HEMA 2 FINAL EXAM

Leukemia

• Leukemia is a disease characterized by the abnormal, uncontrolled proliferation and accumulation of one or more of the hematopoietic cells.
• It is a malignancy of leukocytes in the blood and bone marrow.

Symptoms of Leukemia

• Fatigue and weakness
• Increased infections
• Bleeding and bruising
• Anemia
• Swollen lymph nodes
• Enlarged spleen or liver
• Bone pain or tenderness

Classification of Leukemia

• Based on duration: acute (days to 6 months), subacute (2 to 6 months), and chronic (1 or 2 years or more)
• Based on the number of white blood cells (WBCs) present in peripheral blood: acute leukemia (>30% blast in peripheral blood and bone marrow)

World Health Organization (WHO) Classification

• Defines acute leukemia as >20% peripheral blood and bone marrow blasts
• Subdivides leukemia based on: cellular morphology, cytochemical stains, immunophenotyping, cytogenetic abnormalities, and clinical syndrome

Cytochemical Analysis

• Uses specialized stains to detect cellular enzymes and other chemicals in peripheral blood films and bone marrow aspirate smears
• Helps differentiate hematologic diseases, especially leukemias

Immunophenotyping (Flow Cytometry)

• Identifies cells based on the types of markers or antigens present on the cell's surface, nucleus, or cytoplasm
• Helps identify the lineage of cells using antibodies that detect markers or antigens on the cells

Acute Lymphoblastic Leukemia (ALL)

• Subdivided into three categories based on the FAB classification:
  • ALL L1: lymphoblasts are small and homogenous, with scanty cytoplasm and inconspicuous nucleoli
  • ALL L2: lymphoblasts are large and heterogenous, with abundant cytoplasm and nucleoli
  • ALL L3 (Burkitt-Type): lymphoblasts are large, homogenous, and vacuolated, with rarest subclass and poor prognosis

Acute Myeloid Leukemia (AML)

• Subdivided into five categories based on the FAB classification:
  • MO: acute myeloid leukemia, minimally differentiated
  • M1: acute myeloid leukemia without maturation
  • M2: acute myeloid leukemia with maturation
  • M3: acute promyelocytic leukemia
  • M4: acute myelomonocytic leukemia
  • M5B: acute monoblastic leukemia with maturation

Lymphoproliferative Disorders

• Hairy cell leukemia: a type of lymphoproliferative disorder characterized by small B lymphocytes with abundant cytoplasm and fine (“hairy”) cytoplasmic projections.
• Bone marrow produces too many abnormal B-lymphocytes, more common in males than females.
• Cytochemical features: strong acid phosphatase reaction, not inhibited by tartaric acid or tartrate-resistant acid phosphatase (TRAP) stain.

Mantle Cell Lymphoma

• Affects the B-cells within the lymph nodes, particularly the "mantle zone" - the outer area surrounding the center.
• A subtype of non-Hodgkin lymphoma (NHL), considered fast-growing compared to other lymphomas.
• Originates from B-cells in the lymph nodes.
• Characterized by medium-sized lymphoid cells with irregular nuclear outlines, derived from the follicular mantle zone.

Follicular Lymphoma

• Originates from germinal center B cells and recapitulates follicular architecture in most cases.
• Numerous closely spaced follicles replace the normal nodal architecture.

Burkitt Lymphoma

• Characterized by medium-sized, highly proliferating lymphoid cells with basophilic vacuolated cytoplasm.
• Lymphoid proliferation is diffuse, with a prominent “starry sky” pattern at low magnification.
• WHO classification lists three variants: endemic (occurring predominantly in Africa), sporadic, and immunodeficiency-associated.

Mycosis Fungoides and Sézary Syndrome

• Mycosis fungoides: the most common cutaneous lymphoma, affecting T lymphocytes.
• Sézary cells: small to medium-sized lymphoid cells with irregular nuclear outlines (cerebriform nuclei).

Myeloproliferative Disorders (MPDs)

• Interrelated clonal hematopoietic stem cell disorders characterized by excessive proliferation of one or more mature myeloid cell lines (e.g., granulocytes, erythrocytes, megakaryocytes, or mast cells)

Janus Kinase 2 (JAK2)

• A gene that provides instructions for making a protein involved in cellular signaling pathways that regulate blood cell growth and division in the bone marrow
• JAK2V617F mutation leads to the production of an abnormal JAK2 protein, promoting uncontrolled growth and division of blood cells

Myeloproliferative Neoplasms (MPNs)

• Essential Thrombocythemia (ET)
• Polycythemia Vera (PV)
• Idiopathic Myelofibrosis (IMF)
• Chronic Myelogenous Leukemia (CML)
• Chronic Neutrophilic Leukemia (CNL)
• Varies Nucleated Erythrocytes/Megakaryocytes in Myeloproliferation (VNEL)

Chronic Myelogenous Leukemia (CML)

• Stem cell disorder affecting granulocytic, monocytic, erythrocytic, and megakaryocytic cell lines
• Characterized by the presence of the Philadelphia chromosome (90% of cases) and BCR/ABL1 abnormality
• Patients without the Philadelphia chromosome usually have a poorer prognosis

Myelofibrosis with Myeloid Metaplasia (Primary Myelofibrosis/Agnogenic Myelofibrosis)

• Characterized by fibrosis and granulocytic hyperplasia of the bone marrow, with granulocytic and megakaryocytic proliferation in the liver and spleen
• Associated with splenomegaly, ineffective hematopoiesis, and marrow hypercellularity
• JAK2 V617F mutation is involved in the pathogenesis (65% of PMF patients) and presence of Dacryocytes

Essential Thrombocythemia (ET)

• Chronic MPD characterized by thrombocytosis (>1000x109/L) with spontaneous aggregation of functionally abnormal platelets
• JAK2 V617F mutation is found in 50-60% of ET patients, supporting the diagnosis of ET
• Clinical manifestations include hemorrhage, platelet dysfunction, and thrombosis

Polycythemia Vera (PV)

• Characterized by an absolute increase in RBC, WBC, and platelets
• JAK2 V617F mutation is detected in 90-97% of patients with PV
• Also known as primary absolute polycythemia or polycythemia Rubra vera
• Patients exhibit a ruddy skin coloration due to increased RBC concentration and blood viscosity
• Increase RBC mass, decreased EPO, and increased RBC, WBC, and platelet count

Pathophysiological Classification of Polycythemia

• Relative polycythemia: normal RBC mass, increased hematocrit, normal EPO, usually due to dehydration, diarrhea, burns, or shock
• Absolute polycythemia: primary absolute polycythemia (PV), secondary polycythemia with appropriately increased EPO (e.g., hypoxia, high altitudes), and genetic polycythemia (e.g., primary familial congenital polycythemia, Chuvash polycythemia)