A retrospective analysis was conducted on the clinical data of a patient with adrenal hemangioblastoma (HB), pathologically confirmed at the First Medical Center of Chinese PLA General Hospital. A review of the literature relating to adrenal HB was also undertaken. The patient was a 36-year-old male in whom a right adrenal mass was incidentally detected during a physical examination. The mass measured approximately 4.7 cm×4.2 cm and had a CT attenuation value of approximately 55 HU. MRI showed an irregular mass with a slightly long T1, mixed long/short T2 signals, mildly high signal intensity on diffusion weighted imaging, and a slightly low signal on apparent diffusion coefficient. No signal drop was observed on opposed-phase imaging. Dynamic contrast-enhanced scanning revealed progressive, marked enhancement. 68Ga DOTATATE PET-CT demonstrated a slightly hypodense mass in the right adrenal gland (maximum standardized uptake value 17.3). Functional evaluation showed an elevated chromogranin A (CgA) level of 294.64 pmol/L (normal range: 64-204 pmol/L), with no other abnormalities detected. The preoperative diagnosis was pheochromocytoma, and the patient underwent surgery after adequate preoperative preparation with phenoxybenzamine hydrochloride. Immunohistochemical results-S-100 (focal weak+), melan-A (-), inhibin-α (partial+), FLI-1 (+), CK (-), Syn (partial+), CgA (-), Ki67 (2%+), CD34 (+), CD31 (+), and desmin (-)-confirmed the diagnosis of adrenal HB. Genetic testing detected no VHL gene mutation. No recurrence or metastasis was observed during more than two years of follow-up. A review of the literature revealed that this was the first reported case of adrenal HB in China. Globally, only six cases have been reported to date, four of which were clearly related to von Hippel-Lindau syndrome. Adrenal HB is exceptionally rare and lacks characteristic clinical manifestations. Significant enhancement of the solid component with flow-void vessels on MRI is considered a relatively distinctive imaging feature. Definitive diagnosis relies on pathology and immunohistochemistry. Surgical resection remains the primary treatment, and the prognosis is generally favorable.

Von Hippel Lindau (VHL) disease is a rare autosomal dominant disease with multi organ involvement. A 45yr old female, Known case of VHL with a diagnosis of renal cell carcinoma, pancreatic neuroendocrine tumour and spinal hemangioblastoma was scheduled for open partial nephrectomy. She underwent excision of cerebellar hemangioblastoma with ventriculoperitoneal shunt insertion 2 yrs back. During pre anesthetic check up, the functionality of ventriculoperitoneal shunt was confirmed radiologically and neuroendocrine tumor workup was done to rule out pheochromocytoma. Intraoperatively, the hemodynamic response was attenuated and care was taken during positioning and handling patients as it may have effects on ICP. Post operative pain was managed by continuous erector spinae plane infusion. Knowledge about the disease and associated lesions helped us to effectively manage perioperatively.

Binocular fusion normally relies on a “cyclopean eye” that integrates image disparities between the two eyes into a single coherent percept. When fusion fails, how the brain chooses its spatial reference frame remains unclear. Here, we report a rare case of a 44-year-old man who developed multiple-directions diplopia following surgical resection of a cerebellar vermis hemangioblastoma. Clinical tests showed deficits in several extraocular muscles. Experimentally, in binocular and dichoptic viewing, perception was always anchored to the left eye with the right eye's image misaligned, whereas monocular viewing produced no diplopia. Crucially, the patient could voluntarily switch to the right eye as reference, which was independent of stimulus shape similarity, stimulus exposure order, or participant response demands. This case offers a unique window to understand the relationship between automatic sensory integration and top-down control in binocular vision: When cyclopean fusion breaks down, visual perception adapts to a single-eye reference frame that can be flexibly influenced by attention.

