Von Hippel-Lindau (VHL) syndrome is an autosomal dominant disorder caused by mutations in the VHL tumor suppressor gene, characterized by visceral cysts and neoplasms including pheochromocytomas, renal cell carcinoma (RCC), pancreatic tumors, and central nervous system (CNS) hemangioblastomas, etc (1–3). VHL syndrome is classified into distinct clinical subtypes (Type 1, 2A, 2B, and 2C) based on whether specific neoplasms (such as pheochromocytoma and RCC) are present or absent (2, 4). Globally, this autosomal dominant disorder affects approximately 1 in 36,000 individuals (5, 6), yet its diagnosis is frequently delayed due to nonspecific initial manifestations and variable penetrance (7–9). The multisystem involvement and complexity of VHL-related lesions pose significant therapeutic challenges.

Pheochromocytoma, a hallmark of VHL syndrome, results from excessive catecholamine secretion. This typically causes paroxysmal or sustained hypertension by overstimulating adrenergic receptors. Hypertension in this context represents a secondary etiology, distinct from primary (essential) hypertension, with its pathogenesis directly linked to tumor-derived catecholamine excess. Chronic exposure to elevated catecholamines induces systemic hemodynamic disturbances, including persistent vasoconstriction and endothelial dysfunction, which collectively contribute to end-organ damage. Notably, sustained hypertension may precipitate catastrophic vascular complications such as aortic dissection—a life-threatening condition characterized by intimal tear and false lumen formation. Despite the well-established role of hypertension in aortic wall degeneration, aortic dissection remains exceptionally rare in VHL syndrome.

Herein, we present a unique case of VHL syndrome type 2B manifesting with multisystem involvement—Stanford type B aortic dissection, pheochromocytoma, RCC, multiple cysts, and cerebellar hemangioblastoma with obstructive hydrocephalus. This case vividly illustrates the severe therapeutic challenges and critical decision-making points in managing such complex presentations.

We describe a 50-year-old male (Height: 170 cm, Weight: 65 kg, BMI: 22.49 kg/m²) with a family history of VHL syndrome (Family pedigree illustrated in Figure 1 ).

The patient’s medical history began over a decade ago when he initially presented with dizziness and was diagnosed with hypertension (peak blood pressure: 170/100 mmHg) at a local hospital. The initial diagnostic workup was limited to confirming elevated blood pressure and lacked a standardized assessment for secondary causes. Specifically, no biochemical screening for catecholamine excess or dedicated adrenal imaging was performed, leading to a delay in diagnosing the underlying pheochromocytoma by more than ten years. Despite this diagnosis, the patient demonstrated poor adherence to the prescribed antihypertensive therapy, likely due to insufficient awareness of his condition’s severity. Four years prior to admission, surveillance imaging incidentally identified a left adrenal nodule (1.0×1.0 cm) and a right renal lesion (1.0×1.0 cm), yet no further diagnostic evaluation or intervention was initiated. Notably, one month before presentation, routine surveillance revealed a Stanford type B (DeBakey III) aortic dissection, prompting urgent endovascular aortic stent graft placement at another institution. The decision for emergent endovascular repair was made by the vascular surgery team at the referring hospital in accordance with standard aortic dissection management guidelines.

The patient was admitted to our department for further management of progressively enlarging left adrenal and right renal masses. A recent contrast-enhanced abdominal CT scan demonstrated substantial growth of the lesions, with the left adrenal mass measuring 4.1×3.5 cm and the right renal mass 3.5×3.5 cm ( Figure 2 ). Upon adjusting the window width during image analysis, an additional renal mass measuring 1.3 × 1.4 cm was identified in the right kidney ( Supplementary Figure 1 ). The imaging characteristics were consistent with pheochromocytoma and RCC. Subsequent serological evaluation revealed markedly elevated normetanephrine levels ( Supplementary Table 1 ), which definitively confirmed the diagnosis of pheochromocytoma. Additionally, multiple hepatic, pancreatic and bilateral renal lesions were observed in the liver, pancreas and bilateral kidneys, radiologically consistent with hepatic hemangiomas and simple pancreas/renal/hepatic cysts ( Figure 3 , the number of renal cysts > 30).

