Dysplastic gangliocytoma of the cerebellum in a cat.

A 2.5-year-old cat presented with progressive ataxia and lethargy. Magnetic resonance imaging (MRI) showed enlargement of the cerebellum and herniation of cerebellar vermis. Postmortem examination confirmed the MRI findings, and histopathology showed numerous large dysplastic neurons populating and displacing the Purkinje cell layer and extending into the molecular and granular layers of the cerebellum. The lesion was diagnosed as dysplastic gangliocytoma of the cerebellum. In humans, this tumor is often associated with Cowden syndrome, a genetic disorder characterized by multiple hamartomas and an increased risk of developing certain neoplasms, known to be linked to a germline mutation of the phosphatase and tensin homolog (PTEN) gene. Reduction in PTEN nuclear and cytoplasmic immunohistochemical labeling of dysplastic neurons in this case suggested a possible PTEN mutation involved in the tumorigenesis. This report provides a detailed pathology description of the tumor and the use of neuronal and PTEN markers which will help guide pathologists presented with this rare condition in the future.

Outcome of a dog undergoing definitive-intent intensity-modulated radiation therapy for an intranasal ganglioneuroma.

An 11-year-old intact male Shiloh Shepherd was presented for evaluation of epistaxis, decreased nasal airflow, and destructive caudal nasal lesion identified using CT. Histopathologic evaluation of the nasal mass was consistent with a ganglioneuroma. The dog was treated with 10 × 4.2 Gy using IMRT technique. Post radiation therapy (RT), improvement in clinical signs were noted. Tumor progressed in size based on CT evaluation at 49 days, 3, and 6 months post-treatment. A grade 2 oral mucositis was the only RT side effect noted. Radiation therapy as described above was completed without evidence of high-grade radiation toxicities and has potential to improve clinical signs but failed to induce tumor response.

Intestinal ganglioneuroma in a neonatal Japanese black calf - Short communication.

A 1-day-old male calf presented with clinical signs of severe progressive abdominal distension. Abdominal radiographic and ultrasonic images revealed several loop-like structures in the small intestine, which were indicative of gas retention. Experimental laparotomy was performed. However, the calf died during surgery. At necropsy, a round, well-circumscribed mass (3 × 3 × 2.5 cm) was found in the jejunal wall, and the jejunal lumen was narrowed. The mass was firm and had white to grey appearance on the cut surface. Histologically, the submucosa and the muscle layer were diffusely thickened due to abundance of neural tissues comprising several fascicles of nerve fibres and large aggregates of ganglion cells. Some ganglion cells contained basophilic Nissl substances in their cytoplasm. Immunohistochemically, these cells were positive for S-100 and synaptophysin. Ultrastructural examination revealed that the neoplastic ganglion cells contained dense core vesicles in the cytoplasm. Based on these findings, the neoplastic lesion was diagnosed as ganglioneuroma in the jejunum.

Ganglioneuromatosis of the Gallbladder in a Dog with Cholecystitis and Cholestasis.

A 2-year-old entire female mixed-breed dog was presented with signs of cholestasis. Abdominal ultrasonography revealed a gallbladder with a thickened and hyperechoic wall and luminal calculi. Exploratory laparotomy with cholecystectomy was performed and histopathological examination of the specimens from the cholecystectomy demonstrated extensive proliferation of large, prominent nerves containing ganglion cells with no atypia mainly located in the gallbladder mucosa. The neural nature of these components was confirmed by immunohistochemical labelling with antibodies specific for synaptophysin, glial fibrillary acidic protein, S100 protein and neurofilaments. Based on these findings, the lesion was diagnosed as ganglioneuromatosis. Reports of ganglioneuromatosis in animals have so far been restricted to the intestine. This is the first case of ganglioneuromatosis affecting the gallbladder in an animal in which no intestinal involvement was apparent.

Lingual ganglioneuroma in a dog.

