Parathyroid cancer is a malignant formation of the parathyroid gland (PTG), occurring with severe hyperparathyroidism. The clinic of the disease is characterized by hypercalcemia (anorexia, vomiting, weight loss, thirst, polyuria, bone pain, muscle weakness, lethargy), dysphonia, the presence of a palpable tumor in the neck. Osteoporosis, nephrolithiasis, arrhythmias develop. Pathology is diagnosed according to the results of laboratory tests (PTH, calcium, phosphorus), echography, CT of the neck and mediastinum, scintigraphy, fine needle biopsy. Surgical treatment – extended en bloc resection of the PTG with hemithiroidectomy.
ICD 10
C75.0 Malignant neoplasm of the [parathyroid] gland
Meaning
Parathyroid cancer (PTC) refers to rare types of endocrine cancer. In the structure of all oncopathology, it occupies about 0.005%, the annual incidence is 11:10 million of the population. According to various data, from 1 to 5% of cases of primary hyperparathyroidism (PHPT) are caused by prostate cancer. The average age at diagnosis is 40-50 years, isolated cases of parathyroid cancer have been described in children. There are no gender differences. The relevance of ROSC in endocrine oncology is determined by the development of an extremely severe form of hyperparathyroidism, uncontrolled hypercalcemia with high mortality.
Causes
In most cases, parathyroid cancer occurs sporadically, but there are many reports of familial cases of oncopathology. Most often, patients with hereditary and sporadic prostate cancer have a mutation in the type 2 hyperparathyroidism gene CDC73 on chromosome 1q2.5. Thus, the development of prostate cancer may be associated with the following reasons:
- The genetic factor. Parathyroid carcinoma develops in 15% of patients with HPT-JT syndrome, the components of which are also PHPT, jaw tumors, thyroid carcinomas, uterus, kidneys, testicles. Patients with MEN’s syndrome 1 and 2A, familial isolated hyperparathyroidism are prone to the occurrence of PTC.
- Other diseases of the pancreas. Cases of malignant transformation of hyperplastic pancreatic tissue against the background of its chronic hormonal stimulation are described. Malignancy of solitary adenoma of the parathyroid gland is also possible.
- Irradiation of the head and neck. There are reports of the development of PTG carcinoma in patients who have undergone radiotherapy of tumors for other oncological diseases: cancer of the larynx and pharynx, nasal cavity, tongue, salivary glands, etc.
- Other factors. Some mutagenic factors can provoke the occurrence of a malignant tumor of the parathyroid glands: intoxication with heavy metals and drugs (aluminum salts, lithium), increased natural radiation background, etc. Parathyroid carcinoma can occur against the background of thyroid pathologies: nodular goiter, thyroid cancer.
Pathogenesis
In the presence of an inactivating mutation in the CDC73 gene, the expression of the parafibromine protein, which is a tumor suppressor, is disrupted. As a result, uncontrolled growth and division of parathyroid cells occur, which acquire malignant potential. More than 90% of pancreatic carcinomas are hormonally active, secreting parathyroid hormone (PTH). At the same time, due to defects in calcium-sensitive receptors, tumor cells lose the ability to regulate the synthesis of PTH on the principle of negative feedback.
Hyperproduction of PTH leads to the development of the clinical syndrome of hyperparathyroidism, accompanied by the release of calcium from cells into plasma (hypercalcemia). Violation of calcium homeostasis causes a wide range of clinical manifestations affecting the neuromuscular, bone, urinary, digestive, cardiovascular, and visual systems. The course of calcium-dependent processes in tissues changes, calcification of organs, hypophosphatemia occurs.
Pathomorphology
Macroscopically, parathyroid cancer is a dense node, the average size of the tumor is about 3.5 cm. In 50% of cases, the tumor mass is enclosed in a capsule. On the incision, the neoplasia has a lobular structure, gray-pink or brownish color.
Microscopic examination of tumor tissue reveals the predominance of main cells, oncocytes or a mixed structure, cellular polymorphism, nuclear atypia. Among the main morphological criteria for parathyroid cancer, the following are distinguished: trabecular structure, high mitotic activity (including atypical mitoses), foci of necrosis, signs of invasive growth.
Classification
There is no official universally recognized classification of parathyroid cancer to date. There is a working version of TNM-staging, proposed in 2017 by the American Joint Committee on Cancer Control:
- Tis – a tumor of the pancreas that is suspected of malignancy (atypical neoplasia) is determined;
- T1 – the tumor is localized in the parathyroid gland, there is an invasion of the surrounding fiber;
- T2 – the tumor grows in the thyroid tissue;
- T3 – the tumor grows into nearby structures: lymph nodes, recurrent nerve, trachea, esophagus, thymus gland;
- T4 – tumor invades large vessels, vertebral column.
N1 – metastasis of prostate cancer in regional l/n:
- N1a – prelaryngeal, paratracheal, anterior mediastinum;
- N1b – cervical on one or both sides, retropharyngeal.
M1 – metastasis to distant organs.
Symptoms
The clinical picture of ROSH is determined by the syndrome of hyperparathyroidism. Unlike benign hyperparathyroidism, in cancer, its symptoms are characterized by a sharp manifestation and significant severity.
