{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T03:01:26Z","timestamp":1792119686284,"version":"4.4.0"},"reference-count":47,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,11,21]],"date-time":"2017-11-21T00:00:00Z","timestamp":1511222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Histopathology"],"published-print":{"date-parts":[[2018,2]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Metastatic melanoma involving the epidermis and\/or upper dermis may show significant histological overlap with primary cutaneous melanoma, especially the nodular subtype. Proper histopathological classification is crucial to appropriate staging and management, but is often challenging. The aim of this study was to identify helpful histopathological features for differentiating epidermotropic\/dermal metastatic melanoma (<jats:styled-content style=\"fixed-case\">EDMM<\/jats:styled-content>) and primary nodular melanoma (<jats:styled-content style=\"fixed-case\">PNM<\/jats:styled-content>).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and results<\/jats:title><jats:p>A cohort of <jats:styled-content style=\"fixed-case\">EDMM<\/jats:styled-content>s (<jats:italic>n<\/jats:italic> = 74) and <jats:styled-content style=\"fixed-case\">PNM<\/jats:styled-content>s (<jats:italic>n<\/jats:italic> = 75) was retrospectively reviewed for various histopathological features, and the data were compared between groups by the use of univariate analysis. Features significantly associated with <jats:styled-content style=\"fixed-case\">EDMM<\/jats:styled-content> included a tumour size of &lt;2 mm, an absence of tumour\u2010infiltrating lymphocytes and plasma cells, monomorphism, and involvement of adnexal epithelium. Features associated with <jats:styled-content style=\"fixed-case\">PNM<\/jats:styled-content> included a polypoid (exophytic) configuration, prominent tumour\u2010infiltrating plasma cells (<jats:styled-content style=\"fixed-case\">TIP<\/jats:styled-content>s), a tumour size of &gt;10 mm, ulceration, epidermal collarettes, a higher mitotic rate, necrosis, multiple phenotypes, significant pleomorphism, and lichenoid inflammation. In multivariate analysis, a logistic regression model including large tumour size, ulceration, prominent <jats:styled-content style=\"fixed-case\">TIP<\/jats:styled-content>s, lichenoid inflammation and epidermal collarettes was highly predictive of <jats:styled-content style=\"fixed-case\">PNM<\/jats:styled-content>. Six (8%) <jats:styled-content style=\"fixed-case\">EDMM<\/jats:styled-content>s from three patients showed an \u2018epidermal\u2010only\u2019 or \u2018epidermal\u2010predominant\u2019 pattern closely simulating <jats:italic>in\u2010situ<\/jats:italic> or microinvasive melanoma. Two of these cases were tested by fluorescence <jats:italic>in\u2010situ<\/jats:italic> hybridisation, which confirmed clonal relationships with their corresponding primary melanomas.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This is the first comprehensive histopathological comparison of <jats:styled-content style=\"fixed-case\">EDMM<\/jats:styled-content> and <jats:styled-content style=\"fixed-case\">PNM<\/jats:styled-content>. Recognition of the above histopathological associations should aid in the correct classification and staging of cutaneous melanoma. Epidermotropic metastatic melanomas may occasionally show an epidermal\u2010only\/epidermal\u2010predominant pattern; accurate diagnosis requires prudent clinical correlation and, when necessary, ancillary molecular tests.<\/jats:p><\/jats:sec>","DOI":"10.1111\/his.13384","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T18:18:50Z","timestamp":1504808330000},"page":"472-480","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Comprehensive histopathological comparison of epidermotropic\/dermal metastatic melanoma and primary nodular melanoma"],"prefix":"10.1111","volume":"72","author":[{"given":"Stephanie L","family":"Skala","sequence":"first","affiliation":[{"name":"Department of Pathology University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David P","family":"Arps","sequence":"additional","affiliation":[{"name":"Consolidated Pathology Consultants Libertyville IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lili","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Biostatistics University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly B","family":"Cha","sequence":"additional","affiliation":[{"name":"Department of Dermatology University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul W","family":"Harms","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Ann Arbor MI USA"},{"name":"Department of Dermatology University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleodor A","family":"Andea","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Ann Arbor MI USA"},{"name":"Department of Dermatology University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas R","family":"Fullen","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan Ann Arbor MI USA"},{"name":"Department of Dermatology University of Michigan 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 University of Michigan Ann Arbor MI USA"},{"name":"Department of Dermatology University of Michigan Ann Arbor MI USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,11,21]]},"reference":[{"key":"e_1_2_7_2_1","volume-title":"Melanoma treatment (PDQ): health professional version. PDQ cancer information summaries","author":"PDQ Adult Treatment Editorial Board","year":"2017"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.23.4799"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2005.03.006"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0b013e318165641a"},{"issue":"2","key":"e_1_2_7_6_1","first-page":"635","article-title":"Completely regressed primary cutaneous melanoma\u2014difficulties in diagnosis and classification","volume":"55","author":"M\u0103rg\u0103ritescu I","year":"2014","journal-title":"Rom. J. Morphol. Embryol."