PD-L1 expression in sebaceous carcinomas

Maelle Saliba1, Muhammad Shaheen1, Rana El Hajj1

  • 1Department of Pathology and Laboratory Medicine, American University of Beirut Medical Center, Cairo Street, Beirut, Lebanon.

Abstract

Insights

Sebaceous carcinoma (SC) often resists traditional treatments. This study found PD-L1 expression in many SCs, suggesting potential for immune checkpoint inhibitors, especially in extraocular cases.

Area of Science:

  • Oncology
  • Immunology
  • Dermatopathology

Background:

  • Traditional systemic treatments for advanced sebaceous carcinoma (SC) demonstrate limited efficacy.
  • Characterizing the tumoral immune microenvironment is crucial for evaluating immune checkpoint inhibitors (ICIs) in SC treatment.

Purpose of the Study:

  • To investigate the expression of programmed death-ligand 1 (PD-L1) and CD8+ T-cells in sebaceous carcinoma.
  • To assess the correlation between PD-L1 expression, CD8+ T-cell infiltration, and clinicopathologic features, including Human Papilloma Virus (HPV) status.
  • To determine the potential of PD-L1-targeted immunotherapies for SC treatment.

Main Methods:

  • Retrospective analysis of 173 resected sebaceous carcinoma (SC) cases.
  • Immunohistochemical assessment of PD-L1 expression on tumor cells (PD-L1+Tu) and immune infiltrates (PD-L1+Inf), and CD8+ T-cell density.
  • Calculation of combined positive scores (CPS) for PD-L1, correlating with lesion size, location, age, gender, and HPV status.

Main Results:

  • A therapeutically relevant combined positive score (CPS) for PD-L1 was observed in 51.4% of cases.
  • Higher PD-L1 expression and CPS were associated with larger lesion size and extraocular location.
  • Increased CD8+ T-lymphocyte density correlated significantly with higher PD-L1 expression and CPS, with infiltrates denser at the tumor periphery. HPV was detected in 8.4% of cases without significant association with PD-L1 or CPS.
  • Significant PD-L1 expression was noted, but with higher heterogeneity in extraocular versus periocular SCs.

Conclusions:

  • A substantial proportion of sebaceous carcinomas express PD-L1 at levels potentially responsive to immunotherapy.
  • The findings support further investigation into anti-PD-L1 immunotherapies, particularly for extraocular SC.
  • Prospective studies are warranted to evaluate the efficacy of PD-L1-targeted treatments in specific SC subtypes.