness" sensation
What is a common early presentation that brings individuals with MDS to medical attention?
"Progressive anemia"
What is a non-specific symptom commonly associated with myelodysplastic syndrome?
Pallor
What contributes to the homing of neoplastic Langerhans cells?
Expression of CCR6 and CCR7
What is a characteristic morphological feature of proliferating Langerhans cells?
Cytoplasm with Birbeck granules
Which tyrosine kinases are commonly associated with myeloid tumors?
BCR-ABL and mutated JAK2
Which ligand is relevant for the migration of neoplastic Langerhans cells into lymphoid organs?
CCL19
What is the consequence of BCR-ABL and mutated JAK2 activation in myeloproliferative neoplasms?
Constitutive growth signal mimicry
What is a characteristic feature of Birbeck granules found in Langerhans cells?
Tennis racket-like appearance
Why do neoplastic Langerhans cells express both CCR6 and CCR7?
For skin and bone migration
What transformation can myeloproliferative neoplasms undergo?
'Spent' phase with marrow fibrosis
What is characteristic of the cytoplasm in proliferating Langerhans cells?
Numerous Birbeck granules
What role do platelet-derived growth factor and TGF-ẞ play in the pathogenesis of myelofibrosis?
Promote fibroblast mitosis
What result is observed due to circulating HSCs taking up residence in extramedullary hematopoietic organs?
Decreased red cell production
Which factor contributes to the moderate to severe anemia seen in primary myelofibrosis?
Suppression of marrow function
What is the consequence of fibrosis progression in the bone marrow?
Development of hypocellular areas
What is the relationship between primary myelofibrosis and PCV/ET according to the text?
Distinct entities
What symptom is commonly associated with primary myelofibrosis due to extramedullary hematopoiesis?
Splenomegaly
Which factor contributes to the disordered red cell production at extramedullary sites?
Incompletely understood reasons
What is the outcome of TGF-B promoting collagen deposition in primary myelofibrosis?
Formation of fibrotic tissue
Which cellular feature distinguishes the spent phase of other myeloproliferative neoplasms from primary myelofibrosis?
Clusters of atypical megakaryocytes
What is a characteristic morphological feature of megakaryocytes in the fibrotic marrow space of primary myelofibrosis?
Cloud-like shapes
What pathological change occurs in very late stages of primary myelofibrosis within the fibrotic marrow space?
Transformation into bone (osteosclerosis)
What is a common finding in the blood of individuals with primary myelofibrosis that aids in diagnosis?
Leukocytosis and thrombocytosis
What contributes to the markedly enlarged spleen seen in advanced primary myelofibrosis?
Extensive extramedullary hematopoiesis
What is a key histological feature found within dilated sinusoids in fibrotic marrow in primary myelofibrosis?
Hematopoietic elements
What cellular change can be observed in the very late stages of primary myelofibrosis within the fibrotic marrow space?
'Cloud-like' megakaryocytes
'Osteosclerosis' seen in advanced primary myelofibrosis primarily results from the conversion of what tissue?
'Fibrotic' tissue
What is the hallmark of primary myelofibrosis?
Developing obliterative marrow fibrosis
What is the main pathologic feature in primary myelofibrosis?
Deposition of collagen by neoplastic fibroblasts in the marrow
What is the typical median survival time for essential thrombocytosis?
12 to 15 years
What is the therapy for essential thrombocytosis primarily aimed at suppressing?
Thrombopoiesis
Which disorder is characterized by long asymptomatic periods punctuated by occasional thrombotic or hemorrhagic crises?
Essential Thrombocytosis
What genetic mutations are most likely to lead to thrombotic complications in essential thrombocytosis?
JAK2 mutations
What leads to marrow failure in primary myelofibrosis?
"Obliterative marrow fibrosis"
What characteristic blood findings reflect marrow fibrosis in the text?
Teardrop-shaped red cells
"Extensive deposition of collagen in the marrow by nonneoplastic fibroblasts" leads to what in primary myelofibrosis?
