Malignant nonteratoid ocular medulloepithelioma in a llama (Llama glama).

A 6-year-old female llama presented with buphthalmos of its right eye owing to the presence of an intraocular mass. The affected globe was enucleated and submitted for microscopic examination. The intraocular mass was diagnosed as malignant medulloepithelioma. Within the following months, the llama developed soft tissue masses, which completely filled the right orbital cavity and expanded the cranial portion of the right mandibular bone, and enlarged mandibular lymph nodes. Euthanasia was elected 30 months after the initial diagnosis. The carcass was submitted for postmortem examination, which revealed the presence of medulloepithelioma metastases within the right orbit, mandible, mandibular lymph nodes, lungs, liver, and mesenteric and sublumbar lymph nodes. The primary intraocular tumor and its metastases were composed of neoplastic undifferentiated neuroepithelial cells, which formed tubules, Flexner-Wintersteiner and Homer Wright rosettes, and rare solid sheets. Electron microscopy showed that tumor cells were connected by desmosome-like junctions and contained rare intracytoplasmic basal bodies. Neoplastic cells were positive for vimentin, nestin, microtubule-associated protein 1B, S-100 protein, and glial fibrillary acidic protein (GFAP). To the best of the authors' knowledge, this is the first report of a malignant nonteratoid ocular medulloepithelioma with distant metastases in a llama and of the ultrastructural and extended immunohistochemical characterization of a nonteratoid medulloepithelioma in this species.     

Multicentric nerve sheath fibrosarcomas of multiple cranial nerve roots in two dogs

Nerve sheath fibrosarcomas of the left 5th through 8th cranial nerve roots were diagnosed in 1 dog and of the left 4th through 8th cranial nerve roots in another dog. Clinical signs in both dogs included head tilt to the left, circling to the left, left hemiparesis and proprioception deficits, rotary nystagmus, left-sided atrophy of masticatory muscles, and cutaneous hypalgesia of the left side of the face. Cranial nerve roots from both dogs were incorporated in discrete, firm, encapsulated, lobulated, tan masses of various sizes that compressed adjacent brain stem and cranial nerves. There were no regional or distant metastases; however, there was enlargement of nerve roots adjacent to the masses. The masses were composed of bundles and sheets of anaplastic, polymorphic to spindle-shaped cells that infiltrated cranial nerves and ganglia and extended into the brain along nerve roots. Masses contained various amounts of collagen and reticulin fibers, but no mucopolysaccharide ground substance. There was no myelin or S-100 protein associated with neoplastic cells. The tumors appeared to have a multicentric origin from cranial nerve sheaths.     

Morphologic and immunohistochemical features of two spontaneous peripheral nerve tumors in Wistar rats

Morphologic features and S-100 protein immunoreactivity of a benign and malignant peripheral nerve sheath tumor were studied in two Wistar rats. Neoplasms that developed in untreated control rats from tumor bioassays were S-100 protein positive and had similar histopathologic features. Each peripheral nerve sheath tumor was encapsulated and composed of spindle cells arranged around small thin-walled blood vessels. Palisaded tumor cells were in the benign peripheral nerve sheath tumor while cells of the malignant peripheral nerve sheath tumor had cellular atypia and moderate numbers of mitoses. Ultrastructural examination of the malignant peripheral nerve sheath tumor revealed cells with external lamina and interdigitation of cytoplasmic processes. Intracytoplasmic concentric lamellae were seen; they were regularly spaced with a periodicity of about 15 nm. Such structures, indistinguishable from myelin sheaths, have not been commonly associated with peripheral nerve sheath tumors in man. Electron microscopy and immunohistochemistry were useful in the diagnosis of these tumors as Schwannomas and in differentiation from other spindle cell tumors.     

