ERG Immunoreactivity in Blastic Hematolymphoid Neoplasms: Diagnostic Pitfall in the Workup of Undifferentiated...

Undifferentiated malignant neoplasms pose diagnostic challenges, and reliable immunohistochemical markers with well-characterized staining profiles are desirable when characterizing them. Our initial observation of erythroblast transformation specific regulated gene-1 (ERG) reactivity in myeloid sarcomas led us to broadly explore the utility of ERG as a marker of immature hematolymphoid neoplasms presenting in extramedullary sites. We stained 207 immature and mature hematolymphoid lesions as well as 39 benign hematolymphoid tissues and found weak-to-moderate ERG immunopositivity in 15 of 16 (94%) acute myeloid leukemias/myeloid sarcomas, including 4 of 5 (80%) CD34-negative/CD117-negative acute myeloid leukemias/myeloid sarcomas. ERG positivity was also seen in all 9 cases of B-lymphoblastic and T-lymphoblastic leukemia/lymphoma, all 3 cases of hematogone hyperplasia, and all 4 cases of systemic mastocytosis. ERG was negative in 148 mature B-cell and T-cell lymphomas, including 2 high-grade B-cell lymphomas and 2 blastoid variant mantle cell lymphomas; 23 histiocytic/dendritic cell neoplasms; 2 indolent T-lymphoblastic proliferations; and 2 blastic plasmacytoid dendritic cell neoplasms. We conclude that ERG immunoreactivity may pose a significant diagnostic pitfall in the workup of undifferentiated malignant neoplasms, particularly those presenting in extramedullary sites.