{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T09:07:50Z","timestamp":1783933670229,"version":"3.55.0"},"reference-count":34,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T00:00:00Z","timestamp":1783900800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Dermatopathology"],"abstract":"<jats:p>Histopathologic melanoma diagnosis extends beyond melanocytic cytology to encompass non-melanocytic features: solar elastosis patterns, stromal regression, adnexal relationships, epidermal reaction patterns, and the host inflammatory response. These \u201cold school\u201d low-power clues are particularly valuable on sun-damaged skin, where benign nevi, reactive melanocytic hyperplasia, and melanoma in situ share overlapping features. Quantitative data support two elastosis-based signs: the \u201cumbrella sign\u201d (reduced elastosis beneath the lesion\u2019s central third; PPV (Positive Predictive Value) for nevus, 96%, and NPV (Negative predictive Value) for melanoma, 74%; calculated from raw cohort data) and the \u201cpurple fiber sign\u201d (100% specificity, 30% sensitivity for nevus), both from a cohort of 81 actinically damaged lesions. Regression\u2014identified by compressed elastic layers displaced to the reticular dermis, fibrosis, melanophages, and inflammation\u2014aids diagnosis but complicates distinction from surgical scar. The maturation state of tertiary lymphoid structures (TLSs) within the regression zone, ranging from immunosuppressive immature aggregates to anti-tumoral mature structures with germinal centers, may explain the variable prognostic significance of histologic regression. Epidermal hyperplasia over thick melanomas reflects angiogenesis-related changes, while effacement is a practical red flag in spitzoid lesions. Ancillary tests are most productive when morphology has already framed the differential. These non-melanocytic clues remain indispensable as the foundation for rational ancillary testing.<\/jats:p>","DOI":"10.3390\/dermatopathology13030032","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T08:05:31Z","timestamp":1783929931000},"page":"32","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non-Melanocytic Histopathological Clues for Melanoma Diagnosis: A Practical Review of Solar Elastosis, Stromal Regression, and Epidermal Reaction Patterns. Do Old-School Clues Still Matter?"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8084-4307","authenticated-orcid":false,"given":"Michail","family":"Sofopoulos","sequence":"first","affiliation":[{"name":"Department of Histopathology, Andreas Syngros Hospital of Cutaneous and Venereal Diseases, 16121 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Massi, G., and LeBoit, P.E. (2014). Histological Diagnosis of Nevi and Melanoma, Springer. [2nd ed.].","DOI":"10.1007\/978-3-642-37311-4"},{"key":"ref_2","unstructured":"Ackerman, A.B., Jacobson, M., and Vitale, P. (1991). 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