Anterior Skull Base Resection of Esthesioneuroblastoma (Endoscopic)

Abstract

First described by Berger in 1924, esthesioneuroblastoma (ENB) remains a rare sinonasal tumor believed to originate from specialized sensory olfactory cells. To date, the literature includes 1,000 recorded cases of ENB. Patients with ENB often present with non-specific symptoms, most often chronic nasal obstruction or epistaxis. Careful examination may reveal a pink or brown polyploid mass in the nasal cavity. Overall, ENB may demonstrate various growth patterns ranging from slow, indolent progression to aggressive invasion with widespread metastasis.

Current literature indicates that ENB should be treated with a combination of surgical resection and postoperative radiation therapy with or without chemotherapy. However, significant controversy remains regarding the appropriate surgical approach. This video demonstrates a transnasal endoscopic approach, which has gained significant popularity over the previous two decades compared to classic “open” approaches. Although this approach demonstrates improved perioperative outcomes while still achieving oncologic margins, further work is required to evaluate long-term survival.

Case Overview

Background

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant neuroectodermal tumor of the nasal cavity. They arise from specialized sensory olfactory cells found within the superior nasal concha, the upper aspect of the nasal septum, the roof of the nasal cavity, and the cribriform plate of the ethmoid bone. ENB has also been referred to as olfactory placode tumor, esthesioneurocytoma, esthesioneuroepithelioma, and esthesioneuroma.

Overall, ENBs are estimated to comprise 2% of all sinonasal tract malignancies. These tumors are extremely rare with an incidence estimated at 0.4 per million people.¹ There is a paucity in the literature assessing ENBs with only an estimated 1,000 cases described since 1924.^2, 3

Focused History

ENB may occur at any age, though evidence indicates a bimodal distribution centered around the second and sixth decades of life.¹ These tumors occur equally in both men and women with no currently known lifestyle, environmental, or geographic risk factors.

The typical patient with ENB presents with non-specific symptoms. Approximately 70% of patients will report chronic nasal obstruction while 50% present with epistaxis. Less common symptoms involve those due to invasion of local structures and include eye pain, proptosis, diplopia, excess lacrimation, ear pain, otitis media, and headaches. Although these tumors are believed to arise from olfactory cells, anosmia is an uncommon complaint, found in approximately 5% of patients. Case series have previously reported the following paraneoplastic syndromes associated with ENB, which may be attributable to ectopic secretion of hormones: Cushing’s syndrome, humoral hypercalcemia of malignancy, and syndrome of inappropriate antidiuretic hormone release.^4-6 

Physical Exam

As with any patient presenting with concerns for sinonasal tract malignancy, a thorough physical examination is necessary. Focus should be centered around the neurologic, ophthalmologic, and head and neck examinations. Careful examination of the nasal cavity may reveal a pink or brown friable, polyploid mass in patients with ENB. 

Imaging

All patients suspected of ENB should undergo both computed tomography (CT) imaging and magnetic resonance imaging (MRI).⁷ CT imaging of ENBs will reveal a homogeneous soft tissue mass originating from the nasal vault. There are no specific CT characteristics of ENBs. This imaging modality, however, is useful for assessing invasion of the surrounding osseous structures, including the cribriform plate, fovea ethmoidalis, and lamina papyracea. It is also useful for surgical planning.

On MRI, ENBs will appear hypointense on T1-weighted sequences while appearing intermediate to hyperintense on T2-weighted images. Peritumoral intracranial cysts may also be visualized on CT, which is highly suggestive of a diagnosis of ENB. Although CT is superior in assessing osseous involvement, MRI is the better imaging modality to assess soft tissue invasion, allowing for the detection of dural or parenchymal compromise. Furthermore, MRI may be utilized to differentiate between entrapped nasal secretions and neoplasm.

Due to the significant incidence of cervical node metastasis, imaging of the neck is also recommended. One study found that the principal site of distant metastasis is bone.⁸ As these patients may present asymptomatically, bone scan has been suggested as a routine component of ENB evaluation.⁹

Natural History

ENB exhibits a wide range of growth patterns. Most are considered to be slow-growing and indolent. If identified as being confined to the nasal cavity, ENBs have an excellent prognosis. A subset of tumors, however, is observed to be highly aggressive with widespread metastasis portending poor outcomes. The most common site of metastasis is the neck, which has been observed in 5–8% of patients at initial presentation.¹⁰ The incidence of distal metastasis has been estimated to be 7% at initial presentation with the most common sites being bone and lungs. Metastasis has also been detected in the liver, mediastinum, adrenal glands, ovaries, spleen, parotid glands, and the spinal epidural space.¹¹

There are currently two clinical staging systems for ENBs. Kadish staging is the more commonly used. It was initially described in 1976 and was modified in 1993 by Morita to include metastasis.^12-13 The Kadish system stratifies patients based on the extent of their disease as determined by imaging:

Stage A – Confined to nasal cavity.
Stage B – Involvement of one or more paranasal sinuses.
Stage C – Extension beyond nasal cavity and paranasal sinuses.
Stage D – Regional lymph node or distant metastasis.

