Monoclonal gamma-T-cell receptor rearrangement in vulvar lichen sclerosus and squamous cell carcinomas.
Risk factors for vulvar squamous cell carcinoma (SCC) are human papilloma virus (HPV) infections and lichen sclerosus (LS). The significance of monoclonal gamma-T-cell receptor (gamma-TCR) rearrangement in the lymphoid infiltrate of LS and the consequence for vulvar carcinogenesis is unknown. One hundred sixty-one biopsies of vulvar LS and SCC, with and without LS, were examined for monoclonal gamma-TCR rearrangement and HPV16 expression, and for the expression of B- and T-cell markers and fascin. Monoclonal gamma-TCR rearrangement was identified in 8 of 17 patients with LS and 11 of 21 patients with SCC arising in LS with only occasional HPV16 DNA detection. None of the 19 SCC without LS showed monoclonal gamma-TCR rearrangement, but 14 of 19 patients had strong HPV16 detection. The lichenoid infiltrate of LS with germline configuration consisted predominantly of T cells (CD8 > CD4), along with numerous B cells. However, in biopsies with monoclonally rearranged gamma-TCR, CD4-positive T cells dominated along with B cells and fascin-positive cells in the lichenoid infiltrate and in deeply located lymphocyte aggregates (LAs). These LAs additionally contained fascin-positive dendritic cells with only individual CD8, CD57, and granzyme-positive cells. LAs in biopsies with germline configuration demonstrated numerous T cells (CD8 >CD4), but only single peripheral B cells, CD57, and fascin-positive lymphocytes. Our data suggest that monoclonal gamma-TCR rearrangement is characteristic for and limited to LS and SCC arising in LS, raising the question for a LS-associated antigen. We interpret B cells, CD4-positive T cells, and fascin-expressing dendritic cells within LS as a cellular immune response to antigen or proliferating T-cell clones. The resulting local immune dysregulation in LS may provide a permissive environment for the development of a SCC.
Regauer
Sigrid
S
Institute of Pathology and Departmentof Obstetrics and Gynecology, University of Graz, Graz, Austria. sigrid.regauer@kfunigraz.ac.at
Reich
Olaf
O
Beham-Schmid
Christine
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D015334:Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D018459:Lichen Sclerosus et Atrophicus / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000235:genetics* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014846:Vulvar Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology
D016692:Receptors, Antigen, T-Cell, gamma-delta