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 Table of Contents  
CASE REPORT
Year : 2021  |  Volume : 1  |  Issue : 4  |  Page : 742-744

Aggressive retinal hemangioblastoma with scleral penetration in Von-Hippel-Lindau syndrome


Department of Ophthalmology, Government Medical College, Kozhikode, Kerala, India

Date of Submission02-Dec-2020
Date of Acceptance04-Mar-2021
Date of Web Publication09-Oct-2021

Correspondence Address:
Dr. Ferzana Mohammed
Department of Ophthalmology, Government Medical College, Kozhikode, Kerala - 673 008
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijo.IJO_3585_20

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  Abstract 


Retinal hemangioblastoma is associated with Von-Hippel–Lindau syndrome. Here, we report the case of a 50-year-old man who had a retinal hemangioblastoma that penetrated the sclera and presented as an extra-ocular mass. Computerized tomography of the abdomen showed bilateral renal cell carcinoma, renal, and pancreatic cysts. A provisional diagnosis of Von-Hippel–Lindau syndrome was made. Enucleation of the eyeball was done, and the diagnosis of retinal hemangioblastoma was confirmed by histopathology and immunohistochemistry. Though rare, retinal hemangioblastomas can present with extrascleral extension. In such cases, enucleation may be the only alternative.

Keywords: Extrascleral extension, retinal capillary hemangioblastoma, retinal capillary hemangioma, Von-Hippel–Lindau syndrome


How to cite this article:
Mohammed F, Somasundaran S, Poothatta J, Unnikrishnan S. Aggressive retinal hemangioblastoma with scleral penetration in Von-Hippel-Lindau syndrome. Indian J Ophthalmol Case Rep 2021;1:742-4

How to cite this URL:
Mohammed F, Somasundaran S, Poothatta J, Unnikrishnan S. Aggressive retinal hemangioblastoma with scleral penetration in Von-Hippel-Lindau syndrome. Indian J Ophthalmol Case Rep [serial online] 2021 [cited 2021 Oct 18];1:742-4. Available from: https://www.ijoreports.in/text.asp?2021/1/4/742/327679



Retinal hemangioblastoma is one of the earliest and frequent findings in Von-Hippel–Lindau syndrome (VHL).[1] The ocular complications of retinal capillary hemangioblastomas include exudative retinopathy, tractional retinal detachment, and neovascular glaucoma.[2] Scleral infiltration and extrascleral extension of the tumor are rare.[3] We report a case of a 50-year-old man who had an aggressive retinal hemangioblastoma with scleral penetration.


  Case Report Top


A 50-year-old man from South India came to us with a gradually increasing mass in the left eye for seven months. He had no vision in the left eye following trauma to the eye in childhood. His family history revealed a sister who had died of pancreatic carcinoma.

There was no perception of light in the left eye. A large, red, well-defined soft, globular mass could be seen arising from the left superior limbus and extending posteriorly, measuring 16 mm × 14 mm × 10 mm. This mass was immobile, but the overlying conjunctiva was movable with dilated episcleral and conjunctival vessels. The left cornea was opaque [Figure 1]. The right eye had 6/6 vision. The fundus examination of the right eye showed an orangish-red, elevated lesion measuring 2.5 mm horizontally and 1.5 mm vertically in the inferotemporal periphery, with a dilated and tortuous artery and draining vein [Figure 2].
Figure 1: (a) A soft, immobile globular mass filling the palpebral fissure with overlying dilated conjunctival and episcleral vessels. (b) The mass arises from superior limbus and partly obscures the opaque cornea. (c and d) The surrounding conjunctiva is thickened and congested

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Figure 2: (a) - Fundus picture of the left eye showing the feeder artery in the inferotemporal quadrant (marked with a black arrow) (b) The feeder artery leads to an orangish-red nodule suggestive of retinal hemangioma (marked with a yellow asterisk)

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We performed magnetic resonance imaging (MRI) of the orbit. It showed distortion of the left globe with a broad-based, intraocular altered signal intensity lesion. The lesion was arising from the chorioretinal layer, filling the posterior segment, and was extending exophytically in the anterosuperior aspect with sclera thinning. There were intense post-contrast enhancement and multiple T2 flow voids within the lesion [Figure 3]a, [Figure 3]b, [Figure 3]c. On ultrasound, the lesion showed multiple arterial feeders and draining veins, suggesting a highly vascular tumor. Computerized tomography (CT) of the abdomen showed bilateral multiple renal cell carcinoma (RCC) with renal and pancreatic cysts [Figure 3]d. Thus, we made a provisional diagnosis of Von-Hippel–Lindau syndrome, retinal hemangioma with extrascleral extension in the left eye, and peripheral retinal capillary hemangioma in the right eye. In the left eye, metastasis from renal cell carcinoma was kept as a differential diagnosis.
Figure 3: (a) MRI - Axial view showing an intraocular isointense lesion in T1 Extending from chorioretinal layer filling posterior segment and extending exophytically (b) - MRI - Axial view showing a hyperintense lesion in T2 weighted image (c) Sagittal MRI T2 weighted image shows the hyperintense lesion extending anteriorly and superiorly with scleral thinning (d) CT Abdomen - Right kidney shows a hypointense lesion suggestive of renal cysts (marked with a white asterisk) and the heterogeneous lesion in left kidney is suggestive of renal cell carcinoma (marked with a grey asterisk)