In 1992, Dulguerov developed a system of stratifying patients based on tumor-node-metastasis classification.¹⁴ This system is more precise in its classifications with recognition of early cribriform plate involvement as well as differentiation between intracranial but extradural invasion and true brain compromise. A study comparing both systems found that more advanced staging with either was inversely correlated with disease-free and overall survival, but the Dulguerov system was better at discriminating outcomes. This was especially true in patients classified as Kadish stage C, which has been criticized for being a heterogeneous group.¹⁵

Options for Treatment

There is no consensus regarding an algorithm that may be used to determine the optimal treatment modality for patients with ENB. Overall, there is an agreement in the literature that surgical excision with postoperative radiation therapy with or without chemotherapy is the best approach. However, controversy exists regarding the proper approach. Open craniofacial resection has classically been used, but the transnasal endoscopic approach has become more common in recent years. In general, patients who present in the early stages of the disease may be adequately treated solely with transnasal endoscopic approaches, whereas patients with advanced disease may require open surgery. Current practices are often determined by the surgeon and center experience.

Rationale for Treatment

In our patient, the transnasal endoscopic approach was recommended based on the size and clinical staging of the tumor. Overall, this approach has lower morbidity with current literature suggesting comparable outcomes to open craniofacial resection in treating early stage ENBs.¹⁶

Special Considerations

For patients staged at Kadish A, the transnasal endoscopic approach may be considered as the sole treatment modality. For patients in Kadish B and C, a combination of surgical excision and radiation therapy should be considered. Patients with distant metastasis are considered poor surgical candidates.

Discussion

ENB remains a rare sinonasal tract malignancy. Since it was first described by Berger in 1924, there have only been approximately 1,000 cases published in the literature. Overall, these tumors exhibit a wide range of growth patterns from slow and indolent to highly aggressive with distant metastasis. In general, the literature agrees that ENB should be treated through surgical excision with postoperative radiation therapy with or without chemotherapy in patients considered to be good surgical candidates. However, controversy remains regarding the appropriate approach. Over the past two decades, the transnasal endoscopic approach has gained popularity with recent literature reporting similar or improved short-term and long-term outcomes compared to open craniofacial resection.

The gold standard of treatment for ENB is currently craniofacial resection. This operation, however, has a high risk of perioperative complications from cerebrospinal fluid leakage, meningitis, seizures, and intracranial hemorrhage. The incidence of these events has been estimated to be between 30–60%.¹⁶ With continued improvements in technology, the utilization of transnasal endoscopic approaches has gained popularity. In addition to avoiding significant facial scarring, this technique has been demonstrated to reduce the incidence of complications.¹⁷ Although there was initial concern that endoscopic surgery did not allow for adequate visualization, it has been demonstrated that this approach may achieve oncologic margins if performed by experienced surgeons.¹⁸ 

Initial meta-analysis performed in 2009 suggested that endoscopic surgery had comparable long-term outcomes to traditional open surgery. In their study of 361 patients treated for ENB, Devaiah and colleagues noted significantly improved survival rates in patients who underwent only transnasal endoscopic surgery.¹⁹ In fact, this study reported 100% survival for this subgroup; however, they noted that this finding was misleading. Compared to patients who were treated with a transnasal endoscopic approach, those that underwent open surgery were more likely to have advanced disease classified as Kadish C and D tumors. In addition, there were more cases of long-term follow-up in the open surgery group. The average time of recurrence for ENB has been estimated to be between 2–6 years with cases being reported up to 19 years after initial resection.¹¹ Though it presented promising results, this initial meta-analysis may not completely capture outcomes following transnasal endoscopic surgery for ENB.

In response to the limitations of the Devaiah study, Fu et al. performed a meta-analysis that controlled for tumor stage and histologic grade.¹⁶ Assessing 609 patients treated for ENB between 2000 and 2014, this study compared outcomes between endoscopic and open surgery in the overall cohort, in patients classified as Kadish C or D only, and in patients classified as Hyman III and IV only. On univariate analysis of the entire cohort, patients that were treated utilizing a transnasal endoscopic approach had improved overall survival and disease-specific survival. However, there were no inter-group differences when assessing locoregional control and metastasis-free survival. Similar results were observed in subpopulation analysis of both advanced stage and high-grade tumors. These findings suggest that patients treated endoscopically have similar rates of recurrence but experience decreased incidence of mortality compared to their counterparts undergoing open procedures. Similar to the Devaiah meta-analysis, Fu postulated that this may be due to more cases of long-term follow-up in the open surgery group. In addition, patients who initially underwent transnasal endoscopic surgery and who develop recurrence may benefit from improved salvage techniques as a majority of these cases were performed more recently.

In conclusion, treatment of ENB through transnasal endoscopic surgery has become more widely accepted over the past two decades. Although short-term outcomes with this approach appear to be more favorable compared to open craniofacial resection, controversy remains regarding long-term survival. As cases of recurrence have been noted to occur decades after initial treatment, future work is necessary to assess the long-term outcomes of this procedure.

Disclosure

Author C. Scott Brown also works as editor of the Otolaryngology section of the Journal of Medical Insight.

Statement of Consent

The patient referred to in this video article has given their informed consent to be filmed and is aware that information and images will be published online.