Highly Skewed Immunohistochemical αβ:γδ Ratios for T-Cell Receptors Can Be Detected in Reactive Duodenal Biopsies: A Potential Pitfall in the Diagnosis of T-Cell Lymphoma.

Abstract

T-cell receptors (TCRs) are classified as αβ- and γδ-chain groups. T-cell lymphoma (TCL) has been shown to express either αβ or γδ TCRs. Immunohistochemical stains for TCR-BetaF1 (TCR-BF1) (αβ) and TCR-delta (γδ) have been used clinically for classifying and diagnosing TCL in various organs. Outside of celiac disease, T-cell expression and distribution of TCR-BF1 and TCR-delta in the duodenum are largely unknown. To examine TCR-BF1 and TCR-delta expression in various duodenal pathologic processes. We collected 50 duodenal biopsy specimens with various inflammatory and infectious etiologies, such as celiac disease, inflammatory bowel disease, protein-losing enteropathy, chimeric antigen receptor T-cell (CAR-T)-related enteritis, and immune checkpoint inhibition. Five cases with no pathologic findings and 3 TCL cases were included for comparison. We performed immunohistochemistry for CD3, TCR-BF1, and TCR-delta on biopsy tissue. Low-power field estimates and manual high-power field counts were performed to assess TCR-BF1:TCR-delta ratios in T cells and the relative distribution of T cells in duodenal mucosa. In all non-TCL cases, TCR-BF1 T cells were more prevalent than TCR-delta T cells. Celiac disease showed less TCR-BF1:TCR-delta skewing than other conditions (mean, 1.97 versus 26.21-320). Expression of TCR-BF1 is more prevalent than TCR-delta in duodenal T cells in normal duodenum and across multiple nonneoplastic processes. Outside of celiac disease, the TCR-BF1:TCR-delta T-cell ratios can be highly skewed toward TCR-BF1 in such duodenal biopsy samples. As such, the assessment of TCR-BF1:TCR-delta T-cell ratios via immunohistochemistry can mistakenly infer T-cell monoclonality and thus should be interpreted with caution in the assessment of T-cell lymphoma.