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Year : 2016  |  Volume : 64  |  Issue : 10  |  Page : 783-785

An interesting case of angiogenesis in cavernous hemangioma

1 Department of Ocular Pathology and Sri Sankaradeva Nethralaya, Guwahati, Assam, India
2 Sri Sankaradeva Nethralaya, Guwahati, Assam, India

Date of Submission20-Apr-2016
Date of Acceptance22-Sep-2016
Date of Web Publication1-Dec-2016

Correspondence Address:
Dipankar Das
Department of Ocular Pathology, Uveitis and Neuro-ophthalmology Services, Sri Sankaradeva Nethralaya, Beltola, Guwahati - 781 028, Assam
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0301-4738.195005

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Cavernous hemangioma is the most common orbital tumor in adult. There is lot of literatures for clinicopathological features of this tumor. These tumors had been studied for the model of angiogenesis in many of the experimental setups. We present a case of 34-year-old male with this tumor in the left eye with computerized tomography evidence. Postsurgical laboratory findings gave interesting evidence of tumor angiogenesis with tumor endothelial cells and sprouting of the small vessels endothelial cells. Podosome rosette could be conceptualized from the characteristic patterns seen in the tumor.

Keywords: Cavernous hemangioma, podosome rosettes, sprouting, tumor endothelial cells

How to cite this article:
Das D, Bhattacharjee K, Deka P, Bhattacharjee H, Misra DK, Koul A, Kapoor D, Deka A. An interesting case of angiogenesis in cavernous hemangioma. Indian J Ophthalmol 2016;64:783-5

How to cite this URL:
Das D, Bhattacharjee K, Deka P, Bhattacharjee H, Misra DK, Koul A, Kapoor D, Deka A. An interesting case of angiogenesis in cavernous hemangioma. Indian J Ophthalmol [serial online] 2016 [cited 2023 Feb 8];64:783-5. Available from: https://www.ijo.in/text.asp?2016/64/10/783/195005

Cavernous hemangioma is the most common tumor seen in adult chiefly in female.[1],[2] The pathogenesis of hemangioma, perhaps, poorly understood among the other tumors of the orbit.[3],[4],[5] Hemangioma is characterized by proliferation of endothelial cells with multiple laminations of basement membranes (BMs) with gathering of cellular rudiments.[3],[4],[5],[6] Endothelial cells in the blood vessels and tumor endothelial cells (TECs) have typical features in physical condition.[5],[6],[7] Tumor blood vessels have uneven diameters, and they are delicate, permeable, and have anomalous blood flow.[4],[5],[6] In tumor, blood vessel arises from preexisting one by the course of angiogenesis.[6],[7],[8] Angiogenesis is characterized by closing of extracellular matrix endothelial cells by mitosis and sprouting.[4],[5],[6],[7],[8],[9] It was observed long before that the tumor blood vessels have uncharacteristic morphologically.[6],[7],[8],[9] TECs are irregular in size and contour extending outward, and tips of some TECs may penetrate the lumen creating an intracellular gap in vessels wall.[6],[7],[8],[9] Sometimes nearby tumor cells filled the gap junction.[6],[7],[8],[9] Abnormal sprouts resembling pointed tip-like extension and may be there in oxygen scarce stage in the tumor microsurroundings.[6],[7],[8],[9],[10] We present a case of unilateral proptosis with intraconal cavernous hemangioma with various interesting macroscopic and microscopic findings.

  Case Report Top

A 34-year-old male presented with proptosis of the left eye (OS) in November 2014 since 2 years with occasional pain and blurred vision. There was no history of trauma, surgery, and any ocular disease. The systemic history was unremarkable. On ophthalmic examination, relative afferent pupillary defect was seen in the OS. Best-corrected visual acuity was 6/6, N6 right eye (OD), 6/18 with pinhole improvement to 6/9, N10 (OS). Axial proptosis was noted with Hertel's exophthalmometry measurement of 14 mm in the OD and 20 mm in OS. There were no ocular motility restrictions in either eye. Slit lamp and fundus examination revealed normal anterior and posterior segments in both the eyes (OU). Intraocular pressure was normal in OU.

Computerized tomography scan of the orbit and brain in OS revealed a retrobulbar mass, well delineated and intraconal in location, displacing the optic nerve medially [Figure 1]. The lesion was contrast enhanced revealing a provisional diagnosis of intraconal cavernous hemangioma.
Figure 1: (a) Computerized tomography scan of brain and orbit with intraconal orbital mass and (b) Gross bluish black encapsulated cavernous hemangioma

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Left sided lateral orbitotomy under general anesthesia was planned and carried out under proper consent. The specimen was sent to ocular pathology laboratory where encapsulated bluish black mass measuring (22.1 mm × 16.18 mm × 12.24 mm) was documented [Figure 1]. Grossly, the tumor showed surface vascularity over the capsule. Surface vessels were in different dimensions and were also seen piercing the capsule. After dissecting a small portion of capsule, numerous TECs were seen, some of which formed a pattern of endothelial podosome rosette which was documented. Sprouting of TEC and the blood vessels with intracellular gap junctions among the TECs was observed. Endothelial cells on the surface of the blood vessels and TEC were seen under high power objective illumination of microscope (Axioskop 40 with AxioCam MRc camera). Microscopic appearance showed capsulated vascular tumor with numerous dilated blood vessels of varying sizes filled with red blood cells and lined by endothelial cells. Some of the endothelial cells showed sprouting of its extension, which were also documented under microscope [Figure 2] and [Figure 3]. Pericytes and fibrocytes with varied morphology were seen in intervening stroma. Some of the lymphocytic collections were seen at the edges of the lumen of the blood vessels. All the microscopic findings were consistent with cavernous hemangioma, and interesting finding of surface blood vessel and TECs was similar to some of the established cell culture tumor model in vitro experimental pathology. Immunohistochemistry (IHC) of the tumor showed CD31, CD34, actin, and vimentin positive. Periodic acid-Schiff showed positive for the BM.
Figure 2: Sprouting of end of small vessels in gross with suspected angiogenesis (×400, unstained specimen)

