JPC SYSTEMIC PATHOLOGY
Signalment (JPC# 320229): Leopard frog (Rana pipiens)
HISTORY: Large abdominal mass found at necropsy.
HISTOPATHOLOGIC DESCRIPTION: Kidney: Effacing 90% of renal architecture and extending to submitted borders is a multilobular, unencapsulated neoplasm composed of polygonal cells arranged in variably sized (up to 500 µm in diameter), irregularly shaped tubules and papillary projections, supported by a fine fibrovascular stroma. Neoplastic cells are closely packed, cuboidal to columnar with variably distinct cell borders, and contain a moderate amount of eosinophilic, granular cytoplasm. The neoplastic cells frequently pile up to 4 to 10 cell layers deep. Nuclei are round to oval, centrally to basally positioned, with coarsely stippled chromatin and up to two variably indistinct nucleoli. Mitotic figures are fewer than 1 per 10 high powered fields. There are numerous round, up to 15 um in diameter, eosinophilic, intranuclear viral inclusion bodies that are peripheralize the chromatin. Neoplastic structures are occasionally cystic and contain variable amounts of flocculent eosinophilic material. Multifocally, remaining tubules are ectatic and lined by attenuated epithelium and contain sloughed epithelial cells and debris. Within remaining parenchyma, there is a mild, multifocal lymphocytic inflammation and minimal hemorrhage.
MORPHOLOGIC DIAGNOSIS: Kidney: Renal adenocarcinoma, with eosinophilic intranuclear viral inclusions, Northern leopard frog (Rana pipiens), amphibian.
ETIOLOGIC DIAGNOSIS: Ranid herpesvirus renal adenocarcinoma
CAUSE: Ranid herpesvirus (RaHV-type1)
CONDITION: Lucké's tumor of leopard frogs, Lucké’s renal adenocarcinoma
- Ranid herpesvirus is a herpesvirus that affects leopard frogs, causing renal adenocarcinoma
- Family Alloherpesviridae
- Family includes herpesviruses of fish and amphibians, with four genera: Ictalurivirus, Salmonivirus, Cyprinivirus, and Batrachovirus
- RaHV-1 has tropism for renal convoluted tubules
- Tumor invasion and metastasis is temperature dependent
- Warm=metastasis, increased growth, no viral inclusions/light microscopy
- Cool=rare metastasis, replication in renal tubules, visible inclusion bodies
- The virus infects frog eggs and tadpoles as they develop in the water during the spring
- Adults that are first exposed to virus are not susceptible to renal carcinomas
- Virus has a tropism for developing renal cells and appears to be latent until animals are over two years old; carcinomas develop in the third or fourth summer of the frog's life
- Tumor grows rapidly during the summer and may expand sufficiently to kill the frog; tumor growth halts with hibernation in the autumn
- Digestion of types I & IV collagen is dependent on higher ambient temperatures (due to increased collagenase activity at higher temps), resulting in dormancy of tumor growth in the winter
- During the summer (the calid phase), high environmental temperatures are invasion permissive; no evidence of viral inclusions or particles are found during the summer
- During the winter (the algid phase), invasion is arrested because of low environmental temperatures (7-21 degrees Celsius); virus replicates in the convoluted tubules of the kidney, causing host cell lysis and excretion of the virus into the urine
- By lowering the environmental temperature of the host frog, tumor cells may be converted from the virus-free summer form to the less permissive winter state
- Virus is excreted into the urine and is expelled into the pond at the end of hibernation where it infects eggs and tadpoles in the spring; age at exposure and population density of the group may also affect the tendency of tumors develop
- Metastasis is more likely at higher temperatures
TYPICAL CLINICAL FINDINGS:
- Tumors do not have an obvious effect on the health of the frogs until the tumor destroys essentially all useful kidney tissue or metastasizes to critical tissues (lungs, liver)
