Characterizing parathyroid carcinomas and atypical neoplasms based on the expression of programmed death-ligand 1 expression and the presence of tumor-infiltrating lymphocytes and macrophages

Background: Four distinct tumor microenvironments have been proposed based on the expression of programmed death-ligand 1 and the presence of tumor-infiltrating lymphocytes: immunotype I (adaptive resistance, tumor-infiltrating lymphocytes+ and programmed death-ligand 1+); immunotype II (immunologic ignorance, tumor-infiltrating lymphocytes– and programmed death-ligand 1–); immunotype III (intrinsic induction; tumor-infiltrating lymphocytes– and programmed death-ligand 1+); and immunotype IV (tolerance, tumor-infiltrating lymphocytes+ and programmed death-ligand 1–). These subtypes may predict tumor response to immunotherapy. We hypothesized that parathyroid neoplasms may have tumor immunogenic expression that can later be used to guide treatment. Methods: We assessed retrospectively the immunohistochemical expression of programmed death-ligand 1 and the presence of tumor-infiltrating lymphocytes (CD3+ and CD8+) and macrophages (CD68+) in parathyroid carcinomas and in atypical parathyroid neoplasms treated at the M. D. Anderson Cancer Center from 1996 to 2016. Using intratumoral digital image analysis, the programmed death-ligand 1 H score was calculated with a standardized formula for predominant staining. The tumor-infiltrating lymphocytes per square millimeter of intratumoral areas were quantified. Results: Within 30 specimens (17 parathyroid carcinomas and 13 atypical parathyroid neoplasms), there was no difference in the median programmed death-ligand 1 H score between the two groups (P =.57). Four parathyroid carcinoma cases had programmed death-ligand 1 H scores ≥1 associated with CD3+ and CD8+ tumor cell density; 2 of them had distant metastases. Parathyroid carcinomas had a lesser median CD3+ density (P =.04) and a lesser median CD8+ density (P =.07) than did atypical parathyroid neoplasms. Median CD68+ density did not differ between groups (P =.22). Conclusion: Parathyroid carcinomas tended to have immune-ignorant and immune-tolerant microenvironments within the neoplasm (immunotypes II and IV). Of the parathyroid carcinoma microenvironments, 17 had patterns of programmed death-ligand 1 and tumor-infiltrating lymphocytes expression (immunotype I), suggesting possible benefit from immunotherapy. In addition, both parathyroid carcinomas and parathyroid neoplasms expressed CD68+. Further exploration of these potential biomarkers as a target in cancer therapies is needed.