Thymus cancer

ALSO KNOWN AS: Thymic cancer, thymoma, thymic carcinoma, thymic carcinoids

RELATED CONDITIONS: Myasthenia gravis, pure red cell aplasia, autoimmune disorders (including lupus and rheumatoid arthritis), Hypogammaglobulinemia

DEFINITION: Thymus cancer is a malignant tumor in the thymus, a small organ in the upper chest where the body makes and matures T lymphocytes (a type of white blood cell involved in immune responses). When thymic cells acquire mutations, normal cells may be replaced by cancerous ones. The majority of thymic cancers are thymomas, with thymic carcinoma and thymic carcinoids being much less common.

Risk factors: Thymic tumors are most prevalent in middle-aged or adults between forty and sixty. Men and women have similar incidence rates. There is some evidence that thymomas may be hereditary, although specific gene mutations have not yet been identified.

Several disorders are associated with thymic cancer. Myasthenia gravis, characterized by severe muscle weakness, develops in about 30 to 65 percent of people with thymoma. Red cell aplasia, characterized by a lack of red blood cell formation, also affects about 5 percent of thymoma patients. Additionally, people with autoimmune disorders, in which the immune system incorrectly targets the body’s tissues, also have an increased risk of thymic cancers.

Etiology and the disease process: The thymus has two major cell types—lymphocytes and epithelial cells. When lymphocytes are transformed into cancerous cells, this may lead to Hodgkin disease and non-Hodgkin lymphomas. Thymic cancers arise from either the cortical or medullary epithelial cells.

The exact etiology of thymus cancer remains unclear. An early event that may occur in the development of thymomas is a TP53 mutation. The protein produced by this gene regulates the cell cycle, and loss-of-function mutations can allow damaged or abnormal cells to divide and replicate. Another genetic mutation possible in thymic cancer is the overexpression of the epithelial growth factor receptor (EGFR), which is involved in signal transduction pathways that activate proteins and transcription factors to subsequently turn on genes involved in survival and proliferation.

The World Health Organization’s classification system of thymic cancers is based on their microscopic appearance:

• Type A (rare): Cells are spindle-shaped or oval epithelial cells, and they do not appear to be malignant.
• Type AB: Cells look like Type A, except that there are also some lymphocytes mixed in with the tumor.
• Type B1: Cells look like Type A, except that there are many lymphocytes mixed in with the tumor.
• Type B2: Epithelial cells appear abnormal and have large nuclei, and there are several lymphocytes.
• Type B3: This type has few lymphocytes and mostly consists of thymic epithelial cells that look pretty close to normal.

While Types A-B3 describe thymomas, Type C thymic cancers are known as thymic carcinomas. Thymic carcinomas have abnormal cells and are likely to spread outside the thymus. They are divided into low-grade and high-grade carcinomas based on how aggressive the tumor is and how likely it is to spread.

Thymic carcinoids are often associated with disorders of the endocrine system. These aggressive tumors can spread outside the thymus.

Incidence: Four hundred cases of thymic cancers are diagnosed annually in the United States. Thymomas comprise most cases, while the remaining are thymic carcinomas and carcinoid tumors.

Symptoms: In many cases, there are no symptoms. However, signs include long-lasting coughs, chest pain, and trouble breathing when they occur. These symptoms are often the result of thymic tumors constricting air passages or blood vessels. Obstructing blood flow may also lead to swelling in the arms or face. Other symptoms include low levels of red blood cells, fatigue and muscle weakness, and an increased risk of infection.

Screening and diagnosis: An X-ray of the chest is often the first procedure to detect thymic cancer. Follow-up imaging tests include computed tomography (CT), a more sensitive X-ray that produces cross-sectional images. CT scans provide information regarding a tumor's size, shape, and position and identify enlarged lymph nodes that may also have cancerous cells. Magnetic resonance imaging (MRI) scans, which use radio waves and magnets instead of X-rays, are another sensitive test providing sectional body scans. Finally, positron emission tomography (PET) is a newer form of imaging that scans the entire body. PET generally uses radioactive glucose (a form of sugar) as a tracer. The radioactivity is absorbed by the cancer cells and then detected with a special camera.

The most definitive procedure to diagnose thymic cancer is a biopsy, in which a piece of the tumor tissue from the thymus is removed by a needle or surgery and then analyzed under the microscope.

Thymomas are staged using the Masaoka system. Since thymic carcinomas and thymic carcinoid tumors are rare, there is no separate staging system for these cancer types. However, the Masaoka system is sometimes used for thymic carcinomas. The stages of the Masaoka system include:

• Stage I: The cancer remains within the thymus.
• Stage II: The cancer has spread to the chest cavity lining or nearby fat tissue.
• Stage III: The cancer has spread to areas within the chest, including the outer layer of the heart, lungs, or blood vessels.
• Stage IVA: The cancer has spread throughout the heart, lungs, or both.
• Stage IVB: The cancer has spread to blood or lymph systems.

Treatment and therapy: For Stage I thymoma, surgical removal of the thymus is the standard treatment. In other stages, the thymus and any tissues the cancer may have spread are removed. Radiation therapy may be performed if patients are unable to undergo surgery if the tumor has spread to too many tissues, if there is still a residual tumor mass after surgery, or if the tumor is inoperable because it is next to major arteries or veins in the chest. In the later stages, radiation therapy may also be given after surgery to decrease the risk of recurrence or spreading.

Chemotherapy drugs used to treat thymic cancers include doxorubicin, cisplatin, cyclophosphamide, etoposide, and ifosfamide. These drugs may be used alone or in combination and may be administered before surgery to reduce tumor size or after surgery if tumor cells still remain.

Corticosteroids may be used for tumors where surgery is impossible and patients fail to respond to radiation. The drug octreotide is a therapy for advanced thymic cancers. Octreotide blocks the ability of cancerous thymic cells to bind the hormone somatostatin, leading to cell death or slower rates of proliferation.

After surgery or therapy, patients should have checkups, including blood work and chest X-rays, every six to twelve months to monitor for recurrence.

Prognosis, prevention, and outcomes: Survival rates depend on the cancer stage at diagnosis. The average five-year survival rates for thymomas are 95 percent for Stage I, 78 percent for regional spread, and 38 percent for distant spread. However, some survivors experience recurrence. For patients with thymic carcinomas, about 35 percent survive for at least five years.

There are no specific guidelines for preventing thymic cancers. However, following a healthy diet, which is high in fruits and vegetables and low in fat, has been shown to prevent the development of many cancers.

Bibliography

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