Neuroendocrine Carcinoma of the Larynx and Pharynx: A Clinical and Histopathological Study

Abstract

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.

Clinical Behavior, Mutational Profile and T-Cell Repertoire of High-Grade Neuroendocrine Tumors of the Head and Neck

“…OS in these eight patients was durable despite three patients relapsing after therapy. Contrary to prior studies, where induction chemotherapy has been seldom used and where most patients underwent either upfront surgery followed by (C)RT or upfront CRT, in our series, we show that multimodality organ-preservation approaches using induction PE-based chemotherapy followed by platinum-based CRT constitute a successful therapeutic strategy for HN NECs [4,7,[14][15][16][17]19]. Similar organ-preservation strategies are widely used in squamous cell carcinomas of the head and neck, particularly in patients with laryngeal cancer [23].…”

“…As expected, most patients were male and past or current tobacco smokers, in agreement with the well-known association between tobacco and NECs of the HN region [1,3,4,7,[12][13][14][15][16][17][18][19][20][21][22]. Most tumors were either small-cell or mixed-cell carcinomas, harbored a very high proliferative index (>90%), expressed prototypical neuroendocrine markers such as synaptophysin and/or chromogranin and presented with locally advanced or metastatic disease, developing, in descending order, from major and minor salivary glands, sinonasal structures and the larynx, all these concordant with prior reports (Table 5 summarizes the most relevant studies conducted to date in HN NECs) [1,3,4,7,[12][13][14][15][16][17][18][19][20][21][22]. As shown in Figure 4, while median OS since IDx and since the R/M setting were not reached, some patients died early, possibly reflecting late diagnosis or biologically more aggressive diseases.…”

Top 10 Histological Mimics of Neuroendocrine Carcinoma You Should Not Miss in the Head and Neck

“…The most clinically urgent NEN subtype is NEC, a poorly differentiated, highly proliferative, malignant tumor of poor prognosis exhibiting significant tumor necrosis and destructively invasive features [3]. In the head and neck region, NEC may develop within the paranasal sinuses, the nasal cavity, the oro-and hypopharynx, the salivary glands, the oral cavity, and the larynx [7][8][9][10][11]. NEC of the head and neck region is further divided into small cell neuroendocrine carcinoma (SCNEC), large cell neuroendocrine carcinoma (LCNEC), and mixed NEC with non-neuroendocrine neoplasms [8].…”

Neuroendocrine Neoplasms of the Head and Neck: A Case Report on an Oropharyngeal Presentation

“…Histologically they present as small cell tumors with scant cytoplasm and characteristic immunohistochemical markers of neuroendocrine cells, the most relevant chromogranin and synaptophysin. The Ki67 nuclear proliferation marker index will determine the degree of potential replication of the tumor [ 3 ]. The presentation in the head and neck area is rare, particularly in the oropharynx, where only 52 cases have been identified up to the year 2021 [ 4 ].…”

“…Histologically they present as small cell tumors with scant cytoplasm and characteristic immunohistochemical markers of neuroendocrine cells, the most relevant chromogranin and synaptophysin. The Ki67 nuclear proliferation marker index will determine the degree of potential replication of the tumor [3].…”