Intratracheal parathyroid gland: an unexpected diagnosis

Abstract

Ectopic or supernumerary parathyroid tissue has been generally described in the literature in cases found during workup for parathyroid adenoma. We present two unique cases of intratracheal parathyroid gland, a rare occurrence that has not yet been described in the literature. In both cases, the masses were found incidentally and showed no clinical or laboratory evidence of hyperparathyroidism. In both cases, surveillance was chosen as the method of treatment. We present this case series to increase awareness of this potential diagnosis.

Background

Supernumerary parathyroid glands are present in 3% to 20% of the patients per previous reports, with the total number of glands encountered varying from 5 to 11 in cadaveric studies. Glands may be small or in close proximity to normal gland, as well as more distal in location.

Reports have shown supernumerary or ectopic parathyroid glands in retropharyngeal, retrolaryngeal or retro-oesophageal locations, anterior or posterior mediastinum, thymus, anterior cricoid or intrathyroidal. Ectopic parathyroid tissue presenting with signs of hyperparathyroidism is typically consistent with a parathyroid adenoma. Ectopic parathyroid glands that do not present with hyperparathyroidism have been referred to as non-functioning adenomas, or in one case, an ectopic parathyroid gland. There have been sporadic cases in the oropharynx, nasopharynx or carotid sheath. There have been no previous reported cases of parathyroid gland in an intratracheal location.

Case presentation

Case 1

A 36-year-old woman initially presented after imaging workup for neck pain showed a paratracheal mass.

Case 2

A 73-year-old man with a T1 squamous cell carcinoma of the glottis was referred prior to commencing radiation therapy as a PET (positron emission tomography) scan revealed an incidental right parathyroid adenoma.

Investigations

Case 1

Coronal CT showed a lesion measuring 1.9 cm x 1.6 cm abutting the left side of the trachea in the subglottic region (figure 1).

Figure 1.

Coronal image of lesion measuring 1.9 cm x 1.6 cm abutting left side of trachea.

Bronchoscopy showed normal vocal cords with an area of 25% narrowing on the left lateral portion of the trachea. This was also partially visualised on in-office flexible laryngoscopy (figure 2). The mass appeared tan and smooth with prominent vascular markings. The airway was patent. A biopsy was obtained via transbronchial needle biopsy in order to obtain a diagnosis. Transbronchial fine needle aspiration and cytology smears of the mass were hypercellular. The cells were arranged in flat sheets, with small acini and singly dispersed. Capillaries were noted with larger groups of cells forming pseudopalisades around the capillaries. The cells had uniform round nuclei with evenly dispersed chromatin. Cytoplasmic quality varied from abundant and vacuolated to densely granular. The cytomorphology was therefore consistent with parathyroid tissue (figure 3). After histopathological diagnosis, parathyroid hormone (PTH) and calcium levels were obtained. The PTH and calcium were within normal limits, corroborating a diagnosis of non-functional parathyroid adenoma or normal ectopic tissue.

Figure 2.

Bronchoscopy showing 25% narrowing on the left lateral portion of the trachea.

Figure 3.

Fine needle aspirate smear demonstrating hypercellularity with flat sheets and small acinar arrangements of parathyroid cells. Diff-Quik 20x.

Case 2

PET imaging showed a 1.4 cm x 0.9 cm rapidly enhancing nodule posterolateral to the trachea below the level of cricoid with extension through the wall of the trachea to the submucosa (figure 4). Technetium (99mTc) sestamibi scan showed PTH tissue. Please see reports carefully as to what made this an adenoma. The imaging was suggestive of intratracheal parathyroid adenoma.

Figure 4.

Positron emission tomography axial imaging showed a 1.4 cm x 0.9 cm rapidly enhancing nodule posterolateral to the trachea below the level of cricoid with extension through the wall of the trachea to the submucosa at the level of the tracheo-oesophageal groove.

Flexible laryngoscopy in clinic revealed laryngeal changes consistent with squamous cell carcinoma. The vocal cords were mobile bilaterally, and there was no subglottic or intratracheal mass observed. The decision was made to not proceed with any biopsies of the parathyroid adenoma. PTH and calcium levels were obtained and were within normal limits, suggesting a non-functional parathyroid adenoma.

