—  SHORT COURSE #41  —

Pathology of the Thyroid Gland

Case 2 - Chronic Lymphocytic Thyroiditis (Hashimoto's Disease; Autoimmune Hypothyroidism)

Zubair W. Baloch and Virginia A. LiVolsi


Clinical History
A 76 year old woman presented to her physician with weakness and feeling tired. On examination, a small goiter (estimated weight: 50 grams) was noted. Multiple nodules (up to 1 cm) were noted bilaterally. Thyroid function tests showed decreased T4, elevated TSH and presence of antithyroid antibodies (1:600).

FNA of two of the larger nodules showed thyroiditis and atyical nuclei were seen raising the possibility of neoplasm.

Thyroid lobectomy (side with the largest nodules) was undertaken. The gross specimen showed a lobulated tan tissue with indistinct nodularity.


Case 2 - Figure 1 - Lymphocytic Thyroiditis
Case 2 - Figure 2 - Lymphocytic Thyroiditis


Case 2 - Figure 3 - Lymphocytic Thyroiditis
Case 2 - Figure 4 - Lymphocytic Thyroiditis

Diagnosis: Chronic lymphocytic thyroiditis (Hashimoto's disease; autoimmune hypothyroidism)

Discussion:
Classic chronic lymphocytic thyroiditis is more common in women (ratio female to male about 20 to1), encompasses a spectrum of clinical and pathologic changes, ranging from an absence of symptoms of thyroid dysfunction to hypothyroidism and rarely, hyperthyroidism, from a large goiter to an atrophic gland, and from scattered clusters of infiltrating lymphocytes to extensive chronic inflammation and scarring with almost complete loss of follicular epithelium. Hence a number of classification schemes have been proposed over the years. I prefer a modified scheme based on the classification of Mizukami et al:

Chronic thyroiditis-subtypes
Focal
Hyperplastic
Oxyphilic
Fibrotic

It is probably correct to state that except for branchial or thymic rests that may be embryologic remnants in the thyrooid, any lymphocytes in the gland are abnormal and probably reflect an immunologic reaction. Hence one can see scattered lymphocytes without any other pathology and without any clinical manifestations, but this is probably autoimmune disease. It is only when the process is well developed that clinical and pathologic changes are discerned.

Various circulating antithyroid antibodies and other immune phenomena occur, including in situ immune complex deposition and basement membrane changes in the gland and expression of major histocompatibility complex antigens on the thyroid cells. The thyroiditis may be found in the same families in which idiopathic hypothyroidism and Graves' disease are common. It may follow typical Graves' disease.

The hyperthyroid variant of autoimmune thyroiditis is closely related to Graves' disease and may be almost identical in its gross and microscopic appearance to the latter condition.

If the thyroiditis is slight and focal, then the thyroid is normal in size and contains scattered infiltrates of lymphocytes, predominantly T-cells. Some of the infiltrates contain lymphoid follicular centers, mostly B-cells. The thyroid follicles involved by the infiltrates appear atrophic; they have lost part or all of their colloid.

A small number of plasma cells (mostly IgG-positive) are mixed with lymphocytes. Glands involved by this focal thyroiditis typically are asymptomatic; therefore, the thyroiditis is discovered when thyroid tissue is surgically removed for other reasons, or the process is found at autopsy. Focal lymphocytic thyroiditis probably represents the mild or early form of autoimmune thyroiditis. When focal lymphocytic thyroiditis is more than minimal and the foci of involvement are larger and more numerous, occasional follicular cells undergo metaplasia toward oxyphilic cells. Part of a lobe sometimes may be extensively involved by lymphocytic thyroiditis, with minor changes occurring elsewhere in the gland; hence, nodularity may result (nodular Hashimoto's thyroiditis).

In more advanced cases of autoimmune thyroiditis, little or no normal parenchyma is visible. The gland on gross examination is enlarged, and its cut surfaces are fleshy and pale.

Microscopic examination shows that many follicles are small, the amount of colloid is decreased, and infiltrates of lymphocytes, plasma cells, and macrophages are extensive. Lymphoid follicular centers are numerous, and their antibody-producing B-cells are polyclonal; those containing immunoglobulin G are the most numerous. T-cells are most frequent among the epithelial cells and in the interstitial tissue away from lymphoid follicles. Inflammatory giant cells may be scattered through the damaged follicles; their presence should not lead the pathologist to mistake autoimmune thyroiditis for subacute thyroiditis.The amount of connective tissue in the gland often increases. Some follicular cells appear atrophic or damaged; many are hyperplastic or metaplastic (oncocytic or Hürthle cells; squamous metaplasia). The solid cell nests have been suggested as the origin of the latter. Rarely cystic lesions believed to be of branchial origin have also been noted in the lateral aspects of the thyroid in severe thyroiditis.

Most cases of adult hypothyroidism (idiopathic myxedema) not related to pituitary failure, radiation, or surgical thyroidectomy represent a form of autoimmune thyroiditis. These glands are fibrotic and usually small, with a few nests of abnormal epithelial cells; scattered small groups of lymphocytes and plasma cells are present.

Some patients with autoimmune thyroiditis have one or more episodes of painless enlargement of the gland accompanied by transient thyrotoxicosis and reduced radioiodine uptake followed by transient and less commonly permanent hypothyroidism. The episodes may occur postpartum and recur with subsequent pregnancies. Biopsies have demonstrated that the thyroid may have diffuse or focal lymphocytic thyroiditis. The entities of "silent thyroiditis" or postpartum thyroiditis have been shown to fall into the spectrum of autoimmune thyroid disease.

Numerous molecular biologic approaches to understanding the autoimmune thyroid disorders (Graves' disease and chronic thyroiditis) are being studied in numerous laboratories around the world. Both animal models and human patients are being studied. An excellent review has been recently published (Weetman cited below).

References

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