A malar granular cell tumor in a djungarian hamster

'Granular cell' tumor observed in the malar subcutis of a Djungarian hamster was examined to determine its cellular origin. Histologically, the tumor consisted of a solid growth of oval or spindle-shaped large cells with abundant cytoplasm filled with eosinophilic granules that were periodic acid-Schiff-positive and diastase-resistant. Immunohistochemically, the tumor cells were positive to anti-vimentin and anti-desmin antibodies and a few cells showed positivity to anti-actin antibody as well. They did not react to myoglobin, S-100 protein, and glial fibrillary acidic protein (GFAP). Electron microscopic studies revealed that the tumor cells had pinocytotic vesicles, dense plaque and microfilaments. The first granular cell variant of myogenic tumor reported here in Djungarian hamsters was differentiated from granular cell tumor of Schwann cell origin.     

Nine cases of granular cell tumors in B6C3F1 mice

The histological characteristics of 9 cases of granular cell tumors (GCTs) observed in B6C3F1 mice were examined to determine their cellular origin. Seven of the 9 cases were found in the uterus and other 2 cases were in the subcutaneous tissue. Tumor cells had abundant granules in the cytoplasm which were stained with PAS and were resistant to diastase treatment. Ultrastructurally, the granules were identified as lysosomes. The cell surface had cytoplasmic processus showing interdigitation with adjacent cells. A character feature of the tumor cells was the presence of a desmosome-like structure on their cell surface but no basal lamina was demonstrated. Although GCTs have been considered to be derived from Schwann cells on the basis of their ultrastructural features and S-100 protein-immunopositive findings, the absence of basal lamina in the present cases may raise a controversy as to their origin.     

Granular cell variants in a rat schwannoma. Evidence of neurogenic origin of granular cell tumor (myoblastoma).

A large, intraabdominal rat schwannoma had numerous granule-containing cells cytologically identical to cells of granular cell tumor (myoblastoma). The small eosinophilic granules stained positively by the periodic acid-Schiff (PAS) reaction, with intensity not reduced by diastase pretreatment. Granules stained positively with the Tibor Pap silver impregnation for reticulin and by electron microscopy were identical to myoblastoma cell granules. The nuclei of granular cells were morphologically identical to those of the neoplastic Schwann cells. The granular cells were in numerous foci within the tumor, frequently were seen in mitosis, and possessed an extremely variable volume of cytoplasm. They seemed to evolve from neoplastic Schwann cells. Cells with only a narrow perinuclear rim of granular cytoplasm were of the same size and general configuration as adjacent neoplastic Schwann cells, while cells with increasing volumes of granular cytoplasm were increasingly swollen and round. One area of the tumor was composed almost entirely of such large cells and was histologically identical to classic granular cell tumor.     

Tumor-specific diagnostic marker for transmissible facial tumors of Tasmanian devils: immunohistochemistry studies

Devil facial tumor disease (DFTD) is a transmissible neoplasm that is threatening the survival of the Tasmanian devil. Genetic analyses have indicated that the disease is a peripheral nerve sheath neoplasm of Schwann cell origin. DFTD cells express genes characteristic of myelinating Schwann cells, and periaxin, a Schwann cell protein, has been proposed as a marker for the disease. Diagnosis of DFTD is currently based on histopathology, cytogenetics, and clinical appearance of the disease in affected animals. As devils are susceptible to a variety of neoplastic processes, a specific diagnostic test is required to differentiate DFTD from cancers of similar morphological appearance. This study presents a thorough examination of the expression of a set of Schwann cell and other neural crest markers in DFTD tumors and normal devil tissues. Samples from 20 primary DFTD tumors and 10 DFTD metastases were evaluated by immunohistochemistry for the expression of periaxin, S100 protein, peripheral myelin protein 22, nerve growth factor receptor, nestin, neuron specific enolase, chromogranin A, and myelin basic protein. Of these, periaxin was confirmed as the most sensitive and specific marker, labeling the majority of DFTD cells in 100% of primary DFTD tumors and DFTD metastases. In normal tissues, periaxin showed specificity for Schwann cells in peripheral nerve bundles. This marker was then evaluated in cultured devil Schwann cells, DFTD cell lines, and xenografted DFTD tumors. Periaxin expression was maintained in all these models, validating its utility as a diagnostic marker for the disease.     

Dermal malignant melanoma in a horse with multifocal pancytokeratin expression.

