Endocrine Abstracts

Introduction: Medullary thyroid carcinoma (MTC) accounts for up to 10% of thyroid cancers. Many of these patients present a syndromic phenotype, with multiple endocrine neoplasias, termed multiple endocrine neoplasia type 2 (MEN2), a genetic condition characterized by mutations in the RET gene. Despite many advances in the molecular biology of this disease, little is known about the immunopathology of the MTC tumor microenvironment.

Objective: The overall objective of this study was to investigate the immunophenotypic characteristics of infiltrating leukocytes in tumors of patients with MEN2 and MTC, correlating them with clinical-laboratory and anatomopathological data.

Methods: Twenty-six patients with histopathologically confirmed MTC were investigated. Patient tissues were reviewed to select the most representative areas for the construction of a tissue microarray (TMA). Immune cell markers, including tumor-associated macrophages (CD68) and subsets of tumor-infiltrating lymphocytes (CD3, CD4, CD8, CD20), as well as markers of immune activation (Granzyme-B, PD-L1), were analyzed. The presence of concomitant chronic lymphocytic thyroiditis was assessed by pathological scrutiny in normal parenchyma adjacent to the tumor. Statistical analysis was performed to investigate associations between immune markers and patient clinical characteristics.

Results: Three patients with MTC presented concomitant chronic lymphocytic thyroiditis. These patients showed a tendency toward a more aggressive clinical presentation with larger tumors (P = 0.07) and lymph node metastases in lateral compartments (P = 0.03). Our results demonstrated more frequent immune cell infiltration in malignant tissues compared to adjacent thyroid tissue. There was a significant association between PD-L1 and CD68 expression in various regions, suggesting a possible role of tumor-associated macrophages in the MTC immune microenvironment. The absence of CD68 cells was associated with the absence of thyroiditis in various tissue regions, indicating a possible immune escape mechanism of MTC. However, no significant associations were found between the presence of immune markers and the clinical status of patients during follow-up.

Conclusions: This study provides insights into the immunological processes in the MTC tumor microenvironment, highlighting the possible influence of tumor-associated macrophages and their relation to thyroiditis presence. However, further research is needed to fully understand the role of the immune system in MTC and its clinical relevance for patient prognosis and treatment.