Hema midterms exam

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Questions and Answers

Which of the following genetic abnormalities is most closely associated with the development of Chronic Myeloid Leukemia (CML)?

  • Philadelphia chromosome, leading to BCR-ABL1 fusion (correct)
  • Inversion of chromosome 16
  • Deletion of the long arm of chromosome 5
  • Mutation in the FLT3 gene

A patient presents with suspected Chronic Myeloid Leukemia (CML). What cytogenetic abnormality serves as a definitive diagnostic marker for CML?

  • Trisomy 21
  • Reciprocal translocation between chromosomes 9 and 22 (correct)
  • Deletion of chromosome 13
  • Inversion of chromosome 8

What is the functional consequence of the BCR-ABL1 fusion protein in the pathogenesis of Chronic Myeloid Leukemia (CML)?

  • Constitutive activation of tyrosine kinase activity, leading to increased cell proliferation (correct)
  • Impaired DNA repair mechanisms, resulting in genomic instability
  • Unregulated expression of cell cycle inhibitors, causing cell cycle arrest
  • Inhibition of apoptosis through downregulation of BCL-2

In Chronic Myeloid Leukemia (CML), the BCR-ABL1 fusion gene leads to the production of an abnormal tyrosine kinase. What is the primary mechanism by which this abnormal kinase contributes to the disease?

<p>It continuously phosphorylates cytoplasmic proteins, activating signal transduction pathways. (B)</p> Signup and view all the answers

What cellular adhesion process is disrupted by the loss of genetic segments in the ABL1 gene in Chronic Myeloid Leukemia (CML)?

<p>Reduced adhesion to stromal cells due to altered F-actin binding (D)</p> Signup and view all the answers

In the context of diagnosing Myeloproliferative Neoplasms (MPNs), what is the significance of the BCR-ABL1 fusion gene's presence or absence?

<p>Its presence is specifically required for the diagnosis of Chronic Myeloid Leukemia (CML). (D)</p> Signup and view all the answers

What is a key diagnostic feature that helps differentiate Atypical Chronic Myeloid Leukemia (aCML) from Chronic Myeloid Leukemia (CML)?

<p>Absence of the Philadelphia chromosome and BCR-ABL1 fusion gene in aCML. (C)</p> Signup and view all the answers

What is a key change in the World Health Organization (WHO) classification of Myeloproliferative Neoplasms (MPNs) compared to the prior French-American-British (FAB) classification system?

<p>Reduction of the minimum blast count threshold required to differentiate MPNs from Acute Leukemias (ALs). (A)</p> Signup and view all the answers

Which of the following findings is most indicative of the accelerated phase of Chronic Myeloid Leukemia (CML)?

<p>Increased proportion of blasts in the peripheral blood or bone marrow (C)</p> Signup and view all the answers

What is the underlying mechanism behind the development of hyperuricemia and uricosuria in patients with Chronic Myeloid Leukemia (CML)?

<p>Increased catabolism of purines due to high cell turnover (B)</p> Signup and view all the answers

A patient with suspected Chronic Myeloid Leukemia (CML) has a normal leukocyte alkaline phosphatase (LAP) score. What does this suggest?

<p>Requires further investigation as CML typically presents with decreased LAP. (B)</p> Signup and view all the answers

In a patient with Polycythemia Vera (PV), what genetic mutation is most commonly implicated in the pathogenesis of the disease?

<p>JAK2 V617F mutation (A)</p> Signup and view all the answers

Why are neoplastic clonal stem cells considered 'hypersensitive or independent of EPO' in Polycythemia Vera (PV)?

<p>Due to constitutive activation of erythropoietic signaling pathways regardless of EPO levels. (B)</p> Signup and view all the answers

What is the significance of the JAK2 V617F mutation's location in the pseudokinase domain?

<p>It disrupts the inhibitory function of the pseudokinase domain, resulting in constitutive tyrosine kinase activity. (D)</p> Signup and view all the answers

In managing Polycythemia Vera (PV) through therapeutic phlebotomy, what hematocrit levels are typically targeted to reduce the risk of thrombotic complications?

<p>&lt;45% in men and &lt;42% in women (A)</p> Signup and view all the answers

A patient with Essential Thrombocythemia (ET) presents with increased megakaryopoiesis and thrombocytosis. What criteria must be met to rule out other BCR-ABL1 positive neoplasms?

<p>Must not meet WHO criteria for other BCR-ABL1 positive neoplasms (C)</p> Signup and view all the answers

Which of the following genetic mutations is commonly associated with Essential Thrombocythemia (ET)?

<p>JAK2, MPL, and CALR mutations (D)</p> Signup and view all the answers

What characteristic morphologic feature of megakaryocytes is most suggestive of Essential Thrombocythemia (ET) over other Myeloproliferative Neoplasms (MPNs)?

<p>A large, mature morphology, with little to no granulocyte/erythroid proliferation (B)</p> Signup and view all the answers

How does the presence of 'giant bizarre platelets, platelet aggregates, micromegakaryocytes, megakaryocyte fragments' manifest in the peripheral blood smear (PBS) of a patient with Essential Thrombocythemia (ET)?

<p>As a sign of increased platelet production, accompanied by abnormal platelet morphology. (D)</p> Signup and view all the answers

In the management of Essential Thrombocythemia (ET), what is the primary goal of cytoreductive therapy using alkylating agents like hydroxyurea?

<p>To reduce the platelet count in order to prevent thrombotic and hemorrhagic complications. (D)</p> Signup and view all the answers

What is a distinctive feature of Primary Myelofibrosis (PMF) that differentiates it from other Myeloproliferative Neoplasms (MPNs)?

<p>Prominent splenomegaly and ineffective hematopoiesis. (A)</p> Signup and view all the answers

What is the best explanation for why fatigue is a commonly reported symptom in patients with Primary Myelofibrosis (PMF)?

<p>Ineffective hematopoiesis and anemia due to bone marrow fibrosis. (D)</p> Signup and view all the answers

What finding on bone marrow biopsy would be most indicative of Primary Myelofibrosis (PMF)?

