Nasal cavity, paranasal sinuses, nasopharynx
Other malignant tumors
Olfactory neuroblastoma
Author: Bin Xu, M.D., Ph.D.
Editorial Board Member: Kelly Magliocca, D.D.S., M.P.H.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 29 September 2020
Last staff update: 18 August 2022
Copyright: 2004-2023, PathologyOutlines.com, Inc.
PubMed Search: Olfactory neuroblastoma
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Radiology description | Radiology images | Prognostic factors | Diagrams / tables | Case reports | Treatment | Clinical images | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Electron microscopy description | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Xu B. Olfactory neuroblastoma. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/nasalolfactoryneuroblastoma.html. Accessed September 25th, 2023.
Definition / general
- Malignant neuroectodermal tumor commonly located at superior aspect of nasal cavity showing neuroblastic differentiation (El-Naggar: WHO Classification of Head and Neck Tumours, 4th Edition, 2017)
- Thought to arise from olfactory membrane or olfactory placode (plate-like thickening of embryonic ectoderm from which a nerve ganglion or sensory organ will develop) which extends from roof of nasal cavity in fetus to midnasal septum and superior turbinate
- Not related to neuroblastoma elsewhere in body
Essential features
- Originated and centered around cribriform plate of nasal cavity
- Small blue round cell tumor with lobulated growth pattern and abundant neuropil
- Homer Wright pseudorosettes and Flexner-Wintersteiner rosettes may be seen
- The most important prognostic factors are Hyams grade and Kadish stage
Terminology
- Also called esthesioneuroblastoma, esthesioneuroepithelioma or olfactory placode tumor
ICD coding
Epidemiology
- Patients of all ages, 2 to 90 years
- No obvious gender, ethnic or familial predilection
- Annual incidence of 0.4 per million (Mod Pathol 2017;30:S1, Head Neck Pathol 2009;3:252)
- 2% of all sinonasal neoplasms
Sites
- Usually confined 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
- Theorized to originate from specialized sensory neuroepithelium located in superior nasal cavity, including cribriform plate of ethmoid, nasal roof, superior nasal concha and superior nasal septum (Mod Pathol 2017;30:S1, Head Neck Pathol 2009;3:252)
Etiology
- None identified
Clinical features
- Usually presents with nonspecific syndromes of nasal obstruction, epistaxis, headache and rhinorrhea (Mod Pathol 2017;30:S1, Head Neck Pathol 2009;3:252)
- Rare symptoms include anosmia, visual disturbance, paraneoplastic syndromes (e.g. syndrome of inappropriate antidiuretic hormone secretion (SIADH))
Radiology description
- Typical finding is a dumbbell shaped mass centered at cribriform plate
Radiology images
Images hosted on other servers:
Tumor extending into cribriform plate and lateral lamella
Large, avidly enhancing skull base mass in left nasal cavity
Olfactory neuroblastoma, a. coronal view, b sagittal view
Prognostic factors
- 20% develop regional or distant metastases, usually to cervical lymph nodes and lung; late recurrence (after 10 years) is common
- Grade and stage are the most important prognostic factors
- Hyams histologic grade (Table 1) is the most widely used grading system which encompasses six histologic features and is an independent prognostic factor (Head Neck Pathol 2015;9:51, Hyams VJ. Olfactory neuroblastoma (Case 6) In: Batsakis JG, Hyams VJ, Morales AR, editors, Special tumors of the head and neck, Chicago: ASCP Press; 1982. pp. 24-29)
- Kadish staging system (Cancer 1976;37:1571, Head Neck 2017;39:1962, Head Neck Pathol 2015;9:51) and Morita modification (Table 2) (Head Neck Pathol 2015;9:51, Neurosurgery 1993;32:706) are the staging systems that are most commonly used: the 5 year survival for stages A, B and C are 75%, 68% and 41%, respectively (Mod Pathol 2017;30:S1, Head Neck Pathol 2009;3:252)
Diagrams / tables
Table 1: Hyams grade for olfactory neuroblastoma
Table 2: Staging systems of olfactory neuroblastoma
| Grade I | Grade II | Grade III | Grade IV | |
| Architecture | Lobular | Lobular | Variable | Variable |
| Fibrillary matrix | Prominent | Present | Minimal | Absent |
| Mitosis | Absent | Present | Prominent | Marked |
| Necrosis | Absent | Absent | May present | Common |
| Nuclear pleomorphism | Absent | Moderate | Prominent | Marked |
| Rosettes | Homer Wright | Homer Wright | Flexner- Wintersteiner |
Flexner- Wintersteiner |
Table 2: Staging systems of olfactory neuroblastoma
Kadish staging:
Morita modification:
|
Case reports
- 30 year old woman and 67 year old woman with varied atypical clinical presentation (J Clin Diagn Res 2016;10:PD01)
- 35 year old man with divergent differentiation (Head Neck Pathol 2017;11:531)
- 41 year old man with multifocal ectopic olfactory neuroblastoma (Am J Case Rep 2016;17:268)
- 43 year old woman with a mass in the right nasal cavity (Head Neck Pathol 2016;10:256)
- 44 year old man with aberrant pattern of cytokeratin expression (Head Neck Pathol 2017;11:262 )
Treatment
- Complete surgical excision (may require craniofacial resection), with radiation therapy or chemotherapy
Clinical images
Images hosted on other servers:
Nasal endoscopy
Bifrontal craniotomy
Gross description
- Red-gray, highly vascular, polypoid mass
Microscopic (histologic) description
- Low grade olfactory neuroblastoma usually contains nests and lobules of monotonous tumor cells with round nuclei, indistinct nucleoli and scanty cytoplasm in association with a vascular-rich to hyalinized stroma; fibrillary neural matrix may be present
- High grade tumors may show solid growth, marked mitotic activity, nuclear pleomorphism, necrosis and no neuropil
- Homer Wright pseudorosettes: neoplastic cells palisading around a central zone of fibrillar neural matrix; their presence in a nasal tumor is characteristic for olfactory neuroblastoma
- Flexner-Wintersteiner rosettes: palisading tumor cells surrounding a true central lumen
- Perivascular pseudorosettes may be present but are non-specific
- Other findings: melanin pigment, neurons, divergent differentiation (e.g. rhabdomyoblastic, glandular and squamous differentiation)
Microscopic (histologic) images
Contributed by Bin Xu, M.D., Ph.D.
