{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T18:32:57Z","timestamp":1789237977517,"version":"build-2803163510"},"reference-count":47,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"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":["J Cutan Pathol"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Digital papillary adenocarcinoma (DPA) is a rare neoplasm that can exhibit local recurrence and distant metastasis. We present a series of eight cases of DPA showing two distinct clinical presentations, morphologies, immunophenotypes, and molecular features. Four cases were characterized by painless, slow\u2010growing nodules located on the digits. The lesions were small, well\u2010defined, and confined in the dermis. Histopathologically, these tumors were composed of glandular structures lined by cuboidal epithelium with luminal papillary infoldings. Only rare mitotic figures and minimal squamoid differentiation were present, and cellular necrosis was absent. All four cases were positive for the BRAF V600E immunohistochemistry but negative for p16, low\u2010risk and high\u2010risk HPV in situ hybridization (ISH). In contrast, the remaining four cases were characterized by painful, rapidly growing masses on the digits. These four lesions were located in the deep dermis and consisted of a solid, tightly packed papillary architecture lined by atypical epithelioid cells with inconspicuous nucleoli. Cellular necrosis, numerous mitotic figures, and prominent squamoid differentiation were seen. All cases were negative for the BRAF V600E IHC. However, they showed strong, patchy to diffuse reactivity for p16 and were positive for low\u2010risk HPV ISH and negative for high\u2010risk HPV ISH. Our findings suggest that the current classification of DPA encompasses tumors that show two discrete pathogenic pathways \u2014 <jats:italic>BRAF<\/jats:italic> mutation or low\u2010risk HPV infection. DPAs with low\u2010risk HPV infection exhibit aggressive clinical features, high\u2010grade morphology, marked squamoid differentiation, and wild\u2010type <jats:italic>BRAF<\/jats:italic>. DPAs with <jats:italic>BRAF V600E<\/jats:italic> have less aggressive clinical features, low\u2010grade morphologic findings, mild to absent squamoid differentiation, and negative HPV infection.<\/jats:p>","DOI":"10.1111\/cup.14386","type":"journal-article","created":{"date-parts":[[2023,2,9]],"date-time":"2023-02-09T11:04:03Z","timestamp":1675940643000},"page":"568-576","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Two distinct pathogenic pathways of digital papillary adenocarcinoma \u2014 <i>BRAF<\/i> mutation or low\u2010risk <scp>HPV<\/scp> infection"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5371-6251","authenticated-orcid":false,"given":"Chau M.","family":"Bui","sequence":"first","affiliation":[{"name":"Department of Pathology Cedars Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6318-460X","authenticated-orcid":false,"given":"Tatsiana","family":"Pukhalskaya","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Rochester School of Medicine and Dentistry  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7301-8274","authenticated-orcid":false,"given":"Bruce R.","family":"Smoller","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Rochester School of Medicine and Dentistry  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2908-9128","authenticated-orcid":false,"given":"Hatice Betul","family":"Zengin","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Rochester School of Medicine and Dentistry  Rochester New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saleh","family":"Heneidi","sequence":"additional","affiliation":[{"name":"Department of Pathology Cedars Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Vail","sequence":"additional","affiliation":[{"name":"Department of Pathology Cedars Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Makhoul","sequence":"additional","affiliation":[{"name":"Department of Pathology Cedars Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bonnie","family":"Balzer","sequence":"additional","affiliation":[{"name":"Department of Pathology Cedars Sinai Medical Center  Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31826320ec"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102230.2009.03490.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/CCID.S71323"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0560.1987.tb00488.x"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12593\u2010010\u20100028\u20101"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2008.07.038"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpra.2020.03.001"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/1346\u20108138.14159"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.2165\/00128071\u2010200708040\u201000007"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000478\u2010200006000\u201000002"},{"key":"e_1_2_8_12_1","article-title":"Aggressive digital papillary adenocarcinoma","volume":"15","author":"Laun J","year":"2015","journal-title":"Eplasty"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2012.46.4693"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/ijd.13712"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamcollsurg.2021.01.019"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/modpathol.2011.48"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjd.17446"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anndiagpath.2015.08.002"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000001694"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379\u2010022\u201001094\u20108"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100560.1984.tb00398.x"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022\u2010202X.2004.23530.x"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00441\u2010013\u20101716\u20105"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00105-007-1448-0"},{"key":"e_1_2_8_25_1","first-page":"34","volume-title":"Skin Pathology","author":"Weedon D","year":"2020"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2017.02.028"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAT.0b013e32835af778"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1034\/j.1600-0560.2003.00031.x"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/his.12767"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001426"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/cup.12720"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20440"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2017.10.004"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20440"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/gcc.20168"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.2165\/00128071\u2010200708030\u201000005"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22105077"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1067\u20102516(00)80008\u20103"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humpath.2017.12.002"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600\u20100560.1987.tb00122.x"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.5826\/dpc.0402a04"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1755\u2010148X.2010.00778.x"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10092320"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201014\u20102667"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0b013e31828b6be4"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clon.2018.10.004"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.144"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.21037\/jgo\u201020\u2010610"}],"container-title":["Journal of Cutaneous Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cup.14386","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cup.14386","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cup.14386","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T16:46:20Z","timestamp":1692549980000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cup.14386"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,8]]},"references-count":47,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6]]}},"alternative-id":["10.1111\/cup.14386"],"URL":"https:\/\/doi.org\/10.1111\/cup.14386","archive":["Portico"],"relation":{},"ISSN":["0303-6987","1600-0560"],"issn-type":[{"value":"0303-6987","type":"print"},{"value":"1600-0560","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,8]]},"assertion":[{"value":"2022-08-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-01-03","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}