The current report describes a malignant melanoma in the dermis of a 13-year-old bay Thoroughbred mare. Microscopic examination revealed that tumor cells were arranged in cords and packets within an abundant collagenous stroma containing scattered myxomatous foci. Tumor cells stained positively for S-100, neuron-specific enolase, and vimentin and some contained melanin granules. Some clusters of tumor cells were also positive for pancytokeratin. Expression of epithelial cell markers has been described in small numbers of human melanomas but has not been reported previously in equine melanomas.     

Malignant melanoma of the eyelid in a red squirrel (Sciurus vulgaris orientis)

A 6-year-old male red squirrel (Sciurus vulgaris orientis) developed bilateral tumors of upper and lower eyelids. The tumors in the left lid recurred despite surgical removal. Necropsy revealed metastasis to the lung. The neoplastic cells were epithelioid and highly pleomorphic, and only a few cells contained melanin granules. Occasionally melanoma cells were immunoreactive for S100, neuron-specific enolase and vimentin, and a small number of cells for cytokeratin. Ultrastructurally, the presence of premelanosomes was confirmed in the cytoplasm. Possible presence of cytokeratin-positive neoplastic melanocytes should be taken into account when differentiating a nonpigmented epithelioid melanoma from other tumors such as anaplastic carcinomas.     

Colonic ganglioneuromatosis in a horse

Ganglioneuromas are complex tumors that arise in peripheral ganglia and are composed of well-differentiated neurons, nerve processes, Schwann cells, and enteric glial cells. The term ganglioneuromatosis (GN) denotes a regional or segmental proliferation of ganglioneuromatous tissue. This report describes an 8-year-old mixed breed horse with GN in a 25-cm segment of small colon. Grossly, the lesion consisted of numerous sessile to pedunculated nodules extending from the serosal surface. Histologic examination revealed the nodules to consist of fascicles of spindle-shaped cells consistent with Schwann cells, clusters of neurons, supporting enteric glial cells, and thick bands of perineurial collagen. Most of the nodules coincided with the location of the myenteric plexus and extended through the outer layer of the tunica muscularis to the serosal surface. Neuronal processes were demonstrated within the lesion with electron microscopy. With immunohistochemistry neurons were positive for neuron specific enolase (NSE) and S-100 and the Schwann cells and enteric glial cells were positive for S-100 and glial fibrillary acidic protein (GFAP). The pathogenesis of GN is poorly understood. GN, although rare, should be included in the differential diagnosis of gastrointestinal tumors in the horse.     

Gastric stromal tumors in two rhesus macaques (Macaca mulatta)

Two female rhesus monkeys (Macaca mulatta, 10 and 24 years old) developed microcytic anemia and became terminally ill. At necropsy, large gastric masses were present, and, in one case, there were widespread abdominal metastases. Except for slightly atypical patterns, at the light microscopic level, the lesions resembled smooth muscle tumors. Ultrastructurally, however, cells in both tumors resembled primitive mesenchyme, while in one of the tumors, there were some characteristics of Schwann cells. No ultrastructural features of smooth muscle were present in either tumor. Vimentin and S-100 were detected immunohistochemically in both tumors. S-100 staining was more intense in the tumor with ultrastructural features of Schwann cells. Actin and desmin were not expressed in either gastric tumor, but diffusely stained a uterine tumor that was concomitantly present in one of the rhesus monkeys. The uterine tumor also exhibited typical ultrastructural features of smooth muscle. In the past, gastrointestinal stromal tumors in all species were thought to be of smooth muscle origin. Recently in human pathology, this conventional viewpoint has given way to the realization that there is a spectrum of neural crest and mesenchymal tumors. We report two gastric stromal tumors in two rhesus monkeys that histologically resembled smooth muscle tumors but were of neuroectodermal and primitive mesenchymal origin.     

Tail-base mass from a "horse of a different color"

A 14-year-old bay Thoroughbred gelding was presented for evaluation of a mass at the base of the tail. The mass had been present for 1 year, and recently had begun to increase in size. Additional masses were found around the eye and shoulder. A fine-needle aspirate of the tail-base mass revealed highly anaplastic round to polyhedral cells containing dark green to black cytoplasmic granules interpreted to be melanin. Histologically, the mass was composed of pleomorphic, poorly pigmented, round to polyhedral cells interpreted to be neoplastic melanocytes. With immunohistochemistry, the cells were positive for vimentin and S-100, but negative for pancytokeratin and Melan-A. The cytologic and histopathologic diagnoses were amelanotic melanoma. The horse was treated with cimetidine, but the tumor continued to progress. In this report, we describe the cytopathologic features of an aggressive amelanotic melanoma in a non-grey horse and emphasize the unique correlation between cytologic and histologic findings.     

