VHL mutation

Genetic testing identified a pathogenic VHL mutation: NM_000551.4(VHL):c.508G>A, consistent with VHL type 2C phenotype. Systematic screening for other VHL-associated lesions was negative. This case highlights the diagnostic challenge posed by clinically silent pheochromocytomas and underscores the importance of genetic evaluation in atypical adrenal tumors.

Branched-chain amino acid metabolism and IL4I1 are pivotal in the progression of ccRCC. AS classification and the AIS score present a robust framework for personalized treatment strategies, while IL4I1 shows potential as a novel therapeutic target to enhance treatment efficacy.

While CCPCE can be morphologically indistinguishable from CCPRCT and share PAX8+/KRT7+/CAIX+ immunoreactivity, typically negative staining for RCC/GATA3 coupled with the generally low stage and good outcome for CCPRCT may favor CCPCE in challenging scenarios. Except for VHL mutations in a syndromic setting, CCPCE lacks other molecular alterations of CCRCC (e.g., SETD2, PBRM1, BAP1), although further confirmatory studies are needed.

This study demonstrated that strict morphologic and immunohistochemical criteria can distinguish most CCRCCs mimicking CCPRCT from CCPRCT. The diagnosis of CCPRCT should be expanded to include tumors with monoallelic VHL alteration exhibiting typical morphologic and immunohistochemical features.

P1, N=40, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business decision and not related to safety concerns

P2, N=6, Active, not recruiting, Columbia University | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Jan 2026 --> Jan 2027

Off-label treatment with belzutifan was initiated. Regression of the pulmonary lesion with ongoing complete remission at 12 months of follow-up was observed. This case highlights the importance of molecular profiling for personalized therapy in rare tumor entities.

Our pilot data suggest that transcript levels of the genes involved in Krebs cycle, hypoxia, PI3K/AKT/mTOR, and RAS/RAF/ERK signaling pathways indicate their potential suitability as a candidate diagnostic marker. The results from this pilot study form the basis for a larger project to investigate gene transcription in an expanded cohort of patients who have undergone surgery for PCC.

Tumor profiling also uncovers actionable mutations in oncogenes like RET and VHL, which can be targeted with specific therapies. This review explores the integration of tumor molecular features with germline genetic data to refine diagnosis, risk assessment, and therapeutic strategies in hereditary cancer.

Endoscopic ultrasound with fine-needle aspiration was performed and standard cyst fluid analysis was nondiagnostic, but cyst fluid NGS identified a pathogenic VHL mutation. This case highlights the utility of cyst fluid NGS in uncovering hereditary cancer syndromes when conventional analyses are inconclusive.

Identification of the VHL gene mutation required genetic counseling of all family members, during which a similar mutation was identified in the younger brother. Surgical treatment is the main method of treating FHL syndrome, but advances in genetic research technologies provide new opportunities for the treatment of tumors associated with this syndrome.

Approximately 40% of PPGL harbor germline mutations, whereas somatic alterations account for additional subsets. Mutations in SDHx, VHL, RET, NF1, and other susceptibility genes define molecular clusters with distinct signaling pathways and clinical behavior, underscoring the importance of multidisciplinary, lifelong management.