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Congenital tumours and tumour-like lesions represent a group of rare disorders in both veterinary and human medicine that arise from tissue remnants and are detected during pregnancy or within the first 2-3 months of life. Different forms of congenital tumours and congenital tumour-like lesions have been reported in calves and their development is poorly understood. They often pose a diagnostic challenge and the referring nomenclature occasionally may be equivocal. Previous reports regarding tumour-like lesions, soft tissue tumours, vascular tumours, round cell tumours and neoplasms of the nervous, peritoneum and urogenital systems are summarized in this review, and the role of genetic factors in the development of these conditions is discussed.

The assessment of prognostic markers is key to the improvement of therapeutic strategies for cancer patients. Some promising markers may fail to be applied in clinical practice, or some useless markers may be applied, because of misleading results ensuing from inadequate planning of the study and/or from an oversimplified statistical analysis. This commentary illustrates and discusses the main issues involved in planning an effective clinical study and the subsequent statistical analysis for the prognostic evaluation of a cancer marker. Another aim is to extend the most applied statistical models (ie, those using Kaplan-Meier and Cox) to enable the choice of the best-suited methods for study endpoints. Specifically, for tumor-centered endpoints like tumor recurrence, the issue of competing risks is highlighted. For markers measured on a continuous numerical scale, a loss of relevant prognostic information may occur by setting arbitrary cutoffs; thus, the methods to analyze the original scale are explained. Furthermore, because the P-value is not a sufficient criterion to assess the usefulness of a marker in clinical practice, measures for evaluating the ability of the marker to discriminate between “good” and “bad” prognoses are illustrated. Several tumor markers are considered both in human and veterinary medicine. Given the similarity between markers for human breast cancer and canine mammary cancer, an application of the statistical methods discussed within the article to a public dataset from human breast cancer patients is shown.

Tumor grading is a method to quantify the putative clinical aggressiveness of a neoplasm based on specific histological features. A good grading system should be simple, easy to use, reproducible, and accurately segregate tumors into those with low versus high risk. The aim of this review is to summarize the histological and, when available, cytological grading systems applied in veterinary pathology, providing information regarding their prognostic impact, reproducibility, usefulness, and shortcomings. Most of the grading schemes used in veterinary medicine are developed for common tumor entities. Grading systems exist for soft tissue sarcoma, osteosarcoma, multilobular tumor of bone, mast cell tumor, lymphoma, mammary carcinoma, pulmonary carcinoma, urothelial carcinoma, renal cell carcinoma, prostatic carcinoma, and central nervous system tumors. The prognostic relevance of many grading schemes has been demonstrated, but for some tumor types the usefulness of grading remains controversial. Furthermore, validation studies are available only for a minority of the grading systems. Contrasting data on the prognostic power of some grading systems, lack of detailed instructions in the materials and methods in some studies, and lack of data on reproducibility and validation studies are discussed for the relevant grading systems. Awareness of the limitations of grading is necessary for pathologists and oncologists to use these systems appropriately and to drive initiatives for their improvement.

This report describes an unusual mesenchymal differentiation in a canine benign mixed mammary tumour. A 13-year-old crossbreed female dog was submitted to surgery to remove an inguinal mammary nodule. The tumour was composed of mammary epithelium and mesenchymal populations, not only of cartilage and bone but also of myoid cells. PTAH demonstrated cross striation of striated muscle, and immunohistochemistry highlighted striated muscle expressing desmin and calponin, and smooth muscle expressing desmin, SMA, and calponin. The tumour was diagnosed as a benign mixed tumour with leio- and rhabdomyoid differentiation. There was no tumour recurrence after one year of clinical follow-up. In conclusion, the well-differentiated features of leiomyocytes and rhabdomyocytes and the growth pattern define the benign origin of the mesenchymal component, which has been confirmed by a benign outcome; therefore, the knowledge of this kind of differentiation is helpful to avoid misdiagnoses.

In a study aimed at identifying early biomarkers of renal rejection, a 4-month-old commercial gilt weighing 60 kg underwent unilateral nephrectomy and a subsequent renal transplantation. The study ...

Placenta is essential for the development of the fetus, and its impaired function can lead to a negative outcome (i.e., neonatal mortality). In dogs, investigations on placenta histology and neonatal outcome in healthy bitches are lacking, and a contribution is provided in this study to emphasize the use of placenta histology in practice. Fifty-one placentas from 11 litters were collected during cesarean section, classified according to the litter size (large (L) or small (S)) and the outcome, this latter as healthy (Group 1) or dead within 7 days (Group 2). The placenta/puppy weight ratio (PPR) was calculated, and specimens were formalin-fixed and paraffin-wax embedded, and on the resulting histological slides, capillary density (CD) was quantified. Among necrosis, calcification, and intravascular leucocytes, only the presence of multifocal-confluent necrosis (significantly more frequent in Group 2) was associated with a higher risk of death within 7 days (odds ratio = 30.7). Mixed logistic regression ruled out the effect on death both of a bitch and cesarean type (programmed vs. emergency). PPR and CD values were associated with litter size, large litters had lower PPR (p &lt, 0.01) and higher CD (p &lt, 0.05) than small litters. The relationship between PPR and CD was negative and significant (p &lt, 0.01). Necrosis was a frequent finding in canine placentas, but only when multifocal-confluent was it associated with a poor outcome. The litter size influenced PPR (lower in L) and CD (higher in L), and this is likely due to the plasticity of placenta adaptation.