<p>Intense fibrosis with dry tap on aspiration. (C)</p> Signup and view all the answers

What statement best describes the proposed relationship or link between PV, ET, and PMF with respect to the JAK2 mutation?

<p>The resulting phenotype is dependent on the stage of differentiation of hematopoietic stem cells (HSC) at the time of JAK2 mutation. (A)</p> Signup and view all the answers

In the context of Myelodysplastic Syndromes (MDS), what is the primary significance of the term 'dys'?

<p>It indicates an abnormality in the morphology and/or function of cells. (D)</p> Signup and view all the answers

What is the central pathophysiological characteristic that defines Myelodysplastic Syndromes (MDS)?

<p>Progressive cytopenias resulting from defects in erythroid, myeloid, and/or megakaryocytic maturation. (B)</p> Signup and view all the answers

Why is simultaneous proliferation and apoptosis of hematopoietic cells a crucial component in the pathophysiology of Myelodysplastic Syndrome (MDS)?

<p>It causes peripheral blood cytopenias due to ineffective hematopoiesis and increased cell death. (A)</p> Signup and view all the answers

How do genetic mutations impact the phenotypic characteristics observed in Myelodysplastic Syndromes (MDS)?

<p>Genetic mutations result in abnormal cellular differentiation and increased apoptosis, contributing to cytopenias. (A)</p> Signup and view all the answers

In contrast to Myeloproliferative Neoplasms (MPNs), what is a distinguishing characteristic of the cytogenetic findings typically observed in Myelodysplastic Syndromes (MDS)?

<p>MDS is characterized by varied cytogenetic findings that are not typically those associated with MPNs. (B)</p> Signup and view all the answers

What factor primarily dictates the increased risk of transformation to Acute Myeloid Leukemia (AML) in Myelodysplastic Syndromes (MDS)?

<p>The accumulation of genetic mutations leading to impaired differentiation and uncontrolled proliferation. (B)</p> Signup and view all the answers

How does the median age at diagnosis for Myelodysplastic Syndromes (MDS) generally influence treatment strategies and prognosis?

<p>Older patients with MDS may receive less intensive treatments due to comorbidities and a higher risk of treatment-related complications. (C)</p> Signup and view all the answers

In distinguishing between Myeloproliferative Neoplasms (MPN) and Myelodysplastic Syndromes (MDS), what key cellular feature differentiates MPNs from MDS?

<p>MPNs are characterized by expansion, excessive production, and accumulation of mature blood cells, whereas MDS is defined by progressive cytopenias. (D)</p> Signup and view all the answers

What is the clinical significance of identifying 'Clonal Cytopenia of Unknown Significance' (CCUS) in a patient?

<p>CCUS suggests an increased risk of progression to Myelodysplastic Syndrome (MDS) or other hematologic malignancies, warranting close monitoring. (C)</p> Signup and view all the answers

How does 'Clonal Hematopoiesis of Indeterminate Potential' (CHIP) differ from 'Clonal Cytopenia of Unknown Significance' (CCUS) in the context of Myelodysplastic Syndromes (MDS)?

<p>CHIP involves the presence of dysplasia without cytopenia, whereas CCUS has cytopenia but lacks dysplasia. (D)</p> Signup and view all the answers

What role do inherited (germline) mutations play in the etiology of Myelodysplastic Syndromes (MDS)?

<p>Germline mutations can predispose individuals to MDS, particularly in cases with associated bone marrow failure syndromes. (A)</p> Signup and view all the answers

How does the pathophysiology of Myelodysplastic Syndromes (MDS) relate to the concept of 'myeloid bias'?

<p>Myeloid bias, a consequence of sustained activation of TLRs, promotes the accumulation of mutations and contributes to the development of MDS. (C)</p> Signup and view all the answers

What is the role of inflammasome activation and pyroptosis in the pathogenesis of Myelodysplastic Syndromes (MDS)?

<p>Inflammasome activation triggers pyroptosis, a form of inflammatory cell death that contributes to ineffective hematopoiesis in MDS (C)</p> Signup and view all the answers

Despite a frequently cellular bone marrow in Myelodysplastic Syndromes (MDS), cytopenias are a common feature. What best explains this paradox?

<p>The cytopenias are a consequence of hematopoietic stem cell aging and ineffective hematopoiesis. (D)</p> Signup and view all the answers

How does dysplasia contribute to the progression from a pre-leukemic state to Acute Myeloid Leukemia (AML) in the context of Myelodysplastic Syndromes (MDS)?

<p>Dysplasia represents abnormal cellular development that may progress to cancer, including AML, with additional mutations. (C)</p> Signup and view all the answers

What finding regarding dysplastic cells must be present to meet WHO criteria for a diagnosis of MDS?

<p>At least 10% dysplastic cells in any hematopoietic lineage. (D)</p> Signup and view all the answers

In Myelodysplastic Syndromes (MDS), what implication does the presence of Auer rods have on classification and prognosis?

<p>Auer rods indicate transformation to Acute Myeloid Leukemia (AML) and classify the case as MDS/AML according to ICC criteria. (C)</p> Signup and view all the answers

What feature distinguishes MDS with low blasts and isolated 5q deletion (MDS-5q) from other subtypes of MDS?

<p>MDS-5q is associated with anemia alone, dysplastic megakaryocytes, and is often responsive to lenalidomide. (A)</p> Signup and view all the answers

In the context of MDS with mutated SF3B1 (MDS-SF3B1), how does the SF3B1 mutation impact the phenotype and prognosis of the disease?

<p>SF3B1 mutation is associated with ringed sideroblasts and a generally favorable prognosis. (A)</p> Signup and view all the answers

What is the significance of biallelic TP53 inactivation in MDS-biTP53 regarding disease outcome?

<p>Biallelic TP53 inactivation is associated with poor prognosis due to increased genomic instability and resistance to therapy. (D)</p> Signup and view all the answers

In the context of Myelodysplastic Syndromes (MDS) with increased blasts (MDS-IB), how does the blast percentage impact classification according to the WHO criteria?

