Feline mammary carcinoma is highly malignant and generally associated with a poor prognosis, although studies suggest the range of survival times in affected cats is broad. Histologic grading of these tumors is achieved using the Elston and Ellis system, originally developed for human breast cancer. In cats, however, classification using this method has variable prognostic value. Therefore, objectives of this study were (1) to evaluate the Elston and Ellis grading system for feline mammary carcinoma in a predominantly spayed population and (2) to determine whether modification of this system or development of a novel system improved the prognostic value of histologic grading. Survey data and histologic features for 108 carcinomas from 97 cats were analyzed with respect to overall survival. Elston and Ellis grading failed to correlate significantly with overall survival. Using multivariable analysis, lymphovascular invasion, nuclear form, and mitotic count each demonstrated independent prognostic significance (P ¼ .008, <.001, and .004, respectively). Modifications of the Elston and Ellis system and a novel grading system were proposed based on these results; all showed significant correlation with overall survival (P < .001). Median survival times were 27, 29, or 31 months for grade I; 14, 12, or 14 months for grade II; and 13, 5, or 8 months for grade III carcinomas using the mitotic-modified Elston and Ellis, the revised Elston and Ellis, or the novel grading system, respectively. Based on this retrospective study, adoption of the species-specific systems as proposed here may improve the prognostic value of histologic grading for feline mammary carcinoma.
The alkaline phosphatases comprise a heterogeneous group of enzymes that are widely distributed in mammalian cells. They often are associated with cell membranes, but their exact physiologic function is unknown. Despite this, alkaline phosphatase activity is a very useful serum biochemical indicator of liver disease, particularly cholestatic disease. However, increases in the activity of alkaline phosphatase in serum and other body fluids may reflect physiologic or pathologic changes beyond those of hepatic origin. For example, nonhepatic increases in serum alkaline phosphatase activity are found in young animals, in pregnant and lactating females, and in association with high fat diets. Bone disease, endocrine disease, neoplasia, and other disorders can result in increased alkaline phosphatase activity. In addition, alkaline phosphatase activity may be increased due to induction by certain drugs such as glucocorticoids and anticonvulsants. In this article, we will review the physiologic and pathologic factors influencing the activity of alkaline phosphatase in serum and other body fluids, with an emphasis on disorders beyond liver disease. (Vet Clin Pathol. 2007;36:223-233)
Amputation is commonly performed to both treat and diagnose conditions affecting the digits of dogs. Although histopathologic evaluation of these digits is routinely done, data on the prevalence and prognosis of neoplasms of the digit are scarce. The records of multiple veterinary diagnostic laboratories were searched to identify submissions of amputated digits from dogs. Four hundred twenty-eight separate submissions were reviewed for diagnosis, age, sex, limb of origin, and digits affected, and the original submitting clinics were surveyed to determine clinical outcome of the animal. No diagnosis could be agreed upon in 24 animals, and these were excluded from the study. Kaplan-Meier product-limit method was used to determine the disease-free interval and survival time. Neoplastic disease was identified in 296 of 404 submissions, with exclusively inflammatory lesions composing 108 cases. A total of 30 different neoplastic processes were identified. In 233 (77.7%) of the neoplastic cases, a malignant tumor was identified. Squamous cell carcinoma was the most commonly identified tumor (n = 109, 36.3%), and 11 of 42 dogs for which clinical follow-up information was available developed metastatic disease. Squamous cell carcinoma of the digit appears to have a greater metastatic potential than that occurring elsewhere in the body. Other common diagnoses included melanoma (n = 52, 17.3%), soft-tissue sarcoma (n = 29, 9.7%), and mast cell tumor (n = 20, 6.7%). Melanomas were associated with poor prognoses, with a median survival time of 365 days.
