Diagnostic utility of novel marker TRIM63 ISH in the workup of uterine perivascular epithelioid cell tumors.

Among soft tissue tumors, TRIM63 in situ hybridization (ISH) represents an emerging biomarker often positive in alveolar soft part sarcoma (ASPS) and perivascular epithelioid cell tumor (PEComa). However, its expression among gynecological tract mesenchymal tumors has been largely unexplored. Herein, we investigate sensitivity/specificity for TRIM63 ISH in uterine PEComas to aid in distinction from relevant differential diagnostic entities. A total of 33 PEComas, 35 leiomyosarcomas (LMS), 2 smooth muscle tumors of uncertain malignant potential (STUMP), and 10 leiomyomas underwent whole-slide TRIM63 ISH staining on a representative section of tumor. One ASPS was also identified and served as a positive control (not included in sensitivity and specificity calculations). Expression was quantified using a modified H-score system (range 0-12 with negative = 0, weak = 1-4, moderate = 5-8 or strong = 9-12). TRIM63 ISH was positive (H score > 0) in 28/33 (85%) PEComas, with a median H-score of 6; 24/33 (73%) had at least moderate expression (H score ≥ 5). Twenty-five (71%) LMS had H-score of 0, although 1 case had strong expression. Weak expression was also seen in 1 STUMP (50%) and 5 leiomyomas (50%); one leiomyoma had moderate expression (10%). The ASPS had strong expression (H-score 12). Employing a cutoff of > 0 TRIM63 positivity yielded a sensitivity of 85% and specificity of 64% for the diagnosis of uterine PEComa. Using a cutoff of at least moderate (≥ 5) expression decreased sensitivity to 73% but increased specificity to 96%. In the appropriate morphologic context, moderate to strong TRIM63 ISH expression may be a useful adjunct biomarker to conventional immunohistochemistry in the diagnosis of uterine PEComa.