A case report of hemangioblastoma mimicking a meningioma with unusual clinical presentation

Nien-Tzu Liu; Hong-Wei Gao; Chun-Jung Juan; Da-Tong Ju; Yu-Chun Lin

doi:10.4103/jmedsci.jmedsci_171_19

CASE REPORT

Year : 2021 | Volume : 41 | Issue : 1 | Page : 41-44

A case report of hemangioblastoma mimicking a meningioma with unusual clinical presentation

Nien-Tzu Liu, Hong-Wei Gao, Chun-Jung Juan, Da-Tong Ju, Yu-Chun Lin
Department of Pathology, National Defense Medical Center, Tri-Service General Hospital, Taipei, Taiwan

Date of Submission	25-Sep-2019
Date of Decision	31-Dec-2019
Date of Acceptance	09-Aug-2020
Date of Web Publication	12-Sep-2020

Correspondence Address:
Nien-Tzu Liu
Department of Pathology, 3F, No. 325, Sec. 2, Chenggong Road, Neihu, Taipei City 114
Taiwan

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/jmedsci.jmedsci_171_19

Abstract

Hemangioblastomas (HBs) are uncommon tumors that occur as sporadic lesions or multiple lesions associated with von Hippel–Lindau (VHL) disease. We report a case of a 77-year-old male with an unusual clinical presentation of HB mimicking meningioma, involving the left anterior temporal fossa, skull, infratemporal fossa, and orbit, and compressing the lateral rectus muscle and optic nerve causing exophthalmos, without a diagnosis of VHL-related HB.

Keywords: Hemangioblastoma, Von Hippel–Lindau disease, anterior temporal fossa, infratemporal fossa, exophthalmos

How to cite this article:
Liu NT, Gao HW, Juan CJ, Ju DT, Lin YC. A case report of hemangioblastoma mimicking a meningioma with unusual clinical presentation. J Med Sci 2021;41:41-4

How to cite this URL:
Liu NT, Gao HW, Juan CJ, Ju DT, Lin YC. A case report of hemangioblastoma mimicking a meningioma with unusual clinical presentation. J Med Sci [serial online] 2021 [cited 2021 Mar 1];41:41-4. Available from: https://www.jmedscindmc.com/text.asp?2021/41/1/41/294942

Introduction

As a benign slow-growing tumor of adults, hemangioblastomas (HBs) represent 1.5%–2.5% of all intracranial tumors,^[1] typically occurring in the cerebellum, brain stem, and spinal cord. Supratentorial and peripheral nervous system location of the tumors is rare.^[2]

Patients were within the age range of 50–60 years with male predominance. These tumors occur sporadically (accounting for 70% of cases) or in association with inherited von Hippel–Lindau (VHL) disease (accounting for 30% of cases).

There is a characteristic radiographic appearance on both computerized tomography (CT) and magnetic resonance imaging (MRI) for HB, as well as a distinct prolonged vascular stain on cerebral angiography.^[9] MRI is the preferred imaging modality, but in rare cases, angiography is better for the detection of occult vascular nodules that may not be apparent on standard imaging. MRI studies typically show a gadolinium-enhancing mass with an associated cyst in approximately 75% of the cases. The solid component is usually peripherally located within the cerebellar hemisphere. Flow voids may be seen within the nodule due to enlarged feeding and draining vessels. Evidence of calcification is usually absent on imaging. Spinal cord HBs are often associated with a syrinx.

Symptoms of intracranial HB generally arise from impaired cerebrospinal fluid flow due to a cyst or solid tumor mass, resulting in an increase in intracranial pressure and hydrocephalus. Cerebellar deficits such as dysmetria and ataxia can also occur. HBs produce erythropoietin, which cause secondary polycythemia in approximately 5% of the patients.^[11]

Total tumor resection is recommended, and the prognosis and surgical outcomes of sporadic central nervous system (CNS) HBs are favorable if surgical resection can be performed successfully, which is typically possible, based on the experience of the surgeon.

