Encapsulated thyroid neoplasms with nuclear features of papillary carcinoma: Histological and molecular evidence that subtypes with variable extension of papillary formation may still behave favorably

Since the definition of “noninvasive follicular thyroid neoplasm with papillary-like nuclear features”, the evaluation of the tumor capsule and the architectural pattern in encapsulated neoplasms with nuclear features of papillary carcinoma has gained greater importance in the pathologist's practice. The present study aims to expand the concept of non-invasive encapsulated thyroid lesions to neoplasms with variable extent of papillae formation, focusing mainly on histological and molecular characteristics with prognostic significance. We retrospectively evaluated the anatomopathological variables of 103 encapsulated thyroid neoplasms with nuclear features of papillary carcinoma. We investigated the presence of mutations in the BRAF and NRAS genes using Sanger Sequencing in 81 cases. Tumor capsule infiltration was the histological feature associated with vascular invasion (p = 0.050) and lymph node metastasis (p = 0.024), being more frequent in tumors with papillary architecture and thick capsule. The mutation in the BRAF gene was identified mainly in tumors with a higher percentage of papillae formation (p = 0.008⁻³), in those with infiltration of the tumor capsule (p = 0.004) and in most neoplasms smaller than or equal to 10 mm (p = 0.006⁻¹). Tumors without mutations in the BRAF gene showed a lower frequency of lymph node metastasis (p = 0.027). Tumor capsule infiltration proved to be a prerequisite for vascular invasion and lymph node metastasis, and the papillary architectural pattern of the neoplasm presented as the main anatomopathological characteristic associated with its occurrence. Encapsulated neoplasms with papillae formation without BRAF mutation, with no evidence of vascular invasion and without tumor capsule infiltration may represent a subtype with a favorable prognosis.