key: cord-0916883-3keht8ge authors: Cho, Sung-Jin; Lee, Hyun-A; Hong, Sunhwa; Kim, Okjin title: Uterine adenocarcinoma with feline leukemia virus infection date: 2011-12-19 journal: Lab Anim Res DOI: 10.5625/lar.2011.27.4.347 sha: c6be64927ed61a5ec6ad9e947934aea286e2f46e doc_id: 916883 cord_uid: 3keht8ge Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have been poorly characterized to date. In this study, we describe a uterine adenocarcinoma in a Persian cat with feline leukemia virus infection. At the time of presentation, the cat, a female Persian chinchilla, was 2 years old. The cat underwent surgical ovariohystectomy. A cross-section of the uterine wall revealed a thickened uterine horn. The cat tested positive for feline leukemia virus as detected by polymerase chain reaction. Histopathological examination revealed uterine adenocarcinoma that had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions. Based on the histopathological findings, this case was diagnosed as a uterine adenocarcinoma with abdominal metastasis. To the best of our knowledge, this is the first report of a uterine adenocarcinoma with feline leukemia virus infection. Uterine adenocarcinomas have been reported in most domestic species but are considered rare except in rabbits and cows [1] . The prevalence of uterine adenocarcinoma in rabbits after 5 years of age has been reported to be 79% [2] . Because rabbits are induced ovulators that are often housed individually, laboratory rabbit and possibly many pet rabbits are under almost constant estrogen stimulation. Virgin rats have a similar high incidence of endometrial adenocarcinomas [3] . Cats, another species that exhibit induced ovulation, may also be subjected to long periods of unopposed estrogen stimulation, but the frequent practice of neutering queens, and the tendency to periodically breed or induce ovulation in sexually intact queens, may explain the low prevalence of endometrial adenocarcinoma in cats [4] . In women, postmenopausal hormone replacement therapy, estrogen in particular, is considered a risk factor for endometrial adenocarcinoma; both estrogen-dependent and higher-grade estrogen-independent adenocarcinomas are recognized [5] . Viruses cause cancer in amphibians, fish, fowl, rodents, cats, cattle, and subhuman primates, and if humans were to be exempt from such a general biological phenomenon, it would be a circumstance unparalleled in the history of parasitism. In fact, evidence is accumulating that some human cancers are virally induced. For example, Burkitt's lymphoma, nasopharyngeal carcinoma, cervical cancer, and Kaposi's sarcoma are thought to be caused by herpesviruses, which are able to remain latent in the host for many years [6] . Feline leukemia virus (FeLV) is an exogenous retrovirus, belonging to the genus Gammaretrovirus, which infects domestic cats and, sporadically, wild cats as well [7, 8] . FeLV causes a wide range of proliferative diseases in cats, including lymphoid and myeloid leukemia [9] . Feline endometrial adenocarcinomas are uncommon malignant neoplasms that have to date been poorly characterized. In this study, a case of uterine adenocarcinoma case is described in a Persian cat with FeLV infection. At the time of presentation, the cat was a 2-year-old female Persian chinchilla ( Figure 1A ). She presented with vaginal discharge and interrupted vomiting, and was given a health examination. Abdominal sonography and radiography demonstrated abnormal enlargement of the uterus in the abdominal cavity. The blood analysis revealed neutrophilia and lymphopenia. The concentrations of progesterone and estrogen in blood were evaluated and the results revealed normal ranges. The cat underwent surgical ovariohystectomy. During the laparotomy, thickening and inflammatory lesions of the omentum and spleen were observed ( Figure 1B ). The results of bacterial culture with omentum and spleen samples were negative for pathogenic bacteria. The ovariouterus and the omentum were removed surgically, submitted to gross examination, and trimmed. Cross-sections of the uterine wall revealed a thickening of uterine horn ( Figure 2 ). Additionally, yellowish contents were observed in the lumen of the uterus. The trimmed tissues were fixed in 10% neutral buffered formalin and embedded in paraffin. Four-micrometer sections were made and stained with hematoxylin and eosin (H&E) for histopathological examination. The histopathological analysis revealed adenocarcinoma in the uterus and omentum ( Figure 3 ), but no pathological changes were observed in the ovary. The adenocarcinoma had metastasized to the omentum, resulting in thickening and the formation of inflammatory lesions (Figure 4 ). Based on these histopathological findings, the case was diagnosed as uterine adenocarcinoma with abdominal metastasis. The cat made a complete recovery following an ovariohysterectomy and [21] . Genomic DNA was isolated from blood using an AccuPrep The PCR-amplified samples were evaluated for the presence of PCR amplicons corresponding to FeLV, FIP, FIV, FPV, FHV, FCV, Heart worm, Feline