"Obliterative marrow fibrosis"
What condition is often associated with abnormally large platelets and basophilia based on the text?
Primary myelofibrosis
Which cells enter circulation from sites of extramedullary hematopoiesis due to marrow distortion in the text?
Immature cells
What is a common feature of many infiltrative disorders of the marrow according to the text?
Leukoerythroblastosis
Which of the following conditions may present with teardrop-shaped red cells and leukoerythroblastosis similar to primary myelofibrosis?
Metastatic tumors
What is a characteristic blood finding seen in primary myelofibrosis according to the text?
Dacryocytes
In primary myelofibrosis, what leads to the premature release of nucleated erythroid progenitors from sites of extramedullary hematopoiesis?
Marrow distortion
What are abnormal red cell shapes seen in primary myelofibrosis known as?
Dacryocytes
What do nucleated erythroid precursors and dacryocytes indicate in peripheral blood smear according to the text?
Primary myelofibrosis
What is a dominant clinical feature of Langerhans cell histiocytosis?
Development of seborrheic lesions
Which cells are most prominently affected in Langerhans cell histiocytosis?
Eosinophils
What is a common consequence of extensive marrow infiltration in Langerhans cell histiocytosis?
Anemia and thrombocytopenia
Which term is used to describe the destructive bone lesions seen in Langerhans cell histiocytosis?
Osteolytic lesions
What is a significant symptom associated with Langerhans cell histiocytosis?
Recurrent ear infections
Which organ is likely to be affected by hepatosplenomegaly in Langerhans cell histiocytosis?
Lungs
Which type of cells are characteristically found in unifocal and multifocal unisystem Langerhans cell histiocytosis?
Eosinophils, lymphocytes, and plasma cells
In unisystem Langerhans cell histiocytosis, where do bone lesions most commonly occur?
Spine and skull
What symptom can occur as a result of involvement of the posterior pituitary stalk in unisystem Langerhans cell histiocytosis?
Diabetes insipidus
What can be the result of calvarial bone defects in unisystem Langerhans cell histiocytosis?
Hand-Schüller-Christian triad
What treatment modality can cure unifocal disease in some instances according to the text?
Surgery
What is a common symptom seen in multifocal unisystem Langerhans cell histiocytosis in young children?
Erosive bony masses
What is the primary function of the spleen as described in the text?
Filtering the blood and immune responses to blood-borne antigens
What are the white pulp follicles in the spleen composed of?
Lymphocytes capable of developing into germinal centers
Which statement accurately describes Pulmonary Langerhans cell histiocytosis based on the text?
40% are associated with BRAF mutations.
What is the characteristic feature of the periarteriolar lymphatic sheath within the white pulp follicles?
Eccentric collar of T lymphocytes
What does the comment 'may regress spontaneously upon cessation of smoking' suggest about Pulmonary Langerhans cell histiocytosis?
It is influenced by smoking habits.
Which cell type is primarily involved in reacting to blood-borne antigens in the spleen?
T lymphocytes
What is the main characteristic that distinguishes red pulp from white pulp in the spleen?
Gray specks indicating lymphoid follicles
What does the presence of BRAF mutations in 40% of Pulmonary Langerhans cell histiocytosis cases suggest?
Potential neoplastic origin in some instances
What structural feature of the spleen allows blood cells to squeeze through gaps in the endothelial lining to reach the sinusoids?
Trabeculum
Which route is taken by only a small fraction of blood in the spleen's circulation system?
From cords to spleen
In which condition do red cells become trapped in the cords of the spleen due to decreased deformability?
Sickle cell anemia
What process involves the phagocytosis of blood cells and particulate matter by macrophages in the spleen?
Pitting
What is the term for the process where red cells are examined closely by macrophages in the cords of the spleen?
Erythrocyte scrutiny
Which phenomenon involves red cells undergoing extreme deformation during passage from cords into sinusoids?
'Open' circulation
What is the primary function of macrophages in the spleen related to blood cell examination?
'Pitting' of red cells
In which structure of the spleen do blood cells squeeze through gaps to reach sinusoids in a slow compartment circulation?
