human herpesvirus 8

**Virology** - Family Herpesviridae, subfamily Gammaherpesvirinae (like EBV/HHV-4). Enveloped, linear dsDNA virus; replicates in the nucleus. - Establishes latency in B cells (and endothelial cells). Latency-associated nuclear antigen (LANA-1) tethers the viral episome to host chromatin and is the diagnostic marker on immunohistochemistry. - Transmission: saliva (main route, especially in endemic regions), sexual contact (notably among men who have sex with men), organ transplantation, and less commonly blood or vertical transmission.

**Pathophysiology** - Viral genes hijack host cell signaling and promote angiogenesis and cell proliferation while blocking apoptosis. Examples: viral cyclin (v-cyclin, a D-cyclin homolog), viral IL-6, viral GPCR (drives VEGF production), and v-FLIP (activates NF-κB). - LANA-1 inhibits p53 and Rb. - Loss of T-cell immunity (HIV, transplant immunosuppression) allows viral reactivation and tumor growth. In HIV, ART with immune reconstitution often causes KS to regress.

**Associated diseases** 1. **Kaposi sarcoma**: a low-grade vascular endothelial neoplasm. - Violaceous/red-purple macules, plaques, or nodules on skin and mucosa (palate); can involve the lungs, GI tract, and lymph nodes. - Histology: proliferating spindle cells forming slit-like vascular spaces, extravasated RBCs, hemosiderin, and inflammatory cells. Cells are LANA-1 positive. - Variants: classic (older men of Mediterranean/Eastern European descent, lower extremities, indolent), endemic/African (can be aggressive, including in children), epidemic/AIDS-associated (most common in the US), and iatrogenic/transplant-associated. - Treatment: restore immunity (ART in HIV, reduce immunosuppression); localized therapy (radiation, intralesional therapy); liposomal doxorubicin or paclitaxel for advanced disease. 2. **Primary effusion lymphoma (body cavity lymphoma)**: B-cell non-Hodgkin lymphoma presenting as pleural, pericardial, or peritoneal effusions without a mass; often co-infected with EBV; seen in HIV. 3. **Multicentric Castleman disease (KSHV-associated)**: lymphoproliferative disorder with fever, lymphadenopathy, splenomegaly, and cytopenias; driven by viral IL-6.

**High-yield differentials and pearls** - **Bacillary angiomatosis** (Bartonella henselae/quintana) mimics KS: red-purple vascular papules in HIV patients. Biopsy shows neutrophilic infiltrate with organisms on Warthin-Starry stain, and it responds to erythromycin/doxycycline. KS shows spindle cells that are LANA-1 positive. - **Other HIV-related malignancies**: Primary CNS lymphoma (EBV), Burkitt/DLBCL (EBV), and cervical cancer (HPV). - **Other human herpesviruses**: HSV-1 (HHV-1), HSV-2 (HHV-2), VZV (HHV-3), EBV (HHV-4), CMV (HHV-5), HHV-6 (roseola/exanthem subitum), HHV-7, HHV-8 (KS). - **Diagnosis**: clinical appearance plus biopsy with LANA-1 immunohistochemistry; PCR for viral DNA can also be used. - **Treatment note**: antivirals like ganciclovir do not treat established KS well; treatment centers on immune restoration and chemotherapy.