Veterinary Pathology

  • Diagnostic Exercise: Metastatic Calcification in Guinea Pigs 1 luglio 2015
    Villano, J. S., Fann, M. K., Suckow, C. E., Cooper, T. K.
    Seven male Hartley guinea pigs, 3 to 18 months old, died or had to be euthanized because of nonspecific clinical signs unresponsive to supportive treatment. Gross necropsy and histopathology findings in all animals included severe soft tissue calcification affecting the myocardium, kidneys, and occasionally the liver.
  • Immunohistological Description of Nongestational Ovarian Choriocarcinoma in Two Female Mice With Conditional Loss of Trp53 Driven by the Tie2 Promoter 1 luglio 2015
    Castiglioni, V., Ghahremani, M. F., Goossens, S., Maglie, M. D., Ardizzone, M., Haigh, J. J., Radaelli, E.
    Nongestational ovarian choriocarcinoma (NGCO) is a tumor of germ cell origin seldom described in nonhuman species. Few spontaneous cases are reported in macaques and mice, with the B6C3F1 strain overrepresented. This report describes 2 cases of ovarian choriocarcinoma in nulliparous female mice with conditional loss of Trp53 under the Tie2 promoter. The mouse line was maintained on a mixed genetic background including Crl: CD1(ICR) and 129X1/SvJ strains. In both cases, affected ovary was partially replaced by blood-filled lacunae lined by neoplastic trophoblast-like giant cells. Immunohistochemically, neoplastic cells expressed folate-binding protein and prolactin and were invariably negative for p53. To the authors’ knowledge, this is the first report characterizing this entity in a genetically engineered mouse (GEM) line. Considering that germ cells (the cell population from which NGCO originates) constitutively express Tie2 receptor, it can be speculated that Tie2-driven deletion of Trp53 may have played a role in the development of these tumors.
  • Immunohistochemical Expression of Angiogenic Factors by Neoplastic Epithelial Cells Is Associated With Canine Prostatic Carcinogenesis 1 luglio 2015
    Palmieri, C.
    The dog is the only species, other than humans, in which spontaneous prostatic cancer occurs; therefore, dogs are a valuable model for the study of factors that regulate tumor progression. Angiogenesis is important in the development and spread of a variety of cancers, including prostate cancer. To better define the role of cancer epithelial cells in prostate cancer neovascularization, immunohistochemical staining for angiogenic factors (vascular endothelial growth factor [VEGF], platelet endothelial cell adhesion molecule–1 [PECAM-1], Tie-2, and fibroblast growth factor–2 [FGF-2]) was performed on formalin-fixed, paraffin-embedded tissues from 10 normal prostates, 15 hyperplastic prostates, and 11 prostatic carcinomas from dogs. Normal and hyperplastic epithelial cells were negative for PECAM-1, VEGF, and Tie-2, while the same markers were expressed with a variable intensity of cytoplasmic staining by neoplastic cells. Mild to moderate FGF-2 staining was detected in all normal prostates with less than 10% of positive cells, mainly distributed in the basal layer. The percentage of FGF-2–positive hyperplastic cells was variable, with both basal and secretory cells exhibiting a perinuclear to diffuse cytoplasmic staining. The mean number of positive cells and the intensity of staining were higher in prostatic carcinomas than normal and hyperplastic prostates. Moreover, microvessel density analyzed on PECAM-1–stained slides was increased in prostate cancer compared with normal and hyperplastic prostates. Therefore, prostatic neoplastic cells are capable of simultaneous expression of various angiogenic factors and may increase tumor proliferation and angiogenesis in a paracrine and autocrine fashion.
  • Encephalitozoonosis in 2 South American Fur Seal (Arctocephalus australis) Pups 1 luglio 2015
    Seguel, M., Howerth, E. W., Ritter, J., Paredes, E., Colegrove, K., Gottdenker, N.
