Parathyroid cysts

INTRODUCTION — Primary hyperparathyroidism is usually caused by a parathyroid adenoma, occasionally by primary parathyroid hyperplasia, and rarely by a parathyroid cyst or parathyroid carcinoma. Parathyroid cysts are rare lesions of the neck or mediastinum, with over 300 cases reported in the literature [1-8]. In a review of 6621 patients who had neck ultrasound investigations performed at a single center from 2003 to 2007 (mainly for evaluation of thyroid diseases), a parathyroid cyst was diagnosed in five cases [6].

This topic will provide an overview of parathyroid cysts. Other aspects of primary hyperparathyroidism are discussed elsewhere.

●(See "Primary hyperparathyroidism: Pathogenesis and etiology".)

●(See "Primary hyperparathyroidism: Clinical manifestations".)

●(See "Primary hyperparathyroidism: Diagnosis, differential diagnosis, and evaluation".)

●(See "Primary hyperparathyroidism: Management".)

●(See "Preoperative localization for parathyroid surgery in patients with primary hyperparathyroidism".)

●(See "Parathyroid exploration for primary hyperparathyroidism".)

●(See "Parathyroid carcinoma".)

CLASSIFICATION — Parathyroid cysts can be divided in five categories based upon the presumed mechanism of cyst formation [9]:

●Developmental, arising from vestigial remnants of the third and fourth branchial clefts

●Developmental, arising from vestigial remnants of Kursteiner canals

●Coalescence of microcysts into macrocysts

●Degeneration of an adenoma, or rarely carcinoma, into a pseudocyst

●Accumulation of fluid in the parathyroid gland, forming a retention cyst

CLINICAL PRESENTATION — A parathyroid cyst may present as an asymptomatic neck mass or may be discovered as an incidental finding during neck surgery or imaging procedures (carotid ultrasonography, neck computed tomography [CT], magnetic resonance imaging [MRI], chest radiography) performed for unrelated reasons [1,10]. They more commonly occur in the fourth and fifth decade of life, although pediatric cases have rarely been described [3,8,11]. In 65 to 85 percent of cases, they are located in the neck, usually involving the lower parathyroid glands, whereas the rest can occur between the mandible and mediastinum [8,12]. They may occasionally have an intrathyroidal location [13]. Although these cysts vary in size, on average measuring 3 to 5 cm, cysts as large as 10 to 12 cm have been reported [3,8,12]. They do not take up radioiodine or technetium and thus appear as "cold" nodules on thyroid radionuclide scans [14]. MRI, CT, and ultrasound demonstrate the cystic nature of the lesion (image 1).

Local symptoms depend on the size and location in the neck. When large parathyroid cysts are located in the mediastinum, they can cause dyspnea, dysphagia, or hoarseness [3,15]. Acute airway compromise due to hemorrhage in a mediastinal cystic parathyroid adenoma has been reported [16]. In a review of 93 patients with mediastinal parathyroid cysts, 9.5 percent had evidence of recurrent nerve injury [9].

Parathyroid cysts are usually nonfunctional [8,17]. In a systematic review of 359 cases, 62 percent of patients with parathyroid cysts had normal serum calcium, phosphorus, and parathyroid hormone (PTH) levels [8]. In another review of 1769 case records of parathyroid surgeries, there were 48 cystic parathyroid lesions, of which 41 were functional parathyroid lesions [18]. The large predominance of functional parathyroid cysts in the latter study probably reflects referral bias of patients with primary hyperparathyroidism to an endocrine surgical referral center [18].

Functional cysts occur more often in men and are more likely to be secondary to degenerative changes in a parathyroid tumor [8]. The clinical presentation of functioning parathyroid cysts is similar to that of nonfunctioning cysts (asymptomatic or compressive symptoms depending on size and location). Some patients may have symptoms of primary hyperparathyroidism [3]. Although the majority of functional parathyroid cysts cause mild hypercalcemia, patients may present with symptoms of acute parathyroid crisis [1,3,5], as illustrated by the following cases:

●In one study, 11 of 325 patients who underwent parathyroid surgery had parathyroid cysts. Two of the 11 patients had very high serum concentrations of calcium (17.1 and 14.1 mg/dL [4.3 and 3.5 mmol/L], respectively) and PTH, as well as nausea and altered consciousness [17]. In both patients, large areas within the cyst showed acute and chronic organization consistent with cystic degeneration of a parathyroid adenoma.

●Severe hypercalcemia (16 to 23 mg/dL [4 to 5.75 mmol/L]) and very high serum PTH concentrations (333 to 1472 pg/mL), a profile typical of parathyroid carcinoma, have been reported in other cases [5,19-21]. In two cases, a giant tumor of the mandible [21] and an expansile rib lesion were described [9], presumably developing in response to markedly elevated PTH values.

A discussion on acute parathyroid crisis is located elsewhere. (See "Primary hyperparathyroidism: Clinical manifestations", section on 'Parathyroid crisis'.)

