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Lymph node (LN) metastasis in canine mast cell tumor (MCT) can affect prognosis and postsurgical treatment recommendations; however, routine histological single-section examination may underestimate the incidence of metastases. This prospective study aimed at determining whether longitudinal step-sectioning of the entire LN allows for a more reliable detection of metastases. Dogs with MCT undergoing resection of the primary tumor and regional lymphadenectomy were enrolled. Formalin-fixed LNs were bisected longitudinally, both halves were embedded in paraffin and histological sections prepared at 200 μm steps. The nodal mast cells were classified according to the Weishaar classification. First-section evaluation (FSE; ie, examination of the first section obtained from the blocks) and whole LN step-section evaluation (SSE) were compared. Fifty-eight LNs were included. The median number of sections per LN was 6 (range, 3–28). FSE with toluidine blue (TB) revealed 27 (47%) nonmetastatic (HN0), 14 (24%) premetastatic (HN1), 9 (15%) early metastatic (HN2), and 8 (14%) overtly metastatic (HN3) LNs. SSE with TB resulted in upgrading the LN status in 2 cases (HN2 to HN3; HN0 to HN1). Evaluation of the first section plus an additional step-section resulted in 100% accuracy. Compared with SSE with TB, the accuracy of FSE with HE was 98% for HN3 LNs and 74% for HN2 LNs. FSE appears to reliably allow for the detection of LN metastasis in MCT, although examination of a further parallel section at a 200 μm step may increase the accuracy. A metachromatic stain is recommended for the identification of early metastases.

In canine cutaneous mast cell tumours (cMCTs), histologic grade and clinical stage are the most important prognostic factors, with high-grade tumours and metastatic lymph nodes (LNs) significantly influencing the evolution of disease. However, it is uncertain whether histologic grade and clinical stage should be given equal weighting value in patient prognostication and management. Dogs with low- and high-grade cMCTs and at least one overtly metastatic sentinel LN undergoing standardized treatment, consisting of surgical excision of the cMCT, lymphadenectomy and chemotherapy, were retrospectively included. The aim was to determine whether, at the same clinical stage, histologic grade retained prognostic relevance. Sixty dogs were included: 26 had a high-grade cMCT tumour and 34 had a low-grade cMCT. Median follow-up was 367 days (range, 187-748) in the high-grade group, and 1208 days (range, 180-2576) in the low-grade group. Median time to progression was significantly shorter in the high-grade group than in the low-grade group (214 days versus not reached; p .001), as well as tumour-specific survival (545 days versus not reached; p .001). On multivariable analysis, a high histologic grade and incomplete margins retained prognostic significance for both tumour progression and tumour-specific death. In dogs with cMCT and at least one overtly metastatic LN undergoing multimodal treatment, histologic grade significantly correlated with outcome. Overall prognosis was not unfavourable, even in the high-grade group, further supporting that a multimodal therapeutic approach, addressing primary tumour and sentinel LN, should be offered. Whether chemotherapy should be incorporated in the therapeutic planning of low-grade cMCTs remains to be defined.

Feline oral squamous cell carcinoma (FOSCC) is a frequent and progressively invasive tumour. Early lesions are difficult to recognize based on the sole clinical examination and may be misinterpreted as non-neoplastic. Mutations of TP53 and epigenetic alterations of specific genes are present in FOSCC and may be early detected. Aim of this prospective study was to investigate the DNA methylation pattern of a 17-gene panel and TP53 mutational status of FOSCC cytological samples obtained by oral brushing. Results were compared with a control group, in order to validate this non-invasive procedure for the screening of FOSCC. In FOSCC, the same analyses were carried out on the corresponding histological sample, if available. Thirty-five FOSCC and 60 controls were included. Mutations of TP53 were detected in 17 FOSCC brushings (48%) and in none of the controls (P

