Solid Thyroid Follicular Nodules with Longitudinal Nuclear Grooves: Clinicopathologic, Immunohistochemical, and Molecular Genetic Study of 18 Cases

Abstract

Context.—Follicular thyroid nodules can be a source of diagnostic difficulties, particularly when they display atypical features commonly associated with malignancy, such as nuclear grooves. Objective.—To differentiate lesions with atypical features from similar-appearing benign and malignant lesions. Design.—Eighteen cases of atypical follicular thyroid nodules characterized by a solid growth pattern and prominent longitudinal nuclear grooves were studied and examined for clinicopathologic characteristics. Results.—The lesions occurred in 16 women and 2 men aged 36 to 88 years and measured from 0.2 to 1.5 cm. The tumors were well circumscribed and noninvasive, and histologically characterized by a predominantly solid growth pattern with rare scattered follicles or a combination of solid growth pattern with minor follicular areas. A striking feature seen in all cases was the occurrence of longitudinal nuclear grooves. Immunohistochemical stains showed negativity for cytokeratin 19 (CK19) and HBME-1 in 8 cases; in the other 10, there was focal positivity for HBME-1 in 4 cases and diffuse positivity in 6. All cases were negative for galectin-3 and for CK19, with the exception of 1 case, which was CK19+/HBME-1-. Next-generation sequencing of 16 cases with a 161-gene panel detected 14 single nucleotide variants in 12 cases, predominantly NRAS and HRAS mutations. Clinical follow-up ranging from 18 to 72 months (median, 43.7 months) did not disclose any evidence of recurrence or metastases. Conclusions.—We interpret these lesions as low-grade, indolent follicular proliferations that need to be distinguished from papillary thyroid carcinoma, follicular adenoma, and noninvasive follicular thyroid neoplasms with papillary-like nuclear features.