DIAGNOSIS — A parathyroid cyst should be suspected in a patient who has a cystic mass in the neck or mediastinum that yields water-clear fluid on aspiration. Elevated parathyroid hormone (PTH) concentration in aspirated cyst fluid is diagnostic. In case series, intact PTH measurement in the cystic fluid ranged from 80 to over 4,000,000 pg/mL [1,3-5,7]. In patients with nonfunctioning parathyroid cysts, serum PTH and calcium are normal, whereas they are elevated in patients with functioning parathyroid cysts. The mechanism by which cystic PTH levels reach the peripheral circulation is unknown.

Diagnostic evaluation — The evaluation of a neck mass includes history, physical examination, an imaging study, and, usually, fine-needle aspiration (FNA) biopsy. The location of the mass may suggest a specific etiology. Masses in the central neck most commonly represent tissue that is thyroid or parathyroid in origin (parathyroid less common). The most commonly used imaging techniques include ultrasound and contrast computed tomography (CT). Microcysts of the parathyroid gland are primarily found in aging glands, often incidentally noted on autopsy [2]. Generally, they have little clinical significance. Macrocysts of the parathyroid gland are larger than 1 cm, and these require clinical investigation.

●Fine-needle aspiration – FNA biopsy is the preferred diagnostic approach for most neck masses and is typically performed using a 25- or 27-gauge needle on a 20 mL syringe. Image-guided (typically ultrasound) FNA is preferable to palpation-guided FNA and is the only option for nonpalpable lesions. (See "Evaluation of a neck mass in adults", section on 'Imaging studies' and "Evaluation of a neck mass in adults", section on 'Diagnostic studies'.)

The initial cytologic evaluation is to rule out a thyroid cyst, which is far more common than a parathyroid cyst. The nature of the aspirate may suggest a particular etiology. Thyroid cyst fluid is more often straw colored. Hemorrhagic or pink-colored fluid may be found in cystic thyroid nodules that contain thyroid cancer, and chocolate-colored fluid suggests hemorrhage in a thyroid nodule that occurred at least one week before aspiration. The absence of colloid on cytologic analysis increases the suspicion that the mass is not of thyroid origin [10]. In such cases, measurement of thyroglobulin in the aspirate can differentiate thyroid from nonthyroid lesions (thyroglobulin present in the former, absent in the latter) [10]. (See "Cystic thyroid nodules", section on 'Fine-needle aspiration'.)

Water-clear fluid on aspiration in the absence of cellular material is suggestive of a parathyroid cyst. In such cases, the aspirate should be submitted for measurement of intact PTH. Elevated PTH concentration in aspirated cyst fluid is diagnostic of a parathyroid cyst [22].

●Laboratory studies – If a cystic mass is determined to be a parathyroid cyst, serum intact PTH and calcium should be measured to determine functionality.

Differential diagnosis — The differential diagnosis of parathyroid cysts includes thyroglossal duct cyst, branchial cleft cyst, cystic thyroid lesion, and parathyroid carcinoma [2]. In contrast to parathyroid cysts:

●Thyroglossal duct cysts are usually in the midline and move with deglutition. (See "Thyroglossal duct cyst, thyroglossal duct cyst cancer, and ectopic thyroid".)

●Branchial cleft cysts are usually present in childhood and typically are located just inferior to the angle of the mandible and anterior to the sternocleidomastoid muscle. (See "Differential diagnosis of a neck mass", section on 'Branchial cleft cyst'.)

●Thyroid cysts have elevated thyroglobulin levels, but not elevated PTH levels. (See "Cystic thyroid nodules".)

●The histopathologic examination of a cystic parathyroid carcinoma shows capsular and blood vessel invasion. (See "Parathyroid carcinoma".)

Imaging modalities such as CT and ultrasound cannot differentiate parathyroid cysts from thyroid cysts, and many parathyroid cysts can be intrathyroidal and may be mistaken for cold thyroid nodules [2,23]. Although sestamibi scan can be positive [20], it is not reliable (eg, negative in two of two cases of functioning parathyroid cysts [23], and positive in the case of a thymic cyst [24]).

PATHOLOGY — Parathyroid cysts are histopathologically characterized by a smooth inner surface wall with a membranous lining, a solitary layer of cuboidal epithelium, and parathyroid tissue within the cyst wall [2,12]. They are rarely malignant. However, atypical cystic parathyroid adenoma is a very unusual clinical entity that may exhibit some pathologic features of carcinoma, but angioinvasion and/or metastases are not present [20]. No specific molecular changes have been reported in parathyroid cysts.

TREATMENT — The treatment of parathyroid cysts is based upon clinical experience and data presented in case series.

Functioning cysts

●Symptomatic – The optimal treatment of symptomatic functioning parathyroid cysts is surgical resection. Resection can be achieved through a cervical approach in all cysts located in the neck and in over two-thirds of mediastinal cysts. Thoracotomy or median sternotomy may be required for some mediastinal cysts [9]. Robotic resection of a mediastinal parathyroid cyst has been described [25]. Patients with functioning large cysts may be more likely to develop postoperative symptomatic hypocalcemia [18]. (See "Parathyroid exploration for primary hyperparathyroidism", section on 'Postoperative hypocalcemia'.)