'Open circuit'
What is the key feature of the spleen's architecture that facilitates examination of blood cells by macrophages in the cords?
'Trabeculum'
What is the major clinical manifestation of splenic insufficiency due to splenectomy or autoinfarction?
Leukopenia
What is the syndrome characterized by anemia, leukopenia, and/or thrombocytopenia due to splenomegaly?
Hypersplenism
Which of the following is NOT a symptom associated with splenomegaly?
Hematuria
What is the probable cause of cytopenias in hypersplenism?
Enhanced phagocytosis
What major clinical complication should asplenic individuals be vaccinated against?
Sepsis from encapsulated bacteria
What is the major manifestation of disorders of the spleen?
Splenomegaly
What does splenic insufficiency due to splenectomy or autoinfarction lead to?
Increased susceptibility to sepsis
What is the primary function of dendritic cells in the spleen?
Presentation of antigens to T lymphocytes
In what condition does the spleen become a major site of compensatory extramedullary hematopoiesis?
Thalassemia
What is a common consequence of splenomegaly?
Thrombocytopenia
What is a characteristic of the spleen during fetal development?
Becomes a minor site of hematopoiesis at birth
Which cells are mainly responsible for antibody production in the spleen?
Plasma cells
Which condition leads to a substantial increase in the platelet mass sequestered in the spleen?
Essential thrombocytosis (ET)
What can cause systemic venous congestion related to cardiac decompensation?
Issues with the left side of the heart
What type of cells are typically found throughout the white and red pulp in congestive splenomegaly?
Plasma cells
What is a common cause of portal or splenic vein hypertension?
Intrahepatic disorders affecting venous drainage
Which condition may lead to necrosis of white pulp follicles in the spleen?
Brucellosis
In which condition do neutrophils, plasma cells, and occasionally eosinophils appear in the spleen's white and red pulp?
Tuberculosis
Which condition may evoke splenomegaly along with cirrhosis of the liver?
Cirrhosis of the liver from alcohol consumption
How can congestive splenomegaly be caused?
Impairment of extrahepatic portal vein function
What is a rare occurrence in congestive splenomegaly due to chronic venous outflow obstruction?
Abscess formation
What can lead to splenic congestion due to infiltrating tumors?
Carcinomas of the stomach or pancreas
Which condition can cause a form of splenic enlargement referred to as congestive splenomegaly?
Portal vein thrombosis
What may lead to white pulp follicles necrosis in the spleen?
Hemolytic streptococcus
In what condition does thrombosis of the splenic vein typically occur?
Heart valve diseases
Which factor is usually implicated in systemic venous congestion cases related to cardiac decompensation?
'Pipe-sempat' syndrome
What can lead to engorgement and fibrosis in the spleen over time?
'Obm' obstruction
What is the primary pathologic feature in primary myelofibrosis?
Bone marrow fibrosis
How do circulating HSCs contribute to the progression of myelofibrosis?
By promoting fibroblast proliferation
What contributes to the development of AML according to the provided text?
Bone marrow inflammation
In myelodysplastic syndromes, what is the typical percentage of myeloid blasts in the overall marrow cellularity?
Approximately 15%
What distinguishes the megakaryocytes observed in patients with Polycythemia Vera?
Abnormal nuclear lobulation
What influences the homeostasis of lymphocytes in peripheral (secondary) lymphoid tissues?
Chemokine gradients
What is a common feature of many infiltrative disorders of the marrow according to the text?
Dysplastic changes
What is the main function of the 'thymic university' mentioned in the text?
Educating T cells to distinguish between self and non-self antigens
Which cell type predominates in the thymus along with thymic epithelial cells?
Mature T lymphocytes
What are the main characteristics of thymic epithelial cells in the cortex, as described in the text?
Polygonal shape with abundant cytoplasm and dendritic extensions
What is the role of fibrous extensions of the capsule in the thymus?
Connecting marrow to the thymus for T cell maturation
Which type of cells create Hassall corpuscles in the thymus?
Medullary epithelial cells
What leads to the decline in thymic production of T cells during adulthood?
