Parathyroid Carcinoma - Stages, Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Parathyroid carcinoma or parathyroid cancer is a rare condition affecting the parathyroid glands. The symptoms of parathyroid carcinoma are similar to that of parathyroid adenoma, a more common and noncancerous tumor of the parathyroid gland. Therefore, diagnosing parathyroid carcinoma is difficult, and a definitive diagnosis is often made after surgery. Most symptoms of parathyroid carcinoma occur due to an increased amount of parathyroid hormone in the body due to associated hyperparathyroidism. Moreover, signs of hypercalcemia (elevated blood calcium levels) also dominate the clinical picture of the disease.

What Is a Parathyroid Gland?

The parathyroid glands are small glands located behind the thyroid gland. It regulates calcium and phosphorus levels and plays a vital role in maintaining bone health. The parathyroid gland synthesizes and secretes the parathyroid hormone (parathormone), which is the hormone that regulates the release of calcium into the blood, absorption of calcium from food by activating vitamin D, conserving calcium by kidneys, and regulation of phosphate levels in the blood via actions of the kidneys. The parathyroid glands can become underactive or overactive due to various factors; this leads to conditions known as hypoparathyroidism or hyperparathyroidism, respectively. In addition, several disorders can affect parathyroid gland functioning, including conditions like parathyroid adenoma (noncancerous growth in the parathyroid) and parathyroid carcinoma (cancer).

What Is Parathyroid Carcinoma (Cancer)?

Parathyroid carcinoma or parathyroid cancer is a rare cancer affecting the parathyroid glands. Cancer usually develops sporadically (randomly with no apparent cause), but several risk factors may increase the chances of developing parathyroid carcinoma in an individual. Parathyroid carcinoma leads to a hyperactive parathyroid gland, also known as hyperparathyroidism, which leads to the overproduction of parathyroid hormones. This can lead to a condition known as hypercalcemia (increased amount of calcium in the blood); this increased amount of calcium in the blood can cause kidney stones, weaken the bones, and interfere with heart and brain functioning. Therefore, treating hypercalcemia associated with parathyroid carcinoma is essential before it causes kidney failure and other complications.

What Are the Types of Parathyroid Carcinoma?

Based on their ability to produce excess parathyroid hormone, parathyroid carcinoma can be of two types:

1. Hormonally Functional Parathyroid Carcinoma: This type of parathyroid carcinoma is characterized by the ability of cancer to produce excess parathyroid hormone. This accounts for approximately 90 percent of parathyroid cancers. The symptoms of the condition will be due to hyperparathyroidism and hypercalcemia. In case of prolonged hypercalcemia due to hormonally functional parathyroid carcinoma, kidney failure (or other organ failures) can lead to the patient’s death.

2. Hormonally Non-Functional Parathyroid Carcinoma: In this type of parathyroid carcinoma, parathyroid hormones, and calcium levels stay within the normal range. This type of parathyroid carcinoma accounts for 10 percent of all parathyroid carcinoma. The condition's symptoms are due to the tumor's obstruction of the surrounding structures in the neck. The patient will complain of difficulty swallowing, speaking, hoarseness of the voice, and shortness of breath.

What Are the Other Names of Parathyroid Carcinoma?

Several other names of parathyroid carcinoma are:

• Parathyroid cancer.

• Parathyroid neoplasm.

• Malignant neoplasm of the parathyroid gland.

• Parathyroid adenocarcinoma.

• Malignant parathyroid gland tumor.

• Malignant parathyroid gland neoplasm.

• Cancer of the parathyroid glands.

What Are the Stages of Parathyroid Carcinoma?

The staging of cancer determines the following criteria:

• Location of the cancerous tumor.

• Whether cancer has metastasized (spread) to the other parts of the body.

Multiple imaging tests help in determining the stage of the carcinoma, and depending on this; parathyroid carcinoma occurs in three stages:

1. Localized Parathyroid Carcinoma: Cancer or the tumor is present within the parathyroid gland and does not spread to the surrounding gland structures.

2. Metastatic Parathyroid Carcinoma: Cancer, in this stage, has spread to other parts of the body from where it has begun. Cancer usually spreads via tissues, lymph nodes, and blood circulation. The tissues grow into nearby structures leading to the spread of cancer. Moreover, cancer can enter the lymphatic system and the blood circulation, from where it can reach distant parts and organs of the body through blood vessels and lymph nodes. But metastatic cancer is the same as primary cancer; for example, if parathyroid carcinoma spreads to the lungs, the cancer cells in the lungs will be the parathyroid cancer cells.

3. Recurrent Parathyroid Carcinoma: When the parathyroid carcinoma returns even after treatment, the condition is known as recurrent parathyroid carcinoma. The common sites of parathyroid carcinoma recurrence are the neck's tissues and lymph nodes. Parathyroid carcinoma recurs in about 50 percent of the patients post-surgery, and it can come back within 2 to 20 years after the surgery. Elevated blood calcium levels after surgery are usually the first sign of recurrence.

How Common Is Parathyroid Carcinoma?

• Parathyroid carcinoma is an uncommon type of cancer, accounting for 0.005 percent of all cancers.

• About 1,000 cases of parathyroid carcinoma have been reported to this date globally.

• The condition is slightly more prevalent in countries like Japan and Italy as compared to the United States.

• Parathyroid cancer affects men and women equally, and it usually occurs after the age of 30 years.

What Are the Causes and Risk Factors for Developing Parathyroid Carcinoma?

