The 5th edition of WHO classification of tumors of endocrine organs: changes in the diagnosis of follicular-derived thyroid carcinoma

Abstract

The 5^th edition of the World Health Organization (WHO) classification of endocrine tumors was released in 2022. Several novelties have been introduced concerning the nomenclature and histopathological diagnosis of follicular-derived thyroid neoplasms. Tumor types have been sharply classified according to prognostic risk categories into benign tumors, low-risk neoplasms and malignant neoplasms. A grading system for differentiated thyroid carcinomas has been implemented with the aim of improving the stratification of tumors. Particular attention has been paid to the molecular profile of well-differentiated histotypes. In this review, the main changes introduced by the latest edition of the WHO system are presented. The practical effects on the diagnostic pathology of thyroid tumors, along with the clinical implications expected with the new classification scheme, are critically discussed.

Keywords: Diagnostic pathology; Endocrine pathology; Follicular-derived thyroid cancer; WHO classification system.

Fig. 1

The World Health Organization classification of follicular cell-derived thyroid neoplasms, 5^th edition. Thyroid tumors have been subdivided into benign tumors, low-risk neoplasms and malignant neoplasms. Red squares indicate the newly introduced subtypes. Abbreviations: NIFTP noninvasive follicular thyroid neoplasm with papillary-like nuclear features, WDT-UMP well-differentiated tumor of uncertain malignant potential, IEFV-PTC invasive encapsulated follicular variant papillary thyroid carcinoma, PTC papillary thyroid carcinoma, FTC follicular thyroid carcinoma, OCA oncocytic thyroid carcinoma, DHGTC differentiated high-grade thyroid carcinoma, PDTC poorly differentiated thyroid carcinoma, ATC anaplastic thyroid carcinoma

Fig. 2

Representative histopathologic images of invasive encapsulated follicular variant PTC (a, b) and infiltrative follicular subtype of PTC (c, d) (haematoxylin/eosin staining). a, b The minimally invasive encapsulated follicular variant PTC shows focal invasion of the neoplastic capsule with a mushroom aspect (original magnification ×4 and ×10, respectively). In the insect, the neoplastic cells show mild nuclear atypia (original magnification ×60). c, d The infiltrative follicular subtype of PTC exhibits a pattern of growth towards the adjacent thyroid parenchyma without evidence of neoplastic capsule (original magnification ×4 and ×10, respectively). In the insect, the nuclear atypia of the conventional PTC is more evident than that observed in the invasive encapsulated follicular variant PTC (original magnification ×60)

Fig. 3

The scheme shows how well-differentiated thyroid carcinomas can be separated according to their molecular landscape. As a rule, papillary thyroid carcinomas (PTCs) are BRAF-like neoplasms that encompass the classical type (C-PTC) and other subtypes, including also the infiltrative follicular subtype (IF-PTC). RAS-like lesions include the invasive encapsulated follicular variant PTC (IEFV-PTC), highlighted by a red square, and the follicular thyroid carcinoma (FTC). Oncocytic thyroid carcinomas, although belonging to well-differentiated thyroid carcinomas, have not been included in the scheme because they do not show a BRAF-like nor a RAS-like molecular profile. Abbreviations: FTC follicular thyroid carcinoma, IEFV-PTC invasive encapsulated follicular variant papillary thyroid carcinoma, PTC papillary thyroid carcinoma, C-PTC classic papillary thyroid carcinoma, IF-PTC infiltrative follicular papillary thyroid carcinoma subtype

Fig. 4

Histopathological pictures of high-grade follicular-derived thyroid carcinoma cases (haematoxylin/eosin staining). a High-grade follicular subtype PTC (original magnification ×20); in the insect, arrows indicate mitotic figures at higher magnification (x60). b Picture showing a differentiated high-grade follicular subtype PTC (upper left corner) and poorly differentiated (insular and solid growth patterns) component (original magnification ×10). c Differentiated high-grade carcinoma showing follicular subtype PTC in association with wide areas of tumor necrosis (original magnification ×10; “n” indicates necrosis). d High-grade tall cell PTC subtype (original magnification ×60; arrow indicates a mitotic figure)