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Ann Thorac Surg 1999;67:581-590
© 1999 The Society of Thoracic Surgeons

Current Review

Mediastinal parathyroid cysts revisited

Thomas W. Shields, MDa, Steven C. Immerman, MDa

a Department of Surgery, Northwestern University Medical School, Chicago, Illinois, USA

Address reprint requests to Dr Shields, Northwestern University Medical School, 250 E. Superior St, Suite 201, Chicago, IL 60611-2950
e-mail: dapril{at}nmh.org


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Addendum
 Footnotes
 Acknowledgments
 References
 
Background. A case of a functioning mediastinal cyst is presented.

Methods. A comprehensive review of the literature found 93 patients in whom a parathyroid cyst or cysts extended into, or was completely contained within, the mediastinum. Including our patient, there were 46 men and 45 women, and the gender was not recorded in three.

Results. The cysts were located in the anterosuperior region in 56 patients, in the middle region of the mediastinum in 26, and in the anterior, prevascular region in 12. Thirty-nine patients had functioning cysts associated with hyperparathyroidism of varying severity; seven patients presented with a hypercalcemic crisis. Local symptomatology consisted of a neck mass, respiratory distress, and occasional dysphagia or chest pain. Recurrent laryngeal nerve paresis was present in nine patients, and innominate vein compression or thrombosis was present in two. The cysts in all but four patients were treated by open surgical excision; two were treated by thoracoscopy, and two patients only had fine-needle aspiration of the cyst. The cyst was excised via a cervical approach in 67 patients and by a thoracotomy or median sternotomy or a variation thereof in 23. There was no operative mortality and morbidity was minimal.

Conclusion. Surgical resection was successful in all and remains the treatment of choice for mediastinal parathyroid cysts.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Addendum
 Footnotes
 Acknowledgments
 References
 
The parathyroid glands were described initially by the Swedish anatomist Sandström in 1880, and he was the first to identify a macroscopic cyst in a parathyroid gland [1]. It was not until 1905 that a parathyroid cyst was removed from the neck by Goris, a Belgian surgeon [2]. The first report of the removal of a parathyroid cyst from the mediastinum was published by de Quervain at the Chirugischen Klinik des Inspelspitals in Bern, Switzerland in 1925 [3]. Since then, numerous reports of one or more cases and reviews of the literature have been published. The anatomic location, protean clinical manifestations, and biochemical activity of these uncommon mediastinal parathyroid cysts have been described in varying detail.

Mediastinal parathyroid cysts can vary in size from a macroscopic cyst 0.5 cm in diameter to a giant cyst of 12 cm or larger in its greatest dimension [4, 5]. Most cysts are grossly thin-walled, translucent, and unilocular. The fluid contained therein is colorless but at times can be opalescent, gray, or serosanguinous in appearance. Microscopically, the thin fibrous wall is lined by a single layer of cuboidal or low columnar cells, and islets of normal parathyroid cells are found within the fibrous tissue of the wall. Infrequently, larger masses of parathyroid tissue are present within the cyst [6, 7]. Thymic tissue, fatty tissue, or calcifications have been identified within the cyst wall [8–13]. In addition to the typical parathyroid cyst, a second variety has a thicker layer of parathyroid cells on the inner surface, and, in all these lesions, a well-defined macroscopic cyst 1 to 5 cm or greater in diameter is readily identified [6, 14]. Very rarely, a multiloculated cyst is present [11, 15]. Calcifications also have been present in the walls of these cysts [16]. These cysts are often referred to as cystic parathyroid adenomas but, just as often, they are simply referred to as parathyroid cysts [6, 14, 17, 18]. The fluid within these latter cysts can be colorless but more often is darkish brown, suggesting previous hemorrhage or degeneration within the adenomatous structure [14, 15]. Of interest, one of this variety of parathyroid cyst was a 1.3-cm cystic chief cell adenocarcinoma contained within the substance of the thymus [18]. A mediastinal parathyroid cyst is usually solitary, but, rarely, more than one cyst might be found in a single patient [4, 17]. The typical cyst usually has a scanty blood supply, but a vascular pedicle could be identified [19]. The cystic adenoma, on the other hand, tends to have a more identifiable blood supply [5].

