{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T15:24:52Z","timestamp":1785684292082,"version":"3.56.0"},"reference-count":19,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,1,31]],"date-time":"2019-01-31T00:00:00Z","timestamp":1548892800000},"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":[[2019,4]]},"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Distinguishing benign nodal nevus from metastatic melanoma can be diagnostically challenging, with important clinical consequences. Recently, the loss of epigenetic marker, 5\u2010hydroxymethylcytosine (5\u2010hmC) expression by immunohistochemistry has been found in melanomas and atypical melanocytic neoplasms.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>About 41 metastatic melanomas and 20 nodal nevi were retrieved. Nuclear 5\u2010hmC (brown) and cytoplasmic Melan\u2010A Red (red) double immunohistochemical staining was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Total or partial loss of nuclear expression of 5\u2010hmC was noted in 40\/41 metastatic melanomas; these tumor cells were strongly positive for Melan\u2010A Red, except in one case of desmoplastic melanoma. All cases of nodal nevus showed uniformly retained nuclear expression of 5\u2010hmC accompanied by strong Melan\u2010A Red cytoplasmic staining. In two cases containing both nodal nevus and metastatic melanoma, all tumor cells were positive for Melan\u2010A Red, but a nuclear expression of 5\u2010hmC was selectively absent only in the melanoma tumor cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Dual 5\u2010hmC\/Melan\u2010A Red immunohistochemistry is highly specific in distinguishing nodal nevus from metastatic melanoma. Our protocol for brown and red chromogens used in this study provides excellent color contrast and is easy to interpret. Furthermore, this dual staining method allows the preservation of limited tumor tissue, which could be used for potential molecular studies.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cup.13412","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T09:53:53Z","timestamp":1547200433000},"page":"261-266","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Diagnostic utility of dual 5\u2010hydroxymethylcytosine\/Melan\u2010A immunohistochemistry in differentiating nodal nevus from metastatic melanoma: An effective first\u2010line test for the workup of sentinel lymph node specimen"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0324-7557","authenticated-orcid":false,"given":"Andrew B.","family":"Siref","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine Cedars\u2010Sinai Medical Center  Los Angeles 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