Search

Beginning in 2015, athymic nude sentinel mice from conventional, medium-, and high-security facilities presented to the Comparative Pathology Laboratory (CPL) with weight loss, diarrhea, and/or rectal prolapse. Regardless of whether clinical signs were present or absent, the gross observation of ceco-colonic thickening corresponded histologically to pleocellular typhlocolitis with mucosal hyperplasia and lamina proprial multinucleated cells. A subset of affected sentinels exhibited granulomatous serositis and hepatosplenic necrosis with multinucleated cells. Initial suspicion of mouse hepatitis virus infection was excluded by polymerase chain reaction, electron microscopy, and serology. Multinucleated giant cells were confirmed as macrophages by positive immunoreactivity to Mac-3 and Iba-1 and negative immunoreactivity to pancytokeratin. From conventional and medium-security facilities, Helicobacter species were identified in 40 of 143 (27.9%) mice, with H. hepaticus accounting for 72.5% of identified Helicobacter species. Other agents included opportunistic bacterial infection (41/145, 28.3%), murine norovirus (16/106, 15.1%), and pinworms (2/146, 1.4%). From high-security facilities, only Enterobacter cloacae was identified (2/13, 15.4%), and no evidence of Helicobacter sp., murine norovirus, or pinworms was present. No potentially infectious disease agent(s) was identified in 71 of 146 (48.6%) affected nude sentinels from conventional and medium-security facilities and 11 of 13 (84.6%) affected nude sentinels from high-security facilities. No statistically significant differences in histologic lesion scores were identified between Helicobacter-positive and Helicobacter-negative mice. Thus, proliferative typhlocolitis with multinucleated giant cells was considered a nonspecific histologic pattern associated with a variety of primary and opportunistic pathogens in athymic nude mice.

Twenty feline vaccine-associated sarcomas were examined by transmission electron microscopy. Tumors contained pleomorphic spindle cells, histiocytoid cells, and giant cells. Most tumors contained myofibroblasts, which had morphologic features similar to those of fibroblasts. These cells were further distinguished by subplasmalemmal dense plaques and thin cytoplasmic actin myofilaments organized as elongated bundles concentrated at irregular intervals forming characteristic dense bodies. Intracellular crystalline particulate material was found in 5 of the 20 tumors. Energy dispersive X-ray spectroscopy was used to identify the crystalline material within one tumor as aluminum-based. One tumor from a feline leukemia virus-infected cat contained budding and immature retroviral particles.

The bcl-2 family of genes encodes proteins that influence apoptosis. In the present immunohis-tochemical study, the topographic distribution of bcl-2 protein was examined in healthy feline fetal, neonatal, and adult tissues, a feline renal cell line, and feline tumors obtained from a veterinary hospital. The topographic distribution of bcl-2 in healthy tissues was similar to that described in human tissues. In lymphoid tissues, follicular mantle cells strongly expressed bcl-2. In complex and differentiating epithelium, bcl-2 expression was detected in stem cell and proliferation zones. Bcl-2 expression was also detected in lower crypts of the intestine and in skin basal layers. The feline Crandell kidney cells expressed bcl-2 diffusely throughout the cytoplasm. Of 180 tumors examined, bcl-2 was expressed almost uniformly in cutaneous basal cell tumors, thyroid adenomas, and mammary carcinomas and in 50% of the lymphomas examined. Bcl-2 may play a role in blocking apoptotic cell death in a broad range of normal feline tissues, whereas dysregulated bcl-2 may extend the life of certain tumors or render certain tumors resistant to therapy because most chemotherapeutic and radiotherapeutic agents eliminate tumor cells by triggering apoptosis.

Human basal epithelium (myoepithelium)-specific (312C8–1) and luminal epithelium-specific (13H5) cytokeratin antibodies were applied to frozen sections of normal canine mammary tissues (seven), benign adenomas and hyperplasias (five), mixed tumors (12), and adenocarcinomas (18) to determine if epithelial subsets could be discriminated by the use of an avidin biotin peroxidase complex immunohistochemical procedure. The 312C8–1 and 13H5 antibodies were consistently reactive with basal and luminal epithelium, respectively, in the normal mammary gland (7/7) and in benign adenomas and hyperplasias (5/5). Mixed mammary tumors had similar basal and luminal epithelial reactivity and also had proliferating spindle-shaped stromal cells that were reactive with 312C8–1 (10/12) and 13H5 (4/12). The adenocarcinomas were subclassified into basal, luminal, and basal/luminal on the basis of 312C8–1 reactivity (4/18), 13H5 reactivity (2/18), and dual reactivity with mutually exclusive anatomic distribution (11/18), respectively. Those tumors with dual immunoreactivity were indicative of noninvasive carcinomas. Dogs with neoplasms that were reactive with 312C8–1 and nonreactive with 13H5 had local recurrence or distant metastasis within 2 weeks to 6 months after diagnosis. Other antibodies used for comparison were pan cytokeratin AE1/AE3, actin HHF35, and vimentin. 312C8–1 and 13H5 antibodies are specific for canine mammary basal and luminal epithelium, respectively, and by employing these antibodies, the origin and differentiation of canine mammary neoplasms can be determined more accurately than on the basis of hematoxylin and eosin-stained tissue alone.

