Neurosurg Focus 12 (5):Article 4, 2002, Click here to return to Table of Contents Esthesioneuroblastoma: clinical presentation, radiological, and pathological features, treatment, review of the literature, and the University of Virginia experience ROD J. OSKOUIAN, JR., M.D., JOHN A. JANE, SR., M.D., PH.D., AARON S. DUMONT, M.D., JONAS M. SHEEHAN, M.D., JEFFREY J. LAURENT, M.D., AND PAUL A. LEVINE, M.D. Departments of Neurological Surgery and Otolaryngology–Head and Neck Surgery, University of Virginia School of Medicine, Charlottesville, Virginia Esthesioneuroblastoma is a rare and malignant upper nasal cavity neoplasm involving the anterior skull base. Treatment includes surgery, radiotherapy, chemotherapy, or a combination. The ideal treatment modality has yet to be determined. Esthesioneuroblastoma often lies in proximity to the optic nerves, optic chiasm, and the orbit. Resection risks damaging these critical structures, and radiotherapeutic techniques, similar to those applied for paranasal sinus tumors, may damage these vital structures and result in late sequelae such as blindness and cortical necrosis. Management strategies for this neoplasm lack uniformity, and there is no universally accepted staging system. In this paper the authors discuss the clinical presentation, radiological and pathological features, and treatment of this rare, malignant skull base neoplasm, as well as review the literature. They also present their results and treatment regimen, which includes preoperative radio- and chemotherapy or 1) craniofacial resection if the lesion has a significant intrac- erebral component, or 2) frontal sinus resection if little intracranial extension exists. KEY WORDS • esthesioneuroblastoma • radiation therapy • chemotherapy • skull base tumor L’esthesioneuroepitheliome olfactif, a term coined by Since the original papers,2,3 numerous studies have been Berger and Luc3 in 1924, was originally used to describe published, in each of which the patient population was a nasal mass that exhibited cellular rosettes and fibrils. limited and the treatment regimens multiple.29,62 Although The astonishing observations made by these authors were the data reported in these studies have been of great inter- the recognition of the superior location of the mass in the est over the years, the clinical and scientific merits have anterior nasal cavity and realization that it developed from been diminished because of the small population sizes and the olfactory placode. Two years later Berger and Cou- the varied treatment protocols. tard2 reported a similar but slightly different case, in which the tumor was termed esthesioneurocytome olfactif, and in 1929, a third variant was named esthesioneuroblas- tome.55 These two initial reports were followed by a slew CLINICAL PRESENTATION of others in which this most elusive tumor of the superior Because sinonasal malignant lesions are rare and diffi- nasal vault was characterized. Based on the classification cult to distinguish from their benign counterparts, their of McCormack and Harris,45 some authors initally be- diagnosis is challenging. These similarities between be- lieved that there were three types of esthesioneuroblas- nign and malignant lesions at initial presentation may lead tomas. McCormack and Harris classified the tumor as an to a significant delay in the diagnosis of malignancy. esthesioneuroepithelioma if it exhibited rosettes, an esthe- Given the absence of classic symptoms, patients are often sioneuroblastoma if it had pseudorosettes, or an esthesio- not examined until they present with nasal obstruction, neurocytoma if neither rosettes nor pseudorosettes were headache, nasal pain, excessive lacrimation, epistaxis, an- present. osmia, and visual changes.16 The most common complaint is longstanding unilateral nasal obstruction that has been Abbreviations used in this paper: CSF = cerebrospinal fluid; present for months, sometimes years, before presentation. CT = computerized tomography; MR = magnetic resonance; The disease is initially demonstrated with a bimodal age PNET = primitive neuroectodermal tumor; pPNET = peripheral distribution; it peaks first between age 10 and 20 years and PNET; TNM = tumor node metastasis; UVA = University of later between age 50 and 60 years, and is slightly more Virginia. common in females.7 The tumor can spread submucosally Neurosurg. Focus / Volume 12 / May, 2002 1 Unauthenticated | Downloaded 09/25/21 01:13 AM UTC R. J. Oskouian, et al. in all directions, thereby involving the paranasal sinuses, perintense to gray matter on T2-weighted images. Mul- 1 nasal cavity, and surrounding structures. These lesions tiplanar T2-weighted MR images provide excellent con- can cross the cribriform plate and invade the brain or seed trast