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Figure 3: Outgrowth of small twig of sprouting from endothelial surface of blood vessel (H and E × 400)

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  Discussion Top

Sprouting angiogenesis is an enlargement of new capillary blood vessels arising out of preaccessible ones.[1],[7],[8],[9] It was long being discussed that how a new vessel could arise from the exiting one when the metabolic needs in the adjoining tissue is similar.[7],[8],[9] It has been documented in various conditions such as neovascularization in diabetes, pannus in synovium of joints in rheumatoid arthritis, vascular system complications, and in tumor biology.[7],[8],[9] In tumors, sprouting angiogenesis is not only seen in primary tumors but also in micrometastasis and obvious metastasis.[2],[3],[4],[5],[6],[7],[8],[9],[10] In all these conditions, sprouting angiogenesis was seen in oxygen deficient area where angiogenesis starts with activation of endothelial cells by various growth factors that bind to the specific sites.[7],[8],[9],[10] Extracellular matrix and BM surrounding the endothelial cells despoiled locally by activated factors.[7],[8],[9],[10] By the process of polarization, the migrating endothelial cells are created within the lumen, and immature blood vessels are formed. The entire development of angiogenesis is firmly prescribed by positive and negative regulators, the stability of which determined the level of ongoing angiogenesis.[7],[8],[9],[10]

In 1980, fibroblast growth issue was developed which stimulates major steps in angiogenesis. Thereafter, vascular endothelial growth factor played a major role in prompt of various blood vessels in diverse organs.[7],[8],[9],[10]

Our case was a 34-year-old male presented with proptosis in OS for 2 years. After surgery, the specimen was meticulously examined for its small vascular pattern over that tumor's capsule and its surrounding. TECs were important morphological structures that were documented and compared with the endothelial cells of the surface blood vessels. A pattern of endothelial podosome rosette [Figure 4] was another pathological structure that was seen and adjoining to them, the TEC showed intracellular gap junctions [Figure 5] and [Figure 6]. Sprouting of blood vessels could be seen in very high power objective of microscope and compare with stained section. IHC for CD34 showed positivity demarcating the structures of endothelial cells of the blood vessels.
Figure 4: Structure simulating podosome rosette formed by tumor endothelial cell and small blood vessels encircling the rosette

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Figure 5: Comparative size of tumor endothelial cell and endothelial cells of small blood cells

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Figure 6: The gap junction of tumor endothelial cell in direct examination of the tissue under high power objective of compound microscope (×400)

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We have seen in our case that there was a strong pathological evidence of tumor angiogenesis with sprouting of the blood vessels. TEC which was mostly evident in the model conceptualized for tumor angiogenesis play a significant role in the biology of vascular tumor such as cavernous hemangioma.


This study was financially supported by Sri Kanchi Sankara Health and Educational Foundation, Guwahati, India.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Mulliken JB, Glowacki J. Hemangiomas and vascular malformations in infants and children: A classification based on endothelial characteristics. Plast Reconstr Surg 1982;69:412-22.  Back to cited text no. 1
Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature 2000;407:249-57.  Back to cited text no. 2
Mulliken JB. Diagnosis and natural history of haemangiomas. In: Mulliken JB, Young AE, editors. Vascular Birthmarks: Haemangiomas and Vascular Malformations. 2nd ed. Philadelphia: W. B. Saunders; 1988. p. 41-62.  Back to cited text no. 3
Kopelow SM, Foos RY, Straatsma BR, Hepler RS, Pearlman JT. Cavernous hemangioma of the orbit. Int Ophthalmol Clin 1971;11:113-24.  Back to cited text no. 4
McNab AA, Wright JE. Cavernous haemangiomas of the orbit. Aust N Z J Ophthalmol 1989;17:337-45.  Back to cited text no. 5
Sullivan TJ, Aylward GW, Wright JE, Moseley IF, Garner A. Bilateral multiple cavernous haemangiomas of the orbit. Br J Ophthalmol 1992;76:627-9.  Back to cited text no. 6
Martin A, Komada MR, Sane DC. Abnormal angiogenesis in diabetes mellitus. Med Res Rev 2003;23:117-45.  Back to cited text no. 7
Koch AE. Angiogenesis as a target in rheumatoid arthritis. Ann Rheum Dis 2003;62 Suppl 2:ii60-7.  Back to cited text no. 8
Cao Y, Hong A, Schulten H, Post MJ. Update on therapeutic neovascularization. Cardiovasc Res 2005;65:639-48.  Back to cited text no. 9
Ferrara N, Davis-Smyth T. The biology of vascular endothelial growth factor. Endocr Rev 1997;18:4-25.  Back to cited text no. 10


  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]

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