Impact of second-opinion pathology review process on diagnostic accuracy in sarcoma: Experience from the NTUH Center of Excellence for Sarcoma.

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Background: Sarcoma is a rare and heterogeneous group of malignancies requiring accurate histopathological diagnosis to guide appropriate treatment. Previous studies have shown that sarcoma is among the tumor types with the highest diagnostic discrepancy rates following expert pathology review. With the establishment of the National Taiwan University Hospital (NTUH) Center of Excellence for Sarcoma (CES), we implemented a standardized second-opinion pathology review process to improve diagnostic accuracy and treatment quality. Methods: At the NTUH CES, cases with pathology not originally reviewed by NTUH sarcoma pathologists undergo mandatory second review. Original pathology materials (slides and/or tissue blocks) were retrieved for re-evaluation and, where necessary, additional immunostaining or molecular testing. Results were documented in the NTUH electronic medical record system. Diagnostic discrepancies were classified using a five-tier clinical-impact system based on Taiwan Society of Pathology Society criteria: N1 (malignant → benign) and N2 (benign → malignant) representing major upgrading or downgrading, as well as N3 (major treatment impact), N4 (minor treatment impact), and N5 (uncertain impact) for the remaining. Results: Between January 2023 and December 2025, the CES requested second-opinion pathology review for 230 external cases of mesenchymal tumors that had been pathologically diagnosed as (or clinically suspected to be) sarcoma. Overall, 22.6% (52/230) of cases had a revised diagnosis. Based on the five-tier criteria, 3 (5.7%), 8 (15.4%), 20 (38.5%), 17 (32.8%), and 4 (7.6%) cases were classified as N1, N2, N3, N4, and N5, respectively. Four cases initially diagnosed as sarcoma were reclassified as non-sarcoma malignancies. The most common revised sarcoma diagnoses were dedifferentiated liposarcoma (n = 8, 15%), leiomyosarcoma (n = 5, 9.6%), and malignant peripheral nerve sheath tumor (n = 3, 5.7%). Among the eight N2 cases, diagnoses included leiomyosarcoma (n = 5), low-grade fibromyxoid sarcoma (n = 1), undifferentiated pleomorphic sarcoma (n = 1), and sarcoma NOS (n = 1). Conclusions: A revised diagnosis occurred in 22% of all the secondary-reviewed cases, with nearly 60% (N1 + N2 + N3) having major clinical impact on treatment decisions. These findings support a standardized second-opinion pathology review expert pathology review as a key component of quality assurance in sarcoma care within a center-of-excellence model.