Simple Summary Multidrug resistance of neoplastic cells to chemotherapeutic drugs is a phenomenon mediated by several molecular mechanisms. Among these, P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) counteract the intracellular load of multiple drugs, preventing their efficacy. The basal (intrinsic) cellular expression can be further stimulated by drug exposure. P-gp and BCRP are a subject of intense investigation both in human and veterinary oncology since a better understanding of how their expression is distributed across different tumors allows planning alternative therapeutic strategies. In canine mammary carcinomas, a phenotypic classification similar to the one widely adopted for breast cancer is currently employed. For Basal- and Normal-like phenotypes, chemotherapy is still the main option. In this study, we observed that canine mammary carcinomas bear a high intrinsic expression of both P-gp and BCRP, regardless of their molecular phenotype, and their presence does not influence the outcome. Abstract P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) are major actors in multidrug resistance (MDR) phenomenon in both human and canine mammary carcinomas (CMCs). The aim of this study was to investigate an association between the intrinsic expression of P-gp and BCRP compared to the immunophenotypes and outcome in CMCs. Fifty CMCs were evaluated at immunohistochemistry (IHC) for P-gp, BCRP, Estrogen receptor alpha (ER), Progesterone receptors (PR), Human Epidermal Growth Factor Receptor type 2 (HER2), basal cytokeratins 5/6 (CK5/6), Epidermal Growth Factor Receptor 1 (EGFR), and Ki67 proliferation index. P-gp and BCRP positive cases were, respectively, 52% and 74.5%, with a significantly higher expression of BCRP than P-gp. Five immunophenotypes were defined in 37 out of 50 CMCs: 9 (24.3%) Luminal A, 5 (13.5%) Luminal B, 9 (24.3%) HER2 overexpressing, 9 (24.3%) Triple-negative basal-like, and 5 (13.5%) Triple-negative non-basal-like. In all CMCs at least one marker was expressed. Follow-up data were available for 25 animals. The average cancer-specific survival was 739 ± 444 days. A number of CMCs bear a high expression of P-gp and BCRP but no significant association was found between their expression and the immunophenotypes, Ki67 index, the histological grade, and tumor-related death.

Simple Summary The detection of abdominal masses in dogs is a common finding in clinical practice. While data regarding masses in specific abdominal organs are available in the literature, studies comparing the site distribution of benign versus malignant lesions are scarce. The aim of this study was to retrospectively describe the tissue distribution and diagnosis of surgically excised abdominal masses in a canine population. A total of 123 abdominal masses were classified based on the organ of origin and histologically classified as non-neoplastic (39), benign neoplasia (15), and malignant neoplasia (69). Gastrointestinal masses were more likely to be malignant than masses in other sites. The masses not associated with any organ were significantly larger than the genital and splenic lesions, and no association between size and malignancy was found. This case series suggests that, while the size of the lesion cannot be used as a parameter to predict the probability of a mass being malignant neoplasm, the gastrointestinal site may be used for this scope, providing useful information for primary care clinicians. Abstract The detection of an abdominal mass represents a common finding in clinical practice. The aim of this study was to retrospectively describe the tissue distribution and diagnosis of abdominal masses amenable to surgical removal in a canine population. Dogs with abdominal masses with a minimum diameter of 3 cm were selected. Cases were classified, based on the anatomical location, as splenic, gastrointestinal, hepatobiliary, genital, and masses not associated with any organ. Masses were surgically removed and formalin-fixed for the histological examination. Collected data were statistically analyzed. A total of 123 masses were collected from 122 dogs. Sixty-nine masses were classified as malignant neoplasia, 15 as benign, and 39 as non-neoplastic. The abdominal masses were 5.8-fold more likely to be malignant if located in the gastrointestinal tract (p = 0.01). A significant association between the size and the site of the masses was identified, the masses not associated with any organ being larger than the genital and splenic lesions (p = 0.008). This case series describes the most frequent location in association with the histopathological diagnosis of canine abdominal masses and suggests that the gastrointestinal location was related to a higher risk of representing a malignant neoplasm.

