Elsevier

The Lancet Oncology

Volume 2, Issue 11, November 2001, Pages 683-690
The Lancet Oncology

Review
Esthesioneuroblastoma: a meta-analysis and review

https://doi.org/10.1016/S1470-2045(01)00558-7Get rights and content

Summary

Our objective was to review recent developments in diagnosis, staging, and treatment of esthesioneuroblastoma (ENB). A meta-analysis of publications between 1990 and 2000 was carried out, and studies were classified according to their main subject: origin/aetiology of ENB, histopathological diagnosis, and treatment. Data so far point to the basal progenitor cells of the olfactory epithelium as the origin of ENB. Histopathological diagnosis remains difficult and is based on results of antigen expression detected through a panel of antibodies by immunohistochemistry. RT-PCR of HASH expression could be a specific marker of ENB. Overall and disease-free survival at 5 years averaged 45% (SD 22) and 41% (SD 21) in the studies included in the metaanalysis. Survival in Hyams' grades I-II was 56% (SD 20) compared with 25% (SD 20) in grades III-IV (odds ratio 6·2). In patients with metastases in cervical lymph nodes (on average 5% of the total) survival was 29%, compared with 64% for patients with N0 disease (odds ratio 5·1). Survival according to treatment modalities was 65% for surgery plus radiotherapy, 51% for radiotherapy and chemotherapy, 48% for surgery, 47% for surgery plus radiotherapy and chemotherapy, and 37% for radiotherapy alone. The histopathological grading according to Hyams and the presence of cervical lymph-node metastases emerged as prognostic factors. A combination of surgery and radiotherapy seems to be the optimum approach to treatment. The exact role of chemotherapy in treatment protocols is still unclear. The role of elective neck dissection is unclear.

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

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

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