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Immunohistochemical Staining of B7-H1 PD-L1 on Paraffin-embedded Slides of Pancreatic Adenocarcinoma Tissue
Published on: January 3, 2013
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.
Background:
Traditional systemic treatments for unresectable, recurrent, and/or advanced sebaceous carcinoma (SC) are ineffective. Tumoral immune microenvironment characterization is essential for considering immune checkpoint inhibitors as a treatment option.
Methods:
A total of 173 resected SCs were reviewed. Clinical information, lesion size, and location were collected. Microscopic examination documented histopathologic features and expression of immunohistochemical markers PD-L1 and CD8. PD-L1 percentage was assessed amongst tumor (PD-L1 + Tu) and immune infiltrating cells (PD-L1 + Inf). Each case was attributed a combined positive score (CPS) following Head and Neck squamous cell carcinoma recommendations. PD-L1 expression was evaluated according to clinicopathologic parameters. Human Papilloma Virus presence (HPV) was analyzed using PCR microarray scanning.
Results:
A therapeutically relevant CPS was seen in 51.4% of cases. Higher PD-L1 + Tu, PD-L1 + Inf, and CPSs were positively associated with greater lesion size and an extraocular location. No association was seen with patient age or gender. 9.2% of SCs showed PD-L1 + Tu ≥ 1, while 52.0% showed PD-L1 + Inf ≥ 1. A higher CD8 + T-lymphocyte density was significantly associated with a higher CPS, PD-L1 + Tu, and PD-L1 + Inf. Tumor-associated T-cell infiltrate's density was higher along tumor periphery. HPV-16, HPV-43, HPV-52, and HPV-66 were detected in 8.4% of SCs. There was no significant association between HPV status, PD-L1 expression, and CPS. A significant number of SCs express PD-L1 at therapeutic levels. Nevertheless, PD-L1 expression shows a higher intertumoral heterogeneity, in extraocular than in biologically distinct periocular cases.
Conclusion:
Our data support the need for large-scale prospective studies evaluating anti-PD-L1 immunotherapy mainly in extraocular SC treatment.
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.

