PATZ1 Immunohistochemistry Aids in the Diagnosis of PATZ1-Rearranged Sarcomas

PATZ1-rearranged sarcomas are diagnostically challenging due to their rather non-specific morphology and immunophenotype. These tumors are characterized by bland, round-to-spindled cells within a fibromyxoid matrix with variable microcysts, fibrous septa, hyalinized vessels, and cellular whorls. PATZ1-rearranged sarcomas are often positive for neural, skeletal muscle, and epithelial markers. Identification of these tumors is further complicated by the cryptic nature of the characteristic EWSR1::PATZ1 fusion, which generally makes fluorescence in situ hybridization analysis unreliable if rearrangement is not detected. As a result, costly and time-intensive molecular assays are often currently necessary for definitive diagnosis. The purpose of this study was to assess immunohistochemistry (IHC) for PATZ1 as a surrogate for detecting the gene fusion. In total, 533 tumors from whole-tissue sections and tissue microarrays were evaluated, including 14 PATZ1-rearranged sarcomas as well as other benign and malignant mesenchymal neoplasms. IHC for PATZ1 was positive in 12/14 (86%) PATZ1-rearranged sarcomas. Of the remaining tumor types, 495 (95%) were negative for PATZ1. Notably, PATZ1 expression was observed in a subset of other tumor types, including myoepithelial carcinoma (2/4; 50%), myoepithelioma (2/15; 13%), rhabdomyosarcoma (RMS) (13/99; 13%), desmoplastic small round cell tumor (1/10; 10%), dermatofibrosarcoma protuberans (1/10; 10%), myxoid liposarcoma (1/16; 6%), schwannoma (1/22; 5%), and malignant peripheral nerve sheath tumor (3/70; 4%). The 13 RMS cases that were positive were classified as embryonal (n = 7), alveolar (n = 5), and RMS, not otherwise specified (n = 1). In conclusion, PATZ1 IHC is moderately sensitive and specific for PATZ1-rearranged sarcomas, and it may be a helpful diagnostic marker for this challenging tumor. Although most tumors with morphologic overlap with PATZ1-rearranged sarcomas are negative for PATZ1 by IHC, expression in a subset of myoepithelial tumors and RMS represents a potential diagnostic pitfall.