Esthesioneuroblastoma (ENB) is an uncommon malignant neoplasm of nasal vault.

1. Presesnter: Dr. Prashant Surkar,
DNB, Radiation Oncology,
RGCI & RC

2. o Esthesioneuroblastoma (ENB) is an uncommon
malignant neoplasm of nasal vault, believed to arise
from the olfactory epithelium.
o In 1924, Berger and Luc first described the tumor in
the french medical literature under the name
esthesioneuroepitheliome olfactif.

3.  The exact cell origin of esthesioneuroblastoma is
controversial.
 Jacobson vomeronasal organ
 Sphenopalatine ganglion
 Ectodermal olfactory placode,
 Autonomic ganglia in the nasal mucosa,
 Olfactory epithelium.

4.  Presence of neuro filaments in
esthesioneuroblastoma supports a neuronal crest
origin.
 Recently ENB has found to express the human
homologue (HASH)of the MASH (mammalian
homologues of drosophila achaete-scute) gene.
 ENB should be regarded as originating from the basal
cells of the olfactory neuroepithelium.

5.  Based on the reports in the literature, approximately
1,200 cases of esthesioneuroblastoma (ENB) have
been identified since 1924.
 ENB has an estimated incidence of 4 cases per 10
million individuals and accounts for approximately
5% of all sinonasal tumors.

6.  Race-no familial prevalence and reported in all races
and on all continents.
 It affects males and females with similar frequency.
 Esthesioneuroblastoma occurs in a wide range of age
groups (3-90 y).
 There exists a bimodal peak of occurrence in the
third and sixth decades of life.

7. o No clear etiology in humans.
o Nitrosamine compounds-in rodents,
o In cats –type-c retrovirus

8.  History: no specific symptoms.
 The average delay between the appearence of the
first symptoms and the diagnosis is 6 months.
 Most frequent symptom-unilateral nasal
obstruction(70%) followed by epistaxis(46%).
 Facial and oral symptoms are rare.
 Physical: reddish-gray tumor arising in the upper
nasal cavity.

9.  Nasal and paranasal squamous cell carcinoma
 Sinonasal polyposis
 Choanal polyp
 Juvenile angiofibroma
 Neuroendocrine carcinoma
 Embryonal rhabdomyosarcoma
 Ewing sarcoma
 Extramedullary Plasmacytoma
 Malignant Melanoma
 Metastatic Cancer With Unknown Primary Site
 Non-Hodgkin Lymphoma

10. o Lab studies.
o Imaging- CT
MRI
o Procedures:
Biopsy

11. CT scan:
o A direct coronal fine-cut scan(3mm) is the initial
radiological study of choice.
o No specific appearance-homogeneous soft tissue mass
with uniform and moderate contrast enhancement.
o CT scan is essential for correct staging & to evaluate bony
erosion.
o An unusual but characteristic imaging feature of ENBs is
the presence of cysts at the tumor-brain interface.

12. Coronal CT scan of the orbits and sinuses shows a large, enhancing,
and expansile mass occupying the ethmoid air cells that is invading
the cribriform plate and breaking through to the left anterior cranial
fossa

13. MRI:
o To better delineate sinonasal and intraorbital
extension or an intracerebral extension.
o ENB appears as hypointense to gray matter on t1
weight images and isointense/hyperintense to gray
matter on t2 weighted images.

14. Contrast-enhanced T1-weighted MRI demonstrated a large lesion that
originated in the paranasal sinuses and extended through the cribriform
plate into the anterior cranial fossa.

15.  Since most ENBs express somatostatin receptors, the
use of scintigraphy with a radiolabelled somatostatin
analog (Octreoscan) has been proposed.
 A preliminary study of this technique found it to be
clinically useful, for discriminating between
postoperative changes and residual or recurrent
tumor.

16. o Well differentiated ENB exhibits homogenous small
cells with uniform round-to-oval nuclei with
rosette/pseudorosette formation and eosinophilic
fibrillary intercellular background material.
o True rosettes(flexner-wintersteiner)-refer to a ring of
columnar cells circumscribing a central oval to round
space, which appears clear on sections.