Treatment

The current recommendation for management of a parathyroid adenoma with hyperparathyroidism is preoperative localisation with a sestamibi scan, and surgical excision.¹ The six known cases of non-functional parathyroid adenomas reported in literature^2–5 were all surgically removed. Poppe et al reported a parathyroid adenoma with atypical features, which was surgically removed due to concern of a pre-cancerous lesion.² Development of cancer may be a concern for all ectopic glands, and this mandates either close surveillance or complete excision for definitive management of these lesions.

Fine needle aspiration (FNA) can be used as a diagnostic tool,¹ but there is a risk of tumour seeding if cytology reveals parathyroid carcinoma.⁶ Dimashkieh and Krishnamurthy⁷ developed criteria to help distinguish parathyroid from thyroid tissue on FNA: presence of stippled nuclear chromatin, usual presence of vascular network with attached epithelial cells and the frequent occurrence of single cells. Agarwal et al⁸ had consistent findings in regards to these FNA criteria, but suggested ancillary studies in addition to FNA cytology for definitive diagnosis of parathyroid tissue due to low sensitivity of detecting parathyroid tissue and some overlapping histological features with thyroid tissue.⁸

As was seen in our first case, FNA was necessary to confirm the diagnosis and was far less invasive than surgical excision, especially considering the asymptomatic nature of the lesion and unusual location. Prompt diagnosis of intratracheal parathyroid tissue in this way is necessary in preventing unnecessary intervention or disruption of functional tissue.

Outcome and follow-up

Case 1

Due to the asymptomatic nature of the mass, the patient elected for surveillance. CT imaging and laboratories were ordered annually. The patient was counselled about airway precautions and the importance of compliance due to the sensitive location of the mass. The mass has not changed in size and no laboratory abnormalities or symptoms have developed.

Case 2

Due to concurrent diagnosis of squamous cell carcinoma of the larynx, the decision was made to continue with radiation therapy with the recommendation to proceed with removal of parathyroid adenoma after completion of radiation therapy. Once the patient completed radiation, he returned to clinic to discuss surgical management and additional options. The patient instead elected for surveillance due to the asymptomatic nature of the mass and morbidity of surgery. He will continue to be monitored by endocrinology and undergo repeat imaging annually for this mass.

Although both patients elected for surveillance, we caution before proceeding with this management. There are no established guidelines for these cases, and the decision to proceed with surgery versus surveillance should be considered on a case-by-case basis. Surgical removal is ideal due to the concern that parathyroid carcinoma cannot be completely ruled out. Our patients did not want surgery due to the morbidity of the procedure and asymptomatic nature of the mass. Both patients were heavily counselled on the risks of surveillance. However repeat scans showed no further increase in the size of the masses (Please confirm that this statement is accurate). We emphasise cautious judgement when encountering these cases.

Discussion

Parathyroid adenomas are relatively common and affect 0.2% to 0.5% of the population,⁹ which presents with asymptomatic hypercalcaemia 80% of the time.^{4 10–12} The classic symptomatic patients with skeletal, renal, gastrointestinal, neurological and psychiatric manifestations are rare today due to addition of routine measurement of serum calcium levels in the 1970s.¹³ Ectopic parathyroid tissue has been generally described in literature in cases found during workup for parathyroid adenoma. Reports have shown supranumerary or ectopic glands in retropharyngeal, retro laryngeal, retrotracheal or retro-oesophageal location, anterior or posterior mediastinum, thymus, anterior cricoid or intrathyroidally.4 9 14–19 There have been sporadic cases in oropharynx, nasopharynx or carotid sheath.^{9 20} Phitayakorn¹⁷ showed superior ectopic parathyroid glands may be found in the tracheo-oesophageal groove, retro-oesophageal, intrathyroidal, within the carotid sheath and para-oesophageal locations, while inferior ectopic parathyroid tissue was located in the thymus, anterosuperior mediastinum, intrathyroidal, in the thyrothymic ligament and submandibular locations. To our knowledge, these are the first cases of intratracheal benign parathyroid tissue or adenoma. We have not excluded the possibility of the parathyroid tissue being an ectopic gland versus a non-functioning parathyroid adenoma. Ectopic thyroid glands are referred to as functioning parathyroid adenomas aside from six cases of non-functional parathyroid adenomas reported in literature.^2–5 Uludağ et al²¹ describes a case of ectopic parathyroid tissue that did not present with hyperparathyroidism, which he refers to as an ectopic parathyroid gland. The correct nomenclature has not been established due to the rarity of ectopic parathyroid tissue without clinical hyperparathyroidism. There have been no previous reports of intratracheal parathyroid gland.