A mediastinal parathyroid cyst can be asymptomatic, being diagnosed on a routine neck examination or a routine chest x-ray. At times, the mass will become apparent on swallowing when the patient is in the supine position and the neck is extended [7]; this type of cyst is similar to the so-called goitre plongeaut. When the cyst is present as a palpable mass at the base of the neck, it often is referred to as a cervical mediastinal cyst, but they are considered in the global category of mediastinal parathyroid cysts. The cyst might cause dyspnea as a result of marked tracheal deviation or narrowing or might produce dysphagia due to esophageal compression. Hoarseness due to paresis of one of the vocal cords as the result of pressure or tension on the ipsilateral recurrent laryngeal nerve has been reported infrequently [12, 19–24]. Left innominate vein compression or thrombosis also has been recorded [13, 25].

Many mediastinal parathyroid cysts are associated with hyperparathyroidism and are classified as functioning cysts [4–7, 15, 17, 18]; the cysts not associated with this disease state are designated as nonfunctioning cysts. The hyperparathyroid state associated with a functioning cyst can be asymptomatic and diagnosed only on serum determinations of consistently elevated levels of calcium or elevated serum levels of circulating parathyroid hormone (PTH). In most patients so afflicted, however, one or more of the clinical manifestations of hyperparathyroidism, including acute hypercalcemic crisis, occurs [5, 26, 27]. In one patient, the functioning cyst was one of the endocrine neoplasias associated with a multiple endocrine neoplasia type I syndrome [28]. A patient with severe hyperparathyroidism associated with a large mediastinal parathyroid cyst was treated recently by one of us (SCI).

The patient, a 57-year-old white man, was seen in mid 1997. He had a history of pain in the lower right chest wall with inspiration, a mild, nonproductive cough, and a lump on his left leg that appeared after a previous episode of minor trauma. The leg lesion was warm and tender on palpation. The patient had noted that his legs had been bowed for many years.

Medical history revealed that he had a fracture of his left wrist in 1992. At that time radiographs showed a cystic lesion at the fracture site. In 1993 the patient passed a calcium phosphate kidney stone. The serum calcium levels were not evaluated at the time of either of these episodes.

The physical examination results were normal except for tenderness along the right rib cage and the presence of a hard prominence in the left leg, which appeared to be attached to the tibia. The overlying skin was not erythematous but was slightly warm.

Results of laboratory studies were normal except that serum calcium was 13.4 mg/dL (normal 8.5 to 10.5 mg/dL) and phosphorus was 1.8 mg/dL (normal 2.5 to 4.5 mg/dL). The patient’s PTH level was over 10 times the normal laboratory value.

The chest radiographs showed a right paratracheal mass with deviation of the trachea to the left (Fig 1). In addition, there was a large right-sided pleural-based mass with associated destruction of the right seventh and eighth ribs posterolaterally. A computed tomographic (CT) scan of the chest with contrast medium disclosed a 6 x 6-cm mediastinal mass in the right paratracheal area. The mass displaced the trachea and esophagus to the left (Fig 2). Also noted was a large, expansile, destructive lesion involving one of the ribs on the right side. The chest wall lesion measured approximately 5 x 3 cm. Radiographs of the left tibia and fibula showed a bubbly bone lesion of the tibia, indicative of a brown tumor. Bone scan showed increased areas of radiotracer uptake in the distal left tibia, and in the right eighth and ninth ribs. Dramatic bowing of the legs was seen.



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  		Fig 1. (A) Posteroanterior radiograph shows a right superior mediastinal mass and a right-sided chest wall mass that on biopsy was found to be a brown tumor of the rib cage. (B) Right lateral radiographic view shows a large mediastinal mass located in the retrotracheal portion of the visceral compartment.

 


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  		Fig 2. Computed tomographic scans at different levels of the large right-sided mass located in the retrotracheal portion of the visceral compartment of the mediastinum. Note calcification in the wall of the mass.

 
CT-guided fine-needle aspiration biopsies of the right chest wall mass and tibial lesion were nondiagnostic. Results of core needle biopsy the tibial lesion demonstrated resorptive changes consistent with hyperparathyroidism, and the chest wall lesion was diagnosed as a brown tumor of hyperparathyroidism.

The clinical diagnosis of mediastinal parathyroid adenoma or functioning cystic adenoma with resulting hypercalcemia was made. The patient underwent a standard right posterolateral thoracotomy, and a 9 x 8-cm lobulated, partially cystic mass was removed from the upper middle mediastinum inferior to the subclavian artery and lateral to the trachea and esophagus. It was directly posterior to the superior vena cava, and its blood supply could be seen coming from a large vessel descending from the neck. The cystic mass was 151 g. Once the cystic fluid was removed, the lesion weighed 58 g. Frozen section examination revealed a cystic parathyroid adenoma.