17. o Pseudo-rosettes(homer-wright) rosettes are
characterised by a looser arrengement and presence
of fibrillary material within the lumen.
o Undifferentiated ENB characterized by anaplastic
hyperchromatic small cells with numerous mitoses
and scant cytoplasm.

18. o ENB is positive for S-100 protein and neuron-specific
enolase.
o It is negative for cytokeratin, desmin, vimentin, actin,
glial fibrillary acidic protien and common leucocytic
antigen.

20. o Kadish et al- first proposed,
o A—limited to nasal fossa.
o B—extends to the PNS.
o C---extension beyond the PNS.

21. o T1– involving the nasal cavity and/or pns(excluding
sphenoid).
o T2- including sphenoid with extension to or erosion
of the cribriform plate.
o T3- into the orbit/protruding into the anterior cranial
fossa, without dural invasion.
o T4- involving the brain.
o N0- no nodes,
o N1-any form of cervical ln mets.
o M0-no distant mets, m1 with mets

22. o Surgery.
o Radiation.
o Chemotherapy.

23.  Kadish stage A- either surgery or radiation therapy
yields locoregional control rates exceeding 90%.
 Stage B- Single modality therapy and surgery
followed by adjuvant radiation therapy have been
suggested. But the optimal therapy for stage B
lesions is not clear because of the heterogeneity of
these tumors.
 Stage C- Surgery with adjuvant radiation is generally
used.

24.  Surgery remains the primary treatment for
esthesioneuroblastoma (ENB) and offers the best
chance for locoregional control as well as survival.
 Both open and endoscopic craniofacial resection have
achieved complete surgical resection with tumor-free
margins.
 In the last 20 years, craniofacial resection followed by
radiation therapy has been repeatedly referred to as
the “gold standard” for treatment.

25. oStandard techniques include external megavoltage
beam and a 3-field technique; an anterior port is
combined with wedged lateral fields to provide a
homogeneous dose distribution.
oThe dose varies from 5500-6500cGy.
oElective nodal irradiation is not generally
recommended because the incidence of nodal
relapseis <15%.

26.  A possible role of proton beam radiotherapy, intensity-
modulated radiotherapy, and stereotactic radiation has
been suggested.
 Several institutions have reported that intensity-
modulated radiotherapy can provide good tumor control
with low rates of radiation-induced toxicity, in children as
well as in adults.
 There are case reports describing the use of CT-guided
interstitial high-dose-rate brachytherapy.
 However, prospective clinical trials confirming the
efficacy of these modalities have not yet been
completed.

27.  Among 783 nasal cavity cancers identified from the
SEER database, 103 (13.2%) were
esthesioneuroblastomas; the median survival time
for patients with these tumors was 88 months and
the overall 5-year survival rate was 63.6%.

28.  A series of 72 patients treated at MD Anderson
Cancer Center between 1982 and 2002 included :
 Esthesioneuroblastoma-31 pts,
 Sinonasal undifferentiated carcinoma-16 pts
 Neuroendocrine carcinoma-18 pts, and
 Small cell carcinoma-7 pts.
 The overall survival rates at 5 yrs -93.1% for
esthesioneuroblastoma.
 The local control rates at 5 yrs-96.2%.
 Regional failure rate at 5 yrs-8.7%

30. Chemotherapy is recommended for palliative
treatments or as part of a multimodality treatment
in patients with advanced or metastatic disease.
In University of Virginia protocol, patients with
advanced disease (eg, Kadish stage C) are treated
first with 2 cycles of cyclophosphamide (300-650
mg/m2) and vincristine (1-2 mg) with or without
doxorubicin, followed by 50 Gy of radiotherapy,
which then is followed by a craniofacial resection.

31.  With this regimen, the 5-year and 10-year actuarial
survival rates are 72% and 60%, respectively.
 Similar results have been obtained without
chemotherapy, and how much chemotherapy
contributed to the cure rates is unclear.