G. Avallone

The Spectrum of Canine Cutaneous Perivascular Wall Tumors: Morphologic, Phenotypic and Clinical Characterization

Perivascular wall tumors (PWTs) are defined as neoplasms deriving from mural cells of blood vessels, excluding the endothelial lining. The spectrum of human cutaneous PWT includes glomus tumor, hemangiopericytoma (HEP), myopericytoma, angioleiomyoma/sarcoma, angiomyofibroblastoma, and angiofibroma. The purpose of this study was to revise clinical presentation, cytology, histopathology, and immunohistology of canine cutaneous PWT with cytology typical of canine HEP. Diagnosis was established on the basis of vascular growth patterns (staghorn, placentoid, perivascular whorling, bundles from media) and immunohistology, including 7 smooth muscle markers and the cell membrane ganglioside of unknown origin recognized by the antibody 3G5 (CMG-3G5). Twenty cases were included. Ages ranged from 6 to 13 years; 12 dogs were males and 8 were females, and there was a prevalence of crossbreeds. Tumors arose from a single site with preferential acral location (10/20). Cytology revealed moderate to high cellularity in all cases, cohesive groups of cells (19/20), capillaries (18/20), and bi- to multinucleated cells (18/20). Six myopericytomas, 5 angioleiomyomas, 2 angioleiomyosarcomas, 2 HEP, 1 angiofibroma, and 1 adventitial tumor were identified. A definitive diagnosis was not possible in 3 cases. Smoothelin, heavy caldesmon, desmin, myosin, calponin, and CMG-3G5 were the most valuable markers to differentially diagnose canine PWT. Similar to reports in humans, canine HEP embodied a spectrum of neoplastic entities arising from different vascular mural cells. Before canine PWTs are assimilated into one prognostic category, a consistent classification and characterization of their biology is necessary. As proposed in humans, HEP should also be considered a diagnosis of exclusion in dogs.

Diagnostic accuracy of brush cytology in canine chronic intranasal disease

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.

Cutaneous Lymphoma at Injection Sites: Pathological, Immunophenotypical, and Molecular Characterization in 17 Cats.

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.

Tyrosine Kinase Receptor Expression in Canine Liposarcoma

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.

Canine Gastrointestinal Spindle Cell Tumors Efficiently Diagnosed by Tissue Microarray-Based Immunohistochemistry:

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.

Glomeruloid Microvascular Proliferation, Desmoplasia, and High Proliferative Index as Potential Indicators of High Grade Canine Choroid Plexus Tumors:

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.

Spindle Cell Lipoma in Dogs

Spindle cell lipoma (SCL) is a benign neoplasm of the adipose tissue that may resemble an undifferentiated soft tissue sarcoma (STS). This report describes the histopathological features of 6 SCLs in dogs. All SCLs were located in the subcutis and were composed of bland, occasionally vacuolated spindle cells intermixed with ropey collagen and myxoid matrix. Sudan IV stain performed in 1 case demonstrated the lipid content of vacuoles. Mature adipocytes represented less than 10% of the neoplasm in 3 cases and were absent in the remaining 3. Average mitotic count in 10 high-power fields was 0.17. Neoplastic cells were immunohistochemically positive for vimentin and negative for S100 protein, smooth muscle actin, factor VIII-ra, and MDM2. Awareness of SCL and its specific histopathological features is essential to diagnose this specific tumor. Further studies are needed to document the biological behavior of these tumors in dogs.

Antioxidant enzymes in canine mammary tumors

Abstract Spontaneous mammary tumors are very common in bitches. The involvement of oxidative stress and the function of antioxidant enzymes in cancerogenesis have been studied in depth in human medicine, while data in veterinary medicine are still fragmentary. The main aim of this study was to evaluate the activity and the expression of superoxide dismutases (Cu-ZnSOD and MnSOD) and the activity of catalase (CAT) in canine mammary tumors in comparison with the adjacent healthy tissue. Six female dogs (mean age 10.4 years) were included in this study. After surgery, fresh tumor and healthy tissue samples were immediately frozen in dry ice and stored at −80°C for biochemical analyses, while the remaining parts were used for histopathological analysis. Enzyme activity was measured by spectrophotometric assays and protein expression by western blotting. In canine mammary tumors, Cu-ZnSOD activity and expression increased significantly compared with healthy control tissues (p=0.03). MnSOD showed a significantly lower activity in tumoral tissues at stage 2 (p<0.05), while a significant increase of expression was measured in tumors. CAT activity was significantly higher in healthy tissues respect to tumors (p=0.015). These variations of antioxidant enzymes activities and expression could be related to an increase of oxidative stress in breast cancer tissues and could be considered as biomarker candidates for neoplastic transformation.

Primary osseous melanoma in the tibia of a dog.

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.