Notably, our evaluation revealed a persistent aortic dissection extending from the distal descending aorta to the abdominal aorta, raising concerns regarding the efficacy of the prior endovascular stent grafting. To elucidate whether this represented disease progression or incomplete exclusion of the false lumen, we conducted a comparative analysis of pre- and post-procedural CT imaging. The dissection morphology and extent demonstrated no significant interval change, indicating failure of the initial endograft to achieve complete sealing. Further scrutiny of the CT angiography identified the left renal artery originating from the false lumen ( Figure 4 ). Therefore, complete endovascular exclusion of the dissection flap would thus risk compromising left renal perfusion, potentially leading to ischemic nephropathy—a therapeutic dilemma corroborated through MDT consultation with the original surgical team.

The diagnosis was established through a combination of imaging and biochemical findings. The adrenal mass displayed classic radiological characteristics of pheochromocytoma, including well-circumscribed borders, heterogeneous enhancement, and persistent contrast retention. The renal mass exhibited enhancement patterns highly suggestive of RCC. The concurrent presence of multiple pancreatic and renal cysts further indicated a systemic disorder. Together, the clinical triad of pheochromocytoma, RCC, and multiple visceral cysts—supported by a significant family history—led to a presumptive diagnosis of VHL syndrome, prompting further multidisciplinary investigations for confirmation and staging.

Prompted MDT investigations included: (1) pedigree analysis revealing an autosomal dominant inheritance pattern ( Figure 1 ), with four affected relatives across three generations: maternal death from VHL-associated RCC, a deceased sibling with cerebellar hemangioblastoma, an afflicted nephew with visceral manifestations, and an eldest daughter confirmed with germline VHL mutation under targeted therapy; (2) Brain magnetic resonance imaging (MRI) identifying heterogeneously enhancing lesions in the left cerebellar hemisphere and vermis, radiologically confirmed as cerebellar hemangioblastoma with fourth ventricular obstruction and secondary hydrocephalus ( Supplementary Figure 2 ); (3) systematic screening via testicular ultrasonography and advanced ophthalmological imaging (optical coherence tomography (OCT) and ultra-widefield fundus angiography), both yielding unremarkable findings.

The patient’s clinical presentation fulfills the diagnostic criteria for VHL syndrome and aligns with VHL type 2B per the revised classification system (2, 4) (The chronological sequence of the patient’s clinical course is summarized in Supplementary Figure 3 ).

Our case delineates a rare and severe presentation of VHL syndrome type 2B, exceptionally complicated by aortic dissection—a previously unreported association. The concurrence of a catecholamine-secreting tumor, aortic dissection, renal malignancies, and a neurosurgical emergency exemplifies the profound therapeutic dilemma inherent in multisystem VHL disease and underscores the imperative for MDT coordination.

This case highlights three pivotal clinical insights for managing VHL syndrome with multisystem involvement: First, VHL-associated pathologies (e.g., pheochromocytoma-driven hypertension) may confer unique susceptibility to aortic dissection. Second, systematic screening for catecholamine-secreting tumors is imperative in patients with resistant hypertension to mitigate cardiovascular crises inherent to this multisystem disorder. Third, MDT care frameworks—integrating genetic, surgical, and oncologic expertise—are essential to resolve therapeutic dilemmas posed by competing life-threatening conditions. These findings reinforce that early recognition of multisystem complexity and proactive MDT coordination are critical to optimizing outcomes in VHL syndrome. Furthermore, this case reinforces the critical importance of screening for secondary hypertension, particularly in cases of early-onset, resistant, or paroxysmal hypertension, to identify underlying and potentially treatable conditions such as pheochromocytoma before catastrophic complications occur.