Keywords
endoscopy - esthesioneuroblastoma - skull-base - olfactory preservation - craniofacial
Introduction
Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant
tumor of neuroectodermal origin arising from the olfactory epithelium. These tumors
are often unilateral slow-growing masses presenting in the orbital rim or ethmoid
sinuses. ENB comprises 1 to 5% of intranasal tumors[1]
[2]
[3]
[4] and represents < 1% of all malignant tumors.[5] Diagnosis of ENB tends to occur late in the disease course, most commonly presenting
in the second and fifth decades of life as unilateral nasal obstruction and epistaxis.[6]
[7]
[8] Other presenting symptoms reported in the literature include headache, cheek fullness,
proptosis, epiphora, retrobulbar pain, vision changes, infraorbital neuralgia, cranial
nerve deficits, olfactory dysfunction, altered mental status, nausea, vomiting, and
neuroendocrine abnormalities.[9]
[10]
[11]
Traditional first-line treatment for ENB is craniofacial resection (CFR) with postoperative
radiation therapy. The goal of surgery is to achieve a gross total resection with
histologically negative margins. Although the importance of radiation and chemotherapy
remains controversial in the literature,[12]
[13] surgical treatment in combination with adjuvant radiation and/or chemotherapy has
undeniably improved outcomes since the first description of ENB in the literature
in 1924.[8]
[12]
[14]
[15] More recently, the purely endoscopic endonasal approach (EEA) has increased in popularity,
proving to be an effective method for ENB resection. This technique offers the benefits
of reduced morbidity and mortality compared with traditional CFR while achieving comparable
oncologic results.[13]
[14]
[15]
[16] Although critics argue that the endoscopic technique limits the ability to achieve
a complete en bloc resection, a partial or unilateral resection may be appropriate
in select cases. Here we describe a case of olfactory preservation after a unilateral
transcribriform transethmoidal resection of ENB.
Clinical Presentation
A 28-year-old woman presented to the outpatient otolaryngology clinic complaining
of chronic bilateral nasal congestion. Direct endoscopic visualization revealed a
left-sided mass of the sphenoethmoid recess. Magnetic resonance imaging (MRI) demonstrated
a 2.8 × 2.2 × 1.0 cm contrast-enhancing soft tissue lesion in the left nasal cavity
with erosion of the cribriform plate ([Fig. 1]). Preoperative histology was consistent with ENB. Preoperative University of Pennsylvania
Smell Identification Test (UPSIT)[16] revealed normal olfaction.
Fig. 1 Preoperative (A) sagittal and (B) coronal T1-weighted postcontrast magnetic resonance
imaging demonstrating a 2.8 × 2.2 × 1 cm enhancing soft tissue lesion in the left
nasal cavity located medial and inferior to the middle turbinate.
The patient underwent EEA resection via a unilateral transcribriform transethmoidal
approach. The olfactory apparatus (epithelium, cribriform plate, and olfactory bulb)
was removed en bloc with the tumor, sectioning the olfactory tract 1 cm posterior
to the tumor margin ([Fig. 2]). This spared the right olfactory apparatus. Intraoperative frozen pathologic sections
(ipsilateral olfactory tract, contralateral olfactory epithelium, cribriform dura
and bulb) were obtained to confirm histologically negative surgical margins. A multilayered
closure was performed using fascia, rigid buttress, and a vascularized nasoseptal
flap with fibrin-based tissue sealant. No intraoperative complications were encountered.
Postoperatively, the patient experienced a vigorous aseptic meningitis requiring high-dose
steroid therapy for 7 days.
Fig. 2 Intraoperative endoscopic image, left nasal cavity, demonstrating en bloc dissection
of the olfactory apparatus prior to resection. The transition from tumor to normal
olfactory tract is evident (arrow). GR, gyrus rectus; OE, olfactory epithelium; OT,
olfactory tract; T*, tumor.
Immediate postoperative MRI revealed no evidence of residual tumor, and no adjuvant
radiation therapy was prescribed. The patient was maintained on a regimen of nasal
hygiene with twice daily nasal saline spray and routine rhinologic follow-up. Nasal
debridement occurred on an as-needed basis at 10 days and 3 weeks postoperatively.
