A follicular adenoma is defined as an encapsulated neoplasm of thyroid follicular epithelial differentiation that lacks evidence of invasive growth and does not exhibit the nuclear features of papillary carcinoma [1]. Its malignant counterpart, follicular carcinoma, is actually a diagnosis of exclusion, defined as “a malignant epithelial tumor showing evidence of follicular cell differentiation and not belonging to any other distinctive types of thyroid malignancy” [2]. Follicular carcinoma is subdivided into two general categories: widely invasive tumors that usually lack a capsule and exhibit extensive, clear-cut invasion of surrounding stroma and minimally invasive tumors that invade only into a surrounding capsule. Widely invasive follicular carcinoma is not easily confused with follicular adenoma; as a result, the remainder of this chapter will deal with the differential diagnosis between follicular adenoma and minimally invasive follicular carcinoma.

Both follicular adenomas and minimally invasive follicular carcinomas tend to present similarly as a solitary thyroid nodule, though follicular carcinomas tend to be larger overall. Patients with large tumors may complain of compressive symptoms like dyspnea, coughing, or hoarseness. Almost all patients with these tumors are euthyroid. Because the defining feature of minimally invasive follicular carcinoma is an architectural one (details below), a definitive diagnosis cannot be made by fine-needle aspiration. Both follicular adenoma and follicular carcinoma are likely to be diagnosed as “suspicious for a follicular neoplasm” or “atypical cells of undetermined significance” by fine-needle aspiration [3].

Surgical intervention—at minimum, a thyroid lobectomy—is required to make the diagnosis of follicular adenoma or minimally invasive follicular carcinoma. A patient receiving the diagnosis of follicular adenoma requires no additional therapy. In contrast, the treatment of minimally invasive follicular carcinoma is somewhat controversial. Many experts advocate for completion thyroidectomy with subsequent radioactive iodine, although others have argued that a lobectomy alone may be sufficient, particularly in tumors that exhibit only capsular invasion [4]. Because follicular carcinoma only rarely metastasizes to lymph nodes, a prophylactic lymph node dissection is not recommended [4].

Grossly, follicular adenomas and minimally invasive follicular carcinomas have an appearance that is essentially identical: a solitary, well-circumscribed nodule with a well-developed capsule (Fig. 19.2a). At the microscopic level, follicular carcinomas generally tend to be larger; exhibit more hypercellular growth with microfollicular, trabecular, and solid growth patterns; and possess thicker tumor capsules when compared to follicular adenomas. However, the sole histologic feature that distinguishes follicular adenoma from minimally invasive follicular carcinoma is the presence of invasive growth. Specifically, a follicular carcinoma must exhibit capsular and/or vascular invasion. While this may sound relatively straightforward on its face, any practicing pathologist knows that determining the presence of invasive growth in a follicular neoplasm can be very challenging and is fraught with pitfalls.

Vascular invasion is generally regarded as more reliable than capsular invasion for the diagnosis of minimally invasive follicular carcinoma, and the criteria are strict [2]. To qualify as vascular invasion, the vessel in question needs to be either within the capsule or immediately outside of it; vessels inside the tumor itself should not be considered (Fig. 19.2a). The vessel wall must have a clear-cut endothelial lining and a muscle wall. In addition, the focus of tumor must be attached to the vessel wall with protrusion into the lumen (Fig. 19.2b). Tumor that is “free-floating” within a vessel may represent artifactual detachment from surgery or from the grossing station and therefore does not qualify. Similarly, tumor simply “bulging” into a vessel should not be regarded as truly invasive growth. Ideally, the tumor thrombus should be lined by an endothelial layer, though not all authorities agree on the importance of this finding [2, 5]. In addition, some investigators regard the presence of fibrin thrombi as helpful evidence of true vascular invasion [5].