成人TFE3重排腎細胞癌之臨床與病理多樣性：病例系列報告與文獻回顧

呂孟軒¹、宋文瑋^1,2

¹中山醫學大學附設醫院 泌尿科；²中山醫學大學 醫學系

Clinical and Pathological Diversity of TFE3-Rearranged Renal Cell Carcinoma in Adults: A Case Series with Literature Review

Meng-Hsuan Lu¹, Wen-Wei Sung^1,2

¹Department of Urology, Chung Shan Medical University Hospital;

²School of Medicine, Chung Shan Medical University

Introduction: TFE3-rearranged renal cell carcinoma (Xp11.2 translocation RCC) is a rare, aggressive malignancy defined by TFE3 gene fusions. Classified as a molecularly defined renal carcinoma by WHO, it accounts for only 1% to 1.5% of adult RCC cases with an aggressive clinical course. We report two adult cases (a 39-year-old male and a 32-year-old female) to illustrate unique clinical presentations and diagnostic challenges in managing this rare disease.

Case Presentation: The first case involves a 39-year-old male incidentally diagnosed with a 9-cm left renal mass during an appendicitis workup. CT showed heterogeneity, central necrosis, and calcification. After a laparoscopic left radical nephrectomy, histopathology confirmed Grade 3 infiltrating carcinoma (pT3a) with sinus and venous involvement. IHC (PAX8/CD10/AMACR+, TFE3 nuclear+, CK7/CAIX-) confirmed TFE3-rearranged RCC, excluding clear cell and Type 2 papillary subtypes. Due to suspected pulmonary metastasis on postoperative CT, Sunitinib was initiated. At two-year follow-up, the patient remains stable with no recurrence and minimal progression of sub-centimeter pulmonary nodules. The second case involves a 32-year-old female with a breast cancer history who presented with progressive abdominal distention. CT revealed a 10-cm left renal tumor and a concomitant 22-cm pelvic mass. Preoperative staging showed no distant metastasis. Biopsy suggested unclassified RCC (PAX8/AMACR/focal CK+; CK7/CD117/melanocytic-). She then underwent left radical nephrectomy and ATH/BSO. Histopathology showed a Grade 3 neoplasm with papillary architecture and psammoma bodies. Strong TFE3/CD10/AMACR expression with negative CK7/CAIX confirmed pT2b TFE3-rearranged RCC. The patient remains under quarterly CT surveillance.

Discussion: Adult TFE3-rearranged RCC exhibits a female predominance and typically carries a poorer prognosis due to advanced staging at diagnosis. Morphologically, it frequently mimics common malignancies like clear cell or papillary RCC. The diagnostic hallmark is the immunophenotype: TFE3-rearranged RCC characteristically lacks CK7 and CAIX expression, which is critical for differentiation. Radical excision remains the primary treatment for localized disease. For advanced cases, targeted therapies like Sunitinib may provide disease control, as evidenced by Case 1’s 24-month stability. Recent NCCN guidelines also highlight combination therapies with immune checkpoint inhibitors for metastatic disease.

Conclusion: Adult TFE3-rearranged RCC is highly aggressive. Suspect it in papillary renal tumors with a CK7-negative IHC profile. Accurate TFE3 IHC diagnosis is essential. Early surgery and targeted therapies offer the best opportunity for disease control in this challenging population.