{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T04:08:46Z","timestamp":1791864526446,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2018,12,5]],"date-time":"2018-12-05T00:00:00Z","timestamp":1543968000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Anatomic Pathology Project Funding Committee of the Department of Pathology, Michigan Medicine"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2019,2]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>Primary cutaneous neuroendocrine carcinoma, or Merkel cell carcinoma (<jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content>), cannot be distinguished morphologically from small\u2010cell neuroendocrine carcinomas (Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>) from other sites. Immunohistochemistry is required to confirm cutaneous origin, and is also used for detection of sentinel lymph node (<jats:styled-content style=\"fixed-case\">SLN<\/jats:styled-content>) metastases of <jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content>. Cytokeratin 20 (<jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>20) expression is commonly used for these purposes, but is negative in some <jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content> cases, and has unclear specificity. We evaluated immunohistochemistry for neurofilament and <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>20 in <jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content> compared with Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> from other sites.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>We evaluated neurofilament expression in 55 <jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content> specimens from 39 unique patients, including nine <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>20\u2010negative <jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content> tumours. Neurofilament expression was observed in 42 of 55 (76.4%) <jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content> cases, including seven of nine (77.8%) <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>20\u2010negative <jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content> cases. Neurofilament was expressed in nine of 12 (75%) Merkel cell polyomavirus\u2010positive tumours and five of 10 (50%) virus\u2010negative tumours. Compared to a standard immunohistochemical panel (cytokeratin cocktail and <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>20), neurofilament was 87.5% sensitive for detecting <jats:styled-content style=\"fixed-case\">SLN<\/jats:styled-content> metastases. Neurofilament and <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>20 expression was also assessed in 61 extracutaneous Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> from 60 unique patients, with primary sites including lung (27), bladder (18), cervix (3), gastrointestinal tract (3), sinonasal tract (2) and other sites (7). The specificity of neurofilament and <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>20 for <jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content> versus non\u2010cutaneous Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content> was 96.7% and 59.0%, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Neurofilament has superior specificity to <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>20 in distinguishing <jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content> from non\u2010cutaneous Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>. Neurofilament is frequently expressed in <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>20\u2010 and virus\u2010negative <jats:styled-content style=\"fixed-case\">MCC<\/jats:styled-content> tumours. Limitations of neurofilament immunohistochemistry include lower sensitivity than <jats:styled-content style=\"fixed-case\">CK<\/jats:styled-content>20 and subtle staining in some tumours. However, our findings indicate that neurofilament is useful for excluding non\u2010cutaneous Sm<jats:styled-content style=\"fixed-case\">CC<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13758","type":"journal-article","created":{"date-parts":[[2018,9,22]],"date-time":"2018-09-22T01:44:12Z","timestamp":1537580652000},"page":"504-513","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":47,"title":["Neurofilament is superior to cytokeratin 20 in supporting cutaneous origin for neuroendocrine carcinoma"],"prefix":"10.1111","volume":"74","author":[{"given":"Lauren M","family":"Stanoszek","sequence":"first","affiliation":[{"name":"Department of Pathology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0650-1266","authenticated-orcid":false,"given":"May P","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Pathology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"},{"name":"Department ofDermatology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nallasivam","family":"Palanisamy","sequence":"additional","affiliation":[{"name":"Department of Urology Vattikuti Urology Institute Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shannon","family":"Carskadon","sequence":"additional","affiliation":[{"name":"Department of Urology Vattikuti Urology Institute Henry Ford Health System Detroit MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javed","family":"Siddiqui","sequence":"additional","affiliation":[{"name":"Department of Pathology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv M","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pathology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"},{"name":"Department ofDermatology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly L","family":"Harms","sequence":"additional","affiliation":[{"name":"Department ofDermatology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Lowe","sequence":"additional","affiliation":[{"name":"Department of Pathology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"},{"name":"Department ofDermatology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R","family":"Fullen","sequence":"additional","affiliation":[{"name":"Department of Pathology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"},{"name":"Department ofDermatology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0802-2883","authenticated-orcid":false,"given":"Paul W","family":"Harms","sequence":"additional","affiliation":[{"name":"Department of Pathology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"},{"name":"Department ofDermatology Michigan Medicine\/University of Michigan Health System Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,12,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cll.2017.05.004"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-0702"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6494"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1877"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1152586"},{"key":"e_1_2_7_7_1","unstructured":"NCCN Clinical Practice Guidelines in Oncology Merkel Cell Carcinoma Version I.2018.2017. 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