Well-differentiated Neuroendocrine Carcinoma of the Larynx: Confusion of Terminology and Uncertainty of Early Studies

Hunt, Jennifer L.; Barnes, Leon; Triantafyllou, Asterios; Gnepp, Douglas R.; Devaney, Kenneth O.; Stenman, Göran; Halmos, György B.; Bishop, Justin A.; Skálová, Alena; Willems, Stefan M.; Hellquist, Henrik; Rinaldo, Alessandra; Ferlito, Alfio

doi:10.1097/pap.0000000000000236

Cited by 8 publications

(4 citation statements)

References 26 publications

(24 reference statements)

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“…Some cases of typical carcinoid would be reclassified as atypical carcinoid, while some cases of atypical carcinoid probably represent examples of large cell neuroendocrine carcinoma. In addition, several laryngeal atypical carcinoids have been diagnosed in the past as metastatic laryngeal paraganglioma [ 8 ].…”

Section: Historical Perspectivesmentioning

confidence: 99%

“…Therefore, the management and prognosis were, and probably still are, often not appropriate. In 2019, Hunt et al [ 8 ] proposed the following terminology: well-differentiated neuroendocrine carcinoma to indicate typical carcinoid tumor, moderately differentiated neuroendocrine carcinoma to indicate atypical carcinoid tumor, poorly differentiated neuroendocrine carcinoma–small cell carcinoma to indicate small cell carcinoma, and poorly differentiated neuroendocrine carcinoma–large cell to indicate large cell carcinoma. The 2024 World Health Organization (WHO) classification suggests a modified terminology [ 9 ].…”

Section: Terminology and Classificationmentioning

confidence: 99%

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Some Considerations on Laryngeal Neuroendocrine Neoplasms

Ferlito

2024

Oncol Ther

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Section: Historical Perspectivesmentioning

confidence: 99%

Section: Terminology and Classificationmentioning

confidence: 99%

Some Considerations on Laryngeal Neuroendocrine Neoplasms

Ferlito

2024

Oncol Ther

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“…Laryngeal cancers are predominantly (95%) squamous cell carcinomas (SCC), followed by neuroendocrine neoplasms of the larynx, which are the most common non-squamous tumors of the larynx, despite their rarity (4,5).…”

Section: Introductionmentioning

confidence: 99%

Reduced expression of secretogranin VGF in laryngeal squamous cell carcinoma

Gabanella,

Maftei,

Colizza

et al. 2023

Oncol Lett

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Laryngeal cancer accounts for one-third of all head and neck tumors, with squamous cell carcinoma (SCC) being the most predominant type, followed by neuroendocrine tumors. Chromogranins, are commonly used as biomarkers for neuroendocrine tumors, including laryngeal cancer. It has been reported that secretogranin VGF, a member of the chromogranin family, can be also used as a significant biomarker for neuroendocrine tumors. However, the expression and role of VGF in laryngeal carcinomas have not been previously investigated. Therefore, the present study aimed to determine the expression levels of VGF in laryngeal SCC (LSCC). The present study collected tumor tissues, as well as serum samples, from a cohort of 15 patients with LSCC. The results of reverse transcription-quantitative PCR, western blot analysis and immunofluorescence assays showed that the selective VGF precursor was downregulated in patients with LSCC. Notably, in tumor tissue, the immunoreactivity for VGF was found in vimentin-positive cells, probably corresponding to T lymphocytes. The current preliminary study suggested that the reduced expression levels of VGF observed in tumor tissue and at the systemic level could sustain LSCC phenotype. Overall, VGF could be a potential biomarker for detecting neoplastic lesions with a higher risk of tumor invasiveness, even in non-neuroendocrine tumors.

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“…In the HN-NEC patients, the treatment and survival results correlate with the disease stage, which is primarily determined by the degree of tumor differentiation and has not significantly changed with advances in diagnostics and treatment (e.g., the introduction of modern radiotherapy (RT) techniques and systemic treatments). While the disease-specific survival (DSS) for the notoriously rare well-differentiated (WD) HN-NECs is excellent, fewer than 20% of patients with PD tumors survive for five years after diagnosis [ 10 , 13 ]. As the curative potential of local therapies (surgery and radiotherapy) is eventually limited to the very early stage of the disease, in the majority of patients, the addition of systemic therapy is indicated to counteract microscopic or clinically overt metastases.…”

Section: Introductionmentioning

confidence: 99%

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

Strojan

Šifrer

Ferlito³

et al. 2021

Cancers

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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.

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Well-differentiated Neuroendocrine Carcinoma of the Larynx: Confusion of Terminology and Uncertainty of Early Studies

Cited by 8 publications

References 26 publications

Some Considerations on Laryngeal Neuroendocrine Neoplasms

Some Considerations on Laryngeal Neuroendocrine Neoplasms

Reduced expression of secretogranin VGF in laryngeal squamous cell carcinoma

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

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