A case of olfactory ganglioneuroblastoma in a dog: immunohistochemical comparison with olfactory neuroepithelia and olfactory neuroblastomas.

In the present study, histopathological and immunohistochemical findings of olfactory ganglioneuroblastoma in a dog were compared to those of canine olfactory neuroepithelia and neuroblastomas. Olfactory ganglioneuroblastoma consists of ganglion cell-like tumor cells with Schwannian stroma and neuroblast-like tumor cells. Immunohistochemically, ganglion cell-like tumor cells were immunopositive for synaptophysin, ß3-tubulin, and tyrosine hydroxylase, Schwannian stroma was immunopositive for GFAP and SOX2, and neuroblast-like tumor cells were immunopositive for OLIG2, ß3-tubulin, SOX2, cytokeratin AE1/AE3, and p63. The immunohistochemical results of olfactory neuroepithelia and olfactory neuroblastomas were similar to those of neuroblast-like tumor cells. These results suggest that the ganglion cell-like tumor cells in the present case have a sympathetic neuron immunophenotype, whereas neuroblast-like tumor cells have an olfactory neuroepithelial immunophenotype.

Olfactory neuroblastoma in a domestic cat and review of the literature.

Nasal tumors account for less than 10% of all feline neoplasms, with lymphoma, followed by adenocarcinoma, and squamous cell carcinoma, the most commonly reported. Nasal neuroectodermal tumors, including olfactory neuroblastoma (ONB), are scarcely described, and their tumorigenesis is largely unknown. Here we report the cytological, histological, and immunohistochemical features of a feline ONB. We also provide a pathological review of nasal neuroendocrine neoplasms in cats. A 7-year-old Burmese cat was evaluated for sneezing, occasional epistaxis, and upper respiratory noise for 8 months. Computed tomography (CT) imaging revealed a 7 × 5 × 3 mm irregular mass effacing and expanding the nasal cavity, which extended to the nasopharynx. Cytologically, neoplastic cells were round to polygonal and had a round nucleus with finely stippled chromatin, a single small nucleolus, and abundant pale blue cytoplasm, which contained abundant fine pale pink granules. They exhibited mild cellular atypia, anisocytosis, and mild to occasionally moderate anisokaryosis. Rhinoscopic biopsies revealed a densely cellular, malignant neuroepithelial neoplasm. Cells were arranged in densely packed trabeculae and formed Homer Wright and Flexner-Wintersteiner-like rosettes, with rare mitotic figures and scant supportive fibrovascular stroma. Immunohistochemically, neoplastic cells were positive for vimentin, cytokeratin AE1/AE3, COX-2, and beta-tubulin and negative for S-100, chromogranin A, CD117, and epithelial membrane antigen (EMA). An ONB was diagnosed based on histological and immunohistochemical findings. Interestingly, and similar to nasal carcinomas, neoplastic cells diffusely neo-expressed COX-2. To the authors' knowledge, there is no previous evidence of COX-2 in feline ONB. Histopathology and immunohistochemistry are required for a definitive diagnosis of ONB.

Excisional biopsy and radiotherapy for management of an olfactory neuroblastoma in an axolotl (Ambystoma mexicanum).

CASE DESCRIPTION: A 4-year-old sexually intact male leucistic axolotl (Ambystoma mexicanum) was presented with a 2-week history of dysrexia and difficulty swallowing. CLINICAL FINDINGS: Physical examination revealed a 1-cm-diameter intraoral mass on the rostral aspect of the palate and swelling of the left nasal fossa. Local invasion into the left nasal fossa was suspected during oral examination. The lesion was marginally excised, and an incompletely excised olfactory neuroblastoma was diagnosed histologically. Five weeks later, physical examination revealed persistent erythema, delayed healing of the rostral portion of the palate, and a mild facial deformity associated with a white mass in the nasal cavity. TREATMENT AND OUTCOME: 6 weeks after excision, adjuvant electron (6-MeV) beam radiotherapy was initiated for treatment of the incompletely excised olfactory neuroblastoma and likely presence of a recurrent mass. The protocol consisted of 4 weekly fractions of 8 Gy each (total, 32 Gy) with the axolotl under anesthesia. No acute adverse radiation effects were noted following radiotherapy. The oral erythema resolved after the third session. No recurrence was observed 2 months after treatment, and the owners reported no abnormal signs at home. The axolotl died 3.5 months after radiotherapy was completed (8 months after marginal excision of the tumor) secondary to an environmental management failure. Postmortem histologic evaluation showed no evidence of neoplasia. CLINICAL RELEVANCE: In axolotls, olfactory neuroblastoma should be considered in the differential diagnosis of intraoral palatal masses. This report describes the first application of radiotherapy for treatment of an olfactory neuroblastoma in an axolotl.