},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.2820360931"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.1980.tb00977.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19930915)72:6<1909::AID-CNCR2820720619>3.0.CO;2-S"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(195301)6:1<1::AID-CNCR2820060102>3.0.CO;2-C"},{"key":"e_1_2_7_11_1","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1001\/archderm.1978.01640130031009","article-title":"Epidermotropically metastatic malignant melanoma","volume":"114","author":"Kornberg R","year":"1978","journal-title":"Arch. Dermatol."},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0b013e3181b34a19"},{"key":"e_1_2_7_13_1","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1038\/modpathol.2011.182","article-title":"Objective assessment of blood and lymphatic vessel invasion and association with macrophage infiltration in cutaneous melanoma","volume":"25","author":"Storr SJ","year":"2011","journal-title":"Mod. Pathol."},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000372-199108000-00011"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478-199411000-00008"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.2011.01694.x"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e3181a1ef36"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/030089160409000125"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2006.07396.x"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2230.2003.01371.x"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1309\/R8N1CN04KKFV6M7T"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.3800833"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.959840"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000372-200106000-00001"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2014.09.028"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(197508)36:2<485::AID-CNCR2820360227>3.0.CO;2-M"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-8-362"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31825a5b45"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.dad.0000204761.40199.3f"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1080\/00313020412331282708"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-4362.2001.01214.x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.1992.tb01369.x"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1067\/mjd.2001.114579"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000372-199502000-00011"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1747.2002.01871.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/00000372-198712000-00005","article-title":"Plasma cells within the infiltrate of primary cutaneous malignant melanoma of the skin: a confirmation of its histoprognostic value","volume":"9","author":"Mascaro JM","year":"1987","journal-title":"Am. J. Dermatopathol."},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2016.28"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-11-3218"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2011.37.8539"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000164"},{"key":"e_1_2_7_41_1","first-page":"1350","article-title":"Lymphocytic reaction around primary and metastatic melanomas","volume":"63","author":"Payan HM","year":"1970","journal-title":"South. Med. J."},{"key":"e_1_2_7_42_1","first-page":"43","article-title":"Tumor\u2010infiltrating lymphocytes in lymph node melanoma metastases: a histopathologic prognostic indicator and an expression of local immune response","volume":"74","author":"Mihm MC","year":"1996","journal-title":"Lab. Invest."},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms16024343"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2559.1992.tb00988.x"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0b013e32832eabd5"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1097\/CMR.0000000000000277"},{"key":"e_1_2_7_47_1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1684\/ejd.2015.2522","article-title":"Complete regression of melanoma skin metastases after electrochemotherapy plus ipilimumab treatment: an unusual clinical presentation","volume":"25","author":"Brizio M","year":"2015","journal-title":"Eur. J. Dermatol."},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2133.2006.07370.x"}],"container-title":["Histopathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fhis.13384","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/his.13384","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T23:27:44Z","timestamp":1695857264000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/his.13384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,11,21]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2018,2]]}},"alternative-id":["10.1111\/his.13384"],"URL":"https:\/\/doi.org\/10.1111\/his.13384","archive":["Portico"],"relation":{},"ISSN":["0309-0167","1365-2559"],"issn-type":[{"value":"0309-0167","type":"print"},{"value":"1365-2559","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,11,21]]},"assertion":[{"value":"2017-05-28","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-09-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2017-11-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}