Postoperatively the patient’s serum calcium decreased to as low as 7.2 mg/dL, but with only minimal symptoms, which were treated easily with dietary calcium supplementation; otherwise, the postoperative course was uneventful.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Addendum
 Footnotes
 Acknowledgments
 References
 
In reviewing the literature relative to mediastinal parathyroid cysts, it became apparent that many conflicting statements have been made regarding the number, anatomic location, and clinical presentation of these cysts. Not only is this true among the many reviews, but misstatements have occurred in individual reports as well. To clarify the conflicting data, we reviewed the potentially pertinent literature that has been published since De Quervain’s report in 1925 until December 31, 1997. Included in the global category of mediastinal parathyroid cysts are all reported parathyroid cysts, typical and cystic adenomas, that have been described or have been shown by accompanying illustrations to have extended partially from the neck through the thoracic inlet into the mediastinum or to have been completely contained within the mediastinum.

Rather than classifying these mediastinal cysts as primarily functioning or nonfunctioning, as is commonly done, we decided to classify each cyst as to its anatomic location. Three areas were defined. The first is the anterosuperior mediastinum, which we have defined as the retrosternal space above and dorsal to the innominate vessels and anterolateral to the trachea (the pretracheal portion of the visceral compartment of the mediastinum). The second is the middle mediastinum, defined as the retrotracheal portion of the visceral mediastinal compartment, extending posteriorly to the anterolateral border of the thoracic spine. The third location is the true anterior, prevascular compartment of the mediastinum. The localization of each cyst into one of these three areas was determined by the information given in the history, physical examination, radiographic features including CT scans and magnetic resonance imaging, sonograms when present, and operative findings in each report. Extension of a cyst located primarily in the pretracheal space into the retrotracheal space and vice versa can occur. Rarely can a pretracheal cyst enter the anterior compartment [13]. In many reports, the information was incomplete, but a reasonable location of each cyst could be made.

Functioning parathyroid cysts were documented by elevated serum calcium levels and elevated serum PTH levels, when the latter was determined, and by their return to normal levels after removal of the cyst. The presence of PTH within the cystic fluid is now known to be diagnostic of a parathyroid cyst, but this finding alone does not denote the presence of hyperparathyroidism [29–32]. Data were also collected regarding the age and gender of the patients, the site and size of the cysts, significant symptomatology or findings, and the treatment rendered.


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Addendum
 Footnotes
 Acknowledgments
 References
 
Ninety-four patients with a mediastinal parathyroid cyst or cysts as defined, including the patient presented in this report, were identified. In 56 patients (59.5%), 59 cysts were located or partially descended into the anterosuperior space (Table 1). In 26 patients (27.6%), the cyst was in the middle compartment (Table 2). In 12 patients (12.7%), the cyst descended into (2 patients) or was completely contained (10 patients) within the anterior mediastinal space (Table 3). In this latter group four cysts were intrathymic [18, 71, 73, 75]. There were 46 men and 45 women, and the gender was not recorded in 3 patients. The youngest patient was 24 years old and the oldest was 83 years old. The distribution of patients by age was almost equal in each of the fourth through eighth decades of life. Forty-seven cysts were located on the right, 41 on the left, and two in the midline. Whether the cyst was on the right or left side was not noted for seven cysts. Nine patients (9.5%) had evidence of recurrent nerve injury preoperatively [12, 17, 20–24, 57, 64].


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  		Table 1. Parathyroid Cysts Located in the Anterosuperior Mediastinum

 

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  		Table 2. Parathyroid Cysts Located in the Middle Mediastinum

 

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  		Table 3. Parathyroid Cysts Located in the Anterior Mediastinum

 
Thirty-nine patients (41.4%) had functioning cysts; in 17 the cyst was in the anterosuperior space (30.3%, 17 of 56), in 16 the cyst was in the middle compartment (61.5%, 16 of 26), and in 6 the cyst was in the anterior prevascular space (50%, 6 of 12). There were 20 men, 17 women, and the gender not recorded in 2 in the functioning group. Three women and four men presented in hypercalcemic crisis [5, 26, 27, 50, 66]. Two additional patients had questionable functioning cysts, but hyperparathyroidism was not sufficiently documented in these cases [24, 48]. Another patient had a "functioning" cyst removed, but hyperparathyroidism persisted until a missed adenoma was removed [17]. In one other patient, an intrathymic cyst was associated with a parathyroid adenoma, and the source of the hyperparathyroidism could not be determined [75].