Atrophy of the organ
What is the main function of T cells educated in the 'thymic university'?
Distinguishing between self and non-self antigens
'Thymic university' aims to educate T cells primarily about which concept?
'Recognition of non-self antigens'
'Thymic university' education leads to the development of T cells that can differentiate between:
'Self and non-self antigens'
What is a unique characteristic of Hassall corpuscles in the thymus?
Create keratinized cores
What is the most common predisposing condition for splenic rupture according to the text?
Infectious mononucleosis
In which age group does the thymus undergo progressive involution after puberty?
Older adults
What is the embryological origin of the thymus according to the text?
Third and fourth pair of pharyngeal pouches
What is the significance of the physical insult that leads to spontaneous splenic rupture?
It impacts spleens with an underlying condition
Which organ has gained prominence in cell-mediated immunity according to the text?
Thymus
What is the usual weight range of the thymus at birth?
$10$ to $35$ grams
What does a rapid enlargement of the spleen result in according to the text?
$5(7 + 3)$ thin capsule formation
Which event often follows a dramatic spontaneous splenic rupture according to the text?
$9(3 - 1)$ intraperitoneal hemorrhage
What is the characteristic color of older, more fibrotic splenic infarcts mentioned in the text?
Pale yellow-gray
In which myeloproliferative neoplasm is extramedullary hematopoiesis seen causing a massively enlarged spleen?
Myelofibrosis
What structures are functionally identical to the normal spleen and can be found at any place within the abdominal cavity?
Accessory spleens
What condition makes accessory spleens clinically important, especially in hematology disorders like hereditary spherocytosis?
Accessory spleens
Which benign growths may arise in the spleen, including lymphangiomas and chondromas?
Fibromas and osteomas
What common cardiac finding is associated with thymic enlargement?
Cardiac malformations
What percentage of postmortem examinations show the presence of accessory spleens, according to the text?
~20-35%
What is the main significance of thymic 'hyperplasia' mentioned in the text?
It can be mistaken radiologically for a thymoma
In the classification system for thymomas mentioned in the text, how many histologic subtypes are considered?
Three
Where do most thymomas usually occur in the body?
Anterior superior mediastinum
What is the main utility of the WHO classification system for thymomas based on the text?
Defining prognostic features
What distinguishes tumors classified as cytologically malignant thymic carcinoma?
Cytologically benign but invasive behavior
What age group do most thymomas usually occur in?
Over 40 years
Which gender is more commonly affected by thymomas according to the text?
Both genders equally
What is the key feature used to classify thymomas in the system discussed in the text?
Surgical stage and cytologic features
Which term is used to describe the appearance of B-cell germinal centers within the thymus?
Thymic follicular hyperplasia
In what percentage of cases of myasthenia gravis is thymic follicular hyperplasia found?
65-75%
Which condition is most frequently associated with thymic follicular hyperplasia?
Graves disease
What is the significance of finding a cystic thymic lesion in a symptomatic patient?
Suggests potential neoplasm, particularly lymphoma or thymoma
What is the primary difference between isolated thymic cysts and neoplastic thymic masses?
Effect on adjacent normal thymus
Where are B-cell germinal centers usually present in the normal thymus?
Present in small numbers, if at all
What is the predominant cause of thymic follicular hyperplasia according to the text?
Chronic inflammatory and immunologic states
What is a distinct feature of invasive thymomas?
Are benign but locally invasive
Which characteristic is commonly observed in noninvasive thymomas?
Mainly composed of medullary-type epithelial cells
What sets apart noninvasive thymomas from the invasive variety?
Capable of metastasizing
Which feature is characteristic of mixed thymomas?
Denser infiltrate of thymocytes
What is a key histological feature of medullary-type epithelial cells in thymomas?
Sparse infiltrate of thymocytes
What is the most distinctive variant of Thymic carcinomas microscopically?
Polygonal neoplastic epithelial cells
What is a characteristic feature of Malignant thymoma, type I?
Few reactive lymphoid cells interspersed
What is a clinical feature associated with Thymomas in about 40% to 45% of cases?
