Metastatic Canine Phaeochromocytoma with Unusual Manifestation.

We report the clinical, pathological and immunohistochemical characteristics of a phaeochromocytoma (PCC) in a 9-year-old male neutered Golden Retriever dog. The dog presented with acute onset of deteriorating cervical pain but was otherwise normal on general physical and neurological examinations. Magnetic resonance imaging of the cervical spine revealed a focal, extramedullary, infiltrative, poorly demarcated, heterogeneous mass with moderate contrast enhancement at the left cranial articular process of C2, associated with osteolysis and pathological fractures of C2, and marked soft tissue trauma. Due to the severe lesions and grave prognosis, the dog was euthanized. Post-mortem examination revealed severe enlargement of the right adrenal gland due to a neoplasm of the adrenal medulla. C2 was lytic and there was a white, well-demarcated, firm neoplastic mass in the surrounding musculature. Neoplasms were also present in, and adjacent to, the prostate gland and in pulmonary lymph nodes. Histologically, the neoplasms were composed of dense sheets and nests of small, round to polyhedral cells with frequent palisading along fine connective tissue septa, karyomegaly, multinucleated cells and frequent mitotic figures. Immunohistochemically, neoplastic cells expressed chromogranin A and synaptophysin. Gross, microscopic and immunohistochemical findings support the diagnosis of PCC, originating from the right adrenal gland, with multiple metastases in the cervical spine, prostate gland and pulmonary lymph nodes. This case highlights the difficulty of intra-vitam diagnosis of PCC as its manifestation can be highly variable. PCC should be considered as a rare but possible differential diagnosis for painful vertebral masses in elderly dogs.

Four Cases of the Melanotic Variant of Malignant Nerve Sheath Tumour: a Rare, Aggressive Neoplasm in Young Dogs with a Predilection for the Spinal Cord.

Four cases of a rare melanotic variant of malignant nerve sheath tumour (MNST) in dogs are described. All four cases presented with neurological clinical signs due to multicentric, intradural, intra- and extraparenchymal neoplasms that surrounded the spinal and cranial nerves and infiltrated the adjacent spinal cord and brain. The dogs were young (3 months to 3 years of age), all were female and four different breeds were represented. Characteristic histological features were interweaving fascicles of spindle-shaped cells, sometimes with an architecture reminiscent of Antoni A and B patterns. Some spindle cells showed prominent cytoplasmic melanin pigmentation and such cells were positive by Masson-Fontana stain. Immunohistochemistry performed in three cases was positive for S100 and vimentin, strongly positive for melan A in the melanized cells and negative for glial fibrillary acidic protein and periaxin. Non-melanized cells did not express melan A. Transmission electron microscopy findings in one case were consistent with a peripheral nerve sheath tumour and demonstrated cytoplasmic pre-melanosomes and melanosomes. Melanotic variants of MNSTs are rare in animals with only a solitary report of two previous canine cases in the literature.

Central nervous system metastasis of an intradural malignant peripheral nerve sheath tumor in a dog.

An 8-yr-old French Bulldog was presented with a non-ambulatory tetraparesis. Magnetic resonance showed an intradurally located mass at the level of the right second cervical nerve root. The mass was surgically removed and the dog was ambulatory within 4 d. A 10-mo post-surgical imaging follow-up revealed a recurrence of the primary mass and another intradural/intramedullary mass at the level of the first thoracic vertebral body. Overall histological features were suggestive of malignant peripheral nerve sheath tumor (MPNST) for both masses. Immunohistochemistry was found weak but diffusely positive for S-100 and neurono-specific enolase for both masses. A diagnosis of primary MPNST for the cervical mass and of metastasis for the thoracic mass was made, possibly disseminated via the subarachnoidal space. To our knowledge, the central nervous system metastasis of MPNSTs has not previously been reported in dogs. The clinician should be aware that these tumors, albeit rarely, can metastasize to the central nervous system.