Identification of prognostic factors for perivascular wall tumours (PWTs) is desirable to accurately predict prognosis and guide treatment. 100 and two dogs with surgically excised PWTs without distant metastasis were retrospectively enrolled in this multi-institutional study, and the impact of pre-treatment leukocyte parameters, clinical and histopathological variables on local recurrence (LR) and overall-survival time (OST) were evaluated. Increasing values of white blood cell count (WBCC), neutrophil count (NC) and neutrophil-to-lymphocyte ratio (NLR) were significantly correlated with the hazard of LR in univariate analysis. WBCC and NC remained prognostic when adjusted for margins, grade, tumour size, location and skin ulceration, but lost their significance when adjusted for mitotic index and necrosis, whilst NLR remained prognostic only when close margins where categorised as infiltrated. Castrated males had a higher hazard of LR than intact males in univariate analysis, but significance was lost in multivariate models. Ulcerated PWTs and those located on the distal extremities had a higher hazard of LR both in univariate and multivariate analysis. Histological grade, necrosis, mitotic count, and infiltrated margins were all associated with LR both in univariate and multivariate analysis. Boxer breed, older age, ulceration, grade III, necrosis >50% and higher mitotic count were correlated with shorter OST, although breed and age lost their significance in multivariate analysis. Prognostication of surgically excised PWTs should be based on both clinical and histopathological variables. If validated in further studies, leukocyte counts and NLR may aid the clinician in identifying dogs at higher risk of LR before treatment.

Standardization of tumor assessment lays the foundation for validation of grading systems, permits reproducibility of oncologic studies among investigators, and increases confidence in the significance of study results. Currently, there is minimal methodological standardization for assessing tumors in veterinary medicine, with few attempts to validate published protocols and grading schemes. The current article attempts to address these shortcomings by providing standard guidelines for tumor assessment parameters and protocols for evaluating specific tumor types. More detailed information is available in the Supplemental Files, the intention of which is 2-fold: publication as part of this commentary, but more importantly, these will be available as “living documents” on a website ( www.vetcancerprotocols.org ), which will be updated as new information is presented in the peer-reviewed literature. Our hope is that veterinary pathologists will agree that this initiative is needed, and will contribute to and utilize this information for routine diagnostic work and oncologic studies. Journal editors and reviewers can utilize checklists to ensure publications include sufficient detail and standardized methods of tumor assessment. To maintain the relevance of the guidelines and protocols, it is critical that the information is periodically updated and revised as new studies are published and validated with the intent of providing a repository of this information. Our hope is that this initiative (a continuation of efforts published in this journal in 2011) will facilitate collaboration and reproducibility between pathologists and institutions, increase case numbers, and strengthen clinical research findings, thus ensuring continued progress in veterinary oncologic pathology and improving patient care.

Subcutaneous spindle cell tumours characterized by whorling growth patterns are common in dogs and are identified as a distinct entity. These tumours were misnamed as hemangiopericytomas (HPCs) because of some minor morphological parallels with their human counterparts. In veterinary medicine, the cell of origin of HPC has been under debate for a long time. Some authors have suggested a perivascular origin while others a perineural one. The evidence of the orientation of the neoplastic cells around the vessels and the expression of contractile proteins supported a perivascular origin while S100 expression and an inconsistent vascular connection supported a perineural origin. Despite the morphological similarities with peripheral nerve sheath tumours in humans, the perineural origin was supported mainly by the expression of markers with low specificity. On the contrary, the majority of studies have supported the perivascular origin of 'old' canine HPC. Since a variable degree of myoid-pericytic differentiation was described, the term perivascular wall tumours (PWTs) were suggested to substitute HPC. Once the diagnostic criteria of PWTs were defined, the clinical behaviour and prognostic variables were investigated, demonstrating differences as compared with the group of canine soft tissue sarcomas (STSs) in general. PWTs are less aggressive, mostly locally invasive, and rarely metastasizing. Their behaviour seems to be less influenced by histological grade, suggesting that canine STSs are heterogeneous. The study of the biological behaviour of specific STS tumour types may be valuable in detecting differences which have passed unnoticed when STSs have been studied concomitantly.

An 11 yr old male Drahthaar dog was presented for dysuria, pollakiuria, and history of uroliths. Abdominal ultrasound revealed a subcapsular fluid-filled lesion of the left kidney, suspected cholecystitis, and a splenic infarct. The renal lesion was fully drained and cytology of the renal subcapsular and perirenal fluids revealed septic exudate. Bacterial culture of the urine, bile, and perirenal and subcapsular fluids were all positive for Staphylococcus pseudintermedius. Antimicrobial therapy was instituted based on culture sensitivity. After 7 days the dog re-presented for vomiting and abdominal pain, and a focal intestinal injury was suspected based on abdominal ultrasound. Enterectomy of an ischemic jejunal loop, a partial splenectomy, and excision of the left renal subcapsular abscess were performed. The renal parenchyma was left intact. Histopathology confirmed the diagnosis of a renal subcapsular abscess, intestinal infarction, and focal pyogranulomatous splenitis. Cholecystitis was confirmed by bile cytology and culture. No major complications and no recurrences were encountered at 1 yr follow-up. This is the first report of a renal subcapsular abscess in the dog, with septic complications, and treated with a kidney-sparing surgery.

