David Deng

Overview: Thymoma is a rare abnormal growth of tissue of the epithelial cells of the thymus,
which is located in the anterior mediastinum. It is classically associated with myasthenia gravis.
Thymomas are commonly surgically removed; chemotherapy is used if complete resection is not
practical. Causes of and risk factors for thymoma remain to be found.
Epidemiology: Thymomas are relatively rare, occurring about 0.13 per 100,000 person-years, or
about 415 cases per year in the United States. They occur mainly in people 40-60 years of age
and more commonly in African Americans and Asians/Pacific Islanders. There are no known
causes or risk factors that are highly associated with thymomas. Patients with thymoma have an
increased risk for all cancers, and may have a significant increase in risk of B-cell non-Hodgkin
lymphoma (which may be due to T-cell dysfunction in thymoma), soft tissue sarcomas, and
gastrointestinal cancers.
Clinical Presentation: Thymomas generally present either as an incidental finding on imaging
in an asymptomatic patient, with paraneoplastic symptoms, or because of mass effect and
compression of anatomic structures around the thymus.
On imaging with CT or MRI, normal thymus shows a triangular shape best seen at the level of
the aortic arch (normal thymus not seen on chest x-ray). Thymic hyperplasia will mostly be seen
on CT as a diffusely and symmetrically enlarged thymus with smooth borders and maintenance
of the normal thymic shape. Thymoma will usually present on radiograph as a unilateral, welldemarcated mass averaging 5 cm with smooth or lobulated contours from a single lobe of the
thymus; locally advanced disease may have irregular borders with the adjacent lung and
elevation of the hemidiaphragm because of phrenic nerve involvement.
The classic paraneoplastic syndrome found in patients with thymoma is myasthenia gravis, a
disease where antibodies are formed against the acetylcholine nicotinic postsynaptic receptors,
causing progressively decreased muscle strength with use and recovery of muscle strength after
rest, notably affecting extraocular muscles. About half of thymoma patients are affected by
myasthenia gravis, but only 15% of myasthenia gravis patients also have thymoma. Other
paraneoplastic associated with thymoma include pure red cell aplasia, an autoimmune related
hypoplasia of red blood cell precursors (found in 5-15% of thymoma patients) and
hypogammaglobulinemia plus pure white blood cell (less than 5% of thymoma patients), which
presents with recurrent infections, lymphadenopathy, and diarrhea.
Mass effects of thymomas include chest pain, cough, dyspnea, dysphagia, phrenic nerve palsy,
and superior vena cava syndrome, which presents with edema of . More disseminated cases can
present with pleural or pericardial effusions.
Diagnostic studies: CT is the best imaging study for thymoma, but MRI can also be done for a
patient to assess an anterior mediastinal mass and whether it is resectable. Chemical shift MR
imaging with in-phase and out-of-phase gradient can be used to differentiate between thymoma
and non-neoplastic thymic enlargement. Some of the possible differential diagnoses of an
anterior mediastinal mass include thymoma, thymic carcinoma, retrosternal thyroid, lymphoma,
mediastinal germ cell tumor. Thyroid function tests and germ-cell tumor markers such as fetoprotein -hCG can be utilized to distinguish other diagnoses from a thymoma.
Relevant Preoperative Studies: Generally if radiography shows a well-circumscribed mass in
the thymus, biopsy is not needed. Biopsy may be performed if the diagnosis is not clear, if the
mass invades adjacent structures, or if lymphoma or germ cell tumor is suspected. Pulmonary
function along with degree of myasthenia gravis is used to determine if it is reasonable to resect
a phrenic nerve that has become involved with a thymoma (not reasonable to resect both phrenic
nerves because that would cripple respiration). Staging of thymomas is critical for creating an

David Deng
optimal treatment plan for the patient; the Masaoka staging system is most widely used. In stage
I thymoma, the tumor is completely encapsulated microscopically and macroscopically. In stage
II thymoma, there is invasion through the capsule: stage IIA is microscopic transcapsular
invasion and stage IIB is macroscopic invasion into surrounding fat or adherent but not
penetrating the mediastinal pleura or pericardium. Stage III thymoma has pericardial or lung
involvement; in stage IIIA there is macroscopic invasion into pericardium or lung without great
vessel invasion, and in stage IIIB there is macroscopic invasion into pericardium or lung with
great vessel invasion. Stage IV thymoma is disseminated; pleural or pericardial dissemination in
stage IVA, lymphatic or hematogenous metastases in stage IVB.
Surgical and Non-surgical interventions: If a patients imaging shows that complete removal
of tumor is possible, then surgery should be done to completely remove the thymoma as the first
step. General current management guidelines are the following: Stage I thymomas should be
completely resected without adjuvant therapy, stage II thymomas should also be completely
resected but with some consideration of adjuvant therapy. Stage IIIA thymomas should be
completely resected before or after adjuvant therapy, and stage IIIB thymomas can include some
combination of chemotherapy, radiation, or surgery of technically possible. Stage IV thymomas
should only be surgically resected if metastases can be resected; otherwise use chemotherapy and
radiation. For surgical resection, the most common method involves the sternum-splitting
approach, also called extended transsternal thymectomy because it fully exposes the
mediastinum to allow complete removal of the thymus and associated fat/structures. Other
methods that are less widely used and have less clinical data include extended-cervical
thymectomy and minimally invasive thymectomy via video-assisted thoracoscopy or robotassist. After a complete resection, follow-up long-term is recommended for surveillance of late
relapse of thymoma with a CT scan, and if a relapse is found, it should be treated with a curative
intent.
Patients who still have positive surgical margins or have gone through an incomplete resection
should be treated with radiotherapy for the residual tumor.
In medically inoperable and technically inoperable patients, chemotherapy and radiation are
used. Some of the chemotherapy regimens include CAP (cisplatin, doxorubicin, and
cyclophosphamide), CAP with prednisone, CAP + vincristine, PE (cisplastin and etoposide), and
VIP (etopside, ifosfamide, and cisplatin). These patients may be encouraged to participate in
formal clinical trials if possible.
Benefits/risk/complications: In patients that have myasthenia gravis with thymoma, most
patients either have a complete remission of myasthenia gravis or more commonly show an
improvement with a decreased need for medications. Even though the thymus is the primary site
of T-cell maturation, surgery to remove a thymoma does not seem to cause immune deficiency in
adults. Sometimes a transient postoperative increase in myasthenic gravis symptoms occurs in
certain patients with expiratory weakness, vital capacity of less than 2 L, high serum
acetylcholine receptor antibody, or high intraoperative blood loss. Patients undergoing a
myasthenia crisis or acute exacerbation of myasthenia gravis should not undergo surgery and
should instead receive plasmaphresis.
Outcomes: The overall prognosis of thymoma patients correlates highly with the stage of the
thymoma and its ability to be completely resected. The 5 year prognosis of stage I thymoma is
over 90%, for stage II thymoma it is about 80%, for stage III thymoma it is about 60-65%, and
for stage IV thymoma it is about 20-30%. Prognostic value of histological grading remains
unclear.

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