Neuroendocrine tumors (NETs) of the head and neck are rare and include a range of diverse neoplasms broadly categorized into two subsets. Group I NETs, characterized by epithelial differentiation, comprise carcinoids (well-differentiated neuroendocrine carcinomas [NECs]), atypical carcinoids (moderately differentiated NECs) and small and large cell carcinomas (poorly differentiated NECs). NECs mainly arise from the larynx, followed by the paranasal sinuses, salivary glands, and oropharyngeal mucosa. In general, non-laryngeal NECs are associated with higher risk of metastasis/recurrence, depending on localization and grading. Group II NETs are neurally-derived and include paragangliomas, schwannomas, and rarer tumors such as olfactory neuroblastomas, extra-osseous Ewing’s sarcomas, and malignant peripheral nerve sheath tumors. NETs are therefore clinically and pathologically heterogeneous and certain types can be hormonally-active. The management of the patients affected with such rare and heterogeneous neoplasms is often uncharted and difficult. Well-differentiated NECs are typically located in the larynx and localized; surgery is usually curative. In contrast, atypical moderately differentiated NECs of the larynx are associated with high incidence of lymph node metastasis, therefore, elective neck dissection is often indicated. Medullary thyroid carcinomas have histological similarities to these tumors, and both may produce calcitonin. Poorly differentiated small cell NECs of the salivary glands appear to have a better prognosis compared to similar tumors originating at other head and neck sites, including the larynx, where nearly 90% patients develop distant metastasis. A classic example of large cell NEC is sinonasal undifferentiated carcinoma, which has a 25% risk of recurrence. In this regard, large cell NECs should be distinguished from olfactory neuroblastoma and lymphoepithelioma which entail a different treatment approach. In metastatic or inoperable NETs demonstrating somatostatin receptor positivity, the use of radionuclide therapy offers a possible therapeutic option. Olfactory neuroblastomas are distinctive in comparison to neuroblastomas of other regions. Good outcome is achieved with surgery and adjuvant radiotherapy or chemotherapy. Mucosal malignant melanomas can also exhibit neuroendocrine differentiation. These highly aggressive tumors present low median survival rates and a wide variety of histological appearances. Paragangliomas are highly vascularized neoplasms. Amongst all types, carotid body tumors are the most seen. Multiple tumors can be seen in familial forms of the disease. Paragangliomas are primarily treated with surgery or radiosurgery. Targeted therapy remains a promising approach for the future. Overall, the management of neuroendocrine tumors of the head and neck presents considerable challenges due to their specific anatomical, clinical, histopathological, and molecular characteristics. In most cases, rarity entails lack of sufficient evidence in the literature. This Research Topic will focus on the management of such neoplasms with the aim to create a platform for sharing clinical experiences and research studies. This will help in providing guidance and updates for clinicians caring for patients affected with NETs of the head and neck region.
Neuroendocrine tumors (NETs) of the head and neck are rare and include a range of diverse neoplasms broadly categorized into two subsets. Group I NETs, characterized by epithelial differentiation, comprise carcinoids (well-differentiated neuroendocrine carcinomas [NECs]), atypical carcinoids (moderately differentiated NECs) and small and large cell carcinomas (poorly differentiated NECs). NECs mainly arise from the larynx, followed by the paranasal sinuses, salivary glands, and oropharyngeal mucosa. In general, non-laryngeal NECs are associated with higher risk of metastasis/recurrence, depending on localization and grading. Group II NETs are neurally-derived and include paragangliomas, schwannomas, and rarer tumors such as olfactory neuroblastomas, extra-osseous Ewing’s sarcomas, and malignant peripheral nerve sheath tumors. NETs are therefore clinically and pathologically heterogeneous and certain types can be hormonally-active. The management of the patients affected with such rare and heterogeneous neoplasms is often uncharted and difficult. Well-differentiated NECs are typically located in the larynx and localized; surgery is usually curative. In contrast, atypical moderately differentiated NECs of the larynx are associated with high incidence of lymph node metastasis, therefore, elective neck dissection is often indicated. Medullary thyroid carcinomas have histological similarities to these tumors, and both may produce calcitonin. Poorly differentiated small cell NECs of the salivary glands appear to have a better prognosis compared to similar tumors originating at other head and neck sites, including the larynx, where nearly 90% patients develop distant metastasis. A classic example of large cell NEC is sinonasal undifferentiated carcinoma, which has a 25% risk of recurrence. In this regard, large cell NECs should be distinguished from olfactory neuroblastoma and lymphoepithelioma which entail a different treatment approach. In metastatic or inoperable NETs demonstrating somatostatin receptor positivity, the use of radionuclide therapy offers a possible therapeutic option. Olfactory neuroblastomas are distinctive in comparison to neuroblastomas of other regions. Good outcome is achieved with surgery and adjuvant radiotherapy or chemotherapy. Mucosal malignant melanomas can also exhibit neuroendocrine differentiation. These highly aggressive tumors present low median survival rates and a wide variety of histological appearances. Paragangliomas are highly vascularized neoplasms. Amongst all types, carotid body tumors are the most seen. Multiple tumors can be seen in familial forms of the disease. Paragangliomas are primarily treated with surgery or radiosurgery. Targeted therapy remains a promising approach for the future. Overall, the management of neuroendocrine tumors of the head and neck presents considerable challenges due to their specific anatomical, clinical, histopathological, and molecular characteristics. In most cases, rarity entails lack of sufficient evidence in the literature. This Research Topic will focus on the management of such neoplasms with the aim to create a platform for sharing clinical experiences and research studies. This will help in providing guidance and updates for clinicians caring for patients affected with NETs of the head and neck region.