A standard open surgical resection was done in 90 patients. In 67 patients (74.4%), the cyst was removed by a cervical approach. In 23 patients (25.5%), including the present patient, thoracotomy, median sternotomy, or a variation thereof, was performed. Surgical resection was successful in all cases except the patient with the parathyroid adenoma [17]. No deaths have been reported, and major morbidity was absent in almost all cases. Minor and temporary signs of mild hypocalcemia in the early postoperative period after the removal of a functioning cyst occurred in some patients. One patient had an esophageal injury that resulted in a wound infection and a temporary esophageal cutaneous fistula [7]. A second patient with a large right-sided cyst in the middle compartment had a right recurrent laryngeal nerve injury at the time of resection [65]. In a third patient, a urinary infection resulted in septicemia that was treated successfully with antibiotics [26]. In two patients a thorascopic approach was used [67, 68]. Two patients were treated only by fine-needle aspiration of the cystic fluid and appropriate medical management as indicated; in a patient with a small functioning cyst in the middle mediastinum, aspiration alone was curative, and in an older patient with hypercalcemic crisis, aspirations as a palliative maneuver was done because the patient refused surgical resection [60, 66].

In addition to these 94 cases, other mediastinal parathyroid cysts have been reported, including two cases by Scholz and colleagues [76],* which appeared to have been reported subsequently and thus were not included in the present review. In several cases listed in the review by Hirano and associates [67], the sources could not be confirmed in Index Medicus nor were they included in any other reviews; thus they were not included. In two other patients a cervical parathyroid cyst was in contact with or attached by a cord to a superior pole of the thymus. From the description supplied, the cyst in each case appeared to be confined to the neck [46, 77]. Finally, another case was alluded to by Delaunay and associates [22] that was published as a Thèse de Médicine (Rouen) in 1984 by Nicaise, which was unobtainable.


   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Addendum
 Footnotes
 Acknowledgments
 References
 
There are many theories concerning the origin of parathyroid cysts, including (1) fluid gradually accumulates within a parathyroid gland to form a retention cyst [78, 79]; (2) they have been suggested to be derived from vestigial remnants of the Kürsteiner canals [80, 81]; (3) the cyst is formed by the coalescence of preexisting microcysts that have been described in 50% of the parathyroid glands at autopsy [82, 83]; (4) they develop from embryologic remnants of the third or fourth branchial cleft [84–86]; and (5) they are the end result of cystic degeneration of a parathyroid gland or a preexisting adenoma or hyperplastic gland. This latter hypothesis was initially suggested by Alagna in 1908 [87] and appears to be a major factor in the development of many of the parathyroid cysts, as noted by numerous authors [14, 18, 26, 32, 44, 68].

Regardless of the actual origin, most mediastinal parathyroid cysts that are located in or extend into the anterosuperior space appear to be associated with an inferior parathyroid gland (embryologic parathyroid III). A superior gland (embryologic parathyroid IV) infrequently has been the source [43], as has a supernumerary fifth gland [18]. Conversely, cysts in the middle compartment are associated with an original superior gland (parathyroid IV) in at least one fifth of the cases [11, 21, 27, 28, 65]. This situation is not difficult to visualize because a displaced superior parathyroid gland (parathyroid IV) most often migrates laterally into the retrotracheal prevertebral space. The displaced gland occupies the same plane or is behind the the esophagus. The presence of a parathyroid gland in this space was reported in 7% of the autopsy specimens examined by Gilmour and in 1% of the specimens studied by Wang [88, 89]. The latter investigator also reported the presence of 34 parathyroid adenomas in the low retrotracheal space in the neck or in the superior aspect of this space in the mediastinum in 112 patients who were reoperated on for persistent hyperparathyroidism [90]. Other authors have emphasized the finding of a previously undetected superior parathyroid adenoma in this area [91]. Such displaced tissue readily might be envisioned as the source of a parathyroid cyst in the middle mediastinal area as defined; however, documentation of the source is lacking for many cysts in the middle compartment because most patients with these cysts do not undergo a neck dissection. The superior gland is not always the source; we noted that in one case in which a neck dissection was done, the missing gland was the right inferior parathyroid [5]. The cysts in the anterior compartment are associated mainly with an inferior gland or an occasion with a fifth supernumerary gland [73].