<p>MDS with increased blasts includes subtypes MDS-IB1 (5-9% BM blasts or 2-4% PB blasts) and MDS-IB2 (10-19% BM blasts or 5-19% PB blasts or Auer rods). (B)</p> Signup and view all the answers

What role does cytogenetic analysis play in differentiating between Myelodysplastic Syndrome with mutated SF3B1 and thrombocytosis (MDS/MPN-SF3B1) and other Myelodysplastic/Myeloproliferative Neoplasms?

<p>Cytogenetic analysis confirms the SF3B1 mutation and helps exclude other MPN-related cytogenetic abnormalities in MDS/MPN-SF3B1. (C)</p> Signup and view all the answers

How does the presence or absence of an SF3B1 mutation guide the diagnosis of MDS/MPN with ring sideroblasts and thrombocytosis NOS (Not Otherwise Specified)?

<p>SF3B1 mutation is not required, but the presence of ≥15% ring sideroblasts is necessary for diagnosis in the absence of SF3B1 mutation. (C)</p> Signup and view all the answers

What is the role of JAK2p.V617F or biologically similar mutations in the classification of MDS/MPN with SF3B1 mutation and thrombocytosis?

<p>A concurrent JAK2p.V617F or biological similar mutation is required for the diagnosis of MDS/MPN with SF3B1 mutation and thrombocytosis. (D)</p> Signup and view all the answers

Which of the following is a diagnostic procedure used in the evaluation of lymphoid leukemias, serving as the gold standard for both leukemias and lymphomas?

<p>Excisional Biopsy (A)</p> Signup and view all the answers

A patient presents with lymphocytosis and increased inflammatory C-reactive protein (CRP). While these findings are non-specific, what does their presence suggest in the context of lymphoid neoplasms?

<p>The symptoms and lab findings are reflective of the organ involved by the neoplasm (A)</p> Signup and view all the answers

What is the rationale behind utilizing biochemical analysis in the diagnostic approach for lymphoid leukemias and lymphomas?

<p>To evaluate organ systems for tumor involvement, assess prognosis, and indirectly measure tumor burden (C)</p> Signup and view all the answers

A researcher is investigating the reasons for discrepancies in laboratory diagnoses of lymphoid neoplasms. What potential pitfall should they consider regarding antigen marker detection?

<p>Some lymphoid neoplasms can be characterized by mismatched antigenic patterns not found in normal mature cells, and some clonal populations may not be detected by specific markers. (A)</p> Signup and view all the answers

Which factor is most critical when using staging systems such as Ann Arbor or Lugano classifications for lymphoid malignancies?

<p>The distinction between limited and advanced disease in Lugano classification for Non-Hodgkin's lymphoma. (D)</p> Signup and view all the answers

In Acute Lymphoblastic Leukemia (ALL), how does the age of the patient typically correlate with disease prognosis and subtype prevalence?

<p>ALL is most prevalent in childhood, particularly between 2-5 years, with risk factors increasing with age, potentially impacting prognosis (B)</p> Signup and view all the answers

How do genetic abnormalities and gene rearrangements influence the classification and subtyping of T-ALL/T-LBL, as defined by the WHO classification?

<p>T-ALL/T-LBL is classified into subtypes based on the presence of abnormal gene rearrangements with Early T-precursor ALL as one subtype. (A)</p> Signup and view all the answers

What is the most critical implication of identifying specific immunophenotypic markers, such as CD34, TdT, and HLA-DR, in both B-ALL and T-ALL?

<p>These are common markers that help confirm the diagnosis of ALL and may aid in assessing the disease's aggressiveness. (D)</p> Signup and view all the answers

In the context of genetic and molecular findings in Acute Lymphoblastic Leukemia (ALL), how does the presence of a KMT2A rearrangement in B-ALL/LBL typically impact the prognosis, and in which age group is it most commonly observed?

<p>It is associated with a poor prognosis, especially in young infants with B-ALL/LBL. (C)</p> Signup and view all the answers

How does the presence or absence of mutation in the Heavy Chain Immunoglobulin Gene (IGHV) relate to disease progression and clinical outcome in Chronic Lymphocytic Leukemia (CLL)?

<p>IGHV mutated CLL is associated with a more mature phenotype and better outcome (D)</p> Signup and view all the answers

What is the significance of sustained presence of at least 5 x 10^9/L circulating B lymphocytes in the context of IWCLL criteria, and how is clonality determined for diagnostic purposes?

<p>It is a key diagnostic criterion for CLL, with clonality established through flow cytometry. (A)</p> Signup and view all the answers

What are the key morphologic characteristics observed in Chronic Lymphocytic Leukemia (CLL) cells, and how do these features contribute to the formation of 'smudge cells'?

<p>Small, mature cells with minimal cytoplasm, dense nuclei, that are fragile and easily damaged during slide preparation. (C)</p> Signup and view all the answers

How does prolymphocytic transformation affect Chronic Lymphocytic Leukemia (CLL) and what is the significance of assessing prolymphocyte percentage in bone marrow (BM) or peripheral blood smear (PBS)?

<p>Prolymphocytic transformation signifies a more aggressive disease, necessitating the assessment of prolymphocyte percentage in BM or PBS to guide management strategies. (A)</p> Signup and view all the answers

A patient with CLL is being evaluated for prognosis. What implication does the presence of CD38 and ZAP-70 have on the disease and what genetic factors contribute to the worst prognosis?

<p>They indicate higher proliferative capability and contribute to a poor prognosis with TP53 mutations and del(17p) associated with worst outcomes. (B)</p> Signup and view all the answers

Monoclonal B-cell lymphocytosis (MBL) is characterized by a monoclonal B-cell population. What key factor distinguishes MBL from CLL, and what is the typical clinical presentation of MBL?

