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Olfactory Neuroblastoma

Esthesioneuroblastomas

Olfactory neuroblastoma is a neuroendocrine malignant tumor arising from the olfactory stem cells and contains both endocrine and neuronal characteristics. It can secrete various hormones, leading to paraneoplastic syndromes, introducing additional difficulty in diagnosing the patient.


Presentation

Olfactory neuroblastoma (ONB) or esthesioneuroblastoma is a malignancy derived from the neuroendocrine cells. Infrequent in the sinonasal tract, it is possibly caused by mutations in the olfactory stem cells localized in the superior part of the nasal cavity. Particularly areas near the cribriform plate and olfactory nerve are affected [1].

Typical patients for ONB are those in the middle age (40-50 years of age), although patients may present almost at any decade of life [2]. They come with a unilateral nasal obstruction caused by a mass lesion which can provoke diplopia or proptosis if invasion into the orbit exists. Other symptoms include epistaxis and inability to sense smells (otherwise known as anosmia). Headaches and sinusitis can also be concluded [3].

Some cases may develop paraneoplastic syndromes (PS) typical for the neuroendocrine malignancies [3]. These syndromes arise when the tumor secretes hormones causing a certain effect on the target tissues. Syndrome of inappropriate antidiuretic hormone secretion (SIADH), ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS), hypertension caused by catecholamine secretion and humoral hypercalcemia of malignancy (HHM) are documented. PS affecting the nervous system like opsoclonus-myoclonus-ataxia (OMA), can occur [4]. The mimicry between tumor cells and the body tissues may be observed, being responsible for autoimmune tissue degeneration [5].