TYPICAL GROSS FINDINGS:
- Unilateral or bilateral, off-white, nodular mass greater than 1mm
- Masses may replace up to 95% of the renal tissue, displace adjacent organs and occasionally fill the abdominal cavity
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Tubules and papillary projections of neoplastic epithelial cells forming structures resembling renal tubules with occasional solidly cellular regions
- Cells lining tubules are larger, cuboidal to columnar and often pseudostratified
- Eosinophilic inclusions (Cowdry type A) are seen in frogs collected in the winter or maintained at a low temperature
- Mitotic figures frequently observed in tumors in the summer
- Distinctive neoplasm in leopard frogs
- Other known members of Alloherpesviridae:
- Ranid herpesvirus 2 is associated with massive edema
- Ranid herpesvirus 3 has been associated with a proliferative dermatitis
- Ictalurid herpesvirus 1 (channel catfish virus)
- Cyprinid herpesvirus 1 (carp pox herpesvirus)
- Cyprinid herpesvirus 2 (hematopoietic necrosis herpesvirus of goldfish)
- Cyprinid herpesvirus 3 (koi herpesvirus)
Adapted from MacLachlan, Dubovi (2017)
Viruses that can induce tumors in Domestic or Laboratory Animals or Humans
|Virus||Type of Tumor|
|Poxviridae/Leporipoxvirus||Rabbit and squirrel fibroma virus||Fibromas and myxomas|
|Poxvirinae/Yatapox||Yaba monkey tumor virus||Histiocytoma in monkeys|
|Herpesviridae: Alphaherpesvirinae||Marek’s disease virus||T cell lymphoma in fowl|
Cottontail rabbit herpesvirus
|B cell lymphoma, etc
Lymphoma in baboons
Lymphoma in rabbits
|Alloherpesviridae||Lucke frog herpesvirus||Renal adenocarcinoma in frogs|
|Papillomaviridae||Bovine papillomavirus 4
Bovine papillomavirus 7
Cottontail rabbit papillomavirus
|Papillomas, carcinoma of intestine/bladder
Papillomas, carcinoma of eye
Papillomas, skin cancer
Squamous cell carcinoma
|Polyomaviridae/Polyomavirus||Murine polyomavirus||Tumors in newborn rodents Central nervous system|
Viruses that can induce tumors in Domestic or Laboratory Animals or Humans
|Woodchuck hepatitis virus||Hepatocellular carcinoma|
|Duck hepatitis virus||Hepatocellular carcinoma|
|Avian Leukosis virus
Rous sarcoma virus
Avian myeloblastosis virus
|Lymphoma, leukemia, osteopetrosis, nephroblastoma in fowl
Sarcoma in fowl
Myeloblastosis in fowl
|Betaretrovirus||Mouse mammary tumor virus
adenocarcinoma virus (jaagsiekte virus)
Pulmonary adenocarcinoma sheep
|Gammaretrovirus||Feline Leukemia virus
Feline sarcoma virus
Murine leukemia/sarcoma virus
Sarcoma in cats
Leukemia, lymphoma, sarcoma
|Deltaretrovirus||Avian reticuloendotheliosis virus
Bovine Leukemia virus
|Reticuloendotheliosis in fowl
B cell lymphoma, leukemia
- Carlson DL, McKinnell RG, Rollins-Smith LA, Sauerbier W. The presence of DNA sequences of the Lucké herpesvirus in normal and neoplastic kidney tissue of Rana pipiens. J Comp Pathol. 1994;110(4):349-55.
- O’Rourke DP, Schultz TW. In: Anderson LC, Fox JG, Loew FM, Quimby FW, eds. Laboratory Animal Medicine. 2nd ed. London, England; Academic Press; 2002:817-818.
- Granoff A. Herpesvirus and the Lucké tumor. Cancer Res. 1973; 33(6):1431-1433.
- Green DE, Harshbarger JC. Spontaneous neoplasia in amphibia. In: Wright KM, Whitaker BR, eds. Amphibian Medicine and Captive Husbandry. Malabar, FL: Krieger Publishing; 2001:365-368.
- Lucke´ B. Carcinoma in the leopard frog: its possible causation by a virus. J Exp Med. 1938; 68(4):457–468.
- MacLachlan JN, Dubovi EJ, eds. Fenner’s Veterinary Virology. 5th ed. London, UK: Academic Press; 2017:77, 191, 213, 215.
- Origgi FC, et al. Ranid herpesvirus 3 and proliferative dermatitis in free-ranging wild common frogs (Rana temporaria). Vet Pathol. 2017;54(4):686-694.
- Skinner MS, Mizell M. The effects of different temperatures on herpesvirus induction and replication in Lucké’s tumor explants. Lab Invest. 1972;26(6):671.