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.

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRβ, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.

Canine spindle cell mammary tumor (CSCMT) is an infrequent canine mammary tumor (CMT) composed of spindle or fusiform cells, which represents a challenge for pathologists and clinicians. Mammary tumors submitted for histopathology from 1998 to 2013 and compatible with CSCMTs were retrospectively selected. The tumors were diagnosed based on the hematoxylin and eosin (HE)–stained section; malignant tumors were graded using a canine soft tissue sarcoma grading scheme and a canine mammary tumor grading scheme, and they were further assigned a diagnosis based on immunohistochemistry (IHC) for pancytokeratin, cytokeratin 14, p63, calponin, vimentin, Ki-67, CD31, desmin, myosin, smooth muscle actin, glial fibrillary acidic protein, and S-100. The origin of the tumors was assessed as mammary, skin, or unknown. The prevalence of CSCMT was 1% of all CMTs. CSCMTs included 3 benign tumors (1 angioma and 2 benign myoepitheliomas) and 67 malignant tumors that after IHC were diagnosed as malignant myoepithelioma (64%), carcinoma and malignant myoepithelioma (19%), hemangiosarcoma (8%), undifferentiated sarcoma (5%), peripheral nerve sheath tumor (3%), and fibrosarcoma (2%). The diagnosis based on the HE-stained section differed from the diagnosis after IHC in 75% of the malignant cases. The majority of malignant CSCMTs were solitary (57%) large tumors (6.42 ± 3.92 cm) with low metastatic potential and high survival rate (8% tumor-related mortality). Higher sarcoma grade was associated with older age ( P = .034) and greater tumor size ( P = .037). Malignant CSCMTs need to be evaluated by IHC to ensure the histotype and the relatively benign clinical behavior, despite their large size.

In routine diagnostic activity, pathologists may be confronted with nervous system tumors. The lack of clinical information, economic restrictions for additional testing, and the lack of expertise in neuropathology may render the diagnosis challenging. The goals of this study were to assess the agreement in diagnosing nervous system tumors in domestic carnivores among 4 board-certified surgical pathologists without particular expertise in neuropathology and a neuropathologist expert, and to investigate the utility of special stains frequently used in routine diagnostic laboratories. Forty-six tumors (7 cats, 38 dogs, and 1 unknown carnivore) were retrieved and 1 hematoxylin and eosin–stained slide per tumor was selected. Diagnoses (tumor type and subtype) were formulated based on histological features and available clinical information. Confidence in the diagnosis was also scored. Subsequently, a panel of histochemical and immunohistochemical stains (Gordon Sweet silver stain and immunohistochemistry for AE1/AE3, vimentin, glial fibrillary acid protein, S100, neuron-specific enolase and neurofilament) was evaluated by the pathologists, who either confirmed or changed their original diagnoses. Intraobserver and interobserver agreement and confidence in relation to diagnosis before and after analysis of special stains were assessed. The use of special stains increased the complete agreement among surgical pathologists, with regard to tumor type, from 63% to 74%. Cases with a high confidence score had a higher interobserver agreement than cases with a low confidence score. These results suggest that pathologists without expertise in neuropathology agree in the diagnosis of most nervous system tumors, and special stains available in most laboratories only slightly increase this agreement.

Case summary A 10-year-old male neutered domestic shorthair cat was presented with a 4 month history of slow, progressive swelling and intermittent multifocal bleeding of the distal right forepaw that progressively developed after cephalic vein catheterisation for anaesthesia. The procedure was performed for dental calculus removal. Initial clinical and biopsy (superficial biopsy) findings matched two differential diagnoses: progressive angiomatosis and acquired peripheral arteriovenous fistula (AVF). AVF was suspected based on Doppler ultrasound examination that identified multiple abnormal sinusoidal neoformed branching vessels with turbulent high-velocity flow spectrum at the confluence of the artery and vein, and high-velocity arterialised flow in the vein. Owing to rapid and severe progression of lesions after biopsy, the owner requested amputation of the cat’s limb. A definitive diagnosis of acquired iatrogenic peripheral AVF was based on deep-tissue microscopical evaluation. High numbers of arterioles and venules in superficial and deep dermis embedded in oedematous stroma were connected to dilated and tortuous vessels with irregularly thickened walls in deep dermis and panniculus. Vasculitis and vascular thrombosis and thickening (attributed to local hypertension) were common findings. No bone or muscular invasion were observed. The cat was doing well 3 years after surgery. Relevance and novel information This report describes a case of iatrogenic acquired peripheral AVF following venous catheterisation in a cat, fully documented for the first time by a combination of clinical findings, ultrasound imaging, complete histopathology and follow-up history.

