“Hairy” cells in acute promyelocytic leukemia: Excess myeloperoxidase with formation of needle-shaped crystalline projections on the cytochemical stain in a case with variant morphology
Authors: Bin Wu, Grant Harrison, Endi Wang
Journal: American Journal of Hematology (2016)

A 45-year-old female was initially found to have mild pancytopenia on routine laboratory evaluation. Three weeks later, she presented to the emergency department with copious hematuria. Physical examination was remarkable for a low grade fever, buccal mucosa petechiae, scattered ecchymoses on the bilateral shins, thighs and arms, and a hematoma of the left knee. Complete blood cell count revealed white blood cells of 1.4 × 109/L (reference, 3.2–9.8), hemoglobin of 10.2 g/dL (reference, 12.0–15.5), and platelets of 33 × 109/L (reference, 150–450). A laboratory coagulation profiling demonstrated a prothrombin time of 15.4 sec (reference, 9.5–13.1), prothrombin INR of 1.3 (reference, 0.9–1.1), activated partial thromboplastin time of 32.2 sec (reference, 26.8–37.1), fibrinogen of <100 mg/dL (reference, 213–435) and a D-dimer of 36,940 ng/mL fibrinogen-equivalent units (reference, <500). Review of the peripheral blood smear showed moderate/severe pancytopenia with rare immature granulocytes. Examination of the bone marrow aspirate smear revealed numerous blasts with high nuclear-cytoplasmic ratio and relatively scant basophilic cytoplasm. Many cells exhibited cytoplasmic blebs (A). A few cells displayed a relatively abundant cytoplasm with coarse azurophilic granules. However, Auer rods were not identified. Cytochemical stain for myeloperoxidase (MPO) showed intense staining in the blasts with many having their nuclear contours obscured. Interestingly, many cells had multiple needle shaped crystalline inclusions highlighted by the stain. The inclusions protruded out of the cell surface forming “hairy” like radial projections (B). Flow cytometric analysis demonstrated that the blast population displayed high side scatter features and expressed bright MPO, bright CD33, heterogeneous CD13, dim CD117, dim CD4 and dim CD19, but was essentially negative for HLA-DR, CD34 and CD2. Fluorescence in situ hybridization analysis detected the fusion of PML/RARA genes in 94% of the interphase nuclei (C), confirming the diagnosis of acute promyelocytic leukemia. Treatment with all-trans-retinoic acid combined with anthracycline was subsequently started. Early diagnosis of acute promyelocytic leukemia (APL) is critical for starting the specific treatment, and identification of cytological features would prompt diagnostic Fluorescence in situ hybridization (FISH) study for PML/RARA fusion. In contrast to typical APL cases, the majority of leukemic cells in this case had relatively scant cytoplasm without identifiable Auer rods or Faggot cells. Nonetheless, multiple needle-like crystalline inclusions in individual leukemic cells were highlighted by the cytochemical MPO stain, leading to further pursuit and confirmation of the diagnosis. Cytochemical MPO stain, either using benzidine base or 3,3′-diaminobenzidine as substrate, enhances the detection of Auer rods according to the literature 1. However, an APL with formation of crystalline hairy projections due to excess MPO on the cytochemical stain has not been reported to the best of our knowledge. This case emphasizes a careful examination of cytochemical MPO stain in acute myeloid leukemia to avoid unnecessary delay of the diagnostic studies for APL (Fig. 1). A: Bone marrow aspirate smear showing many abnormal promyelocytes with no prominent azurophilic granules or Auer rods (Wright-Giemsa stain). B: Intense staining and crystalline formation in abnormal promyelocytes on the cytochemical stain for MPO (benzidine dihydrochloride as substrate); Inset: the staining pattern of the control. C: FISH for PML/RARA fusion (dual color-dual fusion) on the aspirate smear: A standard pattern for abnormal signals consists of one red (intact allele of PML), one green (intact allele of RARA) and two yellows (fusion of PML/RARA and reciprocal fusion, respectively) in individual interphase nucleus.