Esthesioneuroblastoma overview

# Overview
Esthesioneuroblastoma, also known as olfactory neuroblastoma, is a rare form of cancer involving nasal cavity and believed to arise from the olfactory epithelium. It can cause loss of vision, and taste. Esthesioneuroblastomas are undifferentiated tumors of neuroectodermal origin derived from the olfactory epithelium. The tumor cells are mitotically active and are the precursor cells that develop into sustentacular and neuronal cells. They usually present as a soft tissue mass in the superior olfactory recess involving the anterior and middle ethmoid air-cells on one side and extending through the cribriform plate into the anterior cranial fossa. Based on the duration of symptoms, esthesioneuroblastoma may be classified into two subtypes neuroblastoma proper and neuroendocrine carcinomas. Genes involved in the pathogenesis of esthesioneuroblastoma include chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q. On gross pathology, soft and hemorrhagic, polypoid appearance, and rich and fragile vascular supply of the tumor are characteristic findings of esthesioneuroblastoma. On microscopic histopathological analysis, arrangements of cells into rosettes or pseudorosettes are characteristic findings of esthesioneuroblastoma. The incidence of esthesioneuroblastoma is approximately 0.4 per 100,000 individuals worldwide. Esthesioneuroblastoma can present in a wide range of age groups; however, it is mostly noted in a bimodal distribution, occurring most frequently in the second and sixth decades of life. There is no racial predilection to the esthesioneuroblastoma. There are no established risk factors for esthesioneuroblastoma.
If left untreated, 10%-62% of patients with esthesioneuroblastoma may progress to develop metastasis. Common complications of esthesioneuroblastoma include tumor recurrence and metastasis. 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. The five-year mortality rate of patients with esthesioneuroblastoma is approximately 56% and 20% for grade I and II and grade III and IV tumors, respectively. The ten-year mortality rate of patients with esthesioneuroblastoma is approximately 67% and 34% for grade I and II and grade III and IV tumors, respectively. Symptoms of esthesioneuroblastoma include nasal obstruction, epistaxis, ear pain, otitis media, hyposmia, nasal discharge, facial pain, changes in vision, lacrimation, facial numbness, and anosmia. Common physical examination findings of esthesioneuroblastoma include reddish-gray, polypoid mass located in the upper nasal fossa, epistaxis, nasal discharge, nasal pain, facial swelling, trismus, proptosis, diplopia, anosmia, serous otitis media, cervical lymphadenopathy, retropharyngeal lymphadenopathy, decreased visual acuity, extraocular movement paralysis, altered mental status, and frontal headaches. Biopsy may be helpful in the diagnosis of esthesioneuroblastoma. Findings on biopsy diagnostic of esthesioneuroblastoma include small, round-to-oval cells with coarsely granular chromatin, prominent nuclear membranes, multiple small nucleoli, and scant cytoplasm with pseudorosette or occasional Homer-Wright rosettes separated by fibrous septa. Calcification and necrosis are sometimes seen, and mitotic figures are rare. On head and neck CT, esthesioneuroblastoma is characterized by soft tissue attenuation, with relatively homogenous enhancement. Head and neck MRI scan is diagnostic of esthesioneuroblastoma. On head and neck MRI, esthesioneuroblastoma is characterized by heterogenous intermediate signal on T1 and T2weighted MRI and  variable enhancement on T1 contrast with gadolinium. The predominant therapy for esthesioneuroblastoma is surgical resection followed by postoperative irradiation. Adjunctive radiation/chemotherapy may be required. The optimal therapy for esthesioneuroblastoma depends on the stage at diagnosis and regional or distant metastasis.

# Historical Perspective
Esthesioneuroblastoma was first discovered by Berger and Luc, in 1924.

# Classification
Based on the duration of symptoms, esthesioneuroblastoma may be classified into two subtypes neuroblastoma proper and neuroendocrine carcinomas.

# Pathophysiology
Genes involved in the pathogenesis of esthesioneuroblastoma include chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q. On gross pathology, soft and hemorrhagic, polypoid appearance, and rich and fragile vascular supply of the tumor are characteristic findings of esthesioneuroblastoma. On microscopic histopathological analysis, arrangements of cells into rosettes or pseudorosettes are characteristic findings of esthesioneuroblastoma.

# Causes
Genes involved in the pathogenesis of esthesioneuroblastoma include chromosomal gains in 7q11 and 20q and deletions in 2q, 5q, 6p, 6q, and 18q.

