The immune cell infiltrate in the microenvironment of vulvar Paget disease

Gynecol Oncol. 2018 Dec;151(3):453-459. doi: 10.1016/j.ygyno.2018.09.026. Epub 2018 Sep 28.

Abstract

Background: Non-invasive vulvar Paget disease (VPD) is a rare skin disorder mainly affecting elderly women. Recently, the immune modulator imiquimod was reported as an effective treatment option. Knowledge about the immune microenvironment of VPD is lacking.

Methods: This study investigates the basic characteristics of the immune infiltrate in VPD (n = 10); moreover the influence of imiquimod was studied (n = 6). Immunohistochemistry for CD4, CD8, CD14, CD20, CD56 and FoxP3 was performed. The infiltrates of VPD were compared to vulvar high-grade squamous cell intraepithelial lesions (HSIL) (n = 43), a HPV induced vulvar premalignancy with known response to imiquimod cream, and healthy controls (n = 30). Immune cell counts in samples taken before and after treatment were compared.

Results: The microenvironment in VPD differs from the healthy vulvar skin and vulvar HSIL. VPD is characterized by a decrease in immune cells in the epithelium and an abundant number of immune cells in the stroma, consisting predominantly of T cells. The intraepithelial CD8+/Foxp3+ ratio and number of CD56+ increased after imiquimod therapy, whereas the numbers of CD14+ cells decreased which may point to a treatment-induced type 1 immune response.

Conclusions: The epithelium in VPD contains less immune cells, but a dense stromal immune infiltrate. Changes in immune cell counts after immune modulation in relation to clinical responses should be further investigated.

Keywords: Imiquimod; Immune infiltrate; Vulvar Paget disease.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Humans
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Middle Aged
  • Paget Disease, Extramammary / drug therapy
  • Paget Disease, Extramammary / immunology*
  • Treatment Outcome
  • Tumor Microenvironment
  • Vulvar Neoplasms / drug therapy
  • Vulvar Neoplasms / immunology*