Feline primary cutaneous lymphomas (FPCLs) account for 0.2% to 3% of all lymphomas in cats and are more frequently dermal nonepitheliotropic small T-cell tumors. Emergence of FPCL seems unrelated to feline leukemia virus (FeLV) serological positivity or to skin inflammation. A total of 17 cutaneous lymphomas with a history of vaccine injection at the site of tumor development were selected from 47 FPCLs. Clinical presentation, histology, immunophenotype, FeLV p27 and gp70 expression, and clonality were assessed. A majority of male (12/17), domestic short-haired (13/17) cats with a mean age of 11.3 years was reported. Postinjection time of development ranged from 15 days to approximately 9 years in 5 cats. At diagnosis, 11 of 17 cats had no evidence of internal disease. Lymphomas developed in interscapular (8/17), thoracic (8/17), and flank (1/17) cutaneous regions; lacked epitheliotropism; and were characterized by necrosis (16/17), angiocentricity (13/17), angioinvasion (9/17), angiodestruction (8/17), and peripheral inflammation composed of lymphoid aggregates (14/17). FeLV gp70 and/or p27 proteins were expressed in 10 of 17 tumors. By means of World Health Organization classification, immunophenotype, and clonality, the lesions were categorized as large B-cell lymphoma (11/17), anaplastic large T-cell lymphoma (3/17), natural killer cell–like (1/17) lymphoma, or peripheral T-cell lymphoma (1/17). Lineage remained uncertain in 1 case. Cutaneous lymphomas at injection sites (CLIS) shared some clinical and pathological features with feline injection site sarcomas and with lymphomas developing in the setting of subacute to chronic inflammation reported in human beings. Persistent inflammation induced by the injection and by reactivation of FeLV expression may have contributed to emergence of CLIS.

Tissue microarray (TMA) is a time- and cost-saving technique allowing the simultaneous immunohistochemical evaluation of multiple tissue samples. The aim of this study was to assess the efficacy of TMA at classifying canine gastrointestinal spindle cell tumors as gastrointestinal stromal tumor (GIST), smooth muscle tumor (SMT), and non-GIST/non-SMT based on the expression of α-smooth muscle actin (α-SMA), desmin, and CD117. Thirty-four cases were investigated on TMAs, sampling 2 cores each. Immunohistochemistry was performed on TMAs and full sections, and the results were compared. Comparing full sections, TMA specificity and sensitivity were 100% and 93.8%, respectively, for α-SMA; 100% and 80.8% for desmin; and 100% and 100% for CD117. TMA allowed the identification of 6 of 6 GISTs, 25 of 26 SMTs, and 2 of 2 non-GIST/non-SMTs. One SMT was misdiagnosed as non-GIST/non-SMT. Based on these results, TMA-based immunohistochemistry is efficient at diagnosing canine gastrointestinal spindle cell tumors and might be applied on large caseloads in a research setting.

Introduction: Canine smooth muscle tumours (SMTs) occur mostly in the gastrointestinal and female genital tracts, while soft tissue SMTs are reported rarely. In man, soft tissue leiomyomas are prevalent in cutaneous and subcutaneous tissues, while leiomyosarcomas develop more frequently in retroperitoneal, pelvic or intra-abdominal tissues in women. This study describes the clinicopathological features of canine soft tissue SMTs. Materials andMethods: Cases were collected retrospectively, clinical data retrieved and diagnoses confirmed by re-evaluation of HE-stained slides and by immunohistochemistry. Mitotic count, atypia, necrosis and histological grade were assessed.Oestrogen (OR) and progesterone (PR) receptor expression was evaluated immunohistochemically. Results: Twenty-three cases were collected: eight leiomyomas and 15 leiomyosarcomas (seven grade I, six grade II, two grade III). Thirteen dogs were female (5 neutered) and 10 male (one neutered). Eleven SMTs were subcutaneous (five in the limbs, four perineal, two perianal); five were pelvic, five retroperitoneal, one intra-abdominal and one in the oral cavity. Seven of 10 retroperitoneal/pelvic SMTs were found in female (70%) and three in male dogs. Two perineal leiomyosarcomas and one pelvic leiomyoma expressed OR. One retroperitoneal leiomyoma expressed PR. All OR- and/or PR-positive SMTs occurred in intact females. Conclusions: Canine soft tissue SMTs were more frequently subcutaneous (limbs and perianal/perineal region) and retroperitoneal (including pelvic). Retroperitoneal SMTs were more common in female dogs, paralleling human SMTs. OR and PR expression in some cases suggests the existence of a distinct subset of canine soft tissue SMTs that may display different behaviour, to be assessed in future studies.

