Esthesioneuroblastoma (olfactory neuroblastoma)

Esthesioneuroblastoma arises from the olfactory neuroepithelium of the upper nasal vault and cribriform plate, and its position against the anterior skull base means it grows into the orbit and the frontal lobes as readily as into the sinuses. It presents with nasal obstruction, bleeding and loss of smell, and is staged by the Kadish system (A: nasal cavity; B: paranasal sinuses; C: beyond, including orbit and skull base; D: nodal or distant metastases, added later) and graded by Hyams (I to IV) on the degree of differentiation, rosettes, necrosis and mitotic activity; Hyams grade is the strongest predictor of survival, with low-grade tumours behaving indolently and high-grade tumours recurring early and spreading to neck nodes and distant sites. Immunohistochemistry (synaptophysin, chromogranin, S100 sustentacular cells) separates it from sinonasal undifferentiated carcinoma, NUT carcinoma, melanoma and lymphoma, which share the site. Most tumours express somatostatin receptor 2, which allows DOTATATE PET imaging and, in relapse, radioligand therapy; IDH2 mutations, typical of sinonasal undifferentiated carcinoma, occur in a subset of high-grade esthesioneuroblastomas.

Treatment is multimodal. Craniofacial resection through a combined transfacial and transcranial approach was the standard from the 1970s, and expanded endonasal endoscopic resection with skull base reconstruction now achieves equivalent margins with less morbidity in experienced hands; postoperative radiotherapy is recommended for almost all patients because it improves local control, and intensity-modulated or proton therapy spares the optic pathways and brain. Chemotherapy, usually cisplatin with etoposide, is given as induction for Kadish C and D or Hyams III to IV tumours, sometimes with radiotherapy for unresectable disease, and elective neck irradiation is considered for high-grade tumours because late nodal recurrence is common. Recurrence occurs in up to a third of patients, often years or decades later, so surveillance MRI continues indefinitely; relapses are treated with repeat surgery, re-irradiation or radioligand therapy with lutetium-177 dotatate where the tumour takes up the tracer, and platinum-etoposide or temozolomide for metastatic disease. Because of the tumour's rarity, care belongs in a skull base team, and prospective data are limited to registry series.