Clinical Review & Education

Clinical Problem Solving | PATHOLOGY

Bilateral Thyroid Nodules Oscar Trujillo, MD, MS; Navneet Narula, MD; Paula Ginter, MD; Ashutosh Kacker, MD, BS

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Figure. Histologic images of hematoxylin-eosin–stained sections from the thyroid. A, Thyroid follicles destroyed by inflammatory cells consisting of lymphocytes, histiocytes, and giant cells (original magnification ×10). B, Destroyed follicle containing an admixture of histiocytes, lymphocytes, plasma cells, and neutrophils (original magnification ×20). C, Follicular epithelium replaced by histiocytes and giant cells (original magnification ×20).

A woman in her 60s presented with bilateral thyroid nodules discovered by her endocrinologist 2 weeks prior to being referred to an otolaryngologist. Her medical history was remarkable for hypertension, hypercholesterolemia, depression, and gastroesophageal reflux disease. She had a history of smoking but quit in 1998. She had throat discomfort and coughing episodes but denied any fevers, chills, dysphagia, odynophagia, constitutional symptoms, and previous radiation exposure. Findings from the physical examination were normal except for greater fullness on palpation on the right side than the left. Ultrasonography showed a 3.2 × 2.1-cm nodule in the upper to mid pole of the right lobe and a 2.3 × 1.5-cm nodule in the upper pole of the left lobe. A sample from fine-needle aspiration (FNA) of both nodules showed cells suspicious for papillary thyroid cancer.

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A total thyroidectomy demonstrated 3 tan nodules in the right lobe measuring 0.5 cm, 0.5 cm, and 0.4 cm in their greatest dimensions in the upper, middle, and lower poles, respectively. Nodules were not identified in the isthmus or left lobe. The entire thyroid capsular surface was smooth and unremarkable. On the cut section, the thyroid parenchyma in both lobes was nearly effaced by white fibrous tissue. Hematoxylin-eosin–stained sections exhibited thyroid follicles destroyed by inflammatory cells consisting of lymphocytes, histiocytes, and giant cells (Figure, A), and at medium power they revealed destroyed follicles containing an admixture of histiocytes, lymphocytes, plasma cells, and neutrophils (Figure, B) and follicular epithelium replaced by histiocytes and giant cells (Figure, C). What is your diagnosis?

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Clinical Review & Education Clinical Problem Solving

Diagnosis Subacute (de Quervain) thyroiditis

Discussion Subacute thyroiditis is a painful but self-limited thyroid disorder, believed to be caused by viral infection or postviral inflammation resulting in destruction of follicular epithelium with loss of follicular integrity. 1 It presents in women more often than in men approximately 3 or 4:1, usually within the fourth or fifth decade of life.2 Onset is typically rapid and may be in the setting of a recent upper respiratory tract infection. Typically on examination the thyroid will be either symmetric or asymmetric, tender, swollen, and/or firm, and there can be either focal or diffuse areas affected. Occasionally the affected area migrates throughout the gland during illness.1 It also fever and/or elevated inflammatory markers (eg, erythrocyte sedimentary rate [ESR]) are present and the fever may be of unknown origin.2 During the inflammatory phase of the disease there is an acute, typically reversible, reduction of thyroidstimulating hormone (TSH), during which no new hormone synthesis occurs, and triiodothyronine 3 (T3) and T4 levels remained elevated until either thyroxine-binding globulin (TGB) is exhausted or healing begins.1 Normal hormone production begins after the acute inflammatory process ceases, typically 2 to 5 months later.2 However, a small percentage of patients may be clinically hypothyroid beyond this period.2 The proposed mechanism of the disease process is the presence of either viral antigens or antigens released from body tissues, secondary to inflammation, that bind to macrophages.3 On encountering cytotoxic T cells, the microphages become activated and destroy follicular cells. In the early stage, the disease is characterized by the presence of neutrophils, mature lymphocytes, epithelioid cells, and degenerated follicular cells.2 There is also prominent cellular debris and abundant colloid in the background,2 low TSH levels, high T3 and T4 levels, and symptoms of hyperthyroidism secondary to acute

