The MEDLINE database was searched with the combination ‘esthesioneuroblastoma’ and ‘olfactory neuroblastoma’, from 1990 to 2000, without language tags. The search was supplemented by cross-checking of the references in each publication. Among the 242 articles retrieved, we excluded 53 that did not report directly on ENB cases, 12 that dealt with radiology issues, ten reviews on ENB, and 13 reviews of treatments for base-of-skull neoplasms of mixed histology. We arbitrarily decided to
ReviewEsthesioneuroblastoma: a meta-analysis and review
Section snippets
Methods
Because of the small number of patients, Hyams' histopathological grades (Table 2; Figure 2) are commonly analysed in two groups (grades I and II versus grades III and IV). Since in most cases data were reported in this way only, we also used this grouping. Outcome according to the clinical staging of the Kadish, as well as the Dulguerov-Calcaterra classifications, were tabulated, but not statistically analysed because present meta-analysis statistical methods are geared to comparison of two
Results
The 26 studies2, 4, 5, 6, 8, 43, 54, 55, 56, 57, 58, 60, 61, 62, 63, 64, 65, 66, 68, 69, 70, 71, 72, 73, 77, 78 reported on 390 patients with ENB. Overall survival at 5 years could be extracted from 25 studies; the mean was 45% (SD 22), with extremes of 86%58 and zero.57 Disease-free survival at 2 years was found in 17 studies2, 43, 54, 55, 56, 57, 58, 60, 62, 65, 66, 68, 67, 68, 69, 70, 71, 73, 78, that at 3 years in 20 reports4, 6, 8, 43, 54, 55, 56, 57, 58, 60, 62, 65, 66, 68, 69, 70, 71, 72
Discussion and review
ENB remains a rare disease. Skolnik and colleagues were able to find only about 100 reported cases in the world literature up to 1966.79 More recently, in an extensive review of published studies36, Broich and colleagues found about 1000 new cases reported. The majority of these (80%) have been reported during the past 20 years, almost certainly owing to better recognition of this disease entity by pathologists, although the possibility of a rising incidence cannot be entirely ruled out.
Origin
The exact cell of origin of ENB is controversial. Proposed sources include Jacobson's vomeronasal organ, the sphenopalatine ganglion, the ectodermal olfactory placode, Loci's ganglion, autonomic ganglia in the nasal mucosa, and the olfactory epithelium.36 Although a neuronal or neural crest origin is supported by the presence of neurofilaments in ENB11, until recently33, little evidence linked ENB directly to the olfactory epithelium.
The olfactory neuroepithelium is a unique neurosensory organ,
Histopathological diagnosis
The diagnosis of ENB by light microscopy is not difficult when the tumour is well differentiated and consists of homogeneous small cells with uniform round to oval nuclei, with rosette or pseudorosette formation, and eosinophilic fibrillary intercellular background material. True rosettes (Flexner-Wintersteiner rosettes) consist of a ring of columnar cells circumscribing a central oval or round space, which appears clear on traditional pathological sections. Pseudorosettes (Homer Wright
Clinical data
There have been no precise epidemiological studies, but our unpublished data suggest that ENB represents about 5% of all nasal malignant tumours. ENB affects male and female patients with similar frequency and can be found in all agegroups.2, 36
There is no specific symptom for ENB, as for most nasal and paranasal malignant diseases.2 The average delay between the appearance of the first symptom and the diagnosis is 6 months.2 The commonest symptoms are a unilateral nasal obstruction (70%),
Treatment
A combination of surgery and radiotherapy is the most frequently used approach, and the one achieving the highest cure rates. Despite the lack of support for single-modality treatment regimens54, a substantial number of patients are treated by surgery or radiotherapy alone. The difference in survival between the combined treatments and radiotherapy alone is significant (Table 3). Although surgery alone, a combination of radiotherapy and chemotherapy, and triplemodality treatment (surgery,
Prognosis
Treatment results before the availability and use of modern diagnostic techniques were probably flawed by the inclusion of cases of sinonasal undifferentiated carcinoma and sinonasal neuroendocrine carcinoma. Although the metaanalysis found a 5-year survival of 45%, most large studies quoted survival around 70%.2, 6, 7, 64 The most frequent recurrence is local, with rates around 30%.7, 8, 64 Craniofacial resection followed by radiotherapy seems to result in fewer recurrences – around 10%.2, 61
Search strategy and selection criteria
References (92)
- et al.
Expression of cell adhesion molecules in the olfactory system of the adult mouse: presence of the embryonic form of N-CAM
Dev Biol
(1988) - et al.
Esthesioneuroblastoma: a comparison of two treatment eras
Int J Radiat Oncol Biol Phys
(1988) - et al.
Regulation of gene expression in the olfactory neuroepithelium: a neurogenetic matrix
Prog Brain Res
(1991) - et al.
Sinonasal undifferentiated carcinoma: a 10-year experience
Am J Otolaryngol
(1996) - et al.