Swelling
  • Facial symptoms include swelling, pain, and lack of sensation. Oral symptoms include loose teeth, and the loss of teeth, as well as ulcers in the mouth.[wisegeek.com]
  • Olfactory Neuroblastoma Symptoms Symptoms of olfactory neuroblastoma include the following: nasal obstruction and epistaxis anosmia headache nausea facial swelling or pain ocular proptosis or decrease in vision with decreased movement of extraocular muscles[mountsinai.org]
  • A patient presented with nasal swelling and left-sided nasal obstruction, epistaxis, and diplopia. Examination revealed broadening of the nasal dorsum with a fleshy pink mass in both nasal cavities.[ncbi.nlm.nih.gov]
Fatigue
  • However, we report the highly unusual case of a patient with an esthesioneuroblastoma who presented with atypical symptoms of headaches, sinus congestion, and fatigue before acutely losing consciousness.[experts.umn.edu]
  • His main complaint was xerostomia, and he had anosmia, moderate fatigue, and frontal pressure headaches requiring opiate pain medication.[journals.plos.org]
Cushingoid
  • 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.[ncbi.nlm.nih.gov]
  • In the first case, she presented the Cushingoid appearance with systemic edema and her tumor was removed surgically. ACTH secretion by the tissue was confirmed by immunohistochemistry.[ncbi.nlm.nih.gov]
  • She had no Cushingoid appearance, and there was no edema.[jco.ascopubs.org]
Rhinorrhea
  • Most of the presenting symptoms include nasal obstruction, nasal bleeding, anosmia, rhinorrhea, and headache. In this present report, we describe a 79-year-old man who presented with bilateral nasal congestion for more than 1 year.[ncbi.nlm.nih.gov]
  • Patients often present with nasal obstruction, rhinorrhea, recurrent epistaxis, hyposmia, or anosmia.[experts.umn.edu]
  • She had a recent history of clear rhinorrhea and frequent nosebleeds. CT and MRI scan revealed a large mass in the left nasal cavity extending into the frontal lobe ( figure 1 ).[n.neurology.org]
  • Esthesioneuroblastoma: Cerebrospinal fluid rhinorrhea and widespread metastasis. J Otolaryngol. 1986. 15: 80-4[surgicalneurologyint.com]
  • Clinical presentation is usually secondary to nasal stuffiness and rhinorrhea or epistaxis. Presentation is often delayed and symptoms may have been present for many months.[radiopaedia.org]
Nasal Congestion
  • A 43-year-old female presented with persistent nasal congestion with intermittent epistaxis without resolution for the preceding 5 years.[ncbi.nlm.nih.gov]
  • In this present report, we describe a 79-year-old man who presented with bilateral nasal congestion for more than 1 year. Nasoendoscopy showed a huge, smooth, mucosal tumor in the nasopharynx with extension to the posterior nasal septum.[ncbi.nlm.nih.gov]
  • A 27-year-old woman was referred to our hospital for headache, nasal congestion, and decreased olfactory sensation. Imaging showed a mass measuring approximately 5 cm   4 cm in the right frontal lobe, which also filled the right nasal cavity.[ncbi.nlm.nih.gov]
  • A 62-year-old woman presented with an 11-month history of worsening nasal symptoms of rhinorrhoea, anosmia, nasal congestion and intermittent epistaxis. MRI revealed a large mass in the upper nasal vault.[ncbi.nlm.nih.gov]
  • Symptoms Olfactory neuroblastomas typically cause loss of sense of smell (anosmia), epistaxis (nasal bleeding), nasal congestion/obstruction, vision loss and headache.[pacificneuroscienceinstitute.org]
Aspiration
  • This tumor has been seldom diagnosed by direct fine needle aspiration (FNA). Metastatic ONB was diagnosed by FNA. The patient was a 40-year-old female with a polypoid mass in the nasal cavity and ipsilateral cervical lymphadenopathy.[ncbi.nlm.nih.gov]
  • The report describes how fine-needle aspiration cytology identified the metastatic spread and contributed to its clinical management. The use of ancillary procedures in differential diagnosis of small round-cell tumors is reviewed.[ncbi.nlm.nih.gov]
Nausea
  • Olfactory Neuroblastoma Symptoms Symptoms of olfactory neuroblastoma include the following: nasal obstruction and epistaxis anosmia headache nausea facial swelling or pain ocular proptosis or decrease in vision with decreased movement of extraocular muscles[mountsinai.org]
  • The symptoms of ENB can be classified into: Nasal - Obstruction, epistaxis, discharge, unilateral polyp, and anosmia Neurological - Headache and nausea Oral - Loose teeth, non-healing following tooth extraction and oral ulcers Facial - Swelling, pain,[skullbaseinstitute.com]
  • Except for occasional nausea and vomiting, which had started during the first weeks of pregnancy, she had no complaints.[jco.ascopubs.org]
  • Intracranial extension may lead to neurological symptoms such as changes in mental status, headaches, nausea and vomiting, seizures, and eventually coma and death.[med.uth.edu]
Proximal Muscle Weakness
  • While waiting resection, she acutely developed severe proximal muscle weakness, lethargy and lower extremity oedema. Blood glucose was elevated, and hypokalaemic metabolic alkalosis was noted.[ncbi.nlm.nih.gov]
Muscle Weakness
  • While waiting resection, she acutely developed severe proximal muscle weakness, lethargy and lower extremity oedema. Blood glucose was elevated, and hypokalaemic metabolic alkalosis was noted.[ncbi.nlm.nih.gov]
Proximal Muscle Weakness of the Lower Extremity
  • While waiting resection, she acutely developed severe proximal muscle weakness, lethargy and lower extremity oedema. Blood glucose was elevated, and hypokalaemic metabolic alkalosis was noted.[ncbi.nlm.nih.gov]
Purpura
  • 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.[ncbi.nlm.nih.gov]
Chemosis
  • A 73-year-old woman presented with exophthalmos, left chemosis, decreased visual acuity, and diplopia. CT scan revealed a heterogeneous mass with isolated maxillary sinus, orbital floor, and lower eyelid invasion.[ncbi.nlm.nih.gov]
Headache
  • Only four cases of olfactory neuroblastoma isolated in the sphenoid sinus have been described in English literature and the frequency of presenting symptoms with cranial neuropathies and headache.[ncbi.nlm.nih.gov]
  • We report a case of a 78-year-old woman who presented with frontal headache and proptosis of the right eye. CT revealed a nasoethmoid mass with diffuse calcifications.[ncbi.nlm.nih.gov]
  • A 41-year-old man presented with left nasal obstruction and occasional left epistaxis associated with headache. Endoscopic examination of the nasal cavities and computed tomography suggested bilateral polypoid masses.[ncbi.nlm.nih.gov]
  • Original complaints were severe headaches and eye pain; death occurred from intracranial extensions 6 months and 1 year after diagnosis.[ncbi.nlm.nih.gov]
  • A 27-year-old woman was referred to our hospital for headache, nasal congestion, and decreased olfactory sensation. Imaging showed a mass measuring approximately 5 cm   4 cm in the right frontal lobe, which also filled the right nasal cavity.[ncbi.nlm.nih.gov]
Meningism
  • Gross total resection was achieved, but annual follow-up magnetic resonance imaging showed a new enhancing mass in the left parietal meninges mimicking meningioma without local recurrence at 5 years after the first operation.[ncbi.nlm.nih.gov]
  • Here, we report the largest series of intracranial meningeal metastases of ONBs from M.D. Anderson Cancer Center and the University of Toronto.[ncbi.nlm.nih.gov]
  • These include infection, meningitis, pneumocephalus, and blindness. There is a 10-15% change of developing one of these complications, and patients undergoing surgery for esthesioneuroblastoma have a five-year survival rate of 50-80%.[wisegeek.com]
  • Because complete eradication of the rhinorrhea and meningitis required 9 weeks of treatment, radiation therapy was started 10 weeks after the surgery.[surgicalneurologyint.com]

