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Translocation Carcinomas of the Kidney After Chemotherapy in Childhood

Pedram Argani, Marick Laé, Edgar T. Ballard, Mahul Amin, Carlos Manivel, Brian Hutchinson, Victor E. Reuter, Marc Ladanyi

From the Departments of Pathology and Oncology, The Johns Hopkins Hospital, Baltimore, MD; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY; Department of Pathology, Children's Hospital Medical Center, Cincinnati, OH; Department of Pathology, Emory University, Atlanta, GA; and Department of Pathology, University of Minnesota, Minneapolis, MN

Address reprint requests to Marc Ladanyi, MD, Memorial Sloan-Kettering Cancer Center, Department of Pathology, 1275 York Avenue, New York, NY 10021; e-mail: ladanyim{at}mskcc.org

PURPOSE: Children who survive cancer are at more than 19-fold increased risk of developing another malignancy. Renal cell carcinoma (RCC) occurring as a secondary malignancy is uncommon. Translocation RCC, bearing TFE3 or TFEB gene fusions, are recently recognized entities for which risk factors have not been identified.

PATIENTS AND METHODS: We describe the clinical, pathologic, cytogenetic, and molecular data on six translocation RCCs that arose in five young patients who had received chemotherapy.

RESULTS: The ages at time of diagnosis of the RCC ranged from 6 to 22 years. Histologically, these tumors showed typical features previously described for translocation RCCs. At the molecular level, three tumors contained the ASPL-TFE3 fusion, two contained Alpha-TFEB, and one contained PRCC-TFE3. The intervals between chemotherapy and the diagnosis of RCC ranged from 4 to 13 years. The indications for the antecedent chemotherapy were varied and included acute promyelocytic leukemia, acute myeloid leukemia with t(9;11), bilateral Wilms' tumor, systemic lupus erythematosus, and conditioning regimen of bone marrow transplant for Hurler's syndrome. Only the latter patient had also received radiation. Hence, among 39 genetically confirmed translocation RCCs in our personal experience, six (15%) have arisen in patients who had received cytotoxic chemotherapy.

CONCLUSION: Cytotoxic chemotherapy may predispose to the development of renal translocation carcinomas.

Supported in part by National Institutes of Health Grant No. RO1 CA95785 (M.L.).

Presented in part at the 2005 United States and Canadian Academy of Pathology Annual Meeting, San Antonio, TX, March 1, 2005.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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