<p>MBL is defined by &lt; 5 x 10^9/L circulating B lymphocytes, usually asymptomatic, without end-organ damage. (C)</p> Signup and view all the answers

How does the presence or absence of evidence regarding adenopathy or organomegaly influence the differentiation between Monoclonal B-Cell Lymphocytosis (MBL), and Chronic Lymphocytic Leukemia (CLL)?

<p>Their presence is a factor in determining the diagnosis. (A)</p> Signup and view all the answers

What treatment approach has demonstrated a complete response rate in approximately 90% of patients diagnosed with T-prolymphocytic leukemia (T-PLL)?

<p>Anti-CD52 antibody (alemtuzumab). (A)</p> Signup and view all the answers

A patient is diagnosed with Hairy Cell Leukemia. Which of the following combinations of symptoms and primary organ involvements is most indicative of this condition?

<p>Splenomegaly, cytopenias, and primary involvement of the spleen, blood, and bone marrow. (D)</p> Signup and view all the answers

What clinical characteristics and diagnostic criteria distinguish Large Granular Lymphocytic (LGL) Leukemia from other lymphoid disorders?

<p>Circulating LGLs persistent for more than 6 months in either cytotoxic T-cells or NK cells. (A)</p> Signup and view all the answers

What are the key diagnostic differences between T-large granular lymphocytic leukemia and NK-large granular lymphocytic leukemia concerning cell markers and clonality?

<p>T-LGL leukemia involves clonal expansion of cytotoxic T cells with CD3+ and CD8+ expression. Whereas, NK-LGL leukemia shows clonal expansion of NK cells with CD3- and CD56+ expression. (C)</p> Signup and view all the answers

Which of the following is the most significant rationale for using flow cytometry in diagnosing mature lymphoid neoplasms?

<p>To define the degree of maturation and identify the lineage of interest and determine the clonality. (B)</p> Signup and view all the answers

In what manner do recurrent drenching night sweats, unexplained weight loss, and persistent fever as 'B symptoms' contribute to the clinical assessment of a patient with a suspected lymphoid neoplasm?

<p>Impacts the staging and management of lymphomas. (C)</p> Signup and view all the answers

What role do cytopenias play in distinguishing between MBL and CLL, considering their diagnostic criteria and clinical presentation?

<p>Cytopenias are commonly associated with CLL, whereas their absence is a feature of MBL. (B)</p> Signup and view all the answers

In the context of Large Granular Lymphocytic Leukemia (LGL), what implications does the detection of restricted Killer-cell immunoglobulin-like receptor (KIR) expression have on disease classification and pathogenesis?

<p>Provides evidence supporting the clonal nature of the cells. (D)</p> Signup and view all the answers

What therapeutic mechanisms of action are associated with alkylating agents and nucleoside analogues in the context of lymphoid leukemia treatment?

<p>Induction of DNA damage and interference with DNA synthesis. (C)</p> Signup and view all the answers

Which route of transmission is LEAST commonly associated with the Human T-cell Lymphotropic Virus-1 (HTLV-1) that is linked to Adult T-cell Leukemia/Lymphoma (ATLL)?

<p>Respiratory droplets (C)</p> Signup and view all the answers

In a patient diagnosed with the leukemia phase of Acute T-cell Leukemia/Lymphoma (ATLL), which combination of cell surface markers is MOST likely to be observed?

<p>CD3+, CD4+, CCR4+, CD25+ (D)</p> Signup and view all the answers

Which therapeutic strategy is LEAST likely to be effective in the acute subtype of Adult T-Cell Leukemia/Lymphoma (ATLL)?

<p>Single-agent chemotherapy (A)</p> Signup and view all the answers

What is the MOST critical factor that distinguishes endemic Burkitt Lymphoma from other subtypes of Burkitt Lymphoma?

<p>Geographic location and association with <em>Epstein-Barr virus</em> (EBV) (D)</p> Signup and view all the answers

Which clinical scenario would MOST strongly suggest a diagnosis of Immunodeficiency-associated Burkitt Lymphoma over the other subtypes?

<p>A young adult with a history of solid organ transplant presents with CNS involvement. (B)</p> Signup and view all the answers

Why is the presence of a "Starry Sky" pattern on bone marrow or lymph node biopsy MOST clinically relevant in the diagnosis of Burkitt Lymphoma?

<p>It indicates the presence of numerous macrophages engulfing apoptotic tumor cells. (D)</p> Signup and view all the answers

Given the generally incurable nature of Follicular Lymphoma (FL), what is the MOST critical long-term management strategy for patients following initial treatment?

<p>Maintenance therapy to prolong remission and manage disease progression. (B)</p> Signup and view all the answers

Which histopathological feature is MOST critical in distinguishing Follicular Lymphoma (FL) from reactive follicular hyperplasia?

<p>Disruption of normal lymph node architecture by monotonous follicles (A)</p> Signup and view all the answers

In the WHO grading system for Follicular Lymphoma (FL), what dictates a 'poorer outcome'?

<p>The presence of more than 15 centroblasts per high-power field (HPF) (C)</p> Signup and view all the answers

How does Cyclin D1 overexpression contribute to the pathogenesis of Mantle Cell Lymphoma (MCL)?

<p>By accelerating the cell cycle progression from G1 to S phase (B)</p> Signup and view all the answers

What clinical presentation is MOST likely to indicate a diagnosis of Mantle Cell Lymphoma (MCL) rather than other small B-cell lymphomas?

<p>Extensive lymphadenopathy with gastrointestinal tract involvement in an older male (D)</p> Signup and view all the answers

A patient diagnosed with Mantle Cell Lymphoma (MCL) is found to be SOX11 negative. What is the MOST accurate implication of this finding?

<p>The MCL is more likely to be aggressive and have a poorer prognosis. (C)</p> Signup and view all the answers

What is the PRIMARY rationale for considering MYC gene rearrangement as a critical diagnostic and prognostic factor in Diffuse Large B-Cell Lymphoma (DLBCL)?