PurposeOcular involvement is exceedingly uncommon, and to date, no conjunctival hibernoma has been reported in humans. We present the first such case in a patient with von Hippel-Lindau (VHL) syndrome.Case reportA 32-year-old woman with genetically confirmed type 1 VHL disease presented with a long-standing, progressively enlarging, painless subconjunctival mass in her only functional eye. Systemic history included multiple cerebellar hemangioblastomas, bilateral nephrectomy for renal cell carcinoma, and an endolymphatic sac tumor. Ophthalmic examination revealed a firm, elevated, subepithelial nodular lesion on the bulbar conjunctiva of the left eye, partially prolapsing beyond the palpebral fissure. The lesion was non-tender, non-ulcerated, and showed no surface inflammation. The eye had phthisis bulbi and residual retinal hemangioblastoma. Orbital magnetic resonance imaging demonstrated a 1.2 × 0.9 × 0.7 cm homogeneous, well-circumscribed lesion, hyperintense on T2-weighted fat-suppressed images, confined to the conjunctiva without scleral, orbital, or bony involvement. Surgical excision revealed a cream-gray, lobulated mass composed of multivacuolated eosinophilic cells with granular cytoplasm. Immunohistochemistry showed strong S-100 positivity and low Ki-67, consistent with hibernoma. Despite a positive deep margin, the patient declined further surgery; no recurrence was observed at three months.ConclusionThis is the first documented case of conjunctival hibernoma in humans and the second reported association with VHL. Conjunctival hibernoma should be considered in the differential diagnosis of vascular conjunctival lesions, particularly in patients with VHL.

IntroductionTumor-to-tumor metastasis (TTM) is a rare phenomenon where a malignant tumor (“donor”) metastasizes to a benign tumor (“recipient”). In the central nervous system (CNS), hemangioblastoma (HGB) is the second most common recipient after meningioma, typically linked to von Hippel-Lindau (VHL) disease. We report the first case of TTM involving breast cancer metastasizing to sporadic HGB unrelated to VHL.Case PresentationA 61-year-old woman, with bilateral breast cancer treated 17 years earlier, presented with right-sided ataxic hemiparesis. MRI showed a gadolinium-enhanced mass in the right cerebellum, initially diagnosed as a metastatic brain tumor. After stereotactic radiotherapy failed to improve her symptoms, surgical resection was performed via an occipital trans-tentorial approach. Intraoperatively, a reddish, vascular tumor with a xanthochromic area was found and completely resected. Pathology revealed two distinct components: HGB and metastatic breast carcinoma, confirming TTM. No evidence of VHL was detected.DiscussionTo date, 29 cases of TTM to HGB have been reported in the CNS, predominantly involving renal cell carcinoma as the donor, most of which were associated with VHL disease. Our case is unique as it represents the first instance of TTM from breast cancer to a sporadic HGB. The pathogenesis of TTM remains unclear, though factors such as recipient tumor vascularity and favorable microenvironment are proposed. The rarity of non-VHL-associated TTM in HGB emphasizes the need for further case accumulation to elucidate the underlying mechanisms.ConclusionWe report the first case of TTM involving metastatic breast cancer to a sporadic HGB in the CNS, unrelated to VHL. This case highlights the importance of considering TTM in the differential diagnosis of CNS tumors, even in the absence of VHL. Accumulating further cases may improve understanding of TTM pathogenesis and guide diagnostic and therapeutic approaches.

