Case 3 -
Edmund S. Cibas
Brigham & Women's Hospital
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31 year old man with longstanding juvenile rheumatoid arthritis and chronic renal
failure. Now with diffuse enlargement of the thyroid. Thyroid FNA (all images: Papanicolaou-stained
Case 3 - Figure 1
The smears contained several chunks of dense orange-red material with irregular edges.
Case 3 - Figure 2
Another field shows two additional chunks of dense orange-red material with irregular edges.
Case 3 - Figure 3
High magnification reveals dense, hyaline material with embedded elongated nuclei.
Case 3 - Figure 4
Some fragments appear acellular.
Case 3 - Figure 5
Other fragments contain occasional stretched and distorted nuclei.
Case 3 - Figure 6
Some fragments contain more numerous nuclei. Aside from their occasionally distorted appearance, the nuclei lack atypia.
Case 3 - Figure 7
A Congo red stain on the smear shows apple- green birefringence under polarized light.
Case 3 - Figure 8
An autopsy 3 years later revealed an enlarged thyroid gland with extensive interfollicualr and parafollicular amyloid deposition.
Case 3 - Figure 9
The elongated nuclei seen on FNA correspond to the nuclei of fibroblasts and endothelial cells entrapped in amyloid deposits.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Papanicolaou-stained smears from this 1990 case were sparsely cellular. There were only rare sheets of
benign follicular cells and scant colloid. The diagnostic findings, easy to overlook, consisted of
chunks of orange-red, hyaline-like material with embedded elongated nuclei.
The differential diagnosis includes:
Examined out of context, the smears can be misinterpreted as a spindle-cell proliferation like
Riedel's thyroiditis or a schwannoma. The distorted, spindle-shaped nuclei are, in fact, merely normal
thyroid fibroblasts and endothelial cells embedded in dense amyloid deposits. The embedded elongated
nuclei are in fact a characteristic feature of amyloid goiter on FNA, highlighted by Gharib and Goellner
in a letter to the New England Journal of Medicine in 1981 (see references). Although amyloid goiter can
be nodular, it is more often a diffuse enlargement, as in this case, making Riedel's thyroiditis and a
neoplasm unlikely. Other amyloid- containing neoplasms like medullary carcinoma and the rare
plasmacytoma of the thyroid are similarly unlikely causes of a diffuse thyroid enlargement.
- Riedel's thyroiditis
- medullary carcinoma
- amyloid goiter
This case of amyloid goiter was unforgettable because: 1. it illustrates a very
rare entity, but one that can be diagnosed by FNA; 2. it is easily misdiagnosed as a spindle-cell lesion
because the elongated nuclei are "red herrings;" 3. it is an elegant example of a difficult case made
easy by the integration of clinical and other diagnostic data. The key to the diagnosis in this case lay
in the integration of the clinical history of a chronic illness (juvenile rheumatoid arthritis) and the
clinical signs (a diffuse rather than nodular thyroid enlargement) with the curious but distinctive
cytologic findings. Follow-up: This patient developed systemic amyloidosis and lived for 3 years after
this FNA. He eventually succumbed to sepsis. The thyroid at autopsy weighed 370 grams (normal, 25
grams) and showed marked amyloid deposition.
Review of the Literature/Treatment Options:
Amyloid goiter (AG) was first described
in the 1850s. It is a diffuse or nodular enlargement of the thyroid gland, sometimes with alarming
clinical symptoms such as rapid growth (over several months), dyspnea, dysphagia, or hoarseness.
Patients are usually euthryoid. AG occurs in association with both primary and secondary amyloidosis,
more commonly in the latter. Patients with AG associated with secondary amyloidosis have a chronic
illness; common examples include rheumatoid arthritis (as in this case), inflammatory bowel disease, and
tuberculosis. Amyloid deposits in the thyroid in patients with secondary amyloidosis consist of AA
proteins. The AA protein fibrils are derived by proteolysis from a larger serum protein called serum
amyloid-associated protein that is synthesized in the liver. Production of SAA is increased in
inflammatory states as part of the "acute phase response." AG related to secondary amyloidosis also
occurs with hereditary diseases like familial Mediterranean fever (FMF). In FMF, the deposits consist
also of AA proteins, suggesting that this form of amyloidosis is also related to recurring bouts of
inflammation. Pathologically, the thyroid interstitium is infiltrated by dense amyloid deposits.
Infiltration/replacement of the thyroid by adipose tissue is a common finding, and adipocytes can be seen
on FNA. There may be a lymphocytic infiltrate, and some cases have by multinucleated giant cells. The
diagnosis can be established by FNA. Follicular cells are typically scant. The diagnosis rests on
recognizing amyloid, which is similar to but more dense than colloid. Amyloid is described as sinilar to
but more dense than colloid. It stains green or orange-red with alcohol-fixed Papanicolaou-stained
preparations. The amyloid in amyloid goiter contains stretched and distorted fibroblast nuclei. These
embedded elongated nuclei are a characteristic feature of amyloid goiter on FNA, a fact that was
highlighted by Gharib and Goellner in a letter to the New England Journal of Medicine in 1981. These
authors championed FNA as a cost-effective, low-morbidity method for the diagnosis of AG. A conclusive
diagnosis rests on identifying the characteristic apple-green birefringence with the Congo red stain.
There is no effective medical treatment of AG. Patients with dyspnea or dysphagia may be treated by
partial or total thyroidectomy for symptomatic relief.
Fine needle aspiration is an effective method for the diagnosis of amyloid goiter.
- Gharib H, Goellner JR. Diagnosis of amyloidosis by fine- needle aspiration biopsy of the thyroid [Letter]. N Engl J Med 1981;305:586.
- Hamed G, Heffess CS, Shmookler BM, Wenig BM. Amyloid goiter: a clinicopathologic study of 14 cases and review of the literature. Am J Clin Pathol 1995;306-312.
- Ozdemir BH, Uyar P, Ozdemir FN. Diagnosing amyloid goiter with thyroid aspiration biopsy. Cytopathol 2006; 17: 262-66.
- Villa F, Dionigi G, Tanda ML, Rovera F, Boni L. Amyloid goiter. Int J Surg 2008; 6 (Suppl 1: 16-8).
- Yaeger KA, Hysell C, Pitman MB. Diagn Cytopathol 2009. Yidiz L, Kefeli M, Kose B, Baris S. Amyloid goiter: two cases and a review of the literature. Ann Saudi Med 2009; 29: 138-41.