The phenomena of severe hypercalcemia occur earlier than others and are characteristic of all patients. Its signs are increased thirst, nausea with vomiting, loss of appetite, polyuria, constipation. Patients complain of pronounced weakness, constant fatigue, noticeable weight loss. In 30-70% of patients with parathyroid carcinoma, a palpable tumor in the neck is detected at the time of diagnosis. There is hoarseness of the voice due to paresis of the recurrent nerve.
More than 85% of patients suffer from various bone pathologies. Most of them note pain in muscles, bones, joints, gait changes, frequent fractures. Targeted examination reveals bone deformities, osteoporosis, bone cysts, fibrotic osteitis, etc.
Approximately the same number of patients develop changes from the urinary organs. The most common are urolithiasis, nephrocalcinosis, and chronic renal failure. Parathyroid cancer is characterized by severe gastrointestinal tract lesions: erosive gastritis, peptic ulcers of the stomach and duodenum, pancreocalcinosis, pancreatitis.
Cardiovascular disorders are represented by arrhythmias, arterial hypertension, calcification of blood vessels and heart valves. Possible deposition of calcium in the cornea with the development of keratitis. CNS lesions caused by hypercalcemia include depression, psychosis, and frequent headaches.
Complications
A large tumor node can cause symptoms of compression of the neck organs (suffocation, dysphagia, superior vena cava syndrome), requiring immediate surgical assistance. The most dangerous emergency condition associated with parathyroid cancer is a hypercalcemic crisis, accompanied by indomitable vomiting, dehydration, severe muscle hypotension. High mortality in this condition is due to critical electrolyte disorders and cardiovascular insufficiency.
Cancer of the parathyroid glands more often metastasizes to the thyroid, mediastinum and lungs, less often distant metastatic foci are detected in the liver, pancreas, adrenal glands, bones. Often there are local relapses of the grove.
Diagnostics
Patients with signs of PHPT get an appointment with an endocrinologist, whose task is to find out the causes of this syndrome. Already at the initial treatment, 30-75% of patients have a palpable tumor node on the anterior surface of the neck. Further diagnostic tactics include:
- Laboratory tests. The level of parathyroid hormone in parathyroid cancer is 3-10 times higher than the reference values, which is an important diagnostic sign. The plasma calcium level is >3 mmol/l. The blood phosphorus index is lowered.
- Prostate ultrasound. On the echography, a hypoechoic tumor of a heterogeneous structure is visualized, having no clear boundaries, with pronounced calcification.
- CT. Neck CT is used to assess the local prevalence of PTC. CT scans of the mediastinum, abdominal cavity, and spine allow to identify metastases.
- Fine needle biopsy. It is not recommended as a method of primary diagnosis of PTC, since it is accompanied by the risk of implantation metastases. It is usually used to diagnose cancer recurrence. The final diagnosis is made after histological examination of the removed neoplasm.
- Additional research. To assess bone mineral density, X-ray densitometry and the study of bone resorption markers are resorted to. The degree of kidney damage is assessed according to ultrasound data, indicators of the nephrological complex. In order to detect ulcerative gastrointestinal defects, EDS is performed. Other visceral lesions are detected using abdominal ultrasound, targeted echography.
Differential diagnosis
Symptoms similar to parathyroid cancer can occur in a number of other pathological conditions. In this regard, during the diagnosis, it is necessary to exclude:
- benign PHPT;
- atypical adenoma of the pancreas;
- ectopia of parathyroid tissue;
- postoperative parathyroidism;
- other oncopathologies associated with hypercalcemia: breast cancer, lung, kidney, ovarian cancer, hemoblastosis, bone metastases, etc.
Due to the fact that parathyroid cancer is a rare pathology, the diagnosis of parathyroid carcinoma is more often made intraoperatively.
Treatment
Surgical treatment
The main method of treatment of parathyroid carcinoma is its removal. During the operation, they are guided by oncological principles. Depending on the prevalence of parathyroid cancer , the following types of interventions are performed:
- Extended PTG resection with hemithireodectomy. It is recognized as the “gold standard” of surgical treatment of parathyroid cancer. As part of en bloc resection, the affected thyroid gland, parathyroid tissue, as well as the ipsilateral lobe of the thyroid gland with an isthmus are removed.
- Parathyroidectomy. Currently, the removal of the PTG together with the tumor is not considered a sufficiently radical operation. After such a volume of resection, local relapses of the disease occur 6 times more often than after removal by a “single block”.
In some cases, thyroidectomy is indicated. It is recommended to supplement any volume of resection with lymphadenectomy.
Conservative therapy
Drug therapy is used in patients with hyperparathyroid crisis, as well as with an inoperable tumor. The main purpose of such treatment is to reduce the level of blood calcium. For this purpose, calcimimetics, calcitonin preparations, bisphosphonates, etc. are prescribed. Radiation therapy and chemotherapy for parathyroid cancer are not carried out due to their ineffectiveness.
Prognosis and prevention
Prostate cancer is characterized by a high frequency of postoperative relapses (30-50%), which occur on average after 3 years. The earlier the relapse or metastasis of the tumor occurred, the worse the prognosis. The five–year survival rate, depending on the volume of surgical resection, is at the level of 45-85%, ten-year – 50-70%. All operated patients are shown lifelong observation of an endocrinologist, oncologist.
Primary prevention consists in excluding the effects of carcinogens, timely treatment of background diseases of the PTG and thyroid gland. To reduce the likelihood of postoperative recurrence of parathyroid cancer, the choice in favor of extended radical resection allows.