<p>MYC rearrangement is often associated with aggressive disease and may lead to treatment resistance. (B)</p> Signup and view all the answers

In the context of Diffuse Large B-Cell Lymphoma (DLBCL), what does 'concordant' bone marrow involvement signify regarding disease staging and management?

<p>The bone marrow involvement mirrors the nodal/extranodal sites, suggesting widespread disease. (C)</p> Signup and view all the answers

What is the PRIMARY significance of distinguishing between germinal center B-cell-like (GCB) and non-germinal center B-cell-like (non-GCB) subtypes of Diffuse Large B-Cell Lymphoma (DLBCL)?

<p>It influences prognosis and guides treatment strategies. (B)</p> Signup and view all the answers

How does the association of Marginal Zone Lymphoma (MZL) with chronic antigen stimulation influence its treatment approach?

<p>It suggests that targeting the chronic antigen source may lead to lymphoma regression. (D)</p> Signup and view all the answers

Why is Splenic Marginal Zone Lymphoma (SMZL) often associated with 'villous lymphocytes' in the peripheral blood?

<p>These cells reflect the lymphoma's origin in the splenic marginal zone, where lymphocytes have specific morphological features. (A)</p> Signup and view all the answers

What is the KEY histological difference between Nodal Marginal Zone Lymphoma (NMZL) and other small B-cell lymphomas that impacts its classification and diagnosis?

<p>The distinct growth pattern and cellular composition within the lymph node. (A)</p> Signup and view all the answers

How does the clinical behavior of Mycosis Fungoides (MF) typically differ from that of Sézary Syndrome (SS), influencing treatment strategies and prognosis?

<p>MF is indolent and primarily confined to the skin, while SS is aggressive with systemic involvement. (C)</p> Signup and view all the answers

Why are Pautrier microabscesses considered a significant diagnostic feature in Mycosis Fungoides (MF)?

<p>They contain malignant T-cells exhibiting cerebriform nuclei within the epidermis. (A)</p> Signup and view all the answers

What is the PRIMARY diagnostic criterion used to differentiate Sézary Syndrome (SS) from other cutaneous T-cell lymphomas?

<p>The triad of erythroderma, generalized lymphadenopathy, and Sézary cells in the skin, lymph nodes, and peripheral blood. (B)</p> Signup and view all the answers

How does the presence or absence of the Anaplastic Lymphoma Kinase (ALK) protein in Anaplastic Large Cell Lymphoma (ALCL) influence its clinical behavior and prognosis?

<p>ALK-positive ALCL is more common in younger patients and generally has a better prognosis. (A)</p> Signup and view all the answers

In the context of Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL-NOS), what is the MOST significant challenge in achieving effective treatment outcomes?

<p>The heterogeneity in clinical presentation and lack of targeted therapies. (C)</p> Signup and view all the answers

What key feature differentiates Hodgkin Lymphoma from Non-Hodgkin Lymphoma in terms of disease spread and extranodal involvement?

<p>Hodgkin Lymphoma spreads contiguously and rarely involves extranodal sites. (D)</p> Signup and view all the answers

Why is the identification of Reed-Sternberg cells crucial in the diagnosis of Classic Hodgkin Lymphoma (CHL)?

<p>These cells are pathognomonic for CHL and confirm the diagnosis. (D)</p> Signup and view all the answers

Flashcards

Myeloproliferative Neoplasm

Clonal hematopoietic disorders caused by genetic mutations in HSCs.

Philadelphia chromosome

Confirms diagnosis through reciprocal translocation between chromosomes 9 and 22, leading to BCR-ABL1 fusion.

Chronic Myeloid Leukemia (CML)

Single genetic mutation in HSCs leading to clonal overproduction of myeloid cells.

BCR-ABL1 fusion protein formation

ABL1 proto-oncogene translocation from chromosome 9 to chromosome 22.

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Kinases

Enzymes that catalyze the transfer of phosphate groups regulating various cellular processes.

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Signal transduction pathways activation in CML

Results in increased clonal proliferation of myeloid cells.

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Leukocytosis with left shift

Increased white blood cells with immature cells in the peripheral blood.

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Leukocyte Alkaline Phosphatase (LAP)

Enzyme found in secondary granules of PMNs, used to assess activity in CML.

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Polycythemia Vera (PV) Pathogenesis

Neoplastic clonal stem cells are hypersensitive to or independent of EPO for cell growth

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JAK2 protein

Protein: tyrosine kinase associated with cytokine receptors. Includes JH1 (kinase activity) and JH2 (pseudokinase domains).

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JAK2 V617F mutation

Mutation in 95% of PV cases creating constitutively active erythropoietic signal transduction independent of EPO.

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PBS: Increased RBCs, granulocytes, and platelets

Increased red blood cells, granulocytes, and platelets.

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Therapeutic phlebotomy goal

Maintain hematocrit levels <45% in men and <42% in women.

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Essential Thrombocythemia

Increased megakaryopoiesis and thrombocytosis (>600 x 109/L).

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Major diagnostic criterion for ET

Megakaryocyte proliferation with large, mature morphology, little to no granulocyte/erythroid proliferation.

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CALR mutation

Mutation in ET where the normal function is to modulate JAK-STAT pathway.

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Giant Bizarre Platelets

Mutation affects JAK-STAT modulation.

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Goals of ET treatment

Reduction of platelet count and controlling fibrosis.

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Primary Myelofibrosis

Splenomegaly with ineffective hematopoiesis, leukoerythroblastosis, fibrosis, and increased megakaryocytes.

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Constitutional symptoms of PMF

Fatigue, bone pain, night sweats.

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Linking PV, ET and PMF

Hypothesized dependence on differentiation stage. Direct platelet differention if JAK2 is mutated.

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BM Biopsy in PMF

Dry tap and Cellularity (increased granulocytic, megakaryocytic hypercellularity).

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PBS in PMF

Dacrocytes, Nucleated RBCs and polychromatophilia.

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Treating PMF

Alkylating agents in myeloproliferative disorders used to treat hydroxyurea.

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Key BM Finding

Enlarged BM sinuses without fibrosis.