Platelet-derived growth factor signalling pathways play a fundamental role in inducing and sustaining the proliferative and prosurvival stimuli in canine osteosarcomas (cOSAs). The increased expression of platelet-derived growth factor receptors (PDGFRs) α and β, and their cognate ligands, were almost invariably observed in cOSAs and OSA-derived cell lines. In particular, overexpression of PDGFRβ-mediated signalling pathways was found in both the tumour microenvironment, where it drives stromal cell recruitment, and in neoangiogenesis, such as in tumour cells where it triggers aberrant proliferation, migration and local invasion. The majority of the pathological consequences of PDGFRβ signalling are because of aberrant expression. In fact, epigenetic dysregulation of oncogenes throughout demethylation of their promoter has emerged as a pivotal mechanism driving oncogenesis. The aim of this study was to assess the methylation status of the PDGFRβ promoter and to clarify its role in modulating the expression of the tyrosine kinase receptor in canine osteosarcoma. The CpG island of the PDGFRβ promoter was identified using a mixed in silico and experimental approach, and a method based upon the methylation-sensitive high-resolution melting assay for quantitatively and precisely assessing the methylation status of the promoter was then set up. The method herein described was then exploited to assess the methylation status of the promoter in a case series of cOSAa. COSAs consistently but variably expressed PDGFRβ. However, the promoter was almost completely demethylated, and its methylation status did not correlate with the expression levels. This finding supported the hypothesis that post-transcriptional regulatory mechanisms may act in cOSAs.

OBJECTIVE To determine an optimal time interval between amputation and initiation of adjuvant chemotherapy (TIamp-chemo) in dogs with appendicular osteosarcoma without distant metastases and whether TIamp-chemo was associated with outcome. ANIMALS 168 client-owned dogs treated at 9 veterinary oncology centers. PROCEDURES Data were collected from the dogs’ medical records concerning potential prognostic variables and outcomes. Dogs were grouped as to whether they received chemotherapy within 3, 5, 7, 10, 15, 20, 30, or > 30 days after amputation of the affected limb. Analyses were performed to identify variables associated with time to tumor progression and survival time after limb amputation and to determine an optimal TIamp-chemo. RESULTS Median TIamp-chemo was 14 days (range, 1 to 210 days). Median time to tumor progression for dogs with a TIamp-chemo ≤ 5 days (375 days; 95% CI, 162 to 588 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (202 days; 95% CI, 146 to 257 days). Median overall survival time for dogs with a TIamp-chemo ≤ 5 days (445 days; 95% CI, 345 to 545 days) was significantly longer than that for dogs with a TIamp-chemo > 5 days (239 days; 95% CI, 186 to 291 days). CONCLUSIONS AND CLINICAL RELEVANCE Findings indicated that early (within 5 days) initiation of adjuvant chemotherapy after limb amputation was associated with a significant and clinically relevant survival benefit for dogs with appendicular osteosarcoma without distant metastases. These results suggested that the timing of chemotherapy may be an important prognostic variable.

Surgery-induced stress and anesthesia-related immunosuppression are believed to play a critical role in human oncology patients. Studies have hypothesized that anesthesia influences patients' outcome, promoting tumor recurrence and metastasis. Aim of the study was to investigate whether anesthesia promoted relapse in dogs with diffuse large B-cell lymphoma (DLBCL). Medical records were searched for dogs with DLBCL, that were in complete remission (CR) after the same chemo-immunotherapy protocol. Dogs receiving anesthesia were included if the procedure was performed while in CR. Time to relapse (TTR) was obtained via Kaplan–Meier method. Association between anesthesia and relapse was assessed using a nested case-control design and estimated using conditional logistic regression. Sixty-one dogs with DLBCL were included. Overall median TTR was 329 days (95% CI, 281–377). Forty-eight (79%) dogs relapsed during the study period, while 13 (21%) were still in CR at data analysis closure. Eighteen (30%) dogs received anesthesia with opioids, propofol, and isoflurane or sevoflurane. The relative risk of lymphoma relapse for dogs undergoing anesthesia was significantly higher compared with dogs not undergoing anesthesia, with an odds ratio of 3.09 (P = 0.019) on multivariable analysis. Anesthesia may promote relapse in dogs with DLBCL treated with chemo-immunotherapy, although a role of perioperative stress cannot be ultimately excluded. Considering the high frequency of anesthetic procedures required for diagnostic and therapeutic protocols among oncology patients, it is of utmost interest to characterize the effects of single anesthetic agents on the immune system. Further prospective studies are needed to better define the impact of anesthesia on patients' outcome.

