Macrofollicular Variant of Papillary Thyroid Cancer: A Clinicopathologic and Molecular Review

Abstract

Context: The macrofollicular variant of papillary thyroid carcinoma (MFVPTC) is a rare entity; this variant is a well-differentiated tumor with predominance of macrofollicles lined by cells showing the nuclear features of papillary thyroid carcinoma (PTC). It is claimed to be clinically nonaggressive with a low incidence of metastasis. It is very important to correctly recognize this entity, it might clinically represents a dangerous source of diagnostic error, since it can be easily misinterpreted as a benign disease such as goiter, macrofollicular adenoma, Grave's disease, or hyperplastic nodule. The objective of this article was to provide an update overview of the clinical, cytologic, histologic, and immunohistochemistry (IHC) as well as the molecular characteristics of MFVPTC. Evidence Acquisition: This rare subtype of papillary thyroid carcinoma was first described in 1991. We performed a comprehensive online literature review since its first description up to this date. Results: MFVPTC is a rare variant of papillary thyroid carcinoma that can be extremely difficult to diagnose preoperatively; however, IHC stains and molecular studies might help to differentiate this neoplasm from other thyroid entities. Conclusions: This review highlights the diagnostic difficulties that both clinicians and pathologists face when dealing with follicular variants of papillary thyroid carcinoma. While IHC and gene mutation studies are helpful in narrowing down the differential diagnosis, these techniques need further improvements in order to increase their diagnostic accuracy.