All About Thymoma & Thymic Carcinoma

Autor: OncoLink Team
Contribuidor de contenido: Charles Wood, MD
Fecha de la última revisión: 17 de marzo de 2020

What is the thymus?

The thymus gland is a small organ that lies under the breastbone, in the upper part of the chest (known as the anterior mediastinum). The thymus is part of the immune system and is responsible for developing T lymphocytes. Lymphocytes move through the body and help fight infection. As we age, the thymus shrinks and is replaced with fat, but in some people, a part of it remains in adulthood.

What is thymoma/thymic carcinoma?

Thymoma and thymic carcinoma are two different types of thymus cancer. Thymoma is usually a slow-growing tumor that often does not spread beyond the thymus gland. It is the most common tumor seen in the anterior mediastinum in adults. Thymic carcinoma, on the other hand, is less common but more aggressive. It is often harder to treat because it tends to spread quickly to other areas of the body (metastasize). Both tumors typically start in thymic epithelial cells.

Thymoma/thymic carcinoma are both rare types of cancer. There are an estimated 400 cases (combined) per year in the United States or about 1.5 persons per million diagnosed with thymoma/thymic carcinoma.

The World Health Organization (WHO) has developed a classification system for thymoma. This system defines 6 types of thymoma, based on the cells that make up the tumor. The histological type is used in combination with other factors to determine staging and treatment options.

Type

Subtype Name

Subtype Characteristics

Type A

Spindle cell or medullary thymoma

  • Cells are spindle-shaped or oval epithelial cells that appear fairly normal-looking.
  • Accounts for 4-7% of all thymomas.
  • About 17% of cases may be associated with myasthenia gravis (an autoimmune disease that causes weakness and fatigue of muscles under voluntary control in the body).

Type AB

Mixed thymoma

  • Cells appear like type A, but also include non-neoplastic lymphocytes.
  • Accounts for 28-34% of all thymomas.
  • About 16% of cases may be associated with myasthenia gravis.

Type B1

Lymphocyte-rich thymoma (also referred to as lymphocytic thymoma, predominantly cortical thymoma, organoid thymoma)

  • Cells show many lymphocytes in the tumor, but the cells of the thymus look healthy.
  • Accounts for 9-20% of all thymomas.
  • About 57% of cases may be associated with myasthenia gravis.

Type B2

Cortical or polygonal cell thymoma.

  • Presence of many lymphocytes and abnormal thymus cells.
  • Accounts for 20-36% of all thymomas.
  • About 71% of cases may be associated with myasthenia gravis.

Type B3

Epithelial thymoma (also referred to as atypical thymoma, squamoid thymoma and well-differentiated thymic carcinoma).

  • Cells contain few lymphocytes and abnormal thymic cells.
  • Accounts for 10-14% of all thymomas.
  • About 46% of cases may be associated with myasthenia gravis.

Type C

Thymic Carcinoma

  • Thymic epithelial tumor.
  • Cells look like carcinomas in other organs.
  • Always lack immature lymphocytes.
  • Not usually associated with myasthenia gravis.
  • Several subtypes: squamous cell (epidermoid), baseloid, lymphoepithelioma like, sarcomatoid, clear cell, mucoepidermoid, papillary, undifferentiated.

 

 

What causes thymoma/thymic carcinoma and am I at risk?

The cause of thymoma is unknown. Risk factors have not been found. It affects men and women equally and is most often seen in people 50-60 years old. People with thymoma may have other diseases of the immune system. Myasthenia gravis (MG), an autoimmune condition that causes the muscles to become weak, is the syndrome most often associated with thymoma. MG may be present in about 30% of people with thymoma. Because myasthenia gravis is more common than thymoma, only 10-15% of patients diagnosed with MG also develop thymoma.

What screening tests are available for thymoma/thymic carcinoma?

There are no available screening tests for thymoma/thymic carcinoma. Almost half of those who have thymoma/thymic carcinoma have no symptoms when their tumor is found. Thymoma is often found incidentally (by chance) when an x-ray or CT scan is performed for another reason.

What are the signs of thymoma/thymic carcinoma?

About one-third of patients have no symptoms when thymoma/thymic carcinoma is diagnosed. If symptoms are present, they include cough, chest pain, shortness of breath, hoarseness, decreased appetite, and trouble swallowing. Rarely, thymoma/thymic carcinoma tumors can press on the superior vena cava (SVC), leading to a complication called SVC syndrome. The SVC is the main blood vessel that brings blood from the upper body to the heart. Symptoms of SVC syndrome include swelling in the neck, chest and face, swelling of the visible veins in the upper body, headaches, and dizziness. SVC syndrome is a serious condition that requires immediate medical attention.

