Abstract
Simple SummaryNeuroendocrine carcinomas (NECs) of the head and neck are rare. The presented series of 20 patients with laryngeal and pharyngeal NECs is population-based and one of the largest published to date. We analyzed the treatment results according to the type of therapy and the role of various standard (synaptophysin-chromogranin-CD56, Ki-67, p16, HPV, and EBV) and some novel (INSM1 and PD-L1) neuroendocrine markers or potential prognosticators. The results indicate the following: (1) laryngeal and pharyngeal NECs accounted for 0.43% and 0.17% of the cases in the corresponding tumor groups, respectively; (2) neuroendocrine differentiation can be reliably determined by INSM1 immunohistochemistry; (3) the prognosis was determined by the nodal stage and TNM stage but not by the histological grade (which refers to moderately and poorly differentiated NECs); (4) except in well-differentiated NECs and early-stage (T1-2N0-1) moderately/poorly differentiated NECs, aggressive multimodal therapy is needed; and (5) the p16, HPV, and EBV statuses failed to show any prognostic value.Neuroendocrine carcinomas (NECs) of the head and neck are rare and the experience scanty. The Cancer Registry of Slovenia database was used to identify cases of laryngeal and pharyngeal NECs diagnosed between 1995–2020. Biopsies were analyzed for the expression of standard neuroendocrine markers (synaptophysin, chromogranin, CD56), INSM1, Ki-67, p16, and PD-L1 (using the combined positive score, CPS). In situ hybridization for human papillomavirus (HPV) and Epstein–Barr virus (EBV) was performed. Twenty patients (larynx, 12; pharynx, 8) were identified. One tumor was well differentiated (WD), five were moderately differentiated (MD), and 14 were poorly differentiated (PD). Disease control was achieved solely by surgery in 4/4 MD/PD T1-2N0-1 tumors. Eight patients died of the disease, seven of which were due to distant metastases. All three traditional markers were positive in 11/17 NECs and the INSM1 marker in all 20 tumors. Two of fourteen p16-positive tumors were HPV-positive, but all three nasopharyngeal NECs were EBV-negative. Three tumors had CPSs ≥ 1. In conclusion, INSM1 was confirmed to be a reliable marker of neuroendocrine differentiation. Except in WD and early-stage MD/PD tumors, aggressive multimodal therapy is needed; the optimal systemic therapy remains to be determined. p16, HPV, and EBV seem to bear no prognostic information.
Highlights
Primary neuroendocrine carcinomas (NECs) of the head and neck (HN-Neuroendocrine carcinomas (NECs)) are rare.Their exact incidence is not known, and only estimates are available for the most common subgroups of these tumors, such as small-cell NECs (SCNECs) or those growing in the larynx, representing 0.27% and 0.38% of the head and neck tumor cases [1,2]
The available information on head and neck (HN-NEC) is limited to case reports or small series, which reflects the poor experience of clinicians with this disease
Our experience confirms a high prevalence of INSM1 positivity in laryngeal and pharyngeal NECs which corroborates previous findings that proposed its use as a first-line and stand-alone marker of neuroendocrine differentiation for head and neck tumors [12]
Summary
Primary neuroendocrine carcinomas (NECs) of the head and neck (HN-NEC) are rare.Their exact incidence is not known, and only estimates are available for the most common subgroups of these tumors, such as small-cell NECs (SCNECs) or those growing in the larynx, representing 0.27% and 0.38% of the head and neck tumor cases [1,2]. A large-cell NEC (LCNEC) was defined as an independent histological entity in 2005 and was traditionally not separated from other MD HN-NECs [5,6,7,8]; only since 2017 has LCNEC been formally classified in the poorly differentiated (PD) category [9]. Due to their sporadic occurrence, only reports of individual cases or small patients’. The utility of traditional neuroendocrine markers (synaptophysin, chromogranin, and CD56) can be limited due to their wide range of sensitivities (individual or combined, 50–80%) and expression in tumor types other than neuroendocrine neoplasms, as well as the uncertain fidelity of cytoplasmic staining (i.e., weak and/or focal reactivity) [12]
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