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AOBPa Pathology study materials
AOBPa Pathology study resources

AOBPa Pathology: Hematopathology: Lineages, Marrow, and the Molecular Overlay

AOBPa Pathology · Work through your exam, one topic at a time.

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Hematopathology: Lineages, Marrow, and the Molecular Overlay

Hematopathology questions integrate morphology, immunophenotype, and genetics. The candidate should be able to place a neoplasm in its lineage and maturation stage, then attach the defining molecular lesion.

Concepts to master

  • Lineage and maturation: myeloid vs. lymphoid; precursor (blast) vs. mature. Acute leukemias are defined by ≥20% blasts in marrow or blood (with exceptions such as certain translocations that define leukemia regardless of blast count).
  • Immunophenotype: myeloblasts (CD13, CD33, MPO), B-lymphoblasts (CD19, CD10, TdT), T-lymphoblasts (CD3, TdT), and mature B cells (CD20, surface immunoglobulin).
  • Lymphomas: Hodgkin (Reed-Sternberg cells, CD15+/CD30+, CD45−) vs. non-Hodgkin; follicular lymphoma (BCL2 translocation, t(14;18)); Burkitt (MYC, t(8;14), "starry sky").
  • Myeloproliferative vs. myelodysplastic: proliferation with effective maturation vs. ineffective maturation with dysplasia and cytopenias.
  • Coagulation and transfusion: DIC (schistocytes, low platelets, prolonged PT/aPTT, low fibrinogen, elevated D-dimer); hemolytic transfusion reaction timing.

Traps

The classic trap is calling a marrow "leukemic" by blast percentage alone when a defining translocation (e.g., t(15;17) in APL) makes the diagnosis regardless of count. Another is confusing Hodgkin (CD45 negative) with non-Hodgkin (usually CD45 positive). Do not equate lymphadenopathy with lymphoma - reactive follicular hyperplasia is common.

Rule of thumb

For any hematologic neoplasm, run the three-axis grid: lineage (myeloid/lymphoid/B/T/NK), maturation (precursor vs. mature), and defining genetics. The diagnosis usually falls out of the intersection.

Worked example

A young adult with a rapidly growing jaw mass; biopsy shows medium-sized cells with "starry sky" macrophages and a high proliferation index. The cells are B cells with a MYC rearrangement, t(8;14). The diagnosis is Burkitt lymphoma - a mature B-cell neoplasm with a very high Ki-67. The trap is choosing a precursor B-lymphoblastic leukemia because of the "blast-like" appearance; the mature B phenotype and MYC translocation settle it.