Real-World Experience With TRBC1 Immunohistochemistry Across Cutaneous T-Cell Lymphoma Subtypes:A Large Cohort Study

Area of Science:

• Immunohistochemistry
• Dermatopathology
• Oncology

Background:

• T-cell receptor beta-chain constant region 1 (TRBC1) immunohistochemistry (IHC) is used to identify clonal αβ T-cell populations.
• Its real-world performance in cutaneous T-cell lymphoma (CTCL) and related infiltrates is not well-characterized.

Purpose of the Study:

• To evaluate the diagnostic performance of TRBC1 IHC in CTCL and related conditions.
• To compare TRBC1 IHC with T-cell receptor (TCR) clonality testing.
• To assess the utility of digital image analysis for TRBC1 quantification.

Main Methods:

• A cohort of 665 biopsies with paired TCR clonality testing was analyzed.
• TRBC1 IHC was performed and scored manually by three readers.
• Digital image analysis (QuPath) was used for observer-independent quantification.
• Clinicopathological classification included mycosis fungoides (MF), MF/Sézary syndrome, and reactive conditions.

Main Results:

• TRBC1 IHC demonstrated 85.8% sensitivity and 79.8% specificity at the <15%/>85% threshold.
• Monotypic TRBC1 expression predicted neoplasia, with increasing odds for higher-grade MF and CTCL.
• Polytypic TRBC1 expression strongly associated with reactive disease.
• Digital quantification agreed with manual reads and tracked molecular clonality.
• Discordance analysis revealed a false-negative bias in MF-Patch and a false-positive bias in reactive biopsies.

Conclusions:

• TRBC1 IHC is a valuable tool for diagnosing CTCL, showing good sensitivity and specificity.
• A TRBC1-first approach, reserving reflex TCR testing for ambiguous cases, can optimize diagnostic accuracy and reduce costs.
• Digital image analysis provides a reliable method for TRBC1 quantification, supporting observer-independent assessment.