Lymphoma is the most common feline upper respiratory tract (URT) tumor. Primary nasal and nasopharyngeal lymphomas have been evaluated as distinct pathological entities; however, data on their differing clinical behavior are missing. A total of 164 endoscopic- guided URT pinch biopsies were formalin fixed and routinely processed. Imprint cytological specimens were stained with May Grünwald-Giemsa. Immunohistochemistry for anti-CD20, CD3, FeLVp27, and FeLVgp70 was performed. Prognostic significance of clinicopathological variables was investigated by univariate and multivariate analysis. Lymphoma was diagnosed in 39 cats (24%). Most cats with lymphoma were domestic shorthair (32 [82%]), were male (F/M = 0.56), and had a mean age of 10.3 years (range, 1–16 years). Lymphomas were primary nasal in 26 cats (67%), nasopharyngeal in 6 (15%), and in both locations (combined lymphomas) in 7 cats (18%). Neoplastic growth pattern was diffuse in 35 cases (90%) and nodular in 4 (10%). Epitheliotropism was observed in 10 cases (26%). Tumor cells were large in 15 cases, were small and medium in 11 cases each, and 2 had mixed cell size. Submucosal lymphoplasmacytic inflammation was observed in 23 cases (59%). Cytology was diagnostic for lymphoma in 12 of 25 cases (48%). A B-cell origin prevailed (34 [87%]). Feline leukemia virus (FeLV) p27or gp70 antigen was detected in 21 lymphomas (54%). URT lymphomas were aggressive, with survival varying from 0 to 301 days (mean, 53 days). Epitheliotropism in 8 B-cell lymphomas (80%) and in 2 T-cell lymphomas (20%) correlated with prolonged survival. Age younger or older than 10 years had a negative prognostic value. Lymphoplasmacytic inflammation and FeLV infection may represent favoring factors for URT lymphoma development.

The expression of tyrosine kinase receptors is attracting major interest in human and veterinary oncological pathology because of their role as targets for adjuvant therapies. Little is known about tyrosine kinase receptor (TKR) expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this study was to evaluate the immunohistochemical expression of the TKRs fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor–β (PDGFRβ); their ligands, fibroblast growth factor 2 (FGF2) and platelet-derived growth factor B (PDGFB); and c-kit in canine LP. Immunohistochemical labeling was categorized as high or low expression and compared with the mitotic count and MIB-1–based proliferation index. Fifty canine LPs were examined, classified, and graded. Fourteen cases were classified as well differentiated, 7 as myxoid, 25 as pleomorphic, and 4 as dedifferentiated. Seventeen cases were grade 1, 26 were grade 2, and 7 were grade 3. A high expression of FGF2, FGFR1, PDGFB, and PDGFRβ was identified in 62% (31/50), 68% (34/50), 81.6% (40/49), and 70.8% (34/48) of the cases, respectively. c-kit was expressed in 12.5% (6/48) of the cases. Mitotic count negatively correlated with FGF2 ( R = –0.41; P < .01), being lower in cases with high FGF2 expression, and positively correlated with PDGFRβ ( R = 0.33; P < .01), being higher in cases with high PDGFRβ expression. No other statistically significant correlations were identified. These results suggest that the PDGFRβ-mediated pathway may have a role in the progression of canine LP and may thus represent a promising target for adjuvant cancer therapies.

BACKGROUND: Canine cutaneous perivascular wall tumors (c-PWT) are soft tissue sarcomas recently identified when hemangiopericytomas were reclassified. No previous clinical data are available for c-PWT. HYPOTHESIS/OBJECTIVES: To define the clinical behavior and prognostic role of clinical and pathological variables in a homogeneous population of c-PWT. ANIMALS: Fifty-five c-PWT in 53 client-owned dogs at first presentation undergoing surgery. METHODS: Retrospective case series. The endpoint was the relapse of tumor (local and/or distant). The prognostic values of clinical (age, sex, weight, site and tumor size, adjuvant therapy) and pathological (status of surgical margins, histological grade, mitosis, percentage of tumor necrosis) variables were investigated by univariate and bivariate analyses (P < .05). The pattern of associations between variables was explored by multivariate correspondence analysis (MCA). RESULTS: Twelve dogs had a relapse. Ten dogs had local recurrence, 1 had metastatic disease, and 1 had both. The estimated probability of local recurrence was 0.02, 0.08, 0.20, and 0.24 at 6 months, 1, 2, and 3 years, respectively. Size of the tumor was a significant prognostic factor while status of margins had only a clinically relevant hazard ratio. In MCA evaluation, young age, tumor size (< 5 cm), grade I, and location in the extremities were associated. Association was also observed for older age, tumor size (> 5 cm), grade II, and other location. CONCLUSION AND CLINICAL IMPORTANCE: C-PWT tend to locally recur a long time after surgery. An early diagnosis of c-PWT associated with small tumor size (< 5 cm) and clean surgical margins ensures a good prognosis independently of histological grade.

