Structural alterations in tumor-draining lymph nodes before papillary thyroid carcinoma metastasis.

Abstract

The purpose of this study was to define and characterize the thyroid tumor-draining lymph nodes in genetically engineered mice harboring thyroid-specific expression of oncogenic Braf^V600E with and without Pten insufficiency. After intratumoral injection of methylene blue, the lymphatic drainage of the thyroid gland was visualized in real time. The thyroid gland/tumor was resected en bloc with the respiratory system for histological analysis. Although mice harboring Braf^V600E mutations were smaller in body size compared with their wild-type (WT) littermates, the size of their thyroid glands and deep cervical lymph nodes were significantly larger. Additionally, the tumor-draining lymph nodes showed increased and enlarged lymphatic sinuses that were distributed throughout the cortex and medulla. Tumor-reactive lymphadenopathy and histiocytosis, but no frank metastases, were observed in all mice harboring Braf^V600E mutations. The tumor-draining lymph nodes undergo significant structural alterations in immunocompetent mice, and this may represent a primer for papillary thyroid carcinoma (PTC) metastasis.