Renal hemangioblastoma (HB) is a rare extra-central nervous system mesenchymal neoplasm molecularly defined by recurrent mTOR pathway alterations and lacking VHL abnormalities, distinct from its central nervous system counterpart. While rare renal cell carcinomas (RCCs) exhibiting HB-like features have been documented, their clinicopathological spectrum, biological behavior, and molecular underpinnings remain incompletely characterized.This study characterizes a multi-institutional series of 9 cases of RCC with HB-like features. All tumors presented as well-circumscribed, solitary renal masses (median size, 2.6cm), with 8 out of 9 cases demonstrating thick fibromuscular capsules. All cases uniformly lacked necrosis, mitotic activity, and vascular invasion. Histologically, the tumors demonstrated a variable proportion of the RCC component (5-50% tumor volume, mean:10%) with clear to pale eosinophilic cells forming tubules, acini, or tubulocystic structures blending with the dominant HB-like component; one case showed discrete compartmentalization of the RCC component, forming distinct papillary and tubulocystic structures adjacent to HB-like areas. Immunohistochemically, RCC components expressed epithelial markers (AE1/AE3, cytokeratin 7, CAM5.2), while HB-like components expressed stromal markers (α-inhibin, S100 protein). Critically, both components consistently expressed PAX8, vimentin, carbonic anhydrase IX, CD10, neuron-specific enolase, and GPNMB (8/9). Targeted next-generation sequencing revealed universal mTOR pathway alterations: mutually exclusiveMTORmutations (5 cases) orTSC2mutations (4 cases), with noVHLalterations or 3p25 deletions identified. Over a median follow-up of 50months (range, 4-114months), 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.

Background: Perioperative myocardial injury is a common complication following noncardiac surgery, linked to significant morbidity and mortality. With over 300 million surgeries performed worldwide annually, this number has increased by more than 100 million in the past two decades.Case: A 42-year-old woman underwent elective craniotomy for a right cerebellar hemangioblastoma and was admitted to the intensive care unit (ICU) postoperatively. On day three, she developed typical chest pain, inferior ST-elevation myocardial infarction (STEMI), and cardiogenic shock. Her medical history included the use of euthyrox following a total thyroidectomy 15 years prior, with no prior cardiac issues. Upon examination, she was conscious but had low blood pressure (58/41 mmHg), an elevated heart rate (103 bpm), and cold extremities. Her troponin I level was elevated at 9383.0 ng/mL. The diagnosis was major postoperative myocardial infarction.Therapy: The patient received aspirin, atorvastatin, heparin, norepinephrine, and dobutamine for shock management, with close hemodynamic monitoring. By day six, her condition improved, and her electrocardiogram (ECG) was normal. By day nine, she was transferred to the high care unit.Discussion: Myocardial injury after noncardiac surgery (MINS) includes both myocardial infarction and ischemic myocardial injury, which may not meet the Universal Definition of Myocardial Infarction. MINS usually occurs within 30 days of surgery, especially within the first 72 hours. Its causes are multifactorial, including plaque rupture, oxygen supply-demand imbalance, arrhythmias, and pulmonary embolism. Studies suggest that cardiovascular therapy, including aspirin and statins, is effective. Aspirin reduces 30-day mortality, while statins offer long-term benefits through anti-inflammatory effects. Low-dose aspirin, statins, and Renin-Angiotensin System inhibitors are recommended.Conclusion: MINS is a serious postoperative complication, even in patients without a history of cardiovascular disease, as demonstrated in this case. Prompt recognition and appropriate therapy with aspirin, heparin, and statins, along with close monitoring, can lead to significant clinical improvement.

