Diagnosis Of Olfactory Neuroblastoma Research Articles

Proceedings of the 2023 North American Society of Head and Neck Pathology Companion Meeting, New Orleans, LA, March 12, 2023: Navigating New Developments in High Grade Sinonasal Neuroendocrine and Neuroectodermal Neoplasms.

Although the definitions of sinonasal neuroendocrine and neuroectodermal neoplasms did not change substantially in the 5th edition WHO Classification of Head and Neck Tumours, the diagnosis of olfactory neuroblastoma (ONB), small cell neuroendocrine carcinoma, and large cell neuroendocrine carcinoma remains quite challenging in practice. Ambiguities surrounding the amount of keratin expression allowable in ONB and the amount of neuroendocrine differentiation seen in sinonasal undifferentiated carcinoma (SNUC) lead to significant diagnostic discrepancies at the high grade end of this tumor spectrum. Furthermore, a group of problematic neuroepithelial tumors that show overlapping features of ONB and neuroendocrine carcinoma have never been recognized in formal classification schemes. Since publication of the 5th edition WHO, two new tumor entities have been proposed that help resolve these problems. Olfactory carcinoma is defined by high grade keratin-positive neuroectodermal cells with frequent intermixed glands and shows recurrent Wnt pathway, ARID1A, and RUNX1 alterations. IDH2-mutant sinonasal carcinoma is a molecularly-defined category that encompasses tumors with undifferentiated (SNUC), large cell neuroendocrine, and neuroepithelial phenotypes. This review will provide a practical overview of these emerging entities and their application to diagnostic challenges in the post-WHO sinonasal neuroendocrine and neuroectodermal tumor classification.

Olfactory neuroblastoma: case report and focus on cancerogenesis

Background: Neuroendocrine neoplasms (NENs) of the nasal cavity, paranasal sinuses and nasopharynx account for a wide spectrum of histotypes. They can range from indolent form to highly aggressive tumors. Olfactory neuroblastoma, like most sino-nasal NENs, represents a rare neoplasm that prompts diagnostic pitfalls. From a morphological perspective, olfactory neuroblastoma can mimic many nasal neoplasms but a proper recognition is mandatory for its aggressive behaviour. Case presentation: A case of olfactory neuroblastoma in a 85 years old woman is reported. The neoplasm has been surgical removed from the nasal cavity with a clinical and radiographic diagnosis of nasal polyp. Correct diagnostic definition has needed a complete histological and immunohistochemical characterization of the tumoral tissue in surgical pathology laboratory. Conclusion: The correct diagnosis of olfactory neuroblastoma directs the clinical management that is unique for this neoplasm in comparison to other nasal ones. Bicranial-facial surgery or a trephination procedure represent the most common approach for the treatment of this malignancy. Their success determine disease prognosis.

SSTR2 Expression in Olfactory Neuroblastoma: Clinical and Therapeutic Implications.

Somatostatin receptor 2 (SSTR2) expression has previously been documented in olfactory neuroblastoma (ONB). Here, we fully characterize SSTR2 expression in ONB and correlate staining results with clinicopathologic parameters including Hyams grade.We also assess SSTR2 immunohistochemistry expression in various histologic mimics of ONB to assess its diagnostic functionality. 78 ONBs (51 primary biopsies/excisions and 27 recurrences/metastases) from 58 patients were stained for SSTR2. H-scores based on intensity (0-3 +) and percentage of tumor cells staining were assigned to all cases. 51 histologic mimics were stained and scored in an identical fashion. 77/78 (99%) ONB cases demonstrated SSTR2 staining (mean H-score: 189, range: 0-290). There were no significant differences in staining between primary tumors and recurrences/metastases (mean H-score: 185 vs 198). Primary low-grade ONB had somewhat stronger staining than high-grade tumors (mean H-score: 200 vs 174). SSTR2 expression had no prognostic value when considering disease-free or disease-specific survival. SSTR2 staining is significantly higher in ONB than its histologic mimics (mean H-score: 189 vs 12.9, p < 0.001) suggesting a potential use of the marker in diagnosis of ONB. In conclusion, SSTR2 is consistently expressed in ONB suggesting a role for somatostatin-analog based imaging and therapy in this disease. More generally, SSTR2 may be another marker of neuroendocrine differentiation in ONB.