A mass was found at the base of the dorsum linguae of a male 11-year-old Labrador retriever. The tumor comprised of ganglion cells and Schwannian cells with Verocay bodies. The ganglion cells were positive for neuron-specific enolase, S-100, nerve growth factor receptor, and beta III tubulin. The Schwannian cells were positive for neuron-specific enolase, S-100, nerve growth factor receptor, and glial fibrillary acidic protein. The lingual mass was diagnosed as a ganglioneuroma. To our knowledge, there has been no previous report of a lingual ganglioneuroma in a dog.

Cardiac ganglioneuroma in a juvenile pig.

A cardiac mass (3 × 5 × 3 cm) was detected at the base between the right auricular wall and right vena cava of a slaughtered 6-month-old female mixed-breed pig during a meat inspection. The tumor comprised infiltrative prominent interweaving fascicles of Schwann cells with Verocay bodies. Moreover, the ganglion cells were scattered or aggregated throughout the neoplastic tissue. The ganglion and Schwann cells had neither cellular atypism nor mitosis. On the basis of the bearing site as well as the morphological and immunohistochemical features, this is the first case of a cardiac ganglioneuroma in a pig.

Ileal ganglioneuromatosis in a piglet: histopathological and immunohistochemical studies.

Ganglioneuromatosis (GNM) is a rare condition characterized by the benign proliferation of ganglion cells, nerve fibres and supporting cells of the enteric nervous system. Necropsy examination of a female piglet weighing 4 kg revealed a well-demarcated 20 cm segment of terminal ileum with thickening of the wall. Microscopically, the lamina propria was infiltrated by enteric glial cells and large ganglion cells. Within the submucosal and muscular layers, aggregates of neurons were interlaced by Schwann cells and enteric glial cells arranged in concentric rings. Immunohistochemically, the neurons were weakly labelled for S-100 and neuron-specific enolase, Schwann cells expressed S-100 and vimentin and enteric glial cells expressed glial fibrillary acidic protein and S-100. Pathological and immunohistochemical findings supported the diagnosis of ileal GNM.

Transmural ileal ganglioneuromatosis in a young Boer goat (Capra hircus).

A diagnosis of transmural ileal ganglioneuromatosis was made in a 15-day-old goat that was found dead following a period of diarrhoea and inappetence. Grossly, the entire length of the wall of the ileum was pale and firm with a variably segmental to transmural thickening. Microscopically, the ileal transmural thickening was due to a diffuse proliferation of both ganglionic and glial cells forming cell nests or packets that infiltrated the wall and into the mesentery surrounding a mesenteric lymph node. The neoplastic ganglionic cells were immunoreactive for S100, synaptophysin and triple neurofilament, while the glial spindle cells were immunoreactive with glial fibrillary acidic protein, S100 and laminin confirming their Schwann cell identity. Nerve fibres expressing neurofilament protein 200 and phosphorylated neurofilament (SMI-31) were observed rarely. Ganglioneuromatosis is defined as diffuse exuberant proliferation of all components of the intestinal ganglionic plexuses. In man, the transmural form has more grave clinical consequences than a focal pattern and is commonly associated with germline mutations in the RET proto-oncogene. Whether there is any comparable molecular genetic abnormality in animals remains unknown; however, ganglioneuromatosis needs to be included in the differential diagnosis of tumours of the autonomic enteric nervous system.

Small intestinal ganglioneuromatosis in a dog.

A 9-year-old female neutered collie-cross dog was presented with a 2-month history of persistent diarrhoea, weight loss and intermittent vomiting. Abdominal ultrasonography revealed one loop of jejunum with a markedly thickened and multifocally hyperechoic wall, without loss of wall layering. Laparotomies were performed for biopsy and resection of affected intestine. Histopathological examination revealed small intestinal ganglioneuromatosis (GN). The dog recovered well from surgery and the diarrhoea resolved. Eleven months later the dog has gained weight and remains asymptomatic. This is the first report of small intestinal GN affecting a mature dog, in which pathology was localized to the mucosal lamina propria and surgical treatment resulted in a successful outcome.