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What does "dys" mean?

Abnormal in morphology and/or function.

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What does "myelo" refer to?

Relating to myeloid cell lineage (immature or mature).

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What does "-poietic" mean?

The process of cell formation.

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What is Myelodysplastic Syndrome/Neoplasm (MDS)?

Acquired clonal hematologic disorders characterized by progressive cytopenias.

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What are Progressive Cytopenias?

Low blood cell counts in the peripheral blood.

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Apoptosis in MDS

Occurs simultaneously with proliferation in the early stages of MDS.

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What are Pre-MDS conditions?

Conditions occurring before a full MDS diagnosis.

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What is Clonal Cytopenia of Unknown Significance (CCUS)?

Lack of dysplasia and MDS-related mutation.

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What is Clonal Hematopoiesis of Indeterminate Potential (CHIP)?

Lack of dysplasia and peripheral cytopenia.

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Secondary MDS mutations

Mutations from therapy, chemicals or radiation.

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Pathophysiology of MDS involves:

Abnormal innate immune activation, proinflammatory signaling.

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Overexpression of TLRs on HSCs

Leads to sustained activation, myeloid bias and mutations.

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Inflammasome activation

Activation leading to pyroptosis.

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Hallmark of MDS

Progressive cytopenias, despite a cellular bone marrow.

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Ineffective hematopoiesis

Activation of pyroptosis.

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Dysplasia

Abnormal cells within a tissue or organ.

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PBS/BM findings - WHO thresholds

WHO's threshold = at least 10% cells with dysplasia in a lineage.

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Dyserythropoiesis found in

Oval macrocyte (most common), hypochromic microcytes, and dimorphic RBC population.

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BM findings: Dyserythropoiesis

RBC precursors with >1 nucleus, abnormal nuclear shapes.

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Dysmyelopoiesis (PBS)

Persistence of basophilia in mature WBC.

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FAB Classification

Classifies based on morphology, dysplasia amount, and blasts number.

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Lymphoid Neoplasms

Malignancies originating from lymphoid progenitor cells or mature lymphocytes; can involve blood, bone marrow, and/or lymphoid tissues.

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Lymphadenopathy

Enlargement of lymph nodes due to proliferation or infiltration of lymphocytes or other immune cells.

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Splenomegaly

Enlargement of the spleen, often due to increased workload or infiltration by abnormal cells.

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Hepatomegaly

Enlargement of the liver, commonly caused by viral infections, alcohol abuse, or infiltration by neoplastic cells.

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B Symptoms

Symptoms such as fever, night sweats, and weight loss associated with certain cancers and infections.

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Lymphocytosis

Increased number of lymphocytes in the blood.

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Flow Cytometry

Technique used to identify and count cells based on their physical and chemical characteristics.

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Immunophenotyping

Technique that identifies cells based on surface markers, aiding in the classification of hematologic neoplasms.

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FISH (Fluorescence In Situ Hybridization)

A genetic test used to detect specific DNA sequences, chromosomal abnormalities, and gene rearrangements.

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Biochemical Analysis

Analysis of blood and other bodily fluids to assess organ function and detect abnormalities.

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Fine-Needle Aspiration

Removal of a small piece of tissue or fluid for diagnostic examination under a microscope.

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PET with FDG

Radiological imaging technique using radioactive glucose to detect metabolically active tissues.

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Ann Arbor Staging

System for staging cancers, originally for Hodgkin's lymphoma, now used for other lymphomas.

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Lugano Classification

A staging system for lymphomas, particularly useful for non-Hodgkin lymphomas.

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International Prognostic Index (IPI)

Prognostic tool that assesses risk in patients with aggressive non-Hodgkin lymphoma.

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Acute Lymphoblastic Leukemia (ALL)

A type of acute leukemia that affects lymphoid cells, more common in children.

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B-ALL

A subtype of acute lymphoblastic leukemia affecting B cell progenitors.

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T-ALL

A subtype of acute lymphoblastic leukemia affecting T cell progenitors.

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Prolymphocytic Progression

Disorder characterized by a high count of abnormal prolymphocytes in bone marrow or peripheral blood

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Smudge Cells

Damaged lymphocytes observed in peripheral blood smears, often associated with CLL.

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Rai/Binet Classification

Staging methods for CLL, assessing the severity and extent of the disease.

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CLL (Chronic Lymphocytic Leukemia)

A type of indolent B-cell lymphoma affecting older adults, often asymptomatic at diagnosis.

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Monoclonal B-Cell Lymphocytosis (MBL)

The presence of a monoclonal B-cell population in the blood at low levels, without other signs of leukemia.

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Non-Hodgkin's Lymphoma (NHL)

A diverse group of malignancies affecting lymphocytes, often presenting with lymphadenopathy, splenomegaly, and B symptoms.

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Adult T-Cell Leukemia/Lymphoma (ATLL)

A post-thymic neoplastic disorder of T cells, associated with HTLV-1, and transmitted through transplacental routes, breastfeeding, blood, and intercourse.

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Acute ATLL

A clinical subtype of ATLL characterized by aggressive behavior and extensive extranodal involvement of peripheral blood and skin.

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Leukemia phase of ATLL

Marked leukocytosis with the presence of "flower cells," CD3+, CD4+, CCR4+, CD25+, and CD7-and 8-.

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Acute ATLL prognosis

A subtype of ATLL with a poorer outcome and a median survival of 8 months.

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Chronic ATLL prognosis

A subtype of ATLL with a better outcome, often managed with interferon-alpha, azidothymidine (AZT), anti-CCR4 antibody (Mogamulizumab), and HSCT.

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Burkitt Lymphoma (BL)

Aggressive malignancy of mature B cells characterized by rapid tumor growth.

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Endemic Burkitt Lymphoma

Commonly affects children in equatorial Africa, presenting with extranodal involvement (orbit, mandible) and positive for EBV genome.

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Leukemic Phase of Burkitt lymphoma

Primarily involves the blood and bone marrow, characterized by B cells with finely clumped chromatin and deeply basophilic cytoplasm with distinct vacuoles.