Case Report

A 77-year-old male presented to our hospital with progressive headache, insomnia, and painful sensation over the left eye for 2 years. He had visited the ophthalmology clinic, where left eye cataract was diagnosed and treated. However, the symptoms persisted after surgical intervention. He was referred to the neurology department due to insomnia. Brain tumor was accidentally found through MRI of the brain. A lobulated strongly but inhomogeneously enhancing tumor, measuring 5.3 cm in size, involving the left anterior temporal fossa, skull, infratemporal fossa, and orbit, causing exophthalmos and compression of the lateral rectus muscle, optic nerve, and temporal lobe was visualized [Figure 1]a and [Figure 1]b. The initial radiological differential diagnoses included meningioma and solitary fibrous tumor.

Figure 1: (a and b) Magnetic resonance image shows a lobulated strongly but inhomogeneously enhancing tumor measuring 5.3 cm involving the left anterior temporal fossa, skull, infratemporal fossa, and orbit, causing exophthalmos, compression of the lateral rectus muscle, optic nerve, and temporal lobe. No perifocal edematous change

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He was admitted to the neurosurgical ward for surgical intervention. Initially, total tumor resection was suggested by the surgeon for a more favorable prognosis and outcome. Instead, craniotomy for partial tumor removal was performed due to the patient's poor health condition and proximity of the tumor to the orbital region. During the operation, the surgeon also sent a frozen section to the department of pathology, and the pathologic differential diagnoses included meningioma, hemangiopericytoma, and HB.

Further histopathological examination of the permanent sections with hematoxylin and eosin staining showed a hypercellular tumor with clear, vacuolated cytoplasm and numerous thin-walled to focal hyalinized vessels [Figure 2]a and [Figure 2]b. The tumor cells were positive for brachyury, S-100, and alpha-antitrypsin and focally positive for epithelial membrane antigen (EMA) and neuron-specific enolase (NSE) but negative for glial fibrillary acidic protein (GFAP), CD34, and signal transducer and activator of transcription 6 (STAT-6) [Figure 3]a, [Figure 3]b, [Figure 3]c, [Figure 3]d, [Figure 3]e, [Figure 3]f. The patient was finally diagnosed with HB, involving the left anterior temporal fossa, skull, infratemporal fossa, and orbit.

Figure 2: (a and b) Photomicrograph shows hypercellular tumor cells with clear and vacuolated cytoplasm, and numerous thin-walled vessels (H and E, ×100 and ×200)

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Figure 3: (a-d) Immunohistochemical staining for glial fibrillary acidic protein, epithelial membrane antigen, CD34, and STAT6 are negative. (e and f) Staining for neuron-specific enolase and brachyury are focally positive

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Genetic tests for VHL gene on chromosome 3p25–26 for the detection of VHL disease are recommended (sensitivity: 86%); however, diagnosis of HB is usually given based on clinical findings including the presence of multiple retinal capillary hemangiomas, other manifestations of VHL disease, or a positive family history.^[12] Neither family history of VHL syndrome nor other tumors and cysts growing in certain areas of the body were identified including endolymphatic sac in the ear, adrenal glands, pancreas, kidneys, or epididymis. Therefore, this is likely a case of non-VHL-related HB. However, further whole-exome and Sanger sequencing of tumor and paired peripheral blood samples for a VHL disease pedigree was not performed.

Postoperative follow-up MRI of the brain showed two small enhancing nodules (about 1.1 cm) over the left temporal base, and residual or recurrent tumor was highly suspected by radiologists. However, the patient refused further surgical intervention and postoperative radiotherapy and continued regular follow-up at our outpatient department every 6 months.

Discussion

HBs are well-circumscribed, highly vascular, lipid-rich, and low-grade neoplasms of uncertain histogenesis. These tumors may be associated with VHL disease. The VHL gene is a tumor suppressor gene, which means it keeps cells from growing and dividing too rapidly or in an uncontrolled way. Mutations in this gene prevent the production of the VHL protein or lead to the production of an abnormal version of the protein. An altered or missing VHL protein cannot effectively regulate cell survival and division and allows tumors and cysts to develop within organs such as the brain, retina, kidney, adrenal gland, pancreas, and genital tract. The VHL tumor suppressor gene is inactivated in both VHL-associated cases and in most sporadic cases. HBs usually occur in adults in their fifth and sixth decades of life, and the average patient age at presentation of VHL-associated tumors is approximately 20 years younger than that of sporadic tumors.^[1] HBs are seen more often in males than in females. However, according to the article by Marin Kuharic in 2017, female predominance in patients with VHL disease compared with male predominance in the general patient group.^[1]

