Thymoma Treatment

Thymoma is a rare tumor originating from the thymus gland located in the mediastinum. It usually has a slow course and is often detected incidentally while investigating another disease. Thymomas may be benign, but some may show invasive features and spread to surrounding tissues.

The question of how thymoma is diagnosed is of fundamental importance in the diagnostic process. The size and spread of the tumor are evaluated with chest CT and MRI imaging methods. The definitive diagnosis is usually established by histopathological examination performed after surgical resection.

The question of what the symptoms of thymoma are is important in terms of clinical awareness. While many patients may have no symptoms, some cases may present with chest pain, cough, and shortness of breath. In addition, thymoma is associated with autoimmune diseases such as myasthenia gravis, and this may provide a clue in diagnosis.

The question of what is applied in the treatment of thymoma varies according to the stage of the tumor. In early stages, surgical resection is the first option. Adjuvant radiotherapy or chemotherapy may be applied when necessary. In advanced-stage cases, multimodal treatment approaches are preferred.

What Is Thymoma?

Thymoma is a rare tumor originating from the thymus gland located in the front part of the chest, behind the sternum. It generally grows slowly and is often detected incidentally. In some cases, it may cause symptoms such as chest pain, shortness of breath, or cough. Thymoma may be associated with autoimmune diseases such as myasthenia gravis. Its treatment may include surgery, radiotherapy, and, when necessary, chemotherapy. Early diagnosis increases treatment success.

With which thymoma symptoms do patients usually present?

In our clinical practice, we generally see thymoma patients in two main groups. The first group is actually the luckiest group: those who have no complaints whatsoever. The proportion of these patients is not negligible. Usually, a mass is detected incidentally on a chest X-ray or tomography performed during a check-up, a pre-employment examination, or for a completely different reason (for example, a persistent cough or a heart check-up). Tumors caught in this “silent” period have a high probability of being early stage because they have not yet caused serious pressure or spread to surrounding tissues, and their treatment success is excellent.

The second group consists of patients who come to us with the effects created by the physical presence of the tumor. When the tumor reaches a certain size, it starts to disturb its neighbors in that narrow anatomical space where it is located.

The compression complaints that may be seen in patients due to thymoma growth are as follows:

• Chest pain
• Cough
• Shortness of breath
• Hoarseness
• Swelling of the face
• Fullness in the neck veins
• Difficulty swallowing

Each of these symptoms gives us clues about which structure the tumor is pressing on. For example, if there is a persistent dry cough or shortness of breath, we may think that the tumor is pressing on the windpipe. Hoarseness indicates that the nerve going to the vocal cords is being compressed by the tumor, which is an important finding in terms of surgical planning. Swelling in the face and arms indicates that the main vein carrying deoxygenated blood to the heart is under pressure, and this is a serious condition requiring urgent intervention.

What kind of relationship exists between Myasthenia Gravis and thymoma?

The most characteristic and perhaps most mysterious feature that distinguishes thymoma from other chest tumors is its close relationship with the immune system. In approximately 30% to 40% of thymoma patients, “Paraneoplastic Syndromes,” which are completely unrelated to the size of the tumor, are seen. The best known and most common of these is Myasthenia Gravis (MG). This is a muscle weakness disease that occurs when the body’s immune system blocks the commands going from nerves to muscles.

What is interesting is that sometimes even a very small, millimetric thymoma can cause severe Myasthenia Gravis symptoms. These patients generally present to neurology clinics, and during the evaluations, a mass in the chest cavity is noticed. In fact, this situation can also be thought of as a kind of “early warning system” because it allows the tumor to be detected at a very early stage.

The symptoms that may be seen in patients in association with Myasthenia Gravis are as follows:

• Drooping eyelids
• Double vision
• General muscle fatigue
• Difficulty swallowing
• Difficulty chewing
• Impaired speech
• Weakness in the arms and legs
• Difficulty climbing stairs

These symptoms usually increase during the day as the person becomes tired and decrease with rest. If these neurological findings are present in a patient and a mass has been detected in the chest cavity, the diagnosis is almost certain. However, the treatment approach changes here; it is not enough just to remove the tumor, the neurological condition must also be managed. Therefore, these patients should be followed jointly by neurology and thoracic surgery specialists.

What are the most reliable imaging methods for diagnosing thymoma?

When suspicion of thymoma arises in a patient or when a shadow is detected incidentally, the backbone of the diagnostic process is radiological imaging. A standard chest X-ray can tell us that there is a “shadow” there, but it cannot provide detailed information about what this shadow is, where it extends, or whether it contains fluid or solid tissue. Therefore, in suspected thymoma, the gold standard examination is Contrast-Enhanced Computed Tomography (CT).

Computed tomography provides us with millimetric sections of the chest cavity. Thanks to these images, we can clearly see the exact size of the tumor, its shape, whether its borders are smooth, and, most importantly, its relationship with surrounding tissues. CT provides the answers to the most critical questions that we as surgeons need to know before entering surgery: Is the tumor attached to the heart? Has it wrapped around the major vessels? Has it spread to the lung lining? The answers to these questions determine the type and extent of the surgery.

