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Case  2 - Discussion

Hematopathology Case

 

 

 

CD34

CD117

 

MPO

Cytogenetic studies positive for t(15;17)(q22;q11.2) with PML/RARA rearrangement

 

Acute Myeloid Leukemia with t(15;17)

(Acute promyelocytic leukemia, Hypogranular Type)

 

Key Features

  • t(15;17)(q22;q12), PML-RARA

  • Nuclei: kidney-shaped, bilobed or butterfly shape

  • Cytoplasmic granules, Auer rods, faggot cells

  • Frequent association with DIC

  • Positive: CD13, CD15, CD33, MPO

  • Negative: HLA-DR, CD34

  • Often negative for CD11b and CD11c

 

CLINICAL FEATURES

  • An acute leukemia with predominant abnormal promyelocytes, 5-8% of AML

  • Age: all age, but most in mid-life

  • Clinical features: a clinical emergency due to frequent association with DIC

MICROSCOPIC FINDINGS

  • Variable nuclear size and shape, often kidney-shaped or bilobed / butterfly shape

  • In most cases, myeloblasts are a minor component and rarely > 20%

  • Hypergranular APL (2/3)

    • Often leukopenia, abnormal promyelocytes with bilobed nuclei

    • Dense cytoplasmic granules; packed or coalescent large, or dust-like; bright pink, red or purple

    • Auer rods:  in 90% cases, can be multiple, numerous and intertwined

    • Faggot cell: cell with bundles of Auer rods

  • Hypogranular/Microgranular APL

    • Peripheral leukocyte count is elevated or markedly elevated due to a rapid doubling time

    • Cytoplasm has a paucity or absence of fine granules, and nuclei are predominantly bilobed

    • Scant Auer rods may be identified

    • More often positive for CD34, CD2 and CD64

    • Strongly associated with FLT3 ITD

    • Can resemble AML with monocytic differentiation, but the "butterfly" nuclei should prompt workup for APL

IMMUNOHISTOCHEMISTRY AND SPECIAL STAINS

  • Markedly increased orthogonal (side) scatter

  • Positive: CD33, CD13, MPO

  • Frequent coexpression of CD2 and CD9

  • Negative: HLA-DR, CD34, CD15

  • NSE weakly positive in 25% cases

ELECTRON MICROSCOPIC FINDINGS

  • Auer rods: hexagonal arrangement of tubular structures with a specific periodicity of about 250nm.

CYTOGENETIC STUDIES

  • t(15;17)(q22;q12):  98% cases, PML-RARA

  • t(11;17)(q23;q12): ZBTB16-RARA, ATRA resistant, non-bilobed, no Auer rods or Pelgeroid cells

  • t(11;17)(q13;q12): NUMA1-RARA, ATRA responsive

  • t(5;17)(q32;q12): NPM-RARA fusion gene. Responsive to ATRA

  • t(17;17)(q11.2;q12): STAT5B-RARA, ATRA resistant

TREATMENT AND PROGNOSIS

  • Both hypergranular and hypogranular APLs have the same characteristic ultrastructural, cytogenetic, molecular and clinical features and both response to treatment with ATRA. They defer mainly in the peripheral blood count, the size and number of the visible granules and the prominence of the abnormal nuclear shape.

  • Particularly sensitive to treatment with all trans-retinoic acid that acts as a differentiating agent

  • Favorable prognosis when treated with all trans-retinoic acid and an anthracycline