Trisomy 8 in primary esthesioneuroblastoma
Cancer Genet Cytogenet
(1991) - et al.
Cytogenetic and pathologic aspects of Ewing's sarcoma and neuroectodermal tumors
Hum Pathol
(1992) - et al.
EWS/FLI-1 rearrangement in small round cell sarcomas of bone and soft tissue detected by reverse transcriptase polymerase chain reaction amplification
Eur J Cancer
(1994) - et al.
Is esthesioneuroblastoma a peripheral neuroectodermal tumor?
Hum Pathol
(1995) - et al.
Absence of EWS/FL11 fusion in olfactory neuroblastomas indicates these tumors do not belong to the Ewing's sarcoma family
Hum Pathol
(1999) - et al.
Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses
Hum Pathol
(1998)
Esthesioneuroblastoma: the role of adjuvant radiation therapy
Int J Radiat Oncol Biol Phys
High dose level radiation therapy for local tumour control in esthesioneuroblastoma
Eur J Cancer
Plasticity of connections of the olfactory sensory neuron: regeneration into the forebrain following bulbectomy in the neonatal mouse
Neuroscience
A membrane phosphoprotein associated with neural development, axonal regeneration, phospholipid metabolism and synaptic plasticity
Trends Neurosci
Mammalian achaete-scute homolog 1 is required for the early development of olfactory and autonomic neurons
Cell
Ewing's sarcoma-routine diagnostic utilization of MIC2 analysis: a Pediatric Oncology Group/Children's Cancer Group Intergroup Study
Hum Pathol
L'esthesioneuroepitheliome olfactif
Bull Assoc Fr Etude Cancer
Esthesioneuroblastoma: the UCLA experience 1970–1990
Laryngoscope
Olfactory neuroblastoma: a clinical analysis of 17 cases
Cancer
Olfactory neuroblastoma and neuroendocrine carcinoma of the anterior skull base: treatment results at the MD Anderson Cancer Center
Skull Base Surg
Successful treatment of esthesioneuroblastoma and neuroendocrine carcinoma with combined chemotherapy and proton radiation: results in 9 cases
Arch Otolaryngol Head Neck Surg
Outcome and analysis of the surgical management of esthesioneuroblastoma
J Otolaryngol
Esthesioneuroblastoma: prognosis and management
Neurosurgery
Aesthesioneuroblastoma
J Laryngol Otol
Induction of olfactory neuroepithelial tumors in Syrian hamsters by diethylnitrosamine
Cancer
Neuroblastomas and neuroendocrine carcinomas of the nasal cavity: a proposed new classification
Cancer
Neuronal origin of human esthesioneuroblastoma demonstrated with antineurofilament monoclonal antibodies
N Engl J Med
The spectrum of olfactory neural tumors: a light-microscopic, immunohistochemical and ultrastructural analysis
Am J Surg Pathol
Esthesioneuroblastoma: intermediate filaments, neuroendocrine, and tissue-specific antigens
Am J Clin Pathol
Olfactory neuroblastoma
The expression of the growth associated protein B50/GAP43 in the olfactory system of neonatal and adult rats
J Neurosci
Chemically induced esthesioneuroepithelioma: ultrastructural findings
Ann Otol Rhinol Laryngol
Esthesioneuroblastoma and neck metastasis
Head Neck
Identification of a human achaete-scute homolog highly expressed in neuroendocrine tumors
Proc Natl Acad Sci USA
Sinonasal esthesioneuroblastoma with intracranial extension: marginal Review Esthesioneuroblastoma tumor cysts as a diagnostic MR finding
AJNR Am J Neuroradiol
Olfactory neuron-specific expression of NeuroD in mouse and human nasal mucosa
Cell Tissue Res
The minimally invasive approach to olfactory neuroblastoma: combined endoscopic and stereotactic treatment
Laryngoscope
Endoscopic cranionasal resection of anterior skull base tumor
Am J Otolaryngol
Activation of retrovirus in transgenic mice: association with development of olfactory neuroblastoma
J Virol
Type C retroviral expression in spontaneous feline olfactory neuroblastomas
Acta Neuropathol
Metastasizing neuroblastomas in mice transgenic for simian virus 40 large T (SV40T) under the olfactory marker protein gene promoter
Cancer Res
Expression of the human Achaetescute 1 gene in olfactory neuroblastoma (esthesioneuroblastoma)
J Neurooncol
Olfactory neuroblastoma is a peripheral primitive neuroectodermal tumor related to Ewing sarcoma
Proc Natl Acad Sci USA
Esthesioneuroblastoma: a general review of the cases published since the discovery of the tumour in 1924
Anticancer Res
Olfactory neuroblastoma is not related to the Ewing family of tumors: absence of EWS/FL11 gene fusion and MIC2 expression
Am J Surg Pathol
Caffeine-derived Nnitroso compounds: V, carcinogenicity of mononitrosocaffeidine and dinitrosocaffeidine in bd-ix rats
Carcinogenesis
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