Background: Splenic marginal zone lymphomas (MZL) in dogs arise from the marginal zone of B-cell follicles and can progress slowly. Objectives: To describe clinical features, treatment, and outcome of dogs with splenic MZL. Animals: Five dogs with naturally occurring MZL. Methods: Clinical, laboratory, and follow-up data were retrospectively reviewed. Diagnosis was based on clinical, histopathological, and immunophenotypic features. Results: All dogs had stage IV disease; among them, 2 were symptomatic (substage “b”) because of splenic rupture. Four dogs underwent splenectomy and adjuvant doxorubicin, and 1 dog underwent surgery only. Three out of the 4 dogs treated with surgery and chemotherapy died of causes unrelated to lymphoma, after 760, 939, and 1,825 days, whereas the remaining dog was alive and in complete remission after 445 days. The dog not receiving any adjuvant treatment had recurrence of the tumor after 180 days. Conclusions and Clinical Importance: Splenic MZL appears indolent and can benefit from splenectomy, with or without systemic chemotherapy.

A 12-year-old, neutered female, Siberian husky, was presented with a 6-months history of progressive abdominal distension, anorexia, and weight loss. The dog appeared normal on physical examination except for marked abdominal distension. A fluid wave was balloted strongly suggesting an abdominal effusion. Ultrasound examination confirmed this clinical finding. Results of the CBC included mild nonregenerative anemia, with an RBC count of 4.9 × 10(6)/µL (reference interval 5.5-8.5 × 10(6)/µL), hemoglobin concentration of 12 g/dL (reference interval 12-18 g/dL), HCT of 36% (reference interval 37-55%), and reticulocytes

Introduction: Canine spindle cell lipoma (SCL) is an uncommon benign spindle cell tumour that might be misdiagnosed as soft tissue sarcoma (STS) because of the high cellularity and paucity of mature adipose tissue. The aim of this report was to define the typical histopathological features of canine SCL. Materials and Methods: Dog signalment, tumour size and site were retrieved from medical records. Haematoxylin and eosin, Masson’s trichrome, alcian blue and PAS staining and immunohistochemistry for vimentin, smooth muscle actin (SMA), S100, factor VIII-related antigen and MDM2 were performed. Mitotic count (MC) and MIB-1 based labelling index (LI) were assessed. Results: Five canine subcutaneous tumours were retrieved. Tumours contained bland spindle cells with sparse eosinophilic cytoplasm, an oval nucleus and an inconspicuous nucleolus, intermixed with ropey collagen and myxoid matrix stained by alcian blue. Three cases contained scattered mature adipocytes (

Background The distinction between adrenocortical tumors and pheochromocytoma can be challenging using clinical findings, diagnostic imaging and laboratory tests. Cytology might be a simple, minimally invasive method to reach a correct diagnosis. Objectives The purpose of this study was to assess the accuracy of cytology in differentiating cortical from medullary tumors of the adrenal glands in dogs and cats. Methods Cytologic key features of adrenocortical tumors and pheochromocytoma were defined by one reference author. Cytologic specimens from primary adrenal tumors were submitted to 4 cytopathologists who were asked to classify the tumors based on the previously defined key features without knowledge of previous classification. Results Twenty specimens from histologically confirmed adrenal tumors (Group 1) and 4 specimens from adrenal tumors causing adrenal-dependent Cushing's syndrome (Group 2) were evaluated by the 4 cytopathologists. Accuracy in differentiating cortical from medullary origin ranged from 90% to 100%, with a Kappa coefficient of agreement between cytopathologists of 0.95. Conclusions The origin of an adrenal tumor can be easily determined by cytology alone in many cases. However, cytology was not reliable in distinguishing benign from malignant neoplasia. Additional studies are needed to assess possible risks and complications associated with fine-needle biopsy of adrenal tumors in dogs and cats.

Canine perivascular wall tumors (cPWTs) arise from vascular mural cells and are included among soft tissue sarcomas (STSs). Most prognostic studies are performed on canine STSs as a general group and regardless of their specific histotype. The aim of this study was to identify pathological parameters and profiles with prognostic impact for cutaneous/subcutaneous cPWTs. Anatomical location, type of growth, surgical margins, and size and depth of the tumor were collected in 56 cPWTs. The association between each pair of variables was evaluated by χ2 test. Multiple correspondence analysis (MCA) was performed to describe the multivariate association of variables and was followed by cluster analysis to identify specific pathological profiles. The prognostic impact of variables and profiles was assessed by Cox regression model. Size and depth were significantly associated with increased relapse probability. Cases with complete surgical margins did not recur. Other single variables were not significantly associated with relapse. Cluster analysis on MCA considering site, depth, margins, and type of growth identified 3 pathological profiles associated with PWT relapse and having a high prognostic impact. Major prognostic factors for cPWTs were tumor size, depth of growth, and pathological profiles.

