Esthesioneuroblastoma (also termed olfactory neuroblastoma) is a small round cell tumor arising from the nasal neuroepithelium that is distinct from primitive neuroectodermal tumors.[1,2,3,4] In children, esthesioneuroblastoma is a very rare malignancy, with an estimated incidence of 0.1 cases per 100,000 per year in children younger than 15 years.
Despite its rarity, esthesioneuroblastoma is the most common cancer of the nasal cavity in pediatric patients, accounting for 28% of cases in a Surveillance, Epidemiology, and End Results (SEER) study. In a series of 511 patients from the SEER database, there was a slight male predominance, the mean age at presentation was 53 years, and only 8% of cases were younger than 25 years. Most patients were white (81%) and the most common tumor sites were the nasal cavity (72%) and ethmoid sinus (13%). In a retrospective, multi-institutional review of 24 pediatric patients with esthesioneuroblastoma, the median age at presentation was 14 years and 75% of patients were female.
Esthesioneuroblastoma can be histologically confused with other small round cell tumors of the nasal cavity, including sinonasal undifferentiated carcinoma, small cell carcinoma, melanoma, and rhabdomyosarcoma. Esthesioneuroblastoma typically shows diffuse staining with neuron-specific enolase, synaptophysin, and chromogranins, with variable cytokeratin expression.
Sixty-six samples of olfactory neuroblastoma and tumor samples from other cancers, including alveolar rhabdomyosarcoma and sinonasal adenocarcinoma, were obtained from nine medical centers and analyzed by genome-wide DNA methylation profiling, copy number analysis, immunohistochemistry, and next-generation panel sequencing. Unsupervised hierarchal clustering analysis of DNA methylation data identified the following four distinct clusters:
Using this information, the authors developed an algorithm that incorporates methylation analysis to improve the diagnostic accuracy of this entity.
Tumors are staged according to the Kadish system (refer to Table 1). Correlated with Kadish stage, survival ranges from 90% (stage A) to less than 40% (stage D). Most patients present with locally advanced–stage disease (Kadish stages B and C) and almost one-third of patients have tumors at distant sites (Kadish stage D).[1,2,3]
Recent reports suggest that positron emission tomography–computed tomography (PET-CT) may aid in staging the disease.
|A||Tumor confined to the nasal cavity.|
|B||Tumor extending to the nasal sinuses.|
|C||Tumor extending to the nasal sinuses and beyond.|
|D||Tumor metastases present.|
The use of multimodal therapy optimizes the chances for survival, with more than 70% of children expected to survive 5 or more years after initial diagnosis.[1,2,3] A multi-institutional review of 24 patients younger than 21 years at diagnosis found a 5-year disease-free survival and overall survival of 73% to 74%.[Level of evidence: 3iiiA] The French very rare tumors group registry identified 18 patients younger than 18 years with esthesioneuroblastoma from 1990 to 2015. After a median follow-up of survivors of 7.6 years (range, 3.8–17.9 years), ten patients developed neuromeningeal progression, whereas no cervical nodal relapses occurred. Only eight patients survived.[Level of evidence: 3iA]
Treatment options according to Kadish stage include the following:
The mainstay of treatment is surgery and radiation. Newer techniques such as endoscopic sinus surgery may offer similar short-term outcomes to open craniofacial resection.; [Level of evidence: 3iiiDii] Other techniques such as stereotactic radiosurgery and proton-beam therapy (charged-particle radiation therapy) may also play a role in the management of this tumor.[3,10]
Nodal metastases are seen in about 5% of patients. Routine neck dissection and nodal exploration are not indicated in the absence of clinical or radiological evidence of disease. Management of cervical lymph node metastases has been addressed in a review article.
Reports indicate promising results with the increased use of resection and neoadjuvant or adjuvant chemotherapy in patients with advanced-stage disease.[2,4,12,13,14]; [Level of evidence: 3iii] Chemotherapy regimens that have been used with efficacy include cisplatin and etoposide with or without ifosfamide;[6,16] vincristine, actinomycin D, and cyclophosphamide with or without doxorubicin; ifosfamide and etoposide; cisplatin plus etoposide or doxorubicin; vincristine, doxorubicin, and cyclophosphamide; and irinotecan plus docetaxel.[Level of evidence: 3iiA]
Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.
The following is an example of a national and/or institutional clinical trial that is currently being conducted:
Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the NCI website and ClinicalTrials.gov website.
Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975. Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered for children and adolescents with cancer. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:
(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)
Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics. At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.
Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%. Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)
Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years. The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 persons. Therefore, all pediatric cancers are considered rare.
The designation of a rare tumor is not uniform among pediatric and adult groups. Adult rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people, and they are estimated to account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[5,6] Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:
Most cancers within subgroup XI are either melanomas or thyroid cancer, with the remaining subgroup XI cancer types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.
These rare cancers are extremely challenging to study because of the low incidence of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
Treatment and Outcome of Childhood Esthesioneuroblastoma
Added text to state that the French very rare tumors group registry identified 18 patients younger than 18 years with esthesioneuroblastoma from 1990 to 2015. After a median follow-up of survivors of 7.6 years, ten patients developed neuromeningeal progression, whereas no cervical nodal relapses occurred. Only eight patients survived (cited Dumont et al. as reference 5 and level of evidence 3iA).
This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® - NCI's Comprehensive Cancer Database pages.
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of childhood esthesioneuroblastoma. It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Childhood Esthesioneuroblastoma Treatment are:
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Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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The preferred citation for this PDQ summary is:
PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Esthesioneuroblastoma Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/head-and-neck/hp/child/esthesioneuroblastoma-treatment-pdq. Accessed <MM/DD/YYYY>.
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Last Revised: 2020-06-08
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