Primary renal synovial sarcoma: a clinicopathological study of 23 cases highlighting the diagnostic value of SS18-SSX, TLE1, and INI1 immunohistochemistry panel

Primary renal synovial sarcoma (PRSS) is an extremely rare neoplasm that presents considerable diagnostic challenges due to its morphological overlap with other renal tumors. In this multicenter study, 23 PRSS cases with confirmed SS18::SSX rearrangements and 112 non-PRSS renal tumors were included. Clinicopathological features and immunohistochemical expression were evaluated. Diagnostic performance of individual markers and their combinations was assessed using sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy, and a practical diagnostic approach for PRSS was proposed. The cohort (n = 23) had a median age of 42.3 years with slight male predominance (56.5%). Most presented with loin pain, and the mean tumor size was 8.7 cm. After a mean follow-up of 25 months, 41.2% (7/17) died of disease. Histologically, 87% (20/23) of cases showed intersecting monophasic spindle-cell morphology with oval‑to‑spindle hyperchromatic nuclei, while 13% (3/23) were biphasic. Key immunohistochemical findings included positivity for SS18-SSX (56.5%), TLE1 (82.4%), BCL2 (75%), and EMA (25%), with reduced/mosaic INI1 expression in 73.9% of cases. SS18-SSX, TLE1, and INI1 formed the optimal diagnostic panel. The criterion of at least two positive or aberrant markers achieved the highest performance: accuracy 94.8%, sensitivity 69.6%, specificity 100%, PPV 100% and NPV 94.1%. Based on these findings, a practical diagnostic approach integrating morphology with SS18-SSX, TLE1, and INI1 immunohistochemistry was proposed. PRSS is a rare malignant tumor with a poor prognosis that presents significant diagnostic challenges. Our immunohistochemical panel (SS18-SSX, TLE1, INI1) enhances diagnostic accuracy and may assist in the triage of cases requiring molecular confirmation.