Abstract Central nervous system (CNS) hemangioblastomas are benign, highly vascular tumors that most commonly arise in the posterior fossa or the spinal cord. CNS hemangioblastomas can be sporadic (in 75% of the cases) or associated with von Hippel-Lindau (VHL) disease, the latter driven by germline mutations in the VHL gene. Somatic VHL mutations are identified in up to 50% of sporadic cases. Alteration of the VHL gene function leads to the dysregulation and accumulation of hypoxia-inducible factor (HIF) – alpha, which in turn activates downstream genes, including vascular endothelial growth factor, that promote tumorigenesis. Belzutifan, a HIF-2 alpha inhibitor, downregulates hypoxia-driven pathways and is approved by the Food and Drug Administration for VHL-associated CNS hemangioblastomas. While surgery and/or radiation are the mainstay of treatment for sporadic, isolated CNS hemangioblastomas, there are limited options in cases of disseminated disease. We describe two cases of sporadic disseminated CNS hemangioblastomatosis with clinical and radiographic response to belzutifan. The first patient is a 61-year-old woman with a remote history of a resected posterior fossa hemangioblastoma who presented decades later with dural-based suprasellar disease compressing the optic chiasm and extensive leptomeningeal disease in the cerebellum and spine. Genetic testing for VHL pathogenic variants was negative, though possible mosaicism was suspected. She achieved a durable complete response on belzutifan 80 mg daily (reduced from 120 mg due to anemia), with no evidence of recurrence at three years. The second patient is a 54-year-old woman who developed diffuse dural and leptomeningeal spinal involvement six years after resection of a right cerebellar hemangioblastoma. Systemic staging was negative. She began belzutifan 120 mg daily and experienced symptomatic improvement at two months. These cases suggest that belzutifan may offer a promising noninvasive therapeutic option for patients with sporadic CNS hemangioblastomas, especially in disseminated cases where conventional therapies are limited.

Abstract Introduction/Objective Hemangioblastomas (HBs) are rare, highly vascular neoplasms of the central nervous system, typically arising intra-axially. They constitute approximately 2.5% of all intracranial tumors and up to 12% of neoplasms in the posterior fossa. Classified as WHO Grade I, HBs generally follow a benign clinical course. Extra-axial presentation is exceedingly rare and presents a significant diagnostic challenge due to radiologic similarity to other pathologies such as dural metastases, vascular schwannomas, or meningiomas. We describe an unusual case of extra-axial hemangioblastoma with atypical histologic and immunohistochemical features, consistent with the cellular variant of HBs Methods/Case Report A 70-year-old female presented with a two-year history of progressive dizziness, confusion, and behavioral changes, with acute exacerbation over recent months. Neuroimaging revealed a 4.8 x 3.5 x 2.8 cm ill-defined, extra-axial lesion in the superior left posterior fossa, associated with significant vasogenic edema, mass effect, and non-communicating hydrocephalus. The lesion appeared radiologically vascular, with a differential diagnosis including meningioma or a vascular neoplasm. Histopathologic analysis demonstrated neoplastic cells with round to oval nuclei, mild to moderate nuclear atypia, prominent vascularity, and focal cytoplasmic vacuolation. No necrosis or increased mitotic activity was observed. Immunohistochemical staining showed focal positivity for inhibin, while markers including GFAP, EMA, progesterone receptor, SSTR2, STAT6, CD34, Brachyury, D2-40, BCL2, CAM5.2, and CD10 were negative. The Ki-67 proliferative index was elevated at 5–7%. Despite the extra-axial location and limited inhibin expression, the findings supported a diagnosis of the cellular variant of hemangioblastoma. Methylation profiling via ISCAB CNS tumor classifier confirmed the diagnosis of hemangioblastoma. This variant is known to demonstrate a higher proliferative index compared to the classic or reticular subtypes, potentially indicating a more aggressive biological behavior and increased risk of recurrence. Results N/A Conclusion Extra-axial hemangioblastomas of the cellular variant are exceedingly rare. Recognition of this entity is critical, particularly in atypical locations with non-classical immunoprofiles. Features such an elevated Ki-67 index may suggest a higher risk for aggressive behavior and recurrence, underscoring the importance of accurate diagnosis for appropriate clinical management

Retro-sigmoid approach for an adult cerebellar hemangioblastoma with foramen magnum extension

