title: 5-Hydroxymethylcytosine expression in metastatic melanoma versus nodal nevus in sentinel lymph node biopsies.
abstract: Sentinel lymph node biopsies are conducted to stage patients with newly diagnosed melanomas that have histopathological attributes conferring defined levels of metastatic potential. Because benign nevic cells may also form 'deposits' in lymph nodes (nodal nevus), the pathological evaluation for metastatic melanoma within sentinel lymph nodes can be challenging. Twenty-eight sentinel lymph node biopsy cases containing either metastatic melanoma (N=18) or nodal nevi (N=10) were retrieved from the archives of the Brigham and Women's Hospital, Department of Pathology (2011-2014). In addition, two sentinel lymph node cases that were favored to represent metastatic disease but whose histopathological features were viewed as equivocal, with melanoma favored, were also included. Dual labeling for the melanocyte lineage marker, MART-1, and the epigenetic marker, 5-hydroxymethylcytosine, a functionally significant indicator that has been shown to distinguish benign nevi from melanoma, was performed on all cases using immunohistochemistry and/or direct immunofluorescence. All (18 of 18) metastatic melanoma cases showed complete loss of 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells, and all (10 of 10) nodal nevus cases demonstrated 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells. In addition, 5-hydroxymethylcytosine staining confirmed the favored diagnoses of metastatic melanoma in the two 'equivocal' cases. Thus, 5-hydroxymethylcytosine may be a useful adjunctive marker to distinguish between benign nodal nevi and metastatic melanoma during the evaluation of sentinel lymph node biopsies for metastatic melanoma.
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Jonathan J
authors.initials: JJ
authors.lastname: Lee
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Granter
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Alvaro C
authors.initials: AC
authors.lastname: Laga
authors.affiliation: 1] Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA [2] Department of Dermatology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Arturo P
authors.initials: AP
authors.lastname: Saavedra
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhan
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Weimin
authors.identifier: 0000000343187154
authors.initials: W
authors.lastname: Guo
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Shuyun
authors.initials: S
authors.lastname: Xu
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: George F
authors.initials: GF
authors.lastname: Murphy
authors.affiliation: Program in Dermatopathology, Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Christine G
authors.initials: CG
authors.lastname: Lian
mesh_terms: D044503:5-Methylcytosine / Q000031:analogs & derivatives; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D003596:Cytosine / Q000031:analogs & derivatives* / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis / Q000175:diagnosis*; D008297:Male; D008545:Melanoma / Q000175:diagnosis*; D008875:Middle Aged; D009506:Nevus / Q000175:diagnosis*; D021701:Sentinel Lymph Node Biopsy; D012878:Skin Neoplasms / Q000175:diagnosis*
chemical_list: D014408:Biomarkers, Tumor; C011865:5-hydroxymethylcytosine; D044503:5-Methylcytosine; D003596:Cytosine
references.citation: Lab Invest. 2012 Mar;92(3):362-70
references.pmid: 22184093
references.citation: Cell. 2014 Jan 16;156(1-2):45-68
references.pmid: 24439369
references.citation: Am J Clin Pathol. 2004 Jan;121(1):58-63
references.pmid: 14750241
references.citation: J Cutan Pathol. 2013 Sep;40(9):796-800
references.pmid: 23808580
references.citation: Cell. 2012 Sep 14;150(6):1135-46
references.pmid: 22980977
references.citation: Am J Surg Pathol. 2007 Aug;31(8):1175-80
references.pmid: 17667539
references.citation: Oncotarget. 2011 Aug;2(8):627-37
references.pmid: 21896958
references.citation: J Dermatol Sci. 2014 Feb;73(2):161-3
references.pmid: 24169492
references.citation: Am J Clin Pathol. 2013 May;139(5):566-73
references.pmid: 23596107
references.citation: J Biomed Nanotechnol. 2013 Sep;9(9):1607-16
references.pmid: 23980508
references.citation: PLoS One. 2012;7(7):e41036
references.pmid: 22829908
references.citation: PLoS One. 2013 May 09;8(5):e62828
references.pmid: 23671639
references.citation: Virchows Arch. 2003 Dec;443(6):745-51
references.pmid: 14576937
references.citation: J Cutan Pathol. 2011 May;38(5):394-400
references.pmid: 21385199
references.citation: EMBO Rep. 2011 Dec 23;13(1):28-35
references.pmid: 22157888
references.citation: Am J Surg Pathol. 1996 Jul;20(7):834-40
references.pmid: 8669531
references.citation: J Natl Compr Canc Netw. 2013 Apr 1;11(4):395-407
references.pmid: 23584343
references.citation: Mod Pathol. 2014 Jul;27(7):936-44
references.pmid: 24390216
references.citation: Mod Pathol. 2013 Jan;26(1):44-53
references.pmid: 22899289
references.citation: Am J Dermatopathol. 2002 Feb;24(1):1-5
references.pmid: 11803273
references.citation: Am J Surg Pathol. 2010 Feb;34(2):231-7
references.pmid: 20087158
references.citation: Exp Dermatol. 2011 Apr;20(4):339-45
references.pmid: 21410764
references.citation: PLoS Med. 2014 Feb 18;11(2):e1001604
references.pmid: 24558354