# Differential Diagnosis
Esthesioneuroblastoma must be differentiated from other tumors with similar histological appearance, such as lymphoma, Ewing sarcoma, melanoma, olfactory/ other (rhabdomyosarcoma or Merkel cell carcinoma), neuroblastoma, and small cell carcinoma. Distinguishing esthesioneuroblastomas from the other tumors is of paramount importance because the tumors respond differently to various treatment modalities.

# Epidemiology and Demographics
The incidence of esthesioneuroblastoma is approximately 0.4 per 100,000 individuals worldwide. Esthesioneuroblastoma can present in a wide range of age groups; however, it is mostly noted in a bimodal distribution, occurring most frequently in the second and sixth decades of life. There is no racial predilection to the esthesioneuroblastoma.

# Risk Factors
There are no established risk factors for esthesioneuroblastoma.

# Screening
According to the United States Preventive Services Task Force, screening for esthesioneuroblastoma is not recommended.

# Natural History, Complications, and Prognosis
If left untreated, 10%-62% of patients with esthesioneuroblastoma may progress to develop metastasis. Common complications of esthesioneuroblastoma include tumor recurrence and metastasis. 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. The five-year mortality rate of patients with esthesioneuroblastoma is approximately 56% and 20% for grade I and II and grade III and IV tumors, respectively. The ten-year mortality rate of patients with esthesioneuroblastoma is approximately 67% and 34% for grade I and II and grade III and IV tumors, respectively.

# Staging
According to a staging system by Kadish, there are four stages of esthesioneuroblastoma based upon the extent of the primary tumor and lymph node or distant metastases. In 1992, Dulguerov and Calceterra proposed a classification based on the tumor, node, metastasis (TNM) system, predicted on CT and MRI findings that can be identified before treatment.

# History and Symptoms
Symptoms of esthesioneuroblastoma include nasal obstruction, epistaxis, ear pain, otitis media, hyposmia, nasal discharge, facial pain, changes in vision, lacrimation, facial numbness, and anosmia.

# Physical Examination
Common physical examination findings of esthesioneuroblastoma include reddish-gray, polypoid mass located in the upper nasal fossa, epistaxis, nasal discharge, nasal pain, facial swelling, trismus, proptosis, diplopia, anosmia, serous otitis media, cervical lymphadenopathy, retropharyngeal lymphadenopathy, decreased visual acuity, extraocular movement paralysis, altered mental status, and frontal headaches.

# Laboratory Findings
Laboratory findings consistent with the diagnosis of  include hypercalcemia, syndrome of inappropriate antidiuretic hormone (SIADH), hyponatremia, and neurological paraneoplastic syndromes.

# CT
On head and neck CT, esthesioneuroblastoma is characterized by soft tissue attenuation, with relatively homogenous enhancement.

# MRI
Head and neck MRI scan is diagnostic of esthesioneuroblastoma. On head and neck MRI, esthesioneuroblastoma is characterized by heterogenous intermediate signal on T1 and T2 weighted MRI and  variable enhancement on T1 contrast with gadolinium.

# Other Imaging Studies
Other imaging studies for esthesioneuroblastoma include angiography/digital subtraction angiography, nuclear medicine, nasal endoscopy, and scintigraphy.

# Other Diagnostic Studies
Biopsy may be helpful in the diagnosis of esthesioneuroblastoma. Findings on biopsy diagnostic of esthesioneuroblastoma include small, round-to-oval cells with coarsely granular chromatin, prominent nuclear membranes, multiple small nucleoli, and scant cytoplasm with pseudorosette or occasional Homer-Wright rosettes separated by fibrous septa. Calcification and necrosis are sometimes seen, and mitotic figures are rare.

# Medical Therapy
The predominant therapy for esthesioneuroblastoma is surgical resection followed by postoperative irradiation. Adjunctive radiation/chemotherapy may be required. The optimal therapy for esthesioneuroblastoma depends on the stage at diagnosis and regional or distant metastasis.

# Surgery
Surgery followed by postoperative irradiation is the mainstay of treatment for esthesioneuroblastoma.

# Primary Prevention
There are no primary preventive measures available for esthesioneuroblastoma.

# Secondary Prevention
Secondary prevention strategies following esthesioneuroblastoma include nasal irrigation with sterile isotonic sodium chloride begins within a few days after packing removal, removal of nasal crusting should be performed regularly during initial postoperative visits, and craniotomy sutures are removed 7-10 days after surgery.