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An incidental thyroid nodule.

A 66-year-old woman was referred by her endocrinologist for a right thyroid nodule. The patient had been followed by her endocrinologist for hypothyroidism, and a recent thyroid ultrasound had revealed a 1-cm hypoechoic right thyroid nodule. The patient underwent fine-needle aspiration (FNA) of the thyroid nodule with findings suspicious for a follicular neoplasm (figure 1, A and B).

The patient underwent a right thyroid lobectomy with no complications. The specimen was sent for pathologic examination, which revealed a 1-cm nodule in the right thyroid gland. Microscopically, the nodule showed a highly cellular, homogenous cell population arranged in nests and trabeculae (figure 2, A). Given these findings, the patient underwent additional immunohistochemistry staining with thyroglobulin (figure 2, B), which confirmed the diagnosis of an intrathyroidal parathyroid adenoma (ITPA).

ITPA is a rare and diagnostically challenging clinical entity. Although its exact incidence is debatable, ITPA occurred at a rate of 1% in Mazeh et al's study of 4,868 patients undergoing parathyroidectomy. (1) They found that 75% of ITPAs were due to ectopic inferior parathyroid glands. In fact, ITPA represents one of the more common locations for ectopic inferior parathyroid glands. Phitayakorn and McHenry found ectopic parathyroid glands in 16% of their 231 patients undergoing parathyroidectomy. Of these patients, 62% were determined to have ectopic inferior glands, 22% of which were intrathyroidal. (2)

Ectopic locations of parathyroid glands are believed to arise from aberrant migration during embryogenesis. The inferior parathyroid gland, arising from the third pharyngeal pouch, has a longer migration and is more likely to be found in ectopic locations. (3)

Parathyroid adenomas, accounting for 75 to 85% of primary hyperparathyroidism, classically present with symptoms of hypercalcemia (nephrolithiasis, abdominal pain, and psychiatric symptoms) and skeletal disease. (4) Our patient did not demonstrate signs or symptoms of primary hyperparathyroidism; however, further investigation after surgery revealed borderline hypercalcemia. She had a history of chronic hypothyroidism, which has been documented by Paloyan Walker et al as having a causal relationship with the development of parathyroid adenomas. (5) Paloyan Walker et al also noted that primary hyperparathyroidism may be masked by hypothyroidism, a clinical picture consistent with our patient's case.

Preoperative diagnosis of ITPAs is essential to determining correct surgical management. Imaging studies can easily mistake ITPAs for thyroid nodules as they both show increased uptake on technetium [sup.99m]Tc sestamibi scans and are hypoechoic on ultrasound. (1) FNA biopsy is a useful diagnostic technique, but definitive diagnosis is difficult because of the similar cytologic characteristics of thyroid and parathyroid lesions. This was demonstrated in the study by Tseleni-Balafout of 29 histologically diagnosed intrathyroidal parathyroid lesions in which only two were correctly diagnosed preoperatively as ITPAs by FNA.

Immunocytochemistry in conjunction with FNA is likely the most helpful aid to diagnosis. Detection of parathyroid hormone (PTH) and chromogranin are strongly associated with parathyroid cell origin, while detection of thyroglobulin is strongly associated with thyroid follicular cell origin. (6) The ITPA in this case showed strong immunoreactivity to PTH.

As in our case, the diagnosis of ITPA frequently occurs postoperatively. Mazeh et al found that, grossly, ITPAs tend to be smaller than non-ITPAs, with a mean weight of 325 mg and 772 mg, respectively. They suggested that this limited growth may be due to space restriction within the thyroid lobe. Parathyroid adenomas also tend to have a more reddish coloration than normal parathyroid tissue. Occasionally, a remnant of normal parathyroid tissue is seen as a yellowish cap in the vicinity of the vascular hilus. (7) On microscopic examination, parathyroid adenomas are predominantly composed of chief cells, which may be scattered diffusely or in a nodular configuration. Compared to chief cells in normal parathyroid glands, the chief cells in adenomas may have enlarged pleomorphic nuclei and cytoplasm that contains minimal amounts of lipids. (7)

This case highlights the challenge in managing ITPAs due to their difficulty in preoperative differentiation from thyroid nodules. As seen with our patient, ITPAs should not only be suspected in patients with primary hyperparathyroidism and a thyroid nodule, but also in those with chronic hypothyroidism and a thyroid nodule. As with non-IT-PAs, the definitive treatment of an ITPA is surgical excision. (4) For those presenting with primary hyperparathyroidism, intraoperative PTH monitoring maybe a helpful adjunct to ensuring ITPA removal. (8)

References

(1.) Mazeh H, Kouniavsky G, Schneider DF, et al. Intrathyroidal parathyroid glands: Small, but mighty (a Napoleon phenomenon). Surgery 2012;152(6):1193-1200.

(2.) Phitayakorn R, McHenry CR. Incidence and location of ectopic abnormal parathyroid glands. Am J Surg 2006;191(3):418-23.

(3.) Feliciano DV. Parathyroid pathology in an intrathyroidal position. Am J Surg 1992;164(5):496-500.

(4.) Fraser WD. Hyperparathyroidism. Lancet 2009;374(9684): 145-58.

(5.) Paloyan Walker R, Kazuko E, Gopalsami C, et al. Hyperparathyroidism associated with a chronic hypothyroid state. Laryngoscope 1997;107(7):903-9.

(6.) Tseleni-Balafouta S, Gakiopoulou H, Kavantzas N, et al. Parathyroid proliferations: A source of diagnostic pitfalls in FNA of thyroid. Cancer 2007; 111 (2): 130-6.

(7.) Grimelius L, Akerstrom G, Bonderson L, et al. The role of the pathologist in diagnosis and surgical decision making in hyperparathyroidism. World J Surg 1991;15(6):698-705.

(8.) Cheng W, MacLennan GT, Lavertu P, Wasman JK. Giant intrathyroid parathyroid adenoma: A preoperative and intraoperative diagnostic challenge. Ear Nose Throat J 2009;88(3):E1-3.

John P. Flynn, MD; Peter A. Morawiecki, MD; Marco A. Ayala, MD

From the Department of Otolaryngology-Head and Neck Surgery, University of Kansas, Kansas City, Kansas (Dr. Flynn and Dr. Ayala); and the Department of Pathology, Captain James A. Lovell Federal Health Care Center, Chicago (Dr. Morawiecki).

Caption: Figure 1. A: Fine-needle aspiration reveals loosely cohesive cells resembling follicular arrangements (Papanicolaou stain, original magnification x100). B: A cohesive cluster of cells is in a vague follicular arrangement (Papanicolaou stain, original magnification x400).

Caption: Figure 2. A: The mass, with trabecular architecture, abuts normal thyroid tissue (hematoxylin and eosin stain, original magnification x40). B: In this immunohistochemistry slide, normal thyroid tissue (left) shows immunoreactivity to thyroglobulin, but the mass (right) shows no immunoreactivity to thyroglobulin (original magnification x100).
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Title Annotation:THYROID AND PARATHYROID CLINIC
Author:Flynn, John P.; Morawiecki, Peter A.; Ayala, Marco A.
Publication:Ear, Nose and Throat Journal
Article Type:Clinical report
Date:Aug 1, 2017
Words:1007
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