Sometimes tomography alone may not be sufficient. We may resort to Magnetic Resonance Imaging (MRI), especially to understand whether the tumor has a cystic (fluid-filled) structure or to evaluate the condition in patients who are allergic to iodinated contrast material. In addition, PET-CT examination may be added to the process to scan whether the tumor has spread to another part of the body (metastasis) or to measure the metabolic activity of the mass. However, CT is indispensable for surgical mapping.

Should a biopsy always be performed in every suspected thymoma?

The general rule in medicine is “no treatment without pathological diagnosis”; in other words, first a biopsy is done, the condition is named, and then surgery is performed. However, thymoma is one of the most important exceptions to this rule. In thymoma management, the decision to perform a biopsy is a highly strategic one that must be made with extreme caution, and it is not routinely applied to every patient. In fact, in most cases, if the tumor appears resectable, we particularly avoid performing a biopsy.

There is a very justified reason for this. Thymomas are generally surrounded by a capsule (membrane). If we pierce this capsule with a biopsy needle, there is a risk that tumor cells will scatter into the needle tract or the chest cavity. In medical terms, we call this “implantation.” In other words, while trying to establish the diagnosis, we may actually raise the stage of the disease and increase the risk of recurrence. For this reason, in masses that radiologically give a typical thymoma appearance and can be completely removed surgically, the safest way is to remove the mass directly by surgery without performing a biopsy.

However, there are, of course, situations in which biopsy is mandatory:

The situations in which a biopsy should be performed are as follows:

• Suspicion of lymphoma
• Tumors too large to be surgically removed
• Presence of distant metastasis
• Planning chemotherapy before surgery
• Atypical radiological appearance

If the tumor is very large, has spread excessively to the surroundings, and must be reduced with chemotherapy before surgery, tissue diagnosis is absolutely necessary to know which medication to administer. Or if imaging suggests lymphoma (lymph node cancer) rather than thymoma, biopsy is again mandatory because the treatment for lymphoma is chemotherapy, not surgery. In such cases, biopsy is generally performed with a needle or through a small incision (VATS).

What do the thymoma types stated in the pathology report mean?

After the tumor is removed from the body, the laboratory part of the process begins. Pathologists examine the tissue under the microscope and make a classification according to the criteria determined by the World Health Organization (WHO). This classification is very important for understanding the “nature” of the tumor. Thymomas are not of one single type; some behave very calmly and benignly, while others behave aggressively like a true cancer. This distinction is one of the main factors that determine whether the patient will need additional treatment (such as radiotherapy) after surgery.

The classification is expressed with letters and numbers.

According to the WHO classification, thymoma types are as follows:

• Type A
• Type AB
• Type B1
• Type B2
• Type B3
• Type C

Type A and Type AB thymomas are generally types that show benign behavior, are encapsulated, and grow slowly. In these, the risk of recurrence after surgery is quite low. When progressing to the Type B group (B1, B2, B3), the activity of the tumor increases. Especially Type B2 and B3 are types with a higher tendency to adhere to or spread into surrounding tissues. Type C is no longer called “Thymoma” but “Thymic Carcinoma.” This is the most aggressive member of the group; its cellular structure resembles cancers of other organs, it grows rapidly, and it has a high potential to spread to distant organs (metastasis).

How is thymoma spread determined with Masaoka staging?

Another factor that is as important as, and even more important than, the cellular type of the tumor (WHO classification) is “Masaoka Staging.” This system shows how far the tumor has spread anatomically. The stage of the disease is the main map that determines both the expectation of recovery after surgery (prognosis) and the need for additional treatment. Staging is usually finalized by the surgeon’s observation during the operation and the pathologist’s evaluation after surgery.

According to the Masaoka system, the stages are as follows:

• Stage I
• Stage II
• Stage III
• Stage IV

Stage I is the best-case scenario, where the tumor is completely within an intact capsule and has not extended outside at all. In Stage II, the tumor has pierced the capsule and microscopically or macroscopically entered the adjacent fatty tissue. In Stage III, things become more serious; the tumor is no longer confined to its own area but has extended to neighboring organs (lung tissue, the pericardium surrounding the heart, or the major vessels). Stage IV is the advanced stage in which the tumor has formed widespread deposits on the lung or heart lining or has spread to distant organs via blood/lymph. The treatment plan is completely shaped according to this stage.

What is the place and importance of surgery in thymoma treatment?

Despite all the developments in medical science, new drugs, and radiation treatments, the unchanging rule and gold standard of thymoma treatment is surgery. As thoracic surgery specialists, our main goal in this disease is the procedure that is referred to in the medical literature as “Complete Resection” or “R0 Resection.” This term means the complete removal of the tumor from the body together with the surrounding safe healthy tissue, leaving behind no visible or microscopic residue.

