Clinical Pearls & Morning Reports
Published November 21, 2018
There is a rare form of renal-cell carcinoma that occurs in young patients who do not have associated risk factors. This form of renal-cell carcinoma is driven by a translocation involving one of the genes in the microphthalmia-associated transcription factor (MiT) family and is often referred to as MiT family translocation renal-cell carcinoma. Read the latest NEJM Case Records of the Massachusetts General Hospital here.
Q: What tumors are known to mimic renal cancer?
A: Oncocytoma is the most common tumor that mimics renal cancer. On imaging, the features of oncocytoma are typically homogeneous and include a classic central scar that correlates histologically with fibrosis. Xanthogranulomatous pyelonephritis is a chronic inflammatory condition that can cause large renal masses and mimic renal cancer on imaging. It is almost always associated with some degree of chronic obstruction of the kidney, which is manifested by hydronephrosis. Renal stones and prominent calcification are also often present.
Q: What are some of the different types of renal cancer?
A: Clear-cell renal-cell carcinoma accounts for approximately 75% of renal cancers, whereas papillary tumors account for approximately 15%. Chromophobe renal-cell carcinoma tends to be slow-growing; it can be associated with familial syndromes such as the Birt–Hogg–Dubé syndrome.
A: TFEB belongs to the group of genes in the MiT family, which includes MITF, TFE3, TFEB, and TFEC. The associated proteins have the ability to homodimerize and heterodimerize, bind to defined enhancer-box DNA sequences, and activate the expression of specific genes. Translocations involving TFE3 and TFEB can be found in renal-cell carcinoma. The resulting tumors are listed in the 2016 World Health Organization classification of renal tumors as MiT family translocation renal-cell carcinomas, namely Xp11 renal-cell carcinoma (with fusion of TFE3) and t(6;11) renal-cell carcinoma (with fusion of TFEB). These tumors share clinicopathological features and are disproportionately seen in young adults and pediatric patients. The tumor cells underexpress epithelial markers and overexpress melanocytic markers and their respective gene (TFE3 or TFEB). A genetic assay to detect gene fusion can be performed to confirm the diagnosis.
A: TFEB translocation tumors account for a clinically significant proportion of pediatric renal cancers but are rare in adults. Clinical suspicion would be higher in young adults than in older adults. Among reported cases, distant metastases are unusual but have occurred. Patients with MiT family translocation renal-cell carcinoma typically present in their late 20s or early 30s.