Esthesioneuroblastoma: Unraveling the Enigma and Emerging Paradigms With a Retrospective Cohort and Review of Literature.

Background Esthesioneuroblastoma (ENB), or olfactory neuroblastoma, is a rare malignancy arising from the olfactory epithelium. Standardized treatment protocols are lacking, and existing knowledge is largely derived from retrospective case series.  Methods  This study was undertaken to evaluate treatment outcomes and toxicities associated with multimodal therapy in a rare malignancy. We retrospectively reviewed the clinical, pathological, radiological, and dosimetric data of patients diagnosed with ENB and treated them at the Regional Cancer Centre, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), between 2015 and 2022. All patients underwent baseline imaging, including contrast-enhanced CT of the head, neck, thorax, and abdomen and MRI of the head and neck. Treatment included combinations of neoadjuvant chemotherapy, craniofacial resection, and intensity-modulated radiotherapy (IMRT). Radiological response assessment and clinical follow-up were performed periodically, with the last follow-up in March 2023.  Results  Around eight patients aged 17-68 years (median: 53 years) were included. Most patients presented with Kadish stage C (n=5), followed by stage D (n=3). T3 disease was predominant (7/8), with nodal involvement in four patients. Histologically, most tumors were Hyams grade 3 (n=7), neuron-specific enolase-positive, with mitotic indices of 7-17/10 high-power field. All patients received IMRT (66-70 Gy); five underwent R0 surgery and adjuvant radiotherapy, while three received radical chemoradiation. Neoadjuvant chemotherapy (cisplatin and etoposide) was administered in seven patients and adjuvant in one. At a median follow-up of 51.5 months, four patients were alive and disease-free, one had locoregional recurrence, and three had died (one due to recurrence, one due to a second malignancy, and one unrelated). Treatment-related toxicities were manageable and generally resolved with supportive care.  Conclusion This case series highlights the feasibility and efficacy of multimodal therapy incorporating surgery, radiotherapy, and chemotherapy in advanced-stage ENB. With careful staging, aggressive local therapy, systemic treatment, and long-term disease control is achievable. However, larger multicentric studies and molecular diagnostics are necessary to formulate management strategies and refine prognostication in this rare tumor.