Association with Myasthenia Gravis
In what way did the malignant thymoma in Figure 13.42 differ from benign thymomas depicted in the same figure?
Invasion into adjacent structures
Which clinical disorder is commonly associated with Thymoma cortical type?
Myasthenia Gravis
What is the morphological appearance of Malignant thymoma, type I?
Round to oval, bland nuclei with inconspicuous nucleoli
What is the invasive behavior seen in the malignant thymoma depicted in Figure 13.42?
'Locally aggressive' invasion into adjacent lung and pericardium
'Benign thymomas of the cortical type' are morphologically identical to which malignant thymoma type?
'Swirling pattern' arrangement of neoplastic cells
'Thymoma cortical associated with myasthenia gravis' suggests that abnormalities in which organ/system might be present?
'Thymus gland'
What is the approximate percentage of thymomas that are encapsulated and noninvasive?
20% to 25%
Which type of thymoma is characterized by a tumor that has cytologically abundant cytoplasm and rounded vesicular nuclei?
Cortical thymoma
What is the survival rate associated with complete excision of thymomas with minimal invasion?
Greater than 90%
Which term describes invasive thymomas that penetrate through the capsule into surrounding structures?
Locally invasive
Thymic carcinoma accounts for approximately what percentage of thymomas?
5%
What is the key feature of thymic carcinomas compared to other thymomas?
Locally invasive behavior
Which characteristic correlates with a propensity for more aggressive behavior in some neoplastic thymoma cells?
Cytologic atypia
With extensive invasion, what is the associated 5-year survival rate?
<50%
What is a distinctive variant of thymic carcinoma that closely resembles nasopharyngeal carcinoma?
Lymphoepithelioma-like carcinoma
Which cells are most often found in thymic carcinomas?
Medullary-type epithelial cells
What percentage of lym- phoepithelioma-like carcinomas contain monoclonal EBV genomes?
50%
Which histologic pattern is NOT commonly described in thymic carcinomas?
Papillary-type
What is a key feature of lymphoepithelioma-like carcinomas?
Sheets of cells closely resembling nasopharyngeal carcinoma
Which feature is characteristic of mixed thymomas?
Mixture of medullary and cortical-type epithelial cells
What is the role of EBV in the pathogenesis of some thymic carcinomas?
"Consistent with" a role in pathogenesis
"A tumor composed of sheets of cells that bears a close histologic resemblance to nasopharyngeal carcinoma" describes which variant?
"Lymphoepithelioma-like" carcinoma
What is the basis for the association between thymomas and autoimmune disorders?
Thymocytes within thymomas produce long-lived CD4+ and CD8+ T cells
Why are only a few small lymphoid cells observed in malignant thymomas?
The tumor has a low mitotic rate
What type of thymoma is more likely to be associated with autoimmune diseases?
Cortical thymoma rich in thymocytes
Which autoimmune disorder is NOT mentioned as being associated with thymomas?
Rheumatoid arthritis
Why do 30% to 45% of thymomas get detected in patients with myasthenia gravis?
Both conditions have similar symptoms
What contributes to the development of diverse autoimmune disorders in individuals with thymomas?
'Education' of T cells in the neoplastic environment
What is uncertain about the basis for the associations between thymomas and autoimmune disorders?
'Education' of T cells within neoplastic environments
What is the most likely reason why some individuals with autoimmune diseases have their thymoma discovered incidentally?
