Lymph node (LN) metastasis is a negative prognostic factor in dogs with cutaneous mast cell tumors (cMCTs). While elective lymphadenectomy of metastatic LNs improves outcome, the benefit of adjuvant medical therapy in dogs with early metastatic (HN2) LNs is debated. The aim of this retrospective multicenter study was to evaluate the therapeutic benefit of adjuvant medical therapy following surgical removal of the primary low-grade cMCT (Patnaik grade 1-2 and Kiupel low-grade) and lymphadenectomy of HN2 LNs by analyzing survival rates and patterns of recurrence.Seventy-three dogs were included: 42 received adjuvant medical treatment (chemotherapy and/or kinase inhibitors), and 31 did not. The median followup time for medically-treated dogs was 619 days: 2 experienced local recurrence, 3 nodal relapse and 4 distant relapse.For dogs undergoing surgery only, the median follow-up time was 545 days.None of them experienced local recurrence, nodal or distant relapse. Time to progression was significantly shorter in dogs receiving adjuvant medical treatment (P = 0.021). A similar tendency was observed for overall survival (P = 0.056).The current study shows that dogs with low-grade cMCTs, that undergo surgical excision of the primary tumor and elective lymphadenectomy of the HN2 regional LN harbor a good prognosis. The use of adjuvant medical treatment in these dogs does not seem to provide any benefit in terms of progression and survival.

Squamous cell carcinoma is the most common malignant oral tumor in cats. The late presentation is one of the factors contributing to the detrimental prognosis of this disease. The immunohistochemical expression of the p53 tumor suppressor protein has been reported in 24% to 65% of feline oral squamous cell carcinomas, but no study has systematically evaluated in this tumor the presence of p53 encoding gene ( TP53 ) mutations. The aim of this retrospective study was to determine whether p53 immunohistochemistry accurately reflects the mutational status of the TP53 gene in feline oral squamous cell carcinoma. Additionally, the prevalence of p53 dysregulation in feline oral squamous cell carcinoma was compared with that of feline non-neoplastic oral mucosa, in order to investigate the relevance of these dysregulations in cancer development. The association between p53 dysregulations and exposure to environmental tobacco smoke and tumor characteristics was further assessed. Twenty-six incisional biopsies of oral squamous cell carcinomas and 10 cases each of lingual eosinophilic granuloma, chronic gingivostomatitis and normal oral mucosa were included in the study. Eighteen squamous cell carcinomas (69%) expressed p53 and 18 had mutations in exons 5–8 of TP53 . The agreement between immunohistochemistry and mutation analysis was 77%. None of non-neoplastic oral mucosa samples had a positive immunohistochemical staining, while one case each of eosinophilic granuloma and chronic gingivostomatitis harbored TP53 mutations. Unlike previously hypothesized, p53 dysregulations were not associated with exposure to environmental tobacco smoke. These results suggest an important role of p53 in feline oral tumorigenesis. Additionally, the immunohistochemical detection of p53 expression appears to reflect the presence of TP53 mutations in the majority of cases. It remains to be determined if the screening for p53 dysregulations, alone or in association with other markers, can eventually contribute to the early detection of this devastating disease.

Canine splenic lymphoid nodules are currently classified as indolent lymphomas (marginal zone lymphoma [MZL], mantle cell lymphoma [MCL]) or nodular hyperplasia (lymphoid [LNH] or complex [CNH] type). Their differentiation can be difficult on morphology, because of similar histologic appearance and poorly defined diagnostic criteria. Thirty-five surgical samples of splenic lymphoid nodules were reviewed in order to assess the diagnostic contribution of immunophenotyping, proliferative activity and clonality (PARR) in differentiating between hyperplastic and neoplastic lesions. Proliferative activity was evaluated by double immunolabeling for Ki-67 and CD79a, in order to separately assess the proliferative activity of B cells and non-B cells. Definitive diagnoses were MZL ( n = 11), MCL ( n = 4), LNH ( n = 10), and CNH ( n = 10). The overall concordance between histology and PARR was above 90%. Lymphomas had a significantly higher percentage of CD79a-positive areas (mean, 36.30%; P = .0004) and a higher B-cell proliferative activity (median Ki-67 index, 5.49%; P = .0012). The threshold value most accurately predicting a diagnosis of lymphoma was ≥28% of B-cell areas, with a Ki-67 index above 3%. Dogs were monitored for a median follow-up time of 870 days (IQR, 569-1225), and no relapses were documented. Overall median survival time was 1282 days. The combination of histology, immunohistochemistry and PARR can improve the diagnostic accuracy for canine splenic lymphoid nodules, although the long-term behavior of these lesions appears similar.

Background While lymphadenectomy of metastatic lymph nodes (LNs) has been associated with improved outcome, the clinical utility of prophylactic lymphadenectomy in dogs with stage I cutaneous mast cell tumors (cMCTs) remains a controversial topic. To assess the therapeutic role of lymphadenectomy of uninvolved regional LNs, the long-term outcome of cMCT-bearing dogs with cytologically negative and surgically unresected regional LNs (observation only, OO) was compared with that of dogs with surgically resected and histologically negative regional LNs (prophylactic regional lymphadenectomy, PRL). Results A retrospective analysis of 64 dogs with a low-grade, completely resected stage I cMCT was performed: 35 (54.7%) dogs were subjected to OO and 29 (45.3%) underwent PRL. Dogs were monitored for a median of 813 and 763 days in the OO group and PRL group, respectively. The number of dogs undergoing MCT progression was significantly higher in the OO group (P = 0.028) and curve comparison revealed a tendency to a better time to progression in the PRL group (P = 0.058). No significant difference in survival time (P = 0.294) was observed between dogs in the OO and PRL groups. Conclusions Our results showed that lack of immediate lymphadenectomy was associated with a higher risk for tumor progression. This preliminary judgement, reinforced by the findings that lymphadenectomy was well tolerated in all cases, and that histopathology provides the definitive assessment of the nodal pathological status, may suggest that prophylactic lymphadenectomy is indicated in the management of stage I MCTs. Larger prospective studies are warranted for generating clinical evidence of this latter hypothesis.

Feline oral squamous cell carcinoma (FOSCC) is characterized by high local invasiveness and early bone lysis. The late diagnosis largely limits the efficacy of therapy and increases treatment-related morbidity. The aim of this exploratory study was to assess the methylation pattern of 10 candidate genes and TP53 mutational status in histologic samples of FOSCC. Results were compared with normal oral mucosa and oral inflammatory lesions, in order to establish a gene panel for FOSCC detection. For 10 cats, the above analyses were also performed on oral brushing samples, in order to explore the utility of these methods for screening purposes. Thirty-one FOSCC, 25 chronic inflammatory lesions and 12 controls were included. TP53 mutations were significantly more frequent in the FOSCC (68%) than in the non-neoplastic oral mucosa (3%; P <.001). Based on lasso regression analysis, a step-wise algorithm including TP53, FLI1, MiR124-1, KIF1A and MAGEC2 was proposed. The algorithm allowed to differentiate FOSCC with 94% sensitivity and 100% specificity (accuracy, 97%). When applying the proposed algorithm on 10 brushing samples, accuracy decreased to 80%. These results indicate that the altered DNA methylation of specific genes is present in FOSCC, together with a significant proportion of TP53 mutations. Such alterations are infrequent in normal oral mucosa and chronic stomatitis in cats, suggesting their involvement in feline oral carcinogenesis and their utility as diagnostic biomarkers. Further studies on a high number of brushing samples will be needed to assess the utility of a screening test for the early detection of FOSCC.