Clinicopathologic and microenvironmental analysis of primary cutaneous CD30-positive lymphoproliferative disorders: a 26 year experience from an academic medical center in Brazil

Diagn Pathol. 2019 Oct 22;14(1):115. doi: 10.1186/s13000-019-0900-7.

Abstract

Background: Primary cutaneous CD30+ lymphoproliferative disorders (pc-CD30-LPD) are a group of clonal T cell lymphoproliferative disorders that despite very similar tumor histology follow different and characteristic clinical courses, suggesting a homeostatic role of the tumor microenvironment. Little is known about tumor microenvironment and there is almost no literature about PD-L1 expression in pc-CD30-LPD.

Methods: This retrospective study presents a fully clinicopathologically characterized series of pc-CD30-LPDs from an academic medical center in Brazil, including 8 lymphomatoid papulomatosis (LyP), 9 primary cutaneous anaplastic large cell lymphoma (pcALCL) and 4 borderline lesions. All the cases were scored for FOXP3+ regulatory T-cells (Treg) and CD8+ cytotoxic tumor infiltrating lymphocytes (TIL) densities, as well as PD-L1 expression in tumor cells and tissue associated macrophages. The CD8+/FOXP3+ ratio was also evaluated.

Results: Among the 21 cases of pc-CD30-LPD, PD-L1 expression is frequent in both tumor cells and tissue associated macrophages in pc-CD30-LPD across categories, suggesting that the PD-L1 axis may be a common feature of pc-CD30-LPDs. While reactive T cell infiltrates vary widely from case to case, a common feature across pc-CD30-LPDs is higher density of CD8 than FOXP3 + T cells. The distribution of T cells within the lesions however differed between LyP and pcALCL: we found that LyP lesions tend to be permeated by CD8+ and FOXP3+ T cells, whereas pcALCL tend to be surrounded by a rim of CD8+ TIL and FOXP3+ Tregs with relatively lower density infiltrates in the center of the lesion.

Conclusions: LyP has a trend to have denser immune cells throughout the lesion, with higher FOXP3+ Treg and CD8+ TIL in the center than the edge comparing with pcALCL. PD-L1+ is frequent in tumor cells and tissue associated macrophages in pc-CD30-LPD. The differential distribution of CD8+ and FOXP3+ TILs in LyP as compared to pcALCL could provide a clue to the relapsing/remitting course of LyP as compared to the less frequent spontaneous regression of pcALCL.

Keywords: CD8; Cutaneous lymphoma; FOXP3; Immunohistochemistry; Primary cutaneous CD30+ T-cell c; Programmed death ligand 1; Regulatory T-cell; Tumor microenvironment.

MeSH terms

  • Academic Medical Centers
  • Adult
  • Aged
  • Brazil
  • Female
  • Humans
  • Ki-1 Antigen / analysis
  • Ki-1 Antigen / immunology*
  • Lymphocytes, Tumor-Infiltrating / pathology
  • Lymphoma, T-Cell, Peripheral / pathology
  • Lymphoproliferative Disorders / diagnosis
  • Lymphoproliferative Disorders / pathology*
  • Male
  • Middle Aged
  • Skin Diseases / diagnosis
  • Skin Diseases / pathology*
  • Skin Neoplasms / diagnosis
  • Skin Neoplasms / pathology*
  • Tumor Microenvironment / physiology*

Substances

  • Ki-1 Antigen