Keywords
olfactory neuroblastoma - esthesioneuroblastoma - skull base - imaging
Introduction
Olfactory neuroblastoma, or esthesioneuroblastoma (ENB), is an uncommon malignant
tumor of neural crest origin, arising from the olfactory epithelium of the superior
nasal cavity. It accounts for ∼ 2 to 6% of the intranasal tumors, with an incidence
of ∼ 0.4 per million.[1]
[2]
[3] The age at presentation is bimodal in distribution in the second and sixth decades
of life and without a gender predilection.[4]
[5]
Staging
The stage of the disease at the initial presentation is highly predictive of survival,
and accurate staging is essential. The Kadish system is the most commonly used approach
to classify the anatomical extent of ENB, although other classifications have been
proposed.[6]
[7]
[8]
[9] The Kadish staging uses three categories, group A, B, and C, as follows: A, tumor
confined to the nasal cavity; B, tumor extends into the paranasal sinuses; and C,
tumor extends beyond the nasal cavity and paranasal sinuses including involvement
of the cribriform plate, skull base, orbit, or intracranial cavity. The modified Kadish
staging system includes a fourth stage for patients with nodal or distant metastases.[10] This system has been criticized because it requires surgical staging, does not routinely
consider metastatic spread, and lacks prognostic value. Additionally, few patients
at initial clinical discovery have group A disease if the staging is strictly applied
because of a high incidence of ethmoid sinus involvement. Simon et al did not find
a single patient in their 20-year experience that presented with stage A disease.[5] Similar observations have been reported in other series, and the overall incidence
of Kadish A disease is estimated at 5%.[11]
[12]
[13]
[14] Modern imaging makes a diagnosis of Kadish A disease less likely.
Despite the inadequacies and attempts to use a TNM classification, the Kadish staging
is the most commonly used.[8] The Dulguerov staging system uses the TNM classification and includes the imaging
data ([Table 1]).[8] Some authors prefer the Dulguerov system because early involvement of the cribriform
plate is recognized in the T2 stage, and intracranial but extradural tumors are separated
from those with true brain involvement.[15]
Table 1
Esthesioneuroblastoma staging system as proposed by Dulguerov[8]
|
Staging
|
Description
|
|
Primary tumor
|
|
T1
|
Tumor involving the nasal cavity and/or paranasal sinuses (excluding sphenoid), sparing
the most superior ethmoid
|
|
T2
|
Tumor involving the nasal cavity and/or paranasal sinuses (including the sphenoid)
with extension to or erosion of the cribriform plate
|
|
T3
|
Tumor extending into the orbit or protruding into the anterior cranial fossa, without
dural involvement
|
|
T4
|
Tumor involving the brain
|
|
Lymph nodes
|
|
N0
|
No cervical lymph node metastasis
|
|
N1
|
Any form of cervical lymph node metastasis
|
|
Distant metastasis
|
|
M0
|
No metastases
|
|
M1
|
Distant metastases
|
Clinical Presentation
ENB presents with epistaxis, nasal obstruction, decreased olfactory function, diplopia,
proptosis, or a combination of these symptoms.[6]
[7]
[9]
[16] Local invasion occurs most frequently into the paranasal sinuses, orbits, and anterior
cranial fossa. Metastatic disease most frequently involves local lymph nodes, with
distant metastasis to the lungs, liver, and bone.[1]
[6]
[8] The incidence of cervical lymph node metastasis ranges from 20 to 30% and reaches
44% in stage C.[2]
[6]
[8]
[17]
[18]
[19] Howell et al described a predictable pattern of metastases to the cervical lymph
nodes, typically involving level II nodes (93%), with frequent involvement of level
I (57%), level III (50%), and retropharyngeal nodes (43%).[20]
Imaging
Imaging plays a key role in the accurate staging of ENB including both computed tomography
(CT) and magnetic resonance imaging (MRI). These imaging modalities should always
be included to correctly assess the extent of the disease. CT should be performed
with thin slices (1 mm thick) and reformatted in both coronal and sagittal planes.
ENB does not have specific CT characteristics, presenting initially as a homogeneous
soft tissue mass in the nasal vault. However, CT is essential for evaluation of the
osseous involvement of the cribriform plate, fovea ethmoidalis, and lamina papyracea
([Fig. 1]). Bone remodeling without destruction is not uncommon, due to the indolent growth
pattern in some cases. The mass shows moderate and uniform enhancement. Scattered
speckled calcifications are occasionally present.[21] CT is also useful to assess regional neck and distant metastasis.[20]
[22]
Fig. 1 Coronal computed tomography of the face in (A, B) bone and (C, D) soft tissue algorithms
demonstrates avidly enhancing esthesioneuroblastoma (E) filling the nasal cavity and
extending into orbits and intracranially (asterisk). The mass has eroded the floor
of the anterior cranial fossa (single arrow) and lamina papyracea bilaterally (double
arrow).
