What is Thymoma?
Thymoma is a form of tumor that originates in epithelial cells of the thymus. It is a very uncommon tumor, and is best known in association with a neuromuscular disorder known as myasthenia gravis. Around 15% of individuals having myasthenia gravis also develop thymoma. It is also the most common type of neoplasm affecting the anterior mediastinum.
Thymoma is the most common form of neoplasm occurring in the anterior mediastinum, and accounts for nearly 20% to 25% of all types of mediastinal tumors and around 50% of all anterior mediastinal masses. Both men and women get equally affected by these tumors. The typical age during diagnosis is approximately 30 or 40 years. However, cases have been reported in almost all age groups, including that of children.
The thymus can be described as a lymphoid organ that is located in anterior mediastinum. During the early life, it is responsible for development and overall maturation of cell-governed immunological functions. Thymus is essentially composed of lymphocytes and epithelial cells. The precursor cells migrate to thymus and then differentiate into lymphocytes. The majority of these lymphocytes eventually get destroyed, and the remaining cells migrate to the tissues and become T lymphocytes.
Thymomas develop when epithelial cells making up the tissues of thymus organ turn malignant. A lymphoma develops when lymphocytes, the other type of cell present in thymus, becomes cancerous. It is not known what exact factors lead to the development of thymomas. It is often closely associated with myasthenia gravis; a condition which involves weakening of muscles. Doctors usually diagnose thymoma while conducting tests for other diseases, especially while carrying out chest X-rays.
Thymoma patients may experience a number of symptoms, or their cases may be asymptomatic. The cancer can get detected during a regular chest x-ray, even when an individual shows no symptoms. The symptoms are not essentially indicative of a thymoma and may also occur due to other factors. The most common features of this kind of neoplasm include:
- Double vision
- Persistent cough
- Drooping eyelids
- Muscle weakness
- Shortness of breath
- Frequent infections
- Difficulty swallowing
- Facial or arm swelling
- Coarseness of the voice
- Pain or pressure felt in the chest
- Anemia (lower count of red blood cells)
- Swelling of neck caused by the tumor exerting pressure on the blood vessels in chest – a condition referred to as superior vena cava obstruction (SVCO)
If an individual is already affected by an autoimmune system disorder like Myasthenia gravis, it may lead the doctor to suspect as well as carry out tests for seeing if there is any thymus gland tumor. Some individuals having a later-stage Thymoma may have a reduced immunity and therefore can be more prone to develop an infection.
Thymoma Associated Conditions
Nearly a third of individuals have their tumors diagnosed due to some form of associated autoimmune disorder. There are a number of conditions that are closely linked with Thymoma. These include:
- Crohn’s disease
- Alopecia areata
- Ulcerative colitis
- Cushing’s disease
- Acute pericarditis
- Addison’s disease
- Hemolytic anemia
- Myasthenia gravis
- Sjögren syndrome
- Pernicious anemia
- Nephrotic syndrome
- Rheumatoid arthritis
- Lupus erythematosus
- Stiff person syndrome
- Limbic encephalopathy
- Sensorimotor radiculopathy
- Acquired pure red cell aplasia
- Systemic lupus erythematosus
- Good’s syndrome (thymoma with combined hypogammaglobulinemia and immunodeficiency)
A thymoma tumor originates in the epithelial cells within the thymus, and numerous microscopic subtypes are currently recognized. Three principal histological forms of thymoma exist at present, depending on the overall appearance of cells under microscopy.
- Type A occurs when the epithelial cells have a fusiform or oval shape, with less lymphocyte count
- Type B occurs when the cells have got an epithelioid shape; this type has three sub-types: the B1 (lymphocyte-rich), the B2 (cortical) and the B3 (epithelial)
- Type AB occurs when the tumor involves a combination of the 2 cell types
The thymic cortical epithelial cells are characterized by an abundant cytoplasm, vesicular nucleus along with nicely divided chromatin; small nucleoli as well as cytoplasmic filaments contacting adjacent cells. The thymic medullary epithelial cells, on the other hand, are spindle-shaped with dense, oval nucleus. Scant cytoplasm thymoma is believed to be much less benign if more of cortical cell features are present.
