Proceedings of the NASHNP Companion Meeting, March 18th, 2018, Vancouver, BC, Canada: Salivary Neuroendocrine Carcinoma—An Overview of a Rare Disease with an Emphasis on Determining Tumor Origin

Abstract

Salivary neuroendocrine carcinomas are rare and the overwhelming majority is high-grade. The parotid gland is the most commonly involved site followed by the submandibular gland. Most arise de novo but rare examples occurring as a high-grade transformation of another type of salivary gland neoplasm exist. There is significant morphologic and immunophenotypic overlap with neuroendocrine carcinomas of other sites, especially the skin. Like cutaneous neuroendocrine (or Merkel cell) carcinomas, approximately three-fourths are cytokeratin 20 positive. Cytokeratin 20 positive salivary neuroendocrine carcinomas are often referred to as being of the 'Merkel cell type' since most other non-cutaneous neuroendocrine carcinomas are cytokeratin 20 negative. Salivary neuroendocrine carcinomas may be challenging to separate from Merkel cell carcinomas of the head and neck on pathologic grounds because the latter often metastasize to the parotid gland. Clinical history is often relied upon to separate primary salivary tumors from cutaneous metastases but may not be helpful in all cases. Here we review the clinical, pathologic and molecular features of salivary neuroendocrine carcinomas focusing on high-grade major salivary gland tumors. The difficulty in separating salivary tumors from metastatic Merkel cell carcinoma will be highlighted.

Small Cell Neuroendocrine Carcinoma of the Parotid Gland: A Chronicle of Publications Based on the Largest Case Series and a Report of the First Greek Case

“…Positive immunoreactivity for CK20 and neurofilament with a dot like pattern, like our case, strongly favors salivary SCC or Merkel cell carcinoma, features that are not detected in pulmonary SCC, which is the most likely metastatic neoplasm [8]. Consequently, the neuroendocrine type of SCC may be further subclassified into Merkel cell and pulmonary varieties on the basis of cytokeratin (CK) 20 immunoreactivity [8,10].…”

“…The overwhelming majority of salivary NECs are high grade with the small cell type outnumbering large cell by 5:1. Well and moderately -differentiated are < 10 cases described in the literature [10].…”

“…New chemotherapeutics agents, such as taxanes, campothecin derivatives (topotecan, irinotecan) and gemicitabine, as single agents, or in combination, have shown activity against SCC [4]. While PD-L1 inhibitors have shown disease response in Merkel cell carcinomas, their efficacy in salivary SCC is unknown [10].…”

“…To this direction radiologic imaging with CT, PET/CT and octreoscan are basic [4]. Chernock, et al reports the difficulties to distinguish primary salivary SCCs from metastases to the salivary glands because morphologic and immunostaining features between cutaneous and salivary NECS may be indistinguishable [10].…”

The biology and treatment of Merkel cell carcinoma: current understanding and research priorities

“…In addition, certain non-lung small-cell carcinomas (SmCCs), such as parotid and uterine cervical primary tumours, also frequently express CK20 and might, therefore, be more challenging to distinguish from MCC, especially in the setting of metastatic MCC from an unknown primary site 3 . Distinguishing between primary parotid SmCC and metastatic MCC of unknown primary is especially problematic, as the parotid is frequently a site of regional MCC metastasis, and primary parotid SmCC is rare 130 . As NGS-based analyses enter more widespread use, MCPyV detection combined with analysis of mutational signatures might be useful for distinguishing MCC (MCPyV-positive or with ultraviolet signature mutations) from metastatic SCLC (MCPyV-negative with smoking signature mutations) 83 .…”