The most common locations of HBs are the cerebellum and sellar/suprasellar and intraventricular regions. In 2017, the article reported by Marin reviewed 1759 HBs, most of which were located in the cerebellum (70%, n = 1230), followed by the fourth ventricle (1.8%), cerebellopontine angle (1.8%), and the craniocervical junction (1.6%).^[1] It is rare in the supratentorial meninges, and clinical presentation may cause local mass effect and obstructive hydrocephalus based on the location. Supratentorial HBs often result from the loss function of both alleles of the VHL gene, accounting for only 1%–6% of all HBs associated with VHL disease. Approximately, 139 cases of supratentorial HBs have been reported to date, of which 82 cases are associated with VHL syndrome.^[14] Among patients with supratentorial HB, 60% of cases were diagnosed with VHL disease. Supratentorial HB is more commonly associated with VHL disease than is infratentorial HB (33%).^{[4],[15],[16]}

Optic nerve HBs are rare tumors that arise from within the optic nerve and both compress and replace normal tissue. Because of their rarity, there are only 35 reported cases in the literature by Lindsay A. McGrath in 2018, which is limited to case reports and small case series. HB of the optic nerve should also be considered in patients presenting with reduced vision, proptosis, and optic nerve pallor.^[10],[17] Based on the imaging findings, our case seems less likely to have originated from the optic nerve.

For pathologists, it is difficult to diagnose HB using frozen sections. There is a characteristic radiographic appearance on both CT and MRI, as well as a distinct prolonged vascular stain on cerebral angiography, especially in rare locations such as the supratentorial aspect and peripheral nervous system. The differential diagnoses of this case included meningioma, solitary fibrous tumor, and metastatic renal cell carcinoma.

HBs are characterized by two main components including stromal cells and abundant vascular cells that may mimic microcystic meningioma by presenting with thickened vessels, but HBs are negative for EMA. The characteristics of numerous lipid-containing vacuoles, resulting in clear-cell morphology, may pose a resemblance to metastatic renal cell carcinoma, which is positive for EMA.^[3],[4] Solitary fibrous tumor that is usually positive staining for CD34, is negative for the stromal component of HBs. In addition, HBs are generally negative staining for GFAP and positive staining for NSE and brachyury.^{[5],[6],[7],[8]} In our case, the tumor was focally positive for NSE and brachyury but negative for GFAP, CD34, and STAT-6. The possibility of a case of HB should first be considered based on the histologic features and the results of immunohistochemical stains.

The prognosis is excellent for most sporadic cases after successful total tumor excision. Therefore, for patients with VHL disease (more likely to develop multiple lesions of HBs) with subtotally resected and recurrent HBs, postoperative radiotherapy may be considered an alternative or adjuvant therapy. Permanent neurological deficits are rare^[12] and can be avoided when CNS HBs are diagnosed and treated early.^[13] The overall mortality of HBs was 10.3%; however, numerous articles only stated the mortality without providing specific information on the cause of death. The most common complications were intracranial (31.5%), followed by infections (27.7%) and complications affecting cranial nerve function (11.4%). In addition, there were no major differences in the outcomes between sporadic and VHL-associated cases.^[1]