Some patients may present with conditions caused by the tumor itself. These include myasthenia gravis, red cell aplasia, and hypogammaglobulinemia. These are autoimmune conditions, where the body’s immune system seems to attack itself.

Some other autoimmune diseases have also been linked to thymoma, including lupus, polymyositis, ulcerative colitis, rheumatoid arthritis, Sjogren’s syndrome, sarcoidosis, and scleroderma. If you have one of these autoimmune diseases, talk with your healthcare team about screening for thymoma.

How is thymoma/thymic carcinoma diagnosed?

Thymoma is usually diagnosed based on x-ray and images of the chest. Laboratory studies, such as routine bloodwork, are not often used.  Biopsy is also rarely done for diagnosis because providers can usually make a diagnosis of thymoma based on imaging like x-ray, CT scan or MRI.  If there is a question of invasion into other nearby parts of the chest, it may be necessary to obtain a tissue sample of the mass, or biopsy, for testing under a microscope. The biopsy is done either by insertion of a needle through the chest wall or by a more invasive surgical procedure under general anesthesia (medicine used to keep you asleep during the surgery). In this procedure, an incision is made above the breastbone and a piece of the tumor is removed. This procedure is sometimes done with the aid of a small camera, or scope, inserted into the chest (called video-assisted thoracoscopy, or VATS).

How is thymoma/thymic carcinoma staged?

Once a thymoma is found, it may be necessary to do more tests to see if the tumor has spread and so that the correct treatment can be recommended. The extent of the tumor spread is also referred to as the "stage."

The Masaoka staging system for staging thymoma/thymic carcinoma is an older method of staging, but is still sometimes used. Staging via this system takes into account (1) the extent of the disease as seen on CT/MRI, (2) spread of the tumor to nearby tissues, (3) histologic typing (the type of cell).

Healthcare providers now often use the TNM system (also called tumor - node - metastasis system). This system describes the size and local invasiveness of the tumor (T), which, if any, lymph nodes are involved (N), and if it has spread to other more distant areas of the body (M). This is then interpreted as a stage somewhere from I (one) denoting more limited disease to IV (four) denoting more advanced disease. Your healthcare provider will use the results of the diagnostic workup to assign the TNM result and will then guide your treatment course.

Both the Masaoka and TNM staging is provided at the end of this article for your reference.

What are the treatments for thymoma/thymic carcinoma?

Surgery

Surgical removal of the tumor is the main treatment for thymoma/thymic carcinoma. The first step is to find out whether or not the tumor is able to be surgically removed (called resectable), which depends on a few factors. If the tumor has spread to nearby tissues and organs, it may not be resectable. In addition, the patient may not be able to undergo surgery due to other, pre-existing medical conditions.

The complete removal of the thymus, a thymectomy, is the most common surgery used in the treatment of thymic cancers. If the tumor is not entirely resectable, your healthcare provider may choose to “debulk” the tumor. This means trying to remove as much of the tumor as is safely possible. Occasionally, chemotherapy or radiation may be used in these cases before surgery in hopes of reducing the size of the tumor, to aid in its removal.

Radiation Therapy

Thymomas are thought to be sensitive to radiation therapy treatment (which is the use of high-energy x-rays aimed at the tumor or area from where the tumor was removed).

There is no need to use radiation for completely removed noninvasive thymoma tumors (stage I). Radiation is nearly always used in stage III or IV tumors after complete or partial surgical removal of the tumor. Whether radiation is needed after complete surgical removal of stage II tumors is unclear and often depends on the patient and the specifics of their tumor. Radiation is often recommended in order to decrease the chance that the tumor will come back in the original site. Radiation may be used in any stage of thymoma where it is not possible to do a safe and complete surgery.

Chemotherapy

The use of chemotherapy for advanced stage tumors has increased. Some of the most commonly used chemotherapy medications include: cisplatin, doxorubicin, carboplatin, cyclophosphamidepacilitaxel, pemetrexed, 5-FU, gemcitabine and ifosfamide. Corticosteroids are non-chemotherapy medications that are sometimes used in thymoma treatment. Several medications are often used in combination. Two common chemotherapy combinations are: PAC (cisplatin, doxorubicin, and cyclophosphamide) or carboplatin with paclitaxel. In some cases, a medication called octreotide can be used in patients with advanced thymoma.

Some thymic cancers may be treated with targeted therapies that focus on specific gene mutations or proteins present in that tumor. Targeted therapies that may be useful in the treatment of thymoma include sunitinib and sorefenib.

