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Kaposi’s sarcoma (KS) is a vascular tumour whose development requires infection by human herpesvirus 8 (HHV-8). Although most commonly found in immunosuppressed patients, such as those AIDS, in the United States, classic KS is often found in older-aged men of European or Mediterranean ancestry without immunosuppression. Involvement of the skin of one’s extremities in classic KS is typically more common than that of viscera or mucocutaneous surfaces.
There are few cases in the literature regarding ocular KS in HIV-negative patients. Involvement of the conjunctiva in an HIV-negative, immunocompetent patient has been previously described.
Here we present a very unusual case of KS of the conjunctiva extending into the orbital space in an HIV-negative patient.
Case Report
A 93-year-old Caucasian male presented with a nodule in the left eye (Fig. 1A). Two violaceous lesions of approximately 5 mm in diameter were also found on the left forearm (Fig. 1B). He has a remote history of a gastrointestinal stromal tumour that was treated with imatinib mesylate (Gleevec, Novartis). All laboratory tests were negative, including HIV. There was no history of acquired or iatrogenic immunosuppression. On examination, best-corrected visual acuity was 20/25 OU. Intraocular pressures were 11 mm Hg in the right eye and 10 mm Hg in the left eye. Fundoscopy was normal in both eyes. Slit-lamp examination findings were within normal limits in the right eye. In the left eye, there was conjunctival hyperemia with a nodule in the inferior fornix. The patient underwent computed tomography of the orbits, which confirmed the conjunctival nodule and showed lateral extension to the orbit (Fig. 1C).
Fig. 1(A) Solid mass at lateral canthus of left eye causing mild ectropion of the lower eyelid. (B) Cutaneous lesions on left forearm found at time of diagnosis. (C) Computed tomography scan of orbit showing invasion of left temporal orbital space. (D) Low magnification (20×) showing well-circumscribed tumour with dilated vessels and extravasation.
Total excision of the nodule was performed, and the specimen was sent for histopathological analysis. At low magnification (20×), a fragment of conjunctiva with a subepithelial tumour was seen (Fig. 1D). The tumour was composed of dilated blood vessels with numerous spindle cells between them. There were also extensive areas of hemorrhage. At high magnification (40×), the intervascular tissue was composed of atypical spindle cells with spindle and hyperchromatic nuclei. Several extravasated red blood cells were observed. Immunohistochemistry for HHV-8 was positive with nuclear expression, which confirmed the diagnosis of KS.
Discussion
HHV-8, or KS-associated herpesvirus, is a dsDNA virus of the gammaherpesvirus family, commonly spread via saliva and blood.
The virus is associated with multiple neoplastic diseases—not only vascular tumours, such as KS, but also B-cell proliferative syndromes, such as primary effusion lymphoma and the plasmablastic variant of multicentric Castleman disease.
The virus enters host cells via the endocytic pathway and is able to infect endothelial cells and immune cells. HHV-8 then expresses multiple viral proteins that help evade innate and adaptive immune responses, allowing long-term latency, primarily inside B cells. Of note, the latency-associated nuclear antigen (LANA) protein is associated with both immune evasion and tumourigenesis, the latter via direct inactivation of p53 and retinoblastoma (Rb) genes.
HHV-8 further promotes tumourigenesis via upregulation of vascular endothelial grown factor–derived and platelet-derived growth factor–derived angiogenesis, as well as activation of the PI3K/Akt/mTOR signalling pathway by expression of human protein homologues, such as viral G-protein-coupled receptor protein and viral IL-6.
KS of the eye may have an appearance similar to vascular lesions, such as hemangiomas, arteriovenous fistulas, pyogenic granulomas, malignant blue nevi, bacterial angiomatosis, and any other vascular malformations.
Immunohistochemistry is a valuable tool for confirming the diagnosis for all forms of KS, especially in the case of patients without a history of HIV or any other form of immunosuppression. As in our patient, KS shows a characteristic feature of spindle-shaped, endothelium-derived tumour cells around vascular slits, often with evidence of extravasation such as hemosiderin, red blood cells, and fibrosis. Immunohistochemistry for CD34 can identify proliferation of endothelial cells,
and LANA-1, which is found uniformly in the nucleus of virtually all HHV-8–infected cells, has been shown to be useful for distinguishing tumours with similar histologic features.
For HIV-negative patients, current treatment options include surgical excision, cryotherapy/laser ablation, radiotherapy, and intralesional chemotherapy. Because the virus establishes residence in the immune system, none of the therapies listed eliminate the possibility of tumour re-emerging elsewhere in the body. For our patient, surgical excision was preferred because the tumour was extending into the orbital space. Because the tumour was well delineated, complete removal of the tumour was performed and there was no need for adjunctive laser or cryotherapy.
KS is typically very sensitive to radiotherapy, but radiation to the ocular space may incur very well-known side effects, such as dry eyes and secondary tumour formation. If patients are on immunosuppression for organ transplant, sirolimus, an mTOR inhibitor, has been shown to be very effective in controlling various cutaneous KS lesions,
Although KS is much more common in HIV-positive males, our case report is a reminder that elderly HIV-negative men can be affected. Despite the conjunctiva being the most affected ocular structure in KS, it is always important to rule out orbital extension. Careful history taking and histopathology can confirm the diagnosis of ocular KS. The treatment level should be appropriate for the stage of disease. New therapies for KS have a potential to be used in the ocular space in the future.
References
Huang C.T.
Chang C.S.
Maa H.C.
Cho S.F.
Liu T.C.
HIV-negative disseminated Kaposi’s sarcoma in a Taiwanese patient.
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