A 71-year-old woman was admitted with angina pectoris. During hospitalization she developed a myocardial infarction (NSTEMI). Laboratory results revealed a mild elevated troponin and an elevated calcium level (3.35 mmol/l). Subsequently, there was a decreased phosphate (0.36 mmol/l [normal 0.81-1.62 mmol/l]) as well as 16-fold elevated serum level of parathyroid hormone (PTH, 1156 ng/l [normal 10-73 ng/l]), indicating a primary hyperparathyroidism. Sonographically a thyroidal node was detected, not clearly demarcated (TIRADS 5). FNA showed a monomorphic, partial follicular cell population with an immunohistochemical positivity for PTH. Magnetic resonance imaging (MRI) showed a 5 cm large tumor at the right caudal pole of the thyroid with compression of the dorsolateral trachea without infiltration. Surgical removal with en bloc resection of the right hemithyroid with parathyroidectomy was performed. Postoperatively the PTH level dropped to 12.1 ng/l. Pathological examination revealed a 5 cm tumor with infiltration of the thyroid and a perineural invasion. The diagnosis of a presymptomatic parathyroid carcinoma could be established. The affirmative histopathological diagnosis of a parathyroid carcinoma can be challenging and is limited to tumors with evidence of invasive growth in adjacent structures such as the thyroid and/or soft tissue, perineural spaces, angioinvasion of capsular and/or extracapsular vessels, and/or documented metastases.
Parathyroid carcinoma (PC) is a very rare malignant neoplasm that occurs sporadically or as part of a genetic syndrome, called hyperparathyroidism-jaw tumor syndrome (HPT-JT). Approximately 1000 cases of PC were reported in the world literature. The incidence is geographically variable with highest rates in Japan and Italy. Histology is the gold standard for a definitive diagnosis. Herein we present a rare incidentally detected case of a PC.
A 71-year-old woman was admitted to the Emergency Department by ambulance with a sudden feeling of faintness and a weakness in both legs. In her medical history she had hypertension and osteoporosis without fractures. Due to a coronary heart disease she received a drug eluting stent (DES) in the left anterior descending coronary artery in 2011. On admission laboratory results revealed a mild elevated troponin I (189 ng/l [normal < 45 ng/l]), initially treated conservatively. On day 2 after hospitalization troponin I level reached 7510 ng/l, qualifying for a non-ST-elevated myocardial infarction (NSTEMI). Subsequently, a percutaneous transluminal coronary angioplasty was performed with insertion of a DES into the right coronary artery. She recovered well from this intervention and troponin I levels dropped to normal levels. Subsequently, a treatment with a dual platelet aggregation inhibitor was initiated (100 mg acetylsalicylic acid and 75 mg Clopidogrel). In parallel to the elevated troponin I on admission, an elevated calcium level of 3.35 mmol/l (normal range 2.15-2.55 mmol/l) was found. Subsequently, there was a decreased serum phosphate (0.36 mmol/l [normal 0.81-1.62 mmol/l]) and vitamin D level (47 nmol/l [normal 50-250 nmol/l]) as well as a 16-fold elevated serum level of parathyroid hormone (PTH) (1156 ng/l [normal 18.4-72 ng/l]).
A symptom of the hypercalcemia was polydipsia and consequently the patient also complained about polyuria, but no other clinical manifestation of hypercalcemia such as nephrolithiasis, bone pain, or dyspepsia was noted. On careful clinical evaluation the patient reported a mild dysphagia. A firm and not mobile node on the right side of the neck was palpable. Sonographically a 5 cm right sided thyroidal mass was detected, not clearly definable from the trachea. Using the Thyroid Image Reporting And Data System (TIRADS), the node was categorized as highly suspicious for malignancy (TIRADS 5). Fine Needle Aspiration (FNA) revealed a monomorphic, partial follicular cell population (Figure
Small monomorphic epithelial cohesive cells and focal follicular arrangements with monomorphic, coarse structured nuclei and a small rim of cytoplasm.
Computer-assisted tomography (CT) as well as a MRI of the neck revealed a 5 cm large tumor at the right caudal pole of the thyroid with compression of the dorsolateral trachea without obvious infiltration, not distinguishable between thyroid and parathyroid, and tracheal stenosis was about 50% (Figure
Axial T1-weighted MR image (1) and postcontrast image (2) show a large mass near the right trachea without infiltration.
A complete surgical removal with en bloc resection of the right hemithyroid with parathyroidectomy was performed. Intraoperatively a large tumor was present, and the recurrent laryngeal nerve could not clearly be identified. Electrostimulation of the assumed nerval structure was unsuccessful. Postoperatively, vocal nerve paresis of the right side was detected in laryngoscopy. After resection PTH values dropped to 90.2 ng/l intraoperatively and postoperatively to 12.1 ng/l. Serum calcium levels normalized to 2.25 mmol/l. While expecting a hungry bone syndrome, a substitution with 1.25-diOH-cholecalciferol and oral calcium was initiated. Without substitution a hypoparathyroidism could lead in the acute phase to tetany with perioral numbness, paresthesia of the extremities, and muscle cramps and in the chronic phase to basal ganglia calcification with movement disorders or dementia, cataracts, or dental defects. Some patients have fewer specific symptoms such as fatigue, hyperirritability, anxiety, or depression and some patients, even with severe hypocalcemia, have no neuromuscular symptoms. Cardiac findings may include a prolonged QT interval, hypotension, heart failure, and arrhythmia. Postoperatively no signs of hypoparathyroidism were obvious, but the patient had dyspnea in context of cardiac insufficiency, averting logopedic voice exercises.
Macroscopic evaluation of the operation specimen revealed a maximal 5 cm large 20g weighing specimen. The cut surface showed a multinodal, partially not clear demarcated protruding greyish-brown firm tumor with hemorrhagic areas, infiltrating the thyroid gland (Figure
Cut surface of the specimen with a large indistinct colorful tumor with fibrous bands, hemorrhage, and infiltration of the thyroid. Focal perceived brown thyroid on the edge.
Tongue-like tumor infiltration of the thyroid.
Pleomorphic cells with focal atypia without mitosis.
Immunohistochemistry: Cytoplasmic positivity for PTH.
Focal perineural invasion and confirmation of malignancy.
PC is an extremely rare malignancy with an annual incidence of approximately 3.5-5.7 per 10 million people [
Up to date, histology is the gold standard in diagnosis of a PC. Although fibrosis and mitotic activity are common in PC, these features are not specific for malignancy. Mitotic figures are present in as many as 80% of PC but they can also occur in substantial numbers of parathyroid adenomas. Mitotic activity can be quite low, but most PC have more than 5 mitoses per 50 high power fields [
The affirmative histopathological diagnosis of a PC can be challenging and is limited to tumors with evidence of invasive growth in adjacent structures such as the thyroid, soft tissue, perineural spaces, and angioinvasion of capsular or extracapsular vessels or documented metastases. This case demonstrates the incidental early finding of a PC on the occasion of a NSTEMI. The early detection of the PC prevented the patient from suffering from further complaints of the primary hyperparathyroidism than the described discrete symptoms.
The case was presented in a poster session in Lugano 2018 at the Swiss Society of Pathology.
The authors declare that they have no conflicts of interest.
The manuscript has been read and approved by all authors.