#00060955

A 63-year-old woman had a history of B-cell acute lymphoblastic leukemia (B-ALL). The pretreatment blasts showed no significant cytoplasmic granules (panel A; original magnification ×1000, Wright-Giemsa stained marrow aspirate smears) and were positive for CD19, CD22, CD10, CD34, and terminal deoxynucleotidyltransferase (TdT) (partial) (panels B-C) and negative for myeloperoxidase (MPO). She relapsed and received blinatumomab. A recent bone marrow biopsy revealed blasts with abundant cytoplasmic granules (panels D-E; original magnification ×1000, Wright-Giemsa stained marrow aspirate smears), raising the differential diagnosis of acute myeloid leukemia (AML). The blasts were positive for CD22, CD10, CD34, and TdT (partial) (panels F-G) and negative for MPO, an immunophenotype exactly the same as pretreatment blasts except without CD19 expression, which was the result of blinatumomab (anti-CD19 antibody) treatment. The blasts were negative for MPO and nonspecific esterase by cytochemistry and positive for CD79a and PAX5 by immunohistochemistry (panels H-I; original magnification ×400, immunohistochemical stain), which further confirmed relapsed B-ALL.One of the main morphologic features distinguishing AML from ALL is cytoplasmic granules in blasts. In ALL, the blasts usually lack cytoplasmic granules. However, ALL may present with significant cytoplasmic granules in blasts (so-called granular ALL), which usually occurs in children (2%-7%) but is extremely rare in adults. This case demonstrates that morphology can shift after treatment, and it is critical to perform immunophenotypic analysis in relapsed leukemia to reach the correct diagnosis.

Noted added by Editor: Sometimes, such granules are seen in B-ALL in the context of Down syndrome-associated B-ALL, Ph+ B-ALLs and possibly 'Ph-like' ALLs described recently and there is speculation that these might represent mitochondria or lysosomes. On the other hand, not infrequently, B-ALL (especially ones with MLL rearrangement) may switch phenotype after anti CD19 therapy (Blinatumomab or CD19 CAR-T) to a B-.Myeloid or Pure Myeloid phenotype and hence flow cytometry is critical for identification of such switch in this setting.