Sinonasal Neuroendocrine Carcinoma (NEC) and olfactory neuroblastoma (ONB): implications of a correct histopathological differential diagnosis

Objective: Poorly differentiated NECs and ONBs are rare sinonasal malignancies showing overlapping morphological features, with difficult differential diagnosis. Notwithstanding, the two histotypes differ significantly in therapeutic strategies and prognosis. Design: Retrospective analysis of patients treated for NEC and ONB from 1999 to 2011 at our Institute. Material and Methods: We performed a revision of histopathological slides, taking advantage of a specific immunohistochemical staining. Results: The patients eligible for present analysis were 28 (12 male and 16 female), from 14 to 79 years old (mean, 55.7 years). The 22 cases of ONB underwent endoscopic endonasal resection (EER) with adjuvant IMRT; the 6 cases of NEC were treated with induction chemotherapy followed by EER with adjuvant IMRT. ONBs were characterized by immunohistochemical positivity for synaptophysin (SYN), chromogranin A (CgA), and S100 in sustentacular cells, whereas they were negative for the cytokeratins (CKs). NECs show strong and diffuse immunoreactivity for CK 8/18 and SYN with low CgA and CKAE1/AE3 expression, without S100-positive sustentacular cells. We found misdiagnosis in three cases of ONBs that showed immunophenotypical features of NECs. The recurrence rates, after a mean follow-up of 60 months (range, 1-153 months), were 2/3 (66.7%) for the misdiagnosed group, 2/19 (10.5%) for the confirmed ONBs, and 2/6 (33.3%) for the NECs. Conclusion: In our experience, these recent advances in histopathological differential diagnosis between NEC and ONB seem to be crucial to properly plan adjuvant or neoadjuvant treatment and also to predict the prognosis of patients. Larger case series are needed to validate these preliminary result