The clinical data and diagnostic process of a cerebellar hemangioblastoma (HB) patient presenting with positional vertigo and nystagmus as initial symptomwere retrospectively analyzed. To identify studies involving patients with positional vertigo secondary to cerebellar tumors misdiagnosed as benign paroxysmal positional vertigo (BPPV), a comprehensive literature search was systematically performed in databases such as PubMed, Wanfang, CNKI, and etc., covering the period from January 2004 to December 2024. The patient presented with positional vertigo as the primary symptom.An initial diagnosis of anterior semicircular canal BPPV was made, but attempts at canalith repositioning therapy proved ineffective. Furtherbrain MRI revealed a cystic mass in the right cerebellum. Histopathological examination of the resected specimen confirmed HB. Twenty-eight patients were included in the literature review, nine of whom were ultimately diagnosed with HB, and lesions predominantly involved midline cerebellar structures, including the nodulus and uvula. Literature analysis revealed that misdiagnosis was most often attributable to isolated positional vertigo, in the absence of specific central nervous system symptoms. And the key differential diagnostic features distinguishing CPPV from BPPV and other disorders included the therapeutic efficacy of canalith repositioning maneuvers and characteristics of positional nystagmus. Clinicians should synthesizea comprehensive evaluation, incorporating medical history, physical examination, auditory-vestibular function tests, and neuroimaging, to identify differential diagnostic features andthereby establish an accurate diagnosis.

Abstract BACKGROUND Von Hippel-Lindau (VHL) disease leads to tumors in the nervous system, including cerebellar and spinal cord hemangioblastomas (CBHB, SCHB), and pheochromocytomas (PCC), involving significant neuro-cancer interactions. Understanding these bidirectional interactions is limited by the absence of accurate genetically engineered mouse (GEM) models. Traditional approaches for modeling localized gene recombination face issues such as off-target effects and systemic toxicity. MATERIAL AND METHODS We employed a novel optochemogenetic (OCG) switch technology, using photoactivatable caged 4-hydroxycyclofen (4-OHC) with localized UV illumination, to precisely induce genetic alterations in specific nervous system compartments (cerebellum, spinal cord) and peripheral nervous tissue (adrenal medulla). Using reporter mice (UBC-CreERT2 mTmGf/+), we optimized this UV-driven method to achieve targeted gene recombination. Subsequently, we created GEM models (UBC-CreERT2 Vhlf/f and UBC-CreERT2 Vhlf/f Ptenf/f) to investigate tumor initiation and progression driven by localized neuro-cancer interactions. RESULTS Preliminary findings validated effective localized gene recombination via the OCG switch, demonstrating specificity without systemic side effects. Conventional systemic induction methods caused rapid lethality, highlighting the necessity for spatially controlled gene recombination to study neural-tumor crosstalk accurately. Ongoing experiments focus on refining UV illumination conditions to effectively model the neural influences on cancer initiation and progression. CONCLUSION Our optochemogenetic approach uniquely enables precise investigation of neural influences on tumor formation and tumor-induced neural alterations specific to VHL disease. These GEM models are expected to uncover novel neural-cancer crosstalk mechanisms, advancing our understanding of cancer neuroscience and paving the way for targeted therapeutic strategies.

Although cerebellar hemangioblastoma is histologically benign, it can exhibit malignant clinical behavior during long-term follow-up. This report presents the case of a 51-year-old male with von Hippel-Lindau (VHL) disease, characterized by multifocal hemangioblastomas in the spine and cerebellum, as well as multiple cystic lesions in the kidneys and pancreas. The patient underwent nine surgeries for recurrent cerebellar hemangioblastomas and received cranial radiotherapy for multiple intracranial masses. Additionally, he was diagnosed with and treated for renal cell carcinoma arising from a renal cyst. This case highlights the potential for cerebellar hemangioblastoma recurrence and malignant progression of associated lesions in VHL disease, even after complete resection.