    Cerebral and disseminated encephalitozoonosis was diagnosed by histopathology, electron microscopy, and immunohistochemistry in 2 free-ranging South American fur seal pups found dead at Guafo Island (43°33'S 74°49'W) in southern Chile. In the brain, lesions were characterized by random foci of necrosis with large numbers of macrophages containing numerous microsporidial organisms within parasitophorous vacuoles. In addition, occasional histiocytes loaded with numerous mature and immature microsporidia spores consistent with Encephalitozoon sp were observed in pulmonary alveolar septa, splenic red pulp, glomerular capillaries, and proximal renal tubules by Gram and immunohistochemical stains. To our knowledge, microsporidial infection in a marine mammal species has not been previously reported.
  • Diagnostic Exercise: Circling and Behavioral Changes in a Cat 1 luglio 2015
    Faller, K., Leach, J., Gutierrez-Quintana, R., Finck, M., Hammond, G., Penderis, J., Marchesi, F.
    A 4-year old spayed male domestic shorthair cat was presented with a history of circling and behavioral changes. Neurologic examination showed mild proprioceptive deficits. The lesion was localized in the forebrain, and magnetic resonance imaging revealed the presence of a large midline intracranial mass extending from the frontal lobe to the tentorial region of the brain. Euthanasia was elected due to poor prognosis. Histopathologic evaluation confirmed the presence of a mass composed by sheets and aggregates of large round/polygonal cells and multinucleate cells associated with deposits of cholesterol clefts, scattered hemorrhages and hemosiderin-laden macrophages. Immunohistochemistry showed that the round/polygonal cells and multinucleate cells were strongly positive for major histocompatibility complex class II antigen, variably positive for CD18, and occasionally positive for S100. Subsets of spindle cells showing variable expression of vimentin, S100, and neuron-specific enolase were also present. The final diagnosis was cholesterol granuloma. Differential diagnosis with meningioma is discussed.
  • p63 and E-cadherin Expression in Canine Oral Squamous Cell Carcinoma 1 luglio 2015
    Mestrinho, L. A., Pissarra, H., Faisca, P. B., Braganca, M., Peleteiro, M. C., Niza, M. M. R. E.
    The expression of p63 and E-cadherin was studied in 22 oral squamous cell carcinomas in the dog according to immunohistochemical techniques. The association between these markers and clinicopathologic parameters was assessed. All tumor cells studied showed enhanced p63 expression. Regarding E-cadherin expression, 17 of 22 cases (77.3%) showed decreased immunoreactivity, and in 13 of 22 cases (59.1%), its expression was cytoplasmic. Neither p63 nor E-cadherin expression patterns were associated with tumor size, bone invasion, or lymph node metastasis. p63 score was related to proliferating cell nuclear antigen proliferative index (P = .020). A statistically significant correlation between the expression patterns of these 2 markers was noted (P = .026). Furthermore, they were related with tumor grade. An atypical p63 labeling and a cytoplasmic E-cadherin staining were statistically related with a higher tumor grade (P = .022 and P = .017, respectively). These findings suggest that changes in p63 and E-cadherin expression are frequent events in oral squamous cell carcinoma in dogs.
  • p62/Sequestosome-1: Mapping Sites of Protein-Handling Stress in Canine Cutaneous Mast Cell Tumors 1 luglio 2015
    Rich, T., Dean, R. T. G., Lamm, C. G., Ramiro-Ibanez, F., Stevenson, M. L., Patterson-Kane, J. C.
    Canine cutaneous mast cell tumors (MCT) are common, frequently malignant neoplasms that are currently graded histologically for provision of prognostic information. Continuing evidence of subsets of MCT within certain grades (with differing survival times) indicate the need for biomarkers that will facilitate better patient stratification and also provide further information on the biological processes involved in progression. We decided to investigate the expression of p62/sequestosome-1 (p62/SQSTM1), a stress-inducible "hub protein" found in all cell types that shuttles rapidly between the nucleus and cytoplasm and is known to play important roles in protein handling and tumorigenesis. The identity of canine p62/SQSTM1 was confirmed in silico and by validation of a commercial antibody using both Western blotting and functional (pharmaceutical-based) analyses in cell culture. Using immunohistochemistry, 3 patterns of p62 expression were identified based on the predominant intracellular localization, that is, nuclear, mixed (nuclear and cytoplasmic), and cytoplasmic. There was a highly significant association with the 2-tier (Kiupel) grade (P < .0001), with all p62-nuclear immunoreactivity being associated with low grade and most p62-cytoplasmic immunoreactivity (93%) with high grade. Most but not all mixed nuclear-cytoplasmic labeling occurred in low-grade MCT; in other (human) tumor types, this pattern has been interpreted as borderline malignant. These data indicate that there is a shift in protein-handling stress from the nucleus to the cytoplasm in association with increasing malignancy in MCT. Studies to identify the processes and drug-able targets involved in this progression are ongoing.
