Neuroendocrine Neoplasms of the Sinonasal Tract: Neuroendocrine Carcinomas and Olfactory Neuroblastoma

Abstract

Neuroendocrine neoplasms (NENs) can occur in organs or tissues that do not contain neuroendocrine cells normally and do not necessarily imply embryologic derivation from the neuroectoderm; but rather reflect a shared phenotype characterized by the expression of multiple genes encoding both endocrine and neuronal features. NENs are rare in the sinonasal tract and are subdivided into epithelial and neural subtypes based on the presence of keratins or neurofilaments, respectively. Although relatively rare, neuroendocrine carcinomas (NECs) and olfactory neuroblastoma (ONB) are the most common neuroendocrine neoplasms of the sinonasal tract. The focus of this review is to highlight recent developments in the pathology of sinonasal NECs and ONB in light of the upcoming update of the World Health Organization (WHO) 2005 classification of tumors of the head and neck.

Keywords: Esthesioneuroblastoma; Nasal cavity; Neuroendocrine carcinoma; Olfactory neuroblastoma; Sinonasal tract.

Fig. 1

Grade 1/well-differentiated NEC composed of monotonous small to medium size cells arranged in trabeculae and vague nests. The nuclei contain stippled chromatin and there are no visible nucleoli (a). The tumor cells are diffusely positive for synaptophysin (b). The differential diagnosis of this tumor includes pituitary adenoma and low-grade ONB

Fig. 2

Grade 2/moderately-differentiated NEC with trabecular and nested architecture in a myxoid background. Isolated mitoses and apoptotic cells are noted in the center of the field (a). Tumor cells are positive for chromogranin (b)

Fig. 3

Grade 3/poorly-differentiated NEC, small cell-type with prominent nuclear molding (a), dot-like keratin (b), weak chromogranin (c), and diffuse expression of CD56 (d)

Fig. 4

Grade 3/poorly-differentiated NEC, large cell-type displaying nested architecture (a), Flexner–Wintersteiner rosettes and frequent nucleoli (b)

Fig. 5

Low-grade ONB composed of individual and confluent nests of small round cells in a slightly hyalinized or edematous stroma (a). Low-grade ONB with Flexner–Wintersteiner rosettes (b). ONB with abundant neurofibrillary matrix (c). High-grade ONB with hyperchromatic nuclei with molding and pseudorosettes (Homer Wright rosettes) (d). Low-grade ONB with strong and diffuse expression of synaptophysin (e) and numerous sustentacular cells highlighted by S-100 (f)

Fig. 6

Rhabdomyoblastic differentiation in ONB characterized by large round cells with deep eosinophilic cytoplasm