Case 5 -

Translocation Carcinoma in Children and Young Adults John N Eble, M.D. Holger Moch, M.D.

Case history: 14 year old boy who felt pain while playing soccer. A CT revealed a mass in the right kidney. A nephrectomy was performed. Macroscopic findings: The tumor measured 7 x 5 x 2 cm. The tumor had a firm, gray-white appearance with irregular borders. The tumor was poorly circumscribed with central location. Diagnosis: Translocation carcinoma in children and young adults In childhood, by far the most common renal neoplasms are nephroblastomas. Renal cell carcinomas are rare in children. The new WHO classification includes new tumor types which occur predominantly in children and young adults. Such tumors include renal cell carcinomas with the ASPL-TFE3 gene fusion and carcinomas with a PRCC-TFE3 gene fusion. Collectively, these tumors have been termed Xp11.2 or TFE3 translocation carcinomas. Renal carcinomas associated with Xp11.2 translocations have a distinctive histopathologic appearance which is that of a carcinoma with papillary architecture comprised of clear cells. Some tumors have a more nested architecture and often feature cells with granular eosinophilic cytoplasm. The translocation carcinomas are characterized by cells with voluminous clear to eosinophilic cytoplasm and prominent nucleoli. Psammoma bodies are sometimes numerous. The tumors have the distinctive immunohistochemical feature of nuclear immunoreactivity for TFE3 protein. Only about 50% express epithelial markers such as cytokeratin and EMA. The carcinomas are defined by several different translocations involving chromosome Xp11.2, all resulting in gene fusions involving the TFE3 gene. TFE3 is a member of the basic-helix-loop-helix family of transcription factors. Both the PRCC-TFE3 and ASPL-TFE3 fusion proteins retain the TFE3 DNA-binding domain. This domain localizes to the nucleus and can act as transcription factor. Very little is known about the clinical behavior of these carcinomas. They usually present at advanced stage. However, their clinical course thus far appears to be indolent. References: Eble JN, et al. Tumours of the Kidney, in Tumours of the Urinary System and Male Genital Organs. 2004, IARC Press: Lyon. Bruder E, et al. Morphologic and molecular characterization of renal cell carcinoma in children and young adults. Am J Surg Pathol 28: 1117-32, 2004. Argani P, et al. Primary renal neoplasms with the ASPL-TFE3 gene fusion of alveolar soft part sarcoma: a distinctive tumor entity previously included among renal cell carcinomas of children and adolescents. Am J Pathol 159: 179-92, 2001. Argani P, et al. A distinctive pediatric renal neoplasm characterized by epithelioid morphology, basement membrane production, focal HMB45 immunoreactivity, and t(6;11)(p21.1;q12) chromosome translocation. Am J Pathol 158: 2089-96, 2001.