Workup

Olfactory neuroblastoma is diagnosed after radiological examination and biopsy specimen analysis. These give valuable clues leading to this disease and provide objective information for future treatment strategy [6]. An endoscopy is used in visualizing the tumor inside the nasal cavity, providing first impressions of the possible size and location. It may resemble a polypoid mass located unilaterally [7].

Computed tomography (CT) and magnetic resonance imaging (MRI) are imperative in providing data about the size, localization, and grade of invasion into adjacent anatomical structures. Extension into the orbit, skull base, sinuses, etc. can be documented during the examination. CT reveals necrotic lesions seen heterogeneously on the scan. MRI findings are based on modality and include an emphasis on the lesions, which can appear calcific or include hemorrhages [7] [8].

A classification based on the invasion of the tumor has been created by Kadish et al. [9] and it contains three tiers:

  • A group - tumor is restricted in the nasal cavity;
  • B group - nasal cavity and paranasal sinuses are affected;
  • C group - malignant lesion invades structures outside the limit of the two previous groups.

A biopsy is essential to confirm the diagnosis. ONB has distinguishing histopathological findings. The cells are pale, contain obscure borders, and are grouped into the nests forming lobules divided by fibrovascular tissues. These lobules can join together to create a layer of vascularized cells. Distinctive Flexner–Wintersteiner rosettes can indicate olfactory differentiation, pseudorosettes or Homer-Wright are identified too [10]. Immunohistochemistry will reveal positive reaction to neuroendocrine markers and those associated with ONB, which are S-100, CD56, calretinin, chromogranin, and synaptophysin. Moreover, olfactory neuroblastoma is generally negative for keratin [11].

Positron emission tomography (PET)-CT is useful in detecting distal metastases [7].