Pathology and immunohistochemistry of a malignant nerve sheath tumor in a pig: case report and brief review of the literature.

A 7-y-old sow with a large mass in the right upper thoracic limb was submitted for autopsy. Grossly, the mass encompassed the right humerus, elbow, and proximal radius and ulna. On cut surface, the mass was solid, lobulated, pale tan, and firm, with multifocal areas of necrosis and mineralization; it replaced the brachial musculature, invading and causing extensive humeral and ulnar osteolysis. The periosteum was roughened and irregular, and there was minor invasion into the elbow joint. Histologically, the mass was composed of densely cellular interweaving streams and bundles of pleomorphic spindle cells embedded in a scant fibrovascular stroma. There was moderate-to-strong, diffuse cytoplasmic or membranous immunoreactivity to claudin-1, laminin, and vimentin; weak-to-moderate, multifocal cytoplasmic and nuclear immunoreactivity to S100 and Sox-10, respectively, and weak cytoplasmic immunoreactivity for neuron-specific enolase. No neoplastic immunolabeling was detected with CD204, CD18, desmin, glial fibrillary acidic protein, ionized calcium-binding adapter molecule 1, melan A, neurofilament, nerve growth factor receptor, smooth muscle actin, or muscle pan-actin. A specific immunomarker for definitive diagnosis of a malignant nerve sheath tumor (MNST) and its differentiation from other nerve tumors or other spindle cell tumors is still lacking in veterinary medicine, and case-by-case or interspecies differences in immunohistochemistry (IHC) expression can occur even when applying a broad diagnostic IHC panel. However, the gross, histologic, and IHC features in our case were consistent with a MNST, an exceedingly rare neoplasm of pigs.

Spinal Cord Compression in a Horse due to a Granular Cell Variant of Neurofibroma.

A neurofibroma of granular cell subtype is described in a 7-year-old horse. The horse had a 3-month history of ataxia affecting the forelimbs and hindlimbs, suggesting a C1-C6 neuroanatomical localization. Post-mortem examination revealed an intradural mass arising from the right sixth cervical spinal nerve and compressing the spinal cord. Histologically, the mass was composed largely of wavy spindle cells (a mixture of Schwann cells, perineurial cells and fibroblasts) intimately associated with ropy collagen fibres. Approximately 25% of the spindle cells were swollen and contained densely-packed, eosinophilic and periodic acid-Schiff-positive cytoplasmic granules. Immunohistochemistry for S100 and glial fibrillary acidic protein antigens labelled a proportion of neoplastic cells, while the cytoplasmic granules were positive for S100 and neuron specific enolase. This is the first report of a neurofibroma with granular cell differentiation in an animal. Granular cell differentiation in other peripheral nerve sheath tumours of animals is briefly discussed.

Compartmental resection of peripheral nerve tumours with limb preservation in 16 dogs (1995-2011).

Peripheral nerve tumours (PNTs) affecting the limbs may lead to chronic pain, lameness and/or monoparesis that is refractory to medical treatment. The most common radical therapy for PNTs has been surgical excision with limb amputation. However, compartmental resection with preservation of the limb has been performed by the authors with favourable clinical results and therefore this bi-institutional retrospective study was undertaken to assess limb function, survival and recurrence. Sixteen dogs that had been diagnosed with PNTs between 1995 and 2011 met the inclusion criteria for this study. In the majority of the cases, good to excellent limb function was achieved. The overall median survival time (MST) was 1303days (42.8 months; range, 14 days-4639 days, [0.5-152.4 months]), with two dogs still alive at time of evaluation. Non-infiltrated margins were the best prognostic indicator; dogs with non-infiltrated margins had a MST of 2227days (P<0.001) compared to dogs with infiltrated margins (MST of 487 days). The 1-year calculated survival rate was 68.8% and the 2- and 3-year calculated survival rates were 62.5%. Surgical treatment with tumour removal and limb spare for proximal and distal PNTs can be successful. Compartmental excision can lead to good limb function, producing survival comparable to limb amputation, and should therefore be considered as an alternative to limb amputation in canine PNTs.