UPSIT smell testing[17] revealed moderate microsomia at 3 months postoperatively and mild microsomia at
18 months postoperatively. The patient remained disease free at last follow-up of
18 months ([Fig. 3]).
Fig. 3 (A) Sagittal and (B) coronal T1-weighted postcontrast magnetic resonance imaging
at 18 months postoperatively showing resection of the bony nasal septum, portions
of the middle nasal turbinates, ethmoidal air cells, and the medial wall of the left
maxillary antrum. No evidence of tumor recurrence is visible.
Discussion
ENB is a rare malignancy with 5- and 10-year survival rates of ∼ 80% and 50%, respectively.[3]
[17]
[18]
[19]
[20] Metastasis is reported at the time of diagnosis in 10 to 33% of cases.[6]
[7]
[21]
[22]
[23]
[24] Despite high rates of cervical metastases, with adequate treatment, ENB carries
a superior prognosis compared with other superior nasal malignancies.[25] First-line treatment for ENB is CFR with postoperative radiation therapy, combining
a bifrontal craniotomy and transfacial approach to achieve true en bloc resection.
This technique is associated with high morbidity and mortality ranging from 30% to
50%.[26]
[27] Potential complications reported in the literature include intracranial hypertension,
cerebrovascular accident, pneumocephalus, cerebrospinal fluid (CSF) leak, orbital
complications, cosmetic complications, infection, and various systemic complications.[17] More aggressive approaches have been reported, using neoadjuvant concomitant radiation
and platinum-based chemotherapy with limited success.[28]
Endoscopic-assisted CFR was first described in the 1990s, combining a bifrontal craniotomy
with an endoscopic endonasal approach, for ENB resection.[29]
[30]
[31] More recently, purely EEA techniques have been used. The benefits of an endoscopic
approach include superior visualization, decreased operative time, reduced length
of hospital stay, less postoperative pain, and avoidance of craniotomy and facial
incision. The literature contains numerous reports of EEA ENB resection, with oncologic
results comparable with that of traditional CFR.[21]
[29]
[32]
[33]
In 1999, Stammeberger et al performed a retrospective review of eight EEA ENB resections,
with gamma knife adjuvant therapy used in select cases. All patients were found to
be alive and disease free after a mean follow-up period of 37.2 months.[32] Castelnuovo reported similar findings with nearly all patients remaining disease
free at 38.1 months, demonstrating that a purely EEA approach can achieve histologically
negative surgical margins. Of note, among this select group of patients, 90% received
adjuvant radiation therapy and one patient received chemotherapy due to advanced disease.[34] Casiano et al support these findings with 80% of patients remaining free of disease
at 31 months postoperatively.[29] Several retrospective studies describe similar experiences with the EEA approach,
some involving late stage tumors.[8]
[29] The shorter follow-up times in the EEA studies relative to CFR studies limits comparison
of these two approaches. Thorough evaluation of ENB resection techniques requires
long-term follow-up because recurrence and metastases have been reported up to 10
years after initial treatment.[35]
To date, a handful of investigators have developed ENB classification schemes aimed
at guiding surgical therapy and demonstrating varying degrees of prognostic significance.[12]
[23]
[36]
[37] The Kadish system, in particular, has been shown to have prognostic significance
for recurrence and 2- and 5-year survival rates. The Kadish system classifies tumors
as follows: Kadish stage A tumors are limited to the nasal cavity, and Kadish extend
into the paranasal sinuses and stage C beyond the paranasal sinuses. Kadish stages
A and B have lower rates of recurrence and increased survival compared with Kadish
stage C.[23]
In 2009, a meta-analysis published by Devaiah et al compared the results for open
and endoscopic ENB resection in 361 patients. Endoscopic surgery was found to improve
survival rates significantly compared with open surgery with no significant difference
in follow-up time between groups. Notably, patients in the open surgical group possessed
more complex tumors. A total of 63% of all open cases consisted of Kadish stages C
and D tumors; 56% of endoscopic and 61% of endoscopically assisted cases were Kadish
stages A and B.[33]
More recently, Komotar et al performed a thorough literature review comparing EEA
with CFR and combined open/endonasal (CN) ENB resection. The study population consisted
of 47 studies with 453 patients divided into three cohorts based on the respective
surgical approach: CFR (n = 318), EEA (n = 102), and CN (n = 33). The study revealed a greater rate of gross total resection for EEA cases (98.1%)
compared with CFR (81.3%). Negative surgical margins were achieved in 93.8%, 95.8%,
and 77.3% of EEA, CN, and CFR cases, respectively. The EEA approach was also associated
with a decreased rate of regional metastases and greater survival at last follow-up.