Spontaneous morbidity primarily affecting female breeders in 3 independent breeding colonies of NSG (NOD.Cg- Prkdcscid I12rgtm1Wjl/SzJ) mice prompted an investigation to uncover the cause of disease. Necropsies were performed on 264 (157 female and 107 male) spontaneously sick, experimentally unmanipulated NSG mice. In sum, 42 mice (15.9%) had acute or chronic renal inflammatory lesions, of which 12 had concurrent histologic evidence of an ascending urinary tract infection. From 94 kidneys cultured for bacterial organisms, 23 (24.5%) grew Enterococcus sp and 19 (20.2%) grew Klebsiella oxytoca. Female mice were twice more likely than males to present with nephritis. These findings indicate that bacterial nephritis is a major contributor to morbidity in the NSG strain.

Seventy-seven feline transplant kidney specimens, obtained from 1 to 3,183 days (9 years) after transplantation, were reevaluated histologically and classified on the basis of the Banff '97 guidelines for human renal transplant kidneys. Overall, this classification system appeared useful in detecting rejection reactions and confirmed the finding in humans that biopsies can diagnose subclinical rejection and therefore are an important diagnostic tool for the follow up of renal transplants. However, on the basis of serum creatinine values, the severity of the acute or active and chronic lesions was not accurately reflected by this scoring system. This is thought to be due to the significant differences in histologic rejection patterns, especially in acute or active rejection, in cats when compared with humans. Tubulitis, lymphocytic glomerulitis, and vasculitis, which are the main pillars of the Banff '97 acute or active rejection scoring system, are either rare or not found in cats. The presence of significant necrotizing glomerulitis and vasculitis in feline renal transplants might imply that the rejection is complicated by acute antibody-mediated rejection. Alternatively, cyclosporine toxicity also should be considered because some of these kidneys show other signs of cyclosporine toxicity. Finally, the significance of subcapsular and interlobular phlebitis, rarely described in human rejection reactions but a distinct entity in cats, is unknown. From this study, it is clear that there are significant differences in the histology of acute or active rejection between humans and cats and that a better understanding of the histologic appearance of renal allografts will be especially beneficial for treatment and prognostic purposes.

Forty-four primary feline vaccine-associated fibrosarcomas and 16 recurrences were examined histologically for detailed morphologic characterization with emphasis on tumor grade, presence of neoplastic multinucleated giant cells, presence and proportion of T and B lymphocytes within the tumor, and thin and intermediate filament contents of neoplastic and stromal cells. The microvascularity and proliferation rates of central and peripheral areas of the tumors were also quantified by computerized image analysis. For primary fibrosarcomas, 11 of 44 (25%) were grade I, 21 of 44 (47.7%) were grade II, and 12 of 44 (27.3%) were grade III. The recurrences followed a similar pattern: 4 of 16 (25%) were grade I, 8 of 16 (50%) were grade II, and 4 of 16 (25%) were grade III. A positive correlation was found between the presence of neoplastic multinucleated giant cells and tumor grade. These cells were present in 9 of 12 (75%) of grade III and none of the grade I tumors. Prominent peritumoral lymphoid aggregates or follicles were present in 59% of the tumors, and many contained high proportions of T lymphocytes, varying from 19 to 87%. All fibrosarcomas were immunoreactive for vimentin and 28 of 44 (64%) were reactive for α-smooth muscle actin. The actin-positive cells were either part of the tumor or formed a capsule around tumor nodules. The peripheral vascularity was significantly higher than the central vascular density but no difference was found in tumor cell proliferation rates between the two areas. Centrally located, fluid-filled micro- or macrocavitations were frequently observed in the large vaccine sarcomas and probably formed secondary to rapid tumor growth and central necrosis.

Expression of p27Kip1 was identified in feline lymphoid tissues by immunohistochemistry. In normal lymphoid tissues, p27Kip1 was detected as a distinct nuclear stain in lymphocytes of the follicular mantle zone and interfollicular small lymphocytes, whereas activated lymphoblasts in the germinal center were negative. Lymphoid hyperplasia was similarly immunolabeled but with an expanded mantle zone and marginal zone of p27Kip1-reactive lymphocytes. Both T- and B-cell lymphomas lacked p27Kip1 immunolabel and were determined to be proliferative based on immunohistochemical detection of the Ki-67 antigen. Scattered p27Kip1- immunolabeled lymphocytes were detected throughout the lamina propria of most specimens characterized as lymphoplasmacytic enteritis. The results of this study suggest that the antiproliferative effect of the cell cycle regulator p27Kip1 is abrogated in feline lymphoma, presumably allowing cells to bypass the G1-S checkpoint of the cell cycle.