Abstract

Prairie dogs (Cynomys spp.) are rodents in the family Sciuridae, which includes ground squirrels, flying squirrels, and woodchucks.² Hepatocellular tumors are common in woodchucks and Richardson’s ground squirrels, and these tumors have been associated with hepadnavirus infection.^1,3,4,8,9 Oncogenesis associated with viral infection in woodchucks is considered a viable model for hepadnavirus infection (hepatitis B) in humans.^5,8 Few formal reports exist of hepatocellular neoplasia in prairie dogs.^7,10,11 A retrospective study was conducted of the incidence and morphologic features of hepatic neoplasia in black-tailed prairie dogs (Cynomys ludovicianus) submitted to Northwest ZooPath. For cases 1–4, selected paraffin-embedded hepatic tissues were stained for hepadnavirus proteins using anti-WH core antibody and anti-WH surface antibody. Sections also were stained using orcein and Victoria Blue stains for detection of WH surface antigen.

From 1994–2002, tissues from 61 prairie dogs were submitted to Northwest ZooPath for histopathology. Of these, 12 (20%) had hepatocellular carcinoma. Three were pets submitted from private veterinary practices. The others were submitted from zoos in the United States. Signalment, history, gross lesions, and nonhepatic lesions are summarized in Table 1. Seven animals were male and five were female. All were adults and ages ranged from young adult to 7 years with average age of 5.1 years in animals of precise known age. Five animals were euthanatized, four died and three were alive at the time this abstract was written. The most common clinical signs were weight loss (four animals), lethargy (four animals), palpable abdominal mass (four animals), and respiratory difficulty (three animals). One or more masses were noted in various liver lobes of all animals. The masses were white to tan, and sometimes cavitated. The most common concurrent lesions were chronic glomerulonephritis (eight animals) and cardiac disease (four animals).

Table 1. Signalment, history, gross pathology, and concurrent lesions for prairie dogs with hepatocellular carcinoma

Tumor morphology, metastases and the results of histochemical and immunohistochemical stains for woodchuck hepatitis virus antigens are summarized in Table 2. All tumors were well differentiated, and determining cell of origin was not difficult even in metastatic lesions. Four patterns were recognized: reticular, pseudoglandular, peloid, and papillary. The trabecular pattern was predominant in ten tumors and the pseudoglandular patter was predominant in two tumors. The peloid pattern was also represented in eight tumors. The papillary pattern was present only in the primary and metastatic foci of case 9. Anaplasia was mild to moderate in most tumors but a marked degree of anaplasia was noted in the metastatic foci of case 9. Seven cases had vacuolar change resembling lipidosis in neoplastic hepatocytes of primary and metastatic tumors. Cavitation and necrosis were noted in five cases. Concurrent portal lymphocytic hepatitis was noted in two cases and two cases had cirrhosis. Two cases had lymphocyte infiltrates within the tumors. One case rarely had eosinophilic intranuclear inclusions in neoplastic cells. Metastasis was noted to lung in five cases. One of these also had metastasis in spleen, and one also had metastasis to heart and mediastinum. The immunohistochemical and cytochemical stains were negative for viral antigen in the tested cases.

Table 2. Tumor morphology, other hepatic lesions, metastasis and woodchuck hepatitis PCR results in prairie dogs with hepatocellular carcinoma

^aTumor pattern listed in order of predominance.
^bAnaplasia included anisokaryosis, karyomegaly and cytomegaly, mitotic figures, multinucleated cells.
+ = mild; ++ = moderate; +++ = marked.
NA = not available.

These cases were similar to hepatocellular carcinoma in woodchucks in that animals were aged, of both sexes, had white to tan masses in various hepatic lobes, had variable morphologic tumor patterns for which the reticular pattern predominated, tumors were well differentiated with slight to moderate degree of anaplasia, and had occasional cavitation and necrosis.⁶ The cases were dissimilar to hepatocellular carcinoma of woodchucks in that metastasis seemed to be more common in prairie dogs, and the tested cases have been negative for viral antigen in histologic sections.⁶ Concurrent hepatitis may have been less common and cirrhosis may have been more common occurrences. The cause for the apparent high incidence of hepatocellular carcinoma in black-tailed prairie dogs submitted to Northwest ZooPath could not be determined. Although viral antigen could not be demonstrated in the tested cases, the similarities of this syndrome to that of hepadnavirus-related hepatocellular neoplasia and hepatitis in humans, woodchucks, and Richardson’s ground squirrels suggest that the condition in prairie dogs may have a viral etiology.

Acknowledgments

We acknowledge the expertise of Histology Consulting Services (HCS) for excellent slide preparation. We also thank the following institutions for submission of cases and for follow-up collaboration: Southwest Animal Hospital (Beaverton, Oregon), Riverside Animal Hospital (Jacksonville, Florida), Sno-Wood Hospital (Woodinville, Washington), and the Animal Health Departments of the San Francisco Zoo, Woodland Park Zoo, Dallas Zoo, Los Angeles Zoo, Fort Worth Zoo, and Detroit Zoo.

Literature Cited

1.  Gerin JL, Cote PJ, Korba BE, Tennant BC. Hepadnavirus-induced liver cancer in woodchucks. Cancer Detect Prev. 1989;14:227–229.

2.  Macdonald DW. Rodents. In: The Encyclopedia of Mammals. London, UK: Andromeda Oxford Limited; 1993:594–595.

3.  Marion PL, Van Davelaar MJ, Knight SS, Salazar FH, Garcia G, Popper H, et al. Hepatocellular carcinoma in ground squirrels persistently infected with ground squirrel hepatitis virus. Proc Natl Acad Sci USA. 1986;83:4543–4546.

4.  Minuk GY, Shaffer EA, Hoar DI, Kelly J. Ground squirrel hepatitis virus (GSHV) infection and hepatocellular carcinoma in the Canadian Richardson ground squirrel (Spermophilus richardsonii). Liver. 1986;6:350–356.

5.  Robinson WS. The role of hepatitis B virus in the development of primary hepatocellular carcinoma: Part I. J Gastroenterol Hepatol. 1992;7:622–638.

6.  Roth L, King JM, Hornbuckle WE, Harvey HJ, Tennant BC. Chronic hepatitis and hepatocellular carcinoma associated with persistent woodchuck hepatitis virus infection. Vet Pathol. 1985;22:338–343.

7.  Snyder RL. Hepatitis and hepatocellular carcinoma in captive prairie dogs (Cynomys ludovicianus). Sonderdruck aus Verhandlungsbericht des XXI Internationalen Symposiums uber die Erkrankungen der Zootiere. Akademic-Verlag, Berlin. 1979:325–334.

8.  Tennant BC, Gerin JL. The woodchuck model of hepatitis B virus infection. ILAR J. 2001;42:89–102.

9.  Tennant BC, Mrosovsky N, McLean K, Cote PJ, Korba BE, Engle RE, et al. Hepatocellular carcinoma in Richardson’s ground squirrels (Spermophilus richardsonii): evidence for association with hepatitis B-like virus infection. Hepatology. 1991;13:1215–1221.

10.  Une Y, Tatara S, Nomura Y, Takahashi R, Saito Y. Hepatitis and hepatocellular carcinoma in two prairie dogs (Cynomys ludovicianus). J Vet Med Sci. 1996;58:933–935.

11.  Woolf A, King J, Tennant B. Primary hepatocellular carcinoma in a black-tailed prairie dog (Cynomys ludovicianus). J Wildl Dis. 1982;18:517–520.