von Hippel-Lindau gene deletion detected in the stromal cell component of a cerebellar hemangioblastoma associated with von Hippel-Lindau disease

doi:10.1016/S0046-8177(97)90075-7

Human Pathology

Volume 28, Issue 5, May 1997, Pages 540-543

https://doi.org/10.1016/S0046-8177(97)90075-7 Get rights and content

Abstract

Central nervous system hemangioblastoma is a neoplasm with characteristic and well-described histopathological features, including proliferation of vascular and stromal cells. Yet, the histogenesis of the stromal cell component and its neoplastic capacity as compared with the vascular component are still controversial. Stromal cells were selectively procured from formalin-fixed, paraffin-embedded archival tissue from a von Hippel-Lindau (VHL) disease patient with a cerebellar hemangioblastoma and studied for loss of heterozygosity (LOH) of the VHL gene locus and associated microsatellite regions. The stromal cells consistently showed LOH. Analysis of mixed stromal and vascular areas of this tumor and four other hemangioblastomas of VHL patients showed that loss of heterozygosity was partially obscured. These preliminary results suggest that the stromal component of hemangioblastomas contains genetic alterations consistent with a neoplastic nature. Additional samples of pure stromal cells need to be analyzed to establish the prevalence of VHL gene deletion in stromal cells of capillary hemangioblastoma and, hence, its pathogenetic significance.

References (20)

S Jurco et al.
Hemangioblastomas: Histogenesis of the stromal cell studied by immunocytochemistry
Hum Pathol
(1982)
Z Nemes
Fibrohistiocytic differentiation in capillary hemangioblastoma
Hum Pathol
(1992)
A Tanimura et al.
Hemangioblastoma of the central nervous system: Nature of the stromal cells as studied by the immunoperoxidase technique
Hum Pathol
(1984)
K Morii et al.
Expression of vascular endothelial growth factor in capillary hemangioblastoma
Biochem Biophys Res Commun
(1993)
FA Jakobiec et al.
Angiomatosis retinae: An ultrastructural study and lipid analysis
Cancer
(1976)
J Mizuno et al.
Immunohistochemical study of hemangioblastoma with special reference to its cytogenesis
Neurol Med Chir
(1993)
TS Frank et al.
A detailed immunohistochemical analysis of cerebellar hemangioblastoma: An undifferentiated mesenchymal tumor
Mod Pathol
(1989)
SC Holt et al.
Capillary hemangioblastoma: An immunohistochemical study
Am J Clin Pathol
(1986)
I Becker et al.
Histogenesis of stromal cells in cerebellar hemangioblastomas
Am J Pathol
(1989)
AP Chaudhry et al.
Ultrastructure of cerebellar hemangioblastoma
Cancer
(1978)

There are more references available in the full text version of this article.

