Abstract

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic neoplasm that can show clinical, morphologic, and immunophenotypic overlap with acute myeloid leukemia (AML). Myeloid cell nuclear differentiation antigen (MNDA) is a nuclear protein expressed by myelomonocytic cells previously reported to be reliably absent in BPDCN and proposed as a useful adjunct for the distinction of BPDCN and AML. We encountered a case of BPDCN that showed strong nuclear expression of MNDA in bone marrow and breast samples, and weak-to-absent expression in skin samples, prompting us to re-evaluate the expression of MNDA in BPDCN. We collected all available archived BPDCN cases collected at our institution in the past 10 years and subjected them to MNDA immunohistochemistry. Molecular profiling was performed on all cases. We found four cases (of 8 total examined; 50%) with convincing site-discordant MNDA expression. MNDA expression was seen in 3/6 (50%) bone marrow samples, 1/2 (50%) breast soft tissue samples, and 3/14 (up to 21%) skin samples, and was not obviously predicted by age, sex, history of myeloid neoplasm, or treatment history. In two cases, MNDA was strongly expressed in two distinct sites (breast/bone marrow, skin/bone marrow), and negative in subsequent samples. Molecular profiling detected variants that are commonly seen in BPDCN. Our findings suggest that MNDA expression in BPDCN is anatomic site-dependent and transient, with non-cutaneous infiltrates showing more frequent expression than cutaneous infiltrates. These results caution against the use of MNDA to exclude BPDCN when considering the differential diagnosis of a blastic extramedullary infiltrate.