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We proceeded with an enucleation in the right eye [Figure 4]a. The histopathologic examination showed cells arranged in lobules separated by thin-walled vessels. The stromal cells had a moderately eosinophilic cytoplasm. They were round to oval cells with fine chromatin [Figure 4]b, [Figure 4]c, [Figure 4]d. On immunohistochemical characterization, the stromal cells were positive for neuron-specific-enolase (NSE), glial fibrillary acid protein (GFAP), vimentin, inhibin and synaptophysin. Background vessels were positive for CD31. Epithelial membrane antigen (EMA), CD10 and S100 were negative. Histopathology and immunohistochemistry were consistent with retinal hemangioblastoma. For the right eye, we performed laser photocoagulation for the hemangioma and advised close follow-up. VHL gene analysis was advised for his family members, but they declined.
Figure 4: (a) The enucleated specimen showing the globe with the protruding mass anteriorly (b) Histopathology of the specimen (b-6×) showed the cells arranged in lobules and separated by thin-walled vessels. (c and d) Magnified view (c-10×, d-40×) shows the round to oval stromal cells with moderately eosinophilic cytoplasm and fine chromatin

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  Discussion Top


Von-Hippel–Lindau syndrome is an autosomal dominant disease. It is characterized by the presence of benign and malignant tumors of the brain, kidneys, pancreas, adrenals, inner ear, and reproductive organs. The most common VHL-associated tumors are hemangioblastomas of the retina and central nervous system. The other associations include renal cysts and renal clear cell carcinoma; pancreatic cysts, pheochromocytomas, paragangliomas, and pancreatic neuroendocrine tumors (PNET); endolymphatic sac tumors of the inner ear; and epididymal and broad ligament cystadenomas.[4],[5]

Retinal hemangioblastomas are benign neoplasms with vascular characteristics originating from the neurosensory retina or optic disc.[6] Retinal hemangioblastomas are frequently bilateral and multiple. The common site is the temporal peripheral retina.[7] There are 2 accepted classification systems for retinal hemangioblastoma. These include the Sigelman classification and the Vails classification [Table 1] and [Table 2].[2]
Table 1: Sigelman classification of retinal hemangioblastoma

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Table 2: Vail's classification of retinal hemangioblastoma

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The treatment of retinal hemangioblastomas depends on the size of the tumor. Small tumors less than 1.5 mm size are treated by thermal laser photocoagulation. For tumors between 1.5 mm to 4.5 mm, multiple sessions of thermal laser photocoagulation may be needed. Alternatively, transscleral cryotherapy can be done. For larger tumors (more than 4.5 mm in size), brachytherapy or endovitreal cryotherapy are the treatment options.[8]

The major complications of retinal hemangioblastomas include macular exudation and tractional retinal detachment. Neovascular glaucoma and phthisis bulbi have also been also reported.[9] On literature search, we found two previous case reports that described extrascleral extension of retinal hemangioblastomas.[3],[10] In the case report by Rodrigues et al., the authors opined that the previous cryotherapy may have caused thinning of the sclera and facilitated extrascleral extension of the hemangioblastoma.[3] In the case report of Menon et al., similar to this case, there was no history of cryotherapy.[10] In this patient, the lack of vision in the left eye since childhood may have contributed to the late diagnosis of the hamangioblastoma.

