Olfactory Neuroblastoma Managed with Endoscopic Sinus Surgery.

Olfactory neuroblastoma (ONB) or esthesioneuroblastoma is a rare malignancy of the nose and paranasal sinuses that originates from the upper nasal vault. We report a rare case of ONB in a 27-year-old female patient with a 2-year history of nasal obstruction, sneezing, nasal discharge, and left eye protrusion. The patient was successfully treated with endoscopic sinus surgery and adjuvant radiotherapy (RT) with 5-year follow-up duration. Studying ONB cases is of great importance due to its rare occurrence, and the lack of literature regarding its management often creates a dilemma leading to nonstandardized treatment methods. Prolonged surveillance is essential due to its late recurrence and endoscopic resection followed by adjuvant RT, which may be a feasible and effective treatment. There is no single case of ONB published yet in Saudi Arabia, and to our knowledge, this is the first case report. Copyright:

INTRODUCTION

Olfactory neuroblastoma (ONB) is a rare neuroectodermal malignancy that occurs in the upper vault of the sinonasal cavity.[1] Epidemiological data show that the incidence of ONB is 0.4 per million population with no gender predilection and show a bimodal age distribution with peak rates at the 2nd and 6th decades of life.[23] The most common anatomic origin of ONB is in the upper vault of the nasal cavity near the cribriform plate, while other sites of origin proposed are ectodermal olfactory placode, Jacobson's organ (vomeronasal organ), sphenopalatine ganglion, the ganglion of loci, autonomic ganglia in the nasal mucosa, and the olfactory epithelium itself.[4]

ONB usually presents as unilateral nasal obstruction followed by epistaxis and less commonly headache, pain, rhinorrhea, excessive lacrimation, anosmia, and visual disturbances, such as diplopia and proptosis.[567] The biological activity of ONB varies from indolent up to highly aggressive, and furthermore, it is considered ectopic if it originates from the lower nasal cavity within one of the paranasal sinuses and exists as an intracranial mass with cribriform plate involvement, or in extremely rare cases, intracranially with no intranasal component.[8] Reported ectopic ONB sites of origin include the anterior ethmoids, sphenoid sinus, maxillary sinus, pituitary gland, nasopharynx, sellar region, nasal cavity inferior meatus, and noise floor.[9] The management of ONB usually follows a multidisciplinary that includes surgery, chemotherapy, and radiotherapy (RT). Cases treated with combination of surgery and RT have shown superior survival rates and life expectancy.[1011] This present study reports the case of a Saudi female patient with a 2-year history of nasal obstruction, sneezing, nasal discharge, and left eye protrusion treated by endoscopic surgical excision RT with a 5-year follow-up duration.

CASE REPORT

We report a 27-year-old female with previously diagnosed hypothyroidism with a 2-year history of bilateral nasal obstruction that was more profound on the left side, sneezing, and nasal discharge followed by left eye protrusion with no visual disturbances, no history of trauma, photophobia, ocular pain, colored halos, floaters, and redness. The patient's complaint worsened when she was a 16-week primigravida with progressively growing left nasal polyp. Drug intake history consisted of levothyroxine. Family history revealed breast cancer in two of her third-degree relatives; otherwise, her medical history was unremarkable. There was no evidence of neck mass on physical examination, and on ocular examination, there was mild proptosis in the left eye. Visual acuity and fundal examination were within normal limits, and there was no pain or restriction with ocular movement. Endoscopic examination showed a polypoid mass on the left side and right nasal septal deviation. A computed tomography (CT) scan of the head without contrast showed a lobulated soft-tissue mass occupying the left side of the paranasal sinuses and nasal cavity. A computed tomography (CT) scan of the head without contrast showed a lobulated soft-tissue mass occupying the left side of the paranasal sinuses and nasal cavity with bony erosions in the left maxillary sinus. Endoscopic sinus surgery was done, and an excisional biopsy from left nasal polyp and left maxillary polyp was obtained. Gross examination showed multiple fragments of whitish-to-dark brown, soft bony tissue of the left nasal polyp, and pale tan tissue fragments of the left maxillary polyp. Hematoxylin-eosin (H and E) staining of specimens showed hypercellular neoplastic proliferation with lobular architecture with infiltrative patterns of small nests of cells in neurofibrillary material, pseudorosettes (Homer Wright rosettes) were focally present, showed scattered mitosis, individual necrotic cells, and scattered patchy necrosis. Neoplastic cells demonstrated indistinct cell borders, moderately pleomorphic nuclei with stippled chromatin. Histological diagnosis was ONB Grade 2–3 based on the Hyams grading system. Immunohistochemical staining for synaptophysin, neuron-specific enolase (NSE), chromogranin, Ki-67, and S-100 protein were positive, while cytokeratin was negative. Postoperative histopathology confirmed a positive result for ONB.