destruction of the follicular cells. Inflammatory cells then begin to aggregate in the damaged follicles and multinucleated giant cells. In the later stage, aspirates are scanty, containing only fibroblasts with a few inflammatory cells, and variable amounts of fibrosis in previously injured areas.2 This is the recovery stage, during which most patients are in a euthyroid state with normal TSH, T3, and T4 levels. Ultrasonography is also commonly used to diagnose thyroid disease. We note several studies investigating the ultrasonographic appearance of subacute thyroiditis and the utility of ultrasonography in its diagnosis. Earlier studies describe ultrasonographic appearances of subacute thyroiditis as “abnormal parenchyma showing homogenous low amplitude echoes.”4(p57) Recent studies using ultrasonography describe multiple hypoechogenic areas in the thyroid parenchyma.4 However, if the disease process is in the healing phase, then fibrosis can appear hyperechoic. Ultrasonography for suspected subacute thyroiditis is most helpful when the clinical picture is not clear or when thyroid scintigraphy or radio iodine uptake level is not available.5 This case suggests that subacute thyroiditis shows FNA changes suspicious for papillary carcinoma. Some studies show that approximately one-third of aspirates from thyroid papillary carcinomas demonstrate lymphocytic components and/or multinucleated giant cells2,6,7 typically pathognomonic for subacute thyroiditis.2 Ultrasonographic findings in this case demonstrated discrete nodules but not the findings described in the literature as “hypoechoic areas either homogenous or multifocal characteristic prior to the healing phase.”4(p59) However, tissue pathology demonstrated histologic features consistent with early and late phases of subacute thyroiditis, possibly complicating the images seen on ultrasonography. Other studies show that ultrasonography, radioimmunoassays, thyroid antibody tests, and cytological diagnosis should be considered to support a diagnose of subacute and other forms of thyroiditis.2,8 Accordingly, multiple diagnostic parameters should be used to support a diagnosis of subacute thyroiditis.

ARTICLE INFORMATION

REFERENCES

Author Affiliations: New York–Presbyterian/ Columbia University and Weill Cornell Medical Center, New York, New York (Trujillo); Weill Cornell Medical College, New York–Presbyterian Hospital, New York (Narula, Ginter, Kacker).

1. Meachim G, Young MH. De Quervain’s subacute granulomatous thyroiditis. J Clin Pathol. 1963;16:189-199.

Corresponding Author: Oscar Trujillo, MD, MS, Department of Otolaryngology, New York–Presbyterian/Columbia University and Weill Cornell Medical Center, 1330 First Ave, Apt 628, New York, NY 10021 ([email protected]). Section Editor: Edward B. Stelow, MD.

2. Öfner C, Hittmair A, Kröll I, et al. Fine needle aspiration cytodiagnosis of subacute (de Quervain’s) thyroiditis in an endemic goitre area. Cytopathology. 1994;5(1):33-40. 3. Rubin RA, Guay AT. Susceptibility to subacute thyroiditis is genetically influenced. Thyroid. 1991;1(2):157-161.

5. Bennedbaek FN, Hegedüs L. The value of ultrasonography in the diagnosis and follow-up of subacute thyroiditis. Thyroid. 1997;7(1):45-50. 6. Löwhagen T, Sprenger E. Cytologic presentation of thyroid tumors in aspiration biopsy smear. Acta Cytol. 1974;18:192-197. 7. Persson PS. Cytodiagnosis of thyroiditis. Acta Med Scand Suppl. 1968;483(suppl):7-100. 8. Jayaram G, Marwaha RK, Gupta RK, Sharma SK. Cytomorphologic aspects of thyroiditis. Acta Cytol. 1987;31(6):687-693.

4. Birchall IWJ, Chow CC, Metreweli C. Ultrasound appearances of de Quervain’s thyroiditis. Clin Radiol. 1990;41(1):57-59.

Published Online: February 13, 2014. doi:10.1001/jamaoto.2013.6712. Conflict of Interest Disclosures: None reported.

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