Multidisciplinary management of patients diagnosed with von Hippel-Lindau disease: A practical review of the literature for clinicians

Larcher, Alessandro; Belladelli, Federico; Fallara, Giuseppe; Rowe, Isaline; Capitanio, Umberto; Marandino, Laura; Raggi, Daniele; Capitanio, Jody Filippo; Bailo, Michele; Lattanzio, Rosangela; Barresi, Costanza; Calloni, Sonia Francesca; Barbera, Maurizio; Andreasi, Valentina; Guazzarotti, Giorgia; Pipitone, Giovanni; Carrera, Paola; Necchi, Andrea; Mortini, Pietro; Bandello, Francesco; Falini, Andrea; Partelli, Stefano; Falconi, Massimo; Cobelli, Francesco De; Salonia, Andrea

doi:10.1016/j.ajur.2022.08.002

Cited by 4 publications

(5 citation statements)

References 113 publications

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“…Re-surgical treatment may be considered for significant neurological deficit symptoms, hemorrhage of HBs tumor, or new cyst enlargement. For sub-completely resected, unresectable lesions, or cornified HBs diffusion, radiation therapy and/or stereotactic or radiosurgery are valid options, with 5-year tumor control rates of 80-90% ( 8 ).…”

Section: Discussionmentioning

confidence: 99%

Von-Hipple Lindau syndrome with family history: a case report and seventeen years follow-up study

Fan,

Wang,

Chen

et al. 2024

Front. Oncol.

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BackgroundVon-Hipple Lindau syndrome is an uncommon autosomal dominant disorder. 17 years ago we diagnosed a young woman with VHL syndrome validated by Sanger sequencing, her family members were genetically tested as well, and 187 healthy people were randomly selected for VHL genetic testing as controls. We analyze the clinical and genetic characteristics of VHL syndrome in a Chinese lineage and with 17-year follow-up.Case presentationA woman was finally diagnosed with VHL syndrome due to the detection of a missense mutation c.353T > C in exon 2 of the short arm of chromosome 3, which resulted in a leucine substitution at amino acid 118 of the encoded protein by a proline, which may be thought the main cause of the disease. The same mutation was observed in two other family members, their clinical symptoms are not entirely identical. However, this mutation was not found in other family members or 187 healthy controls. She clinically presented with central nervous system hemangioblastomas, clear renal cell carcinoma, and pancreatic neuroendocrine neoplasms, despite the multi-organ involvement and several relapses during the disease, the patients survive well for she was treated with aggressive surgery early in the course of the plaguing symptoms, whereas patients who are not aggressively treated have a poorer prognosis.ConclusionThe clinical presentation of VHL syndrome is atypical, and early identification and treatment of VHL syndrome is possible by genetic testing techniques. Multiple relapses occurred during the course of the disease, but early diagnosis and aggressive treatment allowed the patients to survive well.

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Section: Discussionmentioning

confidence: 99%

Von-Hipple Lindau syndrome with family history: a case report and seventeen years follow-up study

Fan,

Wang,

Chen

et al. 2024

Front. Oncol.

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“…RCCs are often multiple and bilateral; however, they tend to have indolent growth. The "watch-and-wait" approach is usually applied to renal masses sized below 3 cm in diameter, and nephron-sparing techniques are considered for tumor ablation [82] (Table 3). Biannual MRI since 20 years Dermatologic examination (every 6-12 months); annual evaluation of parotid glands; annual ultrasound of thyroid gland may be considered; lung CT for symptomatic patients (before scheduled general anesthesia or before long-distance flights); regular colonoscopies, especially in kindreds with family history of colorectal malignancies…”

Section: Hereditary Conditions Associated With Increased Risk Of Rena...mentioning

confidence: 99%

“…Von Hippel-Lindau disease Antiangiogenic therapy and multikinase inhibitors; "Watch-and-wait" approach (lesions < 3 cm in diameter) [82] Anti-HIF2-alpha therapy (belzutifan) [93][94][95][96] Fumarate hydratase deficiency Bevacizumab + erlotinib; multikinase inhibitors; immune therapy [97][98][99][100][101][102][103][104][105] Immediate surgical removal [106] Hereditary pheochromocytoma/ paraganglioma syndrome Immediate surgical removal [72] Hereditary papillary renal cell carcinoma MET inhibitors (crizotinib, capmatinib) [107][108][109] "Watch-and-wait" approach (lesions < 3 cm in diameter) [71,110] Birt-Hogg-Dubé Syndrome mTOR inhibitors (everolimus)? [111] "Watch-and-wait" approach (lesions < 3 cm in diameter) [106] Tuberous sclerosis mTOR inhibitors (everolimus) [112][113][114] "Watch-and-wait" approach for angiomyolipomas, insufficient evidence regarding RCC [115,116] BAP1 tumor predisposition syndrome Insufficient evidence, but immediate surgical removal is suggested [106] Cowden syndrome mTOR inhibitors (everolimus)?…”

