Standardization of canine meningioma grading: Validation of new guidelines for reproducible histopathologic criteria.

Canine meningiomas are currently graded using the human grading system. Recently published guidelines have adapted the human grading system for use in dogs. The goal of this study was to validate the new guidelines for canine meningiomas. To evaluate the inter-observer agreement, 5 veterinary surgical pathologists graded 158 canine meningiomas following the human grading system alone or with the new guidelines. The inter-observer agreement for histologic grade and each of the grading criteria (mitotic grade, invasion, spontaneous necrosis, macronucleoli, small cells, hypercellularity, pattern loss and anaplasia) was evaluated using the Fleiss kappa index. The diagnostic accuracy (sensitivity and specificity) was assessed by comparing the diagnoses obtained with the 2 grading systems with a consensus grade (considered the reference classification). The consensus histologic grade was obtained by agreement between 4 experienced veterinary neuropathologists following the guidelines. Compared with the human grading alone, the canine-specific guidelines increased the inter-observer agreement for: histologic grade (κ = 0.52); invasion (κ = 0.67); necrosis (κ = 0.62); small cells (κ = 0.36); pattern loss (κ = 0.49) and anaplasia (κ = 0.55). Mitotic grade agreement remained substantial (κ = 0.63). The guidelines improved the sensitivity in identifying grade 1 (95.6%) and the specificity in identifying grade 2 (96.2%) meningiomas. In conclusion, the new grading guidelines for canine meningiomas are associated with an overall improvement in the inter-observer agreement and higher diagnostic accuracy in diagnosing grade 1 and grade 2 meningiomas.

A Recurrent Inflammatory Myofibroblastic Tumor-like Lesion of the Splenic Capsule in a Kitten: Clinical, Microscopic and Ultrastructural Description.

OBJECTIVE: To describe the findings of an unusual splenic tumor in a kitten. METHODS: A grossly multinodular mass arising from the splenic capsule of a 7-month-old male Havana kitten was echographically detected and surgically removed by splenectomy, then analyzed microscopically and ultrastructurally. RESULTS: The mass showed features of an inflammatory myofibroblastic tumor. TREATMENT AND OUTCOME: Two months after surgical excision, the mass recurred in the same intra-abdominal area but disappeared after 2 months of anti-inflammatory therapy. Follow-up at 18 months after surgery revealed resolution of the disease. CLINICAL RELEVANCE: Inflammatory myofibroblastic tumor in cats have been rarely reported and are usually in the orbital region. In the present report, an unusual multinodular gross presentation, a recurrence over time, and a favorable clinical course, are described.

Paraneoplastic ganglioradiculoneuritis in a cat with a plasma cell tumour.

CASE SUMMARY: An 8-year-old neutered female domestic longhair cat was presented for investigation of a 48 h history of lethargy and pelvic limb ataxia. MRI of the spinal cord and vertebral column (C1 to sacrum) and brain was unremarkable. Lumbar cerebrospinal fluid analysis revealed pleocytosis and increased protein concentration. Thoracic radiographs and abdominal ultrasound were unremarkable. Anti-inflammatory doses of prednisolone were administered. Clinical deterioration occurred over the following 2 days, with the development of lower motor neuron deficits in both thoracic limbs. On repetition of the MRI, bilateral enlargement, T2-weighted hyperintensity, and marked contrast enhancement of the C7, C8 and T1 nerve roots, spinal nerves and brachial plexuses were observed. Infectious disease testing was negative. An immune-mediated inflammatory process was suspected and immunosuppressive doses of prednisolone were commenced. The clinical signs improved transiently, but marked deterioration occurred after 2 weeks. The patient was euthanased and a post-mortem examination was performed. A lymphocytic inflammatory infiltrate was detected in the C7, C8 and T1 nerve roots and dorsal root ganglia, and neoplastic plasma cells were identified in multiple organs. A diagnosis of non-cutaneous extramedullary plasmacytoma with multiorgan involvement and paraneoplastic ganglioradiculoneuritis was reached. RELEVANCE AND NOVEL INFORMATION: Paraneoplastic ganglioradiculoneuritis in association with a plasma cell neoplasia has not been previously reported in the cat and should be considered as a differential diagnosis for cats with clinical or imaging evidence of an inflammatory process affecting the nerve roots, spinal nerves or brachial plexuses.

Sarcocystis gigantea infection associated with granulomatous eosinophilic myositis in a horse.

