1 Epidemiology and Clinical Presentation

  • Olfactory neuroblastoma (ONB), also referred to as esthesioneuroblastoma, is an uncommonly occurring malignant tumor that arises from the olfactory neuroepithelium of the upper nasal cavity and anterior skull base. Tumors that are large enough may extend posteriorly to the sellar region.

  • ONB represents 2–6 % of all sinonasal malignancies [1, 2].

  • The incidence is 0.4 (per million persons per year).

  • The age distribution of patients is bimodal, in the second and sixth decades of life [2].

  • Common clinical symptoms include unilateral nasal obstruction and epistaxis, but may also include anosmia, visual symptoms, facial pain, lacrimation, headache, and rhinorrhea [2].

  • Primary sellar neuroblastoma is extremely rare [3–6].

2 Imaging Features

  • ONB classically appears as a “dumbbell-shaped” mass, with the waist centered at the cribriform plate.

  • CT imaging will often show speckled calcifications and bony erosion of the lamina papyracea, cribriform plate, and/or the fovea ethmoidalis [2].

  • T1-weighted MR images typically show hypointense to intermediate tumor signal intensity compared with brain. T2-weighted images may show hyperintense regions that often correlate to the cystic regions. There is often avid tumor contrast enhancement, which may be heterogeneous. Cerebral invasion and surrounding edema may occasionally be seen (Fig. 38.1) [2, 7–9].

  • The diagnosis of olfactory neuroblastoma is supported by the MRI finding of peritumoral cysts capping the intracranial portion of the tumor (Fig. 38.2) [9].

  • Cervical lymph node metastases are seen in approximately 36 % of patients at the time of diagnosis [7].

  • 18F-FDG PET/CT is a useful adjunct in patients with ONB and may affect treatment decisions in up to 39 % of patients, when compared with conventional neuroimaging [10].

  • ONB is often staged according to the Kadish criteria. According to this staging system, group A represents tumors limited to the nasal cavity, group B represents tumors localized to the nasal cavity and paranasal sinuses, and group C tumors extend beyond the nasal cavity and paranasal sinuses [11].

Fig. 38.1
figure 1

Olfactory neuroblastoma. (a) Sagittal T1-weighted precontrast image. (b) Coronal T1-weighted gadolinium-enhanced image. (c, d) Axial fat-saturated T1-weighted gadolinium-enhanced image. There is a large, heterogeneously enhancing mass centered in the floor of the anterior cranial fossa. Nodular components are compressing the frontal lobes and are seen inferiorly within the nasal cavities. The mass extends to the left orbit, with medial displacement of the medial rectus. There is marked edema in the left frontal lobe, and the visualized parts of the lateral ventricles are dilated

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Fig. 38.2
figure 2

Olfactory neuroblastoma. (a) Sagittal T1-weighted gadolinium-enhanced image. (b) Coronal T1-weighted gadolinium-enhanced image. A heterogeneously enhancing mass is centered in the floor of the anterior cranial fossa, with components eroding the nasal cavities, sphenoid sinuses, and anterior clivus. The pituitary gland is distinctly seen from the mass on the sagittal plane. There is a small cystic component superiorly abutting the left frontal lobe

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3 Histopathology

  • Classically, ONBs are characterized by small, round, blue cells slightly larger than mature lymphocytes, with a very high ratio of nucleus to cytoplasm, arranged in a lobular pattern (Fig. 38.3a, b).

  • ONB is often graded according to Hyams criteria, which range from Grade I to Grade IV [12]. These criteria are based on several features, including architecture, pleomorphism, neurofibrillary matrix, rosettes, mitoses, necrosis, glands, and calcification. Grade I ONB is characterized by lobular cytoarchitecture, little pleomorphism, prominent neurofibrillary matrix, Homer-Wright pseudorosettes, no mitoses or necrosis, and variable calcification. On the other extreme, Grade IV ONB is characterized by loss of lobular cytoarchitecture, marked pleomorphism, necrosis, mitoses, Flexner-Wintersteiner rosettes, and absent calcification [12].

  • ONBs are typically positive for synaptophysin (Fig. 38.3c), chromogranin, CD56, neuron-specific enolase, neurofilament protein (NFP), and S100 protein [2].

  • The Ki-67 proliferative index is usually high, ranging between 10 and 50 % [2].

Fig. 38.3
figure 3

Olfactory neuroblastoma. (a) Olfactory neuroblastomas are located in the sinonasal submucosa. (b) The tumors are composed of a uniform population of small cells with typical “salt and pepper” or dispersed chromatin. Mitotic activity may be high. (c) The tumors are characteristically strongly immunoreactive for synaptophysin

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4 Clinical and Surgical Management

  • Depending on the stage of disease at the time of diagnosis and the degree of tumor resection, multimodality treatment consisting of surgery, radiation, and chemotherapy is often implemented.

  • One large meta-analysis showed no difference in survival between patients who underwent surgery alone and those who underwent surgery plus radiotherapy at 5 years (78 % vs. 75 %) or 10 years (67 % vs. 61 %) [13].

  • Survival has been associated with Kadish stage and Hyams stage [11, 13]. According to the original Kadish staging, patients with Kadish A tumors had a 5-year survival of 75–91 %, compared with 41–47 % for patients harboring Kadish C tumors [11].

  • Surgical resection may be performed via standard open craniotomy, craniofacial approaches, or more recently, extended endoscopic endonasal approaches [14].

  • In a series of 11 patients by Gallia et al. [14], complete endoscopic endonasal surgical resection was possible in all patients, with no patients demonstrating recurrence at 28 months follow-up.

  • Recent meta-analyses have lent support to equal or more favorable outcomes following endoscopic resection compared with open surgery, although some selection bias exists in the surgical approaches assigned to varying Kadish ONB subtypes [15, 16].

  • The benefits of adjuvant radiation have been debated; some studies have shown a beneficial effect [17] and others have shown no major benefits [13].

  • Recurrence develops in approximately 30–48 % of cases, with a median time to recurrence of 7 years [2, 17].

  • Metastatic lesions to cervical lymph nodes, lungs, and bones may require additional surgery and multimodality treatment [18]. Platinum-based chemotherapy is often utilized [19]. Autologous bone marrow transplantation has helped achieve long-term survival in limited cases.