The individuals had no symptoms related to mediastinal structures impingement
Study Notes
Components of Hematopoietic System
- Bone marrow and cells derived from it (e.g. red cells, platelets, granulocytes, and monocytes)
- Lymphoid tissues (e.g. thymus, lymph nodes, and spleen)
Hematopoietic Stem Cells (HSCs)
- Pluripotent cells that give rise to all blood cells
- Possess two essential properties: pluripotency and self-renewal
- HSCs arise in the mesoderm of the intraembryonic aorta/gonad/mesonephros region during embryonic development
- HSCs migrate to the liver, then to the bone marrow, and finally to the peripheral blood
Blood Cell Development
- HSCs give rise to committed progenitors, which differentiate into specific types of blood cells
- Colony-forming units (CFUs) are committed progenitors that produce colonies of specific blood cells
- Progenitors differentiate into morphologically recognizable precursors, such as myeloblasts, proerythroblasts, and megakaryoblasts
Regulation of Hematopoiesis
- Hematopoietic growth factors regulate the production of blood cells
- Growth factors, such as erythropoietin, granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF), act on specific receptors to stimulate the production of specific blood cells
- Feedback loops involving growth factors maintain the balance of blood cell production
Diseases of Hematopoiesis
- Defects in hematopoiesis can lead to deficiencies in one or more types of blood cells
- Primary tumors of hematopoietic cells can interfere with marrow function
- Genetic diseases, infections, toxins, and nutritional deficiencies can also decrease blood cell production
Leukopenia
- A decrease in the number of circulating white blood cells
- Can be caused by reduced numbers of neutrophils (neutropenia, granulocytopenia) or lymphocytes (lymphopenia)
- Can occur due to ineffective hematopoiesis, suppressed bone marrow function, or increased destruction of white blood cells
Agranulocytosis
- A marked reduction in neutrophils
- Can be caused by inadequate or ineffective granulopoiesis, or increased destruction or sequestration of neutrophils
- Consequences include susceptibility to infections, particularly bacterial and fungal infections
Reactive Proliferations of White Cells
- Leukocytosis: an increase in the number of white blood cells in the blood, often in response to infection or inflammation
- Pathogenesis involves the release of cytokines, growth factors, and adhesion molecules that stimulate the production and release of white blood cells
Disorders of White Blood Cells
- Leukopenias: deficiencies of white blood cells
- Proliferative disorders: expansions of white blood cells, including reactive and neoplastic proliferations
- Neoplastic disorders: malignant proliferations of white blood cells, including leukemias### Leukocytosis
- Leukocytosis is a rapid increase in the egress of mature granulocytes from the bone marrow pool, mediated by tumor necrosis factor (TNF) and interleukin-1 (IL-1)
- Prolonged infection or inflammation stimulates macrophages, bone marrow stromal cells, and T cells to produce increased amounts of hematopoietic growth factors
- Growth factors stimulate the proliferation and differentiation of committed granulocytic progenitors, leading to a sustained increase in neutrophil production
Mechanisms of Leukocytosis
- Increased marrow production:
- Chronic infection or inflammation (growth factor-dependent)
- Paraneoplastic (e.g., Hodgkin lymphoma; growth factor-dependent)
- Myeloproliferative neoplasms (e.g., chronic myeloid leukemia; growth factor-independent)
- Increased release from marrow stores:
- Acute inflammation (e.g., with infection)
- Chronic inflammation (many causes)
- Decreased margination:
- Exercise
- Catecholamines
- Decreased extravasation into tissues:
- Glucocorticoids
Leukocytosis Types and Causes
- Neutrophilic leukocytosis:
- Causes: tissue necrosis (e.g., myocardial infarction, burns), allergic disorders, parasitic infestations, and certain malignancies
- Eosinophilic leukocytosis (eosinophilia):
- Causes: allergic disorders, parasitic infestations, and certain malignancies
- Basophilic leukocytosis (basophilia):
- Rare, often indicative of a myeloproliferative neoplasm
- Monocytosis:
- Causes: chronic infections, bacterial endocarditis, rickettsiosis, and malaria
- Lymphocytosis:
- Causes: viral infections, infectious mononucleosis, and certain autoimmune disorders
Lymphadenitis
- Lymph nodes are discrete, encapsulated structures that contain separate B-cell and T-cell zones
- Activation of resident immune cells leads to morphologic changes in lymph nodes
- Within several days of antigenic stimulation, primary follicles enlarge and develop pale-staining germinal centers
Acute Nonspecific Lymphadenitis
- Caused by bacterial infections, viral infections, and inflammatory disorders
- Morphologic changes: swollen nodes, gray-red color, and engorged sinuses
- Microscopic features: prominent reactive germinal centers, numerous mitotic figures, and scattered neutrophils
Chronic Nonspecific Lymphadenitis
- Caused by chronic infections, autoimmune disorders, and inflammatory disorders
- Morphologic changes: swollen nodes, mild increase in germinal centers, and scattered macrophages
- Microscopic features: follicular hyperplasia, paracortical hyperplasia, and sinus histiocytosis
Hemophagocytic Lymphohistiocytosis
- Characterized by cytopenias and systemic inflammation related to macrophage activation
- Triggers: infection, autoimmune disorders, and cancer
- Pathogenesis: macrophage activation, phagocytosis of blood cell progenitors, and suppression of hematopoiesis
- Clinical features: fever, splenomegaly, hepatomegaly, anemia, thrombocytopenia, and very high levels of inflammatory mediators### Lymphoid Neoplasms
- Lymphoid neoplasms are cancers that affect the immune system, particularly the white blood cells (lymphocytes).
