Background: Staging of mammary carcinomas of dogs and cats is not only important for prognostic purposes, but also to guide therapy, in particular regarding adjuvant chemotherapy. The classical staging system relies on T, the clinical tumor size, N, the clinical nodal stage, and M, distant metastasis, evaluated by the clinician. However, a more precise and reliable staging system is applied to human stage I–III breast cancer, i.e., without distant metastasis, in which T is replaced by the pathologic tumor size (pT), and N is replaced by the pathologic nodal stage (pN), both evaluated by the pathologist. This staging system is strongly associated with patient outcomes, and is used to select treatment options. The purpose of this study was to design a histologic staging system for Canine Mammary Carcinomas (CMCs, part 1 of this article), and Feline Mammary Carcinomas (part 2), inspired from human oncology, and to assess its association with patient outcomes.Materials and Methods: This retrospective study included 433 female dogs with a surgically removed CMC. Patient outcomes were recorded over a 2-years follow up period. CMCs were staged according to pT (greatest diameter in millimeters on histological slides), lymphovascular invasion (LVI), and pN (confirmed by cytokeratin AE1/AE3 immunohistochemistry). The histological stages were defined as: Stage 0 (CMCs in situ, surrounded by a continuous layer of p63+ myoepithelial cells), Stage I (pT1 ≤ 20 mm, LVI–, pN0–pNX, where pNX refers to the absence of lymph node sample), Stage II (pT2 > 20 mm, LVI–, pN0–pNX), Stage IIIA (pT1, LVI+, and/or pN+), and Stage IIIB (pT2, LVI+, and/or pN+).Results: Disease-free-interval, overall survival and specific survival significantly differed by histological stage. For specific survival, median survival times and hazard ratios (HR) by Cox proportional hazards regression (p < 0.0001) were: Stage 0 (median survival not reached; HR = 1.00; N = 89; 21% of the dogs), Stage I (1,720 days; HR = 3.05; p = 0.0018; N = 81; 19%), Stage II (1,181 days; HR = 4.39; p < 0.0001; N = 79; 18%), Stage IIIA (348 days; HR = 10.59; p < 0.0001; N = 79; 18%), and Stage IIIB (163 days; HR = 16.59; p < 0.0001; N = 105; 24%).Conclusion: The proposed histological staging system (invasiveness, pT, LVI, pN) is a very strong prognostic factor for CMCs.

Canine oral melanoma is the first malignancy of the oral cavity in dogs and is characterized by a local invasiveness and a high metastatic propensity. A better knowledge of genetic alterations is expected to improve management of this tumour. Copy number alterations are known characteristics of mucosal melanomas both in dogs and humans. The goal of this study was to explore the prognostic value of somatic focal amplifications on chromosomes (Canis Familiaris [CFA]) 10 and 30 in canine oral melanoma. The cohort included 73 dogs with oral melanoma confirmed by histology, removed surgically without adjuvant therapy and with a minimal follow-up of 6 months. Epidemiological, clinical and histological data were collected and quantitative-PCR were performed on formalin-fixed paraffin-embedded (FFPE) samples to identify specific focal amplifications. The 73 dogs included in the study had a median survival time of 220 days. Focal amplifications on CFA 10 and 30 were recurrent (49.3% and 50.7% of cases, respectively) and CFA 30 amplification was significantly associated with the amelanotic phenotype (P = .046) and high mitotic index (MI; P = .0039). CFA 30 amplification was also linked to poor prognosis (P = .0005). Other negative prognostic factors included gingiva location (P = .003), lymphadenomegaly (P = .026), tumour ulceration at diagnosis (P = .003), MI superior to 6 mitoses over 10 fields (P = .001) and amelanotic tumour (P = .029). In multivariate analyses using Cox proportional hazards regression, CFA 30 amplification (Hazard ratio [HR] = 2.08; P = .011), tumour location (HR = 2.20; P = .005) and histological pigmentation (HR = 1.87; P = .036) were significantly associated with shorter survival time. Focal amplification of CFA 30 is linked to an aggressive subset and constitutes a new prognostic factor.

Background: Feline mammary carcinomas (FMCs) are characterized by a high frequency of metastatic spread. The clinical TNM (Tumor, Node, Metastasis) system is used to describe local, regional, and distant tumor extent within the patient, but few publications confirmed its association with survival in cats with FMC. The purpose of this study was to determine if the histological staging system proposed for dogs in part 1 of this article had significant association with prognosis in cats.Materials and Methods: This retrospective study included 395 female cats with a surgically removed mammary carcinoma, with a 2-year follow-up. Invasiveness (distinction between in situ and invasive FMCs), the pathologic tumor size (pT), lymphovascular invasion (LVI), and the pathologic nodal stage (pN) defined a 5-stage system: Stage 0 (FMCs in situ), Stage I (pT1, LVI–, pN0–pNX), Stage II (pT2, LVI–, pN0–pNX), Stage IIIA (pT1, LVI+ and/or pN+), and Stage IIIB (pT2, LVI+ and/or pN+), where pT1 was ≤20 mm, pT2 was >20 mm, and pNX corresponded to unsampled draining lymph node.Results: Higher histological stages were associated with reduced disease-free interval, overall survival, and specific survival. For cancer-specific survival, by univariate analysis (p < 0.0001), median survival times and 1-year specific survival rates (1ySSR) were: stage 0 (1484 days; 1ySSR = 85%; N = 55; 14% of the cats), stage I (808 days; 1ySSR = 76%; N = 103; 26%), stage II (377 days; 1ySSR = 51%; N = 56; 14%), stage IIIA (448 days; 1ySSR = 60%; N = 83; 21%), and stage IIIB (207 days; 1ySSR = 29%; N = 98; 25%). The histological stages were also associated with specific survival by multivariate analysis (Hazard Ratio (HR) = 2.72 for stage IIIB, HR = 1.76 for stage IIIA, HR = 1.50 for stage II compared with stage I), independently of Progesterone Receptor expression (HR = 0.34 for PR+ compared with PR– FMCs) and tumor-associated inflammation (HR = 1.33 when moderate to severe compared with absent to mild).Conclusion: A same histological staging system could be applied in dogs and cats with mammary carcinoma to refine prognosis assessment. In the near future, a preoperative complete tumor clinical staging and treatment based on the published standard of care should be performed in order to better validate the histological staging system here proposed.

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A 5-y-old female Golden Retriever was presented with a 2-wk history of hyporexia, vomiting, diarrhea, lethargy, weight loss, polyuria, and polydipsia. Clinical examination and ultrasonography revealed multiple organ enlargement with gallbladder and kidney nodules suggestive of disseminated neoplasia. Hematologic and biochemical analyses revealed pancytopenia, hypercalcemia, and monoclonal IgA gammopathy suspicious for a plasma cell neoplasm. Bone marrow and blood smear examination revealed neoplastic atypical cells highly suggestive of lymphoid origin. Autopsy confirmed the presence of homogeneous white masses and multifocal pale infiltrates in the spleen, kidney, small intestine, gallbladder, and urinary tract. Histologic features were consistent with a multicentric atypical plasma cell tumor. Tumor cells were negative for CD204, IBA-1, E-cadherin, CD3, CD5, CD79a, CD20, and PAX5, and positive for MUM1, consistent with plasma cell origin. The presence of > 20% of circulating blastic plasma cells was consistent with primary plasma cell leukemia with plasmablastic morphology, a disease rarely described in veterinary medicine.