Common metastatic carcinoma of California sea lions (Zalophus californianus): Evidence of genital origin and association with novel gammaherpesvirus

Tissues from 10 adult California sea lions (Zalophus californianus, seven f emales and three males) that had metastatic carcinoma in sublumbar area lym ph nodes were examined histologically. A distinctive epithelial proliferati ve lesion interpreted as intraepithelial neoplasia was found in genital tra cts of all ten animals; in vagina (5/7), cervix (7/7), uterus (3/7), penis (3/3) and prepuce (3/3). Intraepithelial neoplasia closely resembled metast atic carcinomas and was directly contiguous with invasive carcinoma in one animal. Rare eosinophilic intranuclear inclusion bodies were found in penil e and preputial intraepithelial neoplasia (one animal), cervical intraepith elial neoplasia (one animal), invasive cervical carcinoma (one animal) and metastatic carcinoma (two animals). Electron microscopic examination of tis sues from two sea lions (one with intraepithelial neoplasia and one with me tastatic carcinoma) demonstrated viral particles consistent with a herpesvi rus. An immunohistochemical stain for the latent membrane protein of Epstei n-Barr virus was positive in intraepithelial neoplasia in one sea lion. Her pesvirus DNA sequences were detected by consensus primer polymerase chain r eaction (PCR) in metastatic carcinomas from all four sea lions from which u nfixed tumor samples were available. Results of sequencing were consistent with a novel gammaherpesvirus in the genus Rhadinovirus. DNA extracted from the four metastatic carcinomas also was tested for papillomavirus by South ern blot and PCR with consensus papillomavirus primers; all samples were ne gative by both methods. These findings support the genital origin of the se a lion carcinoma and implicate a novel gammaherpesvirus as a possible cause .