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Dural-Based Frontal Lobe Hemangioblastoma
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Hemangioblastomas are benign vascular neoplasms that may be associated with von Hippel−Lindau disease. They are more common in men, with a mean age of 36 years, and rarely affect the supratentorial region and, when present in this topography, do not have meningeal impairment. Diagnosis by the radiologic and histopathologic study is difficult, since they are rare and, therefore, forgotten diagnosis, besides they are differential diagnoses with other supratentorial neoplasms.
The present report describes a case of a frontal hemangioblastoma in a 64-year-old woman who presented with seizures. Our imaging studies had as a main hypothesis a frontal meningioma because of dural tail sign, lack of edema, contrast enhancement pattern, and extra-axial location in the supratentorial region, in the frontal lobe, which is uncommon for a hemangioblastoma. The patient underwent microneurosurgery for tumor resection, and the excised tissue was submitted for anatomopathologic evaluation. This study clarified the diagnosis as hemangioblastoma. We followed up the patient at the outpatient clinic for 2 years, with clinical improvement, without tumor recurrence. We also compared the clinical, radiologic, epidemiologic, and anatomopathologic data of the reported case with data from a literature review conducted through the PubMed portal.
Definitive treatment for these lesions is surgical resection. Physicians should be aware that supratentorial meningeal hemangioblastomas can be developed in a patient without von Hippel−Lindau disease and regular follow-up is mandatory.
Imaging of Vascular Disorders of the Spine
2019, Radiologic Clinics of North America
Citation Excerpt :
In cases of subarachnoid hemorrhage with negative cranial angiography, ruptured SAAs should be considered and further imaging workup should be performed.59,60 Accounting for up to 5% of spinal cord tumors, hemangioblastoma is an intramedullary, richly vascular, lesion associated with Von-Hippel Lindau Syndrome (VHL).61–64 One large case series demonstrated that two-thirds of spinal cord hemangioblastomas were sporadic, with another large series demonstrating increased prevalence in VHL than in a nonsyndromic population.61,65
Extraneuraxial hemangioblastoma: A clinicopathologic study of 10 cases with molecular analysis of the VHL gene
2018, Pathology Research and Practice
Less than 250 extraneuraxial hemangioblastomas occurring in paraneuraxial or peripheral sites have been reported to date, sporadically or in the setting of von Hippel-Lindau disease. Seventeen such cases underwent molecular genetic analysis, using either the patient’s peripheral blood in 9 cases or paraffin embedded tumor tissue in the rest. VHL gene mutations were documented in 3/9 cases in which DNA from peripheral blood lymphocytes was used, all with clinically manifest von Hippel-Lindau disease; instead, no VHL gene alterations were found in all of the 8 cases with sporadic extraneuraxial hemangioblastoma in which DNA from tumor tissue was analyzed. Our aim is to investigate the molecular genetic profile of the VHL gene in extraneuraxial hemangioblastoma using paraffin embedded tumor tissues.
The clinical features, histopathology, and molecular investigations of 10 extraneuraxial hemangioblastomas (7 females, 3 males; median age: 47 years) are presented herein. The histopathologic diagnosis was supported by immunohistochemistry (10/10) and electron microscopy (4/10). Molecular genetic analysis was conducted (10/10) for VHL gene mutations, LOH, and gene promoter methylation. Two of the present cases were already published with only limited or no molecular investigations.
Four tumors of the present series were paraneuraxial, and 6 peripheral (2 involved soft tissues, and 4 the kidney). One tumor was von Hippel-Lindau disease-associated, 1 was classified as “hemangioblastoma-only VHLD”, 7 were sporadic, and one was unknown. All were histopathologically analogous to their counterpart located inside the central nervous system. Immunophenotypically, all tumors expressed vimentin, S-100, NSE, and alpha-inhibin (10/10). Ultrastructurally, unbound lipid droplets filled the cytoplasms of the stromal cells. Molecular analysis revealed 3 inactivating mutations (1 germline, two somatic) in the coding sequence of the VHL gene in 2 different extraneuraxial hemangioblastomas, and LOH in 4 (two as a double hit), all non-renal extraneuraxial hemangioblastomas. Methylation analysis failed to disclose promoter methylation in any case.
In conclusion, we report eight new cases from the wide category of extraneuraxial hemangioblastomas (4 paraneuraxial, and 4 renal), one of which was von Hippel-Lindau disease-associated and 7 sporadic. VHL gene alterations were found not only in the von Hippel-Lindau disease-associated tumor, but − for the first time − also in 3 sporadic ones, two of which with novel mutations.
In Reply to the Letter to the Editor “Circumventricular Organ Origin of Hemangioblastoama; Hypothesis for Pathogenesis of Disease”
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Delayed presentation of an arteriovenous malformation after cerebellar hemangioblastoma resection - Case report
2016, International Journal of Surgery Case Reports
Haemangioblastoma has been uncommonly reported to occur in coexistence either temporally or spatially with the development of an arteriovenous malformations (AVM). We present a case of a delayed AVM following haemangioblastoma resection.
44 year old female initially presented with a several week history of headaches, vertigo and nausea and emesis and was found to have a cystic lesion with a solid enhancing component on Magnetic Resonance Imaging (MRI) in the superior aspect of the vermis. She underwent gross total resection and final pathology was consistent with WHO grade I haemangioblastoma. One year later, patient re-presented with headaches, dizziness and left trochlear nerve palsy with rotary nystagmus. Imaging revealed a left posterior tentorial paramedian cerebellar vascular nidus with venous drainage into the left transverses sinus suspicious for arteriovenous malformation. She underwent gross total resection of the lesion. Final pathology confirmed the diagnosis of an arteriovenous malformation.
Recent research supports both haemangioblastoma and AVM are of embryologic origin but require later genetic alterations to develop into symptomatic lesions. It is unclear in our case if the AVM was present at the time of the initial haemangioblastoma resection or developed de novo after tumor resection. However, given the short time between tumor resection and presentation of AVM, de novo AVM although possible, appears less likely.
AVM and haemangioblastoma rarely presents together either temporally or spatially. We present a case of a delayed AVM following haemangioblastoma resection. More research is needed to elucidate the rare intermixture of these lesions.

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Original contributionvon Hippel-Lindau gene deletion detected in the stromal cell component of a cerebellar hemangioblastoma associated with von Hippel-Lindau disease

Abstract

Hum Pathol

Hum Pathol

Hum Pathol

Biochem Biophys Res Commun

Angiomatosis retinae: An ultrastructural study and lipid analysis

Cancer

Immunohistochemical study of hemangioblastoma with special reference to its cytogenesis

Neurol Med Chir

A detailed immunohistochemical analysis of cerebellar hemangioblastoma: An undifferentiated mesenchymal tumor

Mod Pathol

Capillary hemangioblastoma: An immunohistochemical study

Am J Clin Pathol

Histogenesis of stromal cells in cerebellar hemangioblastomas

Am J Pathol

Ultrastructure of cerebellar hemangioblastoma

Cancer

Original contribution
von Hippel-Lindau gene deletion detected in the stromal cell component of a cerebellar hemangioblastoma associated with von Hippel-Lindau disease