eMedicine Specialties > Oncology > Carcinomas of the Central and Peripheral Nervous System

Esthesioneuroblastoma

Author: Michael Somenek, MD, Resident Physician, Department of Otolaryngology, Rush University Medical Center
Coauthor(s): Nicholas C Shera, PhD, Freelance Medical/Scientific Writer; Guy J Petruzzelli, MD, PhD, MBA, FACS, The Charles Arthur Weaver Professor of Cancer Research, Professor and Senior Attending Physician, Director of Head, Neck, and Skull Base Surgery, Department of Otolaryngology, Rush University Medical Center
Contributor Information and Disclosures

Updated: Oct 30, 2009

Introduction

Background

Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare neoplasm originating from olfactory neuroepithelium. Approximately 1,000 cases have been identified since Berger and Luc described the first case in 1924.1 Due to the rare and complex nature of ENB, multiple opinions exist regarding the etiology, optimal staging system, and treatment modalities. These tumors often display varying biologic activity ranging from indolent growth, with patient survival exceeding 20 years, to a highly aggressive neoplasm capable of rapid widespread metastasis, with survival limited to a few months.

Esthesioneuroblastoma. Coronal CT scan of the orb...

Esthesioneuroblastoma. 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. Image courtesy of Michael Lev, MD.

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Esthesioneuroblastoma. Coronal CT scan of the orb...

Esthesioneuroblastoma. 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. Image courtesy of Michael Lev, MD.


Esthesioneuroblastoma. A 39-year-old man presente...

Esthesioneuroblastoma. A 39-year-old man presented with 1 month of decreased vision, left facial numbness, and swelling. Physical examination demonstrated left-sided exophthalmos and blindness. He had also lost his sense of smell. 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. He underwent a bifrontal craniotomy for resection of this tumor.

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Esthesioneuroblastoma. A 39-year-old man presente...

Esthesioneuroblastoma. A 39-year-old man presented with 1 month of decreased vision, left facial numbness, and swelling. Physical examination demonstrated left-sided exophthalmos and blindness. He had also lost his sense of smell. 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. He underwent a bifrontal craniotomy for resection of this tumor.


The prognosis depends on the magnitude of the disease on initial diagnosis. It should be noted that precise histologic diagnosis is difficult because ENBs are often confused with other small round cell neoplasms of the nasal cavity. Despite the difficulties associated with the treatment of ENB, evolving treatment modalities, including surgery, radiation, and adjuvant chemotherapy, have contributed to the better management and increased survival of ENB patients. This article provides an updated summary of ENB, including ongoing research, current thought on pathophysiology, staging, and an update on new surgical techniques used to treat these tumors.

Pathophysiology

Esthesioneuroblastomas (ENBs) are undifferentiated tumors of neuroectodermal origin derived from the olfactory epithelium.2 The tumor cells are mitotically active and are the precursor cells that develop into sustentacular and neuronal cells. Inconsistent histologic presentations initially led to controversy surrounding the exact histologic origin of ENBs, and this ambiguity can confound clinical and prognostic decisions. In essence, ENBs contain variable arrangements of their small cells. Additionally, there exists a variable presence (or absence) of true rosettes and neurofibrillary material.

To date, no certain genetic factor has been identified that can accurately assist in the diagnosis or predict prognosis. This is partially due to the ability to analyze cancer genomes on a whole genome basis. Recently, a tool called array comparative genomic hybridization was applied to the analysis of ENBs.3 Although many alterations were identified in this study, chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q have been confirmed by at least 2 other studies. Interestingly, 20q is a region that has been implicated in other cancers, including breast, ovarian, and squamous cell carcinoma. Still, further experimentation will be required to determine the role of these genomic regions in ENB.

The demonstration of human achaete-scute homologue (HASH1) gene expression, although still investigational, could become the diagnostic procedure of choice.4 The HASH1 gene is involved in olfactory neuronal differentiation and is expressed in immature olfactory cells5 ; therefore, it could be useful in distinguishing ENB from other poorly differentiated small blue cell tumors.

Frequency

United States

The incidence of esthesioneuroblastoma in the United States follows trends observed worldwide.

International

Based on the reports in the literature, approximately 1,200 cases of esthesioneuroblastoma (ENB) have been identified since 1924. Interestingly, 80% of these have been identified in the last 25 years. However, the current data set cannot distinguish between a rising incidence and better recognition of the disease. ENB has an estimated incidence of 4 cases per 10 million individuals and accounts for approximately 5% of all sinonasal tumors. Similar incidence rates have been obtained through epidemiologic studies performed in Denmark.6 To our knowledge, no studies suggest a geographic deviation.

Race

  • Esthesioneuroblastoma (ENB) does not show a predilection toward any individual race. ENB does not show familial prevalence and has been reported in all races and on all continents.

Sex

  • Esthesioneuroblastoma (ENB) affects males and females with similar frequency.

Age

    • Esthesioneuroblastoma (ENB) 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.

