Translocation carcinomas of the kidney after chemotherapy in childhood.
OBJECTIVE
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.


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.


CONCLUSIONS
Cytotoxic chemotherapy may predispose to the development of renal translocation carcinomas.
Department of Pathology, The Johns Hopkins Hospital, Baltimore, MD, USA.
Pedram
P
Argani
Marick
M
Laé
Edgar T
ET
Ballard
Mahul
M
Amin
Carlos
C
Manivel
Brian
B
Hutchinson
Victor E
VE
Reuter
Marc
M
Ladanyi
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000009:adverse effects*; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D002648:Child; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D009363:Neoplasm Proteins / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000235:genetics*; D014178:Translocation, Genetic
D000970:Antineoplastic Agents; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D009363:Neoplasm Proteins; C069203:TFE3 protein, human; C064972:TFEB protein, human