{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T03:13:37Z","timestamp":1792034017242,"version":"4.4.0"},"reference-count":23,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cutan Pathol"],"published-print":{"date-parts":[[2023,12]]},"abstract":"Abstract<\/jats:title>\n \n Background<\/jats:title>\n \n Melanocytic tumors driven by\n MAP2K1<\/jats:italic>\n in\u2010frame deletions are among the most recently described class of melanocytic neoplasms. The reported range of diagnoses and associated genomic aberrations in these neoplasms is wide and includes melanomas, deep penetrating melanocytomas, and pigmented epithelioid melanocytoma. However, little is known about the characteristics of these tumors, especially in the absence of well\u2010known second molecular \u201chits.\u201d Moreover, despite their frequent spitzoid cytomorphology, their potential categorization among the Spitz tumors is debatable.\n <\/jats:p>\n <\/jats:sec>\n \n Materials and Methods<\/jats:title>\n \n We conducted a retrospective search through our molecular archives to identify sequenced melanocytic tumors with\n MAP2K1<\/jats:italic>\n in\u2010frame deletions. We reviewed the clinical and histomorphological features of these tumors and compared them to similar neoplasms reported to date. In addition, we performed single\u2010nucleotide polymorphism (SNP) array testing to identify structural chromosomal aberrations.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Of 27 sequenced tumors, 6 (22%) showed a pathogenic\n MAP2K1<\/jats:italic>\n in\u2010frame deletion (with or without insertion) and were included in this series. Five (83%) were females with lesions involving the upper limb. Histopathologically, all neoplasms were compounded with plaque\u2010like or wedge\u2010shaped silhouettes, spitzoid cytomorphology, and impaired cytologic maturation. All cases showed background actinic damage with sclerotic stroma replacing solar elastosis, variable pagetoid scatter, and occasional dermal mitotic figures (range 1\u20132\/mm\n 2<\/jats:sup>\n ). Five cases (83%) had a small component of nevic\u2010looking melanocytes. Biologically, these tumors likely fall within the spectrum of unusual nevi. Five cases (83%) had a relatively high mutational burden and four (67%) showed an ultraviolet radiation signature. Four cases (67%) showed in\u2010frame deletion involving the p.I103_K104del locus while two cases (33%) showed in\u2010frame deletion involving the p.Q58_E62del locus. SNP array testing showed structural abnormalities ranging from 1 to 5 per case. Five of these cases showed a gain of chromosome 15 spanning the\n MAP2K1<\/jats:italic>\n gene locus.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion and Conclusion<\/jats:title>\n \n Melanocytic tumors with\n MAP2K1<\/jats:italic>\n in\u2010frame deletion could represent another spectrum of melanocytic tumors with close genotypic\u2013phenotypic correlation. They are largely characterized by a spectrum that encompasses desmoplastic Spitz nevus as shown in our series and Spitz and Clark nevus as shown by others. Evolutionary, they share many similarities with tumors with\n BRAF<\/jats:italic>\n V600E mutations, suggesting they are better classified along the conventional pathway rather than the Spitz pathway despite the frequent spitzoid morphology.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cup.14502","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T06:10:12Z","timestamp":1691734212000},"page":"1083-1093","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["MAP2K1<\/i>\n \u2010mutated melanocytic tumors have reproducible histopathologic features and share similarities with melanocytic tumors with\n BRAF<\/i>\n V600E<\/scp>\n mutations"],"prefix":"10.1111","volume":"50","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3776-5053","authenticated-orcid":false,"given":"Ahmed K.","family":"Alomari","sequence":"first","affiliation":[{"name":"Department of Pathology Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Dermatology Indiana University School of Medicine Indianapolis Indiana 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 University of Michigan School of Medicine Ann Arbor Michigan USA"},{"name":"Department of Dermatology University of Michigan School of Medicine Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleodor A.","family":"Andea","sequence":"additional","affiliation":[{"name":"Department of Pathology University of Michigan School of Medicine Ann Arbor Michigan USA"},{"name":"Department of Dermatology University of Michigan School of Medicine Ann Arbor Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon J.","family":"Warren","sequence":"additional","affiliation":[{"name":"Department of Pathology Indiana University School of Medicine Indianapolis Indiana USA"},{"name":"Department of Dermatology Indiana University School of Medicine Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010pathol\u2010012513\u2010104658"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11122041"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000001840"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41379\u2010020\u20100581\u20105"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201000758\u20103"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1097\/DAD.0000000000001795"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1097\/PAS.0000000000001195"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00428\u2010020\u201002940\u20103"},{"key":"e_1_2_9_10_1","volume-title":"WHO Classification of Skin 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