The diagnosis of a mediastinal parathyroid cyst rarely was made preoperatively in the first 75 years of this century; however, Crile and Perryman [12] made a tentative diagnosis of a cervical cyst in 1953 by aspiration of oncocytes suggestive of parathyroid origin, and in 1963 Chimènes and associates [37] identified PTH in the aspirate of a cervicomediastinal cyst in a patient with hyperparathyroidism. Parathyroid scintigraphy yielded positive results in only one patient [68]. However, with the use of CT scans, magnetic resonance imaging, and sonography to establish the mass to be cystic in nature, fine-needle aspiration of a clear, watery fluid is suggestive of the diagnosis. An analysis of the fluid from the cyst that shows increased PTH is diagnostic [29–32]. In both the nonfunctioning and functioning parathyroid cysts the fluid has a PTH level exceeding that of a simultaneous blood serum level; the normal serum level has a range of 50 to 340 pg/mL. The normal range is higher (430 to 1,860 pg/mL) in a C-terminal midregion assay [61]. Silverman and associates [92] discussed the considerable confusion that has existed as the result of the various methods of measuring the PTH levels; they suggested the C-terminal/midregion determination should be the assay of choice. Nonfunctioning cysts have been reported to have PTH levels in the cystic fluid from 6,00 to 416,650 pg/mL with accompanying normal serum levels [30, 32]. Functioning cysts have had PTH levels from over 2,000,000 to higher than 6,000,000 pg/mL [61, 66]. With aspiration, the PTH levels in either type have been shown to decrease [61]. The mechanism by which the high cystic level of PTH gains access to the general circulation and thus affects the level of the serum PTH is unknown. Whether increased permeability through the cyst wall or a greater blood supply to and from the cyst permits the high cystic fluid PTH level to enter the circulation or whether the actual mass of active parathyroid cells is the explanation is unknown. Regardless of the mechanism, once the serum PTH levels is above normal, the sensitive regulatory control between the serum ionized calcium concentration and PTH secretion is lost. As a result, the serum calcium level increases and a hypercalcemic state then exists. The exact manner by which this occurs is still being investigated [93].

All functioning mediastinal parathyroid cysts should be treated surgically, and a complete neck exploration should be done when possible to exclude other parathyroid gland involvement. Nonfunctioning cysts are likewise best removed; although, some advocate needle aspiration alone, because many cervical cysts have been treated successfully in this manner [30–32]. This method might be adequate for small, asymptomatic lesions, but cysts that produce local symptoms, ie, respiratory complaints, dysphagia, recurrent nerve paresis, or innominate vein compression, should be removed.

The surgical access is dictated by the location of the cyst. Almost all cysts in the anterior superior mediastinum as well as many in the anterior mediastinum (prevascular space) can be removed successfully by cervical incision alone. Cysts in or extending into the anterior compartment could require a median sternotomy or a variation thereof. Occasionally, a cyst in the middle mediastinum can be excised by cervical incision but most require a thoracotomy. Special care must be exercised in the removal of large cysts in either the anterior superior or middle areas to prevent injury to the ipsilateral recurrent laryngeal nerve that is in close proximity to these lesions. The role of videothoracoscopic surgical removal of these lesions is still evolving.


   Addendum
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Addendum
Footnotes
 Acknowledgments
 References
 
Two additional case reports of parathyroid cyst have appeared in the Japanese literature since the closing date of this report (December 31, 1998). Hattori and associates (J Jpn Assoc Chest Surg 1998;12:543–48) reported on a 51-year-old asymptomatic man who had a 3-cm, nonfunctioning cyst removed from the right side of the middle mediastinal compartment. Shibata and associates (J Jpn Assoc Chest Surg 1998;12:676–80) treated a 56-year-old asymptomatic man in whom a 3.5 x 3-cm, nonfunctioning cyst associated with the left lobe of the thymus was removed by left-sided video-assisted thoracoscopy.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Addendum
 Footnotes
 Acknowledgments
References
 
Dr. Ryosuki Tsuchia, National Cancer Center, Tokyo, Japan, and Professor Yoh Watanabe, Department of Surgery, Kanazawa University School of Medicine, Kanazawa, Japan, supplied and translated many of the Japanese publications that we could not obtain in the United States. For this we are grateful because their help permitted us to present a more complete review of the literature.


   Footnotes
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Addendum
 Footnotes
Acknowledgments
 References
 
* References 76 through 96 may be obtained from the senior author on request. Back


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Addendum
 Footnotes
 Acknowledgments
 References
 

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