Podcast
Questions and Answers
Which of the following is NOT typically affected by leukemia?
Which of the following is NOT typically affected by leukemia?
What is the primary reason for the accumulation of dysfunctional cells in leukemia?
What is the primary reason for the accumulation of dysfunctional cells in leukemia?
Which of the following is NOT listed as an associated etiological factor for leukemia?
Which of the following is NOT listed as an associated etiological factor for leukemia?
What is a key difference between acute and chronic leukemias regarding cell maturity?
What is a key difference between acute and chronic leukemias regarding cell maturity?
Signup and view all the answers
Which of the following is a subtype of acute leukemia?
Which of the following is a subtype of acute leukemia?
Signup and view all the answers
What are chromosomal aberrations in ALL known to dysregulate?
What are chromosomal aberrations in ALL known to dysregulate?
Signup and view all the answers
A gain-of-function mutation in which gene is commonly observed in T-ALL?
A gain-of-function mutation in which gene is commonly observed in T-ALL?
Signup and view all the answers
Loss-of-function mutations in which gene are frequently found in B-ALL?
Loss-of-function mutations in which gene are frequently found in B-ALL?
Signup and view all the answers
What is the result of the (14;18) translocation in follicular lymphomas?
What is the result of the (14;18) translocation in follicular lymphomas?
Signup and view all the answers
Which genetic alteration is most commonly associated with lymphoplasmacytic lymphoma?
Which genetic alteration is most commonly associated with lymphoplasmacytic lymphoma?
Signup and view all the answers
What characterizes Acute Myelogenous Leukemia (AML)?
What characterizes Acute Myelogenous Leukemia (AML)?
Signup and view all the answers
In Chronic Lymphocytic Leukemia (CLL), what is the primary issue observed?
In Chronic Lymphocytic Leukemia (CLL), what is the primary issue observed?
Signup and view all the answers
Which condition is associated with excessive development of mature neoplastic granulocytes?
Which condition is associated with excessive development of mature neoplastic granulocytes?
Signup and view all the answers
What is a common symptom of Hairy Cell Leukemia?
What is a common symptom of Hairy Cell Leukemia?
Signup and view all the answers
What mutation is strongly associated with Polycythemia vera?
What mutation is strongly associated with Polycythemia vera?
Signup and view all the answers
Chronic Lymphocytic Leukemia is most commonly associated with what?
Chronic Lymphocytic Leukemia is most commonly associated with what?
Signup and view all the answers
What is a leading feature of Acute Myelogenous Leukemia?
What is a leading feature of Acute Myelogenous Leukemia?
Signup and view all the answers
What commonly accompanies the (11;14) translocation?
What commonly accompanies the (11;14) translocation?
Signup and view all the answers
Flashcards
Leukemia
Leukemia
Malignant disorders that affect blood-forming tissues such as bone marrow, lymph system, and spleen.
Leukemia's effect on cell division
Leukemia's effect on cell division
The uncontrolled growth of dysfunctional cells due to a loss of regulation in cell division.
Acute Leukemia
Acute Leukemia
A type of leukemia characterized by rapid proliferation of immature blood cells.
Chronic Leukemia
Chronic Leukemia
Signup and view all the flashcards
Acute Lymphoblastic Leukemia (ALL)
Acute Lymphoblastic Leukemia (ALL)
Signup and view all the flashcards
Acute Myelogenous Leukemia (AML)
Acute Myelogenous Leukemia (AML)
Signup and view all the flashcards
Chronic Lymphocytic Leukemia (CLL)
Chronic Lymphocytic Leukemia (CLL)
Signup and view all the flashcards
Chronic Myeloid Leukemia (CML)
Chronic Myeloid Leukemia (CML)
Signup and view all the flashcards
Chronic Myelogenous Leukemia (CML)
Chronic Myelogenous Leukemia (CML)
Signup and view all the flashcards
Hairy Cell Leukemia
Hairy Cell Leukemia
Signup and view all the flashcards
Polycythemia Vera
Polycythemia Vera
Signup and view all the flashcards
B cell receptor (BCR) and BCL2 overexpression
B cell receptor (BCR) and BCL2 overexpression
Signup and view all the flashcards
Chromosomal deletions and BCL2 overexpression
Chromosomal deletions and BCL2 overexpression
Signup and view all the flashcards
Translocation (14;18) in follicular lymphoma
Translocation (14;18) in follicular lymphoma
Signup and view all the flashcards
Translocation (11;14) in mantle cell lymphoma
Translocation (11;14) in mantle cell lymphoma
Signup and view all the flashcards
MYD88 mutations in lymphoplasmacytic lymphoma
MYD88 mutations in lymphoplasmacytic lymphoma
Signup and view all the flashcards
Study Notes
Benign and Neoplastic Disorders
- Benign qualitative disorders; Benign disorders; Acute and chronic leukemias; Neoplastic myeloid disorders; Lymphoid leukemias are mentioned.