Localized histiocytic sarcoma may occur as a primary lesion in periarticular tissues of large appendicular joints. Treatment options for the primary lesion include radical surgical excision, radiation therapy (RT), or both, in combination with chemotherapy for potential systemic metastases. In an effort to better characterize the time to progression (TTP) following surgical vs non-surgical approaches for periarticular histiocytic sarcoma (PAHS), a contemporary European population of affected dogs was retrospectively surveyed. Medical records were queried for newly-diagnosed PAHS cases undergoing surgery (predominantly limb amputation) or RT followed by systemic chemotherapy. Of 49 dogs, 34 underwent RT and 15 underwent surgery. All dogs received adjuvant chemotherapy. There was no statistically significant difference in TTP or overall survival between groups. The median TTP was 336 days for the operated dogs and 217 days for the irradiated dogs (P = .117). The median overall survival time was 398 days for the operated dogs and 240 days for the irradiated dogs (P = .142). On multi-variable analysis, the variables significantly associated with an increased risk of both tumour progression and tumour-related death were regional lymph node and distant metastasis at admission. Survival and local control rates following RT may be comparable to radical resection. These data may better inform shared decision-making processes between multi-disciplinary care providers and owners.

Objectives The aim of this study was to evaluate the relationship between the ultrasonographic (US) diffuse honeycomb pattern (HCP) of the spleen and a pathological diagnosis in cats, and to assess the influence of transducer type on HCP visualisation. Methods Abdominal ultrasounds of cats with an HCP were reviewed and splenic size, shape, margination, other parenchymal alterations and splenic hilar lymphadenopathy were recorded. When applicable, images acquired with high-frequency linear and curvilinear transducers were compared to determine if an HCP was more frequently demonstrated on high-resolution images. A retrospective review of the corresponding splenic cytohistopathological samples was also performed. Results Thirty-three cats met the inclusion criteria. Five cases were diagnosed by histology and 28 by cytology, confirmed by PCR for antigen receptor rearrangements (PARR) in uncertain cases. There were 15 cases of lymphoid hyperplasia, eight cases of lymphoma (four B cell, three T cell and one large granular lymphocytes), six cats with splenitis, three with extramedullary haematopoiesis and one with histiocytic sarcoma. The prevalence of lymphoma in cats with an HCP of the spleen was 24%. Splenomegaly was the most frequent US feature associated with an HCP and was observed in all lymphoma cases. In the images obtained from both high-frequency linear and micro-convex transducers the visualisation of an HCP was enabled in all cases (24/24) and in 62.5% (15/24), respectively. Conclusions and relevance: Based on our findings, a US HCP of the spleen in cats can be associated with benign and malignant disorders and is infrequently associated with lymphoma in comparison with dogs. Cytological or histological examination, possibly supplemented by PARR, should always be performed for diagnostic support. Use of high-frequency linear transducers is recommended to properly recognise an HCP or subtle changes in splenic parenchyma.

