Abstract
Editor:
As the veterinary pathologist authors of a previous report on the metastatic carcinomas prevalent in California sea lions, 2 we read the recent article in your journal by Colgrove et al 1 with great interest. The authors reported interesting findings on hormone receptors, Ki67 and p53 expression, possible environmental cofactors, and comparative aspects of these remarkably common neoplasms. We applaud their continuing contributions to knowledge of this fascinating viral infection–associated malignancy. However, we take issue with their proposal that the tumors be considered of urogenital origin.
In our study, 2 tissues from 10 sea lions that had metastatic carcinomas in sublumbar lymph nodes were examined in an attempt to locate the primary sites. We found a distinctive lesion that we concluded was intraepithelial neoplasia (IEN), also known as carcinoma in situ, in the genital epithelium of all 10 animals. The affected tissues included vagina, cervix, uterus, prepuce, and penis. Invasive carcinoma of genital tissues was found in 3 animals. In 1 of the 3, transition of IEN to invasive carcinoma was detected. IEN, invasive carcinomas, and metastatic carcinomas were histomorphologically extremely similar. Neither IEN nor invasive carcinoma was found in urinary tissues. We concluded that genital epithelium was the primary site of the metastatic carcinomas and so referred to the disease as sea lion genital carcinoma. We also linked infection with a novel gammaherpesvirus to IEN and metastatic genital carcinoma by histology, immunohistochemistry, electron microscopy, and polymerase chain reaction.
In the recent report, the authors indicated that of 12 animals with metastatic carcinomas, all had genital IEN, 4 had IEN of the distal urethral epithelium, and 1 had more extensive IEN of the penile urethra, extending 10 cm from the distal end of the penis. They found invasive carcinoma in genital tissues of 7 of the 12 and in none of the urinary tissues. Of 4 animals that had genital IEN but no metastatic carcinomas, 1 had urethral IEN and the remaining 3 had insufficient available tissue to assess the urethras. In no case was IEN found in urothelium of the urinary bladder. Based on these findings, the authors proposed that “metastatic carcinomas in sea lions should more accurately be considered urogenital in origin.”
We disagree with this proposal. The evidence of genital origin is strong whereas the evidence of urinary origin is weak. Combining findings of our study and those of the recent study, 22 of 22 sea lions with metastatic carcinoma had genital IEN and 10 of 22 (45%) had invasive carcinoma of genital tissues. No cases of invasive urinary carcinoma were found in either study. One likely reason that foci of invasive genital carcinoma were not found in a greater proportion of cases is the extensiveness of the IEN. Although the mechanism of the intraepithelial spreading that occurs in this disease is unknown, the result is widespread involvement of genital epithelia. Involvement of distal urethral epithelium may well represent intraepithelial spread from the contiguous genital epithelium. In the absence of a single case of invasive urinary carcinoma, one cannot assume that some of the metastatic carcinomas are of urothelial origin; the proposal that these carcinomas be considered urogenital in origin and the use of the term urogenital carcinoma imply that some of these cancerous tumors originate in urothelium. There is no clear evidence that urethral IEN is a precursor to invasive, metastasizing carcinoma. Given current scientific information, we believe that genital carcinoma of California sea lions is the most appropriate designation.