Immunohistochemical evaluation of canine peripheral nerve sheath tumors and other soft tissue sarcomas

Seventeen cases of canine peripheral nerve sheath tumors (PNSTs), 11 malignant PNSTs (MPNSTs), and six benign PNSTs (BPNSTs) were examined. The prognosis in five of six dogs with BPNSTs was excellent, whereas all dogs with MPNSTs died within 2 years after the last surgical resection. One BPNST formed a recurrent mass with features of a MPNST. Histopathologically, the predominant tumor cell of MPNSTs was either spindle or round in shape with epithelioid characteristics. Other atypical cells had abundant granular cytoplasm or were multinucleated giant cells with periodic acid-Schiff-positive cytoplasmic globules. Furthermore, two MPNSTs contained cartilaginous and osseous metaplasia. On the contrary, most BPNSTs exhibited typical features of schwannoma or neurofibroma, whereas two BPNSTs had atypical morphology. One BPNST consisted of epithelioid cell proliferation with some tumor cells revealing nuclear atypia. Immunohistochemically, the expression of vimentin (100%), S-100 (73%), nerve growth factor receptor (NGFR, 64%), and myoglobin (64%) was commonly found in MPNSTs. The two BPNSTs with atypical histologic appearances were positive for vimentin, S-100, NGFR, and neuron-specific enolase, and one of these had moderate immunoreactivity for cytokeratin. Most BPNSTs were positive for glial fibrillary acidic protein, as well as S-100 and NGFR. Although most rhabdomyosarcomas (RMSs) and canine hemangiopericytomas (CHPs) also showed focal immunoreactivity for S-100, most RMSs were intensely positive for myoglobin and negative for NGFR. Most CHPs (80%) exhibited focal alpha-smooth muscle actin (alpha-SMA) expression, whereas all PNSTs were negative. These results indicate that immunohistochemistry for NGFR and alpha-SMA might be useful for differentiating canine PNSTs from RMSs or CHPs, respectively.     

A spontaneously occurring malignant pituicytoma in a male sprague dawley rat

Pituicytoma is an extremely rare neoplasm derived from pituicytes, which are glial cells in the posterior lobe of the pituitary gland. A malignant pituicytoma was found in the intracranial cavity of a 55-week-old male Sprague-Dawley rat. Macroscopically, the tumor was located on the sphenoid bone and involved the pituitary gland. The tumor was composed of sheets of fusiform cells with spindle- or pleomorphic-shaped nuclei and abundant eosinophilic cytoplasms. The cells were arranged in a whirling or irregular growth pattern. Some tumor cells were bizarre multinucleated giant cells with cytoplasmic eosinophilic hyaline droplets. Many tumor cells were strongly positive for vimentin and glial fibrillary acidic protein, and some cells were positive for ED-1 and S-100. These findings closely resembled those of a giant cell glioblastoma derived from the pituitary gland, suggesting anaplastic pituicytoma. From our review of the literature, we believe this is the first report of a spontaneous malignant pituicytoma in a rodent.     

An anaplastic astrocytoma (optic chiasmatic-hypothalamic glioma) in a dog

A tumor located in the optic nerve extended through the optic chiasm, involving the hypophysis and the hypothalamic area in a 3.5-year-old male Boxer dog. It showed a biphasic pattern in which numerous highly fibrillated, well-differentiated pilocytic areas were intermingled with pleomorphic, microcystic tumor tissue. Immunohistochemical analysis of the tumor revealed that most of the neoplastic cells were immunoreactive for S-100 protein, with less intensity for glial fibrillary acidic protein (GFAP) and vimentin. A diagnosis of anaplastic astrocytoma was made on the basis of the histopathologic findings and immunohistochemical results. Moreover, there were similarities with the malignant variant of pilocytic astrocytoma described in human adults as an optic chiasmatic-hypothalamic glioma.     

Pathological features of olfactory neuroblastoma in an axolotl (Ambystoma mexicanum)

A one-year-old, female Mexican axolotl (Ambystoma mexicanum) had a rough-surfaced, polypoid, pink tumor mass of approximately 10 mm in diameter in the oral cavity. Histologically, the tumor extended from the ethmoturbinate region and into the oral cavity and had replaced some of the maxillary bone tissue. The tumor mass was composed of a lobular architecture of small round-shaped tumor cells with occasional Flexner-Wintersteiner-like rosette formation. There were no metastatic lesions in the other organs. Immunohistochemically, the tumor cells were partly positive for several neural markers (class III beta-tubulin, S-100 protein, and doublecortin) and intensely positive for an epithelial marker (cytokeratin AE1/AE3). These results suggest that the present tumor originated from neuroectodermal tissue. Considering the location and histological and immunohistochemical features of the tumor, a diagnosis of olfactory neuroblastoma was made.     

