{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T23:34:14Z","timestamp":1782603254229,"version":"3.54.5"},"reference-count":29,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2020,5,23]],"date-time":"2020-05-23T00:00:00Z","timestamp":1590192000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The possibility of a so-called primary lymph node neuroendocrine carcinoma has been described in the literature. Here we evaluate cases fitting such a diagnosis and find that the cases demonstrate a convincing and pervasive pattern consistent with metastatic Merkel cell carcinoma.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Six cases of primary lymph node Merkel cell carcinoma and one case of metastatic neuroendocrine carcinoma at a bony site, all with unknown primary, were sequenced using a combination of whole-exome and targeted panel methods. Sequencing results were analyzed for the presence of an ultraviolet (UV) mutational signature or off-target detection of Merkel cell polyomavirus (MCPyV).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Four of six primary lymph node cases were positive for a UV mutational signature, with the remaining two cases positive for off-target alignment of MCPyV. One case of neuroendocrine carcinoma occurring at a bony site was also positive for a UV mutational signature.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We find no evidence to corroborate the existence of so-called primary Merkel cell carcinoma of lymph node.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ajcp\/aqaa051","type":"journal-article","created":{"date-parts":[[2020,3,24]],"date-time":"2020-03-24T12:07:34Z","timestamp":1585051654000},"page":"369-380","source":"Crossref","is-referenced-by-count":15,"title":["Is Merkel Cell Carcinoma of Lymph Node Actually Metastatic Cutaneous Merkel Cell Carcinoma?"],"prefix":"10.1093","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3405-4571","authenticated-orcid":false,"given":"Lauren E B","family":"Lawrence","sequence":"first","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atif","family":"Saleem","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malaya K","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanna K","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin A","family":"Pinsky","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"},{"name":"Department of Medicine, Division of Infectious Diseases and Geographic Medicine, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasodha","family":"Natkunam","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1514-7550","authenticated-orcid":false,"given":"Christian A","family":"Kunder","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henning","family":"Stehr","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James L","family":"Zehnder","sequence":"additional","affiliation":[{"name":"Department of Pathology, Stanford University School of Medicine, Stanford, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,5,23]]},"reference":[{"key":"2020080503203627700_CIT0001","doi-asserted-by":"crossref","first-page":"e154","DOI":"10.1097\/DAD.0000000000000614","article-title":"Complete spontaneous regression of Merkel cell carcinoma after biopsy: a case report and review of the literature","volume":"38","author":"Ahmadi Moghaddam","year":"2016","journal-title":"Am J Dermatopathol."},{"key":"2020080503203627700_CIT0002","doi-asserted-by":"crossref","first-page":"5961","DOI":"10.4081\/rt.2015.5961","article-title":"Spontaneous regression of primitive Merkel cell carcinoma","volume":"7","author":"Cirillo","year":"2015","journal-title":"Rare Tumors."},{"key":"2020080503203627700_CIT0003","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.ijscr.2014.11.027","article-title":"Spontaneous regression of Merkel cell carcinoma: a case report and review of the literature","volume":"7C","author":"Pang","year":"2015","journal-title":"Int J Surg Case Rep."},{"key":"2020080503203627700_CIT0004","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1038\/modpathol.2013.250","article-title":"Merkel cell carcinoma of lymph node with unknown primary has a significantly lower association with Merkel cell polyomavirus than its cutaneous counterpart","volume":"27","author":"Pan","year":"2014","journal-title":"Mod Pathol."},{"key":"2020080503203627700_CIT0005","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.chom.2016.04.024","article-title":"Identifying the target cells and mechanisms of Merkel cell polyomavirus infection","volume":"19","author":"Liu","year":"2016","journal-title":"Cell Host Microbe."},{"key":"2020080503203627700_CIT0006","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.yexmp.2012.09.019","article-title":"Detection of Merkel cell polyomavirus in chronic lymphocytic leukemia T-cells","volume":"94","author":"Cimino","year":"2013","journal-title":"Exp Mol Pathol."},{"key":"2020080503203627700_CIT0007","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1186\/s13059-016-0893-4","article-title":"DeconstructSigs: delineating mutational processes in single tumors distinguishes DNA repair deficiencies and patterns of carcinoma evolution","volume":"17","author":"Rosenthal","year":"2016","journal-title":"Genome Biol."},{"key":"2020080503203627700_CIT0008","doi-asserted-by":"crossref","first-page":"3403","DOI":"10.18632\/oncotarget.6494","article-title":"Mutational landscape of MCPyV-positive and MCPyV-negative Merkel cell carcinomas with implications for immunotherapy","volume":"7","author":"Goh","year":"2016","journal-title":"Oncotarget."},{"key":"2020080503203627700_CIT0009","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1038\/modpathol.2015.154","article-title":"Next generation sequencing of cytokeratin 20-negative Merkel cell carcinoma reveals ultraviolet-signature mutations and recurrent TP53 and RB1 inactivation","volume":"29","author":"Harms","year":"2016","journal-title":"Mod Pathol."},{"key":"2020080503203627700_CIT0010","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1038\/s41591-018-0016-8","article-title":"Molecular subtypes of diffuse large B cell lymphoma are associated with distinct pathogenic mechanisms and outcomes","volume":"24","author":"Chapuy","year":"2018","journal-title":"Nat Med."