- White blood cell (WBC) qualitative disorders, acute and chronic leukemias, and neoplastic myeloid disorders and lymphoid leukemias are discussed.
Non-Neoplastic Disorders of White Cells
- A decrease in white blood cells (leukopenia) is a decrease in disease-fighting cells (leukocytes) in the blood Leukopenia is almost always related to a decrease in neutrophils.
- The definition of a low white blood cell count can vary between medical practices.
Definition of Neutropenia
- Absolute Neutrophil Count (ANC) is calculated as WBC x (% bands + segs).
- Normal ANC is 1500/mm³.
- Neutropenia is categorized as mild (1000-1500), moderate (500-1000), and severe (<500).
- Age slightly factors into the definition of neutropenia.
Causes of Neutropenia
- Acquired:
- Infection
- Infiltrative bone marrow disease
- Immune-mediated
- Medication
- Congenital:
- Severe Congenital
- Cyclic neutropenia
- Chronic benign neutropenia of childhood
- Chronic neutropenia of childhood
- Benign Ethnic Neutropenia
- Schwachman Diamond syndrome
Symptoms of Cyclic Neutropenia
- Fevers
- Feeling sick
- Mouth sores/ulcers
- Pharyngitis
- Periodontal disease
- Loss of appetite
- Increased susceptibility to bacterial infections affecting skin, digestive tract, and respiratory system. Infections can be life-threatening.
Reactive Leukocytosis
- An increase in white blood cells (WBCs) in the blood is common in inflammatory states caused by microbial or non-microbial stimuli.
- Leukocytosis is often nonspecific and classified by the affected white blood cell type.
- Leukemoid reaction involves a marked increase in WBCs with left-shifted granulopoiesis, mimicking chronic myelogenous leukemia. It can occur in severe stress or paraneoplastic syndromes.
Infectious Mononucleosis
- Also known as glandular fever or kissing disease.
- Etiological agent: Epstein-Barr virus
- Transmission: Direct contact, blood transfusion
- Incubation period: 4-5 weeks
Reactive Lymphadenitis
- Reactive lymphadenitis is often associated with infections and non-microbial inflammatory stimuli.
- Reactive lymphadenitis is divided into acute and chronic sub-types, non-specific and chronic specific.
- The histologic appearance of the nodes is typically nonspecific.
Clinical Presentation of Infectious Mononucleosis
- Fever
- Pharyngitis
- Lymphadenopathy
- Fatigue
- Atypical lymphocytosis
- Splenomegaly
Cat Scratch Disease
- Cat scratch disease, sometimes called cat scratch fever, is caused by Bartonella spp. bacteria spread in flea dirt.
- Cat scratches can transmit the bacteria to humans.
- The disease is typically mild in healthy people and causes a red sore.
Hemophagocytic Lymphohistiocytosis (HLH)
- HLH is a rare, life-threatening hyperinflammatory syndrome.
- It's caused by severe hypercytokinemia due to a highly stimulated ineffective immune process.
- Phagocytosis of erythrocytes, leukocytes, platelets, and precursors in bone marrow and other tissues by macrophages.
Neoplastic Proliferations of White Cells
- Malignant proliferative diseases are the most important disorders of white blood cells.
- These diseases are categorized as lymphoid neoplasms, myeloid neoplasms, and histiocytoses.
Leukemia
- Leukemia is a group of malignancies affecting the blood and blood-forming tissues (bone marrow, lymph system, and spleen).
- Leukemia occurs in all age groups.
- Leukemia vs Lymphoma: Leukemia involves widespread involvement of bone marrow, with tumor cells often found in peripheral blood. Lymphoma presents as a discrete tumor mass arising from lymph nodes.
Leukemia (Etiology and Pathophysiology)
- Leukemia is associated with the development of various factors: chemical agents, chemotherapeutic agents, viruses, radiation, and immunologic deficiencies.
Leukemia Classification
- Acute vs Chronic: Acute leukemia involves immature hematopoietic cells (clonal proliferation of immature hematopoietic cells) and chronic leukemia involves mature forms of white blood cells. The onset is more gradual in chronic cases.
Acute Lymphocytic Leukemia/Lymphoma (ALL)
- ALL is a group of neoplasms of B or T lymphoblasts.
- Pre-B cells (85%) are often seen in childhood.
- Pre-T cells are sometimes seen in adolescents/males with mediastinal involvement and masses.
