Follicular Thyroid Neoplasms

Follicular thyroid neoplasms are solitary nodules that present as a mass. Follicular adenomas are benign, encapsulated tumors with follicular differentiation that are more common in women, usually occur in adults, and are more common in areas of iodine deficiency. Follicular adenomas measure 1–3 cm and usually are smaller than follicular carcinomas, although size may overlap. Follicular neoplasms lack cytologic features of papillary thyroid carcinoma (PTC). Malignancy in follicular neoplasms requires capsular or vascular invasion. The capsule in follicular carcinomas often is thicker and more irregular than that of adenomas. Various histologic patterns, including microfollicular, macrofollicular, normofollicular, and trabecular growth, may be seen in follicular neoplasms. Areas of papillary architecture may be seen. Follicular neoplasms may have different cytomorphologies, including mucinous, signet ring cell, and clear cell, and may have intratumoral fat. Follicular neoplasms show immunopositivity for thyroid transcription factor 1 (TTF1), thyroglobulin, and keratin and are negative for chromogranin, synaptophysin, and calcitonin. Follicular neoplasms often show RAS mutations, and a few have t(2;3)(q13;p25) involving PAX8 and peroxisome proliferator-activated receptor-γ encoding a fusion protein. Follicular adenomas show increased expression of p27 cell cycle inhibitory protein and decreased Ki67 proliferative indices (LI) compared with follicular carcinomas, and carcinomas with metastases have higher Ki67 LI levels than those without. However, in an individual lesion, these and other immunohistochemical or molecular markers cannot separate benign from malignant follicular neoplasms definitively. Cytologic specimens cannot distinguish benign from malignant follicular neoplasms, as diagnosis of malignancy requires invasive growth. Follicular adenomas are treated with lobectomy and have an excellent prognosis. Follicular carcinomas show capsular and/or vascular invasion. Vascular invasion must occur within or beyond the capsule. Tumors with capsular invasion only (no vascular invasion) have more indolent behavior than those with vascular invasion. Follicular carcinomas with focal capsular and/or vascular invasion have been designated as minimally invasive, whereas those with more extensive invasion have been characterized as widely invasive, although this classification is being used less often. Tumors with extensive vascular invasion often are referred to as angioinvasive follicular carcinomas. Unlike PTC, which has frequent lymph node metastases, follicular carcinomas usually metastasize directly to viscera. Minimally invasive follicular carcinomas have a low mortality rate (3%–5% in some studies), and those with only capsular invasion (no vascular invasion) have a particularly good prognosis. Widely invasive carcinomas are aggressive, with a long-term mortality rate of 50 %.