SAT-146 A Rare Combination of Severe Ectopic Cushing’s Syndrome and Graves Hyperthyroidism: A Case Report

BACKGROUND: Ectopic ACTH secretion (EAS) is a rare cause of Cushing’s syndrome. Olfactory neuroblastoma (ONB) is a malignant tumor derived from the olfactory epithelium and can rarely be a source of ectopic hormone production. There are only 19 reported cases of EAS from ONB. We report a case of severe ectopic Cushing’s due to ONB. Interestingly, the patient also presented with Graves disease, which is an unusual pathophysiologic combination since supraphysiologic levels of glucocorticoids suppress the immune system, thereby ameliorating autoimmune processes. Remarkably, Graves disease improved following the removal of the source of ectopic ACTH. CASE PRESENTATION: A 41year old male presented with epistaxis, anosmia, and headaches. He also reported recent weight gain, muscle weakness, and new onset hypertension. Cross-sectional imaging revealed a right nasal cavity mass with intracranial extension. Endonasal biopsy was consistent with a diagnosis of ONB. Biochemical evaluation demonstrated hypokalemic alkalosis, hyperglycemia, and severe hypercortisolism [ACTH 734 (9-46 pg/ml), am cortisol 110 (2-15 ug/ml), late night salivary cortisol 9.8 and 22.53 (<0.09 ug/dl), 24 hour UFC 41,337.3 (4-50 mcg) and non-suppressed cortisol 110 (1.8 mcg/dl) by 1 mg dexamethasone]. Pituitary MRI showed no sellar pathology. Following a period of cortisol suppression with Ketoconazole then with Etomidate infusion, the patient underwent resection of the ONB, followed by chemo- and radiotherapy, which resulted in improvement of severe hypercortisolism. Histopathology showed positive ACTH immunostaining. Pre-operative evaluation also demonstrated hyperthyroidism: TSH <0.010 (0.3-5uIu/ml), FT4 3.11 (0.89-1.76 ng/dl), normal TT3 0.81 (0.6-1.81 ng/ml). Thyroid auto-antibodies were negative; however, radioiodine scan and uptake demonstrated diffusely increased uptake in the enlarged thyroid gland. Pre-operative euthyroidism was achieved with a combination of methimazole, SSKI and cholestyramine. After 6 months of methimazole therapy the patient presented with hypothyroidism (TSH 72.37, FT4 0.1). Methimazole was discontinued and he achieved euthyroidism on subsequent evaluations. CONCLUSION: EAS due to ONB is a very rare cause of Cushing’s syndrome. To our knowledge, this is the first reported case of a male presenting with EAS and concurrent Graves hyperthyroidism. An extensive review of the literature and seeking expert opinion did not provide a convincing pathophysiologic explanation to this unusual concurrence. We therefore hypothesize that, while the two endocrine conditions were simultaneous, they were likely unrelated.

Esthesioneuroblastoma, Thyroid Gland Carcinoma and Gastrointestinal Stromal Carcinoma

Olfactory neuroblastoma (esthesioneuroblastoma, ЕNB) is a rare tumor arising from the olfactory neuroepithelium. We report a case of ЕNB located in inferior nasal concha, combined with thyroid gland carcinoma and gastrointestinal stromal carcinoma in a 77-year-old man. The tumor was resected endonasally. When the final diagnosis of olfactory neuroblastoma was confirmed by histopathologic examination and immunohistochemical staining, the PET/CT examination was performed. The imaging revealed a small focus of a moderately increased cancer activity in the thyroid region. A gastrointestinal stromal carcinoma was detected one year after the resection of the thyroid gland. We discuss the clinical appearance of ENB, staging systems, diagnosis and management. During the endonasal surgery, ENB was removed entirely. Seven days after operation, in order to monitor the postoperative result, PET/CT was performed and a papillary thyroid cancer was detected. One year after the thyroid surgery, gastroendoscopy showed a neoplastic formation in the stomach. In conclusion, we state that when identified as aggressive tumors such as ENB, it is necessary to provide regular examinations in order to detect distant ENB metastases or other neoplastic localisations.

English

Olfactory neuro-blastoma is a rare malignant neoplasm of the neuro-epithelial origin. A 6 year old female presented with a swelling of right cheek with protrusion of right eyeball over a period of one month. Computed Tomography of the Para-nasal sinuses showed expansion of the right maxillary sinus with intra-orbital extension. A diagnosis of olfactory neuroblastoma was established by histopathology and confirmed by Immunohistochemistry. It was Stage C of Kadish (modified) classification. A right medial Maxillectomy was performed and the entire Tumor was removed.