Treatment

  • There was a significant difference in overall survival between the four treatment groups (p 0.01).[ncbi.nlm.nih.gov]
  • The planned treatment was: chemotherapy (cisplatin/etoposide) and determine treatment dependent on response in 6 patients, surgery and radiotherapy in 16 patients, and single-modality treatment only (surgery, radiotherapy 1) in 2 patients.[ncbi.nlm.nih.gov]
  • Combined treatment modality, including endoscopic endonasal surgery, achieved a better outcome than non-surgical approach.[ncbi.nlm.nih.gov]
  • Because of the rarity and lack of a randomized clinical trial of patients with olfactory neuroblastoma, there is no standard treatment for the disease. The survival period has increased as treatments have been improved since 1980.[ncbi.nlm.nih.gov]
  • Figure 1 shows overall survival curves stratified by treatment groups. Overall Survival of SEER ONB Cases by Treatment Groups.[ncbi.nlm.nih.gov]

Prognosis

  • In 13 patients, 61.5% were diagnosed as late T stage (T3/4), 69.2% late Kadish stage (C/D) and 53.8% were high Hyams grade (I/ II), which indicated poor prognosis.[ncbi.nlm.nih.gov]
  • The grade does not always predict prognosis, however, as metastases can be seen in all grades of olfactory neuroblastoma.[ncbi.nlm.nih.gov]
  • In the 10 cases, 6 were diagnosed as late T stage (T 3 /T 4 ), 6 were at late Kadish stage (C/D) and 3 were at high Hyams grade (Ⅲ), which indicated a poorer prognosis.[ncbi.nlm.nih.gov]
  • In addition, it was found that age may not be an important prognostic factor for intracranial invasive ONB; however, the rate of intracalvarial invasion was found to be a potent marker for predicting the prognosis of patients.[ncbi.nlm.nih.gov]
  • Regarding the prognosis of ONB, a relationship was demonstrated with Hyams' grading, without Kadish staging.[ncbi.nlm.nih.gov]

Etiology

  • Rescently left facial nerve palsy developed, of which etiology due to recurrence or treatment related fibrosis is unclear. Now, the authors are on study the etiology of left facial nerve palsy.[e-crt.org]
  • Methods: We present an atypical case and a review of the literature about the etiology, pathology, clinical manifestations, treatment options and prognosis of these tumours.[scitechnol.com]
  • Though the etiology is unknown[ 2 ], ONB appears to arise from the olfactory membrane of the sinonasal tract and preferentially involves the anatomic distribution of the epithelium overlying the cribriform plate[ 2 ], superior turbinate and the superior[ncbi.nlm.nih.gov]
  • No clear etiology for ENB has been discovered. Herrold in 1963 did produce ENB in Syrian hamsters by administering the auto industry solvent diethylnitrosamine (DENA) by various routes.[web.archive.org]
  • Due to the rare and complex nature of ENB, multiple opinions exist regarding the etiology, optimal staging system, and treatment modalities.[emedicine.com]

Epidemiology

  • General Epidemiology: [1] Prognosis: poor. Wide age range with bimodal distribution - teens and 60s. No sex predilection. Clinical presentation: [1] Nasal obstruction 70%. Epistaxis 50%. Anosmia. Headache.[librepathology.org]
  • Epidemiology Olfactory neuroblastoma is a very rare tumour ( Aetiology and Pathogenesis Unknown Natural History The tumour typically arises from the olfactory epithelium.[ozradonc.wikidot.com]
  • Epidemiology Olfactory neuroblastoma accounts for 1% to 5% of malignant nasal cavity neoplasms. Clinical features These tumours arise across a broad age range with a bimodal peak in the second and sixth decades of life.[e-immunohistochemistry.info]
  • Surveillance Research Program CSBS, Epidemiology, and End Results (SEER) Program Limited-Use Data (1973-2006) Release April 2008. Casiano RR, Numa WA, Falquez AM. Endoscopic resection of esthesioneuroblastoma.[ncbi.nlm.nih.gov]
  • A search of the National Cancer Database by Carey et al identified 1225 cases of ENB. [6] Similar incidence rates have been obtained through epidemiologic studies performed in Denmark. [7] No studies suggest a geographic variation in rates.[emedicine.com]
Sex distribution
Age distribution