Long-term control of olfactory neuroblastoma in a dog treated with surgery and radiation therapy.

BACKGROUND: Olfactory neuroblastoma is a rare malignancy of the nasal cavity in dogs that is thought to arise from specialised sensory neuroendocrine olfactory cells derived from the neural crest. CASE REPORT: An 8-year-old dog was presented for reclusiveness and pacing. On CT and MRI, a contract-enhancing mass was disclosed within the rostral fossa, extending caudally from the cribriform plate into the left nasal sinus. Surgical excision was performed and the diagnosis was histological grade III (Hyams grading scheme) olfactory neuroblastoma. Based on human CT criteria this was high stage (modified Kadish stage C). Surgical excision was incomplete and was followed by curative-intent radiation therapy using a linear accelerator to a total dose of 48 Gy. CONCLUSION: The dog survived 20 months after diagnosis. Although olfactory neuroblastoma is a rare tumour in dogs, aggressive local therapy may allow for prolonged survival, even when the tumour is advanced.

Magnetic resonance imaging features of esthesioneuroblastoma in three dogs and one cat.

OBJECTIVE: Esthesioneuroblastoma is a rare malignant intranasal tumor that originates from the olfactory neuroepithelium of the upper nasal cavity, and can destroy the cribriform plate and expand into the neurocranium. Descriptions of the magnetic resonance features of esthesioneuroblastomas in animals are scarce. The objectives of this study were to report the magnetic resonance imaging features of esthesioneuroblastomas in order to determine distinct imaging characteristics that may help distinguish it from other intracranial tumor types. MATERIAL AND METHODS: Magnetic resonance images of four patients with confirmed esthesioneuroblastomas were reviewed and compared with previously reported cases. RESULTS: The esthesioneuroblastomas appeared as oval-shaped, solitary lesions in the caudal nasal cavity that caused osteolysis of the cribriform plate and extended into the brain in all cases. Signal intensity was variable. Contrast enhancement was mild and varied from homogeneous to heterogeneous. A peripheral cystic component was found in two patients and was reported in only one previous case. Mass effect and white matter edema were marked to severe. Osteolysis of facial bones and extension into the facial soft tissues or retrobulbar space were not present in any of the cases, although this has been reported in the literature. CONCLUSION: A definitive diagnosis of esthesioneuroblastoma based on signal intensity or contrast behavior was not possible. Nevertheless, the presence of a mass in the caudal nasal cavity with extension into the neurocranium seems to be a feature highly suspicious of esthesioneuroblastoma. In contrast to other extra-cranial lesions, the extra-cranial mass was relatively small and destruction of facial bones seems to be rare.

Of mice and men: olfactory neuroblastoma among animals and humans.

Olfactory neuroblastoma (ONB) is a rare tumour of nasal cavity and paranasal sinuses that arises from the olfactory neuroepithelium and has unpredictable clinical course. As the sense of smell is phylogenetically one of the first senses and olfactory neuroepithelium is evolutionary conserved with striking similarities among different species, we performed an extensive analysis of the literature in order to evaluate the similarities and differences between animals and humans on the clinical, morphological, immunohistochemical, ultrastructural and molecular level. Our analysis revealed that ONB was reported mainly in mammals and showed striking similarities to human ONB. These observations provide rationale for introduction of therapy modalities used in humans into the veterinary medicine. Animal models of neuroblastoma should be considered for the preclinical studies evaluating novel therapies for ONB.

Metastasizing Esthesioneuroblastoma in a Dog.

A 7-year-old Afghan hound presented with a history of disorientation, loss of vision, and seizures. Magnetic resonance imaging helped identify a mass at the level of the main olfactory bulb that compressed and displaced adjacent tissues in the cribriform plate into the nasal cavity and nasopharynx. Bony structures were osteolytic. After removing almost 80% of the mass, the tumor recurred a few months later. Due to severe respiratory distress and subsequent to an ultrasound diagnosis of a liver tumor, the dog was euthanized. In addition to the nasal mass, a single nodule in the liver and multiple nodules in the lung were present. All masses had similar cell morphology and were diagnosed as metastasizing esthesioneuroblastoma. The neoplastic cells expressed neuron-specific enolase and chromogranin A, and a few cells within the nasal mass were positive for cytokeratin. This is the first description of a canine esthesioneuroblastoma with distant metastases.

