TFE3-重排腎臟腫瘤：惡性血管旁類上皮細胞瘤與腎細胞癌

林冠廷¹、溫玉清^1,2、林雍偉^1,2

¹臺北市立萬芳醫院泌尿科－委託臺北醫學大學辦理；²臺北醫學大學泌尿學科

TFE3-Rearranged tumor of kidney: Primary Perivascular Epithelioid Cell Tumor (PEComa) versus renal cell carcinoma

Kuan-Ting Lin¹, Yu-Ching Wen^1,2, Yung-Wei Lin^1,2

Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan¹; Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan²

Introduction:

    The presentation of molecular variations plays a crucial role in pathology, as it can contribute to tumorigenesis and may offer potential targets for therapeutic intervention. TFE3, a member of the MiTF family of transcription factors, has emerged as a significant area of study. Kidney tumors with TFE3 gene translocations exhibit considerable morphological heterogeneity. Most of these tumors are renal cell carcinomas (RCCs) that are positive for the immunohistochemical marker PAX8. In contrast, others are mesenchymal neoplasms known as PEComas, a rare group of tumors characterized by perivascular epithelioid cells, which are histologically and immunohistochemically distinctive.

Presentation of case:

Case 1: A 48-year-old female without underlying disease and discomfort. During health examination, a 3.5cm mass located at right lower pole of kidney was found via renal ultrasound incidentally. Abdominal CT revealed right renal mass, suspect urothelial cell carcinoma and RCC was less likely. The patient underwent for robotic-assisted laparoscopic partial nephrectomy and the pathology reported a TFE3-rearranged RCC.

Case 2: A 30-year-old female with no known medical conditions presented with intermittent right flank pain for 7-8 months. A right renal mass approximately 5.6 cm was incidentally detected on abdominal CT on health exam. Renal MRI revealed a right kidney tumor with evidence of intra-tumor hemorrhage, but no obvious fat component. Given the suspicion for renal cell carcinoma, the patient received right laparoscopic radical nephrectomy. Pathological report revealed a TFE3-rearranged PEComa.

 Discussion and conclusion:

 Current literature suggests that TFE3 translocation occurs in renal tubular stem cells, driving the development of RCC, while translocations in mesenchymal stem cells are linked to PEComa. Immunohistochemical markers like CA9 and cytokeratin 7 are often negative in TFE3-rearranged RCC. Notably, cathepsin K expression is expressed in approximately 60% of TFE3-rearranged RCC and typically negative in other common renal cell neoplasms. TFE3-rearranged PEComas show strong cathepsin K and HMB45 expression but are negative for PAX8 and cytokeratins. Both TFE3-rearranged RCC and PEComa are aggressive neoplasms, identified in young age with a slight female predominance. However, TFE3-rearranged RCC tends to be more aggressive and occurs in younger patients. Furthermore, the tyrosine kinase inhibitor cabozantinib, which targets VEGF, MET, AXL, has been shown to downregulate cathepsin K in vitro, presents a potential therapeutic option for the treatment of TFE3-rearranged RCC with cathepsin K positivity. This suggests that cabozantinib may offer targeted treatment for this specific subset of renal tumors.