Malignant Peritoneal Mesothelioma with a Sarcomatoid Growth Pattern and Signet-Ring-Like Structure in a Female F344 Rat

We report a biphasic malignant mesothelioma in an aged female F344/DuCrlCrlj rat. Macroscopically, multiple pale brown nodules were observed in the abdominal cavity with retention of bloody ascites. Histopathologically, the tumor cells spread over the peritoneum and formed masses on the surface and underlying adipose tissues. The tumor cells dominantly proliferated in a solid, nodular or nest-like pattern with modest amount of fibrillar connective tissues, which contained hyaluronan. The tumor consisted of ovoid, polygonal or spindle-shaped cells that possessed eosinophilic cytoplasms including glycogen; some tumor cells showed a signet-ring-like structure. Multinucleated cells and mitosis were found frequently, and direct invasion to intra-abdominal organs and intravascular metastasis to the liver were observed. Immunohistochemically, keratin and mesothelin were strongly positive in most of tumor cells, while vimentin was mainly positive in spindle-shaped cells. Podoplanin was also positive, particularly in the cell membrane of tumor cells. Electron microscopically, tumor cells showed an intercellular desmosome-like structure, basement membrane and microvillus. We diagnosed the case as a malignant peritoneal mesothelioma with a sarcomatoid growth pattern and signet-ring-like structure.     

Otopathy secondary to trigeminal schwannoma in a Quarter Horse

Otitis media secondary to trigeminal nerve (CN-V) paralysis is described in dogs and humans but not in horses. An 18-month-old Quarter Horse colt was presented with history of mastication difficulties and a nonhealing corneal ulcer. Clinical findings were consistent with paralysis of the right CN-V. Computed tomography imaging showed otopathy media and a mass at the root of the CN-V. The colt was euthanised due to poor prognosis. Post-mortem magnetic resonance imaging showed enlargement of the right CN-V which was slightly hyperintense on T2W. Histopathology of the mass revealed fusiform tumoural cells, positive on vimentin- and S100 immunohistochemistry, consistent with a schwannoma. Otitis media was presumed secondary to CN-V paralysis and denervation of the right tensor veli palatini muscle involved in opening of the Eustachian tube. This is the first case of trigeminal schwannoma and secondary otopathy media described in a horse, which highlights the importance of imaging in investigating trigeminal nerve paralysis.     

Iridociliary epithelial tumors in 100 dogs and 17 cats: a morphological study

The morphological features of iridociliary epithelial tumors in 100 dogs and 17 cats were reviewed. Twenty-seven cases were in either Golden Retrievers or Labrador Retrievers. Affected globes were stained for light microscopy with alcian blue, periodic acid Schiff (PAS) and hematoxylin and eosin stains. Selected tissues were examined by immunohistochemistry for vimentin, desmin, cytokeratin, S-100, neuron-specific enolase (NSE), and glial fibrillary acid protein (GFAP). The presence or absence of hyaluronic acid was recorded by staining with alcian blue before and after digestion of the tissue with hyaluronidase. Canine tumors were divided into papillary and solid tumors based on the pattern of growth. Twenty-eight of 57 papillary tumors exhibited invasive behavior including eight of the 57 which showed infiltration of the sclera. Twenty-nine of 43 solid tumors were invasive including 13 of 43 with scleral invasion. Tumors with scleral invasion were designated adenocarcinoma. Tumors of both types could be pigmented or nonpigmented and often contained smooth basement membranes reminiscent of the inner membrane of the nonpigmented ciliary body epithelial cell. All of the feline tumors were nonpigmented and 14 of 16 feline tumors were solid and two of the tumors were papillary. Eighteen of 20 canine tumors and three of four feline tumors stained positive for vimentin. Cytokeratin stain was positive only in a few of the highly aggressive tumors. The finding of pigmented epithelial cells, thick, smooth basement membrane structures, positive staining for vimentin, S-100, and NSE as well as hyaluronic acid deposition were considered to be features which define iridociliary epithelial tumors in dogs. The positive staining for vimentin and NSE are highly specific markers which help to characterize iridociliary epithelium and distinguish this tumor from metastatic epithelial tumors. The finding of solid nonpigmented tumors with small epithelial cells packeted by thin PAS-positive membranes staining positive for vimentin were considered significant features defining iridociliary epithelial tumors in cats. Follow-up information on survival and cause of death was obtained on 43 canine cases and only two feline cases. The average follow-up interval in dogs was 25 months and only two dogs died with lesions that could have been due to metastasis although neither was confirmed. We concluded that neither iridociliary adenomas nor adenocarcinomas is likely to metastasize.     