Lobulated growth,
microcalcification,
abundant fibrillar
neural matrix
Lobulated growth with
infiltration between
submucosal glands
Hyams grade I
olfactory
neuroblastoma
Flexner-Wintersteiner
rosettes
Homer Wright
pseudorosettes
Synaptophysin
diffusely positive
in tumor cells
S100 highlights
sustentacular cells
Positive stains
- Synaptophysin, chromogranin, CD56, neurofilament, S100 in sustentacular cells at periphery of cell nests
- Keratins, e.g. cytokeratin AE1/AE3, CAM5.2 and CK18, are commonly negative, but up to a third may show focal positivity
- INI1
- Area of rhabdomyoblastic differentiation if present is positive for desmin and myogenin
- Calretinin (Am J Surg Pathol 2011;35:1786)
Negative stains
Electron microscopy description
- Dense core neurosecretory granules, microtubules, neuritic processes, neurofilaments (Mod Pathol 2017;30:S1, Head Neck Pathol 2009;3:252)
Molecular / cytogenetics description
- Recent next generation sequencing studies have shown that olfactory neuroblastoma has high level but heterogenous chromosomal instability and copy number alterations (Oncotarget 2016;7:52584)
- Absence of characteristic fusions of other small blue round cell tumors that may occur in the sinonasal tract, e.g. Ewing sarcoma EWSR1 fusion and alveolar rhabdomyosarcoma PAX3 or PAX7 fusion
Sample pathology report
- Nasal cavity, left; biopsy:
- Olfactory neuroblastoma, Hyams grade II (see comment)
- Comment: Immunohistochemistry studies show that the tumor is positive for synaptophysin and chromogranin, whereas negative for cytokeratin. S100 highlighted the sustentacular network. The overall immunoprofile supports the diagnosis.
Differential diagnosis
-
Quite broad; includes all sinonasal small blue round cell tumors (Surg Pathol Clin 2017;10:103)
- Lymphoma: positive for CD45 and other lymphoid markers
- Melanoma: positive for S100, SOX10, MelanA, HMB45
- Small round cell sarcoma:
- Ewing sarcoma: positive for CD99, FLI1, t(11,22) / FLI1::EWSR1 fusion
- Embryonal rhabdomyosarcoma: diffusely positive for desmin and myogenin
- Alveolar rhabdomyosarcoma: diffusely positive for desmin and myogenin, PAX3 or PAX7 fusion
- Mesenchymal chondrosarcoma: NCOA2 fusion
- Carcinoma:
- Small cell carcinoma / poorly differentiated neuroendocrine carcinoma: diffusely positive for cytokeratin, negative for neurofilament and S100
- Sinonasal undifferentiated carcinoma: negative for synaptophysin and chromogranin
- NUT midline carcinoma: positive for NUT
- Adenoid cystic carcinoma: negative for synaptophysin and chromogranin; positive for myoepithelial markers calponin, SMA and S100 and MYB::NFIB fusion
- SMARCB1-deficient sinonasal carcinoma: loss of INI1
Board review style question #1
-
A biopsy of a sinonasal mass from a 50 year old man is shown here:
- The tumor most commonly locates to the lower portion of nasal cavity
- Tumor necrosis, nuclear pleomorphism and high mitotic index are part of the staging system
- The tumor is not associated with similar appearing tumors elsewhere in the body
- SMARCB1 (INI1) immunohistochemistry is lost in this tumor
Which of the following statements is true?
Board review style answer #1
C. Olfactory neuroblastoma is not associated with neuroblastoma elsewhere in the body
Comment Here
Reference: Olfactory neuroblastoma
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Reference: Olfactory neuroblastoma
Board review style question #2
-
Which statement about olfactory neuroblastoma is true?
- The most important prognostic factor is N-MYC amplification
- It is most commonly originated from the medial wall of maxillary sinus
- Most tumors are diffusely positive for CAM5.2
- It may contain areas with rhabdomyoblastic differentiation
Board review style answer #2
D. It may contain areas with rhabdomyoblastic differentiation
Comment Here
Reference: Olfactory neuroblastoma
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Reference: Olfactory neuroblastoma