Renal cell carcinoma with hemangioblastoma-like features (RCC-HB) is a rare renal cell carcinoma (RCC) subtype. It consists of renal cell carcinoma with fibromyomatous stroma (RCC FMS)-like and hemangioblastoma (HB)-like components. However, its molecular characteristics and whether it is a subtype of clear cell renal cell carcinoma (CCRCC), a part of the morphologic spectrum of RCC FMS, or a distinct entity remain unclear. We conducted clinicopathological evaluation, immunohistochemistry testing, and next-generation sequencing (NGS) on seven RCC-HB cases of tumour tissue, non-tumour tissue, and blood samples. The cohort included five female and two male patients, aged 33-68 years, with no personal or family history of syndromic disease. Six cases were unifocal, and one was multifocal. Tumours measured 1.2-6.0 cm and were well-circumscribed by a thick fibrous capsule, with fibromuscular bundles extending into and dividing the lesions. RCC FMS-like regions resembled CCRCC, RCC FMS, or clear cell papillary renal cell tumour (CCPRCT) and showed CK7 positivity. HB-like regions featured polygonal or short spindle-shaped neoplastic stromal cells interspersed with rich capillary networks and were highlighted by S100, α-inhibin, and GPNMB. DNA sequencing revealed pathogenic variants in MTOR, TSC1, and TSC2 in six cases, while one case did not detect these gene mutations. All patients were alive without recurrence or metastasis after surgery, with a mean follow-up of 47.7 months (range: 4-111 months) and a median of 46 months. This is the largest clinicopathological study to date on RCC-HB. Our findings support that the vast majority of RCC-HB harboured TSC/MTOR mutations, different from CCRCC, expanding the morphological spectrum of TSC/MTOR-mutated renal tumours.

AimsSporadic renal cell carcinomas with fibromyomatous stroma (RCC FMS) with coexistent haemangioblastoma (HB)‐like morphology have been previously reported. Such morphology has not, however, been documented in patients with tuberous sclerosis complex (TSC). We evaluated clinicopathologic, immunohistochemical and molecular findings of RCC FMS with HB‐like features in three TSC patients.Methods and resultsAll three patients were females with confirmed germline mutations in TSC1 in the absence of VHL or other alterations. One patient had bilateral nephrectomy with six separate tumours (three in each kidney), and two patients had one tumour each, resected by partial nephrectomy. Prominent fibromuscular stroma was present at the tumoral periphery and surrounding clear cell nests forming tubules and papillary formations (RCC FMS areas), admixed with solid, clear to eosinophilic and spindle cell areas (HB‐like areas). HB‐like areas were variably represented in individual tumours, but in some, HB‐like features were almost exclusive. HB‐like areas were negative for CK7 and showed inhibin‐α and S100 reactivity, in contrast to typical RCC FMS areas, which were CK7 positive, while negative for inhibin‐α and S100. GPNMB, which is consistently expressed in TSC/mTOR altered tumours, was positive in both components. On follow‐up (10 months–21 years), all patients had an indolent course.ConclusionsHB‐like morphology found in RCC FMS in TSC patients represents part of the morphologic spectrum of RCC FMS, which is a previously underreported and underrecognized feature. RCC FMS with HB‐like areas show uniform GPNMB reactivity and are associated with TSC/MTOR alterations, but not with VHL alterations.

Hemangioblastomas (HGBs) are rare, benign, World Health Organization grade 1 vascular tumors, which are most commonly located in the cerebellum, and may occur sporadically or in association with von Hippel-Lindau (VHL) disease, a hereditary VHL-mutated tumor syndrome. Limited data are available regarding factors affecting outcomes after stereotactic radiosurgery (SRS). We aim to provide a contemporary evaluation of SRS for HGBs through an international, multicenter study. In this study, we assess local tumor control and SRS-related complications in patients with intracranial HGBs. A retrospective analysis from 17 centers was performed. Data on patient characteristics, SRS parameters, and outcomes were collected. The study included 104 patients with VHL and 89 sporadic cases, with 433 and 137 tumors, respectively. The median follow-up after the initial SRS was 52 months for patients with VHL and 44 months for sporadic cases. At the last follow-up, tumor control was achieved in 85% of VHL tumors and 76% of sporadic tumors. Radiation-induced changes were identified in 13 (3.5%) VHL cases and 5 (3.8%) sporadic cases. The overall 3-year and 5-year cumulative incidences of tumor progression were 13% and 22% for all tumors, 14% and 25% for VHL, and 13% and 17% for sporadic cases. Tumor progression was more common in cystic than in solid tumors in the sporadic group. Overall survival probability and progression-free survival were better in VHL cases compared with the sporadic group. Older age at SRS, male sex, and multiple tumors were associated with reduced local tumor control in all tumors and in the VHL group, whereas a margin dose >15 Gy was associated with improved local tumor control in both groups. SRS offers an effective treatment of intracranial HGBs, whether VHL-associated or sporadic, with a favorable risk profile. HGBs without a cystic component were more likely to be controlled after SRS in the sporadic group.