All long-term scientific studies unequivocally demonstrate one fact: the most important factor determining the patient’s survival time and disease-free period is whether the tumor was completely cleared at the first surgery. If the tumor capsule is ruptured or part of the tumor is left behind (incomplete resection) in order to avoid damaging vital organs, unfortunately the probability of recurrence rises significantly and survival rates decrease. Therefore, the surgical strategy is based on “complete clearance at all costs.” If necessary, the lung tissue, pericardium, or vessel segment to which the tumor is attached should also be removed en bloc with the tumor.

Are closed methods safe in thymoma surgery?

In the past, when thymoma surgery was mentioned, the only method that came to mind was open surgery (sternotomy), in which the “breastbone” (sternum) was cut and opened from top to bottom. Although this method provided the surgeon with a very wide field of view, the recovery process could be more burdensome for patients. Today, with the development of technology, “Minimally Invasive Surgery,” that is, closed methods (VATS and Robotic Surgery), has come to the forefront.

Especially in early-stage tumors such as Stage I and Stage II, and in masses that are not extremely large in size, closed methods are now becoming the standard treatment. With robotic surgery or VATS, the tumor can be removed by entering through small holes with a camera and instruments without making large incisions in the chest cage.

The advantages provided by closed methods for patients are as follows:

• Less postoperative pain
• Shorter hospital stay
• Less risk of bleeding
• Faster return to daily life
• Better cosmetic results
• Lower infection risk

Thanks to the 3-dimensional view and high maneuverability it provides, robotic surgery offers the surgeon great precision in the narrow mediastinal region filled with critical vessels. However, the most important rule here is not to compromise oncological principles. If the surgeon believes that the tumor cannot be completely removed by the closed method, that it will be fragmented, or that safe margins cannot be achieved, they must switch to open surgery without hesitation. Because cosmetic concerns are not more important than the safety of cancer surgery.

Is there a chance of treatment in advanced-stage thymoma cases?

Although the term “advanced stage” is often frightening for patients, in thymoma it does not mean hopelessness. Thymomas are tumors with a high degree of treatability even in advanced stages (Stage III and IVa). In cases where the tumor surrounds major vessels or spreads to the lung lining, we apply the “Multimodal Treatment” approach, which is a multidisciplinary strategy. In this protocol, not a single branch but surgery, oncology, and radiation oncology act together.

In these patients, treatment is generally started with chemotherapy. The aim here is to shrink the tumor with drug treatment, clarify its borders, and make it more suitable for surgery (neoadjuvant treatment). After chemotherapy, the patient is reevaluated, and if a response is seen, aggressive surgery is planned. These operations are much more extensive than a standard thymectomy. Not only the thymus gland but also the lung lining (pleura) and heart lining (pericardium) where the tumor has spread are completely peeled off and removed. If the pericardium is removed, synthetic patches (mesh) are placed instead to preserve heart function. Thanks to this aggressive approach, it is possible to achieve long-term survival and disease control even in advanced-stage patients.

Is thymoma surgery risky in patients with Myasthenia Gravis?

Cases of thymoma accompanied by Myasthenia Gravis (MG) are “special” cases in terms of surgical and anesthesia management. In these patients, it is not enough to focus only on the removal of the tumor; it is also necessary to prevent the neurological balance from being disrupted. The surgery itself, the medications used, and stress factors may temporarily worsen MG symptoms. Therefore, these patients should definitely be operated on in centers experienced in this field.

The most critical points that should be considered during and after surgery in these patients are as follows:

• Preservation of the phrenic nerve
• Selection of anesthesia drugs
• Respiratory monitoring
• Medication dose adjustment
• Pain control

For the surgeon, the greatest technical challenge and responsibility is the preservation of the nerves called the “phrenic nerve,” which run the diaphragm muscle. These nerves pass right next to the tumor. In MG patients, the respiratory muscles may already be weak due to the disease. If these nerves are damaged during surgery, diaphragm paralysis may develop, and the patient may experience serious difficulty breathing on their own after the operation and may remain on a ventilator for a long time. Therefore, nerve-preserving surgical techniques are of vital importance in MG patients. In addition, the anesthesia team must be very careful in selecting muscle relaxant drugs, because some drugs may trigger an MG crisis.

How long should thymoma follow-up continue?

A successful surgery and the subsequent recovery process do not mean that the treatment is over. By its nature, thymoma is an “indolent,” that is, slow-progressing tumor. This feature causes the risk of recurrence to continue even many years later. While in many other cancer types a 5-year disease-free period is considered “recovery,” in thymoma this period is not sufficient. Cases have been reported in the literature in which recurrence occurred even 10, 15, or 20 years after surgery.

For this reason, follow-up of a patient who has undergone surgery for thymoma should continue for life. In the first years, the chest cavity should be checked more frequently (for example, every 3–6 months), and in later years once a year with Computed Tomography. The aim of these follow-ups is to detect a possible recurrence at the earliest stage. Because even if recurrence develops, there is always something that can be done for thymoma patients; the disease can be brought under control again with repeat surgery, radiotherapy, or next-generation drug treatments. It is as important as the surgery itself that our patients do not neglect this long-term follow-up process in order to protect their health.

Frequently Asked Questions