A malignant and metastasizing feline cardiac ganglioneuroma.

In the current study, a case of a cardiac ganglioneuroma with systemic metastases in a cat is described. A 12-year-old male neutered Japanese domestic cat was brought to a veterinary hospital for dysorexia, coughing, vomiting, and diarrhea. Ultrasonography revealed a mass adjacent to the right atrium. The animal died of respiratory failure 1 month after the first visit to the hospital. At necropsy, an oval-shaped white mass 1.5 cm in diameter was observed within the right auricle. Diffusely, the right ventricle was infiltrated and thickened by the neoplastic lesion. Histologically, the mass was composed of 3 types of neoplastic cells: spindle cells, large polygonal cells, and small undifferentiated cells. Immunohistochemically, the neoplasia was positive for neuronal markers such as ßIII tubulin, S-100a, and protein gene product 9.5. Ultrastructurally, the large polygonal cells were characterized by abundant cytoplasm that included compressed Golgi cisternae and rough endoplasmic reticula and abundant intermediate filaments. A discontinuous basement membrane surrounded the spindle cells. Metastatic foci were found in the lungs, kidney, pancreas, urinary bladder, and adrenal glands. The morphological, immunohistochemical, and ultrastructural characteristics of the tumor cells were consistent with those of ganglioneuroma. The tumor was presumed to originate from the intramural parasympathetic ganglia in the right atrium.

Ganglioneuroma in the small intestine of a juvenile pig.

A mass was located in the small intestine of a slaughtered 6-month-old male Landrace-cross pig that had no clinical abnormalities. This egg-shaped well-circumscribed mass was situated in the submucosal and muscular tissue layers and protruded into the lumen. Histopathologically, the tumor comprised discrete or aggregated ganglion and schwannian cells in neuropil-like tissue. Some ganglion cells contained Nissl substance in their cytoplasm. The ganglion cells stained positive for neuron-specific enolase, class III ß-tubulin, neurofilament, and synaptophysin; the schwannian cells stained positive for vimentin, S-100 protein, and glial fibrillary acidic protein. The tumor was diagnosed as a ganglioneuroma in accordance with these findings. Here, we have reported detailed immunohistochemical findings in addition to the histopathological features of a swine ganglioneuroma.

Ganglioneuroma in the urinary bladder of a dog.

An 11-year-old male Labrador retriever presented with chronic oliguria. Ultrasonography findings revealed a protruding mass at the neck of the urinary bladder. A cystotomy was performed, and the mass was removed by ligation with surgical sutures. Histopathological examination revealed conspicuous foci with a variable number of ganglion cells in the tumor and abundant interwoven bundles of schwannian cells with fine fibers. The ganglion cells were positive for neuron-specific enolase and neurofilament. The schwannian cells were positive for vimentin, S-100 protein, and glial fibrillary acidic protein. Thus, according to the classification of tumor with neuronal cell differentiation, the urinary tumor was diagnosed as a ganglioneuroma.

Small intestinal ganglioneuromatosis in a dog.

A 6-week-old Staffordshire Bull Terrier cross was presented with a 4-week history of vomiting and small bowel diarrhoea. Abdominal ultrasound showed thickening of the distal jejunum and ileum. The dog underwent two exploratory laparotomies, during which grossly abnormal sections of intestine were resected. The patient developed septic peritonitis 48 h after the second surgery, caused by dehiscence of an intestinal anastomosis, and was euthanased. All intestinal tissue samples were examined histopathologically and a diagnosis of gastrointestinal ganglioneuromatosis was made. Intestinal ganglioneuromatosis is rare and this case represents a novel occurrence in the small intestine of a dog.

