Secondary renal neoplasia following chemotherapy or radiation in pediatric patients

• Published in: Human pathology 2020-09, Vol.103, p.1-13
• Main Authors: Gupta, Sounak, Vanderbilt, Chad M., Leibovich, Bradley C., Herrera-Hernandez, Loren, Raghunathan, Aditya, Sukov, William R., Voss, Jesse S., Barr Fritcher, Emily G., Reed, Katelyn A., Lohse, Christine M., Reuter, Victor E., Jimenez, Rafael E., Thompson, R. Houston, Cheville, John C.
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Antineoplastic Agents - adverse effects; Cancer therapies; Chemotherapy; Child; Child, Preschool; Cloning; Female; Histopathology; Humans; Infant; Kidney cancer; Kidney Neoplasms - etiology; Kidney Neoplasms - pathology; Leukemia; Lymphoma; Male; Metastasis; Middle Aged; Neoplasms, Second Primary - etiology; Neoplasms, Second Primary - pathology; Neuroblastoma; Patients; Pediatrics; Radiation; Radiation therapy; Radiotherapy - adverse effects; Renal cell carcinoma; Tumors; Wilms tumor; Young Adult
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2020.07.014

Renal neoplasia occurring as a second malignancy following childhood cancer has been most closely associated with neuroblastoma and Wilms tumor. While some cases have been associated with a genetic predisposition, nearly all are thought to result from “late effects” of therapy-related toxicity that involves chemotherapy or radiation. It is unclear if these tumors are enriched for specific molecular or morphologic characteristics. A query of our institutional nephrectomy registry of 8295 patients for renal neoplasia occurring post-treatment for childhood cancer revealed 6 patients with Wilms tumor, 4 with neuroblastoma, and 1 with acute lymphoblastic leukemia (ALL). Three additional cases of MiT family translocation renal cell carcinoma (RCC), from 2 patients, following chemotherapy for neuroblastoma and systemic lupus erythematosus and another of clear cell RCC post-ALL were included. The most common tumor type was clear cell RCC: 9/19 cases (47.4%), followed by metanephric adenoma and MiT family translocation RCC (3/19, 15.8%). There were no characteristic features to indicate a unique renal neoplasia subtype. Potential syndromic renal neoplasia occurred in 2 patients, metanephric adenomas and oncocytoma in a patient with hyperparathyroidism-jaw tumor syndrome post-treatment of Wilms tumor and a fumarate hydratase-deficient RCC in a patient post-treatment for ALL. The mean age at diagnosis of childhood neoplasia or treatment with chemotherapy or radiation was 4.7 years, and the average time to subsequent renal neoplasia was 31 years. Five (of 14) patients developed metastatic RCC, and there were 2 RCC-related deaths. These results indicate the need for extended clinical follow-up of these patients. •Post-Wilms tumor: 6 patients; postneuroblastoma: 5 patients; others: 3 patients.•Most common tumor type: clear cell renal cell carcinoma, 9/19 cases.•Second most common: metanephric adenoma and TFE3/TFEB rearranged renal cell carcinoma, 3/19 cases.•Potential syndromal associations: hyperparathyroidism-jaw tumor syndrome and hereditary leiomyomatosis and renal cell cancer.•Average time to subsequent renal neoplasia: 31 years.