A Pediatric Nasal Esthesioneuroblastoma Treated by Helical Tomotherapy

Purpose: To compare 3-dimensional conformal radiotherapy (3DCRT) with intensity modulated radiotherapy (IMRT) in the irradiation of pediatric head and neck tumor. Case report: A 13-year old boy with the diagnosis of olfactory neuroblastoma (stage Kadish B), who had postoperative residual disease referred to our clinic for adjuvant radiotherapy (RT). A total of 60 Gy image guided (IG)-IMRT were applied in two phases (50Gy/30 fractions and 10 Gy/5 fractions). Before irradiation, RT planning was performed by in two different therapy techniques, namely 3DCRT and IMRT, and these techniques were compared regarding conformation number (CN) and homogeneity index (HI) for planning target volume (PTV), as well as maximum, minimum and mean doses for selected critical organs and PTV. Results: IMRT planning with helical tomotherapy had an apparent superiority compared to 3DCRT planning, as expected. The patient was maintaining remission after 26 months from RT and no side effect related to RT were detected. Conclusions: Today, irradiation of pediatric tumors with 3DCRT is the standard practice. However, IMRT may be required in case of tumors at close proximity to the critical organs in which high dose of irradiation is indicated.

Esthesioneuroblastoma arising from the middle meatus

A 35-year-old female presented with 13-year history of unilateral recurrent nasal mass, epistaxis and facial pain. Nasal examination revealed a pale glistening mass in the right nasal cavity. On probing, mass was insensitive to touch and bled on handling. Computed tomographic scan showed a mass filling the right nasal cavity, ipsilateral maxillary and ethmoid sinuses. Diagnosis of pansinusitis polyposis was made.Transnasal endoscopy-assisted excision of the mass was done, and the diagnosis of olfactory neuroblastoma was established by histopathology and confirmed by immunohistochemistry. The mass was classified as a Kadish stage B tumor. Further intervention including medial maxillectomyand ethmoidectomy, and complete endoscopic-resection of the tumor from cribriform plate was done via lateral rhinotomy approach. The tumor was found adhered to the lateral wall-the middle meatus and was easily peeled away from the cribriform plate and ethmoids. Patient was referred for radiotherapy. No evidence of loco-regional recurrence or systemic metastasis observed at 10-month follow-up.

Olfactory Neuroblastoma From Ala Of Nose- An Unusual Presentation

Esthesioneuroblastoma(Olfactory neuroblastoma) is a rare malignant neoplasm arising from basal cells within the olfactory epithelium. Its clinnical course is unpredictable with variable correlation between microscopic features and biological behaviour.(1) We report a very indolent case of olfactory neuroblastoma presented only with nasal obstruction due to unilateral mass at the anterolateral aspect of nasal ala of left side. The mass excised via lateral rhinotomy approach and diagnosis of olfactory neuroblastoma was established by histopathology.

Esthesioneuroblastoma chemotherapy and radiotherapy for extensive disease: a case report

Malignant tumors of the nasal cavity are rare. We report the case of a 48 years old man who consulted us with a 2-year history of progressive nasal obstruction, occasional epistaxis, facial pain, and watering of the eyes. A diagnosis of olfactory neuroblastoma was established by histopathology and confirmed by immunohistochemistry. On staging, the mass was classified as a Kadish stage C tumor with extensive involvement of the nasal cavities, nasopharynx, paranasal sinuses and orbit. Endoscopic excision of the mass was done. Traditionally the mainstay of treatment in such locally advanced patients is craniofacial resection followed by adjuvant radiotherapy. Our patient was treated with limited surgery and chemoradiation. Patient is free of recurrence at a follow-up of 5 years. This case report demonstrates the potential efficacy of planned combined modality therapy, including limited surgery and early chemoradiation in the control of locally advanced olfactory neuroblastoma.

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.