Background Most cases of canine chronic intranasal disease cannot be differentiated based on clinical examination alone, and biopsy is often required for a definitive diagnosis. Nonsurgical cytologic and histologic biopsy techniques represent desirable diagnostic approaches. Objective The aim of this retrospective study was to determine the diagnostic accuracy of brush cytology in differentiating non-neoplastic and neoplastic diseases in dogs with chronic intranasal disease. Methods Cytologic samples of lesions in dogs with chronic intranasal disease were obtained by brushing over a 12-year period. All dogs had complete physical examinations as well as radiographic, rhinoscopic, and cytologic evaluation. Histologic diagnosis, follow-up clinical information, or both were used as the gold standard, and dogs free of disease or with no progression of disease at 1 year were considered negative for neoplasia. Indicators of performance of brush cytology in detecting neoplasia were calculated and included sensitivity, specificity, positive and negative likelihood ratios, and diagnostic odds ratio. Results Samples of nasal brushings from 138 dogs were evaluated. Of 62 cases of neoplastic disease, true-positive and false-negative diagnoses were made using cytologic evaluation in 44 (71.0%) and 18 (29.0%) cases, respectively. False-negative diagnoses of neoplasia were not attributed to low cellularity, but to the presence of inflammatory cells that masked neoplastic cells. Brush cytology had a sensitivity of 0.71, specificity of 0.99, positive likelihood ratio of 53.94, negative likelihood ratio of 0.29, and diagnostic odds ratio of 188.33. Conclusions Brush cytology has good diagnostic accuracy for chronic intranasal lesions in dogs.

An eight-year-old entire female boxer was presented with a two-week history of anorexia and lethargy and two-day history of unilateral left epistaxis. Clinical findings and laboratory test results suggested disseminated intravascular coagulation. On blood smear evaluation, occasional large epithelioid-like unclassified cells were detected. Occasionally these cells were organised in small clusters. Bone marrow examination revealed a marked infiltration by a malignant population of the same epithelioid-like cells. The dog was euthanased because of the guarded prognosis. Following histology and immunohistochemistry, a widespread undifferentiated carcinoma of unknown primary origin was diagnosed. To the authors' knowledge, this is the first case of carcinoma cell leukaemia reported in a dog. Carcinoma cell leukaemia is a rare oncological condition previously described in humans, characterised by non-haematopoietic neoplastic cells in peripheral blood. © 2012 British Small Animal Veterinary Association.

Objective— To evaluate recurrence rate and disease-free interval (DFI) of dogs with low-grade soft tissue spindle cell sarcoma of the extremities treated by marginal excision. Study Design— Retrospective study. Animals— Dogs (n=35) with soft tissue low-grade spindle cell sarcoma. Methods— Medical records were reviewed and dogs that had marginal surgical resection of low-grade soft tissue spindle cell sarcoma at or distal to elbow and stifle were included. Results— Histopathologic margins were dirty (12 dogs), clean but close (12), and clean (11). Follow-up after surgery occurred from 210 to 2202 days (minimum, 180 days). Local recurrence and metastatic rates were 10.8% and 0%, respectively. Median DFI and survival time were not reached, because

An 18-month-old, female Cane Corso dog was presented with a suspected primary tumor of the tibia. Plain radiographs and computed tomography (CT) of the tibia were highly suggestive of a primary bone neoplasm. A diagnosis of malignant melanoma was made by cytology. Total body survey radiographs, CT scan of the thorax, and abdominal ultrasound excluded the presence of neoplastic lesions other than in the tibia. Limb amputation was performed. Histology and immunohistochemical analysis of the tibial neoplasm confirmed the diagnosis of a melanoma with secondary metastasis to the popliteal lymph node. The dog was alive and in good physical condition 43 months after surgery.

Introduction - Von Brunn’s nests and cysts are submucosal benign urothelial processes, related to irritative stimuli. They are common findings in the urinary bladder of human beings. Very few cases have been described in dogs and cats. Materials and Methods - We report macroscopic, histopathological and, in one case, immunohistochemical features of these rare forms in the left ureters of two cats, after ureterectomy due to urinary obstruction. Results - In both cases, macroscopical findings were coherent with an isolated, nodular and compact mass of 2.5 cm diameter. Microscopic examination showed considerable thickening of the muscular wall due to multifocal fibrosis, multifocal lacking of the lining epithelium in transverse sections of the ureteral lumen, and foci of urothelial islands in the lamina propria without any cytological atypia or mitosis and with occasional central cystic cavities. Multifocal areas of oedema, hyperemia/hemorrhage, angiogenesis and mild to moderate widespread lymphoplasmacytic infiltrates were also present. The cystic cavities contained macrophages full of lipofuscin, hemosiderin, erythrocytes and eosinophilic amorphous material. In one case, urothelial islands showed intense immunoreactivity for pan-cytokeratin (CK AE1/AE3). Inflammation was poor in the other case, where the urothelium appeared multifocally dilated with focal mucous metaplasia. In both cases, such findings and the anamnesis allowed us to hypothesize that the presence of epithelial islands was consistent with a hyperplastic condition, known as von Brunn’s nests and cysts. Conclusions - It is important to know the histological features of von Brunn nests, since it is not always easy to distinguish these islands from a well-differentiated urothelial carcinoma.