Review of renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions with focus on pathobiological aspect.
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.
Department of Diagnostic Pathology, Kochi Red Cross Hospital, Kochi, Japan. kurochankochi@yahoo.co.jp
Naoto
N
Kuroda
Shuji
S
Mikami
Chin-Chen
CC
Pan
Ronald J
RJ
Cohen
Ondrej
O
Hes
Michal
M
Michal
Yoji
Y
Nagashima
Yukichi
Y
Tanaka
Keiji
K
Inoue
Taro
T
Shuin
Gang-Hong
GH
Lee
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D041321:Chromosomes, Human, X / Q000235:genetics; D050939:Gene Fusion; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D014178:Translocation, Genetic
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D015514:Oncogene Proteins, Fusion; C069203:TFE3 protein, human