Update on Neuroendocrine Carcinomas of the Larynx

Carolina Strosberg, MD; Alfio Ferlito, MD, DLO, DPath, FRCSEd ad hominem, FRCS (Eng, Glasg, Ir) ad eundem, FDSRCS ad eundem, FACS, FHKCORL, FRCPath, FASCP, IFCAP; Asterios Triantafyllou, PhD (Lond), FRCPath; Douglas R. Gnepp, MD; Justin A. Bishop, MD; Henrik Hellquist, MD, PhD, SAPath (Stockh), FRCPath; Primoz Strojan, MD, PhD; Stefan M. Willems, MD, PhD; Göran Stenman, DMD, PhD, FRCPath; Alessandra Rinaldo, MD, FRCSEd ad hominem, FRCS (Eng, Ir) ad eundem, FRCSGlasg, FACS; Juan C. Hernandez-Prera, MD


Am J Clin Pathol. 2019;152(6):686-700. 

In This Article

Abstract and Introduction


Objectives: Laryngeal neuroendocrine carcinomas are heterogeneous neoplasms characterized by neuroendocrine differentiation. Their prognoses are dependent on tumor type, therefore different classifications have been developed. Moreover, other tumors have overlapping pathologic features posing a range of diagnostic possibilities.

Methods: A review of the literature was performed to comprehensively understand the classification and diagnosis of these tumors.

Results: We review the past and present classification systems, with emphasis to the latest 2017 World Health Organization Classification of Head and Neck Tumors. We highlight salient clinicopathologic features and discuss the presumptive etiologic role of human papilloma virus. We share a practical algorithmic approach to the diagnosis of suspected neuroendocrine neoplasms of the larynx including a novel marker for neuroendocrine differentiation, insulinoma-associated protein 1.

Conclusions: Accurate diagnosis and grading of laryngeal neuroendocrine carcinomas is critical for prognostication and therapeutic decision making. The use of an algorithm is instrumental in assuring the exclusion of mimickers.


Laryngeal neuroendocrine carcinomas are malignant heterogeneous epithelial neoplasms characterized by neuroendocrine differentiation. Accurate diagnosis and grading of this group of tumors is critical for prognostication and therapeutic decision making. Consequently, it is imperative to understand how the classification of these tumors has evolved throughout the years and which are the major changes incorporated in the latest World Health Organization (WHO) classification of head and neck tumors. Moreover, neuroendocrine carcinomas of the larynx have distinct clinicopathologic features and their differential diagnoses at this anatomic site are unique. This review clarifies confusions in regard to the nature and classification of these neoplasms and provides a practical approach to the diagnosis of these tumors for practicing pathologists.