Parathyroid carcinoma can occur sporadically or due to mutation (alterations in gene structures) in specific genes. However, the exact cause of the condition is unknown. Moreover, no clear and regular pattern may result in cancer development. The risk factors that may lead to the development of parathyroid carcinoma in an individual include:

• Family history of parathyroid carcinoma. If a person has a family member with parathyroid carcinoma, then their chances of developing parathyroid cancer automatically increase. In addition, several inherited disorders like multiple endocrine neoplasias are also risk factors for parathyroid cancer.

• Familial isolated hyperparathyroidism is an inherited disorder with an overactive parathyroid gland. When a disorder is passed down from parents to their children, it is referred to as an inherited disorder.

• Hyperparathyroidism jaw tumors (HPT-JT) is an inherited condition characterized by hyperactive parathyroid glands.

• Radiation exposure may also increase the risk of developing parathyroid carcinoma.

• Several factors, like carcinoma, occur within adenoma, and prolonged secondary hyperparathyroidism occurs due to celiac disease.

• End-stage kidney diseases are also related to parathyroid carcinoma.

What Are the Symptoms of Parathyroid Carcinoma?

The common signs and symptoms of parathyroid carcinoma include:

• Fatigue.

• Weakness.

• Unusual weight loss.

• Nausea and vomiting.

• Loss of appetite.

• Frequent urination (polyuria).

• Excessive thirst (polydipsia).

• Pain in the bones.

• Kidney problems.

• Stomach pain.

• Constipation.

• Trouble in thinking and concentrating.

• Frequent fractures.

• Presence of a lump in the neck that may be palpable.

• Trouble in swallowing.

• Hoarseness of voice.

How Is Parathyroid Carcinoma Diagnosed?

The diagnosis of parathyroid carcinoma can be tricky due to the similarity of the symptoms of the condition with other conditions like primary hyperparathyroidism and parathyroid adenoma. Therefore, apart from a physical examination, the following tests are done to confirm the diagnosis of parathyroid carcinoma:

• Blood and Urine Examinations: Multiple blood and urine examinations will determine any change in the functioning of the parathyroid gland. Serum calcium levels, serum phosphorus levels, and the levels of parathyroid hormones in the blood are evaluated. 1 mg/dL (milligram per deciliter) elevation above the normal upper range of the blood calcium levels is an indication of primary hyperthyroidism. Whereas, if the blood calcium levels are above 14 mg/dL (milligram per deciliter) or 3 to 4 milligram above the normal range, it will suggest the presence of cancer. The levels of parathyroid hormones will also be sharply elevated in the case of parathyroid carcinoma.

• Imaging Tests: Imaging tests like a CT (computed tomography) scan or MRI (magnetic resonance imaging) are done to evaluate the presence and absence of any tumor, the location, and the extent of the tumor.

• Single-Photon Emission Tomography (SPECT) Scan: Single-photon emission tomography is a type of CT scan in which the presence of malignant cells are determined. Injectable radioactive material is given to the patient through their vein, or another form of radioactive material is inhaled through the nose. This substance travels through blood up to the parathyroid gland. While this happens, a camera will click pictures of the neck from all directions, and a three-dimensional image is processed. As a result, there will be increased activities in areas where cancer cells are present, and these areas will show up brightly in the images.

• Sestamibi Scan: During this test, sestamibi protein is mixed with a radioactive substance and injected into the patient’s vein. This substance travels through blood up to the parathyroid gland. This substance will be readily absorbed and collected in the tumor, showing brightly in pictures.

• Venous Blood Sampling: A blood sample is collected from the veins near each parathyroid gland to check if the gland is producing more parathyroid hormone.

• Biopsy: A sample of tissues may be collected from the tumor and sent to a laboratory for evaluation. This test checks for the presence of cancerous cells in the tumor.

• Surgery: Surgery is often the most common method of diagnosis. The entire parathyroid gland may be surgically excised and sent to the laboratory for evaluation. Generally, a biopsy is not recommended as a separate procedure.

How Is Parathyroid Carcinoma Treated?

The treatment of parathyroid carcinoma includes:

• The definitive treatment for parathyroid carcinoma is surgery. Surgical excision of the entire parathyroid gland is done along with the healthy tissues and structures lining the parathyroid gland. Before surgery, certain blood examinations are done to evaluate serum calcium levels, parathyroid hormone levels, and serum phosphorus levels. Along with some general blood examinations like complete blood count, prothrombin time test and other such tests may be done to evaluate any bleeding and clotting disorders.

• Radiotherapy and chemotherapy have not shown very impactful effects in the treatment of parathyroid carcinoma. Anyway, occasionally, radiation therapy is advised after parathyroid cancer surgery.

• Chemotherapy is the use of certain drugs in a specific number of cycles over a set period to curb the growth of cancer cells in the body. However, this therapy has not helped treat parathyroid cancer.

• Treatment of hypercalcemia associated with hyperparathyroidism in the case of parathyroid cancer should be treated immediately. Often this elevated level of calcium is more fatal than the tumor itself because it may cause organ failure. Some drugs that may be used to treat hypercalcemia are; Bisphosphonates, Calcitonin, Cinacalcet, Denosumab, and Gallium nitrate.

Conclusion:

The prognosis and the effectiveness of the treatment of parathyroid carcinoma depend majorly on the severity of hypercalcemia (elevated blood calcium levels), whether the calcium levels are controllable, the stage of cancer (when cancer spreads to other parts, it is difficult to be treated), whether the complete tumor can be removed surgically, and general health and immunity of the patient. The life expectancy of the condition is highly variable, ranging from 20 to 85 percent expectancy approximately.