Updated: Jul 25, 2022
Author: Kendrix J Evans, MD, MS; Chief Editor: John Geibel, MD, MSc, DSc, AGAF 



Thymoma originates within the epithelial cells of the thymus, a lymphoid organ located in the anterior mediastinum. This organ is located behind the sternum in front of the great vessels; it reaches its maximum weight at puberty and undergoes involution thereafter.

In early life, the thymus is responsible for the development and maturation of cell-mediated immunologic functions. The thymus is composed predominantly of epithelial cells and lymphocytes. Precursor cells migrate to the thymus and differentiate into lymphocytes. Most of these lymphocytes are destroyed, with the remainder of these cells migrating to tissues to become T cells.

A relation between myasthenia gravis (MG) and thymomas was determined incidentally in 1939, when Blalock et al reported the first excision of a thymic cyst in a 19-year-old girl with MG.[1] This patient achieved long-term remission; therefore, thymectomy became the definitive therapy for treatment of generalized MG.

No clear histologic distinction between benign and malignant thymomas exists. The propensity of a thymoma to be malignant is determined by the invasiveness of the thymoma. Malignant thymomas can invade the vasculature, lymphatics, and adjacent structures within the mediastinum. The 15-year survival rate is 12.5% for a person with an invasive thymoma and 47% for a person with a noninvasive thymoma. Death usually occurs from cardiac tamponade or other cardiorespiratory complications.


The thymus gland is located behind the sternum, in front of the great vessels and the pericardium; it can extend laterally to the phrenic nerves (see the images below). The main blood supply is from the internal thoracic arteries; however, the gland also is supplied with blood by the inferior thyroid and pericardiophrenic arteries.

Anatomy of thymus, with emphasis on blood supply a Anatomy of thymus, with emphasis on blood supply and relation to recurrent laryngeal and phrenic nerves.
Lateral view of thymus. Thymic arteries are derive Lateral view of thymus. Thymic arteries are derived from adjacent internal mammary arteries; inferior thymic vein empties into innominate vein. Thymus gland's surrounding vascular and neural structures may be invaded during spread of thymoma.


The etiology of thymomas has not been elucidated; however, these lesions have been associated with various systemic syndromes. As many as 30-40% of patients who have a thymoma experience symptoms suggestive of MG. An additional 5% of patients who have a thymoma have other systemic syndromes, including red cell aplasia, dermatomyositis, systemic lupus erythematosus (SLE), Cushing syndrome, and syndrome of inappropriate antidiuretic hormone secretion (SIADH).


Thymoma is the most common neoplasm of the anterior mediastinum, accounting for 20-25% of all mediastinal tumors and 50% of anterior mediastinal masses. Its peak incidence occurs in the fourth and fifth decades of life; the mean age of patients is 52 years. No sexual predilection exists.


The prognosis is worse for patients with symptomatic thymomas because these patients are more likely to have a malignant thymoma. The single most important factor predicting the outcome of patients with thymomas is evidence of invasion. Histologic characteristics, such as microscopic capsular invasion, should be assessed.[2] The surgeon should perform a gross inspection. Cellular characteristics are inconsequential because they have no impact on patient treatment.

Because of the well-documented propensity for late recurrences, long-term survival should be considered in terms of a 10-year follow-up after treatment of the thymoma. A study conducted by the Memorial Sloan-Kettering Cancer Center reported 5-year and 10-year survival rates for various stages of thymomas (see Table 1 below).[3]

Table 1. Survival of Thymoma by Stage: Memorial Sloan-Kettering Experience (Open Table in a new window)


5-Year Survival

10-Year Survival











Less than 25%


Thymomas are associated with the development of second malignancies. A review of the Surveillance, Epidemiology, and End Results (SEER) database of thymoma cases in the United States (1973-1988) identified 849 cases, of which 66 had second malignancies. There was an excess occurrence of non-Hodgkin lymphoma and soft-tissue sarcoma but of no other specific cancers. Notably, an increase in digestive system cancers (colon/rectum, stomach, esophagus, liver/biliary tract) occurred; however, these increases were not statistically significant.