The only Sarcocystis species currently known to inhabit the fibers of skeletal and cardiac muscles in horses are S. fayeri, S. bertrami, and S. asinus. We describe herein the invasion of myofibers in a horse by S. gigantea, a sheep-specific species with low virulence in the original host. A hunter gelding was referred to a veterinary surgeon in Newmarket (UK). The anamnestic data reported that the horse had an initial history of swelling of the right forelimb with fluid on the front of the carpus and edema spreading up the forearm. Subsequently, 2 firm lumps were found on the left pectoral muscle adjacent to the axilla of the left forelimb. Histologic examination of biopsies from the lumps revealed multifocal granulomatous eosinophilic myositis associated with intact and degenerate encysted parasites, consistent with Sarcocystis spp. Based on amplification and DNA sequencing of the 18S rRNA gene obtained from formalin-fixed, paraffin-embedded tissue blocks, S. gigantea was identified. The presence of sarcocysts in equine skeletal muscles has been considered an incidental finding, and there are only sporadic associated reports of myositis. Our finding suggests that some Sarcocystis spp. have a wider intermediate host range than believed previously, and that Sarcocystis of other species (not considered horse-associated) can invade the muscle fibers of equids, leading to myositis.

Disseminated Langerhans cell histiocytosis presenting as oesophageal disease in a cat.

CASE SUMMARY: An 11-year-old female spayed domestic shorthair cat was referred with a 2-month history of ptyalism, hyporexia and weight loss. Physical examination revealed reduced body condition score (2/9) and decreased skin turgor. Laboratory abnormalities included mild erythrocytosis, elevated creatine kinase, hypercobalaminaemia and hypofolataemia. CT of the head and abdominal ultrasonography were within normal limits. Gastroesophagoscopy revealed mucosal ulceration and possible stenosis of the distal oesophagus. Thoracic radiographs and iodine oesophagram showed a soft tissue opacity in the caudodorsal thorax compatible with a parietal oesophageal mass causing luminal stenosis or an extra-parietal mass causing ventral displacement and compression of the oesophagus. Pulmonary nodules were observed in the cranial lung lobes. CT of the thorax confirmed the oesophageal origin of the mass and the presence of pulmonary nodules scattered throughout the lung parenchyma. The patient was euthanased given the imaging findings and perceived guarded prognosis. Post-mortem examination revealed multifocal nodular lesions affecting the oesophagus, lungs, kidneys and pancreas. Histopathological examination identified atypical round cells characterised by eosinophilic cytoplasm and pale nuclei with prominent nuclear grooves, compatible with neoplastic histiocytic cells. Immunohistochemistry revealed strong expression for CD18, Iba-1 and vimentin. Transmission electron microscopy demonstrated intracytoplasmic organelles consistent with Birkbeck granules of Langerhans cell origin in lesional histiocytes. These findings were compatible with a diagnosis of disseminated Langerhans cell histiocytosis. RELEVANCE AND NOVEL INFORMATION: To our knowledge, this is the first report of disseminated Langerhans cell histiocytosis with oesophageal involvement in a cat.

Inter- and Intraobserver Agreement of Canine and Feline Nervous System Tumors.

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.

Identification of molecular genetic contributants to canine cutaneous mast cell tumour metastasis by global gene expression analysis.

Cutaneous mast cell tumours are one of the most common canine cancers. Approximately 25% of the tumours metastasise. Activating c-kit mutations are present in about 20% of tumours, but metastases occur in the absence of mutations. Tumour metastasis is associated with significantly diminished survival in spite of adjuvant chemotherapy. Available prognostic tests do not reliably predict whether a tumour will metastasise. In this study we compared the global expression profiles of 20 primary cutaneous mast cell tumours that metastasised with those of 20 primary tumours that did not metastasise. The objective was to identify genes associated with mast cell tumour metastatic progression that may represent targets for therapeutic intervention and biomarkers for prediction of tumour metastasis. Canine Gene 1.1 ST Arrays were employed for genome-wide expression analysis of formalin-fixed, paraffin-embedded biopsies of mast cell tumours borne by dogs that either died due to confirmed mast cell tumour metastasis, or were still alive more than 1000 days post-surgery. Decreased gene expression in the metastasising tumours appears to be associated with a loss of cell polarity, reduced cell-cell and cell-ECM adhesion, and increased cell deformability and motility. Dysregulated gene expression may also promote extracellular matrix and base membrane degradation, suppression of cell cycle arrest and apoptosis, and angiogenesis. Down-regulation of gene expression in the metastasising tumours may be achieved at least in part by small nucleolar RNA-derived RNA and microRNA-effected gene silencing. Employing cross-validation, a linear discriminant analysis-based classifier featuring 19 genes that displayed two-fold differences in expression between metastasising and non-metastasising tumours was estimated to classify metastasising and non-metastasising tumours with accuracies of 90-100% and 70-100%, respectively. The differential expression of 9 of the discriminator genes was confirmed by quantitative reverse transcription-PCR.

