(1)
Department of Pathology, Sinai Hospital of Baltimore Pathology, Baltimore, MD, USA
Keywords
FollicularPapillaryAnaplasticMedullaryHyalinizing trabecular adenomaThyroglossalBranchial cleft cystHürthleThe thyroid has two basic cell types: the follicular epithelium (TTF-1, PAX8, and thyroglobulin positive) and the C cells (TTF-1, neuroendocrine marker, and calcitonin positive, thyroglobulin negative). Normal follicular epithelium is low cuboidal. The stroma or interstitium is scant but highly vascular. The thyroid epithelium encloses small cystic spaces called follicles, which are filled with gelatinous thyroglobulin, the raw material used to make thyroid hormone. On the slide, the thyroglobulin is called colloid and is pink and thick.
Inflammatory diseases of the thyroid are not commonly sent to surgical pathology, with a few exceptions detailed in this chapter. Conceptually, they can be classified by type of response :
Acute inflammation and necrosis: acute thyroiditis (usually infectious)
Foreign body giant cells, histiocytes, and lymphocytes, diffuse: subacute or granulomatous thyroiditis (de Quervain disease)
Histiocytes, lymphocytes, and rare giant cells, focal: palpation thyroiditis (a reaction to physical trauma, not a primary inflammatory disease)
Lymphocytic infiltrate with germinal centers: lymphocytic thyroiditis or Hashimoto thyroiditis
Dense fibrosis and chronic inflammation: sclerosing Hashimoto thyroiditis versus fibrosing thyroiditis (Riedel thyroiditis, one of the IgG4-related sclerosing disorders)
Lymphocytic thyroiditis is a descriptive term implying a generalized lymphocytic infiltrate. The term Hashimoto thyroiditis refers to an autoimmune process attacking the thyroid, and it is characterized by the following:
Prominent lymphoplasmacytic infiltrate with germinal center formation (Figure 24.1)
Figure 24.1.
Hashimoto thyroiditis . The thyroid follicles are displaced by germinal centers (arrow).
Small, atrophic follicles with Hürthle cell change (oncocytic change)
Scattered nuclear atypia may be seen in this setting, including large hyperchromatic Hürthle cell nuclei , as well as areas of nuclear clearing and pleomorphism that can simulate papillary carcinoma. Therefore, be cautious about diagnosing papillary carcinoma in the setting of lymphocytic thyroiditis. However, these patients can also get papillary carcinoma.
Graves disease (diffuse toxic hyperplasia) is a hyperplastic, hyperthyroid condition in which autoantibodies stimulate the thyroid-stimulating hormone receptor to produce excess thyroid hormone. In treated form, more commonly seen in pathology, the follicles are large and distended, with prominent papillary infoldings (Figure 24.2). The papillary architecture can become florid, but the nuclear features are not those of papillary carcinoma (discussed later). Scalloping of the colloid is prominent. In untreated Graves disease, on the other hand, the thyroid is highly cellular with minimal colloid.
Figure 24.2.
Graves disease with papillary hyperplasia. These papillary formations are due to hyperplasia of the follicular epithelium. The follicular cells are round and fairly evenly spaced and have dark uniform chromatin (arrow), similar to normal follicles.
Goiter is a nonspecific term for enlargement (hyperplasia) of the thyroid but is often used to refer to the nodular enlargement of the thyroid due to iodine deficiency or enzyme defects. Multinodular hyperplasia may be sampled by fine-needle aspiration (FNA) if a single nodule becomes dominant and suspicious, or the whole gland may be removed for cosmetic or physiologic reasons. The nodules usually fall on the colloid nodule-to-follicular-adenoma spectrum.
The thyroid neoplasms can be broken down into several large categories. The first two categories arise from follicular epithelium but are separated based on cytologic and nuclear features. The first category is made up of follicular-type cells that resemble normal thyroid follicular epithelium. This includes Hürthle cells, which can be found in non-neoplastic thyroid. The second category is papillary carcinoma, of which there are many variants; they have in common a set of diagnostic nuclear features. The third category of neoplasms arises from the neuroendocrine or C cell component of the thyroid; medullary carcinoma is the main entity in this group. Table 24.1 summarizes the architectural and cytologic features of thyroid neoplasms.
Table 24.1.
Summary matrix of architectural and cytologic features of thyroid neoplasms.
Cytology | Macro- or normofollicular nodule | Microfollicular nodule | Papillary pattern | Solid or nested growth |
|---|---|---|---|---|
“Follicular” nuclei | Hyperplastic nodule or follicular adenoma | Follicular adenoma/carcinoma | Graves disease | Follicular carcinoma |
Hürthle cells | Hürthle cell adenoma | Hürthle cell adenoma/carcinoma | Oncocytic variant of papillary carcinoma | Hürthle cell adenoma/carcinoma |
“Papillary” nuclei | Follicular variant of papillary carcinoma | Follicular variant of papillary carcinoma | Papillary carcinoma | Hyalinizing trabecular tumor |
Pleomorphic or squamoid cells | Anaplastic carcinoma | |||
Neuroendocrine nuclei | Medullary carcinoma |
Follicular-Type Lesions
Follicular-type cells are notable for their uniformity. The nuclei tend to be round and monotonous, although they may be enlarged in neoplasms. The overall impression is that of a regular array of cells, without crowded, overlapping, or irregular nuclei (Figure 24.3). The cells should respect each other’s personal space, so to speak. The chromatin should be even and smooth, not cleared out, coarse, or chunky.
Figure 24.3.
Follicular cells . Normal follicular epithelium has round uniform nuclei that tend not to overlap or crowd each other (arrow). This field is a combination of large and small follicles full of colloid and could represent normal thyroid, nodular hyperplasia, or a follicular neoplasm.
Colloid nodule, adenomatoid nodule, and follicular adenoma all describe a spectrum of hyperplastic to neoplastic lesions composed of a nodular cluster of follicular epithelium. This area is somewhat confusing as the same lesion may get different names depending on whether it is seen by FNA or on resection. A colloid nodule is a hyperplastic nodule of large distended follicles in which the ratio of colloid to cells is high (a key finding on FNA). A follicular adenoma is defined as a solitary encapsulated nodule with compression of the surrounding thyroid and is usually composed of small microfollicles with scant colloid (a low colloid to cell ratio; Figure 24.4). This lesion, seen on FNA, is called a follicular neoplasm , as follicular adenoma and carcinoma cannot be distinguished by FNA alone. Finally, there is the adenomatoid nodule , a hyperplastic lesion that has some features of adenoma but usually lacks a well-defined capsule.
