Primary thymic papillary adenocarcinoma with a rare CD5/CD117-negative and PAX8/WT1-positive immunophenotype: A case report.

Primary thymic papillary adenocarcinoma (PAT) is an exceptionally rare epithelial malignancy that poses substantial diagnostic challenges due to its non-specific radiological presentation and highly heterogeneous immunophenotype. The present study reports a case of early-stage PAT in a 48-year-old man with a long-standing history of rheumatoid arthritis. Chest computed tomography (CT) revealed a 3.3-cm, well-circumscribed, lobulated anterior mediastinal nodule demonstrating homogeneous contrast enhancement, radiologically mimicking a benign thymic cyst or thymoma. Following complete resection via video-assisted thoracoscopic surgery (VATS), histopathological examination demonstrated a cystic and solid tumor with conspicuous papillary architecture. Diagnostic interpretation was confounded by an atypical immunoprofile: The tumor was negative for the traditional thymic carcinoma markers CD5 and CD117, yet exhibited diffuse expression of paired box gene 8 and WT1, thereby closely resembling metastatic renal cell carcinoma or mesothelioma. A diagnosis was strongly supported through a rigorous process of exclusion, integrating an extended negative immunohistochemical panel (including Spalt-like transcription factor 4, thyroid transcription factor-1 and D2-40) with the morphological identification of residual atrophic thymic tissue at the tumor periphery. The tumor was classified as Masaoka-Koga stage I PAT, and the patient remained free of recurrence at the 6-month postoperative follow-up. The present case highlights the diagnostic pitfalls of PAT, particularly its deceptively benign imaging appearance and unusual immunophenotype. It emphasizes that CD5/CD117 negativity does not preclude a thymic origin, underscoring the necessity of a comprehensive, exclusion-based approach for accurate diagnosis.