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Burkitt Lymphoma Cytological characteristics

B cells with finely clumped chromatin, deeply basophilic cytoplasm with distinct vacuoles are common.

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Burkitt Lymphoma Treatment

Aggressive, but highly responsive to chemotherapy, with a cure rate of 90% in early disease and 60-80% in advanced disease.

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Follicular Lymphoma (FL)

Neoplastic disorder of germinal B cells, commonly affecting middle-aged to older adults and generally incurable.

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Follicular Lymphoma Presentation

Painless lymphadenopathy with FL cells exhibiting scant cytoplasm, heavily condensed chromatin, and distinct deep nuclear clefts at sharp angles.

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Centrocytes

small, irregular cells with angular appearance, found in FL.

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Centroblasts

Larger, found in FL.

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Follicular Lymphoma Grading

Graded according to the number of large cells, with Grade 3 indicating a poorer outcome.

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Grade 1 Follicular Lymphoma

0-5 centroblasts per HPF

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Grade 2 Follicular Lymphoma

6-15 centroblasts per HPF

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Grade 3 Follicular Lymphoma

15 centroblasts per HPF

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Mantle Cell Lymphoma (MCL)

Characterized by extensive lymphadenopathy, extranodal involvement (GI tract), absolute lymphocytosis in >50%, and t(11,14) leading to overexpression of cyclin D1.

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Mantle Cell Lymphoma info

6% of Non-Hodgkin's Lymphoma, median age: 68 years old, Males > Females, GENERALLY CLINICALLY AGGRESSIVE.

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Diffuse Large B Cell Lymphoma (DLBCL) information

Rapidly expanding painless lymphadenopathy in one or more sites, may be de novo or transformation from a more indolent form of lymphoma

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International Prognostic Index info

International Prognostic Index initially developed from patients with DLBCL

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Indolent B-cell lymphoma

Lymphoma associated with chronic antigen stimulation.

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MALT lymphoma

a common type of MZL, associated with organs that lack obvious lymphoid tissue exposed to chronic inflammation

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Study Notes

Adult T-Cell Leukemia/Lymphoma (ATLL)

  • Post-thymic neoplastic disorder of T cells
  • Associated with HTLV-1 and is transmitted through:
    • Transplacental transmission
    • Breastfeeding
    • Blood
    • Intercourse
  • Four clinical subtypes exist
  • Acute ATLL:
    • Aggressive
    • Extensive extranodal involvement of peripheral blood and skin
  • Leukemia phase:
    • Marked leukocytosis
    • "Flower Cell" presence
    • CD 3+
    • CD 4+
    • CCR 4+
    • CD 25+
    • CD 7- and 8-
  • Acute subtype: poor prognosis with a median survival of 8 months
  • Chronic subtype: better prognosis
  • Treatment options:
    • Interferon-alpha
    • Azidothymidine (AZT)
    • Anti-CCR4 Antibody (Mogamulizumab)
    • HSCT

Burkitt Lymphoma (BL)

  • Aggressive malignancy of mature B cells
  • Rapid tumor growth
  • Three subtypes:
    • Endemic:
      • Common in children
      • Found in Equatorial Africa
      • Extranodal involvement (orbit, mandible)
      • (+) EBV genome
    • Sporadic:
    • Common in Western regions
    • Abdominal disease
    • BM infiltration in 70%
    • CNS involvement in 1/3
    • Immunodeficiency-associated:
      • HIV
      • Post-transplantation
      • Congenital immunodeficiency
      • Primarily involves the blood and bone marrow
  • Leukemia phase:
    • B cells with finely clumped chromatin
    • Deeply basophilic cytoplasm with distinct vacuoles
    • Bone marrow or lymph node biopsy: "Starry Sky" pattern
  • Mature B cell markers:
    • IgD+
    • LCR+
    • CD 10+
    • CD 34 - and TdT-
  • Highly responsive to chemotherapy
  • Curable in 90% with early disease, 60-80% with advanced disease
  • Risk for tumor lysis syndrome

Follicular Lymphoma (FL)

  • Neoplastic disorder of germinal B cells
  • Second most common NHL
  • Disease of middle aged to older adults
  • Generally incurable
  • Painless lymphadenopathy
  • FL cells with the following characteristics:
    • Scant cytoplasm
    • Heavily condensed chromatin
    • Distinct deep nuclear clefts at sharp angles
  • BM biopsy:
    • Localization of tumor cells in a paratrabecular distribution
    • Centrocytes:
      • Small
      • Irregular cells with angular appearance
    • Centroblasts:
      • Larger
  • Round to ovoid nuceli
  • 1-3 nucleoli
  • Graded according to number of large cells
  • Grade 3 = poorer outcome

Mantle Cell Lymphoma (MCL)

  • 6% of Non-Hodgkin’s Lymphoma
  • Median age: 68 years old
  • More common in males
  • Generally clinically aggressive
  • Extensive lymphadenopathy
  • Extranodal: GI Tract
  • PBS:
    • Lymphoma cells in 75%
    • Absolute lymphocytosis in >50%
  • Spectrum of morphologic variants
  • T(11,14), overexpression of cyclin D1
    • SOX11 in cyclin D1 negative
  • Advanced Stage, asymptomatic
    • Watchful waiting
    • Rituximab
  • Advanced Stage, symptomatic
    • Chemotx
    • Chemo-immunotx
    • Radio-immunotx
  • Mantle cell International Prognostic Index (MIPI)
    • Points are assigned based on age, WBC, LDH, and ECOG PS

Diffuse Large B Cell Lymphoma (DLBCL)