Staging of this neoplasm is generally done by the Masaoka Staging System. It is based on anatomic extent of the disease during the point of surgery. Thymoma tumors are normally slow-growing and when they metastasize, they do so only into the nearby structures. These tumors can spread only in three ways; through the tissues, through lymph system and through the blood.
During this stage, the cancer is completely encapsulated and is found only within the thymus. All the cancer cells are within the capsule that surrounds thymus.
In this stage, the cancer has metastasized through capsule and then into the fat surrounding the thymus or the lining of chest cavity. It still has not spread to the nearby organs and lymph nodes.
At this stage, the cancer has already spread to the nearby organs in chest, such as the lungs, the sac around heart, or the large blood vessels carrying blood to heart.
This stage is further subdivided into A and B.
At this stage, the cancer has metastasized widely into linings of the lungs (the pleura) as well as the lining of heart (the pericardium).
During this point, the cancer has metastasized through blood and the lymphatic system to the other organs, like the liver.
Grading of the thymoma tumors is done based on their appearance under a microscope. Thymus gland is composed of the medulla and the cortex, both of which consist of different types of cells. The medulla is comprised of more spindle cells and the cortex is made up of more epithelial cells that line the organs and the cavities of the body. The doctors investigate the tumor under microscope and based on the cells they detect, class the tumor as ‘cortical’ or ‘medullary’. Sometimes, if both epithelial and spindle cells are detected, it is classified as a ‘mixed’ tumor.
The World Health Organization (WHO) has classified the thymus gland tumors according to their grade and type:
- A – Medullary thymoma
- AB – Mixed thymoma
- B1 – Mainly cortical thymoma
- B2 – Cortical thymoma
- B3 – Epithelial thymoma; sometimes also referred to as well-differentiated thymic carcinoma
- C – Thymic carcinoma; known to be high-grade or malignant
The types A and AB are believed to be non-cancerous or benign. Types B1 to B3 are graded as low-grade or slow-growing, or on borderline between benign or malignant. The type C is malignant and cancerous. The type B2, i.e., cortical thymoma, is generally linked with myasthenia gravis.
If the doctor suspects a thymoma, he or she will recommend a CT or a CAT scan to investigate the size as well as the extent of tumor. The lesion will also be sampled by collecting a CT-monitored needle biopsy. If an increased vascular enhancement is detected on CT scans, it can indicate malignancy. Pleural deposits may also point to the same hypothesis. Limited biopsies are often associated with very small risks of mediastinitis or pneumomediastinum as well as an even lower propensity of damage to the heart or the large blood vessels. Diagnosis can be made through a histological examination carried out by a pathologist after collecting tissue samples of the mass. The final tumor classification along with staging is carried out pathologically after the formal surgical management of thymic tumor.
A number of laboratory and imaging tests are carried out to see if a person is having thymoma. These include:
- Liver enzymes
- Full blood count
- Renal function tests
- Protein electrophoresis
- Physical exam and patient history
- Fine-needle aspiration or FNA tests
- Magnetic resonance imaging or MRI scans
- Positron emission tomography (PET) scans
- Posteroanterior (PA) and lateral chest radiographs
- Antibodies to acetylcholine receptor (which are indicative of myasthenia)
Thymoma Differential Diagnosis
A number of conditions exhibit signs and symptoms similar to that of Thymoma. Hence, while determining the presence of this type of tumor; it should be differentiated from all such similar health disorders. The differential diagnoses of Thymoma include distinguishing its symptoms from those of disorders such as:
- Thymic Cysts
- Thoracic Goiter
- Germ Cell Tumor
- Thymic Carcinoma
- Mediastinal Tumors
- Hodgkin Lymphoma
- Fibrous Mesothelioma
- Thymic Carcinoid Tumor
The mainstay for treatment of thymoma is surgery, which can be accompanied by other forms of medical management such as radiotherapy, chemotherapy and hormone therapy. Sometimes, chemotherapy may be conducted prior to surgery or radiotherapy in order to minimize the size of large tumors. This can make the treatment more successful. This mode of using chemotherapy is referred to as neo-adjuvant chemotherapy.
