11/16 - Pathology Of Acute And Chronic Leukemias

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Leukemia

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Clonal proliferation of leukocytes primarily affecting blood and bone marrow

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Leukemias are classified based on....

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cell of origin and type of differentiation

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Cell of origin for acute vs chronic leukemia

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Acute: proliferation involves immature precursor cells (blasts) {20%+ of cells are blasts}

Chronic: proliferation involves more mature leukocytes

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Type of differentiation - myeloid vs lymphocytic leukemia

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Myeloid: granulocytic precursors/granulocytes (can get erythrocytic/megakaryocytic leukemias, but not nearly as common)

Lymphocytic: lymphocytic precursors/lymphocytes, either B or T

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Lymphoma vs leukemia

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Lymphoma - mostly based in the lymph nodes

Leukemia - usually seen first in the blood, mostly based in the blood

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Acute leukemias typically require _____ AND ______

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a block in differentiation AND abnormal proliferation

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Chronic leukemias primarily driven by _____

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abnormal proliferation

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What does abnormal proliferation mean?

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Absence of normal physiologic stimuli

Constitutive activation of growth signals

Defective apoptosis

Dysregulation of cell cycle

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Clinical features of acute leukemia

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• Rapid onset of symptoms of cytopenias (decreased normal cells)
• Anemia: fatigue, pallor, dyspnea
• Neutropenia: infections
• Thrombocytopenia: bleeding
• Symptoms of increased abnormal cells
• Leukostasis (rare): pulmonary edema, mental status changes, ischemia
• Bone pain
• Rarely a mass (granulocytic sarcoma)

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WBC in acute leukemia

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Low, normal, or high (20% of blood or marrow nucleated cells are blasts)

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Survival for acute leukemia

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Survival = weeks to months (rapid death)

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Acute leukemia - high concentration of blasts - specifically acute lymphoblastic leukemia

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Acute Lymphoblastic Leukemia

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• Most common cancer of childhood
  
• B >> T
• Lymphoblasts in blood, bone marrow, lymph nodes, mediastinal mass (T-ALL)
• Immunophenotype: TdT+
• CD19 - B-ALL
• CD2/CD3 - T-ALL

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Acute lymphoblastic leukemia

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Acute myeloid leukemia

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• Affects primarily adults
  
• Blast morphology: large, +/- granules, +/- Auer rods (crystalline-like enzyme inclusions)
• Immunophenotype: myeloperoxidase
• Genetics: recurrent translocations, complex abnormalities (from MDS), normal

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Cell involved in what leukemia?

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Acute Myeloid Leukemia

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Leukemia? Circled structure?

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Acute myeloid leukemia (due to underlying myelodysplasia)

Auer rod

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Acute promyelocytic leukemia

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-Special subtype of AML

-Translocation of 15;17 (15 PML, 17 RARA) causes block in differentiation at the promyelocytic stage

-Cells with abundant Auer rods

-Treated with all-trans retinoic acid

-Good prognosis but potential DIC from Auer rod/granule release

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Leukemia type with these cells?

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Acute promyelocytic leukemia

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Clinical features of chronic leukemias

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• Exclusively adults (lymphoid --> elderly)
  
• Increased mature precursors
• In circulation: peripheral blood cytosis (usually!)
• In reticuloendothelial system: splenomegaly +/- lymphadenopathy
• Decreased normal lymphocyte function (lymphoid) - infections, hypogammaglobulinemia
• Often asymptomatic or mild constitutional sx
• Survival: years to decades

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Chronic lymphocytic leukemia/small lymphocytic lymphoma

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• Most common leukemia
• Elderly, males, familial predisposition
• Morphology: smudge cells
• Immunophenotype:
• 1) B cell antigens - CD19, CD20
• 2) Abnormal CD5 (T cell antigen) on B cells
• 3) CD23
• Requires tx for cytopenias
• Small risk of transformation to aggressive disease

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Cell indicated?

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Smudge cell - chronic lymphocytic leukemia/small lymphocytic lymphoma

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Features on this slide?

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Lymphocyte nucleus appears much more clumpy than normal (soccer ball or turtle shell appearance)

Smudge cells

Chronic lymphocytic leukemia/small lymphocytic lymphoma

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Hairy cell leukemia

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• Males, 50s
• Pancytopenia, splenomegaly
• Morphology: hairy cells
• Immunophenotype:
• 1) B cell antigens (CD19, CD20)
• 2) TRAP (tartrate-resistant acid phosphatase)
• Genettics: BRAF V600E mutation

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Chronic myelogenous leukemia

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• Middle-aged adults

• Leukocytosis with left shift, basophilia, splenomegaly

• t(9;22) BCR-ABL fusion oncogene AKA Philadelphia chromosome

• Responds to tyrosine kinase inhibitors (TKIs) (Gleevac)

• Risk of accelerated phase/blast crisis, resistant to TKIs

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Leukemia associated with this cell type?

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Hairy cell leukemia

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Leukemia associated with this smear?

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Chronic myelogenous leukemia

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Most chronic leukemias are of _____ cell origin

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B cell