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Chediak-Higashi–like granules within leukemic promyelocytes

Chediak-Higashi–like granules within leukemic promyelocytes
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Author: Payal Sojitra and Girish Venkataraman
Category: Myeloid Neoplasms and acute leukemia (WHO 2016) > Acute Myeloid Leukemia > Acute Myeloid Leukemia with recurrent genetic abnormalities > AML with t(15;17)(q22;q12); PML-RARA (and variants)
Published Date: 11/11/2013

A 59-year-old woman with disseminated intravascular coagulation was transferred after a dose of growth factor for “leukopenia.” Laboratory studies showed elevated D-dimer (201?934 ng/mL), with a white blood cell count of 41?000/mm3 (blasts, 19%; promyelocytes, 37%) and platelets of 49?000/µL, at which time all-trans-retinoic acid (ATRA) had already been instituted owing to a high suspicion of acute promyelocytic leukemia (APL). In the peripheral blood smear, a proportion of promyelocytes appeared overtly leukemic (with deeply clefted nuclei), and others appeared nonleukemic (with paranuclear Hof and toxic changes). Notably, several promyelocytes contained numerous immature pink azurophilic granules (panel A). These granules formed small clumps with cytoplasmic clearing (panels B-C) or existed as larger, globular pink structures with Chediak-Higashi–like morphology (panels D-E). Panel F shows a bilobed (coin-on-coin) promyelocyte with finely granular cytoplasm. Flow cytometry identified a CD34-/HLA-DR- myeloid population, whereas fluorescence in situ hybridization confirmed the presence of t(15;17). Chediak-Higashi–like granules are rarely observed in APL. Ultrastructurally, they represent aggregates of immature primary (azurophil) granules that show a crystalline structure and/or vacuolization—a feature lacking in Chediak-Higashi disease. Their occurrence in this case helped confirm a leukemic phenotype amid a confounding growth factor effect and concurrent ATRA therapy before ancillary studies were available.