  • Most common form of Non-Hodgkin’s Lymphoma
  • May arise de novo or transformation from a more indolent form of lymphoma
  • Aggressive but curable in 2/3 of patients
  • Rapidly expanding painless lymphadenopathy in one or more sites
  • Extranodal:
    • GI Tract
    • Testis
    • Bone
  • Bone marrow involvement may or may not be concordant to node/extranodal site
  • DLBCL manifests like leukemic blasts
    • Pleomorphic with large/irregular nuclei
    • Prominent nucleoli
    • Variably clumped chromatin
  • Mutations:
    • tBCL6 gene - (30%)
    • tBCL2 gene, t(14;18) - (20-30%)
      • Also seen in Follicular Lymphoma (FL)
    • MYC gene rearrangement
      • Also seen in Burkitt Lymphoma
  • Two subtypes:
    • Germinal Center DLBCL
      • Favors prognosis
    • Non-germinal Center DLCBL

Marginal Zone Lymphoma (MZL)

  • Indolent B-cell lymphoma
  • Associated with chronic antigen stimulation
  • Three subtypes:
    • Extranodal marginal zone lymphoma of MALT
    • Splenic marginal zone lymphoma
    • Nodal marginal zone lymphoma
  • MALT lymphoma
    • Most common type of MZL
    • Associated with organs which lacks obvious lymphoid tissue exposed to chronic inflammation
    • Stomach is often involved
    • Treatment is symptomatic
  • Splenic Marginal Zone of Lymphoma (SMZL)
    • <1% of Non-Hodgkin’s Lymphoma
    • Adults >50 years old
    • Symptoms:
      • Massive splenomegaly
      • Absolute lymphocytosis
      • Villous lymphocytes (looks like hairy cell leukemia)
    • (-) CD 103, Annexin A
    • Treatment: watch and wait, rituximab
  • Nodal Marginal Zone Lymphoma (NMZL)
    • 1% of Non-Hodgkin’s Lymphoma
    • Adults >50 years old
    • NMZL cells extends from the mantle-marginal zone interface
    • May be associated with Hepatitis C
  • Morphologic variants: Centroblastic, Immunoblastic, Anaplastic, and other rare variants
  • Molecular subtypes: Germinal centre B-cell subtype and Activated B-cell subtype
  • Other lymphomas of large B cells: High-grade B-cell lymphoma, High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, High-grade B-cell lymphoma, NOS, B-cell lymphoma unclassifiable, B-cell lymphoma unclassifiable, with features intermediate between diffuse large, B-cell lymphoma and classic Hodgkin lymphoma
  • Highly curable
  • International Prognostic Index initially developed from patients with DLBCL -Rituximab + combination chemotherapy – standard of care

Mycosis Fungoides/Sezary Syndrome (MF/SS)

  • Cutaneous T-cell lymphoma
  • Disease of the elderly
  • More common in males
  • Mycosis Fungoides
    • 60-70%
    • Confined to the skin
    • May disseminate in later stages
    • Indolent
  • Sezary Syndrome
    • Aggressive
    • Systemic disorder
    • Primarily involves the peripheral blood
    • Worst prognosis
  • Presentation:
    • Erythroderma
    • Generalized lymphadenopathy
    • Sezary cells in skin, lymph nodes, and peripheral blood
    • Diagnosis: requires all three characteristics from above plus at least one of the following
      • increased CD 4+ T cells resulting in a CD 4/CD 8 ratio of 10 or greater
      • a loss of at least one T cell antigen
      • absolute Sezary cell count >1,000 cells/uL in the peripheral blood
  • Treatment:
    • Mycosis Fungoides: symptomatic
      • Topical steroids
      • Nitrogen mustard
      • Phototherapy
    • Sezary Syndrome: has the worst prognosis
      • Chemotherapy
  • CD 4+ T cells
  • MF/SS cells: -Scant cytoplasm -Cerebriform, folded nucleus Mycosis Fungoides: -Psoriatic-like skin lesions -Localization of atypical cells in Pautrier microabscesses in the epidermis

Anaplastic Large Cell Lymphoma (ALCL)

  • T-cell lymphoma presenting with large pleomorphic cells
  • CD 30+
  • Two subtypes:
    • ALK (+):
      • 10-30% of childhood lymphomas
      • Younger individuals
      • Better prognosis
    • ALK (-):
      • Older patients (57 years old)
      • May be associated with breast implants
  • Advanced staged of presentation
  • B symptoms
  • Organ involvement:
    • Lymph nodes
    • Skin
    • Bones
    • Soft tissue (liver, lungs)
  • Treatment:
    • Chemotherapy
    • Monoclonal antibodies
    • HSCT

Peripheral T-Cell Lymphoma, Not Otherwise Specified (PTCL-NOS)

  • T-cell mismatch
  • (-) CD 7, CD 5
  • Variable clinical course
  • Treatment:
    • Combination therapy
    • Monoclonal antibodies

Hodgkin’s Lymphoma

  • Nodal-based disease
  • Rare
  • Younger age group
  • Classic Hodgkin's Lymphoma:
    • 95% of cases
    • Bimodal age distribution (30s, after 50 years old)
    • Cervical/supraclavicular or mediastinal adenopathy
    • Reed Sternberg Cells – "owl’s eye" appearance
      • (+) CD 30, CD 15
      • Seen in lymph nodes
    • 4 subtypes:
      • Nodular sclerosis
      • Lymphocyte-rich
      • Mixed cellularity
      • Lymphocyte depleted
  • Nodular Lymphocyte Predominant Hodgkin Lymphoma (NLPHL)
    • Young adults
    • Peripheral lymphadenopathy
    • Mediastinal adenopathy is uncommon
    • Lymphocytic histiocytic (L&H) cells
  • Spread contiguously
  • Rare involvement of extranodal sites
  • Contain "Reed-Sternberg Cells"
  • Large cells with scant cytoplasm
  • Folded single nucleus
  • Popcorn cells
  • (-) CD 15, CD 30
  • (+) epithelial membrane antigen (EMA) – 50%
  • Treatment
    • Combination Therapy
    • Radiotherapy
    • Immune checkpoint blockade inhibitors

Non-Hodgkin Lymphoma

  • Can spread non-contiguously
  • Involves extranodal sites -Skin -Brain -GI Tract
  • No Reed-Sternberg Cells

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