Section: Disease Therapy Surgical Approachmentioning

confidence: 99%

Hereditary Renal Cancer Syndromes

Yanus,

Kuligina,

Imyanitov

2024

Medical Sciences

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Familial kidney tumors represent a rare variety of hereditary cancer syndromes, although systematic gene sequencing studies revealed that as many as 5% of renal cell carcinomas (RCCs) are associated with germline pathogenic variants (PVs). Most instances of RCC predisposition are attributed to the loss-of-function mutations in tumor suppressor genes, which drive the malignant progression via somatic inactivation of the remaining allele. These syndromes almost always have extrarenal manifestations, for example, von Hippel–Lindau (VHL) disease, fumarate hydratase tumor predisposition syndrome (FHTPS), Birt–Hogg–Dubé (BHD) syndrome, tuberous sclerosis (TS), etc. In contrast to the above conditions, hereditary papillary renal cell carcinoma syndrome (HPRCC) is caused by activating mutations in the MET oncogene and affects only the kidneys. Recent years have been characterized by remarkable progress in the development of targeted therapies for hereditary RCCs. The HIF2aplha inhibitor belzutifan demonstrated high clinical efficacy towards VHL-associated RCCs. mTOR downregulation provides significant benefits to patients with tuberous sclerosis. MET inhibitors hold promise for the treatment of HPRCC. Systematic gene sequencing studies have the potential to identify novel RCC-predisposing genes, especially when applied to yet unstudied populations.

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“…Von Hippel-Lindau disease (VHL) is an autosomal dominant condition, caused by an abnormality of the VHL tumor suppressor gene, with an incidence of approximately 1/36,000 live births (1,2). In 1894, Von Hippel, a German ophthalmologist, reported cases of retinal angiomatosis, and later in 1926, Lindau, a Swedish pathologist, discovered a link between retinal angiomatosis and cerebellar hemangioblastomas.…”

Section: Introductionmentioning

confidence: 99%

“…Chromosome 3 (3p25.3), contains the onco-suppressor gene VHL and encodes a ubiquitin ligase, which degrades hypoxia-inducible transcription factor-alpha 2 (HIF-2a). When VHL genes are inactive, HIF-2a accumulates and activates other genes, such as vascular endothelial growth factor (VEGF), leading to oncogenesis (2).…”

Section: Introductionmentioning

confidence: 99%

Von Hippel Lindau Disease With Multiorganic Localization in a Younger Male Patient – Case Raport and Short Literature Review

Calboreanu-Libu,

Cristea,

Azis

et al. 2023

ARS Medica Tomitana

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Von Hippel-Lindau (VHL) disease is an inherited tumor predisposition caused by mutations in the VHL tumor suppressor gene. Carriers of these mutations face a lifelong risk of developing multisystemic tumors. We present the case of a patient who at the age of 23 presented, following an insidious onset, symptoms of intracranial hypertension. Therapeutic and diagnostic surgical intervention put the stigma of a genetic pathology with permanent life impairment. The multiple surgeries undergone and the lack of early rehabilitation led to the significant impairment of the functional deficit through the appearance of paraparetic motor deficit, balance and walking disorders. The periodic functional evaluation is carried out in the Rehabilitation Hospital of Techirghiol Romania, where he is hospitalized and receives complex treatments by combining natural and physical-kinetic factors. For the last 30 years, significant changes have been made regarding the clinical characteristics and molecular aspects of VHL disease and early genetic diagnosis, but significant challenges remain. The complex multidisciplinary approach of these cases represents a priority in treating these patients.

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Multidisciplinary management of patients diagnosed with von Hippel-Lindau disease: A practical review of the literature for clinicians

Cited by 4 publications

References 113 publications

Von-Hipple Lindau syndrome with family history: a case report and seventeen years follow-up study

Von-Hipple Lindau syndrome with family history: a case report and seventeen years follow-up study

Hereditary Renal Cancer Syndromes

Von Hippel Lindau Disease With Multiorganic Localization in a Younger Male Patient – Case Raport and Short Literature Review

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