How to handle borderline/precursor thyroid tumors in management of patients with thyroid nodules

Kennichi Kakudo


Thyroid carcinomas originating from follicular cells have the prognosis of heterogeneous diseases, but pathologists classify them all as malignant disease. Epidemiologists have issued a stern warning regarding over-diagnosis and overtreatment of patients with indolent thyroid tumors that cause no harm to the patients. Review of the literature revealed that there were several proposals of borderline/precursor tumors to some indolent thyroid carcinomas. Thyroid tumor of uncertain malignant potential (UMP) was first proposed by Williams for encapsulated follicular pattern thyroid tumors to solve problems due to observer variation. Rosai et al. proposed to rename papillary microcarcinoma (PMC) to papillary micro-tumor as the overwhelming majority of them are of no clinical significance. Liu et al. proposed well-differentiated tumor with uncertain behavior (WDT-UB) which covered WDT of UMP (WDT-UMP) and non-invasive encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC). The EFVPTC without invasion was renamed as non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) by an international panel of pathologists. A new prognostic classification of thyroid tumors was proposed by Kakudo et al., in which extremely low risk tumors were grouped in a borderline tumors category. The borderline/precursor thyroid tumors included encapsulated tumors [capsular invasion only follicular carcinoma, encapsulated papillary carcinoma without invasion, WDT-UMP and follicular tumor of UMP (FT-UMP)] and non-encapsulated tumors (PMC). The UMP and NIFTP were incorporated in the 4th edition WHO classification of thyroid tumors as a new tumor entity in chapter 2-2A: other encapsulated follicular patterned thyroid tumors. Their behavior codes were decided to be 1 (borderline or uncertain behavior), and not 0 (benign), 2 (in situ carcinoma) or 3 (malignant). These borderline/precursor thyroid tumors are indolent tumors biologically and should be treated more conservatively than as previously recommended for thyroid follicular cell carcinomas [total thyroidectomy (TTX) followed by radio-active iodine (RAI) treatment] by western clinical guidelines.