IMAGING DIAGNOSIS-ULTRASONOGRAPHIC APPEARANCE OF SKELETAL MUSCLE METASTASES IN A DOG WITH HEMANGIOSARCOMA.

A 13-year-old spayed female German shepherd dog was presented for acute onset of lethargy, anorexia, and disseminated erythematous skin lesions. Thoracic radiographs and abdominal ultrasonographic findings were consistent with metastatic hemangiosarcoma. Multiple, ill-defined, irregularly shaped hypoechoic nodules were also detected within the thoracic and abdominal wall. Hemangiosarcoma metastases to the skeletal muscle were confirmed based on histopathological examination. Multivisceral involvement was also confirmed by necropsy. Metastatic neoplasia should be considered as a differential diagnosis for dogs with ill-defined, irregular, hypoechoic, intramuscular nodules.

Comparison of 2- and 3-category histologic grading systems for predicting the presence of metastasis at the time of initial evaluation in dogs with cutaneous mast cell tumors: 386 cases (2009-2014).

OBJECTIVE: To compare the Kiupel (2 categories) and Patnaik (3 categories) histologic grading systems for predicting the presence of metastasis at the time of initial examination in dogs with cutaneous mast cell tumors (MCTs). DESIGN: Retrospective case series. ANIMALS: 386 client-owned dogs with cutaneous MCTs. PROCEDURES: Medical records of dogs with newly diagnosed, histologically confirmed cutaneous MCTs that had undergone complete clinical staging were reviewed for clinical and histopathologic data. RESULTS: All Patnaik grade 1 MCTs (n = 52) were classified as Kiupel low-grade MCTs, and all Patnaik grade 3 MCTs (43) were classified as Kiupel high-grade MCTs. Of the 291 Patnaik grade 2 MCTs, 243 (83.5%) were classified as Kiupel low-grade tumors, and 48 (16.5%) were classified as Kiupel high-grade MCTs. Dogs with Patnaik grade 3 MCTs were significantly more likely to have metastases at the time of initial examination than were dogs with grade 1 or 2 MCTs (OR, 5.46), and dogs with Kiupel high-grade MCTs were significantly more likely to have metastases than were dogs with Kiupel low-grade MCTs (OR, 2.54). However, 3 of 52 (5.8%) dogs with Patnaik grade 1 tumors, 48 of 291 (16.5%) dogs with Patnaik grade 2 tumors, and 44 of 295 (14.9%) dogs with Kiupel low-grade tumors had metastatic disease. CONCLUSIONS AND CLINICAL RELEVANCE: Findings indicated that in dogs with cutaneous MCTs, prognostication should not rely on histologic grade alone, regardless of grading system used, but should take into account results of clinical staging.

Nasal eucoleosis in a symptomatic dog from Italy.

A dog with chronic muco-purulent nasal discharge, sneezing, reverse sneezing and impaired scenting ability was diagnosed as being affected by nasal eucoleosis based upon rhinoscopic evidence of Eucoleus boehmi in situ, identification of the adult parasites in nasal biopsies, and eggs in the faeces by light and scanning electron microscopy. The dog was successfully treated with a single administration of moxidectin. A second course of moxidectin was required for about 10 weeks after the first treatment, because clinical signs recurred due to a likely re-infection. This second administration, along with measures undertaken to prevent geo- and coprophagic pica, resolved the parasitism, as demonstrated by negative copromicroscopic and rhinoscopic examinations, and prevented reinfestation for the next 4 months. To the best of the authors' knowledge, this represents the first report describing a clinical case of nasal eucoleosis with a demonstration of the adult parasites in situ in a dog from Italy where, until recently, infestation of E. boehmi was only detected by a coprological examination. Veterinarians and parasitologists should be aware of the occurrence of canine infection with E. boehmi. They should include this parasite in the differential diagnoses for animals suffering from upper airway distress and look systematically for it during rhinoscopic and copromicroscopic examinations.