Journal of Kidney Cancer and VHL <p>Journal of Kidney Cancer and VHL (ISSN: 2203-5826) is indexed in <strong>PubMed</strong>,&nbsp;Emerging Sources Citation Index&nbsp;of <strong>Web of Science</strong>, and the Directory of Open Access Journals (<strong>DOAJ</strong>). Journal is dedicated for the dissemination of research findings in kidney cancer and VHL.</p> Codon Publications en-US Journal of Kidney Cancer and VHL 2203-5826 Papillary Renal Cell Carcinoma in Lynch/Muir-Torre Syndrome with Germline Pathogenic Variant in MSH6 and Molecular Analysis <p>Lynch syndrome (LS) is an autosomal dominant inherited disorder due to pathogenic variations in the mismatch repair genes, which predisposes to malignancies, most commonly colon and endometrial carcinoma. Muir-Torre syndrome is a subset of LS with cutaneous sebaceous adenoma and keratoacanthoma in addition to the malignancies. Renal cell carcinoma (RCC) in patients with LS is extremely rare. Only 26 cases have been reported and among them, only two cases of papillary RCC. We report a case of synchronous papillary RCC and colonic adenocarcinoma in an 85-year-old male with Lynch/Muir-Torre syndrome. The LS was diagnosed when he presented with multiple sebaceous adenomas and genetic testing showed a pathogenic variant in <em>MSH6</em> mismatch repair gene. A colonoscopy at that time showed multiple tubular adenomas with high-grade dysplasia. He was lost to follow-up and presented with gastrointestinal bleeding after 20 years. A right colonic mass, and a solid mass in the lower pole of the right kidney, was detected by imaging. Right Colectomy showed a T3N0 mucin-producing adenocarcinoma. Right nephrectomy showed a T3a papillary RCC which was microsatellite stable with <em>MSH6</em>, and <em>KRAS</em> mutation. The 36-month follow-up exams showed additional sebaceous neoplasms, and an absence of metastatic carcinoma. Analysis of the reported cases of RCC in LS show clear cell RCC as the most common type. These tumors showed <em>MLH1</em> mutation most commonly, unlike the urothelial malignancies in LS which involve <em>MSH2</em>. Among the 4 cases of RCC with <em>MSH6</em> mutation, three were in females, indicating some gender differences.</p> Yu Yang Shweta Dhar Jennifer Taylor Bhuvaneswari Krishnan Copyright (c) 2021 Yu Yang, Shweta Dhar, Jennifer Taylor, Bhuvaneswari Krishnan 2021-04-21 2021-04-21 8 2 8 19 10.15586/jkcvhl.v8i2.175 Hypoxia-Inducible Factor-2 Alpha as a Novel Target in Renal Cell Carcinoma <p>Hypoxia-inducible factor (HIF), an important mediator of hypoxia response, is implicated in tumorigenesis in the setting of pseudohypoxia, such as in the inactivation of von Hippel–Lindau tumor suppressor protein (pVHL), leading to development and progression of clear cell renal cell carcinoma (ccRCC). Targeting downstream molecules in HIF pathway, such as vascular endothelial growth factor (VEGF), has led to improvement in clinical outcome for patients with advanced ccRCC, but such therapy thus far has been limited by eventual resistance and treat-ment failure. Following the discovery of HIF-2 alpha playing a key role in ccRCC carcinogenesis, inhibitors targeting HIF-2 alpha have been developed and have demonstrated encouraging efficacy and safety profile in clinical trials. This review discusses HIF-2 alpha as a promising therapeutic target for ccRCC.</p> WonSeok W. Choi Julia Boland Jianqing Lin Copyright (c) 2021 WonSeok W. Choi, Julia Boland, Jianqing Lin 2021-04-07 2021-04-07 8 2 1 7 10.15586/jkcvhl.v8i2.170