Treatment options for dogs with metastatic (stage III) splenic hemangiosarcoma are limited. A doxorubicin-based chemotherapy regimen is commonly administered; however, there are no published data to support this practice. The aim of this study was to investigate the impact of maximum-tolerated-dose chemotherapy (MTD), metronomic chemotherapy (MC) and no adjuvant treatment on outcome in dogs with stage III splenic hemangiosarcoma undergoing splenectomy. Medical records of dogs with stage III splenic hemangiosarcoma that underwent splenectomy followed by MTD chemotherapy, MC or no adjuvant treatment were retrieved. Time to progression (TTP), survival time (ST) and toxicity were evaluated. One hundred three dogs were identified: 23 received adjuvant MTD, 38 MC and 42 were not medically treated. Overall median TTP and ST were 50 (95% confidence interval [CI], 39-61) and 55 days (95% CI, 43-66), respectively. Dogs treated with adjuvant MTD had a significantly longer TTP and ST compared with dogs receiving MC (median TTP, 134 vs 52 days, P = .025; median ST, 140 vs 58 days, P = .023, respectively). Dogs treated by splenectomy only had the shortest median TTP (28 days) and ST (40 days). However, treatment-related adverse events (AEs) were significantly more frequent in the MTD group (P = .017). The outcome for dogs with metastatic splenic hemangiosarcoma is poor. While MTD showed greater efficacy compared to MC, toxicity was higher in this group. Treatment-related AEs need to be carefully balanced against this modest survival prolongation when offering adjuvant MTD to dogs with advanced stage hemangiosarcoma.

In dogs, digit squamous cell carcinoma (SCC) is uncommon. Clinical signs are frequently underestimated, leading to a diagnostic delay. The purpose of this retrospective study was to report our experience regarding the clinical presentation, diagnostic work-up, treatment and outcome of 79 client-owned dogs with SCC of the digit. The greatest majority (84.8%) of dogs was dark-coated. Schnauzers represented approximately one third of the study population, and had a poorer outcome compared with other breeds. The majority of SCCs occurred in the front limbs (61%), and bone lysis was frequently observed (92.4%). Approximately 9% of dogs had involvement of multiple digits, and this was associated with a shorter time to progression (TTP; P = 0.047). Similarly, a duration of clinical signs >90 days was associated with a shorter TTP (P = 0.02). Regional lymph node metastases were documented in 17.7% of dogs at admission and were significantly associated with tumor-related death (P < 0.001). At presentation, none of the dogs had evidence of distant metastasis. Digit amputation achieved adequate local tumor control in the majority of cases. Adjuvant chemotherapy and radiation therapy were carried out in 21.5% of cases, with uncertain benefit. Due to the relatively non-aggressive clinical behavior of digit SCC, chemotherapy should only be offered in the case of metastatic disease. Approximately one fourth of dogs developed de novo SCCs during the follow-up. Careful examination of the digits should be encouraged in breeds considered at high risk and in dogs with a previous history of digital SCC.

Post-treatment outcome in canine glial tumours is described with a broad range of survival times between 2 and 28 months. After surgery or radiation therapy, the tumours may progress locally or spread within the central nervous system. It is unknown if tumour- or patient-specific factors influence prognosis. In humans, glioblastoma involving the subventricular zone has been found to recur distantly, with shortened time to progression and overall survival. We included 32 dogs irradiated for a presumptive primary glial brain tumour in this retrospective cohort study. Tumours were grouped relative to subventricular zone contact and overt ventricular invasion assessing pre-treatment magnetic resonance images. Median time to progression (TTP) for all cases was 534 days (95%CI, 310–758), with a significantly shorter TTP in dogs with lesions at the subventricular zone (median TTP, 260 vs. 687 days; p=.049). Tumours at the subventricular zone progressed more often (p=.001), and more likely as CNS-metastasis (52.9% vs. 13.3%, p=.028). Median overall survival (OS) was 489 days (95%CI, 147–831) and median tumour-specific survival 609 days (95%CI, 382–835). Involvement of the subventricular zone was significantly associated with a shorter tumour-specific survival (median, 306 vs. 719 days; p=.044). Glial tumours contacting the subventricular zone in dogs have a shorter tumour-specific survival and a higher rate of progression and CNS-metastasis. Despite local tumour control, metastasis must be considered and should prompt further treatment approaches.

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.