Conclusion

As the most common location of HB is the cerebellum, this is a rare case report of supratentorial HB, involving the left anterior temporal fossa, skull, infratemporal fossa, and orbit, causing exophthalmos. Owing to the extremely rare location of the tumor in this case, after differential diagnoses such as meningioma, hemangiopericytoma, and metastatic renal cell carcinoma were ruled out, the possibility of HB could not be excluded even though it is a non-VHL-related case. Radiological, pathologic, and immunohistochemical techniques are helpful for diagnosis. Generally, the prognosis and outcomes are favorable after total tumor resection. However, due to the rare incidence of HBs, there are only some small series and case reports available, and the surgical experience with these tumors is limited. Further systemic reviews and follow-up analyses are suggested.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that his name and initials will not be published, and due efforts will be made to conceal his identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Kuharic M, Jankovic D, Splavski B, Boop FA, Arnautovic KI. Hemangioblastomas of the posterior cranial fossa in adults: Demographics, clinical, morphologic, pathologic, surgical features, and outcomes. A Systematic Review. World Neurosurg 2018;110:e1049-62.
2.	Gläsker S, Bender BU, Apel TW, Natt E, van Velthoven V, Scheremet R, et al. The impact of molecular genetic analysis of the VHL gene in patients with haemangioblastomas of the central nervous system. J Neurol Neurosurg Psychiatry 1999;67:758-62.
3.	Hamazaki S, Nakashima H, Matsumoto K, Taguchi K, Okada S. Metastasis of renal cell carcinoma to central nervous system hemangioblastoma in two patients with von Hippel-Lindau disease. Pathol Int 2001;51:948-53.
4.	Kim H, Park IS, Jo KW. Meningeal supratentorial hemangioblastoma in a patient with von hippel-lindau disease mimicking angioblastic meningioma. J Korean Neurosurg Soc 2013;54:415-9.
5.	Bӧhling T, Mäenpää A, Timoen T, Vantunen L, Paetau A, Haltia M. Different expression of adhesion molecules on stromal cells and endothelial cells of capillary hemangioblastoma. Acta Neuropathol 1996;92:461-6.
6.	Böhling T, Turunen O, Jääskeläinen J, Carpen O, Sainio M, Wahlström T, et al. Ezrin expression in stromal cells of capillary hemangioblastoma. An immunohistochemical survey of brain tumors. Am J Pathol 1996;148:367-73.
7.	Ishizawa K, Komori T, Hirose T. Stromal cells in hemangioblastoma: Neuroectodermal differentiation and morphological similarities to ependymoma. Pathol Int 2005;55:377-85.
8.	Wizigmann-Voos S, Plate KH. Pathology, genetics and cell biology of hemangioblastomas. Histol Histopathol 1996;11:1049-61.
9.	Baker KB, Moran CJ, Wippold FJ 2^nd, Smirniotopoulos JG, Rodriguez FJ, Meyers SP, et al. MR imaging of spinal hemangioblastoma. AJR Am J Roentgenol 2000;174:377-82.
10.	McGrath LA, Mudhar HS, Salvi SM. Hemangioma of the optic nerve. Surv Ophthalmol 2018;4:370-4.
11.	Gläsker S, Krüger MT, Klingler JH, Wlodarski M, Klompen J, Schatlo B, et al. Hemangioblastomas and neurogenic polyglobulia. Neurosurgery 2013;72:930-5.
12.	Conway JE, Chou D, Clatterbuck RE, Brem H, Long DM, Rigamonti D. Hemangioblastomas of the central nervous system in von hippel-lindau syndrome and sporadic disease. Neurosurgery 2001;48:55-62.
13.	Gläsker S, Berlis A, Pagenstecher A, Vougioukas VI, van Velthoven V. Characterization of hemangioblastomas of spinal nerves. Neurosurgery 2005;56:503-9.
14.	Pandey S, Sharma V, Pandey D, Kumar V, Kumar M. Supratentorial haemangioblastoma without von hippel-lindau syndrome in an adult: A rare tumor with review of literature. Asian J Neurosurg 2016;11:8-14. [PUBMED] [Full text]
15.	Maher ER, Yates JR, Ferguson-Smith MA. Statistical analysis of the two stage mutation model in von hippel-Lindau disease, and in sporadic cerebellar hemangioblastoma and renal cell carcinoma. J Med Genet 1990;27:311-4.
16.	Miyagami M, Katayama Y, Nakamura S. Clinicopathological study of vascular endothelial growth factor (VEGF), p53, and proliferative potential in familial von hippel-Lindau disease and sporadic hemangioblastomas. Brain Tumor Pathol 2000;17:111-20.
17.	Zywicke H, Palmer CA, Vaphiades MS, Riley KO. Optic nerve hemangioblastoma: A case report. Case Reports in Pathology 2012; 2012:915408.