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Is Olfactory Neuroblastoma Hereditary?

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First described in 1924, olfactory neuroblastoma is an uncommon malignant tumor affecting the superior nasal cavity. It accounts for about 2-3% of all nasal cavity tumors and occurs in about 0.4 people per million per year. It is thought to be derived from basal cells of olfactory neuroepithelium owing to its anatomical location and certain morphological characteristics and expression of proteins exclusive of the olfactory epithelium.⁽¹⁾

Olfactory neuroblastoma can occur at any age ranging from 2-94 years. It usually has a bimodal age of occurrence and occurs at 2nd and 6th decades of life. It can occur in males and females at a similar ratio. The most common presenting symptoms are a unilateral nasal obstruction (70%) and epistaxis (50%). Other less common signs and symptoms include headaches, pain, rhinorrhea, excessive lacrimation, anosmia, and visual disturbances. It is worth noting that though the tumor arises from the olfactory neuroepithelium, anosmia (loss of sense of smell) is not a common complaint and only occurs in about 5% of the patients. There have been reports of isolated cases of olfactory neuroblastoma that secrete vasopressin that can lead to hypertension and hyponatremia. There is a delay in diagnosis of the tumor due to its non-specific presentation and delayed growth.⁽²⁾

The etiology of olfactory neuroblastoma is poorly understood. It originates from immature neural crest cells as the tumor expresses the Drosophila achaete-scute gene (hASH1) in a modified reverse-transcription polymerase chain reaction (RT-PCR). Various researchers have shown chromosome alterations at various gene locations that are related to poorer prognosis (4p/q, 5p/q, 6q), high-risk relapse and metastasis (5p/q, 6q); however, their clinical usefulness in cancer therapy is yet to be determined. Although genetic alterations are noted in olfactory neuroblastoma, especially for recurrent and metastatic stages, there is no link between the hereditary and familial occurrence of the disease.⁽¹⁾

Diagnosis Of Tumor

The imaging studies employed in the diagnosis of olfactory neuroblastoma include CT scan and MRI imaging (with or without contrast medium) that show ‘dumbbell-shaped’ mass extending across the cribriform plate into the cranium.⁽²⁾

The diagnostic confirmation is done by biopsy of the tumor that shows lobular architecture comprising of primitive cells. These circumscribed lobules or nests of tumor cells are present below an intact mucosa that is separated by vascularized fibrous stroma. There is the presence of pleomorphism, rosettes, mitoses, necrosis, glands, and calcification.⁽²⁾

Staging Of Tumor

The staging system proposed by Kadish et al. in 1976 is still used. The staging includes:

Stage A: tumor limited to the nasal cavity

Stage B: tumor involving the nasal cavity and one or more paranasal sinuses

Stage C: extension of the tumor beyond the nasal cavity and paranasal sinuses

Due to delay in presentation and diagnosis, most of the tumors (about 50%) are found in stage C. The survival rate for stage A, stage B, and stage C is 75-91%, 68-71%, and 41-47%, respectively. The overall, 5-year survival for olfactory neuroblastoma is 60-80%. While low-grade tumors have a 5-year survival of 80%, high-grade tumors have a 5-year survival of 40%.⁽²⁾

Management Of Olfactory Neuroblastoma

The best long term results are achieved by complete surgical removal of neuroblastoma by using bi-cranial-facial approach that removes the cribriform plate followed by radiotherapy. In some cases, endoscopic resection can be performed for a limited tumor. For advanced tumors that are a non-resectable or disseminated disease, palliative chemotherapy is the treatment of choice. Autologous bone marrow transplantation has been used to achieve long term survival in limited cases.⁽²⁾

Recurrence is common for olfactory neuroblastoma, which occurs in approximately 30% cases (ranges from 15-70%) within the first 2 years after initial management. Cervical lymph node metastasis (25%) and distant metastases (10%) is noted in all the cases of olfactory neuroblastoma. The most common site of metastases is lungs and bones. The survival is complicated by female gender, age <20 years or >50 years, high grade of the tumor, extensive intracranial spread, distant metastases, recurrence of tumor, and high proliferation index of the tumor.⁽²⁾

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Is Olfactory Neuroblastoma Hereditary?