Monoclonal gamma-T-cell receptor rearrangement in vulvar lichen sclerosus and squamous cell carcinomas

Am J Pathol. 2002 Mar;160(3):1035-45. doi: 10.1016/s0002-9440(10)64924-3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / immunology*
  • Carcinoma, Squamous Cell / pathology
  • Female
  • Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor* / immunology
  • Humans
  • Immunohistochemistry
  • Lichen Sclerosus et Atrophicus / genetics
  • Lichen Sclerosus et Atrophicus / immunology*
  • Lichen Sclerosus et Atrophicus / pathology
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Polymerase Chain Reaction
  • Receptors, Antigen, T-Cell, gamma-delta / genetics*
  • Receptors, Antigen, T-Cell, gamma-delta / immunology
  • T-Lymphocyte Subsets / immunology*
  • Vulvar Neoplasms / genetics
  • Vulvar Neoplasms / immunology*
  • Vulvar Neoplasms / pathology


  • Receptors, Antigen, T-Cell, gamma-delta