Clinical Trials

Clinical trials are designed to determine the value of specific treatments. Trials are often designed to treat a certain stage of cancer, either as the first form of treatment offered, or as an option for treatment after other treatments have failed to work. They can be used to evaluate medications or treatments to prevent cancer, detect it earlier, or help manage side effects. Clinical trials are extremely important in furthering our knowledge of disease. It is through clinical trials that we know what we do today. Talk to your provider about participating in clinical trials in your area. You can also explore currently open clinical trials using the OncoLink Clinical Trials Matching Service.

Follow Up Care and Survivorship

After completion of treatment for thymoma or thymic carcinoma, your healthcare team will monitor you closely. There is no widely accepted follow up schedule for survivors, but likely your team will want to exam you every 3 months for the first 1-2 years after treatment to monitor for late treatment-related side effects and possible recurrence. You may also need to have a chest CT scan every 6 months for 2 years after treatment, and then every year for 5 years if you were treated for thymic carcinoma.

Fear of recurrence, relationships challenges, the financial impact of cancer treatment, employment issues and coping strategies are common emotional and practical issues experienced by survivors. Your healthcare team can identify resources for support and management of these practical and emotional challenges faced during and after cancer.

Cancer survivorship is a relatively new focus of oncology care. With nearly 17 million cancer survivors in the US alone, there is a need to help patients transition from active treatment to survivorship. What happens next, how do you get back to normal, what should you know and do to live healthy going forward? A survivorship care plan can be a first step in educating yourself about navigating life after cancer and helping you communicate knowledgeably with your healthcare providers. Create a survivorship care plan today on OncoLink.

Resources for More Information

ThymomaHope.org

Supports research for thymoma through fundraising as well as offering patients/families a space to share their stories about living with thymoma.

www.thymomahope.org

International Thymic Malignancy Interest Group

www.itmig.org

Masaoka clinical staging of thymoma/ thymic carcinoma

Stage

Description

Stage I

Non-invasive tumor that has not spread into the outer layer (capsule) of the thymus. Macroscopically and microscopically completely encapsulated

Stage II

Thymoma invades beyond the outer boundary of the thymus and into nearby tissue or the pleura.

IIA

The tumor is growing into the outer layer of tissue of the thymus. Micropscopic transcapsular invasion.

Stage IIB

The tumor has grown through the outer layer of the thymus and has invaded nearby fatty tissue, the mediastinal pleura or the pericardium.

Stage III

The tumor is growing into nearby tissues and organs in the neck and upper chest area including the pericardium, the lungs, the SVC and/or the aorta.

Stage IVA

The tumor has spread widely through the pleura and/or the pericardium.

Stage IVB

The tumor has spread to distant organs.

TNM Staging System

American Joint Committee on Cancer, 8th Edition

Primary Tumor (T)

Description

Tx

Primary tumor cannot be assessed.

T0

No evidence of primary tumor.

T1

Tumor encapsulated or extending into the mediastinal fat; may involve the mediastinal pleura.

T1a

Tumor with no mediastinal pleura involvement.

T1b

Tumor with direct invasion of mediastinal pleura.

T2

Tumor with direct invasion of the pericardium (either partial or full thickness).

T3

Tumor with direct invasion into any of the following: lung, brachiocephalic vein, superior vena cava, phrenic nerve, chest wall, or extrapericardial pulmonary artery or veins.

T4

Tumor with invasion into any of the following: aorta (ascending, arch, or descending) arch vessels, intrapericardial pulmonary artery, myocardium, trachea, esophagus.

 

Node (N)

Description

NX

Regional lymph nodes cannot be assessed.

N0

No regional lymph node metastasis.

N1

Metastasis in anterior (perithymic) lymph nodes.

N2

Metastasis in deep intrathoracic or cervical lymph nodes.

 

Metastasis(M)

Description

M0

No pleural, pericardial, or distant metastasis.

M1

Pleural, pericardial, or distant metastasis.

M1a

Separate pleural or pericardial nodule(s).

M1b

Pulmonary intraparenchymal nodule or distant organ metastasis.

 

Stage

T

N

M

I

T1a,b

N0

M0

II

T2

N0

M0

IIIA

T3

N0

M0

IIIB

T4

N0

M0

IVA

Any T

Any T

N1

N0-N1

M0

M1a

IVB

Any T

Any N

N2

Any N

M0-M1a

M1b

Referencias

American Cancer Society, Thymus Cancer, http://www.cancer.org/cancer/thymuscancer/index

National Cancer Institute, Thymoma and Thymic Carcinoma Treatment PDQ, http://www.cancer.gov/types/thymoma/patient/thymoma-treatment-pdq

Berardi, R., Morgese, F., Garassino, M. C., & Cascinu, S. (2015). New findings on thymic epithelial tumors: Something is changing. World Journal of Clinical Oncology, 6(5), 96.