History and Physical Examination

Of patients with a thymoma, one third to one half are asymptomatic, and one third present with local symptoms related to the tumor's encroachment on surrounding structures. These patients may present with cough, chest pain, superior vena cava (SVC) syndrome, dysphagia, and hoarseness if the recurrent laryngeal nerve is involved. One third of cases are found incidentally on radiographic examinations during a workup for myasthenia gravis (MG).

Although development of a thymoma in childhood is rare, children are more likely than adults to have symptoms. Several explanations for the prevalence of symptoms in children have been proposed, including the following:

  • Children are more likely to have malignancy
  • Lesions are more likely to cause symptoms by compression or invasion in the smaller thoracic cavity of a child
  • The most common location for mediastinal tumors in children is near the trachea, resulting in respiratory symptoms

Four cases of patients who presented with severe chest pain secondary to infarction or hemorrhage of the tumor have been reported. Cases of invasion into the SVC resulting in venous obstruction have also been reported.[4] The clinician should be aware of these rare presentations of a thymoma.



Laboratory Studies

The diagnosis of a thymoma usually is clinically based on radiologic findings. Laboratory studies generally are not indicated.

Imaging Studies


Posteroanterior (PA) and lateral chest radiographs can detect most thymomas. On the PA view, the lesion typically appears as a smooth mass in the upper half of the chest, overlying the superior portion of the cardiac shadow near the junction of the heart and great vessels.

The mass usually projects predominantly into one of the hemithoraces. On the right, the silhouette sign is present and the ascending portion of the aortic arch is obliterated. Conversely, if the thymoma is on the left, the silhouette sign is obscured and the aortic knob is identified behind the mass.

Computed tomography

Computed tomography (CT) may delineate a mass further or may detect a smaller tumor that was missed by radiography (see the image below). Chest CT is the imaging procedure of choice in patients with myasthenia gravis (MG). Thymic enlargement should be determined because most enlarged thymus glands visualized on CT represent thymomas.

CT scan clearly illustrates mass in right anterola CT scan clearly illustrates mass in right anterolateral mediastinum.

CT with intravenous contrast dye is preferred to show the relations between the thymoma and surrounding vascular structures, to define the degree of its vascularity, and to guide the surgeon in removal of a large tumor, possibly involving other mediastinal structures.

Positron emission tomography

A case report found positron emission tomography (PET) to be invaluable in confirming the diagnosis of an invasive malignant thymoma.[5] Although CT revealed evidence of an anterior mediastinal mass, PET showed a hypermetabolic mass consistent with this location, thereby raising suspicion of malignancy. Subsequent resection of the mass revealed a minimally invasive thymoma due to capsular invasion. PET should be added to the armamentarium as an available diagnostic modality to aid in staging and excluding extramediastinal involvement.[5]

Fine-Needle Aspiration and Biopsy

If a patient presents with atypical features or is found to have an invasive tumor and is under consideration for induction therapy, a preoperative biopsy is indicated. The limited anterior mediastinotomy (Chamberlain approach) is the standard approach that typically is performed over the projection of the tumor. A thoracoscopic approach for biopsy also can be used.

Controversy exists over the efficacy of fine-needle aspiration (FNA). FNA has been reported by some to be beneficial in making the diagnosis of a thymoma. Performing a core biopsy in conjunction with FNA is a modality that can increase the accuracy with which thymomas can be differentiated from other neoplasms, such as lymphomas and germ cell tumors.

