A 32-year-old HIV-positive man presents to dermatology with multiple lesions on his trunk and extremities. On examination, the structure marked **A** (violaceous-brown plaque) is noted along with similar lesions on the hard palate. His CD4 count is 85 cells/μL and he is not on antiretroviral therapy. A skin biopsy with immunohistochemistry is performed. Which of the following viral antigens would be MOST specific for confirming the diagnosis of AIDS-related Kaposi sarcoma in this patient?

Explanation

## Why HHV-8 LANA-1 antigen is right The violaceous-brown plaques marked **A** in AIDS-related Kaposi sarcoma are caused by Human herpesvirus-8 (HHV-8, also known as Kaposi sarcoma-associated herpesvirus/KSHV). HHV-8 infects vascular endothelial cells, and the viral latency-associated nuclear antigen (LANA-1) drives proliferation of these cells, leading to the characteristic spindle cell proliferation and slit-like vascular spaces seen on histology. Immunohistochemical staining for HHV-8 LANA-1 is the gold standard confirmatory test for AIDS-related Kaposi sarcoma, particularly in a patient with low CD4 count, characteristic violaceous lesions on skin and hard palate, and compatible clinical presentation (AIDS Malignancy Consortium Guidelines; Bolognia Dermatology 4th ed). ## Why each distractor is wrong - **Epstein-Barr virus (EBV) nuclear antigen**: While EBV is associated with other AIDS-related malignancies such as primary CNS lymphoma and oral hairy leukoplakia, it is not the causative agent of Kaposi sarcoma. EBV-positive lesions would not present with the characteristic violaceous plaques and nodules. - **Cytomegalovirus (CMV) immediate-early antigen**: CMV causes opportunistic infections in severely immunocompromised patients (retinitis, esophagitis, colitis) but is not associated with Kaposi sarcoma pathogenesis. CMV does not drive vascular endothelial cell proliferation. - **Human papillomavirus (HPV) E6/E7 proteins**: HPV is associated with cervical cancer, anal cancer, and other squamous cell malignancies in HIV-positive patients, but not with Kaposi sarcoma. The lesions of HPV-related disease do not present as violaceous plaques. **High-Yield:** HHV-8 LANA-1 immunostaining is pathognomonic for Kaposi sarcoma; violaceous plaques on hard palate + low CD4 + HHV-8 LANA-positive = AIDS-KS. [cite: AIDS Malignancy Consortium Guidelines; Bolognia Dermatology 4th ed]