The most important information gained from MRI is differentiating entrapped secretions
from neoplasm because CT is unreliable for this distinction ([Fig. 2]).[22]
[23] MRI is also superior in defining the soft tissue extent and offers a more accurate
assessment of suspected intracranial, orbital, or skull base invasion, and perineural
spread of tumor.[7]
[22]
[24] MRI is also excellent at distinguishing dural involvement from parenchymal involvement
([Fig. 3]).[23]
Fig. 2 Coronal (A) T1-weighted, (B) contrast-enhanced, and (C) T2-weighted images from magnetic
resonance imaging demonstrate a low T1 intensity and avidly enhancing nasal vault
mass extending intracranially (arrow). (C) The T2-weighted sequence shows peritumoral
cyst (double arrow).
Fig. 3 (A, B) Utility of magnetic resonance imaging in the evaluation of dural involvement
as demonstrated by coronal fat-saturated contrast-enhanced images (dashed arrow).
Intracranial extension fills the right olfactory groove (arrow in A). (C) Axial T2-weighted
image shows a clear distinction between low-intensity esthesioneuroblastoma (arrows)
and high-intensity trapped secretions (double arrows). (D) Sagittal reformatted image
from positron emission tomography shows avid tracer uptake within the nasal vault
mass with a large intracranial component.
ENB is usually hypointense to gray matter on T1-weighted images and intermediate to
hyperintense on T2-weighted sequences ([Fig. 2]). The tumor demonstrates avid and homogeneous enhancement except for occasional
areas of necrosis or hemorrhage. Trapped secretions in adjacent sinuses are T2 hyperintense
and differentiated from the tumor. The presence of intracranial cysts is highly suggestive
of, but not diagnostic of ENB. Som et al studied 54 patients who had sinonasal lesions
with intracranial extension and found only three patients with intracranial cysts,
but all three had ENB.[25]
Bony destruction can be seen but frequently not as well as with CT. MRI, however,
is much more accurate in the evaluation of subtle orbital and intracranial invasion
including rare subarachnoid seeding. MRI fat-saturated sequences help distinguish
tumor from orbital fat and muscle: a smooth bowing of the tumor–fat interface suggests
that the lesion is contained by periorbital fascia, whereas an irregular margin favors
frank invasion of the orbit.[26]
[27] However, the definitive diagnosis of invasion of dura and periorbital tissues is
possible only at surgery.[27]
Imaging of the neck in patients with ENB is crucial because neck metastases are found
at presentation in 5% of patients.[7] Further, it has been estimated that > 23% of patients may eventually develop cervical
lymph node metastases.[17] One of the most frequent distant metastasis is to bone, with the spine cited as
the most common location (86%).[28] Cases of asymptomatic bone metastases have been described, and therefore a bone
scan should be included in the diagnostic work-up.[7]
The assessment of recurrent tumor must include both CT and MRI. The imaging characteristics
of the recurrent tumor do not differ from its appearance at initial presentation.[29] The following protocol for follow-up has been suggested: contrast-enhanced MRI performed
2 to 4 months after completion of all therapy, and then repeated every 4 to 6 months
for 5 years and then annually for the patient's lifetime. In addition, an annual chest
radiograph should be performed to exclude the presence of metastases.[14]
Scintigraphic evaluation of ENB has been reported with technetium-99m methylene diphosphonate,
indium-111 bleomycin complex, indium-111 octreotide, technetium-99m ethylcysteinate
dimer, and radioiodinated metaiodobenzylguanidine.[12]
[30]
[31]
[32] More recently, positron emission tomography (PET) with F-18-labeled fluorodeoxyglucose
was used in the staging of ENB in a case with ectopic Cushing syndrome.[33] PET-CT was also found to be accurate not only in staging but also in the posttherapeutic
restaging of ENB.[34] While promising, the data on PET and other scintigraphic methods in evaluation of
recurrent or residual ENB are very limited.
Finally, because ENB is most often a nonvascular tumor, diagnostic and therapeutic
angiographic techniques have no place in the diagnostic work-up of this entity.[35]
Conclusion
Although the imaging characteristics of ENB are somewhat nonspecific, there are patterns
of the disease, such as Kadish grade C, which should strongly suggest this disorder.
Metastatic disease, usually regional, occurs frequently with fairly predictable involvement
of level II nodes but also level I and III and retropharyngeal nodes that are difficult
to assess clinically. Finally, a suggested follow-up scheme is recommended to detect
recurrences at the earliest possible time.