Meningeal dissemination of a pituitary carcinoma to the cauda equina in a dog.

An 8-year-old spayed female border collie dog was diagnosed with an invasive pituitary macrotumor. Five months after radiation therapy, the patient developed paraparesis and lumbosacral pain. Necropsy revealed a pituitary carcinoma with cauda equina drop metastasis. In cases of pituitary masses, meningeal dissemination should be considered if neurologic status declines.

Dissémination méningée d'un carcinome pituitaire à la queue de cheval chez un chien. Une chienne Border collie stérilisée âgée de 8 ans a été diagnostiquée avec une macrotumeur pituitaire invasive. Cinq mois après la radiothérapie, la patiente a développé de la paraparésie et de la douleur lombo-sacrée. La nécropsie a révélé un carcinome pituitaire avec une métastase de la partie inférieure de la queue de cheval. Dans les cas des masses pituitaires, la dissémination méningée devrait être considérée s'il se produit un déclin de l'état neurologique.(Traduit par Isabelle Vallières).

Concomitant Malignant Pulmonary Peripheral Nerve Sheath Tumour and Benign Cutaneous Peripheral Nerve Sheath Tumour in a Dog.

Peripheral nerve sheath tumours (PNSTs) are neoplastic growths derived from Schwann cells, perineural cells or both. Malignant PNSTs (MPNSTs) are uncommon in domestic animals. This report describes the concomitant occurrence of PNSTs in a 10-year-old female cocker spaniel with a clinical history of respiratory impairment. Grossly, there was a large infiltrative mass in the caudal lobe of the right lung; smaller nodules were observed in the other lobes of the right lung. Furthermore, a small encapsulated cutaneous nodule was observed on the left hindlimb. Histopathology of the pulmonary tumours revealed the proliferation of pleomorphic spindle-shaped cells with moderate mitotic index arranged in interwoven bundles and concentric Antoni A and Antoni B patterns; invasion of the adjacent pulmonary tissue was observed. The cutaneous nodule consisted of neoplastic mesenchymal cells in interwoven bundles with concentric whorls, but without the marked anisokaryosis, binucleation and infiltrative growth seen in the pulmonary tumour. Immunohistochemistry revealed that both tumours were immunoreactive for vimentin, glial fibrillary acidic protein and S100 protein, but were negative for factor VIII. These findings are indicative of a MPNST in the lung with a concomitant benign PNST in the limb. This case represents the first report of a primary MPNST in the lung of a dog. This neoplastic growth should be included in the differential diagnosis of primary malignant pulmonary tumours of dogs.

Disseminated peripheral neuroblastoma in a Rhodesian Ridgeback dog.

CASE REPORT: A 4-year-old neutered male Rhodesian Ridgeback dog with right-sided Horner's syndrome, bilateral laryngeal paralysis, neck pain and bilateral hindlimb ataxia was euthanased following deterioration of its neurological status. Necropsy examination revealed an off-white retropharyngeal neoplastic mass (100 × 30 × 30 mm) attached to the base of the skull on the right side and macroscopic nodular metastases in the spleen and three vertebral bodies (C6, C7 and T6), including a nodule attached to the dura at C7. Histological evidence of neuroblastic tumour was detected in these macroscopic lesions, a regional lymph node, bone marrow of a femur and all 15 vertebral bodies (C1-T8) examined, including the three with macroscopic metastases, and in the lumens of small blood vessels in the lungs and liver. Ganglion cell differentiation was detected only in the primary retropharyngeal mass, one splenic nodule and the C7 dural nodule. Neoplastic cells were immunoreactive to neurofilament protein (ganglion cells only), vimentin and synaptophysin, and were negative for S100 protein, GFAP, CD3 and Pax5. CONCLUSION: The diagnosis was disseminated peripheral neuroblastoma, differentiating subtype (International Neuroblastoma Pathology Classification), with likely primary involvement of the right cranial cervical ganglion. This appears to be the first report of neuroblastoma in a dog with widespread occult haematogenous metastasis to bone marrow.