Apart from consulting a cancer specialist, the patient may also be directed to follow up with a neurologist specializing in curing various conditions associated with brain and the nervous system. Treatment may be required for Myasthenia gravis. Since the thymus gland makes a vital part of the immune system of the body, the patient might also be required to see a doctor specializing in treating immune conditions.
It is generally possible to surgically remove the entire tumor if it is contained only within thymus gland, i.e., encapsulated. If the patient has got Stage I Thymoma, it can be completely removed by a surgical procedure, after which no further treatment is usually required.
Sometimes, the thymus gland tumors can metastasize into the nearby structures and organs. However, the extent to which the tumor has spread can often be accurately assessed only during surgery. One may also be required to undergo Thymectomy, a procedure in which the thymus gland is removed. This is a major form of operation which involves making an incision through the breastbone or the sternum.
This mode of treatment makes the use of high energy rays that can destroy the cancer cells, while inflicting as little damage as possible to the healthy cells. If surgery is not able to completely remove all cancer cells, or if the cancer or tumor is very large, the sufferer may be required to undergo radiotherapy treatment.
The doctor may recommend radiotherapy even after a successful surgical treatment in order to reduce the risks of relapse of the cancer. Radiotherapy can be used to reduce the size of the tumor prior to surgery. This can make the surgical treatment more successful.
Chemotherapy uses anti-cancer drugs to fight off the cancer cells. This mode of treatment is sometimes used in case the tumor has metastasized or if the radiotherapy and/or the surgery were not able to produce optimum results. Cancers of the thymus gland can respond quite well to chemotherapy. A combination of various chemotherapeutic drugs is used to treat Thymoma sufferers.
This is a form of cancer treatment that eradicates hormones or prohibits their actions and stops the cancer cells from multiplying and growing. Hormones are chemical substances that are produced by glands within the body which are then circulated through the bloodstream. There are some hormones that might cause certain forms of cancers to grow. Hormone therapy using drugs called Corticosteroids can be carried out to treat Thymoma if there are spots within the cancer cells where the hormones can attach themselves, i.e. receptors. Alternatively, surgery, drugs or radiation therapy can also be used to minimize the production of harmful hormones and/or blocking their activities.
Treatment for recurrent cases of Thymoma
If Thymoma relapses after treatment, the following measures may be taken to hinder further possible instances of tumor:
- Hormone therapy
- Radiation therapy
- Surgery without or with radiation therapy
- A clinical trial focusing on new ways of conducting radiation therapy
- Clinical trial of certain anti-cancer drugs in various new doses or combinations
Cancer research trails are normally carried out to discover new and improved ways of treating cancer. Patients can take part in these clinical trials where new, experimental modes of treatment will be tried out on them. These trials help in adding to the existing knowledge about cancer as well as hint to the future development of new, improvised treatments.
The initial treatment should be followed up regularly by tests that were carried out during diagnosis of the condition. This is necessary to find out how well the treatment procedures are working. Major decisions regarding further care may be required to be made based on these tests. These post-operative tests are also collectively known as Restaging.
A number of complications such as radiation pneumonitis, radiation pericarditis and pulmonary fibrosis have been reported following post-operative radiation therapy. Clinical experts are required to evaluate the possible ratio between risks and benefits of an adjuvant radiation therapy as it might also lead to death.
The outcome for sufferers with this neoplasm depends on a number of factors, such as stage of cancer, type of the cancer cell, the general health of patients as well as recurrence of the condition. Prognosis is generally much worse for the stage III or the IV Thymoma patients compared to the stage I and stage II cases. In some rare instances, invasive growths of this type also can metastasize, normally to the bones, pleura, brain or liver in around 7% of all cases. Individuals with stage III and stage IV tumors may still survive for many years with proper oncological management.
Patients who undergo a thymectomy procedure may experience severe side effects following a yellow fever vaccination; a problem that is probably due to inadequate response of T-cells to the live attenuated vaccine for yellow fever. This has even led to numerous deaths.
The following images display the various areas of the thymus gland affected by this tumor.
Picture 1 – Thymoma
Picture 2 – Thymoma Image