- B and T cell types have similar histology and immunophenotype.
- Chromosome abnormalities are frequent (90% cases), including hyperdiploidy and translocations like t (12;21), t(9;22), and t(4;11).
Chronic Lymphocytic Leukemia (CLL)
- CLL is a cancer affecting blood and bone marrow cells.
- It is a slow-growing type of cancer affecting lymphocytes.
BCR-ABL
- The Philadelphia Chromosome (t9;22) results in a fusion protein BCR-ABL . This is an oncogene.
Follicular Lymphoma
- Follicular lymphoma is a neoplasm of follicle center B cells, comprised of a mix of cleaved follicle center cells (centrocytes) and large non-cleaved follicle center cells (centroblasts).
- A common characteristic of follicular lymphoma is the (14;18) translocation, which fuses the BCL2 gene to the IgH locus on chromosome 14, leading to BCL2 overexpression.
Mantle Cell Lymphoma
- Mantle cell lymphoma is characterized by monomorphous, medium-sized lymphocytes and the absence of centroblasts and prolymphocytes.
- In most Mantle Cell Lymphoma cases, a translocation of the cyclin D1 gene to the IgH locus (11;14) is observed. This results in an overexpression of cyclin D1.
Extranodal Marginal Zone Lymphoma of MALT
- This lymphoma arises from mucosa-associated lymphoid tissue (MALT).
- It can develop in any organ.
- H. pylori infection is a significant risk factor for this specific type of lymphoma.
High-Grade B-Cell Lymphoma
- Includes various subtypes of aggressive B-cell lymphomas, such as Burkitt lymphoma, diffuse large B-cell lymphoma, and Burkitt-like lymphoma.
Burkitt's Lymphoma
- A rare and aggressive B-cell lymphoma subtype commonly affecting children. Often starts outside of lymph nodes.
- A characteristic feature is the translocation of the c-MYC gene.
Pathogenesis of Burkitt Lymphoma
- Relates to c-MYC translocation to the immunoglobulin heavy chain regions or other chromosome regions
- Proto-oncogene MYC is dysregulated, leading to B-cell proliferation.
Multiple Myeloma
- Multiple myeloma is a neoplastic disorder of plasma B cells.
- Characterized by bone marrow infiltration and excess monoclonal immunoglobulins.
- Accounts for 1% of cancers and 10% of hematological malignancies in Europe.
Multiple Myeloma Pathogenesis
- Malignant plasma cells produce interleukin-6 (IL-6), angiogenesis cytokine (VEGF), and monoclonal proteins, accelerating catabolism of normal immunoglobulins.
- Translocation of Ig heavy chain gene to proto-oncogenes (11, 16, 20) and/or loss of chromosome 13.
Multiple Myeloma Clinical Manifestations
- Bone pain (lower back, long bones)
- Generalized malaise, weight loss
- Anemia, thrombocytopenia (bleeding)
- Renal failure (light chain deposits)
- Hypercalcemia symptoms
- Nausea, Fatigue, Thirst, Hyperviscosity
- Headaches, Bruising, Ischemic neurologic symptoms
- Hyperuricemia, Infections, Peripheral neuropathy, Meningitis
Waldenstrom's Macroglobulinemia
- A rare non-Hodgkin lymphoma and a plasmacytic lymphoma.
- Abnormal lymphoplasmacytic (LPL) B-cells accumulate, crowding healthy blood cells in bone marrow and lymph nodes and spleen, and other organs, leading to increased IgM.
- Almost all cases are associated with acquired MYD88 mutations.
Waldenstrom's Macroglobulinemia Presenting Symptoms
- 217 patients with serum monoclonal IgM protein (≥3 g/dl) and > 20% bone marrow involvement.
- Presenting symptoms include asymptomatic cases, anemia, hyperviscosity symptoms, B-symptoms, bleeding, and neurological symptoms.
Acute Myelogenous Leukemia (AML)
- A type of leukemia characterized by uncontrolled proliferation of myeloid cells (myeloblasts, myelocytes, and granulocytes) in bone marrow and blood..
- AML accounts for about a quarter of all leukemia cases.
- AML is characterized by an abrupt and dramatic onset, usually in adults.
- Common complications include serious infections, abnormal bleeding, and uncontrolled proliferation of myeloblasts with marrow and splenic hyperplasia.
Acute Myelogenous Leukemia (AML) Pathophysiology
- Damage to chromosomes caused by chemo, radiation, or viruses causes inhibition/enhancements of the genes responsible for regulation and suppressor genes and thereby apoptotic inhibition and proliferation stimulation.
Acute Myelogenous Leukemia (AML) Morphology
- Key morphologic feature in some forms of AML is Auer rods.