4507 Background: The HIF-2α inhibitor belzutifan is approved for the treatment of patients with VHL disease–associated renal cell carcinoma (RCC), CNS hemangioblastomas (HB), or pancreatic neuroendocrine tumors (pNETs), not requiring immediate surgery based on previously reported results from the ongoing open-label phase 2 LITESPARK-004 study (NCT03401788). Updated results are presented after a minimum of 5 years of follow-up. Methods: Adults with germline VHL alterations, ≥1 measurable nonmetastatic RCC tumor, no tumor > 3 cm that required immediate surgery, no metastatic disease, no prior anticancer systemic treatment, and an ECOG PS of 0 or 1 received oral belzutifan 120 mg once daily until disease progression, unacceptable toxicity, or participant (pt) withdrawal. The primary end point was objective response rate (ORR) in VHL disease–associated RCC per RECIST v1.1 by independent review committee (IRC). Secondary end points included safety, ORR in non-RCC neoplasms, duration of response (DOR), and progression-free survival (PFS) per RECIST v1.1 by IRC. Results: Overall, 61 pts received ≥1 dose of belzutifan. Median study follow-up was 61.8 mo (range, 60.2-70.1). As of the April 1, 2024 data cutoff date, 35 pts (57%) remained on treatment. ORR was 70% for RCC, 50% for CNS HB, and 90% for pNETs. Additional efficacy results are in the Table. Among 14 pts (n = 18 eyes) with retinal HB, 100% (95% CI, 82-100) of eyes showed improvement per ophthalmologic assessment; median DOR for retinal HBs was not reached (NR; range, 8.5-61.0+ mo). At baseline, 59 of 61 pts (97%) had ≥1 prior VHL-related surgery. Within the 5 years before starting belzutifan, 46 of 61 pts (75%) had ≥1 surgery. Since starting belzutifan, 19 of 61 pts (31%) underwent VHL-related surgeries; 4 underwent surgery while on treatment and subsequently discontinued treatment, 8 underwent surgery after discontinuing treatment, and 7 are continuing treatment as of the data cutoff date. Grade 3 treatment-related adverse events (TRAEs) (most commonly anemia [n = 7; 11%]) were reported in 11 pts (18%). No grade 4 or 5 TRAEs occurred. Belzutifan was discontinued in 2 pts (3%) due to TRAEs (grade 1 dizziness and grade 2 intracranial hemorrhage). Conclusions: After 5 years of follow-up, belzutifan continues to demonstrate durable antitumor activity and a manageable safety profile, consistent with prior reports. Most pts remain on treatment after this period. Results continue to support the use of belzutifan in pts with VHL disease–related RCC, CNS HB, and pNETs who do not require immediate surgery. Clinical trial information: NCT03401788 . RCCn = 61 CNS HBn = 50 pNETsn = 20 ORR, % (95% CI) 70 (57-82);7 CRs, 36 PRs 50 (36-64); 6 CRs; 19 PRs 90 (68-99); 13 CRs, 5 PRs DOR, median (range), mo NR (5.8+ to 60.8+) 60.3 (0.0+ to 60.3) NR (11.0+ to 59.6+) 48-mo DOR rate 76% 82% 94% PFS, median (95% CI), mo NR (NR-NR) 63.5 (63.5-NR) NR (NR-NR) 48-mo PFS rate 81% 79% 96%