●Asymptomatic – For the treatment of asymptomatic functioning parathyroid cysts, we use the serum calcium concentration to guide therapy. In the absence of data specifically related to asymptomatic functioning parathyroid cysts, the criteria for surgical intervention are the same as for patients with asymptomatic primary hyperparathyroidism. We suggest surgical intervention for asymptomatic individuals who meet the criteria used to guide surgical intervention in patients with asymptomatic hyperparathyroidism (table 1). For asymptomatic individuals who do not meet the criteria, we observe for symptoms and/or the development of indications for surgery. We measure serum calcium annually. (See "Primary hyperparathyroidism: Management", section on 'Monitoring' and "Primary hyperparathyroidism: Management", section on 'Candidates for surgery'.)

Nonfunctioning cysts

●Symptomatic – Patient with symptoms of compression typically require surgery. For other patients with symptomatic nonfunctioning parathyroid cysts, aspiration of cyst fluid may be curative [1,3]. Surgical resection is an option for symptomatic recurrence after repeated aspiration. Ultrasound-guided percutaneous ethanol ablation is an alternative to surgery in centers where these procedures are performed routinely. However, such procedures could result in fibrosis and recurrent laryngeal nerve palsy [2].

●Asymptomatic – Asymptomatic patients with nonfunctioning parathyroid cysts may require no therapy. Patients should be monitored for the occurrence of symptoms (due to an enlarging parathyroid cyst). In such cases, aspiration and/or surgical resection may be required. For patients who remain asymptomatic, we obtain an ultrasound and serum calcium level in one year, and then less frequently thereafter.

In one case series, curative percutaneous aspiration of cyst fluid was achieved in 10 of 14 patients with nonfunctioning parathyroid cysts, nine with a single aspiration and one requiring a second aspiration [1]. Four of the 14 underwent surgical resection for recurrence of the cyst 6 to 48 months after the initial aspiration [1]. In another series with mean follow-up of 19 months, simple aspiration was successful in 4 of 12 patients (with a 98 percent reduction in cyst volume), and recurrence occurred in eight patients [4].

Ethanol ablation resulted in a significant volume reduction of the cyst, with cosmetic and symptomatic improvement in the eight patients who had recurrence after simple aspiration; two patients required more than one ethanol ablation treatment. No major complications were reported in this series. However, such techniques can be complicated by recurrent laryngeal nerve palsy and fibrosis in surrounding soft tissues, increasing the risk of subsequent surgical procedure in the event of lack of response or recurrence. (See "Cystic thyroid nodules", section on 'Percutaneous interventional ultrasound-guided therapy'.)

SUMMARY AND RECOMMENDATIONS

●Primary hyperparathyroidism is usually caused by a parathyroid adenoma, occasionally by primary parathyroid hyperplasia, but only rarely (<1 percent) by a parathyroid carcinoma or parathyroid cyst. (See 'Introduction' above.)

●Parathyroid cysts are most often located in the neck, but can also occur in the mediastinum. Most are nonfunctional and present as a neck mass or may be discovered as an incidental finding during neck surgery or imaging procedures performed for unrelated reasons. Functional cysts are more likely to be secondary to degenerative changes in a parathyroid adenoma. Although the majority of functional parathyroid cysts cause mild hypercalcemia, patients may present with symptoms of acute parathyroid crisis. (See 'Clinical presentation' above.)

●Elevated parathyroid hormone (PTH) concentration in aspirated cyst fluid is diagnostic. (See 'Diagnosis' above.)

●The differential diagnosis of parathyroid cysts includes thyroglossal duct cyst, branchial cleft cyst, thyroid cyst, and parathyroid carcinoma. (See 'Differential diagnosis' above.)

●The optimal treatment of symptomatic functioning parathyroid cysts is surgical resection.

Treatment of asymptomatic functioning parathyroid cysts depends on the serum calcium concentration. For asymptomatic individuals who meet the criteria used to guide surgical intervention in patients with asymptomatic primary hyperparathyroidism, we suggest surgical intervention rather than observation (table 1) (Grade 2C). For asymptomatic patients who do not meet the criteria, we monitor for symptoms and/or the development of indications for surgery. (See 'Functioning cysts' above and "Primary hyperparathyroidism: Management", section on 'Candidates for surgery'.)

●Patients with nonfunctioning parathyroid cysts and symptoms of compression typically require surgery. For patients with symptoms other than compression, initial aspiration of cyst fluid may be curative. For patients with recurrence of symptoms after repeated aspiration, we suggest surgical excision (Grade 2C). Ultrasound-guided percutaneous ethanol ablation is an alternative to surgery in centers where these procedures are performed routinely. However, such procedures could result in fibrosis and recurrent laryngeal nerve palsy. (See 'Nonfunctioning cysts' above.)

Asymptomatic patients with nonfunctioning parathyroid cysts may require no therapy. Patients should be monitored for the occurrence of symptoms (due to an enlarging parathyroid cyst). For patients who remain asymptomatic and normocalcemic, we obtain an ultrasound and serum calcium level in one year, and then less frequently thereafter, depending on physical exam and documented radiologic growth. (See 'Nonfunctioning cysts' above.)