Persistent CSF Rhinorrhoea, Pneumocephalus, and Recurrent Meningitis Following Misdiagnosis of Olfactory Neuroblastoma

A 41-year-old female patient was admitted with streptococcal meningitis on a background of 5-month history of CSF rhinorrhoea. Imaging revealed an extensive skull base lesion involving the sphenoid and ethmoid sinuses, the pituitary fossa with suprasellar extension and bony destruction. Histological examination of an endonasal transethmoidal biopsy suggested a diagnosis of olfactory neuroblastoma. A profuse CSF leak occurred and the patient developed coliform meningitis. A second endonasal endoscopic biopsy was undertaken which demonstrated the tumour to be a prolactinoma. Following endonasal repair of the CSF leak and lumbar drainage, she developed profound pneumocephalus. The patient underwent three further unsuccessful CSF leak repairs. Definitive control of the CSF leak was finally achieved through a transcranial approach with prolonged lumbar drainage. This case illustrates some of the potentially devastating complications which can occur as a consequence of complex skull base lesions. A multidisciplinary approach may be required to successfully manage such cases.

Olfactory neuroblastoma: Endoscopic- assisted cranial resection

Olfactory neuroblastoma (OAN) is an extremely rare malignant neoplasm of the nasal cavity. Here we report a case of OAN in a 30 years old man presenting with headache, unilateral progressive nasal obstruction and epistaxis. Nasal examination revealed a fleshy pink mass in the left nasal cavity. Computed tomographic scan showed a mass involving the nasal cavity, ethmoid sinuses and anterior cranial fossa. A diagnosis of OAN was established by histopathology and confirmed by immunohistochemistry. The nasal mass was excised via a lateral rhinotomy approach and the cranial extension of the tumor was resected completely from the cribriform plate, fovea ethmoidalis and dura by using endoscopes of different angles. An endoscopic assisted resection of the base of skull from the nasal cavity without a formal craniofacial resection was performed safely with oncologic safety. In this article, the potential advantages of endoscopic techniques along with past, present and future hope for the search for a better outcome of OAN will be discussed.

Olfactory neuroblastoma following treatment for pituitary adenoma

Olfactory neuroblastoma is extremely rare as a second neoplasm. We report an unusual case of olfactory neuroblastoma in a 59-year-old woman who had undergone two operations and received 54 Gy of irradiation for pituitary adenoma 20 years ago. At the time of admission, the patient presented with nasal obstruction and frequent epistaxis. Imaging studies showed a large mass in the nasal cavities and ethmoid sinus, extending to the intracranial area, with no evidence of any recurrence of the previous pituitary adenoma. The tumor was completely excised via a trans-cranial and trans-nasal approach. A diagnosis of olfactory neuroblastoma was established, and the patient was given postoperative chemotherapy. Although relatively uncommon, second neoplasms are an important consideration in the differential diagnosis of patients with new or recurring symptoms after treatment for pituitary adenoma. Furthermore, it is likely that radiation played a critical role in the development of olfactory neuroblastoma in our patient.

P63 Expression in Olfactory Neuroblastoma and Other Small Cell Tumors of the Sinonasal Tract

Olfactory neuroblastoma (ONB) is a rare neoplasm of the head and neck region that is included in the differential diagnosis of other sinonasal tract malignancies. We studied the usefulness of using p63 as an aid in the diagnosis of ONB and other tumors of the sinonasal region. The specimens were 14 ONBs; 4 nasopharyngeal carcinomas (NPCs), nonkeratinizing subtype; 2 NPCs, undifferentiated subtype; 10 sinonasal undifferentiated carcinomas (SNUCs); 7 malignant melanomas; and 2 extranodal natural killer (NK)/T-cell lymphomas. We observed p63 expression in 5 ONBs (36%), 4 nonkeratinizing NPCs (100%), 1 undifferentiated NPC (50%), 2 SNUCs (20%); 0 malignant melanomas (0%); and 1 extranodal NK/T-cell lymphoma (50%). While all cases of NPC with positive staining for p63 showed strong and diffuse immunoreactivity, the ONB, SNUC, and lymphoma cases with positive immunoreactivity showed only focal staining for p63. No p63 expression was observed in malignant melanoma. We think p63 is a useful marker to help distinguish nonkeratinizing or undifferentiated NPC subtypes from various sinonasal tract malignancies. In particular, p63 helps distinguish nonkeratinizing and undifferentiated NPC subtypes from SNUC.