Ectopic parathyroid glands have been attributed to abnormal migration during embryogenesis, with inferior parathyroid glands more likely to be misplaced due to extensive migration. The incidence of inferior ectopic parathyroid glands is 62% vs 38% for ectopic superior parathyroid glands.¹⁷ Phitayakorn et al¹⁷ performed a chart review of patients operated on for hyperparathyroidism and found 37 of 231 (16%) had abnormal ectopic parathyroid gland tissue. This study also showed that ectopic parathyroid gland patients presented with higher serum calcium levels compared with patients with hyperthyroidism and abnormal glands found in normal location.¹⁷ However, we did not find this to be the case in our two patients with intratracheal parathyroid glands. Sekine et al³ postulates that a non-functional parathyroid adenoma with positive PTH staining could be attributed to inactivation of PTH excretion due to lack of blood supply.³ This may be the case considering the unique location of the tissue in our two patients.

Although rare, a diagnosis of parathyroid carcinoma cannot be excluded. Biopsy may be useful in determining the pathology. Shantz and Castleman developed histological criteria for parathyroid carcinoma which is as follows: (1) uniform sheets of (usually chief) cells arranged in a lobular pattern separated by dense fibrous trabeculae, (2) capsular or vascular invasion and (3) mitotic figures within tumour parenchymal cells that must be distinguished from endothelial cell mitoses.²² Grossly, parathyroid carcinomas tend to be non-mobile, lobulated and firm.²³ An average of 50% of parathyroid carcinomas have a greyish-white capsule that adheres to surrounding tissue planes thereby making tumour dissection difficult.²³ In contrast, parathyroid adenomas are soft, round and reddish brown in colour and lack invasion into surrounding tissue planes.²³ Clinically, a palpable neck mass is rare in parathyroid adenoma, whereas it occurs in approximately 76% of parathyroid carcinomas.²³

Although histological criterion for parathyroid carcinoma have been established, none of these are pathognomonic of parathyroid carcinoma and commonly overlap with parathyroid adenoma histology and therefore making histological diagnosis insufficient.^{22 23} Additionally, many of the clinical and gross features of parathyroid carcinoma can also be commonly found in parathyroid adenomas. Consistently, parathyroid carcinoma tends to have markedly elevated calcium and PTH compared with mild elevations seen in parathyroid adenomas.^{22 23} Parathyroid carcinomas clinically present with symptoms of severe hypercalcaemia, with renal involvement in up to 80% of patients, and bone involvement in up to 90% of patients.²⁴

There have been very few reported cases of non-functional parathyroid carcinoma.^25–27 Aldinger et al²⁵ demonstrated two cases of parathyroid carcinoma that was made on a histological diagnosis based on presence of mitotic figures.²⁵ There is continued debate pertaining to diagnosing parathyroid adenoma versus parathyroid carcinoma. The occurrence of metastases is the only unequivocal criterion of malignancy that is generally accepted, but they usually occur late in the course of the disease.²⁴ While we cannot exclude the diagnosis of parathyroid carcinoma, this a rare entity and the diagnosis is more likely parathyroid adenoma based on non-functional nature and clinical picture. We will annually monitor these patients for signs of parathyroid carcinoma such as palpable mass, bone pain and renal involvement along with signs of metastasis.

Learning points.

• Ectopic parathyroid tissue cannot be ruled out in hyperparathyroid patients lacking clinical signs.

• This is the first report of intratracheal parathyroid adenoma in the literature.

• Ectopic parathyroid adenoma should be considered in the differential for a tracheal mass.