Histopathology of retinal hemangioblastomas shows thin-walled blood vessels separated by foamy, vacuolated stromal cells.[11] A reliable immunohistochemical marker to identify hemangioblastomas is alpha-inhibin in the stromal cells. Nestin and synaptophysin may often be positive. Other neural tissue markers - S 100, neuron-specific-enolase (NSE), glial-fibrillary-acid-protein (GFAP) are typically expressed in hemangioblastoma.[12] Conversely, antibodies to epithelial antigens like epithelial membrane antigen (EMA) and cytokeratins do not stain hemangioblastomas. CD10––a good marker for clear cell RCC––is usually negative in hemangioblastoma[13] In this case, the immunostaining of the neural tissue markers (Alpha-Inhibin, NSE, GFAP, Nestin, Synaptophysin) and the immunonegativity of CD10 and antibodies to EMA helped rule out a metastatic clear cell renal carcinoma.[13],[14]


  Conclusion Top


Hemangioblastomas are considered as benign tumors as they are slow-growing, have a limited local invasion and minimal risk of metastasis.[15] This case report highlights that disfiguring complications like extrascleral spread can occur in retinal hemangioblastoma. Hence, timely diagnosis and early therapy of retinal hemangioma in VHL patients is of prime importance.

Acknowledgement

Department of Pathology and Department of Radiodiagnosis, Government Medical College, Kozhikode.

Declaration of patient consent

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

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ruppert M, Gavin M, Mitchell K, Peiris A. Ocular manifestations of Von Hippel-Lindau Disease. Cureus 2019;11:e5319.  Back to cited text no. 1
    
2.
Karimi S, Arabi A, Shahraki T, Safi S. Von-Hippel-Lindau disease and the eye. J Ophthalmic Vis Res 2020;15:78-94.  Back to cited text no. 2
    
3.
Rodrigues M, Iliff N, Eberhart C, Montaner S, Sodhi A. Scleral penetration of an unusually aggressive case of a retinal hemangioblastoma. Can J Ophthalmol 2013;48:e67-71.  Back to cited text no. 3
    
4.
Singh AD, Shields CL, Shields JA. Von Hippel-Lindau disease. Surv Ophthalmol 2001;46:117-42.  Back to cited text no. 4
    
5.
Varshney N, Kebede AA, Owusu-Dapaah H, Lather J, Kaushik M, Bhullar JS. A review of Von Hippel-Lindau syndrome. J Kidney Cancer VHL 2017;4:20-9.  Back to cited text no. 5
    
6.
Valdés-Lara CA, Oyervides-Alvarado JA, Elizondo-Camacho JM, Acón-Ramírez D, García-Aguirre JG. Treatment of capillary hemangioblastoma in Von Hippel-Lindau disease: Case report and online survey of treatment preferences among experts. Case Rep Ophthalmol 2020;11:37-47.  Back to cited text no. 6
    
7.
Şahin Atik S, Solmaz A, Öztaş Z, Eğrilmez E, Uğurlu Ş, Atik T, et al. Von Hippel-Lindau disease: The importance of retinal hemangioblastomas in diagnosis. Turk J Ophthalmol 2017;47:180-3.  Back to cited text no. 7
    
8.
Wiley H, Krivosic V, Gaudric A, Gorin M, Shields C, Shields J, et al. Management of retinal hemangioblastoma in Von Hippel-Lindau disease. Retina 2019;39:2254-63.  Back to cited text no. 8
    
9.
Chew E. Ocular manifestations of von Hippel-Lindau disease: Clinical and genetic investigations. Trans Am Ophthalmol Soc 2005;103:495-511.  Back to cited text no. 9
    
10.
Menon SG, Ramachandran GM, Jacob M, Hegde A, Pai K. Aggressive-fungating retinal hemangioblastoma. [cited 2020 Nov 7]; Available from: https://www.cancerjournal.net/preprintarticle .asp?id=264226.  Back to cited text no. 10
    
11.
Dollfus H, Massin P, Taupin P, Nemeth C, Amara S, Giraud S, et al. Retinal hemangioblastoma in von Hippel-Lindau disease: A clinical and molecular study. Invest Ophthalmol Vis Sci 2002;43:3067-74.  Back to cited text no. 11
    
12.
Epari S, Bhatkar R, Moyaidi A, Shetty P, Gupta T, Kane S, et al. Histomorphological spectrum and immunohistochemical characterization of hemangioblastomas: An entity of unclear histogenesis. Indian J Pathol Microbiol 2014;57:542-8.  Back to cited text no. 12
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13.
Rivera AL, Takei H, Zhai J, Shen SS, Ro JY, Powell SZ. Useful immunohistochemical markers in differentiating hemangioblastoma versus metastatic renal cell carcinoma. Neuropathology 2010;30:580-5.  Back to cited text no. 13
    
14.
Jung SM, Kuo TT. Immunoreactivity of CD10 and inhibin alpha in differentiating hemangioblastoma of central nervous system from metastatic clear cell renal cell carcinoma. Mod Pathol 2005;18:788-94.  Back to cited text no. 14
    
15.
Wizigmann-Voos S, Plate KH. Pathology, genetics and cell biology of hemangioblastomas. Histol Histopathol 1996;11:1049-61.  Back to cited text no. 15
    


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