Thyroid c-cell carcinoma in an African pygmy hedgehog (Atelerix albiventris).

A 3-yr-old African pygmy hedgehog (Atelerix albiventris) was submitted with dysphagia, weight loss, and tetraparesis. A palpable mass was found on the ventral neck. Histologic examination revealed replacement of the thyroid gland by a highly cellular, expansile, and infiltrative mass composed of lobules of polygonal cells separated by fine fibrovascular septa. Examination of ultrathin sections revealed tumor cells with few to many dense-core neuroendocrine granules, approximately 100-200 nm in diameter, and stromal amyloid. Immunohistochemical stains were positive for neuron-specific enolase. Only rare cells had positive immunohistochemical staining for calcitonin. Findings are consistent with a neuroendocrine tumor of C-cell origin. This is the first report of a C-cell carcinoma in a hedgehog.     

A cerebral granular cell tumor in a cat

A cerebral granular cell tumor is described in a 6-year-old, short-haired, female cat. The tumor was observed above the corpus callosum and completely infiltrating the third ventricle. Histologic examination revealed that the tumor was characterized by large cells containing densely packed intracytoplasmic granules and expressed psammoma body-like patterns and cholesterinic degeneration. Immunohistochemical analysis revealed granular neoplastic cells that were diffusely and strongly vimentin-positive, while they did not express cytokeratins, lysozyme, and synaptophysin. Based on morphologic and immunohistochemical findings, the tumor under study was considered to be of meningeal origin arising directly from the meninges or from meningeal elements scattered in the tela choroidea of the third ventricle roof.     

Anterior uveal spindle cell tumor in a cat

Purpose To describe a case of anterior uveal spindle cell tumor in a cat with features similar to spindle cell tumor of blue eyed dogs. Methods A 10‐year‐old female spayed domestic short‐haired cat was referred for an iris mass OS. The mass was solitary, nodular, nonpigmented, located medially, and causing dyscoria. A diagnosis of a benign epithelial tumor was suggested by a FNA of the mass. The cat was lost to follow‐up for 2 years, after which time she re‐presented with glaucoma, blindness and grossly evident iridal mass enlargement OS. Transconjunctival enucleation was performed and the globe submitted for histopathology. Results Histopathology of the enucleated globe revealed the superior iris to be infiltrated and effaced by a large population of neoplastic spindle cells. The cells were arranged in streams and bundles and exhibited Antoni‐A and Antoni‐B tissue patterns, which are characteristic of Schwann cell tumors. Mitotic figures were rare and cellular pleomorphism moderate. Immunohistochemical staining was positive for S‐100 protein and glial fibrillary acidic protein (GFAP), and negative for Melan‐A. Interestingly, there was no histological evidence of glaucoma. Conclusions Based on its histopathologic characteristics, this iris tumor was diagnosed as a Schwann cell variant of a peripheral nerve sheath tumor (PNST) closely resembling the spindle cell tumor of blue‐eyed dogs. Anterior uveal PNST has not been previously reported in cats to the authors’ knowledge. The presence of Antoni type A and type B tissue patterns along with immunohistochemical staining may facilitate a diagnosis of PNST and rule out malignant melanoma.     

Molecular characteristics and pathogenicity of an avian leukosis virus isolated from avian neurofibrosarcoma

Peripheral nerve sheath tumors (PNSTs) are rare in chickens and their etiology remains to be elucidated. In this study, a naturally occurring PNST in a Japanese native fowl (Gallus gallus domesticus) was pathologically examined and the strain of avian leukosis virus (ALV) isolated from the neoplasm was characterized by molecular biological analysis. The fowl presented with a firm subcutaneous mass in the neck. The mass, connected to the adjacent spinal cord (C9-14), was microscopically composed of highly cellular tissue of spindle cells arranged in interlacing bundles, streams, and palisading patterns with Verocay bodies and less cellular tissue with abundant collagen. Immunohistochemically, neoplastic cells were divided into two types: perineurial cells positive for vimentin, glucose transporter 1 (GLUT1), and claudin1; and Schwann cells positive for vimentin, occasionally positive for S-100 alpha/beta but negative for GLUT1. Based on these findings, a diagnosis of neurofibrosarcoma was made. The complete nucleotide sequence of an ALV strain, CTS_5371, isolated from the neoplasm was determined and phylogenetic analysis indicated that the strain was a novel recombinant virus from avian leukosis/sarcoma viruses previously reported. Additionally, experimental infection revealed that CTS_5371 induced the proliferation of Schwann cells and perineurial cells. These results suggest that this ALV strain has the ability to induce PNSTs in chickens.     

