Review of renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions with focus on pathobiological aspect
Naoto Kuroda1, Shuji Mikami2, Chin-Chen Pan3, Ronald J. Cohen4, Ondrej Hes5, Michal Michal5, Yoji Nagashima6, Yukichi Tanaka7, Keiji Inoue8, Taro Shuin8 and Gang-Hong Lee9
1Department of Diagnostic Pathology, Kochi Red Cross Hospital, Kochi, Japan, 2Division of Diagnostic Pathology, Keio University Hospital, Tokyo, Japan, Department of Pathology, 3Taipei Veterans General Hospital, Taipei, Taiwan, 4Uropath Pty Ltd, Western Australia, Australia, 5Sikl’s Department of Pathology, Charles University Hospital Plzen, Czech Republic, 6Department of Molecular Pathology, Yokohama City University Graduate School of Medicine, Yokohama, Japan, 7Department of Pathology, Kanagawa Children’s Medical Center, Yokohama, Japan, and Departments of 8Urology and 9Pathology, Kochi Medical School, Kochi University, Kochi, Japan.
Offprint requests to: N. Kuroda, Department of Diagnostic Pathology, Kochi Red Cross Hospital, Shin-honmachi 2-13-51, Kochi City, Kochi 780-8562, Japan. e-mail: kurochankochi@yahoo.co.jp
Summary. The concept of Xp11.2 renal cell carcinoma (RCC) was recently established as a tumor affecting 15% of RCC patients <45 years. Many patients present with advanced stage with frequent lymph node metastases. Histologically, Xp11.2 RCC is characterized by mixed papillary nested/alveolar growth pattern and tumor cells with clear and/or eosinophilic, voluminous cytoplasm. Neoplastic cells show intense nuclear immunoreactivity to TFE3, while focal immunostaining for melanocytic markers, including melanosome-associated antigen or Melan A in some cases, are also noted. Alpha smooth muscle actin and TFEB are consistently negative. Ultrastructurally, the ASPL-TFE3 RCC variant contains rhomboid crystals in the cytoplasm, similar to that observed in alveolar soft part sarcoma. The fusion of the TFE3 gene with several different genes, including ASPL(17q25), PRCC(1q21), PSF(1q34), NonO (Xq12) and CLTC (17q23) have been identified to date. The behavior of Xp11.2 RCC in children and young adults is considered as indolent even when diagnosed at advanced stage, including lymph node metastasis. However, Xp11.2 RCC in older patients behaves in a more aggressive fashion. Therapy includes nephrectomy with extended lymphadenectomy. There may be a role for new protease inhibitors in advanced inoperable disease. Further research is required to correlate clinical behavior with the expanding genetic spectrum of this tumor, and to establish standard therapy protocols for primary and metastatic lesions. Histol Histopathol 27, 133-140 (2012)
Key words: Xp11.2 RCC, TFE3, Immunohistochemistry
DOI: 10.14670/HH-27.133