Olfactory neuroblastoma in dogs and cats--a histological and immunohistochemical analysis.

Olfactory neuroblastoma (ONB) was identified in 13 dogs and nine cats. The tumours were subjected to microscopical examination and were graded using a human pathological grading system. In the canine and feline tumours there was more necrosis and higher mitotic activity (mitotic index and Ki67 labelling index) than reported in human ONB. Rosettes were a common feature of feline ONBs. A significant correlation was observed between the histological grade and the Ki67 labelling index. The histopathological diagnosis of ONB was confirmed immunohistochemically by demonstration of the neuronal marker neuron-specific enolase (NSE). Two other neuron-specific antibodies specific for microtubule-associated protein-2 (MAP-2) and neuronal nuclei antigen (NeuN) were evaluated. MAP-2 expression proved to have higher specificity than labelling for NSE. NeuN expression was less sensitive and of limited practical value.

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.

Olfactory neuroblastoma in a cat.

CASE SUMMARY: A 12.5-year-old castrated male domestic shorthair cat was presented for evaluation of dyspnea. Physical examination suggested upper airway disease. Computed tomography revealed the presence of a nasopharyngeal mass. Biopsies obtained via rhinoscopy led to a diagnosis of olfactory neuroblastoma. CLINICAL CHALLENGES: Olfactory neuroblastoma (or esthesioneuroblastoma) is a rare malignant neoplasm that arises from olfactory neuroepithelium. It was first described in human medicine in 1924. Clinical signs are variable, and diagnosis may prove challenging as this tumor, which is a differential for spontaneous intranasal tumors in cats, may be mistaken for poorly differentiated carcinomas or round cell tumors. Given its rarity, treatment options for this neoplasm have not been thoroughly evaluated and there is no standard treatment protocol. LITERATURE REVIEW: A review of veterinary and human literature is provided, encompassing clinical signs, staging and grading systems, treatment options and prognostic factors.

Olfactory esthesioneuroblastoma treated with orthovoltage radiotherapy in a dog.

A 13-year-old neutered female mongrel dog presented with a 1-year history of stertorous respiration. On computed tomography examination, a mass was demonstrated in the nasal cavity. Open biopsy of the mass was performed and a diagnosis of olfactory esthesioneuroblastoma was made on histological examination. The dog was treated with orthovoltage x-ray radiation (total dose; 53 Gy given in 14 fractions over an 8 week period). Computed tomography after the twelfth irradiation revealed that tumour size had decreased. Although clinical signs were absent in the 4 months after irradiation, re-growth of the tumour was detected by radiographic evaluation and histological examination. The dog was again treated with orthovoltage x-ray radiation (total dose; 30 Gy given in three fractions over a 4-week period), however, tumour regrowth was again detected 3 months later. Clinical treatment of this tumour type has not been previously reported.

Olfactory neuroblastoma in a horse.

An 11-year-old thoroughbred gelding was euthanatized because of right nasal cavity tumor. The tumor consisted of round to oval cells with a scanty cytoplasm and hyperchromatic nuclei. Homer-Wright rosettes and pseudorosettes, as well as microcysts were seen. Neoplastic cells were immunoreactive to vimentin, S-100 protein, and neuron-specific enolase, glial fibrillary acidic protein and microtube-associated protein in varying degrees, indicating neurogenic nature. Based on these findings, this tumor was diagnosed as an olfactory neuroblastoma. Since this type is an uncommon tumor showing histological variety, the nature is discussed.

Metastatic esthesioneuroblastoma in a horse.

A 17-year-old horse developed severe proptosis of the left eye over a period of 1.5 years. At post-mortem examination a neoplasm was found involving the left ethmoid bone, left maxillary sinus, left orbit, left superior turbinate, and the left eye. Tumour cells were arranged in nests separated by a fine fibrovascular stroma. Immunohistochemically, the tumour cells were labelled by antibodies against neurofilament protein, synaptophysin, glial fibrillary acidic protein and S-100 protein antigen, but were negative for chromogranin A, cytokeratin and desmin. Electronmicroscopically, the cells showed neurosecretory granules with an electron-dense centre and a light halo, and microfilaments. On the basis of macroscopical, light microscopical and ultrastructural findings a diagnosis of a metastatic esthesioneuroblastoma was made.