College of American Pathologists

2013 — June Case of the Month

Posted June 6, 2013


CAP Foundation Online Case of the Month

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After reading the summary, try answering the three related multiple-choice questions below.

A 58-year-old woman presents with a symmetrically enlarged thyroid gland and hypothyroidism. A complete thyroidectomy was performed.

Archive Case and Diagnosis:
This case first appeared as Performance Improvement Program in Surgical Pathology (PIP) 2010, case 14, and is an autoimmune (Hashimoto) thyroiditis.

Criteria for Diagnosis and Comments:
This image consists of a thyroid gland composed of small thyroid follicles containing dense colloid and lined mostly by metaplastic Hurthle cells. The follicles are infiltrated by numerous lymphocytes and plasma cells. Numerous germinal centers are also present. The parenchyma is subdivided by fibrous septa. These features are considered diagnostic of chronic autoimmune (Hashimoto) thyroiditis.

Although thought to be uncommon, Hashimoto thyroiditis has increased in frequency due in part to increasing use of fine needle aspiration (FNA) and serological testing. In fact, a third of women over the age of 70 harbor the autoantibodies of thyroiditis. Hashimoto thyroiditis typically presents as a diffuse, firm, smooth and painless goiter occurring in middle-aged women. Although the patients are usually hypothyroid or euthyroid, a phase of mild hyperthyroidism may precede it. Autoimmune phenomena are present in most patients and include elevated circulating anti-thyroglobulin (TG) and anti-thyroid peroxidase (TPO), the latter offering much greater specificity. Patients may exhibit other signs of autoimmunity such as pernicious anemia, Sjögren syndrome, adrenal insufficiency, oophoritis or diabetes mellitus. The combination of goiter, hypothyroidism and positive antibody tests is clinically diagnostic of this condition. While thyrotoxicosis (Graves disease), another autoimmune disorder, is the result of circulating thyroid stimulatory antibodies, Hashimoto thyroiditis is predominantly the clinical expression of cell-mediated immunity leading to destruction of thyroid cells which, in its severest form, produces thyroid failure and idiopathic myxedema. Clinical presentation with tracheal or esophageal compressive symptoms is unusual except in the fibrous variant. Lymphocytic thyroiditis (an entity containing normal follicles that lack Hürthle cell metaplastic changes) and Hashimoto thyroiditis are now generally considered to be the same process, possibly representing different phases or manifestations of the same disease. Lymphocytic thyroiditis is seen more frequently in children who will typically present with asymptomatic goiter.

Surgically, the gland is usually easily removable with no fixation to surrounding soft tissues. Grossly, the gland tends to be tan-yellow (rather than the usual red-brown), resembling hyperplastic lymph nodal tissue, without grossly obvious colloid. It is typically firm, diffusely enlarged, and has a bosselated surface with lobulation due to increased fibrous tissue. Small size, nodularity, and asymmetric enlargement (particularly in those glands with prominent fibrosis) can also occur. Histologically, the two main findings are small atrophic follicles, many lined by oncocytic (Hürthle; oxyphilic; Askanazy) cells, and lymphoid infiltration including prominent germinal centers. Colloid is usually scant and dense, or absent. Large numbers of plasma cells in addition to macrophages and occasional multinucleate histiocytes may also be seen. While fibrous tissue is typically scanty and located within interlobular septa, broad dense fibrous bands of tissue may dominate in the so-called fibrous variant. The fibrous variant represents about 10% of cases and can cause clinical confusion with carcinoma or Riedel thyroiditis. This variant often presents with significant hypothyroidism, markedly elevated antithyroglobulin antibody titers, and a large symptomatic goiter which can result in local compressive symptoms requiring surgical intervention. Squamous metaplasia is also more commonly seen in this setting. The fibrous variant is likely a progressed form of typical Hashimoto thyroiditis. Alternatively, some elderly patients may present with hypothyroidism and a small atrophic gland which histologically resembles the fibrous variant except for its tiny size. This is termed “idiopathic myxedema”, rather than Hashimoto thyroiditis, because of the absence of goiter and the severity of the hypothyroid state.

Treatment involves watchful waiting in mild cases, thyroid replacement in those patients who are hypothyroid, and surgery in patients who either experience pressure symptoms, rapid enlargement or whose gland is otherwise suspicious for neoplasm. Complications of Hashimoto thyroiditis include lymphoma which, although unusual, must be considered in the presence of rapid glandular growth or pain. Hürthle cell neoplasms and papillary carcinoma both occur with increased frequency in this setting also. All of these can usually be diagnosed, or at least suggested, by FNA.