Histologic Findings

Traditionally, thymomas have been classified into three histologic types according to the cell type that is predominant—lymphocytic, epithelial, or lymphoepithelial. A pathologic classification was developed by the World Health Organization (WHO). In a study conducted in Japan between 1973 and 2001 of a series of 100 resected thymomas, prognostic categories were distinguished by using this WHO classification (see Table 2 below).[6]

Table 2. World Health Organization (WHO) Pathologic Classification and Associated Prognostic Categories (Open Table in a new window)


Histologic Description

Disease-Free Survival at 10 years,* %


Medullary thymoma



Mixed thymoma



Predominantly cortical thymoma



Cortical thymoma



Well-differentiated thymic carcinoma



Thymic carcinoma


*Series of 100 thymomas resected in Japan between 1973 and 2001 using WHO classification.[6]


The Masaoka system is the most commonly accepted staging system for thymomas (see Table 3 below).

Table 3. Masaoka Staging System of Thymomas and Corresponding Therapy (Open Table in a new window)





Encapsulated tumor with no gross or microscopic invasion

Complete surgical excision


Macroscopic invasion into the mediastinal fat or pleura or microscopic invasion into the capsule

Complete surgical excision and postoperative radiotherapy to decrease the incidence of local recurrence


Invasion of the pericardium, great vessels, or lung

Complete surgical excision and postoperative radiotherapy to decrease the incidence of local recurrence


Pleural or pericardial metastatic spread

Surgical debulking, radiotherapy, and chemotherapy


Pleural or pericardial metastatic spread

Surgical debulking, radiotherapy, and chemotherapy

See Thymoma Staging for more information.



Medical Therapy


A few reports in the literature suggest that thymomas are chemosensitive tumors.[7] Potential candidates for chemotherapy include approximately one third of the patients with an invasive thymoma that later metastasizes and all patients with stage IV disease.

Fornasiero et al reported successful cases and some long-term survivors following the administration of a regimen of cisplatin/vincristine/doxorubicin/cyclophosphamide for incompletely resected invasive thymomas or cases with unresectable disease.[8] In 32 patients, a 47% complete and 90% overall response rate was noted with a median survival time of 15 months.

A trial conducted by the European Organisation for Research and Treatment of Cancer reported that among 16 patients with recurrent or metastatic thymomas, five complete remissions and four partial remissions were observed. Median survival time in this study was 4.3 years.


Case reports have documented the administration of oral glucocorticoids resulting in regression of an invasive thymoma. In one case, the patient showed complete regression to the thymoma and associated symptoms and has remained without radiologic recurrence after 12 months.[9]

Multidisciplinary approach

A multidisciplinary approach to therapy for unresectable thymomas has been advocated.[10, 11] In a trial conducted by the M.D. Anderson Cancer Center, 12 patients received a treatment regimen consisting of induction chemotherapy (ie, three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone), surgical resection, postoperative radiation therapy, and consolidation chemotherapy (ie, three courses of cyclophosphamide, doxorubicin, cisplatin, and prednisone).[12]

Of the 12 patients, three (25%) had a complete response, eight (67%) a partial response, and one (8%) a minor response.[12] One patient refused surgery, nine (82%) had complete resections, and two (18%) who had been receiving radiation therapy and consolidation chemotherapy had incomplete resections. All 12 patients (100%) were alive at 7 years, and 10 (73%) were disease-free at 7 years. The authors suggested that aggressive multimodal treatment is effective and may be curative in locally advanced, unresectable, malignant thymomas.

Octreotide (0.5 mg SC q8hr) alone or with prednisone (0.6 mg/kg/day) was evaluated in 38 patients with advanced thymomas that expressed somatostatin receptors.[13] Of the 38, four (10.5%) had a partial response with octreotide alone. Of the 21 patients who received octreotide plus prednisone, two had complete responses and four had partial responses. Octrotide plus prednisone yielded better progression-free survival than octreotide alone. Octreotide therapy may be a valuable treatment option when chemotherapy is ineffective.

See Thymoma Treatment Protocols for more information.