Objectives Feline chronic gingivostomatitis (FCGS) is an oral disease. Cats with FCGS experience intense oral pain. Some cats remain refractory to current therapies based on dental extraction and adjuvant medical treatment; it is therefore necessary to investigate alternative therapeutic targets involved in inflammatory mechanisms and pain, namely the endocannabinoid system (ECS). The present study investigated the expression of cannabinoid receptors type 1 (CB1R) and 2 (CB2R), and cannabinoid-related receptors G protein-coupled receptor 55 (GPR55), transient receptor potential ankyrin 1 (TRPA1) and serotonin 1a receptor (5-HT1aR), in the oral mucosa of healthy cats to determine whether there was altered expression and distribution in cats with FCGS. Methods Samples of caudal oral mucosa were collected from eight control cats (CTRL cats) and from eight cats with FCGS (FCGS cats). Tissue samples were processed using an immunofluorescence assay with cat-specific antibodies, and the immunolabelling of the receptors studied was semiquantitatively evaluated. Results The mucosal epithelium of the CTRL cats showed CB1R, TRPA1 and 5-HT1aR immunoreactivity (IR), while CB2R and GPR55 IR were generally not expressed. In the CTRL cats, the subepithelial inflammatory cells expressed CB2R, GPR55 and 5-HT1aR IR. In the FCGS cats, all the receptors studied were markedly upregulated in the epithelium and inflammatory infiltrate. Conclusions and relevance Cannabinoid and cannabinoid-related receptors are widely expressed in the oral mucosa of healthy cats and are upregulated during the course of FCGS. The presence of cannabinoid and cannabinoid-related receptors in healthy tissues suggests the possible role of the ECS in the homeostasis of the feline oral mucosa, while their overexpression in the inflamed tissues of FCGS cats suggests the involvement of the ECS in the pathogenesis of this disease, with a possible role in the related inflammation and pain. Based on the present findings, ECS could be considered a potential therapeutic target for patients with FCGS.

A 4-year-old intact female domestic short-haired cat was referred for recommendations about adjuvant medical treatment 1month after left forelimb amputation due to periarticular histiocytic sarcoma (HS). At presentation, physical abnormalities were limited to enlarged ipsilateral superficial cervical and axillary lymph nodes. Routine blood analysis, abdominal ultrasound, and thoracic radiology were unremarkable. The cat initially received lomustine without any adverse events. Four weeks later, the cat developed severe acute respiratory distress. Results of thoracic radiographs and transthoracic echocardiographic analysis were suggestive of pulmonary and heart metastasis. Due to the cat's poor clinical condition and prognosis, the owner elected euthanasia, and a necropsy was performed. Based on gross pathology, histopathology, and immunohistochemistry, an HS with nodal, renal, pulmonary, and heart (right auricular and right ventricular) metastases was diagnosed. This case represents the first description of HS with a heart metastasis in a cat, providing further insight into the clinical course and metastatic behavior of this rare malignant neoplasm. Clinicians should be aware of this site of metastasis and consider HS in the list of differential diagnoses for secondary heart tumors in cats.

Recent literature suggests a combination of flow cytometric determination of Ki‐67 and immunophenotype as a reliable tool to classify canine lymphomas. Immunohistochemistry (IHC) on histological samples is the gold standard technique assessing Ki‐67 index. Agreement between IHC and FCM derived Ki‐67 indices has never been investigated. The aim of this study was to investigate the agreement between IHC and FCM in the assessment of Ki‐67 expression/index, in order to evaluate whether FCM may serve as a non‐invasive alternative method for the estimation of proliferative activity in canine lymphoma. Dogs with previously untreated canine lymphoma undergoing diagnostic lymphadenectomy were prospectively enrolled. Ki‐67 expression/index was assessed by FCM and IHC and expressed as percentage of positive cells. 39 dogs classified by histopathology matched the inclusion criteria. With both methods, Ki‐67 expression/index was higher in intermediate/high‐grade lymphomas. Spearman's coefficient of correlation was ρ = 0.57; (95% CI0.33‐0.75) suggesting a moderate correlation. A Bland‐Altman plot revealed a negative constant bias of −3.55 (95% CI: −10.52 to 3.42) with limits of agreement from −45.71 to 38.61. The study confirmed agreement albeit with wide confidence intervals between the values of Ki‐67 expression/index assessed with FCM and IHC. Discrepancies were observed in a subset of cases. Possible explanation could be that Ki‐67 index in IHC is determined in the most proliferative areas of the slide, which could introduce kind of sampling bias, whereas FCM evaluates many more cells in cell suspension. Further studies are warranted to investigate this phenomenon.

