Metastatic Carcinoma of California Sea Lions: Evidence of Genital Origin and Association with Gamma Herpesvirus Infection
Over the last 20 years, there have been several reports of metastatic carcinomas of undetermined origin in California sea
lions.1,2,3 Sixty-six of 370 (18%) adult California sea lions necropsied over a 16 year period at a marine mammal rehabilitation center on the central
California coast had metastatic carcinoma of undetermined origin. Histologically, the carcinomas had squamous differentiation often and glandular differentiation
less frequently. Lymph nodes of the sublumbar area were involved in all 2 cases.
We performed histologic examinations of genitourinary tracts and other tissues of 7 California sea lions that had metastatic carcinomas
similar to those reported. Lymph nodes of the sublumbar area contained carcinomas in all cases. Four were female and 3 were male. Intraepithelial neoplasia (IEN)
similar to the metastatic carcinomas was found in lower genital tracts of all 7. In 1 case, IEN and invasive carcinoma were contiguous. Eosinophilic intranuclear
inclusion bodies were found within IEN in 1 case and within invasive or metastatic carcinoma in 3 cases. By immunohistochemistry, intranuclear inclusion bodies in
IEN stained positively for the latent membrane protein of Epstein-Barr virus. Herpesvirus-like particles were observed in cells of intraepithelial neoplasia and
metastatic carcinoma by transmission electron microscopy.
Molecular characterization of this viral agent is currently underway at UC Davis. DNA extracted from frozen tumors was subjected to polymerase
chain reaction (PCR) using degenerate primers designed for consensus regions of herpesvirus terminase and DNA polymerase genes. DNA extracted from 4 of the above
cases was PCR positive for both of these genes. Subsequent to these preliminary findings, a fragment of the terminase gene has been cloned into a bacterial vector
and sequenced. The nucleotide sequence data indicate that the viral agent is a member of the gammaherpesvirus family. Highly specific primers amplifying an
internal fragment of this cloned region are currently being used in PCR to determine the presence of this agent in larger number of archival samples.
Gammaherpesvirus infections are believed to be involved in the causation of several animal and human cancers. Our findings support the
conclusion that the common metastatic carcinoma of California sea lions arises in the genital tract. A gammaherpesvirus may play a significant role in causing the
1. Brown RJ, AW Smith, GV Morejohn, RL DeLong. 1980. Metastatic adenocarcinoma in two California sea lion, Zalophus c.
californianus. Journal of Wildlife Diseases 16:261-266.
2. Gulland FMD, JG Trupkiewicz, TR Spraker, LJ Lowenstine. 1996. Metastatic carcinoma of probable transitional cell origin in 66
free-living California sea lions (Zalophus californianus), 1979 to 1994. Journal of Wildlife Diseases 32:250-258.
3. Joseph BE, LH Cornell, G Migaki. 1986. Metastatic squamous cell carcinoma in a beached California sea lion (Zalophus
californianus). Journal of Wildlife Diseases 22:281-283.