Adenomas of the thyroid are benign neoplasms derived from follicular epithelium. Follicular adenomas usually are solitary. On clinical and morphologic grounds, they may be difficult to distinguish from a dominant nodule in multinodular goiter, for example, or from less common follicular carcinomas. Although the vast majority of adenomas are nonfunctional, a small proportion produce thyroid hormones (toxic adenomas), causing clinically apparent thyrotoxicosis. In general, follicular adenomas are not forerunners to carcinomas; nevertheless, shared genetic alterations support the possibility that at least a subset of follicular carcinomas arise in preexisting adenomas.
Driver mutations in the TSH receptor signaling pathway play an important role in the pathogenesis of toxic adenomas (see
Fig. 20.6 ). Activating (gain-of-function) somatic mutations in one of two components of this signaling system—most often the gene encoding the TSH receptor itself (TSHR) and, less commonly, the α-subunit of Gs (GNAS)—allow follicular cells to secrete thyroid hormone independent of TSH stimulation (thyroid autonomy). The result of this overabundance is symptomatic hyperthyroidism, with a “hot” thyroid nodule seen on imaging studies. Overall, somatic mutations in the TSH receptor signaling pathway are present in slightly over half of toxic adenomas. Not surprisingly, such mutations also are observed in a subset of autonomous nodules that give rise to toxic multinodular goiters, discussed earlier. Thus, autonomy in both toxic goiter and toxic adenomas stems from the ability of follicular cells to release thyroid hormone independent of trophic factors (i.e., TSH). A minority of nonfunctioning follicular adenomas (<20%) exhibit mutations in RAS or other other genes, genetic alterations that are shared with follicular carcinomas (discussed later).
MORPHOLOGYThetypicalthyroidadenomaisasolitary,sphericallesionthatcompressestheadjacentnonneoplasticthyroid.Theneoplasticcellsaredemarcatedfromtheadjacentparenchymabyawell-defined,intactcapsule(
Fig.20.12A ).Onmicroscopicexamination,theconstituentcellsarearrangedinuniformfolliclesthatcontaincolloid(see
Fig.20.12B ).Occasionally,theneoplasticcellsacquirebrightlyeosinophilicgranularcytoplasm(oxyphilorHürthlecellchange)(
Fig.20.13 ).Similartoendocrinetumorsatotheranatomicsites,evenbenignfollicularadenomasoccasionallyexhibitfocalnuclearpleomorphism,atypia,andprominentnucleoli(endocrineatypia);bythemselves,thesefeaturesdonotconstituteevidenceofmalignancy.Thehallmarkofallfollicularadenomasisthepresenceofanintactwell-formedcapsuleencirclingthetumor.Carefulevaluationoftheintegrityofthecapsuleisthereforecriticalindistinguishingfollicularadenomasfromfollicularcarcinomas,whichdemonstratecapsularand/orvascularinvasion(discussedlater).
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Fig.20.12Follicularadenomaofthethyroidgland.(A)Asolitary,well-circumscribednoduleisvisibleinthisgrossspecimen.(B)Thephotomicro-graphshowswell-differentiatedfolliclesresemblingthoseofnormalthyroidparenchyma.