Acute Myelogenous Leukemia (AML) Diagnositc features
- Leukocytosis, blastemia, and leukemic hiatus
- Auer rods in some subtypes
- Thrombocytopenia and anemia
- Over 20% blasts in bone marrow.
Chronic Myelogenous Leukemia (CML)
- A type of leukemia characterized by excessive development of mature neoplastic granulocytes in bone marrow, which enter the peripheral blood in large numbers and infiltrate the liver and spleen.
- The condition typically manifests as a progressive disease.
Difference between CML and CLL
- Comparison of CML and CLL based on clinical presentation: anemia, sternal tenderness, lymphadenopathy, splenomegaly, bleeding episodes, and WBC counts.
Philadelphia Chromosome
- A reciprocal translocation of chromosomes 9 and 22 (t(9;22)), which is present in 95% of CML cases. The translocation leads to the formation of the BCR-ABL fusion gene, encoding an oncoprotein impacting cell regulation.
Chronic Lymphocytic Leukemia (CLL)
- Characterized by production and accumulation of functionally inactive yet long-lived mature lymphocytes, primarily B cells, with lymph node enlargement throughout the body. Increased infection risk.
Chronic Lymphocytic Leukemia (CLL) Complications
- Complications related to advanced CLL are rare. Advanced stage CLL may result in pain and paralysis due to enlarged lymph nodes.
Hairy Cell Leukemia
- A chronic lymphocytic leukemia type.
- Affects males mostly over 40.
- Characterized by "hairy" appearing cells, and symptoms including splenomegaly, pancytopenia (reduction in blood cell types), infections, and vasculitis.
- Treatment involves alpha-interferon, pentostatin, or cladribine.
Polycythemia Vera
- Characterized by raised packed cell volume (PCV/HCT) values, higher in males (above 0.52) and higher in females (above 0.48).
- Classified as primary, secondary, or apparent, depending on the underlying cause.
- The most common is a primary proliferative polycythaemia. The underlying reason is an activating point mutation in the JAK2 tyrosine kinase.
- The mutation leads to an elevated production of red blood cells, which may lead to cardiovascular problems.
Polycythemia Vera Clinical Features
- May occur in young adults/rare in childhood
- Symptoms of hyperviscosity: headaches, dizziness, blackouts, epistaxis
- Thrombosis (portal and splenic vein), DVT, HTN, poor vision, and/or skin rashes (aquagenic pruritus, erythromelalgia or GIT haemorrhage).
Primary Myelofibrosis (PMF)
- A clonal myeloproliferative neoplasm (MPN) characterized by an increase in the number of megakaryocytes and granulocytes in the bone marrow (BM).
- Often accompanied by fibrosis, and extramedullary hematopoiesis (EMH).
Primary Myelofibrosis (PMF) Signs and Symptoms
- Fatigue, general malaise, dyspnea, anemia, weight loss, fever/night sweats, abnormal bleeding, splenomegaly, and constitutional hypercatabolic syndromes.
Primary Myelofibrosis (PMF) Clinical Features
- Chronic, idiopathic progressive anemia/thrombocytopenia, extramedullary hematopoiesis (HSM).
- Splenomegaly is a common feature.
- Constitutional hypercatabolic syndromes may also be seen (fatigue, fevers, weight loss, night sweats).
- Symptoms may include left upper quadrant discomfort, abdominal pain, and early satiety.
Primary Myelofibrosis (PMF) Diagnosis
- Peripheral Blood Smear (normocytic anemia, granulocytes/platelets, some cases of myelophthisis- characteristic finding, leukoerythroblastosis, and teardrop-shaped RBCs)
- Bone Marrow (cellular phase vs hypocellular phase- ↑ granulocytic and MKcytic, ↓erythrocytic)
- Fibrosis/osteosclerosis often occurs
- Biopsy confirming with reticulin stain is required.
Tumor Lysis Syndrome
- Oncologic emergency triggered by rapid tumor cell lysis, often seen in lymphomas/leukemias during treatment initiation or spontaneously in fast-growing cancers.
- Key features include elevated potassium (K+), phosphate (PO₄⁻³), and uric acid (UA) levels alongside decreases in calcium (Ca²⁺).
- Prevention and treatment involve aggressive hydration, allopurinol/rasburicase to lower uric acid formation.
Studying That Suits You
Use AI to generate personalized quizzes and flashcards to suit your learning preferences.
Related Documents
Description
Test your knowledge on leukemia with this quiz that covers causes, cell maturity differences, and subtypes. Explore the key concepts in both acute and chronic forms of leukemia, as well as associated genetic factors. Can you identify what impacts the disease and its associated mutations?