Future options

Studies have investigated the molecular changes in thymomas. In one study, 10 out of 12 thymomas exhibited epidermal growth factor receptor (EGFR) expression. This information would be useful in selecting patients that may benefit from EGFR inhibitors as part of their treatment regimen. Other areas of investigation include apoptosis-related markers, such as p63, a member of the p53 family. This marker is expressed in virtually all thymomas. Further research pertaining to the biology of thymomas will allow more adequate approaches to treatment.

Surgical Therapy

In most cases of thymoma, initial management is surgical.[7, 11] Surgical excision provides the histologic characteristics of the tumor and provides staging information that helps determine the need for adjuvant therapy. Small and encapsulated thymomas are excised for diagnosis and treatment. In the past, obtaining a preoperative biopsy of large invasive thymomas was shunned for fear of local implantation of tumor cells. Currently, biopsies are performed for these atypical tumors to discover the histology of the tumor and to ascertain its invasive potential.

A single-institution retrospective study was conducted of five patients with stage IVA thymoma treated with pleuropneumonectomy.[14] The median survival was 86 months, and the Kaplan-Meier survival was 75% at 5 years and 50% at 10 years. There was no operative mortality in this study. It has been suggested that in select patients, this approach after a complete resection and neoadjuvant chemotherapy may be promising.[14]

The prognosis for a thymoma patient is based on the tumor's gross characteristics at operation, not its histologic appearance. Benign tumors are noninvasive and encapsulated. Conversely, malignant tumors are defined by local invasion into the thymic capsule or surrounding tissue. As noted (see Staging), the Masaoka system is the most commonly accepted staging system for thymomas.

Although there has been controversy regarding the use of postoperative radiation for invasive thymomas, the preponderance of evidence indicates that all thymomas, except completely encapsulated stage I tumors, benefit from adjuvant radiation therapy.[2]

Preparation for surgery

Preoperative adjuvant radiation therapy has been used to increase the possibility of complete resection when computed tomography (CT) suggests that a tumor is very large or invasive. Although doses of 30-45 Gy have been used in this approach, complete responses rarely have been reported. One caveat to this therapy is that the patient is placed at increased risk for radiation pneumonitis because of the large size of ports required to cover the field.

Patients with a preoperative diagnosis of myasthenia gravis (MG) and a thymoma should optimize their medical condition before surgery by using cholinesterase inhibitors and plasmapheresis if indicated.

Operative details

Although the preferred approach is a median sternotomy to provide adequate exposure of the mediastinal structures and allowing complete removal of the thymus, the cervical approach also is adequate.

If the tumor is small and appears readily accessible, perform a total thymectomy with contiguous removal of mediastinal fat. If the tumor is invasive, perform a total thymectomy in addition to en-bloc removal of involved pericardium, pleura, lung, phrenic nerve, innominate vein, or superior vena cava. Resect one phrenic nerve; however, if both phrenic nerves are involved, do not resect either one, and debulk the area. Clip areas of close margins or residual disease to assist the radiation oncologist in treatment planning.

Controversy persists with regard to whether biopsy or subtotal excision is superior for treating unresectable tumors. Some studies have supported subtotal excision, whereas others have shown no difference between the two modalities. A generally accepted rule is that patients with invasive or residual disease should receive adjuvant therapy.

Minimally invasive approaches

With the advent of video-assisted minimally invasive surgery, many of the traditional thoracic procedures have been abandoned. Video-assisted thoracoscopic surgery (VATS) for thymoma has been described; however, there remains a need for additional long-term data, and the optimal approach is yet to be established.

Roviaro et al performed video thoracoscopy on six patients with thymomas; however, they did not describe the extent of resection, the size of the tumor, or the tumor stage, and long-term follow-up data are unavailable.[15] Kaiser advocated the use of transcervical dissection in conjunction with video thoracoscopy, allowing better exposure.[16]

Mack presented a series of photographs of thymus glands removed by means of thoracoscopy.[17] These photographs confirmed that the thymus gland can be resected completely by experienced surgeons. Long-term follow-up data are required to determine the true efficacy of this procedure in comparison with traditional thymectomy.

