Case 2 - Discussion

Uploaded: 2007-06-07, Updated: 2008-01-02

 

Acute promyelocytic leukemia, Hypogranular Type

 

The Key Features

  • Hypergranular and hypogranular types;

  • Nuclei: kidney-shaped or bilobed / butterfly shape;

  • Cytoplasmic granules, Auer rods, faggot cells;

  • t(15;17)(q22;q12), PML-RARα fusion gene;

  • Frequent association with DIC.

 

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

    • Peripheral leukocyte count is usually decreased;

    • Cytoplasm is often filled with densely packed or coalescent large, bright pink, red or purple granules;

    • In some cases, the cytoplasm is filled with fine dust-like granules;

    • 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.

SUBTYPES OR VARIANTS

  • APL with t(11;17)(q23;q21), PLZF-RARA fusion gene; regular nuclei, many granules, no Auer rods, increased pseudo Pelger-Huet cells; resistent to ATRA;

  • APL with t(11;17)(q13;q21), NuMA-RARA fusion gene

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

DIFFERENTIAL DIAGNOSES

 

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-RARα fusion protein.

  • t(11;17)(q23;q21), PLZF-RARA fusion gene.

  • t(11;17)(q13;q21), NuMA-RARA fusion gene.

  • t(5;17)(q32;q12), NPM-RARA fusion gene

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.

REFERENCES

  • Jaffe ES, Harris NL, Stein H, Vardiman JW, editors. Pathology and genetics of tumours of haematopoietic and lymphoid tissues. World Health Organization classification of tumours. Lyon (France): IARC Press; 2001.