Pathology of the Thyroid Gland
Case 2 -
Chronic Lymphocytic Thyroiditis (Hashimoto's Disease; Autoimmune Hypothyroidism)
Zubair W. Baloch and Virginia A. LiVolsi
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
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.
Diagnosis: Chronic lymphocytic thyroiditis (Hashimoto's disease; autoimmune hypothyroidism)
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:
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
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).
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- Weetman AP. Autoimmune thyroid disease: propagation and progression. Eur J Enodcrinol 2003; 148: 1-9.