Nonspecificity of p30/32(MIC2) immunolocalization with the 013 monoclonal antibody in the diagnosis of Ewing's sarcoma: Application of an algorithmic immunohistochemical analysis

Background: Ewing's sarcoma (ES) and peripheral/primitive neuroectodermal tumors (PNETs) express p30/32M(MIC2), which is detected by the 013 monoclonal antibody (013). This investigation examines the diagnostic specificity and utility of 013 in the differentiation of ES/PNET from its clinical or histologic impersonators. Design: Paraffin sections from seven ES/PNETs, 40 bone/soft tissue lesions and 27 lymphomas, were stained with 013 and a panel of 11 antibodies, using automated immunohistochemistry with steam antigen retrieval. Results: All seven ES/PNETs exhibit 013 membrane-type strong diffuse (SD) immunoreactivity; however, 65% of the bone/soft tissue mimickers (nine of 12 osteosarcomas, seven of nine bone giant cell tumors, three of four rhabdomyosarcomas, three of three synovial sarcomas, one of two alveolar soft-part sarcomas, one of one clear cell sarcoma, one of one osteoblastoma, and one of one chondroblastoma) and 33% of the lymphomas (nine of 15 T-cell and none of 12 B-cell) were immunoreactive (+). ES specimens stained as follows: vimentin, 100% SD; neuron-specific enolase (NSE), 14% SD, 57% weak; chromogranin, smooth muscle actin (SMA), pan-muscle actin (PMA), desmin, S-100, cytokeratin (CK) AE1:3, leukocyte common antigen (LCA), B-cell marker (L-26), and T-cell marker (UCHL-1) were all negative (-). Three osteosarcomas and one bone giant cell tumor simulated the staining reactions of ES. Conclusions: Membrane type SD 013 immunoreactivity points toward, but does not confirm, ES/PNET. Algorithmic analysis of a panel of immunohistochemical stains with vimentin SD+, SMA-, PMA-, S100-, chromogranin-, CK-, and LCA- as key pivot reactions, complement 013 in the diagnosis of ES/PNET. Only UCHL-1 + T-cell lymphomas are 013+, thus a UCHL-1- reaction may also help distinguish ES/PNET from lymphoma. Osteosarcomas and bone giant cell tumors are immunohistochemical mimicks of ES/PNETs, so other determinants (clinical/histologic/ultrastructural) must be used to exclude these potential impersonators.