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��INTRODUCTION

Parathyroid cancer is one of the rarest neoplasms encountered in the human population [1, 2]. There were 224 cases diagnosed from 1988 through 2003, and 1022 cases from 1998 through 2011, described in the American cancer report SEER and the National Cancer Data Base [1, 2]. The estimated incidence is 0.015 per 100,000 in the United States population, with an estimated prevalence rate of .005% [3]. Nonspecific clinical symptoms are connected with hypersecrection of parathormone (PTH), with the resultant consequence being an increased level of total calcium and phosphoranes in the blood.  This often creates complications in the rapid diagnosis and aggressive treatment of parathyroid cancer. There are currently no standardized treatments for parathyroid cancer, with only the previous experiences of clinicians allowing for widely practiced parathyroid cancer therapy.  With currently employed methods, the five-year overall survival rate is 81,1% [2].

CASE REPORT

A previously healthy 57-year-old male who was employed as an engine operator on an oil-rig platform in the Baltic Sea had a bicycle accident on 22 MAR 2014 with loss of consciousness of several hours, retrograde amnesia, some epidermal scraping, and a cut near his right eye. During admission to the Emergency Department, it was discovered that his total calcium was increased to 3,08 mmol/L (norm: 2,20-2,60).  After five days it had normalized to 2,60 mmol/L. Subsequently, he was diagnosed with a tumor in the right parathyriod gland measuring 2,9 x 2,2 cm via ultrasound examination, and a tumor in the right suprarenal gland measuring 2,1 x 1,3 cm (probable adenoma) via abdominal CT examination. A parathormone test was performed because of the increased calcium: the level was 34,6pmol/L (norm: 1,7-92).
Prior to the accident in February 2014, the patient noticed weakness, sleepiness, and polyuria.  He also noted an  elevated blood preassure during the beginning of March 2014, but no medications were prescribed at that time.
Lab tests performed on 01 April 2014 revealed: total calcium 2,64 mmol/L (norm: 2,09-2,54), PTH 34,6 pmol/L (norm: till 3,2) and ionized calcium 1,47 mmol/L (norm 1,12-1,32).  PTH after ten days was 41,46 pmol/L.  Other lab tests which were done were: ACTH 22,16 pg/ml (norm: 7,20-63,60); cortisol 17,4 mig/dl (norm: 6,2-19,4); 25-OH vitamin D total 8,6 ng/ml (norm: 30-80); 17-OH Progesteron 0,67  ng/ml (norm: 0,05-1,6), chromogranin A 56,10 ng/ml (norm: below 100).
Scintigraphy (after injection of 800 Mbq MIBI  Tc99m) was performed on 06 May 2014: there was enhanced uptake in the lower posterior part of the right lobe of the thyroid gland, suggesting an adenoma of the lower right part of the parathyroid gland. (fig.1).
In May 2014, the patient was hospitalized in the Endocrinology Clinic, and hyperparathyroidism was diagnosed, with an adenoma located in the right lower parathyroid gland.  Lab test performed at that time revealed:  total calcium 2,94 mmol/L (norm: 2,09-2,54 );  ionized calcium 1,60 mmol/L (norm: 1,12-1,32); nonorganic phosphorus 0,60 mmol/L (norm: 0,81-1,45); 24-hour urinary calcium collection 5,97 mmol/24h (norm: 2,50-8,00), total urinary calcium 1,99 mmol/L; nonorganic phosphorus  in 24-hour urinary collection 29,10 mmol/24h (norm: 12,90-42,00), total urinary phosphorus 9,70 mmol/l (norm: 13,0-44,0) i PTH 296 pmol/L (norm: till 67); caltitonin below2,0 pg/ml (norm: till 8,4); chromogranin 76,3 ng/ml (norm: 20-150); 25-OH vitamin D total 9,59 ng/ml (norm: 20-60); metanefrin 54,6 mig/24-hours (norm: below 350); ACTH 19,5 pg/ml (norm: 0,0-46,0); cortisol 11,8 mig/dL (norm: 5-25); cortisol in 24-hour urinary collection 35,70 mig/24-hours (norm: 36,0-137,0).
A biopsy of the parathyroid polycystic tumor was performed on 15 May 2014, but the material was non-diagnostic.
The patient was hospitalized again in Endocrinology Surgical Department in June 2014. The total calcium was 2,90 mmol/L (norm: 2,15-2,50); and PTH 64,46  pg/ml (norm: 15,0-65,0). A resection of the right lower parathyroid tumor was performed (macroscopy: grey tumor, Size: about 3 cm).  Total thyroidectomy and peri thyriod lymphadenectomy was performed on 26 Jun 2014. The hisptopathological report revealed parathyroid carcinoma (in carcinoma cells: synaptophizin   negative, TTF-1   negative, CK19   negative, CD 56   negative/positive). Accordingly, because of the fragmentation of the surgical material, total resection was not possible. The cancer had infiltrated the nearest soft tissues, and there were small thromboses in surrounding vessels.
After the surgery, hoarseness appeared (which still exists), and the patient was placed under supplementation of thyroid hormones. There were no active neoplasma in a follow-up PET scan performed on 04 Aug 2014.  The patient had radiotherapy performed, where he received 6MeV  50 Gy (IMRT technique, on the cervical lymph nodes (II, III, IV, VI, VII groups on both sides and Vb on the right side) and 66 Gy on the lesion after resection of the parathyroid tumor between Aug 2014 and Oct 2014. Subsequently, the total calcium had normalized : 2,17 mmol/l (norm: 2,15-2,55). Post-oncological treatment, the patient continues to be under observation and there is no evidence of reccurence (last contact with the patient was in Aug 2016).