  • Solitary Large Intestinal Diverticulitis in Leatherback Turtles (Dermochelys coriacea) 1 luglio 2015
    Stacy, B. A., Innis, C. J., Daoust, P.- Y., Wyneken, J., Miller, M., Harris, H., James, M. C., Christiansen, E. F., Foley, A.
    Leatherback sea turtles are globally distributed and endangered throughout their range. There are limited data available on disease in this species. Initial observations of solitary large intestinal diverticulitis in multiple leatherbacks led to a multi-institutional review of cases. Of 31 subadult and adult turtles for which complete records were available, all had a single exudate-filled diverticulum, as large as 9.0 cm in diameter, arising from the large intestine immediately distal to the ileocecal junction. All lesions were chronic and characterized by ongoing inflammation, numerous intralesional bacteria, marked attenuation of the muscularis, ulceration, and secondary mucosal changes. In three cases, Morganella morganii was isolated from lesions. Diverticulitis was unrelated to the cause of death in all cases, although risk of perforation and other complications are possible.
  • Estrogen Receptor and Signal Transducer and Activator of Transcription 3 Expression in Equine Mammary Tumors 1 luglio 2015
    Hughes, K., Scase, T. J., Foote, A. K.
    Equine mammary tumors are uncommon, and relatively sparse histopathologic and molecular data exist. The present study describes the histopathologic features of 7 such tumors, which exhibited infiltrative growth, intermediate to high mitotic rates, and focally extensive necrosis. The tumors exhibited variably strong staining for vimentin and cytokeratin 14, as well as frequently weak cytoplasmic staining for pan-cytokeratin. E-cadherin expression was strong. Interestingly, a subgroup of the tumors exhibited strong nuclear staining for estrogen receptor α. Three of 7 tumors exhibited nuclear expression of the transcription factor STAT3, suggesting that STAT3 was transcriptionally active. Rare to absent nuclear STAT3 expression was observed in carcinomas exhibiting moderate to intense staining for cytokeratin 14. This investigation confirms previous investigators’ assertions that equine mammary tumors have a malignant phenotype. A subset of the equine mammary tumors exhibited estrogen receptor α expression, suggesting that these tumors may potentially have similar molecular characteristics to their feline and canine counterparts.
  • Immunohistochemical Characterization of Large Intestinal Adenocarcinoma in the Rhesus Macaque (Macaca mulatta) 1 luglio 2015
    Harbison, C. E., Taheri, F., Knight, H., Miller, A. D.
    In rhesus macaques, adenocarcinomas of either the ileocecal junction or colon are common spontaneous tumors in aging populations. The macaque tumors have similar gross and histologic characteristics compared with their human counterpart, but little is known regarding the immunohistochemical expression of proteins that are commonly implicated in the pathogenesis of these tumors in humans. We performed a retrospective review of 22 cases of large intestinal carcinoma in the rhesus macaque and evaluated the expression pattern of a panel of potentially prognostically significant proteins identified from human studies. Histologic characteristics of the tumors included abundant mucin deposition, transmural spread, and lymphatic invasion. All rhesus adenocarcinomas displayed altered expression of 1 or more of CD10, β-catenin, sirtuin 1, cytokeratin 17, and p53 compared with age-matched controls. Zymographic analysis of active matrix metalloproteinases 2 and 9 in the serum from 5 animals failed to reveal statistically significant differences between adenocarcinoma cases and controls. Based on the data presented herein, large intestinal carcinomas in the macaque share many histomorphologic and immunohistochemical similarities to large intestinal tumors in humans. Further validation of this animal model is considered important for the development of novel therapeutics and a better understanding of the pathogenesis.