Primary olfactory neuroblastoma originating from the inferior meatus of the nasal cavity

Olfactory neuroblastoma is a rare malignant tumor of the nasal cavity arising from the olfactory neuroepithelium. It usually presents as a polypoid mass high in the nasal vault including the cribriform plate, superior turbinate, and superior portion of nasal septum. An 89-year-old man visited our office with symptoms of occasional left nasal bleeding and obstruction. On the endoscopic examinations, polypoid mass with bleeding tendency was observed in the left inferior meatus. Biopsy was performed, and the diagnosis of olfactory neuroblastoma was confirmed by histopathologic examination and immunohistochemical staining. The tumor was resected via medial maxillectomy, and the final pathologic report established that it was primary olfactory neuroblastoma that occurred from the inferior meatus. In this report, a literature review was performed on the pathologic characteristics and prognosis of the tumor, and possible hypotheses that olfactory neuroblastoma has originated from the inferior meatus were discussed.

Olfactory Neuroblastoma: A Case Report and Review of the Literature

Malignant tumors of the nasal cavity are rare. We report the case of an elderly woman who consulted us with a 4-year history of progressive nasal obstruction, occasional epistaxis, facial pain, and watering of the eyes. A diagnosis of olfactory neuroblastoma was established by histopathology and confirmed by immunohistochemistry. On staging, the mass was classified as a Kadish stage B tumor. The mass was excised via a lateral rhinotomy approach, and the tumor was peeled away completely from the cribriform plate with endoscopes. The patient underwent postoperative radiation, and she was free of recurrence at follow-up 15 months later.

Olfactory neuroblastoma: The 22-year experience at one comprehensive cancer center

Olfactory neuroblastoma (ONB) is a rare tumor arising from the olfactory neuroepithelium. There is no universally accepted staging system, and treatment approaches lack uniformity. We present one institution's experience with this tumor and the results of therapy. Thirty patients treated for ONB at The University of Texas M. D. Anderson Cancer Center between 1979 and 2002 were retrospectively reviewed. The diagnosis of ONB was histologically confirmed for each patient. The mean follow-up was 7.32 years. In 77% of cases, patients received treatment with surgery followed by postoperative radiation therapy. Sixteen percent received chemotherapy as part of their initial treatment. Overall 5-year and 10-year survival rates were 89% and 81%, respectively. Nine patients whose disease was initially stage C had a recurrence. The mean time for recurrence was 4.67 years. The M. D. Anderson Cancer Center approach to ONB is complete surgical resection, usually involving a craniofacial approach, with postoperative radiation therapy. This approach seems to be curative in early-stage disease. Late recurrence warrants long-term follow-up.

Olfactory Neuroblastoma Causing Ectopic ACTH Syndrome

A 39-year-old woman who presented with typical Cushingoid appearance (moon facies, central obesity, purpura) was admitted to our hospital because of pulmonary infection. She was found to have hypertension, severe hypokalemia, and metabolic alkalosis. Endocrine data revealed elevated plasma levels of ACTH and cortisol with lack of circadian rhythm, non-suppressibility to high-dose dexamethasone, and hyperresponsiveness to CRH stimulation. Although no pituitary mass was detected by MRI of the brain, inferior petrosal sinus sampling showed a step-up of central to peripheral ACTH levels; these data are consistent with the diagnosis of Cushing's disease. She was successfully treated with metyrapone to control hypercortisolemia. Ten months later, a mass was detected in the ethmoid sinus, which was surgically removed. After resection of the ethmoid sinus tumor, her Cushingoid features and hypercortisolemia disappeared, but recurred after enlargement of a second mass in the maxillary sinus. After resection of the maxillary sinus tumor, her hypercortisolemia subsided. Histologically, the tumor tissues from both the ethmoid and maxillary sinus were identical and consistent with the diagnosis of olfactory neuroblastoma. Immunohistochemically, the immunoreactivities of ACTH and POMC were positive in the cytoplasm of tumor cells, and immunoreactive ACTH was demonstrated in both tumor tissues. Thus, this is the second rare case with ectopic ACTH syndrome caused by olfactory neuroblastoma thus far reported.

心転移したと思われるきゅう神経芽細胞腫例

A 35-year-old Korean woman visited our hospital complaining of right nasal discharge and recurrent epistaxis. The intranasal examination showed a telangiectatic polyp on the right, and polypectomy was carried out. Immunohistochemical studies of the polyp showed neuroblastoma. She underwent preoperative irradiation (Liniac 40.5 Gy), Denker's operation and boost radiotherapy (Co60 18 Gy, Remote-Afterloading System), and the tumor was well controlled locally. However, she died of cardiac metastasis one year later.Immunohistochemical examinations with NSE (neuron specific enolase), S-100 protein and vimentin were found to be useful in the diagnosis of olfactory neuroblastoma.