TY - JOUR
T1 - Review of renal carcinoma associated with Xp11.2 translocations/TFE3 gene fusions with focus on pathobiological aspect
AU - Kuroda, Naoto
AU - Mikami, Shuji
AU - Pan, Chin Chen
AU - Cohen, Ronald J.
AU - Hes, Ondrej
AU - Michal, Michal
AU - Nagashima, Yoji
AU - Tanaka, Yukichi
AU - Inoue, Keiji
AU - Shuin, Taro
AU - Lee, Gang Hong
PY - 2012/2
Y1 - 2012/2
N2 - 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 melanosomeassociated 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.
AB - 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 melanosomeassociated 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.
KW - Immunohistochemistry
KW - TFE3
KW - Xp11.2 RCC
UR - http://www.scopus.com/inward/record.url?scp=84863407430&partnerID=8YFLogxK
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M3 - Review article
C2 - 22207547
AN - SCOPUS:84863407430
SN - 0213-3911
VL - 27
SP - 133
EP - 140
JO - Histology and Histopathology
JF - Histology and Histopathology
IS - 2
ER -