between the very high–intensity signal present after the cerebrospinal fluid.61 Such lesions often require resec- sinus fluid or mucosa obstruction and the intermediate- tion via a craniofacial approach. This uncommon neo- intensity signal of the adjacent tumor. plasm is locally aggressive and can metastasize by lym- In assessing CT and MR imaging studies, it is some- phatic and hematogenic routes. Esthesioneuroblastoma is times difficult to determine whether the dura is invaded by an aggressive malignant tumor derived from the special- tumor. Because of the thin fovea and cribriform complex, ized neuroepithelium of the upper nasal cavity; it accounts the dura is often the significant barrier to tumor penetra- for 3% of all endonasal neoplasms.7 In cases of metastatic tion into the brain. Notwithstanding both neuroimaging disease, 20 to 30% will involve the CNS. In these cases studies, it may not be certain that the dura is involved until the neoplasm invades the CNS by growing through the surgery. As a result, the team must be prepared to resect cribriform plate and invading the anterior cranial base. dura and replace it with autogenous fascia, temporalis, or When it has entered the CNS, esthesioneuroblastoma fascia lata, for example, when performing craniofacial re- metastasizes to either the brain parenchyma or lepto- section. Computerized tomography and MR imaging are meninges. complementary examinations performed preoperatively to define the extent of tumor, staging, and surgical approach. The primary advantage of CT studies is that they allow the RADIOLOGICAL FEATURES team to evaluate osseous involvement around the nasal 16 Contrast-enhanced axial and direct coronal CT scan- septum, orbit, and anterior skull base. ning is performed in all patients to obtain all necessary preoperative information, such as proximity to the adja- cent sinuses, in Kadish Stage A or Stage B tumors31 (Table PATHOLOGICAL CHARACTERISTICS 1). The protocols for CT scanning must include axial and Since its first descriptions,2,3 the histogenesis of this coronal scans of 1- to 5-mm-thick slices with intravenous neoplasm has been of debate. This controversy has given contrast. Esthesioneuroblastomas are solid and enhancing rise to a variety of names including esthesioneuro- nasal cavity masses that may manifest erosion into nearby blastoma, olfactory neuroepithelioma, olfactory neuro- osseous structures of the orbital plate of the ethmoid bone, blastoma, and others. Several anatomical origins of esthe- cribriform plate, and fovea ethmoidalis (Fig. 1). In cases sioneuroblastoma have been suggested, including the in which CT scanning reveals nasal roof erosion evidence sympathetic fibers of the anterior nasal cavity, the neu- of intracranial extension, we also recommend acquiring roectodermal cells of the sphenopalatine ganglion, the MR images because they provide a more sensitive assess- 10,12,13,49, 60 olfactory placode, and the vomeronasal organ. ment for unrecognized intracranial lesions. Intralesional 56,58,64 It was not until Obert, et al.,50 demonstrated that the calcification observed on neuroimaging can be considered 42 tumor originated from the superior nasal vault that agree- pathognomonic for esthesioneuroblastoma, and the pres- ment was needed and it was concluded that the tumor was ence of cysts along the intracranial margins of Kadish of neuroectodermal origin and more from the olfactory Stage C lesions in which there is intracranial extension 67 epithelium. Early attempts to categorize these neoplasms also yields a definitive diagnosis. based on gene expression at a molecular level have not In Kadish Stage C disease, it is important to perform T1- correlated with clinical outcomes. weighted gadolinium-enhanced MR imaging to obtain es- Esthesioneuroblastomas are thought to arise from cells sential additional information, particularly when walls in the olfactory epithelium. These malignant cells are of the bones are thinned or eroded. Fat-suppression T1- mitotically active and are precursor cells that give rise to weighted imaging visualizes the tumor more clearly. On sustentacular and neuronal cells. On high-power micro- T1-weighted MR images esthesioneuroblastomas present scopic examination they are shown to have a vascular as homogeneously enhancing tumors with intermediate stroma with fibrovascular components and pseudorosettes signal intensity, whereas on T2-weighted images the orig- (Fig. 2). The tumor is histologically similar to malignant inal intensity is increased. Occasionally in cases in which lesions of the sympathetic ganglia, adrenal medulla, and there is intracranial extension tumor, cysts at the tumor the retina. Common features are small, round neuroep- margins are also present. The main advantage of an MR