Chlamydia, Toxoplasma, Babesia spp., Ehrlichia spp., Haemobartonella felis, Rickettsia spp. and Brucella spp. We were able to visualize bands that were 529 base pairs in length, corresponding to the FeLV amplicon ( Figure 5 ); other feline pathogens tested negative in the PCR assay ( Figure 5 ). Significant changes in the structure of the endometrium are associated with degeneration of luminal epithelium, cystic endometrial hyperplasia, pyometra, and adenocarcinoma [22] . Endometrial tumors of the uterus are rare in domestic animals [23] . Adenocarcinoma of the uterus is very rare in animals, in marked contrast to the prevalence of this tumor in human females [23] . The basic mechanisms associated with these changes are poorly understood. Prolonged exposure to megestrol acetate has been associated with endometrial hyperplasia and pyometra in domestic cats, and progestin contraceptives may have similar effects on zoo felids [24, 25] . Megestrol acetate is a derivative of progesterone and used commonly both in contraception and hormone replacement therapy [26] . Based on available clinical and epidemiological data, it has been long suspected that tumors of the canine female genital tract develop under the influence of ovarian hormones [22] . In this case, however, the animal had not been given a progesterone derivative such as megestrol acetate. FeLV is an exogenous retrovirus causing several diseases in domestic cats, including tumors of most hematopoietic cells, aplastic anemia, myeloproliferative disorders, and immunosuppression [27] . The FeLVs that primarily cause Tcell tumors in cats are transmitted in a horizontal manner [28] , particularly through saliva [29] . The T-cell tropism of these agents is observed even when the virus infects human cells [30] . Although many free-roaming cats become persistently infected with FeLV, only a small fraction develops leukemia or lymphoma. A large number develop lethal opportunistic infections, particularly coronavirus-induced peritonitis [31] . FeLV causes lymphopenia, depressed cellmediated immune responses, thymic atrophy, and depressed humoral responses to T-cell dependent antigens despite the presence of hypergammaglobulinemia [31] . In this study, the cat had uterine adenocarcinoma without pathognomic ovarian lesions or significant hormonal imbalances. The cat also suffered from FeLV infection and lymphopenia. We believe that the uterine adenocarcinoma in this case was probably related to immunogenic depression by FeLV infection, although we cannot rule out the contributions of other factors, such as old age, to the induction of this tumor. To the best of our knowledge, this is the first report of feline uterine adenocarcinoma with feline leukemia virus infection. Tumors of the uterus Comparative pathology of endometrial carcinoma Uncommon frequency of adenocarcinomas of the uterus in virgin Han:Wistar rats Reproduction and reproductive disorders Endometrial carcinoma Viruses as causes of some human tumors? Results and prospectives of the epidemiologic approach of Human Cancer Evaluation of a novel nested PCR for the routine diagnosis of feline leukemia virus (FeLV) and feline immunodeficiency virus (FIV) Feline viruses in wildcats from Scotland Macrophage tropism of feline leukemia virus (FeLV) of subgroup-C and increased production of tumor necrosis factor-α by FeLV-infected macrophages Rapid detection of feline leukemia virus provirus integration into feline genomic DNA A mRNA PCR for the diagnosis of feline infectious peritonitis In vivo lymphocyte tropism of feline immunodeficiency virus Does a feline leukemia virus infection pave the way for Bartonella henselae infection in cats? Detection of active and latent feline herpesvirus 1 infections using the polymerase chain reaction Detection of feline calicivirus, feline herpesvirus 1 and Chlamydia psittaci mucosal swabs by multiplex RT-PCR/PCR Development of a PCR assay for diagnosing swine toxoplasmosis Detection of Babesia vogeli in stray cats of metropolitan Molecular detection and identification of Ehrlichia and Anaplasma species in ixodid ticks Competitive, quantitative PCR analysis of Haemobartonella felis in the blood of experimentally infected cats Role of sand lizards in the ecology of Lyme and other tick-borne diseases in the Netherlands Specific detection of Brucella DNA by PCR Tumors of the female reproductive system Tumors of the genital system Cystic endometrial hyperplasia and endometritis in a dog following prolonged treatment of medroxyprogesterone acetate Endometrial hyperplasia and mineralization in zoo felids treated with melengestrol acetate contraceptives Medroxyprogesterone acetate antagonizes the effects of estrogen treatment on social and sexual behavior in female macaques Feline leukemia virus: Pathophysiology, prevention, and treatment Horizontal transmission of feline leukemia virus Excretion of feline leukemia virus by naturally infected pet cats Susceptibility of human cell lines to feline leukemia virus and sarcoma virus Retroviruses associated with leukemia and ablative syndromes in animals and in human beings