Chromatophoroma in a crevice kelpfish (Gibbonsia montereyensis)

A captive adult crevice kelpfish, Gibbonsia montereyensis, developed a cutaneous mass, approximately 9 × 7 mm on the right side of the head in an area of nonscaled skin. Following surgical debulking, examination of both impression smears and histologic sections of the tumor revealed a predominant population of round to spindloid to polygonal cells with a moderate amount of lightly basophilic cytoplasm. The cytoplasm was filled with round, variably-sized reddish-brown granules that often obscured the nucleus. Nuclei were round to ovoid with coarsely granular chromatin. There was minimal anisocytosis and anisokaryosis. The cytoplasmic granules in histologic sections were weakly positive by the Fontana-Masson method, and staining was eliminated with melanin bleach. Immunohistochemical staining was strongly positive with a murine monoclonal antibody for melan A. As the specificity of melan A for melanophores is not clearly defined in nonmammalian species, the tumor was examined by transmission electron microscopy. Melanophores were not detected. Instead, neoplastic cells were filled with numerous intracytoplasmic organelles with triple-limiting membranes composed of concentric lamellae; these structures were most compatible with pterinosomes, which are the pigment-containing organelles of cells called xanthophores and erythrophores. As both of these organelles are ultrastructurally indistinguishable and as kelpfish skin is known to contain both xanthophores and erythrophores, a diagnosis of a mixed pigment cell tumor or chromatophoroma was made. As the tumor was grossly reddish-brown, the possibility of a neoplastic population of only erythrophores could not be excluded. Pigment cell tumors, arising from cells of the embryonic neural crest, are common in reptiles and bony fish.     

Follicular stem cell carcinoma: histologic,immunohistochemical, ultrastructural,and clinical characterization in 30 dogs

Diagnostic records of 30 primary and one metastatic follicular stem cell carcinomas in 30 dogs were reviewed. Neoplastic cells had a clear cytoplasm and formed lobules and nests surrounded by a basement membrane. Trichoepitheliomatous and apocrine differentiations were noted in 22 of 30 (73%) and 21 of 30 (70%) primary tumors, respectively. Glycogen was present in 20 of 20 (100%) tumors tested, suggesting tricholemmal differentiation. Antibodies against AE1/AE3 cytokeratin, vimentin, and melanA/MART1 stained 29 of 30 (97%), 29 of 30 (97%), and 12 of 27 (44%) primary tumors, respectively. Small amounts of melanin were identified in 14 primary tumors, either on the hematoxylin and eosin-stained section (n = 6), or on the Fontana-stained section (n = 8 of 14). Ultrastructural features of neoplastic cells included cell junction complexes, swollen mitochondria, neuroendocrine-like granules, and intracytoplasmic non-membrane-bound accumulation of proteinaceous material. Features of this neoplasm are consistent with a follicular stem cell origin. Follow-up information was available for eight dogs. Metastases developed in the draining lymph node at the time of excision of the primary tumor (n = 1) or subsequently (n = 3).     

Characterization of uterine granular cell tumors in B6C3F1 mice: a histomorphologic, immunohistochemical, and ultrastructural study

The granular cell tumor is most often a benign neoplasm of uncertain origin. Four uterine granular cell tumors in control and treated female B6C3F1 mice were identified in chronic studies at the National Toxicology Program. Two tumors occurred in untreated control animals and 2 in treated animals receiving different compounds. Tissue sections were evaluated histologically and stained with hematoxylin and eosin, periodic acid-Schiff with diastase resistance, Masson's trichrome, toluidine blue, phosphotungstic acid-hematoxylin, and stained immunohistochemically with a panel of antibodies to muscle (desmin, alpha smooth muscle actin), neural (S-100, neuron specific enolase), epithelial (wide-spectrum cytokeratin), and macrophage (F4/80) markers. The main histomorphologic feature of tumor cells was the presence of abundant cytoplasmic eosinophilic granules that stained positive for periodic acid-Schiff with diastase resistance. Tumors varied in appearance and were comprised of sheets and nests of round to polygonal cells with distinct borders. Nuclei were hyperchromatic, pleomorphic, and centrally to eccentrically located and often contained single nucleoli. Occasional multinucleated giant cells were observed. Tumors were pale pink and homogeneous with trichrome stain and negative with toluidine blue. Three tumors had positive to weakly positive immunoreactivity for desmin, and 1 was positive for alpha smooth muscle actin. Expression of S-100, wide-spectrum cytokeratin, and neuron-specific enolase was negative for all tumors. Ultrastructurally, prominent electron-dense cytoplasmic granules were abundant and contained secondary lysosomes with heterogeneous lysosomal contents. The characteristics of these uterine granular cell tumors were suggestive of a myogenic origin.     

