An unusual mediastinal giant parathyroid adenoma: A rare case report

Abstract

Parathyroid adenoma is the most common cause of primary hyperparathyroidism. Giant parathyroid adenoma is considered a rare subtype of parathyroid adenomas that weigh more than 3.5 grams and cause a small number of adenoma related hyperparathyroidism. We present a case of 68-year-old asymptomatic male patient who had hypercalcemia and markedly high parathyroid hormone level on routine blood testing. Radiological investigations demonstrated a large mediastinal mass that showed peripheral high uptake on sestamibi scan. Histopathology confirmed the diagnosis of giant parathyroid adenoma. Giant parathyroid adenomas can have an atypical radiological appearance and present as a mediastinal mass that resembles other mediastinal masses, making it important to include in the list of possible diagnoses.

Background

The parathyroid glands (PG) are normally 2 pairs in number and located posterior to the thyroid gland with each gland weighing about 40-60 mg [1]. During embryological development, PG migrate from the mediastinum to the neck region [2]. A parathyroid adenoma (PA) that is hyperfunctioning, is the most common cause of primary hyperparathyroidism (PHPT), typically weighs less than one gram [3]. Ectopic parathyroid gland (EPG) occurs when there is an atypical migration of the gland to a final destination such as: intra-thymic, mediastinal, submandibular, or inside the carotid sheath [4]. Similarly, an adenoma may arise in EPG which is then described as ectopic parathyroid adenoma (EPA) [4]. Giant parathyroid adenoma (GPA) is considered a rare subtype of PA's that weigh more than 3.5 grams and cause a small number of PA related PHPT [5].

Case presentation

We present a case of a 68-year-old male, with no significant past medical or surgical histories who was referred from the primary health center to a tertiary hospital due to abnormal routine screening blood test that showed hypercalcemia. The patient was asymptomatic, he denied any history of abdominal pain, constipation, increased urination or irritability. The patient stated that he had been using over-the-counter calcium pills for over 2 months.

His family history was unremarkable for similar presentations or malignancies. His vital signs, electrocardiogram, and physical examination including neck, abdomen and neurological exam were all unremarkable. His blood tests revealed an elevated calcium, high creatinine, low phosphorus, markedly high parathyroid hormone (PTH) level and low hemoglobin (Table 1). Other blood tests like white blood count, C-reactive protein and liver function test were normal.

Table 1.

Summary of the patient's abnormal blood tests.

Lab test	Result	Normal range
Adjusted calcium	3.73 mmol/L	2.2-2.6 mmol/L
Creatinine	143 umol/L	62-106 umol/L
Phosphorus	0.70 mmol/L	0.8-1.5 mmol/L
PTH	1,404 pg/mL	15-65 pg/mL
Hemoglobin	9 gm/dL	13-17 gm/dL
Vitamin D	18 ng/mL	12-19 ng/mL – Insufficiency
		≥20 ng/mL – Optimal value

Chest X-ray of the patient revealed a large mediastinal mass extending to the lower neck region as described in (Fig. 1). Computed tomography (CT) scan of the chest with intravenous (IV) contrast was requested to further evaluate the mass. The scan showed a 3 × 4 × 5 cm right paratracheal and posterior mediastinal low attenuation mass reaching to lower neck (Fig. 2).

Fig. 1.

Frontal chest x-ray. Right paratracheal oval shaped opacity (purple star) causing obtuse margins with adjacent lung (red) and compressing the right tracheal wall (blue). Mass is seen extending above the clavicle. No bone destruction seen.

Fig. 2.

Selected images of CT chest with IV contrast, axial (A and B), coronal (C) and sagittal (D). There is a well-defined oval shaped hypodense posterior mediastinal and right paratracheal mass (purple), reaching to lower neck (A). The mass showed internal thin enhancing septae (green), and partially thick enhancing wall at its superior aspect (red). Note the mass effect on the trachea and esophagus (blue).

