: Von Hippel-Lindau (VHL) disease is an autosomal dominant condition that predisposes affected individuals to a variety of malignant and benign neoplasms. The pathogenetic turning point of this illness is the accumulation of hypoxia-inducible factor (HIF)-1α, a transcription factor of several genes involved in oncogenesis, angiogenesis, tissue regeneration, metabolic regulation, hematopoiesis, and inflammatory responses. From an oncological perspective, increased awareness of the molecular pathways underlying this disease is bringing us closer to the development of specific and targeted therapies. Meanwhile, on the surgical side, improved understanding can help to better identify the patients to be treated and the surgical timing. Overall, pathogenesis research is crucial for developing patient-tailored therapies. One of the actual key topics of interest is the link between the VHL/HIF axis and inflammation. The present study aims to outline the fundamental mechanisms that link VHL disease and immune disorders, as well as to explore the details of the overlap between VHL disease and myasthenia gravis (MG) pathogenetic pathways. As a result, MG becomes a paradigm for autoimmune disorders that might be related with VHL disease.
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