Prior to the discovery of his parathyroid ca., the patient had sometimes experienced higher blood preassure, but he had received no treatment. His surgical history includes a cholecystectmy performed in 2011, as well as two arthroscopies of left knee in 2012 and 2014. He also had an accident where he fell down some steps in 2012. With regards to his family medical history: patient's mother had neoplasma of lymph nodes and tuberculosis when she was 35 years old, and his father had bladder cancer. The patient smoked 10-12 cigarettes per day from the age of 18 till 47, occasionally also consuming alcohol.

DISCUSSION

According to published facts, parathyroid cancer is a rare neoplasm.  It appears that it is only because of the overall experiences of oncologists which allows  the  proper diagnosis, treatment and monitoring of patients with this rare disease. Our observations and the results of the treatment show that surgery with removal of the parathyroid glands with tumor, as well as  healthy nearby tissues, thyroid gland, lymph nodes, and fat tissue with surrounding muscles are the best  treatment [4].  Duckworth at all published a literatury review (approximately 700 cases of the parathyroid carcinoma have been reported to 2013) and his finding were:  the complete surgery is the primary treatment with or without postoperative radiotherapy. Reported five-year survival rates range from 50 to 85% [5]. When surgery is not possible or there are metastases present with hypercalcemia, bisphosphonate or calcium receptor antagonsts can be prescribed. However, moderate success using dacarbazine and denosumab has been reported in refractory response [6]. Denosumab displays an effective treatment for patients with increasing level of calcium in the blood in different cancers, including parathyroid cancer: it was able to lower serum calcium within ten days in 64% of examined patients, and it maintained a durable response [7].
The presence of a higher level of calcium in blood tests should  alert  clinicians to the next diagnostic steps. The measurement of PTH in blood and the presence of its higher level must directly place special attencion on the parathyroid glands. Both benign and malignant parathyroid glands tumors will cause disturbances in hormones and electrolytes.
Available ultrasonography does not always shows tumors in physiologically small parathyroid glands, so additionally there should be computer tomography or scintigraphy performed. Guerin at all compared scintigraphy and  ultrasonographic techniques in parathyroid glands tumor diagnoses. The higher sensivity of scintigraphy (93,3%), positive predictive value of 85,8%, negative predictive value of 73,0%,  compared with ultrasonography (P<0,01), present the superior position of this first technique in diagnosis of parathyroid gland tumors, specially in posterior locations, and in those who have a previous history of thyroidectomy, due to the resultant interpretation difficulties [8].

It appears then, encountering such a rare and sporadic neoplasma in oncological centers, in the near future we may be able to prepare standardized diagnostic and treatment modalities for patients with parathyroid glands cancer. It is becoming clear that many doctors in various specialties must cooperate in the proper diagnosis and treatment of this disease, but equally, many patients will survive.

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