Pathophysiology

  • […] to the cribriform plate and upper nasal vault; rarely in nasopharynx, maxillary or ethmoid sinus ( Mod Pathol 2017;30:S1, Head Neck Pathol 2009;3:252 ) May become locally invasive into paranasal sinuses, nasopharynx, palate, orbit, skull base, brain Pathophysiology[pathologyoutlines.com]
  • […] rare malignant tumor, 15 cases of associated ISM have been reported [ Table 2 ],[ 1 4 5 9 12 14 15 16 17 18 21 22 23 24 26 ] with leptomeningeal dissemination recognized especially in high-grade ONB.[ 9 11 22 ] Although ISM has been reported as a rare pathophysiology[surgicalneurologyint.com]
  • Pathophysiology Esthesioneuroblastomas (ENBs) are undifferentiated tumors of neuroectodermal origin derived from the olfactory epithelium. [1] The tumor cells are mitotically active and are the precursor cells that develop into sustentacular and neuronal[emedicine.com]
  • Department of Physiology and Pathophysiology University of Göttingen Federal Republic of Germany 4. Department of Neuropathology University of Mainz Federal Republic of Germany 5.[link.springer.com]

Prevention

  • One patient had residual intracranial disease due to coagulopathy preventing further resection. Twelve patients remain alive with 10 patients remaining disease-free (follow-up ranging from 11 to 64 months).[ncbi.nlm.nih.gov]
  • Prevention of Esthesioneuroblastoma or Olfactory Neuroblastoma Although no prevention method regarding any cancer has been proved to greatly prevent it from developing, the best prevention method in terms of preventing esthesioneuroblastoma or olfactory[epainassist.com]
  • Following a healthy diet and living as healthy a lifestyle as possible may play a role in your recovery, as well as preventing a recurrence of the cancer.[hopkinsmedicine.org]

References

Article

  1. Jethanamest D, Morris LG, Sikora AG, et al. Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg. 2007;133:276–280.
  2. Bell D, Saade R, Roberts D, et al. Prognostic utility of Hyams histological grading and Kadish–Morita staging systems for esthesioneuroblastoma outcomes. Head Neck Pathol. 2015;9:51–59.
  3. Shah K, Perez-Ordóñez B. Neuroendocrine Neoplasms of the Sinonasal Tract: Neuroendocrine Carcinomas and Olfactory Neuroblastoma. Head Neck Pathol. 2016;10(1):85-94.
  4. Kunc M, Gabrych A, Czapiewski P, Sworczak K. Paraneoplastic syndromes in olfactory neuroblastoma. Contemp Oncol (Pozn). 2015;19(1):6-16.
  5. Pelosof LC, Gerber DE. Paraneoplastic syndromes: an approach to diagnosis and treatment. Mayo Clin Proc. 2010;85:838–54.
  6. Su SY, Bell D, Hanna EY. Esthesioneuroblastoma, neuroendocrine carcinoma, and sinonasal undifferentiated carcinoma: differentiation in diagnosis and treatment. Int Arch Otorhinolaryngol. 2014;18:S149–S156.
  7. Leon-Soriano E, Alfonso C, Yebenes L, Garcia-Polo J, Lassaletta L, Gavilan J. Bilateral Synchronous Ectopic Ethmoid Sinus Olfactory Neuroblastoma: A Case Report. Am J Case Rep. 2016;17:268-273.
  8. Dublin AB, Bobinski M. Imaging Characteristics of Olfactory Neuroblastoma (Esthesioneuroblastoma). J Neurol Surg B Skull Base. 2016;77(1):1-5.
  9. Kadish S, Goodman M, Wang CC. Olfactory neuroblastoma. A clinical analysis of 17 cases. Cancer. 1976;37:1571–6.
  10. Shah K, Perez-Ordóñez B. Neuroendocrine Neoplasms of the Sinonasal Tract: Neuroendocrine Carcinomas and Olfactory Neuroblastoma. Head Neck Pathol. 2016;10(1):85-94.
  11. Bell D, Hanna EY, Weber RS, et al. Neuroendocrine neoplasms of the sinonasal region. Head Neck. 2015;PM:26041714.

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Last updated: 2019-07-11 20:44