Malignant schwannoma in an American buffalo (Bison bison bison)

A case of a malignant schwannoma in a 20-year-old male American buffalo (Bison bison bison) from the Grand Park Zoo, Gyeonggi Province, Republic of Korea is reported. The animal showed no apparent clinical signs before death except for wound on the neck. Grossly, neoplastic nodules of various sizes were observed on the skin, lung, heart, liver, stomach, mesentery and kidney. Histologically, the neoplastic nodules were composed of fusiform cells that formed multidirectional bundles. The tumour cells were arranged in interlacing bands and bundles. The nuclei were atypical, hyperchromatic, with blunt or round ends. In addition, few mitotic figures were observed in the skin, lung, heart, liver, stomach, intestine and kidney. Several immunohistochemical stains, e.g. vimentin, cytokeratin (CK), smooth muscle actin (SMA), S-100 and HMB45, were used in an attempt to differentially diagnose the tumour. The neoplastic cells tested positive to S-100, but negative to vimentin, CK, SMA and HMB45. Based on the above findings, this case was diagnosed as a malignant schwannoma. To the best of our knowledge, this is the first report of a schwannoma in an American buffalo (B. b. bison).     

Spontaneous listeric encephalitis and neuritis in sheep. Light microscopic studies

Sixteen of 17 sheep with spontaneous listeric encephalitis had neuritis characterized by diffuse and focal intrafascicular and perineural accumulations of lymphocytes, plasma cells, macrophages and neutrophils in one or more cranial nerves. Nine sheep had extensive trigeminal neuritis which was usually unilateral. Brain lesions were mainly in the stem and were foci of macrophages or neutrophils or both, malacia, neutrophilic neuronophagia, vascular cuffing, and meningitis. Lesions in the brain and trigeminal ganglia were most severe on the same side as the affected trigeminal nerve. Gram-positive bacilli were in proximal parts of cranial nerves in foci of inflammatory cells and occasionally in morphologically intact nerve fibers. Organisms in the brain were in phagocytes in areas of inflammation and in scattered neurons and axons. The results were consistent with centripetal migration of the infectious agent along one or more branches of the trigeminal nerve to the brain and dissemination in the brain stem occurring, at least partly, along fiber tracts. Intraaxonal movement of bacteria probably is a mechanism involved in the pathogenesis of this disease.     

