Answer: Diffuse toxic hyperplasia (Graves’ disease)

Histology: On gross examination, the thyroid was diffusely and symmetrically enlarged weighing 120 grams. Histologically at low power, the gland appears diffusely hypercellular, and there is an accentuation of the lobular architecture of the thyroid parenchyma. The colloid is sparse, and it is scalloped at its interface with the follicular epithelium. In areas the follicular epithelium projects into the follicle spaces and forms well developed papillary structures. Some of these papillae are lined by cells demonstrating enlarged, hyperchromatic, atypical nuclei.

Discussion: Diffuse toxic hyperplasia (Graves’ disease) is a common cause of hyperthyroidism in women, and it is related to autoimmunity. The histologic findings are variable and reflect the nature and duration of medical therapy prior to thyroidectomy. In untreated or partially treated glands, the colloid is sparse and the follicular epithelial cells are vastly increased in size and number. Projections of hyperplastic epithelium into the follicles can give rise to papillary formation such that one cannot unswervingly equate papillary architecture with papillary thyroid carcinoma. Although this papillary hyperplasia may be quite florid, it is morphologically distinct from the papillary architecture of papillary carcinoma in several respects: 1) diffuse distribution (i.e. not confined to a focal lesion), 2) broad base with stubby projections, 3) lack of complexity (i.e. absence of complex haphazard branching), centripetal orientation of papillary fronds (i.e. tips of papillae point to center of follicles), and orderly alignment of lining follicular epithelium. In medically treated glands, the morphologic changes reflect the activity of the therapy. For instance, there is little change in the gland when medical therapy is directed towards the peripheral activity of thyroid hormone excess (e.g. propanolol). Following radioiodine treatment, the follicular epithelium may exhibit bizarre cytologic atypia as in the present case, with increasing follicle atrophy and interstitial fibrosis over time.