Abstract. Immunohistochemical and histochemical stains are useful adjunct techniques in the diagnosis of canine cutaneous round cell tumors, which can appear histologically similar. We applied a panel of monoclonal antibodies (recognizing tryptase, chymase, serotonin for mast cells; CD1a, CD18, MHC class II for histiocytes; CD3 for T lymphocytes; CD79a for B lymphocytes and plasma cells) and one histochemical stain (naphthol AS-D chloroacetate for chymase activity) to formalin-fixed, paraffin-embedded sections of canine cutaneous mast cell tumors, histiocytomas, lymphosarcomas, plasmacytomas, and unidentified round cell tumors. Of 21 tumors with a histologic diagnosis of mast cell tumor, 7/7 (100%) grade I, 6/7 (85.7%) grade II, and 3/7 (42.9%) grade III tumors were diagnosed as mast cell tumors based on positive staining for tryptase antigen and chymase activity. Mast cells were positive for both tryptase antigen and chymase activity, indicating equal efficacy of tryptase immunohistochemistry and chymase histochemistry. Chymase was detected immunohistochemically in both tumor and nontumor cells, while serotonin was not detected in most mast cell tumors, and thus, neither was useful in the diagnosis of mast cell tumors. Immunohistochemistry to detect CD18 and MHC class II was equally effective in staining histiocytomas, although lymphosarcoma must be ruled out through the use of CD3 and CD79a immunohistochemistry. Immunohistochemistry using three different monoclonal antibodies to human CD1a showed no cross-reactivity in canine histiocytomas and was not useful. A final diagnosis was obtained for 4/5 (80%) of the unidentified tumors, indicating the usefulness of multiple stains in poorly differentiated round cell tumors.
Dogs with a lactate concentration higher than the reference interval at 6 hours were more likely not to survive. These results indicate an association between lactate concentration and outcome and emphasize the importance of serial lactate concentrations in evaluating prognosis.
We examined 12 formalin-fixed paraffin-embedded feline skin tumours which had the histopathological features of fibropapillomas for the presence of papillomavirus (PV) DNA using touchdown polymerase chain reaction (PCR), DNA sequencing and nonradioactive in situ hybridization. Nine of the tumours contained a 102-bp PCR product demonstrated using consensus PV primers that amplify a portion of the L1 gene. The nucleotide sequences are closely related, but not identical to that of ovine PV type 2, rabbit oral PV and reindeer PV. The deduced amino acid sequences had strong homologies with the major capsid protein L1 of deer PV, bovine papillomavirus (BPV) 1 and BPV 2, and European elk PV. Although PV antigens were not detected in any of the tumours by immunohistochemistry, PV DNA was demonstrated in individual mesenchymal cells or cell nests of 4/12 tumours by in situ hybridization. A nonproductive infection of mesenchymal fibroblast-like tumour cells with a papillomavirus would explain the lack of PV antigen expression and the absence of PV DNA in the hyperplastic epithelium. Because these tumours and their pathogenesis are similar to equine sarcoids, we suggest that they should be reclassified as 'feline sarcoids' instead of fibropapillomas.
Abstract. The expression of 5 markers associated with angiogenesis was studied in canine squamous cell carcinomas (SCCs) (n 5 19) and canine trichoepitheliomas (TCPs) (n 5 24). SCCs were assigned histologic grades, and tissue sections from both tumor types were immunohistochemially stained for the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2), as well as intratumoral microvessel density (iMVD), tumor proliferation index (PI), and tumor apoptotic index (AI), using antibodies against VEGF, VEGFR-2, von Willebrand's factor, Ki-67 antigen, and the terminal deoxynucleotidyl transferase-mediated 29-deoxyuridine 59-triphosphate endlabeling method (TUNEL), respectively. VEGF and VEGFR-2 were detected in 17/19 (89.4%) and 19/19 (100%) SCCs and in 17/24 (70.8%) and 20/24 (83.3%) TCPs, respectively. In SCCs, there was substantial correlation between histologic grade and PI (r 5 0.51); and moderate correlation between VEGF and histologic grade (r 5 0.43), VEGFR-2 and histologic grade (r 5 0.47), VEGF and PI (r 5 0.47), and VEGFR-2 and PI (r 5 0.47) (Spearman rank correlation coefficient). In TCPs, there was substantial correlation between VEGF and PI (r 5 0.51) and a moderate correlation between VEGFR-2 and iMVD (r 5 0.36). The median iMVD of SCCs (15.5) was significantly higher than the median iMVD of TCPs (9.05) (P value , .05). It was concluded that VEGF and VEGFR-2 may promote tumor cell proliferation in TCPs and SCCs. An autocrine pathway for VEGF probably operates in canine SCCs and TCPs, as VEGF and VEGFR-2 expression was found in most tumors and was associated with evidence for tumor cell proliferation.
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