Myeloid sarcoma and extramedullary hematopoiesis expand the spectrum of ERG-positive proliferations: an ancillary tool in the diagnosis

ERG overexpression has been linked to acute myeloid leukemia/myeloid sarcoma (MS). The aim of our study was to identify the frequency of ERG immunohistochemical (IHC) expression in MS (n = 21), blastic plasmacytoid dendritic cell neoplasms (BPDCNs; n = 8), extramedullary hematopoiesis (EMH: n = 9), normal and pathological bone marrow trephine biopsies (BM-TBs, n = 18), and the marrow component of adrenal myelolipomas (n = 15). ERG-positive and ERG-negative immunostains were identified in 68.4% and 31.5% of patients with MS, respectively (2–3+, 20% to >90% of cells), while all BPDCNs were negative. ERG + MS cases were over-represented in those of myeloid differentiation when compared with those of pure monocytic/monoblastic differentiation, which were ERG-negative (P=<0.001). ERG was expressed in immature myeloid cells in 100% of cases of EMH, BM-TBs, and adrenal myelolipomas (n = 42), resulting in a sensitivity of 100% in this setting. Negative ERG immunostaining was also 100% sensitive in discriminating cells of erythroid lineage, mature lymphocytes, and reactive or neoplastic plasma cells. Variable IHC expression occurred in megakaryocytes and neutrophils. In summary, we confirmed a high frequency of ERG expression in MS and identified ubiquitous expression in non-neoplastic immature myeloid lineage cells. We believe that ERG can be of diagnostic utility to identify neoplastic and reactive myeloid infiltrates in peripheral tissues and possibly as an ancillary marker to exclude the diagnosis of BPDCNs when positive. However, ERG must be used in an antibody panel, as expression is not limited to myeloid cells.