UNIVERSITAS INDONESIA

OLFACTORY NEUROBLASTOMA: EPIDEMIOLOGY, DIAGNOSIS, AND MANAGEMENT

INDIVIDUAL ASSIGNMENT

An individual assignment presented to Group A Special Senses Module to expand my knowledge to

achive my dream as a seven-star doctor

Stefanus Raditya Purba

1006804823

FACULTY OF MEDICINE

INTERNATIONAL CLASS PROGRAM

JAKARTA

FEBRUARY 2013

OLFACTORY NEUROBLASTOMA (ESTHESIONEUROBLASTOMA)

Olfactory neuroblastoma, also known as esthesioneuroblastoma, is a rare malignant tumor in the nasal cavity originating from olfactory sensory epithelium. This tumor is identified by its variety of symptoms, histologic findings, and progression. This makes the staging system, prognostic evaluation, and best treatment modalities difficult to reach.

Epidemiology

This tumor accounts for about 3-6% of tumors in this area. The first case was described by Berger and Luc in 1924 and after that approximately 1000 cases of olfactory neuroblastoma have been reported worldwide. However, mostly cases (approximately 80% of total cases) were identified in the past 25 years. The incidence is estimated 4 cases per 10 million people worldwide. There is no gender predilection for this tumor. However, some researchers suggested the ratio between male and female is 2:1. For race predilection, this tumor doesn’t have preferred race. It can occurs in all races and found on all continents. No familial prevalence is found too. Olfactory neuroblastoma can also found in all ag groups eventhough there are highest occurence in age group 11 to 20 years and 51 to 60 years. 1, 2

Diagnosis

Microscopic examination

There are differences in histopathologic findings especially between low-grade and high-grade tumors. Low-grade cases had a relatively well-formed lobular architecture, fibrillary background, with relatively well-formed neurophil islands both within and at the periphery of the lobules. Mitoses were occasional and a few rosettes were seen. No necrosis was identified. In contrary, all high-grade cases showed tumor necrosis in addition to nuclear atypia and high mitotic rate, along with sparse fibrillary background, rosettes and neurophil islands. 2, 3

Based on the histopathological findings, the grading is concluded by Hyams grading system as provided below:

Immunohistochemistry testExpression of neuronal markers was heterogeneous, with neuronspecific enolase and synaptophysin being positive in the majority of tumor cells. Staining for S-100 protein and chromogranin showed focal reactivity. Strong nuclear immunoreactivity for DNA topoisomerase II alpha was noted in both low grade and high-grade cases. 2,3,6

Radiology examination

CT Scan

CT scan can be used to detect the mass in nasal area though it cannot distinguish olfactory neuroblastomas from other tumors that arise in the same region. We use direct coronal fine-cut CT scan as the first assessment.

MRI

MRI often is necessary to better delineate sinonasal and intraorbital extension or an intracerebral extension. Using MRI, ENB appears as hypointense to gray matter on T1-weighted images and isointense or hyperintense to gray matter on T2-weighted images. Because details of bony erosion are better demonstrated by CT images, both studies usually are required in the majority of patients. 1, 4,6

From the radiographic examination finding we can classify the tumor using Kadish staging

Management

Surgery

Surgery remains the primary treatment for esthesioneuroblastoma (ENB) and offers the best chance fo control as well as survival. Both open and endoscopic craniofacial resection have achieved complete surgical resection with tumor-free margins.

Open craniofacial resection permits en-bloc resection of the tumor, with assessment of any intracranial extension and protection of the brain and optic nerves. The en-bloc resection should include the entire ipsilateral cribriform plate and crista-galli and the olfactory bulb and overlaying dura should be removed with the specimen. A tumor that does not penetrate the orbit can be encompassed by resecting the lamina papyracea or even small segments of orbital periosteum. Postoperative complications have been reported in 15-40% of cases. Major complications include frontal lobe abscess, infection, and intercranial hemorrhage.

Endoscopic craniofacial resection (ECFR) is relatively new nethod and it is proven to be safe. Firstly, endoscopic approach was limited to Kadish stages A and B but there are successful cases applied to stage C tumor.The benefits of an endoscopic approach include decreased time in surgery, blood loss, morbidity, postoperative complications, and cost.

Radiation therapy

Standard techniques include external megavoltage beam and a 3-field technique. The radiation portals are nowadays planned by integrating pretreatment CT or MRI imaging. The dose varies from 5500-6500cGy. The majority of patients receive < 6000 cGy. These doses are close to or exceed the maximum radiation dose recommended for sensitive structures such as the optic nerve, optic chiasma, brainstem, retina, and lens.

Chemotherapy

Chemotherapy is not recommended for routine treatment of this tumor. Exceptions include palliative treatments or as part of a multimodality treatment in patients with advanced or metastatic disease. Patients with severe tumor are treated first with 2 cycles of cyclophosphamide (300-650 mg/m2) and vincristine (1-2 mg) with or without doxorubicin, followed by 50 Gy of radiotherapy, which then is followed by a craniofacial resection. With this regimen, the 5-year and 10-year actuarial survival rates are 72% and 60% respectively. Nowadays, the promising regimen used is cisplatin (33 mg/m2/d) and etoposide (100 mg/m2/d) for 3 days. This has been followed by proton radiation with excellent results. A more aggressive chemotherapy regimen, a combination of cyclophosphamide, doxorubicin, vincristine, and continuous-infusion cisplatin and etoposide followed by radiation has also been tested with good results. 1,5,6

References:

1. Somenek M. Esthasioneuroblastoma [online]. [cited 2013 February 25]. Available from: URL: http://emedicine.medscape.com/article/278047

2. Sharma S, Sharma MC, Johnson MH, Lou M, Thakar A, Sarkar C. Esthesioneuroblastoma – a clinicopathologic study and role of DNA topoisomerase alpha. Pathology Oncology Research. 2007; 13: 123-130.

3. Ayoub A, Hiari MA. Olfactory neuroblastoma: a case report. Journal of Research in Medical Sciences. 2005; 12: 48-50.

4. Vidya MN, Shivakumar S, Biswas S, Shankar V. Olfactory neuroblastoma: diagnosis difficulty. Online Journal of Health and Allied Sciences. 2010; 9: 1-2.

5. Gil-Carcedo E, Gil-Carcedo LM, Vallejo LA, Campos JM. Esthesioneuroblastoma treatment. Acta Otorrinolaringol Esp. 2005; 56: 389-395.

6. Oskouian RJ, et all. Esthesioneuroblastoma: clinical presentation, radiological, and pathological features, treatment, review of the literature, and the University of Virginia experience. Neurosurg Focus. 2002; 12: 1-9.