e22620 Background: Von Hippel–Lindau (VHL) disease is an autosomal dominant disorder caused by mutations in the VHL gene, predisposing individuals to the development of various neoplasms, including but not limited to cerebellar and spinal hemangioblastomas (CHB and SHB, respectively), pheochromocytomas, pancreatic neuroendocrine tumours (pNET), and renal cell carcinoma (RCC). Belzutifan, an oral HIF-2α inhibitor, offers a novel systemic approach to manage VHL-associated lesions. This study aimed to evaluate the real-world effectiveness and safety of belzutifan in patients with VHL disease at the provincial British Columbia (BC) Cancer VHL Clinic in Vancouver, Canada. Methods: We undertook a retrospective review of patient records between April 2022 and December 2024. Patient demographics, types of VHL related tumors, treatment responses, and adverse events were collected and recorded in a centralized database. Tumor response was assessed according to RECIST 1.1 criteria, categorized as complete response (CR), partial response (PR), stable disease (SD), or progressive disease (PD). Additionally, treatment toxicity and dose reductions were evaluated. Results: Twenty seven patients were started on belzutifan between August 2022 and October 2024. Median age was 37 years (range 21-64). Amongst these, 52% (n = 14) were females and 48% (n = 13) were males. The most common subtype was type 1 VHL (85%; n = 23). In patients with CHB (n = 25), objective response rate (ORR) was 68% (all PR, no CR) and SD was seen in 24% (n = 6). One patient had progression of the cystic component of their CHB. In those with SHB (n = 24), ORR was 54% (46% PR, 8% CR) with SD seen in 46%. In pancreatic lesions (including pNET and cystadenomas; n = 24), ORR was 71% (all PR; no CR). In patients with solid renal lesions (n = 22) ORR was 73% (PR 68% [n = 15] and CR 5% [n = 1]) and SD 27% (n = 6). No patients developed new lesions in any affected areas while on belzutifan. The most common side effects experienced were grade 1 anemia (59%; n = 16) and fatigue (52%; n = 14). Grade 2 hypoxia was reported in 14.8% (n = 4). Dose reductions or temporary treatment break were required in 62.5% of patients (n = 15), most often for anemia (40%; n = 6) and fatigue (53%; n = 8). Amongst these 15 patients, 2 were able to re-escalate to full dose without recurrence of side effects. No patients required permanent treatment discontinuation. Conclusions: Our real-world outcomes demonstrate that belzutifan is effective in treatment of VHL disease and generally being well-tolerated. Further research into long-term outcomes, efficacy for other VHL-associated lesions, such as pheochromocytomas and delineation of mechanism of resistance may expand its therapeutic utility.

Hemangioblastomas are rare, benign, highly vascularized tumors, which among other locations arise in the central nervous system. Due to the tumor's dense vascularity, bleeding and interference with the surrounding brain tissue and vasculature have been reported. Rapid neurological deterioration due to hemorrhage from a hemangioblastoma, especially in spinal locations, has been reported.Rapid clinical deterioration occurred in a 47-year-old male patient with a cerebellar hemangioblastoma and delayed extensive cerebellar ischemia, consecutively. Initial cranial magnetic resonance imaging revealed the tumor with small ischemic areas in the left cerebellar hemisphere. A couple of days later, consciousness dropped significantly and immediate computed tomography revealed extensive ischemia of the left cerebellar hemisphere. Emergency suboccipital decompressive craniectomy and tumor resection were performed. The patient recovered and was discharged to neurological rehabilitation a couple of weeks later.Despite the benign character of hemangioblastomas, life-threatening rapid deterioration due to cerebellar ischemia can occur as reported in this case.

P.208 Case report of a parturient with a cerebellar hemangioblastoma and acute hydrocephalus related to Von Hippel-Lindau disease