Tuberous Sclerosis–Associated Renal Neoplasm

Abstract

A man in his thirties presented with bilateral renal masses and well-controlled hypertension. He had a history of resection of a brain lesion in early childhood. Imaging studies did not reveal cystic lung disease. Bilateral nephrectomies were performed because of end-stage renal disease, and both kidneys were replaced by fibrotic and lobulated masses. Histopathological examination revealed extensive involvement by angiomyolipoma bilaterally. What syndrome should this patient be screened for, and what are some other common associated features?a.Birt-Hogg-Dubé syndrome: benign tumors of the skin and spontaneous pneumothorax secondary to cystic lung diseaseb.von Hippel-Lindau disease: central nervous system hemangioblastomas and pheochromocytomasc.Li-Fraumeni syndrome: osteosarcoma, adrenocortical carcinoma, and central nervous system tumorsd.Tuberous sclerosis complex: subependymal giant cell astrocytomas, cardiac rhabdomyomas, and lymphangioleiomyomatosis Answer: d. Tuberous sclerosis complex: subependymal giant cell astrocytomas, cardiac rhabdomyomas, and lymphangioleiomyomatosis Tuberous sclerosis complex is associated with renal manifestations including renal angiomyolipomas and a wide spectrum of renal neoplasia that have variable morphological features.1Guo J. Tretiakova M.S. Troxell M.L. et al.Tuberous sclerosis-associated renal cell carcinoma: a clinicopathologic study of 57 separate carcinomas in 18 patients.Am J Surg Pathol. 2014; 38: 1457-1467Crossref PubMed Scopus (129) Google Scholar Two major diagnostic features or a combination of 1 major and at least 2 minor diagnostic features are required to establish a clinical diagnosis.2Henske E.P. Jóźwiak S. Kingswood J.C. Sampson J.R. Thiele E.A. Tuberous sclerosis complex.Nat Rev Dis Primers. 2016; 2: 16035Crossref PubMed Scopus (214) Google Scholar Major diagnostic criteria for tuberous sclerosis include hypomelanotic macules (≥3 of ≥5 mm in diameter), angiofibromas (≥3) or fibrous cephalic plaques, ungual fibromas (≥2), shagreen patches, multiple retinal hamartomas, cortical dysplasias, subependymal nodules, subependymal giant cell astrocytomas, cardiac rhabdomyomas, lymphangioleiomyomatosis, and angiomyolipomas (≥2). Tuberous sclerosis complex is an autosomal dominant disorder associated with loss-of-function alterations in TSC1 and TSC2 genes (for expansion of gene symbols, use search tool at www.genenames.org). von Hippel-Lindau disease, secondary to germline alterations in the VHL gene, is associated with clear cell renal cell carcinoma, central nervous system hemangioblastoma, and pheochromocytoma. Li-Fraumeni syndrome, secondary to germline alterations in the TP53 gene, is associated with osteosarcoma, adrenocortical carcinoma, and central nervous system tumors. Finally, Birt-Hogg-Dubé syndrome, secondary to germline alterations in the FLCN gene, is associated with hybrid renal tumors, benign tumors of the skin, and spontaneous pneumothorax secondary to cystic lung disease.