Unresectable nodular and diffuse hepatocellular carcinoma (HCC) have a poor prognosis with limited treatment options. Systemic traditional chemotherapy has been only rarely reported, with unsatisfactory results. The aim of this prospective, non-randomized, non-blinded, single center clinical trial was to investigate safety profile, objective response rate, time to progression and overall survival of sorafenib in comparison with metronomic chemotherapy (MC) consisting of thalidomide, piroxicam and cyclophosphamide in dogs with advanced, unresectable HCC. Between December 2011 and June 2017, 13 dogs were enrolled: seven received sorafenib, and six were treated with MC. Median time to progression was 363 days (95% CI, 191&ndash, 535) in dogs treated with sorafenib versus 27 days (95% CI, 0&ndash, 68) in dogs treated with MC (p = 0.044). Median overall survival was 361 days (95% CI, 0&ndash, 909) in dogs receiving sorafenib, while 32 days (95% CI, 0&ndash, 235) in those receiving MC (p = 0.079). Sorafenib seems to be a good candidate for the treatment of dogs with advanced HCC, due to a benefit in disease control and an acceptable safety profile, offering a good basis on which new randomized prospective clinical trials should be undertaken to compare the efficacy and drawback of sorafenib versus MC or traditional chemotherapy.

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

Lymph node (LN) metastasis is a negative prognostic factor in dogs with cutaneous mast cell tumours (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 multicentre 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 analysing 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 follow-up time for medically treated dogs was 619 days: two experienced local recurrence, three nodal relapse and four 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 = .021). A similar tendency was observed for overall survival (P = .056). The current study shows that dogs with low-grade cMCTs, that undergo surgical excision of the primary tumour and elective lymphadenectomy of the HN2 regional LN harbour 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.

Airway remodeling encompass structural changes that occur as the result of chronic injury and lead to persistently altered airway structure and function. Although this process is known in several human respiratory conditions such as asthma and chronic obstructive pulmonary disease (COPD), airway remodeling is poorly characterized in the feline counterpart. In this study, we describe the spontaneous pulmonary changes in 3 cats paralleling the airway remodeling reported in humans. We observed airway smooth muscle cells (ASMCs) hyperplasia (peribronchial and interstitial), airway subepithelial and interstitial fibrosis, and vascular remodeling by increased number of vessels in the bronchial submucosa. The hyperplastic ASMCs co-expressed α-SMA, vimentin and desmin suggesting that vimentin, which is not normally expressed by ASMCs, may play a role in airway thickening, and remodeling. ASMCs had strong cytoplasmic expression of TGFβ-1, which is known to contribute to tissue remodeling in asthma and in various bronchial and interstitial lung diseases, suggesting its involvement in the pathogenesis of ASMCs hyperplasia. Our findings provide histologic evidence of airway remodeling in cats. Further studies on larger caseloads are needed to support our conclusions on the value of this feline condition as an animal model for nonspecific airway remodeling in humans.

