Newly Diagnosed With Thymoma and Thymic Cancer: First Steps

The thymus sits behind the breastbone. That space is the front of the chest, called the anterior mediastinum. The thymus trains immune cells in childhood, then shrinks with age.

Tumors that start there are grouped as thymic epithelial tumors, or TETs. NCI notes that they are the most common tumors of the anterior mediastinum in adults. There are two main kinds.

Thymoma keeps features of normal thymus tissue. It behaves in a wide range of ways. Thymic carcinoma shows clear cell abnormality and lacks thymus-like features. NCI reports that thymic carcinomas make up about 20% of all TETs.

One line in NCI's summary is worth reading twice. All TETs can turn malignant and can spread. Even a slow one is not benign.

TETs make up about 0.2% to 1.5% of all cancers. NCI puts thymoma incidence at 0.13 cases per 100,000 person-years, using SEER data.

Survival varies widely. NCI reports 5-year survival of 36% for inoperable, locally advanced thymic carcinoma. For metastatic thymoma and thymic carcinoma it is 24%. For thymic carcinoma overall it is 30% to 50%.

TETs also carry the lowest tumor mutational burden of any adult solid tumor. That is why gene changes you can target are uncommon here.

This is what sets thymoma apart. The tumor can trigger autoimmune disease. Doctors call that paraneoplastic disease. NCI gives frequencies.

• Myasthenia gravis is the most common. It appears in roughly 30% to 65% of patients with thymoma. It causes muscle weakness that worsens with use. Eyelids, swallowing, and breathing are often affected.
• Hypogammaglobulinemia, or Good syndrome, occurs in 5% to 20%. Antibody levels fall, raising infection risk.
• Autoimmune pure red cell aplasia occurs in about 4%. The marrow stops making red cells.

NCI also describes B-cell lymphopenia in thymoma-related immune deficiency. That raises the risk of unusual infection. So repeated or odd infections are a finding to report, not bad luck.

Patients with myasthenia gravis tend to be found at an earlier stage. But NCI states that removing the thymus does not always improve the autoimmune disease.

Most patients have no symptoms at diagnosis. NCI reports about one-third do, either from the tumor or from an autoimmune disease.

Listed signs include cough, shortness of breath, chest pain, hoarseness, and phrenic nerve palsy. Superior vena cava syndrome is another. That means blockage of the large vein returning blood from the head and arms.

A mass in this spot is not always a TET. NCI lists other causes to rule out. They include germ cell tumors, lymphomas, metastases, and lung cancer. Two are not cancer at all: thymic hyperplasia and thymic cysts.

NCI gives different scans different jobs. About 50% of thymomas are found while still inside the thymic capsule.

• CT with contrast dye. Usually accurate for tumor size and location. It also shows invasion into vessels, the pericardium, and lungs. Smooth round edges suggest type A thymoma. Irregular edges suggest thymic carcinoma. Calcium deposits suggest type B.
• MRI. Chemical-shift MRI helps separate a tumor from a normal or enlarged thymus. Cardiac MRI is preferred for checking heart muscle. NCI calls MRI better than CT for chest wall invasion.

You may see both in your chart. They are not contradictory; they are different generations.

The Masaoka-Koga system from 1994 is used most often. Stage I is fully encapsulated, with no capsular invasion seen under the microscope. Stage II is invasion into nearby fat or the mediastinal pleura. It also covers microscopic invasion into the capsule. Stage III is invasion into neighboring organs, such as pericardium, lung, and great vessels. Stage IVa is spread across the pleura or pericardium. Stage IVb is spread through lymph or blood.

The AJCC TNM system came from IASLC and ITMIG. It sorts by level of invasion. T1 is encapsulated, or reaching into mediastinal fat. T2 invades the pericardium. T3 invades lung, superior vena cava, phrenic nerve, or chest wall. T4 invades the aorta, heart muscle, trachea, or esophagus.

Pathology reports label thymoma as type A, AB, B1, B2, or B3. NCI gives 10-year disease-free survival by subtype from one series of 100 patients. It was 100% for A and 100% for AB. It was 83% for B1 and 83% for B2. It fell to 36% for B3, and 28% for thymic carcinoma.

NCI is careful here. The subtype alone does not separate slow tumors from aggressive ones. Stage and complete removal carry more weight. Read all three together.

NCI's treatment table is direct.

• Stage I and II thymoma: surgery, with or without radiation afterward.
• Stage III and IV thymoma, operable: surgery followed by radiation, or induction chemotherapy followed by surgery and radiation.
• Stage III and IV thymoma, inoperable: chemotherapy alone, or chemotherapy then radiation. If it becomes operable, surgery and radiation may follow.
• Thymic carcinoma, operable: en bloc resection followed by radiation, with or without chemotherapy.
• Thymic carcinoma, inoperable: chemotherapy, or chemoradiation.
• Recurrent disease: chemotherapy, biological therapies, selected surgery or radiation, and pembrolizumab under clinical evaluation.

For recurrence, NCI reports specific numbers. Pemetrexed gave a response rate of 19.2%. Median overall survival was 28.7 months. A trial pairing capecitabine with gemcitabine drew responses in 41% of thymoma patients.

If either drug is proposed, ask about DPYD testing. NCI explains why. The DPYD gene makes an enzyme that breaks these drugs down. An estimated 1% to 2% of people carry harmful inherited DPYD variants. Patients with the DPYD*2A variant can suffer severe, life-threatening, sometimes fatal toxicity.

NCI notes that the result may lead to avoiding the drug, or cutting the dose by 50%. Testing costs less than $200, though coverage varies. It can also delay therapy by about 2 weeks.

• Weakness that worsens through the day, drooping eyelids, double vision, or slurred speech. These point to myasthenia gravis. Call your team the same day, and go to an emergency department if the weakness is spreading quickly.
• Trouble swallowing or trouble breathing. Call 911. Myasthenic weakness of the breathing muscles is an emergency.
• Swelling of the face, neck, or arms, with bulging neck veins. That is superior vena cava syndrome. Go to an emergency department.
• Fever of 100.4 degrees F, or 38 degrees C, or higher during chemotherapy. CDC calls this a medical emergency, so go straight in. The immune deficiency that can come with thymoma raises the stakes further.
• Repeated infections, or deep fatigue with pale skin. These can signal Good syndrome or pure red cell aplasia. Call your team within a day or two.

NCI advises considering lifelong surveillance, for two reasons. Thymoma can come back after a long gap. It also carries a raised risk of a second cancer. One study of 849 cases from 1973 to 1998 found excess risk of later non-Hodgkin lymphoma and soft tissue sarcoma.

Ask for that schedule in writing, with the interval in months, and ask who owns it after surgery.

• Is this thymoma or thymic carcinoma?
• What WHO subtype letter did pathology assign?
• What is my Masaoka-Koga stage, and what is my TNM stage?
• Is complete resection possible, and would chemotherapy come first?
• If capecitabine or fluorouracil is planned, has DPYD testing been ordered?
• Have I been checked for myasthenia gravis, low immunoglobulins, and anemia?

For related reading, see Cancer Staging, Pathology Reports, and Getting a Second Opinion.

• National Cancer Institute — Thymoma and Thymic Carcinoma Treatment (PDQ), Health Professional Version
• National Cancer Institute — Infection and Neutropenia during Cancer Treatment
• CDC — Fever and Cancer Treatment