Highly metastatic ovarian yolk sac carcinoma in a rat

We investigated a highly metastatic ovarian yolk sac carcinoma in a 52-week-old female Crl:CD(SD) rat. Macroscopically, the present case had severe ascites, bilateral ovarian masses and numerous nodules in the abdominal and thoracic cavities. Histopathologically, these masses and nodules were generally composed of two types of cells mimicking a parietal and visceral yolk sac. The parietal cells were round to polygonal, contained eosinophilic droplets and were arranged in nests and cords in the eosinophilic matrix. Both the intracytoplasmic droplets and the matrix were stained positively with PAS. The visceral cells were cylindriform, and proliferated in papillary and tubular patterns and occasionally formed Shiller-Duval body-like structures. In the dissemination sites, the neoplastic cells proliferated on the surface of the various tissues and often infiltrated into deeper parts of the tissues. Immunohistochemically, both neoplastic cells were positive for α-fetoprotein and keratin, and the eosinophilic matrix was positive for laminin. Ultrastructurally, the parietal cells had dilated rough endoplasmic reticulums, which were filled with electron-lucent laminated structures. The visceral cells had poorly to moderately developed intracytoplasmic organelles and were interconnected with desmosomes. Taken together, the present tumor was diagnosed as yolk sac carcinoma arising from the ovary and was characterized by not only high metastasis but also invasive infiltration with biphasic proliferation of the parietal and visceral cells.     

Cytology of a mass on the meningeal surface of the left brain in a dog

An 11-year-old neutered male Labrador Retriever presented to Tufts University School of Veterinary Medicine for a 2-week history of seizures and altered behavior. Magnetic resonance imaging (MRI) revealed a homogeneously enhancing mass involving the surface of the left temporal, parietal, and occipital lobes of the brain, causing secondary hydrocephalus. Cytology samples obtained during rostrotentorial craniectomy contained abundant amorphous pink material suggestive of neuropil, scattered leukocytes, capillary fragments, large polyhedral nerve cell bodies, and other smaller cells with pale blue cytoplasm that occasionally were vacuolated and contained fine eosinophilic granules. The cytologic diagnosis was neoplasia, possibly meningioma. Ninety days after surgery the patient was euthanized after MRI results confirmed regrowth of the tumor. Histologic samples of the meningeal lesion collected at necropsy consisted of sheets and nests of loosely packed, large polygonal cells that compressed the brain parenchyma. The cytoplasm was eosinophilic and slightly granular, whereas nuclei were dense and eccentric. Neoplastic cells stained positive for S-100 protein, periodic acid-Schiff, and were partially diastase resistant. Vimentin staining was negative. Ubiquitin staining was light but diffusely positive. Ultrastructural features of the neoplastic cells included numerous secondary lysosomes and irregular pleomorphic nuclei. The final diagnosis was meningeal granular cell tumor. This case documents the cytologic and histologic features of an uncommon type of meningeal tumor.     

Disseminated liposarcoma in a dog.

A 9-year-old, female Mongrel dog was presented for posterior hindlimb weakness, inability to stand, and pain in the lumbosacral and pelvic regions. Radiography revealed a lytic lesion extending from L5 to L6 to the ilium. At necropsy, an 8 x 2 to 3.2 x 3 cm, irregular, white, firm mass was identified extending from the left dorsolateral aspect of the L6 vertebrae to the sacrum, crossing the sacroiliac joint to the ilium, and reaching the acetabulum without affecting the joint cartilage. Tumor masses were also present bilaterally near the costochondral junction of several ribs. White, soft nodules were present in the heart, pericardium, lungs, spleen, and kidneys as well. Histologically, osteolysis with disruption of the cortical bone and reactive bone with the presence of multinucleated osteoclasts was noted. Neoplastic cells consisted of variable, small basophilic round cells (SBRC) with very scant cytoplasm, larger polygonal cells with abundant eosinophilic cytoplasm, and vacuolated cells resembling adipocytes. Within the marrow cavity, vacuolated cells with necrosis predominated, whereas in periosteal areas, polygonal and vacuolated cells that were mixed with a lower percentage of SBRC were more common. In the lungs and heart, SBRC predominated, and in the spleen, polygonal cells were more numerous. Tumor cells stained positive for vimentin and S-100 and stained negative for CD99, neuron-specific enolase, synaptophysin, chromogranin A, cytokeratins, desmin, myoglobin, and actin. This tumor most likely arose from the marrow cavity of the L6 and later invaded through the vertebral body into adjacent vertebrae and various visceral sites.     