Engels, E. A. (2010). Epidemiology of thymoma and associated malignancies. Journal of Thoracic Oncology, 5(10), S260-S265.

Enkner, F., Pichlhöfer, B., Zaharie, A. T., Krunic, M., Holper, T. M., Janik, S., ... & Migschitz, B. (2017). Molecular profiling of thymoma and thymic carcinoma: genetic differences and potential novel therapeutic targets. Pathology & Oncology Research23(3), 551-564.

Forquer, J. A., Rong, N., Fakiris, A. J., Loehrer, P. J., & Johnstone, P. A. (2010). Postoperative radiotherapy after surgical resection of thymoma: differing roles in localized and regional disease. International Journal of Radiation Oncology* Biology* Physics, 76(2), 440-445.

Lamarca, A., Moreno, V., & Feliu, J. (2013). Thymoma and thymic carcinoma in the target therapies era. Cancer Treatment Reviews, 39(5), 413-420.

Lemma, G. L., Lee, J. W., Aisner, S. C., Langer, C. J., Tester, W. J., Johnson, D. H., & Loehrer, P. J. (2011). Phase II study of carboplatin and paclitaxel in advanced thymoma and thymic carcinoma. Journal of Clinical Oncology, 29(15), 2060-2065.

Marx, A., Ströbel, P., Schalke, B., & Weis, C. A. (2018). Pathological features of thymoma and thymic carcinoma with therapeutic implications. Mediastinum2(1).Marx, A., & Weis, C. A. (2015). Sunitinib in thymic carcinoma: enigmas still unresolved. The Lancet Oncology16(2), 124-125.

Marx, A., Willcox, N., Leite, M. I., Chuang, W. Y., Schalke, B., Nix, W., & Ströbel, P. (2010). Thymoma and paraneoplastic myasthenia gravis. Autoimmunity43(5-6), 413-427.

Masaoka, A. (2010). Staging system of thymoma. Journal of Thoracic Oncology5(10), S304-S312.

Okuma, Y., Hosomi, Y., Watanabe, K., Nakahara, Y., Takagi, Y., Saito, M., & Okamura, T. (2014, May). Key components of chemotherapy for thymoma and thymic carcinoma: Anthracycline-, carboplatin-, or cisplatin-based chemotherapy. In ASCO Annual Meeting Proceedings 32(15)suppl, e185.

Shelly, S., Agmon-Levin, N., Altman, A., & Shoenfeld, Y. (2011). Thymoma and autoimmunity. Cellular and Molecular Immunology8(3), 199–202. http://doi.org/10.1038/cmi.2010.74

Ströbel, P., Hohenberger, P., & Marx, A. (2010). Thymoma and thymic carcinoma: molecular pathology and targeted therapy. Journal of Thoracic Oncology, 5(10), S286-S290.

Tagawa, T., Okamoto, T., Morodomi, Y., Iwama, E., Nakanishi, Y., Shimamatsu, S., ... & Katsura, M. (2015). P24: The predictive role of the WHO histological classification in the treatment of advanced thymoma. Journal of Thoracic Disease, 7(Suppl 3).

Thomas, A., Rajan, A., Berman, A., Tomita, Y., Brzezniak, C., Lee, M. J., ... & Guha, U. (2015). Sunitinib in patients with chemotherapy-refractory thymoma and thymic carcinoma: an open-label phase 2 trial. The Lancet Oncology16(2), 177-186.

Toker, A., Sonett, J., Zielinski, M., Rea, F., Tomulescu, V., & Detterbeck, F. C. (2011). Standard terms, definitions, and policies for minimally invasive resection of thymoma. Journal of Thoracic Oncology, 6(7), S1739-S1742.

Venuta, F., Anile, M., Diso, D., Vitolo, D., Rendina, E. A., De Giacomo, T., ... & Coloni, G. F. (2010). Thymoma and thymic carcinoma. European Journal of Cardio-Thoracic Surgery37(1), 13-25.

Wei, M. L., Kang, D., Gu, L., Qiu, M., Zhengyin, L., & Mu, Y. (2013). Chemotherapy for thymic carcinoma and advanced thymoma in adults. Cochrane Database Syst Rev, 8.

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