Sestamibi parathyroid scan demonstrated an avid uptake at the periphery of the mass with no washout after 2 h suggesting parathyroid origin of the mass (Fig. 3). Along the course of hospitalization, the patient was treated with IV hydration, 4 doses of intramuscular Calcitonin 256 units, and IV Zoledronic acid 4 mg. Based on the radiological and sestamibi scan findings, parathyroid carcinoma could not be excluded, therefore surgical excision was recommended.

Fig. 3.

Selected images of Technetium 99 m sestamibi scan 20 min post IV injection (A), 2 h post injection (B) and Single Photon Emission Computed Tomography (SPECT) axial view (C) and coronal (D). Peripheral high tracer uptake of the mediastinal mass (red circle) mainly at its superior aspect without central uptake (white star). Note the normal uptake of thyroid gland (blue arrow) at 20 min (A) which typically washes out at 2 h (B).

Postsurgical excision of the mass, the gross pathological examination showed a 3 × 4 × 5 cm mass, weighing approximately 20 grams. It appeared well-circumscribed, unencapsulated, with tan and hemorrhagic cut surfaces (not shown).

Microscopic examination showed a proliferation of parathyroid parenchymal cells with follicular, solid, and nested architecture separated by fibrous bands. The predominant cell types included chief cells (Fig. 4A) and oncocytic (oxyphil) cells, with a minor component of clear cells. No nuclear pleomorphism, mitotic activity or surrounding tissue is seen. By immunohistochemistry, the tumor cells showed positive staining for PTH (Fig. 4B) and CK AE1/AE3, with low proliferative activity by KI-67.

Fig. 4.

Histopathological sections of the mass. A: High power view of the tumor cells shows cellular proliferation of the chief cells (H&E, x40). B: Parathyroid adenoma cells are positive for parathyroid hormone (Immunohistochemistry, 10X).

Discussion

The clinical manifestations of PHPT are mostly related to hypercalcemia [6,7]. Usually, large PAs and parathyroid carcinoma secrete more PTH which in turn can lead to higher calcium levels and severe hypercalcemia symptoms [6,8], however this did not apply to our case. Nonetheless, PHPT is usually diagnosed incidentally on routine testing with elevated calcium and PTH levels [6,8].

This reports a case of a rare large parathyroid mass that involved thoracic and neck anatomical compartments. Given its large size and weight, the mass was labelled as GPA. Radiologically, it was difficult to predict whether the mass originated from an ectopic gland in the mediastinum and extended to the lower neck, or vice versa. The surgical operative notes described the bulk of the mass arising from the posterior mediastinum. Nevertheless, both theories would have had the same management plan. Anatomically, the recognized mediastinal compartments are not restricted by tissue boundaries, accordingly a significantly enlarging mediastinal mass can occupy multiple compartments [9].

Unlike our case, usually PAs are hyper-enhancing on CT [10,11]. On a retrospective study performed on 55 patients with PAs by Randall et al., 92.7 % of the adenomas showed hyperenhancement on CT [10]. However, the adenoma in our case was of low attenuation on CT with only partial mild wall enhancement at its superior aspect and few enhancing septae.

The case had multiple unusual and infrequently encountered characteristics on imaging including adenoma size that aligns with the definition of GPA, involvement of more than one mediastinal compartment including lower neck, and the low attenuation appearance on CT. Concurrent presence of all the aforementioned features in a case is extremely rare and posed a diagnostic challenge as PA was among the differential but not the first diagnosis on CT and chest radiography.

The case presents an unusual and diagnostically challenging rare GPA that involved more than one mediastinal compartment. GPAs can have an atypical radiological appearance and present as a mediastinal mass that resembles other mediastinal masses, making it important to include in the list of possible diagnoses.

Ethical approval

The case report publication was also approved by the head of the department.

Patient consent

The authors of this manuscript declare that an informed consent for publication of this case was obtained from the patient.