VHL mutation

Genetic analysis showed patients one and two presented mutations in the VHL gene, confirming the VHL diagnosis. While the cases presented here follow the general lines for VHL disease, patients are related to each other, present tumors of the nervous system and mutations in the VHL gene, their particularities of presentation and manifestation bring new insights into this rare genetic disease.

Over a median follow-up of 50 months (range, 4-114 months), all patients remained disease-free. Our study confirms that RCC with HB-like features represents a distinct morphological pattern within the HB to RCC with fibromyomatous stroma continuum and establishes its expanded morphological spectrum and indolent biological behavior.

Analyzing this case alongside the literature highlights the need to suspect VHL in young patients with multiple tumors, for whom genetic testing is crucial for definitive diagnosis. While a single case cannot capture the full disease spectrum, it provides valuable clinical insight.

This case underscored the importance of considering hemangioblastoma in the differential diagnosis of rectal submucosal lesions. It highlighted the need for a thorough diagnostic approach that integrates colonoscopic evaluation with histopathological examination, particularly in patients presenting with altered stool consistency or melena. Furthermore, the NGS results implicated that TSC, SDH and PTEN may contribute to hemangioblastoma development. These alterations could constitute a novel diagnostic signature, a premise that warrants definitive investigation through larger, multi-institutional studies.

Using single cell transcriptomics, we show that the VHL-positive and -negative Caki-1 cells are characterized with different proportions of benign and aggressive cells as seen by analysis of specific gene expression. Furthermore, the identified angiogenesis-related genes were linked to affect clinical outcomes in ccRCC patients, suggesting that VHL restoration may mitigate high-risk molecular features.

Pancreatic lesions are common in VHL disease. Mutations in codons 161 and 167 are hotspots in patients with pancreatic lesions, particularly NETs.

This case underscores the importance of considering hereditary genetic syndromes in patients presenting with hypertension and multi-system tumor involvement. Comprehensive evaluation, standardized familial screening, and genetic testing play a crucial role in guiding treatment decisions for affected individuals.

This case highlights an unusual clinical course: a carotid body paraganglioma, initially asymptomatic and successfully resected, developed skeletal metastasis after a prolonged disease-free interval of 7 years. This report underscores the importance of revisiting conventional risk stratification, incorporating genetic testing, and ensuring vigilant, long-term follow-up.

Takotsubo syndrome may be the initial manifestation of VHL-associated pheochromocytoma. Systematic genetic evaluation and family screening are crucial in hereditary tumor syndromes.

Advances in molecular hematology are expected to improve the characterization of "idiopathic erythrocytosis". Results from prospective studies are needed to elucidate the underlying pathology and guide management.

Furthermore, D-mannose reduces glucose uptake and intracellular lactate and NADPH production. To sum up, this study demonstrates that targeting HIF-1α by D-mannose to inhibit metabolic reprogramming is a promising strategy for ccRCC and complements a previously unknown role of D-mannose in cancer treatment.

Here, we reveal markedly different consequences of HIF1A and HIF2A activation, but that both contribute to renal cell-type specific consequences of VHL-inactivation in the kidney. Early involvement of HIF2A in promoting proliferation within the proximal tubular epithelium supports therapeutic targeting of HIF2A early in VHL disease.