Consumption of the epidermis: a suggested precursor of ulceration associated with increased proliferation of melanoma cells.
It has recently been demonstrated that the extent of ulceration and the presence of epidermal involvement that theoretically precede ulceration (consumption of epidermis, COE) or seen subsequent to inflammation (reactive epidermal hyperplasia or re-epithelialization) allowed better prognostic stratification of ulcerated melanoma. Understanding why these histopathologic markers have prognostic potential is important, not least because accurate consensual assessment of ulceration lies at the root of proper staging and clinical management. The authors therefore performed immunohistochemical analyses of tumor cell proliferation (Melan-A/Ki67) and infiltration of inflammatory cells (CD66b neutrophils and CD163 macrophages) to better understand the biology of the epidermal changes described. Tumors with a COE configuration showed 37% (95% CI: 4-54, P = 0.0046) increased tumor cell proliferation compared with tumors of normal epidermal configuration. COE is therefore suggested a precursor of ulceration associated with increased proliferation of melanoma cells. There was no observed correlation between COE and an increased inflammatory response (CD163 macrophages or CD66b neutrophils), which supports that the proliferation drive is noninflammatory. In contrast, the presence of re-epithelialization and/or reactive epidermal hyperplasia demonstrated an 18% (95% CI: 6-53, P = 0.0021) increased density of neutrophils compared with tumor with no evidence of these possibly prolonged late-stage or resolved ulcerations. These results further support the relevance of including these epidermal changes into the definition of ulceration and to define ulceration of a primary melanoma as loss of epidermis with evidence of a host response (infiltration of neutrophils or fibrin deposition) and thinning, effacement, or reactive hyperplasia of the surrounding epidermis.
Departments of *Oncology, and †Pathology, Aarhus University Hospital, Aarhus, Denmark; ‡Plastic Surgery Research Unit, Department of Plastic Surgery, Aarhus University Hospital, Aarhus, Denmark; §The Finsens Laboratory, Rigshospital, and Biotech and Research Innovation Center (BRIC), University of Copenhagen, Copenhagen, Denmark; ¶Department of Oncology, Odense University Hospital, Odense, Denmark; ‖Department of Clinical Biochemistry, Aarhus University Hospital, Aarhus, Denmark; and **Department of Pathology, Herlev Hospital, Herlev, Denmark.
Louise M
LM
Bønnelykke-Behrndtz
Henrik
H
Schmidt
Tine E
TE
Damsgaard
Ib Jarle
IJ
Christensen
Lars
L
Bastholt
Holger J
HJ
Møller
Peter
P
Nørgaard
Torben
T
Steiniche
D049109:Cell Proliferation; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D008545:Melanoma / Q000276:immunology / Q000473:pathology*; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000276:immunology / Q000473:pathology*; D012883:Skin Ulcer / Q000276:immunology / Q000473:pathology*