- They are classified into two main categories: B-cell neoplasms (85-90% of cases) and T-cell neoplasms.
Precursor B-Cell Neoplasms
- B-cell acute lymphoblastic leukemia/lymphoma (B-ALL) is a type of precursor B-cell neoplasm.
- B-ALL is typically seen in children, but it can occur in adults as well.
- Acute lymphoblastic leukemia/lymphoma (ALL) is a neoplasm composed of immature B (pre-B) or T (pre-T) cells, referred to as lymphoblasts.
Peripheral B-Cell Neoplasms
- Chronic lymphocytic leukemia/small lymphocytic lymphoma is a type of peripheral B-cell neoplasm.
- It is characterized by the accumulation of mature B cells in the bone marrow and lymph nodes.
Precursor T-Cell Neoplasms
- T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) is a type of precursor T-cell neoplasm.
- T-ALL is typically seen in adolescents and young adults.
Peripheral T-Cell and NK-Cell Neoplasms
- Peripheral T-cell lymphoma, unspecified, is a type of peripheral T-cell neoplasm.
- Extranodal NK/T-cell lymphoma, nasal type, is a type of peripheral T-cell and NK-cell neoplasm.
Hodgkin Lymphoma
- Hodgkin lymphoma is a type of lymphoid neoplasm that is characterized by the presence of Reed-Sternberg cells.
- It is typically seen in young adults and is often associated with Epstein-Barr virus (EBV) infection.
Pathogenesis of Lymphoid Neoplasms
- Lymphoid neoplasms can arise from genetic mutations, particularly in genes involved in B-cell and T-cell development.
- Chromosomal translocations and gene mutations can lead to the formation of oncogenic proteins that promote cell growth and proliferation.
Risk Factors for Lymphoid Neoplasms
- Genetic factors, such as inherited genetic syndromes, can increase the risk of developing lymphoid neoplasms.
- Exposure to carcinogens, such as benzene, can also increase the risk.
- Infections, such as EBV and human T-cell leukemia virus-1 (HTLV-1), can increase the risk of developing certain types of lymphoid neoplasms.
Clinical Features of Lymphoid Neoplasms
- Lymphoid neoplasms can present with a range of symptoms, including fatigue, fever, and lymph node enlargement.
- Diagnosis is typically made by histologic examination of lymph node biopsies or bone marrow aspirates.
Classification of Lymphoid Neoplasms
- The World Health Organization (WHO) classification of lymphoid neoplasms is based on the cell of origin and the morphologic, immunophenotypic, and genetic features of the neoplasm.
- The classification includes five broad categories: precursor B-cell neoplasms, peripheral B-cell neoplasms, precursor T-cell neoplasms, peripheral T-cell and NK-cell neoplasms, and Hodgkin lymphoma.
Test your knowledge on various blood disorders including B-Cell Neoplasms, Lymphoplasmacytic Lymphoma, and Hodgkin Lymphoma. Questions cover topics like hematopoietic system components, myeloid tissues, and therapeutic conditions related to blood disorders.
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