UV Signature Mutations Reclassify Salivary High-grade Neuroendocrine Carcinomas as Occult Metastatic Cutaneous Merkel Cell Carcinomas.

08:00 EDT 1st May 2019 | BioPortfolio

Summary of "UV Signature Mutations Reclassify Salivary High-grade Neuroendocrine Carcinomas as Occult Metastatic Cutaneous Merkel Cell Carcinomas."

Salivary high-grade neuroendocrine carcinomas (NECs) are rare, occur predominantly in the parotid gland, and are difficult to differentiate from metastatic cutaneous Merkel cell carcinomas (MCCs), which have overlapping morphologic, immunophenotypic, and molecular profiles. Oncogenic Merkel cell polyomavirus (MCPyV), found in 70% to 80% of MCCs, has also been reported in a few salivary NECs, but this is controversial. A promising biomarker to distinguish the 2 tumor types are UV signature mutations. UV signature mutations indicate a sun damage-induced mechanism of pathogenesis and recently have been found to be highly prevalent in MCPyV-negative MCCs but would be inconsistent with salivary origin. Here, we examine UV signature mutations as a molecular marker to distinguish primary salivary high-grade NEC from MCC. Whole exome DNA sequencing was performed on matched tumor-normal tissue from 4 MCPyV-negative high-grade salivary NECs with no other primary source identified, as well as 3 melanomas and 3 lung NECs as positive and negative controls, respectively. UV signature mutations were found in all salivary NECs, when defined as ≥60% of total mutations being C-to-T transitions at dipyrimidine sites, and when compared with known human cancer-related mutational signatures. The presence of UV signature mutations in salivary high-grade NECs strongly favors these to be occult metastatic MCCs. True salivary primary NECs are likely exceedingly rare. When a high-grade NEC is encountered in the salivary gland, the presence of UV signature mutations or MCPyV may be useful to exclude occult unknown primary MCC.


Journal Details

This article was published in the following journal.

Name: The American journal of surgical pathology
ISSN: 1532-0979
Pages: 682-687


DeepDyve research library

PubMed Articles [17331 Associated PubMed Articles listed on BioPortfolio]

A comparison of adult rhabdomyosarcoma and high grade neuroendocrine carcinoma of the urinary bladder reveals novel PPP1R12A fusions in rhabdomyosarcoma.

Some rhabdomyosarcomas and sarcomatoid carcinomas with heterologous rhabdomyosarcomatous elements resemble high-grade neuroendocrine carcinoma, creating a diagnostic difficulty. The purpose of this st...

Immunohistochemical Assessment of BAP1 Protein in Mucoepidermoid Carcinomas.

Mucoepidermoid carcinomas are common malignant salivary gland tumors. Despite recent advances in diagnosis and treatment, there has not been much improvement in outcome of these patients, necessitatin...

A well differentiated neuroendocrine tumor of the jejunum with peritoneal carcinomatosis: A case report.

Neuroendocrine tumors (NETs), belong to a group of neoplasms that arise from neuroendocrine cells and express markers such as synaptophysin and chromogranin A. The digestive system (DS) is the most co...

LINE-1 retrotransposons become deregulated during the development of ovarian cancer precursor lesions.

There is growing evidence that the majority of high-grade serous ovarian carcinomas likely arise from local dissemination of precursor lesions of the fallopian tube. Evolution of these lesions from ea...

Pre-treatment metabolic tumor volume predicts tumor metastasis and progression in high-grade salivary gland carcinoma.

High-grade salivary gland carcinoma (SGC) shows a high rate of metastasis and post-treatment recurrence, resulting in poor patient survival. Therefore, we evaluated the utility of pre-treatment F-FDG ...

Clinical Trials [6168 Associated Clinical Trials listed on BioPortfolio]

FOLFIRINOX in Metastatic High Grade Gastroenteropancreatic Neuroendocrine Carcinomas

The purpose of this study is evaluate the efficacy and safety of FOLFIRINOX in patients with gastroenteropancreatic high-grade neuroendocrine carcinomas. This is a prospective Phase II op...

TEMCAP in Grade 3 and Low Ki-67 Gastroenteropancreatic Neuroendocrine Tumors

GI tract including pancreas is the one of most common primary sites of neuroendocrine tumors. Current grading of neuroendocrine tumors are based on the 2010 WHO classification. This classi...

Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung Neuroendocrine Carcinoma

The purpose of this study is to test the efficacy, safety, and tolerability of the combination of chemotherapy treatment, which could be either Cisplatin or carboplatin and etoposide, and ...

CAPTEM or FOLFIRI as SEcond-line Therapy in NEuroendocrine CArcinomas

This is a randomized phase II non comparative study. Patients with metastatic Neuroendocrine Carcinomas (NEC) Grade 3, will be enrolled in the study and will be randomly assigned to receiv...

Pembrolizumab in Advanced Poorly Differentiated and/or High Grade Neuroendocrine Tumors/Carcinomas

The purpose of this study is to: - Assess overall radiographic response rate (ORR) - Assess progression-free survival (PFS) - Test the safety and tolerability of Pembroli...

Medical and Biotech [MESH] Definitions

A tumor of both low- and high-grade malignancy. The low-grade grow slowly, appear in any age group, and are readily cured by excision. The high-grade behave aggressively, widely infiltrate the salivary gland and produce lymph node and distant metastases. Mucoepidermoid carcinomas account for about 21% of the malignant tumors of the parotid gland and 10% of the sublingual gland. They are the most common malignant tumor of the parotid. (From DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575; Holland et al., Cancer Medicine, 3d ed, p1240)

A malignant epithelial tumor of glandular tissue, especially the salivary glands, characterized by acini with mucus-producing cells and by the presence of malignant squamous elements. Most mucoepidermoid tumors are low-grade lesions readily cured by adequate excision. They may appear in any age group. They grow slowly. If high-grade, they behave aggressively, widely infiltrating the salivary gland and producing lymph node and distant metastases. (Dorland, 27th ed; from DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p575)

A group of carcinomas which share a characteristic morphology, often being composed of clusters and trabecular sheets of round "blue cells", granular chromatin, and an attenuated rim of poorly demarcated cytoplasm. Neuroendocrine tumors include carcinoids, small ("oat") cell carcinomas, medullary carcinoma of the thyroid, Merkel cell tumor, cutaneous neuroendocrine carcinoma, pancreatic islet cell tumors, and pheochromocytoma. Neurosecretory granules are found within the tumor cells. (Segen, Dictionary of Modern Medicine, 1992)

A malignant neoplasm of epithelial cells of the SALIVARY GLANDS, with microcystic architecture, low-grade nuclei, and granular vacuolated cytoplasm.

A carcinoma composed mainly of epithelial elements with little or no stroma. Medullary carcinomas of the breast constitute 5%-7% of all mammary carcinomas; medullary carcinomas of the thyroid comprise 3%-10% of all thyroid malignancies. (From Dorland, 27th ed; DeVita Jr et al., Cancer: Principles & Practice of Oncology, 3d ed, p1141; Segen, Dictionary of Modern Medicine, 1992)

Quick Search


DeepDyve research library

Relevant Topics

The NIH defines a biomarker as "a characteristic that is objectively measured and evaluated as an indicator of normal biologic processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention." A biological molecule f...

Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...

Searches Linking to this Article