Specific intraepithelial localization of mast cells in differentiated vulvar intraepithelial neoplasia and its possible contribution to vulvar squamous cell carcinoma development.
OBJECTIVE
The aetiology of vulvar squamous cell carcinomas (SCC) that are not causally associated with high-risk human papillomavirus remains largely elusive. The aim of this study was to analyse the inflammatory response in its presumed precursor lesions, lichen sclerosus (LS) and differentiated vulvar intraepithelial neoplasia (dVIN), and provide evidence that dVIN is a likely precursor of vulvar SCC.


RESULTS
Immunohistochemical analyses for CD4+, CD8+, CD20+, CD68+, S100+ and tryptase-positive immune cells were performed and quantified in LS (n = 7), dVIN (n = 19), SCC (n = 11), and normal vulvar tissue (n = 8). The subepithelial inflammatory response in dVIN and SCC was comparable, but absent in LS. Abundant intraepithelial mast cells were observed in dVIN only, and confirmed by electron microscopy, toluidine blue staining and cKIT expression. Adjacent keratinocytes displayed increased proliferation as determined by MIB-1 positivity. Electron microscopy revealed intraepithelial mast cell degranulation. Intraepithelial mast cells were not or infrequently observed in vulvar hyperplasia (n = 13), condylomata acuminata (n = 5), keratinocytic intraepidermal neoplasia of sun-exposed skin (n = 15), epidermal hyperplasia of head and neck (n = 12), and psoriasis (n = 3).


CONCLUSIONS
These data indicate that dVIN can be recognized by intraepithelial mast cells and that they might promote the progression of dVIN to SCC.
van de Nieuwenhof
Hedwig P
HP
Department of Obstetrics and Gynaecology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
Hebeda
Konny M
KM
Bulten
Johan
J
Otte-Holler
Irene
I
Massuger
Leon F A G
LF
de Hullu
Joanne A
JA
van Kempen
Leon C L T
LC
D014408:Biomarkers, Tumor / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology; D002454:Cell Differentiation; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008407:Mast Cells / Q000166:cytology* / Q000276:immunology / Q000648:ultrastructure; D011230:Precancerous Conditions / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure; D014846:Vulvar Neoplasms / Q000276:immunology* / Q000473:pathology / Q000648:ultrastructure
D014408:Biomarkers, Tumor