An magnetic resonance imaging (MRI) scan was carried out 2 weeks after the endoscopic operation and showed irregular homogeneously enhanced soft tissue in the form of intermediate signal intensity on the T2 image and low signal intensity on the T1 images seen at the most upper part of the left anterior ethmoidal air cells extending superiorly to the lateral aspect of the crista galli with no cortical involvement. The lesion minimally crossed the midline and encroached on the left orbit to reach the extraconal space. The lesion compressed the medial rectus muscle with no muscular invasion and anteriorly got into the left maxillary sinus with postoperative changes in the left maxillary sinus after left maxillary polyp removal. This presentation corresponded to Kadish Stage B. After a multidisciplinary tumor board discussion, a bimodality treatment approach consisting of endoscopic resection followed by adjuvant RT was considered. The patient was treated with a wide tumor excision by endoscopic sinus surgery, and biopsies were taken from the shaved ruminants from left anterior and posterior ethmoid air cells and frontal recess. CT pan scans were done in which negative results for distant metastasis were found. After that, the patient subsequently received adjuvant external beam radiation for 6 weeks with a total dose of 60 Gy/30 fractions delivered with a step and shoot (S and S) intensity-modulated radiotherapy (IMRT) technique. After proper immobilization, a planning CT simulation with a 3-mm slice thickness was performed. RT was well tolerated without side effects. After a stable period of a 17-month follow-up using nasal endoscopy and imaging, endoscopic findings were suspicious. A re-biopsy was done, which showed a negative left ethmoid sinus involvement and a positive left frontal recess involvement. The patient underwent a second surgery using endoscopic sinus surgery. After that, re-biopsy from all involved sinuses was done and yielded negative results. During the next 38-month follow-up period, the patient remained clinically and radiologically free of disease recurrence.

DISCUSSION

ONB clinical presentation depends on the mass effect or local invasion of the involved part, including the paranasal sinuses, orbits, metastatic spread to cervical lymph nodes, intracranial space, or rarely, distant metastasis, such as the bones.[31213] Symptomatic presentation of ONB most commonly involves unilateral nasal obstruction followed by epistaxis, and less commonly headache, pain, rhinorrhea, excessive lacrimation, anosmia, and visual disturbances such as diplopia and proptosis.[1415] Physical findings include nasal mass, proptosis, extraocular paralysis, neck and nasopharyngeal masses, hyponatremia, Cushingoid appearance, and behavioral changes due to frontal lobe involvement.[1617] It is reported that the biological activity of ONB varies from indolent growth rate with patient survival >20 years up to highly aggressive neoplasm with metastatic spread and patient survival for a few months.[14]

Imaging modalities such as CT and MRI are considered as gold standard imaging modality to diagnose ONB.[918] ONB appears on contrast-enhanced CT as homogeneous soft-tissue mass with moderate and uniform enhancement.[19] CT with no contrast is used to assess the presence of speckled calcification and bone erosion of the cribriform plate, lamina papyracea, and fovea ethmoidalis. MRI uses pre- and post-contrast image after gadolinium injection, where it appears as hypointense areas compared to gray matter on T1-weighted image and hyperintense areas on the T2-weighted image.[919] The classic and characteristic feature of ONB that appears in imaging studies is its “dumbbell-shaped” mass extending across the cribriform plate.[2021]

Kadish et al. established a clinical staging system for ONB in 1976 that has been used until today. This stage includes three classifications: (a) Stage A: tumor limited to the nasal cavity, (b) Stage B: nasal cavity and one or more paranasal sinus, and (c) Stage C: beyond nasal cavity and paranasal sinuses.[22] Morita et al. modified the Kadish system by adding Stage D, which includes cervical lymph nodes or distant metastases.[23] Table 1 demonstrates the different clinical staging systems.

