Drs. Colegrove and Lowenstine Respond

We agree with Lipscomb et al that genital tissues (vulva, vagina, uterus, and cervix in females and penile or prepucial epithelium in males) are most often the primary sites of malignant transformation in sea lions with carcinoma; however, the current manuscript demonstrated that the urethra is also involved. The urethra is defined as part of the urinary tract, not the genital tract; therefore, we preferred to use the term urogenital carcinoma to reflect the occasional involvement of urothelium. Additional support for this contention comes from analysis of cases in the pathology database at the University of California, Davis, Veterinary Medical Teaching Hospital, which contains reports from 166 cases of urogenital carcinoma in California sea lions since 1985. In earlier cases, complete gross and histological examination of lower urinary and reproductive tracts was often not completed due to limited resources, and many of the cases were so advanced with such widespread metastases that determination of a primary site was impossible. However, in more recent years, thorough histological examination of the entire genital and lower urinary tract has been undertaken not only from sea lions stranding from cancer but also from those dying from other causes. This has enabled us to identify neoplastic transformation and tumor progression at a much earlier stage. Although we did not include these data in the current manuscript, urethral involvement without identified involvement of the genital epithelium has been noted in 5 sea lions, bladder in 6, and ureter in 2. Interestingly, all but 2 of these animals were males. Furthermore, our studies have shown that these tumors are likely multicentric. Multiple discrete foci of epithelial proliferation, ranging from hyperplasia without dysplasia to carcinoma in situ (intraepithelial neoplasia) or invasive carcinoma, may be seen at different levels of the reproductive and lower urinary tracts in the same animal, and, as discussed in the manuscript, distinct morphologic difference in neoplastic foci can occur in the same animal. This is not surprising considering the contiguous nature of the epithelium lining the urethra and penis/prepuce of males and vulva and vagina of females and the continuity of epithelium lining the tubular genitalia of females. These findings are also compatible with the nature of the suspected etiologies (ie, viruses, bacterial flora, contaminants, receptor activation) involved in what will likely prove to be a multifactorial pathogenesis. Investigations of the preferred habitat of Otarine herpesvirus-1 (OtHV-1), the virus thought to be associated with these cancers, showed that the virus is most prevalent in the prostate/prostatic urethra in males with and without cancer. Using the term urogenital does not dilute the findings of Lipscomb et al from the 10 cases that they examined but rather expands our understanding of this endemic neoplasm fitting with the biology of OtHV-1, as well as the biology of the tissues and contiguous nature of the epithelium of the lower reproductive and urinary tracts. Thus, urogenital will continue to be the term used in our ongoing investigations of the pathogenesis of these endemic cancers of California sea lions.