In a study of 140 patients with stage I and II thymoma, Chao et al compared perioperative and oncologic outcomes after VATS resection for stage I and II thymoma with those obtained after median sternotomy.[18] No operative deaths occurred, and there were no statistically significant differences in 5-year survival between the two study groups. VATS was associated with better perioperative outcomes (eg, less intraoperative blood loss, greater frequency of extubation in the operating room after surgery, and a shorter length of stay).

In a propensity score-matching analysis, Yang et al compared the safety and feasibility of subxiphoid-approach thoracoscopic thymectomy (SATT; n = 144) and lateral intercostal–approach thoracoscopic thymectomy (LATT; n = 144) for Masaoka-Koga stages 1 and 2 thymoma.[19]  The SATT group had a significantly higher rate of exposure to the bilateral phrenic nerves than the LATT group did, as well as greater maximum length and width of resected tissue. The SATT group also had lower postoperative high-sensitivity C-reactive protein (hs-CRP) levels; better visual analog pain scale (VAS) scores on postoperative days 1, 3, and 7; and better quality of life on postoperative days 30 and 90.

Postoperative Care

Adjuvant radiation therapy[7] in completely or incompletely resected stage III or IV thymomas is considered a standard of care. The use of postoperative radiation therapy in stage II thymomas, however, has been questioned. 

Thymomas are indolent tumors that may take at least 10 years to recur; therefore, short-term follow-up will not depict relapses accurately. Furthermore, the gross appearance of tumor invasiveness is subjective, depending on the opinion of the surgeon. In one report from the Massachusetts General Hospital, five (22%) of 23 patients with stage II disease developed recurrences, leading to a proposed recommendation that postoperative radiation be instituted in all patients with stage II thymoma.[20]

In a study conducted by Curran et al that included 21 patients with stage II and III disease who did not undergo postoperative (total resection) radiation therapy, eight patients had recurrences in the mediastinum.[21] The five patients who received adjuvant radiation did not have recurrences.

A series from Memorial Sloan-Kettering Cancer Center, however, showed that adjuvant radiation therapy did not improve survival or decrease recurrence in stage II and III disease.[3] To reduce the incidence of local relapse, perform postoperative adjuvant radiation therapy in patients without completely encapsulated stage I tumors.

In a retrospective review of 241 patients with thymoma who received radiation therapy after total thymectomy, partial resection, debulking, or biopsy, Wu et al reported 10-year survival rates of 87% for stage I thymoma, 78.7% for stage II, 57.4% for stage III disease, and 24.3% for stage IV.[22] They concluded that surgery and postoperative radiotherapy should be standard for stage II or III but that further research was needed to establish whether this is true for stage I. They also found that the following tended to have a more favorable prognosis:

  • Female patients
  • Patients with early-stage thymoma
  • Patients who underwent surgical extirpation of the neoplasm

A database analysis by Jackson et al found that postoperative radiotherapy was associated with longer overall survival in patients with stage IIB thymoma, but no significant effect could be demonstrated for stage IIA disease.[23]  


Complications (eg, radiation pericarditis, radiation pneumonitis, pulmonary fibrosis) have been reported after postoperative radiation therapy. Deaths from these complications have been reported; accordingly, clinicians must carefully consider the risk-to-benefit ratio of adjuvant radiation therapy.

Long-Term Monitoring

Relapse after primary therapy for a thymoma may occur after 10-20 years. Therefore, long-term follow-up probably should continue to be performed throughout the patient's life.


Questions & Answers


What is thymoma?

What is the anatomy of the thymus gland relevant to thymoma?

What causes thymoma?

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What are the signs and symptoms of thymoma?

Why are symptoms of thymoma more likely to be seen in children more than adults?

Which unusual presentations of thymoma have been reported?


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