Background Melanomas are rare in cats. The eye is the most commonly involved site, whereas few data are available about feline non-ocular melanomas (NOMs). Ki-67 thresholds with prognostic relevance have been established for canine melanomas, but not in cats. This study was undertaken to investigate the relationship between Ki-67 index, tumour characteristics, and clinical outcome in feline NOMs. Histologic samples were retrospectively reviewed. Amelanotic tumours were admitted upon immunohistochemical positivity for Melan A or S100. Evaluated parameters included morphological diagnosis, histotype, junctional activity, degree of pigmentation, vascular invasion, lymphocytic infiltrate, necrosis, mitotic count (MC) and Ki-67 index. Pigmented tumours were bleached before evaluation. Clinical and follow-up information were retrieved via telephone interviews with the referring veterinarians. Results Fifty tumours located in skin (n = 33) and mucosae (n = 17) were included. Forty-eight percent and 95% of amelanotic tumours (n = 21) stained positive for Melan A and S100, respectively. Most achromic tumours were mucosal (P 5, Ki-67 > 20% and lack of treatment administration. On multivariable analysis, only tumour histotype and treatment retained prognostic significance. Conclusions Although the majority of feline NOMs behave aggressively, Ki-67 index, together with other parameters, may contribute to prognostic assessment. Prospective studies on homogeneous populations are warranted to identify reliable threshold values for this marker.

Mast cell tumours (MCTs) are often diagnosed by cytology based on the identification of purple intracytoplasmic granules with methanolic Romanowsky stains, including May-Grünwald-Giemsa (MGG). In clinical practice, aqueous rapid stains (RS) are commonly used, but mast cell granules may not stain properly. Aim of this prospective study was to investigate the frequency of MCT hypogranularity with RS and its potential implications in tumour identification, cytological grading assessment and recognition of nodal metastatic disease. Cytological preparations of canine primary MCTs and metastatic lymph nodes with subsequent histopathological confirmation were included. For each case, good-quality smears were stained with both MGG and RS and comparatively assessed. Eleven of 60 (18.3%) primary MCTs were hypogranular with RS; 9 of them were histologically high-grade tumours and in 3 cases (5%) a definitive MCT diagnosis could not be made. Accuracy in cytological grading assessment (85%) did not differ between RS and MGG. Thirteen of 28 (46.4%) metastatic lymph nodes were hypogranular with RS and 3 independent observers failed to identify nodal MCT metastases in 7% to 18% of RS-stained smears. This study confirms that, in limited cases, RS can be ineffective in staining MCT granules, particularly in high-grade tumours, thus making diagnosis more dependent on experience and quality of preparations. In dubious cases, methanolic stains should be applied. The use of RS is discouraged for the search of nodal metastases, as the identification of isolated mast cells can be more challenging.

Feline large granular lymphocyte (LGL) lymphoma is an uncommon subtype of lymphoma characterized by a grave prognosis and scarce response to chemotherapy. There are limited reports on clinico-pathological and prognostic factors. One-hundred and 9 cats with newly diagnosed LGL lymphoma that underwent initial staging (including hematology, serum biochemistry, thoracic radiographs and abdominal ultrasound), and followed-up were retrospectively evaluated. LGL lymphoma was localized within the gastrointestinal tract with or without extra-intestinal involvement in 91.7% of the cases, and at extra-gastrointestinal sites in 8.3%. Symptoms were frequent. Anemia (31.2%) and neutrophilia (26.6%) were commonly observed, and 14 (12.8%) cats had neoplastic circulating cells. Frequent biochemistry abnormalities included elevated ALT (39.4%) and hypoalbuminemia (28.4%). Twenty (54.1%) of 37 cats had elevated serum LDH. Treatment varied among cats, and included surgery (11%), chemotherapy (23%), corticosteroids (38.5%) and no treatment (27.5%). Median time to progression (MTTP) was 5 days, and median survival time (MST) 21 days. MST was significantly shorter in the case of substage b, circulating neoplastic cells, lack of chemotherapy administration, and lack of treatment response. A small subset of cats (7.3%) survived more than 6 months, suggesting that a more favorable clinical course can be found among LGL lymphoma patients.