Clinical

History

The symptoms of esthesioneuroblastoma (ENB) can be classified into nasal, neurologic, oral, facial, cervical, and ophthalmologic and are as follows:

  • Nasal - Obstruction (70%), epistaxis (46%), discharge, unilateral polyp, anosmia
  • Neurologic - Headache, nausea
  • Oral (rare) - Mobile tooth, nonhealing tooth-extraction site, ill-fitting dental prostheses, ulceration
  • Facial (rare) - Swelling, pain, anesthesia, trismus
  • Cervical - Mass
  • Ophthalmologic - proptosis, extraocular movement paralysis, and blindness,
The average delay between the appearance of the initial symptom and the diagnosis is 6 months, but diagnosis is delayed for years in some cases. Delay is understandable because initial symptoms tend to be subtle and are frequently banal, occurring also in common nasal diseases, including long-term rhinosinusitis or allergic polypoid sinus disease.

Many patients undergo sinus surgery, only to have the diagnosis established as an unexpected pathologic finding. Therefore, sending all the tissue removed during sinus surgery for pathologic examination is important for diagnosis of esthesioneuroblastoma, as is the vigilance of the pathologist in examining the tissue.

For the most part, malignancy is not considered until secondary symptoms such as facial pain and deformity or cranial nerve impairment are observed. However, early referral for an intranasal biopsy is essential to early diagnosis. A patient with a unilateral nasal obstruction and/or recurrent epistaxis lasting longer than 1-2 months should undergo a thorough nasal evaluation by an otolaryngologist, although the cost-effectiveness of this approach has not been evaluated.

Physical

Nasal examination, particularly if aided by endoscopy, reveals a reddish-gray tumor arising in the upper nasal fossa, which bleeds easily with instrumentation. Although this aspect is strictly different from the white, glistening appearance of benign nasal polyps, little differentiates esthesioneuroblastoma (ENB) from other nasal malignancies. Late findings may include signs related to extensive disease such as orbital, cranial, and cervical involvement.

Causes

No clear etiologic agent or exposure has been documented in humans; however, a single case of occupational exposure has been reported in a woodworker.7 Esthesioneuroblastoma (ENB) can be consistently induced by nitrosamine compounds in rodents. In cats with spontaneous ENB or in transgenic mice developing ENB, type C retroviral particles have been demonstrated and classified as feline and murine leukemia virus, respectively. The role of retrovirus sequences in human ENB remains to be evaluated.

More on Esthesioneuroblastoma

Overview: Esthesioneuroblastoma
Differential Diagnoses & Workup: Esthesioneuroblastoma
Treatment & Medication: Esthesioneuroblastoma
Follow-up: Esthesioneuroblastoma
Multimedia: Esthesioneuroblastoma
References
Further Reading
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Keywords

esthesioneuroblastoma, ENB, olfactory neuroblastoma, esthesioneuroepithelioma, olfactory esthesioneuroma, esthesioneurocytoma

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Contributor Information and Disclosures

Author

Michael Somenek, MD, Resident Physician, Department of Otolaryngology, Rush University Medical Center
Michael Somenek, MD is a member of the following medical societies: Alpha Omega Alpha and Sigma Xi
Disclosure: Nothing to disclose.

Coauthor(s)

Nicholas C Shera, PhD, Freelance Medical/Scientific Writer
Disclosure: Nothing to disclose.

Guy J Petruzzelli, MD, PhD, MBA, FACS, The Charles Arthur Weaver Professor of Cancer Research, Professor and Senior Attending Physician, Director of Head, Neck, and Skull Base Surgery, Department of Otolaryngology, Rush University Medical Center
Guy J Petruzzelli, MD, PhD, MBA, FACS is a member of the following medical societies: American Academy of Otolaryngology-Head and Neck Surgery, American Association for the Advancement of Science, American Association of Clinical Anatomists, American College of Surgeons, American Medical Association, American Society for Head and Neck Surgery, American Society of Clinical Oncology, Chicago Medical Society, North American Skull Base Society, Society of Surgical Oncology, Society of University Otolaryngologists-Head and Neck Surgeons, and Southwest Oncology Group
Disclosure: Nothing to disclose.

Medical Editor

Robert C Shepard, MD, FACP, Associate Professor of Medicine in Hematology and Oncology at University of North Carolina at Chapel Hill; Vice President of Scientific Affairs, Therapeutic Expertise, Oncology, at PRA International
Robert C Shepard, MD, FACP is a member of the following medical societies: American Association for Cancer Research, American College of Physician Executives, American College of Physicians, American Federation for Clinical Research, American Federation for Medical Research, American Medical Association, American Medical Informatics Association, American Society of Hematology, Association of Clinical Research Professionals, Eastern Cooperative Oncology Group, European Society for Medical Oncology, Massachusetts Medical Society, and Society for Biological Therapy
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

CME Editor

Rajalaxmi McKenna, MD, FACP, Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems
Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis
Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD, Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine at Tucson; Consulting Staff, Arizona Cancer Center
Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research
Disclosure: GlobeImmune Salary Consulting; Amplimed Consulting fee Consulting; FibroGen Consulting fee Consulting

 
 
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