Canine ocular gliomas: a retrospective study

Objective The purpose of this paper is to classify glial tumors observed in the canine retina and optic nerve, describe the histopathological features and provide prognostic information on these neoplasms. Methods The database of the Comparative Ocular Pathology Laboratory of Wisconsin (COPLOW) was searched to collect canine glioma cases. Clinical and follow-up information was gathered from submission forms and an extensive follow-up survey. Slides were reviewed to describe the histopathological characteristics of the neoplasm and classify them. Immunohistochemistry for Glial Fibrillary Acidic Protein (GFAP) was performed in all cases. Results 18 canine glioma cases were found in the COPLOW database. There was no breed or gender predilection. The mean age was 9.33 ± 3.67 years. Follow-up information was available for 12 dogs, 8 of which were dead at the time of most recent contact, with a survival time ranging from 0 days (globes received after euthanasia) up to 20 months post-enucleation. In 6 of the 8 dogs that had died during this stud), tumor extended to the margin where the optic nerve had been sectioned. Light microscopic examination of the optic nerve of the affected eyes of four dogs that were still alive during this study revealed no tumor at this surgical margin. One neoplasm was classified as low-grade astrocytoma, 5 tumors as medium-grade astrocytoma, 11 tumors as high grade-astrocytoma and 1 tumor as oligodendroglioma. GFAP was positive in all but two tumors. Conclusion Retinal and optic nerve gliomas may be considered as differential diagnoses of intraocular and orbital masses. The metastatic potential appears to be low, but ascending invasion into the ventral aspect of the brain is possible.     

Gliomatosis cerebri in six dogs

Gliomatosis cerebri is a well-recognized entity in human medicine characterized by unusually widespread infiltration of the neuraxis by neoplastic glial cells with relative preservation of brain architecture. This report describes the pathologic features of the disease in six dogs. The dogs ranged from 3 to 9 years of age (mean 6.1 years) without evidence of breed predilection; five of the six dogs were neutered or intact males. The clinical findings were mixed (including depression, circling, cranial nerve deficits), reflecting the diffuse nature of the disease. Histologically, there was remarkably diffuse infiltration of the white and gray matter of the brain by small numbers of elongated neoplastic cells. Areas of greater cellularity formed grossly visible lesions in four cases. Anisocytosis and pleomorphism were greater in areas of higher cellularity. Other features of tumor growth included subpial accumulation, neuronal satellitosis, perivascular cuffing, and tropism for cranial nerve and brain stem nuclei. Neoplastic cells were negative on immunohistochemical stains for glial fibrillary acid protein (GFAP) and leukocyte markers, reflecting the uncertain histogenesis of these unusual neoplasms.     

Cranial teratomas in two domestic ducks (Anas platyrhynchos domesticus).

Teratomas are rare tumors in domestic fowl, and none have been reported in the cranial area of ducks. Clinical signs and gross and microscopic findings associated with a cranial teratoma in two domestic ducks are reported. One tumor arose within the cranial vault and was associated with neurologic signs. The other tumor was subcutaneous and invaded the parietal bone but did not extend into the brain. Both tumors were tridermic.     

Primary subcutaneous leiomyosarcoma of the hamster hind leg

We report the first case of a primary subcutaneous leiomyosarcoma that originated in the hind leg of a hamster and metastasized to the bone marrow, lung and diaphragm. A 10-month-old female Syrian golden hamster was presented with a large, firm, white subcutaneous mass in the right hind leg. The tumor invaded into the bone marrow and small nodules were also present in the lung and diaphragm; however, no tumor masses were found in the visceral organs. Histologically, the tumors were spindle cell sarcomas, composed of densely packed pleomorphic spindle cells with oval to elongate nuclei and moderate amounts of eosinophilic cytoplasm. Immunohistochemically, the neoplastic cells were positive for vimentin, desmin, and smooth muscle actin, but negative for alpha-sarcomeric actin and S-100. Thus, the diagnosis was primary leiomyosarcoma of the hind leg with metastasis to the bone marrow, lung and diaphragm. To the best of our knowledge, this is the first report of spontaneous primary subcutaneous leiomyosarcoma of the hind leg with distant metastasis in laboratory animals.