Background Osteosarcoma (OSA) should be differentiated from other less frequent primary bone neoplasms, metastatic disease, and tumor-like lesions, as treatment and prognosis can vary accordingly. Hence, a preoperative histologic diagnosis is generally preferred. This requires collection of multiple biopsies under general anesthesia, with possible complications, including pathological fractures. Fine-needle aspiration cytology would allow an earlier diagnosis with a significant reduction of discomfort and morbidity. Hypothesis/Objectives The aim of this study was to compare the accuracy of cytological and histologic biopsies in the diagnosis of canine osteodestructive lesions. Animals Sixty-eight dogs with bone lesions. Methods Retrospective study. Accuracy was assessed by comparing the former diagnosis with the final histologic diagnosis on surgical or post-mortem samples or, in the case of non-neoplastic lesions, with follow-up information. Results The study included 50 primary malignant bone tumors (40 OSAs, 5 chondrosarcomas, 2 fibrosarcomas, and 3 poorly differentiated sarcomas), 6 carcinoma metastases, and 12 non-neoplastic lesions. Accuracy was 83% for cytology (sensitivity, 83.3%; specificity, 80%) and 82.1% for histology (sensitivity, 72.2%; specificity, 100%). Tumor type was correctly identified cytologically and histologically in 50 and 55.5% of cases, respectively. Conclusions and Clinical Importance The accuracy of cytology was similar to histology, even in the determination of tumor type. In no case was a benign lesion diagnosed as malignant on cytology. This is the most important error to prevent, as treatment for malignant bone tumors includes aggressive surgery. Being a reliable diagnostic method, cytology should be further considered to aid decisions in the preoperative setting of canine bone lesions.

The aim of this study was to re-evaluate archived samples of canine soft tissue sarcomas (STSs) morphologically consistent with peripheral nerve sheath tumors (PNSTs). In each case, an immunohistochemical panel was applied, including α-SMA, calponin, desmin, S-100, GFAP, NSE and Olig2, in order to assess whether the phenotype was consistent with the tumor histological appearance. Additionally, the expression of EGFR, a marker with potential therapeutic implications in malignant PNSTs, was evaluated. Twenty-one tumors were included. Fourteen cases (66.7%) were positive for one or more muscular markers and were reclassified as perivascular tumors (PWTs). A positive labeling for S-100 was observed in one tumor (4.8%), thus classifi ed as PNST. The other 6 tumors were generically classified as poorly differentiated STSs. No unique histopathological feature was observed within the three groups. NSE and Olig2 labeling was aspecific and not useful for diagnostic purposes. GFAP was negative in all cases. Six cases (28.6%) were positive for EGFR, including the PNST. Even after the application of a wide immunohistochemical panel, distinguishing between PNSTs and PWTs remains a challenge. Finally, a subgroup of cases cannot be classified based on light microscopy alone.

A better understanding of the CT features of different forms of canine and feline adipose tumors would be valuable for improving patient management and treatment. The purpose of this retrospective, cross-sectional study was to describe and compare the CT features of pathologically confirmed lipomas, infiltrative lipomas, and liposarcomas in a sample of canine and feline patients. A total of 50 animals (46 dogs, four cats) and a total of 60 lesions (23 lipomas, 20 infiltrative lipomas, and 17 liposarcomas) were included in the study. Lipomas appeared as round to oval-shaped (n = 21), well-marginated (n = 20) fat-attenuating lesions. Infiltrative lipomas appeared as homogeneous, fat-attenuating masses but, unlike lipomas, they were most commonly characterized by an irregular shape (75%; P < 0.001), and linear components, hyperattenuating relative to the surrounding fat (100%; P < 0.05). Liposarcomas were represented exclusively by heterogeneous lesions with soft tissue attenuating components with a multinodular appearance (76.5%; P < 0.05). Regional lymphadenopathy (n = 10) and amorphous mineralization (n = 4) were also observed in association with liposarcomas. Computed tomography can provide useful information regarding disease location, extent, and involvement of the adjacent structures. Tumor definition and shape were the most useful parameters to differentiate between lipomas and infiltrative lipomas. The presence of a heterogeneous mass, with a multinodular soft tissue component and associated regional lymphadenopathy and mineralization, were features favoring a diagnosis of liposarcoma.

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.