These findings support the notion that purely EEA or CN approaches do not result in
significantly worse surgical and oncologic outcomes compared with traditional CFR,
and they serve as viable alternatives for surgical resection.[38] However, much like the meta-analysis published by Devaiah and colleagues, one must
consider the fact that high-grade tumors (Kadish stage C) are frequently treated with
open surgical approaches, whereas endoscopic techniques are more often used for lower
grade tumors (Kadish stages A and B).[33]
Despite the proven utility and benefits of a purely EEA, this technique is not without
complication. Historically, postoperative CSF leak has been a concern with ENB, particularly
when dural involvement is present.[39]
[40] Fortunately, newly developed endoscopic skull base reconstruction techniques have
proven to be very effective. A new multilayered closure technique, called the gasket
seal, has been used in combination with a vascularized nasoseptal flap for a variety
of anterior skull base lesions with zero incidence of CSF leak in select studies.[41] Other potential complications reported in the literature include intraoperative
bleeding, orbital hematoma, frontal lobe abscess, epistaxis, and prolonged nasal crusting.[42]
Most patients are able to undergo endoscopic resection safely and successfully in
the hands of an experienced team of endoscopic neurosurgeons and otolaryngologists.
However, patients frequently complain of prolonged nasal crusting during the postoperative
period. In a quality of life analysis, 69% and 61% of skull base surgery patients
complained of smell disturbance and nasal crusting, respectively.[43] Given the intimate relationship of ENB with the cribriform plate and olfactory nerves,
olfactory function is often compromised, both from resection of olfactory epithelium
and postoperative radiation-induced atrophic rhinitis. However, olfactory dysfunction
can be reduced with the EEA approach relative to traditional CFR.[38] Castelnuovo et al demonstrate that olfactory preservation is possible with EEA approach
for en bloc or piecemeal resection.[34] Critics of the endoscopic approach argue that this technique limits the ability
to achieve en bloc resection, negatively impacting the rate of oncologic cure. However,
one may make the claim that in the hands of an experienced endoscopic surgeon, there
is little, if any, difference in the degree of tissue removed via the endoscopic approach
compared with CFR. Moreover, the literature supports the notion that piecemeal resection
does not necessarily translate to an increased rate of local recurrence.[21]
[31]
[44]
This case provides further support that olfactory preservation is possible via an
EEA in select cases of ENB. Olfactory preservation should be considered as an end
objective, particularly in patients with low-grade tumors (Kadish stages A and B)
and unilateral disease. Meticulous preoperative planning is necessary for olfactory
preservation while achieving a sound oncologic resection. Preoperative MRI and axial
and coronal computed tomography imaging must be reviewed to assess the extent of soft
tissue invasion and bony erosion. The limitations of the EEA must be taken into consideration
as well. For more extensive lesions that invade laterally into the maxillary sinus,
pterygomaxillary fissure, or infratemporal fossa, and lesions that involve the soft
tissues of the face, traditional CFR may be indicated. Adjuvant radiation therapy
can be used in select cases to increase local control.[3]
[13]
[34]
[45]
[46] Follow-up care with a rhinologist is necessary to ensure proper wound healing. Additionally,
long-term follow-up with direct endoscopic visualization and MRI imaging is advised,
regardless of surgical technique, to monitor for local recurrence and metastasis.
Conclusion
Endoscopic endonasal resection of ENB has demonstrated similar oncologic control while
reducing postoperative morbidity and mortality over traditional transcranial approaches.
This case illustrates the potential to preserve olfaction following en bloc resection
of ENB. Further evaluation of surgical technique is required to improve preservation
while ensuring adequate oncologic resection. Futures studies must incorporate long-term
follow up to adequately assess the rate of oncologic cure compared with traditional
approaches.