Colorectal hamartomatous polyposis and ganglioneuromatosis in a dog.

A 5-month-old female Great Dane puppy was treated for hematochezia, tenesmus, and rectal prolapse by resection of a 10-cm-long segment of colon and rectum. Grossly, the colorectal segment had diffuse mucosal and submucosal thickening with multiple polypoid nodules. The histologic diagnosis was colorectal hamartomatous polyps with ganglioneuromatosis. Duplication of PTEN was detected by quantitative multiplex polymerase chain reaction testing. The presence of 2 hamartomatous colorectal lesions with PTEN mutation is similar to human Cowden syndrome.

Spontaneous ganglioneuroma possibly originating from the trigeminal ganglion in a B6C3F1 mouse.

In a carcinogenicity study, a neuronal tumor in the cranial cavity was observed in a 110-week-old female B6C3F1 mouse. At necropsy, the tumor was seen at the site of the pituitary gland. Histologically, the tumor consisted of well-differentiated ganglion cells, nerve fiber/neuropil-like elements and ganglion-like cells. The tumor was composed mainly of ganglion-like cells, which were arranged in solid sheets interspersed with thin fibrovascular stroma. Nissl substance was detected at the margin in the cytoplasm of well-differentiated ganglion cells, and nerve fibers were identified by the Kluever-Barrera method. Immunohistochemically, the well-differentiated ganglion cells were positive for S-100, neurofilament protein (NF), neuron-specific enolase (NSE), synaptophysin, and chromogranin A. The nerve fiber/neuropil-like elements were positive for S-100, NF, NSE, and glial fibrillary acidic protein (GFAP), and the ganglion-like cells were strongly positive only for NSE and synaptophysin. On the other hand, there were no pituitary cells, such as prolactin-positive or adrenocorticotropic hormone (ACTH)-positive cells in the tumor tissue. Detailed histopathological examination suggested that the tumor might be a ganglioneuroma arising from the trigeminal ganglion. This report provides additional histopathological evidence of peripheral nerve neoplasms in mice.

Ganglioneuroma of the brachial plexus in two cockatiels (Nymphicus hollandicus).

Ganglioneuroma involving the brachial plexus, paraspinal ganglia, and cervical-thoracic spinal cord was diagnosed in 2 adult cockatiels (Nymphicus hollandicus). Both birds had a chronic 1-year history of ataxia and perching difficulty. At necropsy, each bird had a unilateral, firm, gelatinous white to tan multilobular mass at the thoracic inlet expanding and partially obliterating the brachial plexus and cervical spinal cord. Histologically, the masses were characterized by a locally infiltrative neoplasm comprised of spindloid cells forming streams and sheets with interspersed distinct neuron cell bodies consistent with ganglion cells. The spindloid cell population was immunohistochemically positive for neurofilament protein in one of the birds.

Multiple cutaneous ganglioneuromas in a dog.

A 3-year-old male Labrador retriever dog was presented with multifocal small cutaneous nodules, distributed mainly over the thoracic wall, the flank and the scrotum. The dog was otherwise in good health and had no significant past medical history. Radio- and sonographic examination revealed no evidence of internal tumours, including endocrine tumours. Histological examination of two excised samples revealed round, non-ulcerated nodules in the superficial corium, characterized by two different neoplastic cell components and mild inflammation. The first tumour cell population showed histomorphological characteristics of mature ganglion cells; the second featured small, spindle-shaped tumour cells with scant cytoplasm. Both neoplastic cell components expressed vimentin, neurofilament protein, pan-neuronal neurofilament, amyloid-precursor protein and chromogranin A. In addition, the spindle-shaped tumour cells were positive for 2', 3'-cyclicnucleotide 3'-phosphodiesterase. The findings had many histological and immunohistochemical features in common with primary cutaneous ganglioneuromas in humans, enabling the canine tumours to be also classified as multiple cutaneous ganglioneuromas.

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.