Mucocutaneous Presentation of Kaposi Sarcoma in an Asymptomatic Human Immunodeficiency Virus–Positive Man

Regardless of the subtype, the etiology of KS currently is thought to be secondary to infection with human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma–associated herpesvirus (KSHV).¹ Human immunodeficiency virus infection can enhance KSHV expression through the HIV transactivator protein, which activates KSHV oncogenes and angiogenic growth factors to promote the development of KS lesions.^2,6Likewise, KSHV enhances HIV upregulation through latency-associated nuclear antigen, a protein that interacts with HIV Tat protein to further activate long terminal repeats of HIV-1.²

The differential diagnosis of KS is broad. The slightly elevated, pinkish reddish discolorations of KS may resemble verruca plana and/or squamous cell carcinoma on visual observation, whereas nodular KS may resemble giant cell granuloma, pyogenic granuloma, or hemangiopericytoma.^4,7 Cases of KS with lymph node involvement may include a differential diagnosis of lymphoma, angiosarcoma, and bacillary angiomatosis.⁷ Other vascular pathologies that may be considered in the differential diagnosis include vascular tumors (eg, spindle cell hemangioma), fibrohistiocytic tumors (eg, dermatofibrosarcoma protuberans), and a collection of spindle cell mesenchymal tumors.⁸

Kaposi sarcoma progresses through several histologic stages beginning with the patch stage, then progressing to the plaque stage, and finally culminating in the nodular stage. The patch stage is the first stage in KS progression and a crowded dermis can be seen with the formation of slitlike vascular spaces lined by endothelial cells with red blood cell extravasation into the lumens of newly formed vascular channels, hence demonstrating the promontory sign.⁸ In the plaque stage, the promontory sign still is present and there is a greater presence of slitlike spaces, giving the micrograph an overall sievelike appearance. Erythrocytes can be found residing within the clear cytoplasm of spindled endothelial cells, leading to the development of autolumination. Finally, the nodular stage is characterized by a neoplastic proliferation of monomorphic spindle cells that form fasciclelike nests in the dermis.⁸ To distinguish KS from other angioproliferative tumors, one can stain for HHV-8 latent nuclear antigen-1, which is found in the nuclei of infected endothelial cells.^1,8,9

Kaposi sarcoma is treated through a variety of mechanisms depending on the subtype. Classic KS lesions often can be observed as they a follow a benign and nonaggressive course.¹ Highly active antiretroviral therapy is the mainstay of care in AIDS-related KS and has led to regression of lesions and a remarkable decline in the incidence of KS.³ The HAART regimen consists of a protease inhibitor or nonnucleoside reverse-transcriptase inhibitor with the addition of 2 nucleoside reverse-transcriptase inhibitors. More advanced or refractory cases of KS often require dual treatment with HAART and a chemotherapy agent such as pegylated liposomal doxorubicin. Combination therapy has been shown to result in stronger therapeutic responses and lower relapse rates in contrast to HAART alone.⁷ Patients also may consider other treatment modalities to manage KS lesions such as surgical removal of lesions, laser therapy, paclitaxel, interferon alfa, oral etoposide, thalidomide, and topical therapies such as imiquimod cream 5% and alitretinoin.^1,7

Conclusion

Kaposi sarcoma is a rare but concerning dermatologic condition that signals the need for further diagnostic evaluation. Coexpression of viruses such as HIV and HHV-8 can result in a more virulent and rapid progression of KS to encompass both mucous membrane and systemic involvement. Our patient’s lesions were the first presenting sign of HIV infection despite being asymptomatic at the time of diagnosis, which is alarming in the sense that more than 21% of HIV-infected individuals in the United States have not been clinically diagnosed.¹⁰ Inquiry of HIV risk factors and routine screening for HIV should be performed in refractory cases of skin disease as an underlying clue to further investigate the immune system. We present our unique case of mucocutaneous development of KS in an asymptomatic HIV-positive man to stress the importance of KS recognition and management.