Canine intraneural perineurioma

A 6-year-old castrated German Shepherd Dog was presented with a 6-month history of progressive, nonpainful, left pelvic limb paresis. Magnetic resonance imaging revealed atrophy of left-sided epaxial and hypaxial muscles from L5-L7 and an enlarged L5 spinal nerve. Exploratory hemi-laminectomy revealed focally and cylindrically thickened L5 and L6 nerve roots. Histologic evaluation of a surgical biopsy specimen from the L6 dorsal nerve root, and the L5 nerve roots after later amputation revealed distended hypercellular fascicles. This distension was due to widely separated axons surrounded by concentric lamellations formed by neoplastic perineurial cells and their processes. These pseudo-onion bulbs were separated from each other by a basophilic myxoid stroma. The perineurioma cell processes were immunonegative for S-100 (alpha and beta chains) and collagen IV, but were immunoreactive for laminin. The central axons were also immunoreactive for NF-200 and S-100. The proliferative index of the perineurioma cells, as determined by MIB-1 immunoreactivity, was about 3%. Ultrastructurally, the widely separated, interdigitating perineurioma cell processes were connected by desmosomal-like junctional complexes to form continuous circles. Their processes were covered by a discontinuous basal lamina. Each centrally placed axon was normally, thinly, or completely unmyelinated and was surrounded by a normal Schwann cell. These morphologic and immunologic features distinguish this lesion from hypertrophic neuropathy and were consistent with intraneural perineurioma.     

Circulating melanin-containing cells and neutrophils with phagocytized melanin granules in a horse with disseminated melanoma

An 18-year-old, grey, Thoroughbred Cross gelding was referred to the Cummings School of Veterinary Medicine at Tufts University following a 3-week history of low-grade fever of unknown origin, distal limb swelling, and weight loss. Clinical examination identified a few black, round, smooth nodules along the ventral aspect of the proximal tail. Transabdominal ultrasound showed a markedly enlarged heterogenous spleen, hyperechoic liver nodules, and evidence of peritonitis with fibrin deposition. A mature neutrophilia was noted on complete blood count with variable numbers of phagocytized granules within neutrophils. The granules did not stain with Perl's Prussian blue, and were intensely positive when stained with Fontana-Mason, consistent with melanin. On necropsy, the spleen occupied approximately one-third of the abdominal cavity and was diffusely firm with abundant black pigment on cut section. The medullary space of the 18th thoracic vertebra was also diffusely blackened. The splenic, mediastinal, and tracheobronchial lymph nodes were five times the normal size and diffusely pigmented. The final anatomic diagnosis was disseminated malignant melanoma with extensive splenic involvement and hemolymphatic and vascular neoplastic dissemination. To the authors' knowledge, this is the first full report to identify circulating neutrophils containing phagocytized melanin granules, which confirmed an antemortem diagnosis of disseminated melanoma.     

MALIGNANT PERIPHERAL NERVE SHEATH TUMOR IN A CAT

A report of a cat with a cranial tumor of nerve sheath origin is presented. The cranial mass, with a cyst-like character on presentation to the referring veterinarian suggested a benign lesion, but the clinical course was rapid and indicative of central nervous system involvement. The tumor was poorly differentiated by histologic examination, but immunohistochemistry was consistent with Schwann cell origin. Features of peripheral nerve sheath tumors in cats and other species are briefly discussed.     

An osteoid variant of cutaneous melanoma in a dog detected by S100 and melan a markers

Osteoid malignant melanoma is a rare type of melanoma described in humans and dogs with some areas of bone differentiation. In this tumour, the origin of the bone matrix remains unclear. We report one case of this variant with, for the first time, a cutaneous origin in a dog. Malignant melanomas are aggressive tumours. Amelanotic tumours are sometimes difficult to recognize as they require immunohistochemical evaluation for an adequate diagnosis and we have used anti-vimentin, S100, and melan A antibodies for identification. Melan A is less sensitive but more specific than S100 in identifying amelanotic melanomas. This tumour was positive for vimentin, S100 and melan A, including the areas of osteoid. These results suggest osteoid differentiation of tumour cells rather than induced stromal metaplasia.