Table 1

Kadish, Morita, and Dulguerov tumor node metastasis staging systems

Staging system	Tumor extent
Kadish staging
A	Confined to the nasal cavity
B	The nasal cavity plus one or more paranasal sinuses
C	Extension beyond the sinonasal cavities
Morita staging
D	Cervical lymph node involvement or distant metastasis
Dulguerov TNM staging
T1	Involving the nasal cavity and/or paranasal sinuses (excluding sphenoid sinus) sparing the most superior ethmoidal cells
T2	Involving the nasal cavity and/or paranasal sinuses (including sphenoid sinus) with extension to or erosion of the cribriform plate
T3	Tumor extending into the orbit or protruding into the anterior cranial fossa
T4	Tumor involving the brain
N0	No cervical lymph node metastasis
N1	Positive for cervical lymph node metastasis
M0	No distant metastasis
M1	Positive for distant metastasis

TNM: Tumor node metastasis

On histopathological evaluation, H and E staining in low-power magnification showed a Grade 2–3 ONB arranged in lobules and separated by the neurofibrillary matrix [Figure 1a]. Simultaneously, H and E staining in high-power magnification demonstrated Grade 2–3 ONB with sheets of anaplastic tumor cells [Figure 1b].

Figure 1

(a) H and E stain low-power magnification Grade 2–3 olfactory neuroblastoma arranged in lobules and separated by neurofibrillary matrix. (b) H and E stain high-power magnification Grade 2–3 olfactory neuroblastoma with sheets of anaplastic tumor. (c) Tumor cell demonstrating diffuse and strong cytoplasmic positivity for neuron-specific enolase immunohistochemical stain

Hyams' grading system was created using histopathological patterns to grade ONB from Grade 1, which is the most well differentiated up to Grade 4 and is the most anaplastic form based on the presence of neural stroma, the degree of differentiation, mitotic figures, and necrosis.[24] Table 2 illustrates Hyams' histopathological grading system. Immunohistochemical staining plays a vital role in differentiating ONB from other sinonasal small round blue cell tumors, as described by Rooper and Bishop.[15] The most expressed marker is NSE, and ONB is classically reactive for synaptophysin, chromogranin, and S-100 protein limited to the sustentacular cells.[1525] [Figure 1c] is demonstrating diffuse and strong cytoplasmic positivity for NSE immunohistochemical stain.

Table 2

Hyams’ histopathological grading system

Grade	Lobular architecture	Mitotic index	Nuclear polymorphism	Fibrillary matrix	Rosettes	Necrosis
1	Lobular	Absent	Absent	Prominent	HW	Absent
2	Lobular	Low	Moderate	Present	HW	Absent
3	Variable	Moderate	Prominent	Minimal	FW	Rare
4	Variable	High	Marked	Absent	None	Common

HW: Homer Wright rosettes, FW: Flexner-Wintersteiner

It is difficult to determine a standard treatment strategy due to its anatomic location variation, rarity, limited information in the literature, and lack of randomized control trials.[2627] Bailey and Barton reported in their case series of ONB that combined surgery and radiation therapy showed better cure rates, survival rates, and life expectancy than surgery or RT alone.[28] Endoscopic techniques are more commonly used for Kadish A and B stages since they are less invasive lesions, while open surgeries are used with higher stages.[29] In extensive tumor cases, a lateral rhinotomy approach, resection of the nose's lateral wall, and in some cases, complete resection of the cribriform plate could be performed.[30] Prolonged follow-up with imaging modalities is recommended due to late tumor recurrence rates.[28]

CONCLUSION

To our knowledge, this is the first published adult Saudi case of ONB. ONB should be considered a differential diagnosis for nasal and paranasal sinus masses to prevent delay in management. Minimally invasive endoscopic sinus surgery with adjuvant IMRT is a valid choice in this setting and has favorable outcomes. Further studies are needed to assess cases of ONB to achieve optimal management strategies and standard follow-up guidelines.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that her name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

Written consent was taken from the patient. All the authors declare the there is no conflict of interests, including specific financial interests, relationships, and affiliations.