Riedel thyroiditis can theoretically be confused with the fibrous variant of Hashimoto thyroiditis. However, in Riedel thyroiditis, the gland is not just firm but stony hard with poor demarcation from surrounding soft tissues. Tissue planes are absent due to extension of the paucicellular fibrous process outside the gland resulting in dense fibrous tissue enveloping adjacent nerve, fat and muscle. Associated lesions of multifocal (systemic) fibrosclerosis syndrome, such as orbital pseudotumor, retroperitoneal fibrosis, and IgG4-related autoimmune disease, if present, can assist in establishing the diagnosis.

Most primary malignant lymphomas present as an enlarging thyroid mass in elderly women in the setting of Hashimoto thyroiditis, a likely consequence of the chronic antigenic stimulation analogous to salivary lymphomas that arise in the setting of Sjögren syndrome. They are either diffuse large B-cell type or extranodal marginal zone B-cell lymphoma of MALT-type. In contrast to the mixed lymphoplasmacytic appearance of Hashimoto thyroiditis, monotonous sheets of atypical monoclonal B-cells with prominent lymphoepithelial lesions (LEL) and destructive growth typify thyroid malignant lymphoma. While LEL may be seen in autoimmune thyroiditis, they tend to be small with a patchy distribution, whereas those in lymphoma are usually large, numerous and often distend or destroy residual thyroid follicles.

Graves disease and Hashimoto thyroiditis are the two most common autoimmune thyroid conditions and can exhibit overlapping pathologic features including the presence of prominent germinal centers. However, in Graves disease, the thyroid is grossly “beefy” and deep red, and microscopically the follicles are lined by tall, hyperplastic epithelium with “scalloped” colloid rather than the Hürthle cell-lined atrophic follicles in typical Hashimoto thyroiditis. While some cases of Hashimoto thyroiditis can show ambiguous features including less than atrophic follicles, the clinical history including exophthalmos, infiltrative dermopathy, high metabolic level and laboratory studies should readily establish the diagnosis of Graves disease.

The Hürthle cell compartment can become hyperplastic and occasionally true Hürthle cell neoplasms may arise in this setting. Those nodules which are innocuous tend to be small and unencapsulated, but when there is evidence of invasive qualities or vascular permeation, the diagnosis of Hürthle cell carcinoma must be acknowledged.

There is also a higher incidence of papillary thyroid carcinoma in the setting of Hashimoto thyroiditis. Because of the frequent presence of cell overlap, nuclear clearing and nuclear inclusions in Hürthle cell areas, the diagnosis of papillary carcinoma may be difficult to exclude. Definitive diagnosis requires a degree of nuclear grooves and inclusions, nuclear overlap, sclerosis, and scalloped colloid, which exceed those findings seen in foci that mimic papillary neoplasia. Anecdotally, there is an association of Hashimoto thyroiditis, particularly the fibrous variant, with sclerosing mucoepidermoid carcinoma with eosinophilia.

Finally the finding of “focal lymphocytic thyroiditis” is often seen incidentally in surgical specimens, consisting of focal lymphoid aggregates, occasionally with germinal centers, but without the other, and more diffuse, features of Hashimoto thyroiditis. This is considered an innocent finding that is most likely not an early form of diffuse autoimmune thyroiditis.

Supplementary Questions:

Question Diagnostic Set
1. Focal lymphocytic thyroiditis is an early form of Hashimoto thyroiditis. A. True
B. False
2. The fibrous variant of Hashimoto thyroiditis is associated with multifocal (systemic) fibrosclerosis. A. True
B. False
3. The combination of goiter, hypothyroidism and circulating anti-thyroglobulin and/or anti-thyroid peroxidase antibodies is diagnostic of Hashimoto thyroiditis. A. True
B. False


  1. DeLellis RA, Lloyd R, et al, Pathology and Genetics of Tumours of Endocrine Organs. WHO Classification of Tumour. No8. Lyons, France: IARC press;2004;49-133.
  2. Lloyd RV, Douglas BR, Young WF. Endocrine Diseases. AFIP Atlas of Nontumor Pathology, Series I. Washington DC: American Registry of Pathology;2002:91-149.
  3. Rosai J. Rosai and Ackerman’s Surgical Pathology. Vol 1.Mosby, NY. 2004:515-594.

Arthur R. Cohen, MD
Surgical Pathology Committee
Presbyterian Hospital
Charlotte, NC