Imaging diagnosis-paraganglioma of the cauda equina: MR findings.

The magnetic resonance imaging features of a cauda equina paraganglioma in a 5-year-old dog are described. Imaging revealed a well-defined, strongly contrast-enhancing mass invading the adjacent vertebral body and infiltrating the intervertebral foramen bilaterally. Flow void, compatible with increased drainage veins around the mass, and macroscopically visible neovessels in contrast-enhanced magnetic resonance angiography, as reported in numerous human studies, were not visible in this single case. The tumor recurred despite aggressive surgery and radiotherapy. This neoplasm should be considered in the differential diagnosis of cauda equina abnormalities in dogs.

Peripheral neuroblastomas in dogs: a case series.

The peripheral neuroblastic tumours (PNTs) include neuroblastoma, ganglioneuroblastoma and ganglioneuromas. These subtypes reflect a spectrum of differentiation of progenitor cells of the sympathetic nervous system from tumours with predominant undifferentiated neuroblasts to those consisting of neuronal cell bodies that are well differentiated. Peripheral neuroblastoma is a tumour composed of neuroblastic cells with no or limited neuronal differentiation. In dogs, peripheral neuroblastoma is rare. The present report documents nine cases of canine peripheral neuroblastoma, the majority occurring as large masses in the craniodorsal abdominal cavity of young dogs (mean age of 3 years at diagnosis). Microscopically, all of the masses consisted of round to oval cells with a scant cytoplasm and hyperchromatic nuclei. Homer-Wright rosettes and pseudorosettes were evident in three of the nine cases. Neoplastic cells were immunoreactive in varying degrees to S100, neuron-specific enolase, synaptophysin, chromogranin A, tyrosine hydroxylase (one case) and were negative for vimentin, cytokeratin, CD3 and CD79a, indicating a neurogenic nature. Four of the nine cases occurred in Labrador retrievers (44%) and two (22%) in boxers, suggesting a possible breed predisposition.

Primary brachial plexus neoplasia in cats.

Conditions affecting the brachial plexus and its branches can cause lameness and/or neurological deficits. There are few reports of schwannomas in cats. In reported cases, the tumours arose from the dermis or subcutis of the limbs, head and neck and thorax, but there are no reports of primary tumours that arose from the brachial plexus itself. The purpose of this study is to present the clinical, radiological, ultrasonographical and pathological findings of primary brachial plexus tumour in three cats.

Claudin-1 and glucose transporter 1 immunolabelling in a canine intraneural perineurioma.

A 4-year-old male leonberger was diagnosed tentatively with a peripheral nerve sheath tumour of the median nerve based on neurological examination, electrodiagnostic testing and ultrasound evaluation. The lesion was excised and submitted for pathological examination. Histopathology revealed an irregularly enlarged, hypercellular nerve fascicle with neoplastic tissue consisting of a uniform population of spindle-shaped cells arranged in 'pseudo-onion bulb-like' whorls around axons. Minimal anisocytosis and anisokaryosis were present, together with a low mitotic index. Electron microscopy showed spindle cells with a discontinuous basal membrane and intercellular junctions, as well as pinocytotic vesicles. Immunohistochemistry for neurofilament, S100 and glucose transporter 1 was negative, whereas labelling for claudin-1 and laminin was positive. Based on these observations, a definitive diagnosis of intraneural perineurioma was made.

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.

A neurotropic lymphoma in the brachial plexus of a cat.

A 7-year-old, intact male domestic shorthair cat was presented with a progressive, non-weight-bearing lameness of the right forelimb. A neurological examination of the patient at the Small Animal Clinic revealed a paralysis of the radial nerve with sustained cutaneous sensation and a hyperaesthetic response. Further clinical, radiological and pathological findings lead to a diagnosis of a primary, neurotropic B-cell lymphoma in the brachial plexus.

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.