Neuroendocrine neoplasms

2026-08-11   Paola Dal Cin, PhD , Stefano Sioletic, MD 

1.Brigham and Women\'s Hospital , Harvard Medical School, Boston , MA (USA)
2.San Camillo-Forlanin Hospital Rome (Italy)

Keywords
non-cutaneous neuroendocrine neoplasms ,Merkel cell carcinoma, cutaneous neuroendocrine neoplasms

Classification

Definition

Neuroendocrine neoplasms are a relatively rare and heterogeneous tutor types, Cutaneous metastases from non-cutaneous neuroendocrine neoplasms are rare, but a distinction from primary neuroendocrine carcinoma of the skin, such as Merkel cell carcinoma (MCC), is critical to guide clinical management.1 In such cases, the most discriminant markers for a diagnosis of MCC are SATB2 NF expression, and Merkel cell polyomavirus DNA detection. 2

Neuroendocine neoplasms
Merkel cell carcinomaMerkel cell carcinoma (MCC) is a rare and aggressive neuroendocrine skin cancer occurring predominantly in elderly, fair-skinned individuals with chronically sun-damaged skin, most often involving the head and neck, extremities, and trunk. 3 It is classified based on a characteristic neuroendocrine phenotype despite marked molecular heterogeneity between two largely mutually exclusive pathogenetic subtypes, driven by integrated Merkel cell polyomavirus (MCPyV) and expression of viral T antigens or UV signature mutations. MCPyV-positive disease accounts for approximately 80% of cases in Western populations and MCPyV-negative disease for the remainder. Both share overlapping morphology, immunophenotype, and aggressive behaviour,but no statistical difference in their response to immune checkpoint inhibitor (ICI) immunotherapy. 4-7
MCPyV-positive tumors posess a very low tumor mutational burden (TMB) , show clonal viral integration with a truncated large antiginen and a small T antiginen targeting tumor-suppressor proteins as Rb and tp53 . 8,9 MCPyV-negative tumors show extensive ultraviolet-induced damage reminiscent of other skin cancers, with a high TMB , COSMIC UV signatures and frequent TP53, RB1, NOTCH1 , KMTD2, KMT2C, and PIK3CA alterations . 7,10

Article Bibliography

Reference NumberPubmed IDLast YearTitleAuthors
1362222102022Cutaneous metastases of non-cutaneous neuroendocrine neoplasms: A histopathologic review of 15 cases.Hobbs MM et al
2303490282019Diagnostic accuracy of a panel of immunohistochemical and molecular markers to distinguish Merkel cell carcinoma from other neuroendocrine carcinomas.Kervarrec T et al
3390601192024Merkel Cell Carcinoma.Strong J et al
4304976762019Merkel Cell Carcinoma Review.Xue Y et al
5321884902020Clinical and molecular characterization of virus-positive and virus-negative Merkel cell carcinoma.Starrett GJ et al
6332284632021Molecular Pathogenesis of Merkel Cell Carcinoma.DeCaprio JA et al
7349670842022Merkel cell carcinoma: An updated review of pathogenesis, diagnosis, and treatment options.Hernandez LE et al
8305984502019Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response.Park DE et al
9386189602024Polyomavirus-positive Merkel cell carcinoma: the beginning of the beginning.Wong MK et al
10412283012025Molecular Characterization of Polyomavirus-Positive and Negative Merkel Cell Carcinoma.Vaidya P et al

Citation

Paola Dal Cin, PhD ; Stefano Sioletic, MD

Neuroendocrine neoplasms

Atlas Genet Cytogenet Oncol Haematol. 2026-08-11

Online version: http://atlasgeneticsoncology.org/solid-tumor/209384