},{"key":"2020080503203627700_CIT0011","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1158\/1078-0432.CCR-17-0252","article-title":"Pathways impacted by genomic alterations in pulmonary carcinoid tumors","volume":"24","author":"Asiedu","year":"2018","journal-title":"Clin Cancer Res."},{"key":"2020080503203627700_CIT0012","doi-asserted-by":"crossref","first-page":"918","DOI":"10.21147\/j.issn.1000-9604.2019.06.08","article-title":"Genomic dissection of gastrointestinal and lung neuroendocrine neoplasm","volume":"31","author":"Wang","year":"2019","journal-title":"Chin J Cancer Res."},{"key":"2020080503203627700_CIT0013","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1097\/PAS.0000000000001231","article-title":"UV signature mutations reclassify salivary high-grade neuroendocrine carcinomas as occult metastatic cutaneous Merkel cell carcinomas","volume":"43","author":"Sun","year":"2019","journal-title":"Am J Surg Pathol."},{"key":"2020080503203627700_CIT0014","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.1038\/s41467-018-03099-x","article-title":"Integrative genomic profiling of large-cell neuroendocrine carcinomas reveals distinct subtypes of high-grade neuroendocrine lung tumors","volume":"9","author":"George","year":"2018","journal-title":"Nat Commun."},{"key":"2020080503203627700_CIT0015","doi-asserted-by":"crossref","first-page":"D339","DOI":"10.1093\/nar\/gkl1004","article-title":"Genome Information Broker for Viruses (GIB-V): database for comparative analysis of virus genomes","volume":"35","author":"Hirahata","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"2020080503203627700_CIT0016","doi-asserted-by":"crossref","DOI":"10.1186\/s12859-019-2996-x","article-title":"Magic-BLAST, an accurate DNA and RNA-seq aligner for long and short reads","author":"Boratyn","year":"2019;20:405","journal-title":"BMC Bioinformatics"},{"key":"2020080503203627700_CIT0017","article-title":"Identification of viral integration sites in cancer genomes using unmapped reads in targeted next-generation sequencing data","volume":"20","author":"Bowman","year":"2018","journal-title":"J Mol Diagn."},{"key":"2020080503203627700_CIT0018","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.jmoldx.2017.10.007","article-title":"Comprehensive genomic profiling of malignant effusions in patients with metastatic lung adenocarcinoma","volume":"20","author":"Yang","year":"2018","journal-title":"J Mol Diagn."},{"key":"2020080503203627700_CIT0019","article-title":"Clinical implementation of mutational signature analysis","volume":"20","author":"Lawrence","year":"2018","journal-title":"J Mol Diagn"},{"key":"2020080503203627700_CIT0020","doi-asserted-by":"crossref","first-page":"e164","DOI":"10.1093\/nar\/gkq603","article-title":"ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data","volume":"38","author":"Wang","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"2020080503203627700_CIT0021","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1097\/PAS.0b013e31827fcc33","article-title":"A comparison of CMV detection in gastrointestinal mucosal biopsies using immunohistochemistry and PCR performed on formalin-fixed, paraffin-embedded tissue","volume":"37","author":"Mills","year":"2013","journal-title":"Am J Surg Pathol."},{"key":"2020080503203627700_CIT0022","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1158\/1078-0432.CCR-17-1678","article-title":"Merkel cell carcinoma patients presenting without a primary lesion have elevated markers of immunity, higher tumor mutation burden, and improved survival","volume":"24","author":"Vandeven","year":"2018","journal-title":"Clin Cancer Res."},{"key":"2020080503203627700_CIT0023","article-title":"NCCN clinical practice guidelines in","author":"Schmults","year":"2019","journal-title":"Natl Compr Canc Netw"},{"key":"2020080503203627700_CIT0024","doi-asserted-by":"crossref","DOI":"10.1007\/978-1-4614-6608-6","volume-title":"Merkel Cell Carcinoma","author":"Alam","year":"2013"},{"key":"2020080503203627700_CIT0025","doi-asserted-by":"crossref","first-page":"3720","DOI":"10.1158\/0008-5472.CAN-15-0702","article-title":"The distinctive mutational spectra of polyomavirus-negative Merkel cell carcinoma","volume":"75","author":"Harms","year":"2015","journal-title":"Cancer Res."},{"key":"2020080503203627700_CIT0026","article-title":"Metagenomic next-generation sequencing for the identification and quantitation of transplant-related DNA viruses","author":"Carpenter","journal-title":"J Clin Microbiol"},{"key":"2020080503203627700_CIT0027","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1158\/1078-0432.CCR-15-2946","article-title":"Next-generation sequencing of pulmonary large cell neuroendocrine carcinoma reveals small cell carcinoma-like and non-small cell carcinoma-like subsets","volume":"22","author":"Rekhtman","year":"2016","journal-title":"Clin Cancer Res."},{"key":"2020080503203627700_CIT0028","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1159\/000478050","article-title":"Treatment outcomes for metastatic melanoma of unknown primary in the new era: a single-institution study and review of the literature","volume":"93","author":"Utter","year":"2017","journal-title":"Oncology."},{"key":"2020080503203627700_CIT0029","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1038\/s41591-018-0265-6","article-title":"Ultraviolet radiation-induced DNA damage is prognostic for outcome in melanoma","volume":"25","author":"Trucco","year":"2019","journal-title":"Nat Med."}],"container-title":["American Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/ajcp\/article-pdf\/154\/3\/369\/33566507\/aqaa051.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/ajcp\/article-pdf\/154\/3\/369\/33566507\/aqaa051.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,8,5]],"date-time":"2020-08-05T07:21:10Z","timestamp":1596612070000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ajcp\/article\/154\/3\/369\/5843310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,23]]},"references-count":29,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2020,5,23]]},"published-print":{"date-parts":[[2020,8,5]]}},"URL":"https:\/\/doi.org\/10.1093\/ajcp\/aqaa051","relation":{},"ISSN":["0002-9173","1943-7722"],"issn-type":[{"value":"0002-9173","type":"print"},{"value":"1943-7722","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,9]]},"published":{"date-parts":[[2020,5,23]]}}}