Thymoma

Thymoma

• Thymoma is a rare tumor originating from the thymic epithelial cells. It is the most frequent tumor arising from the thymus gland and the most frequent among the anterior mediastinal neoplasms, despite its unusual incidence. ^1 , 2
• •Thymoma was once considered to be either benign or malignant. Even though thymoma may be benign by nature, it can infiltrate beyond the thymus capsule (invasive thymoma) or become malignant if it progresses (thymic carcinoma). A benign tumor restricted to the thymus is the most prevalent kind of tumor, followed by locally invasive tumors and carcinomas. However, it is currently regarded as having a high possibility of being malignant. The best approach to tell if the condition will return following therapy is to assess whether the tumors have spread to other locations. ¹
• •Thymoma is a slow-growing tumor that spreads primarily through local extension. Extrathoracic metastases are infrequent. In fact, metastases are often restricted to the pleura, pericardium, or diaphragm. Thymomas are frequently associated with neuromuscular conditions such as myasthenia gravis; 10% to 20% of individuals with myasthenia gravis have a thymoma. ¹

Epidemiology & Demographics

• •Thymoma primarily affects adults between the ages of 40 and 70; it is relatively rare in children and adolescents.
• •The risk of developing thymoma is comparable for both men and women. ¹

Incidence

• •The incidence of thymomas is remarkably low, at just 1.5 cases per million individuals.
• •Thymomas are more prevalent among African Americans, Asians, and Pacific Islanders. ³

Risk Factors

• •It is not well understood what causes thymomas.
• •Alcohol consumption, smoking cigarettes, and exposure to ionizing radiation do not appear to be risk factors for developing thymomas.

Physical Findings & Clinical Presentation

• •Regarding the clinical presentation, approximately one third of patients are asymptomatic. Those with symptoms typically exhibit chest discomfort, dysphagia, weight loss, appetite loss, cough, or dyspnea. ⁴
• •There is a strong correlation between thymoma and autoimmune paraneoplastic diseases, the most prevalent of which is myasthenia gravis (30% to 50%), followed by thymoma-associated hypogammaglobulinemia (Good syndrome) and thymoma-associated autoimmune pure red cell aplasia. Myasthenia gravis is characterized by eyelid drooping, double vision, drooling, difficulty ascending stairs, hoarseness, and/or dyspnea. ⁵
• •Thymomas can invade the local tissue (such as the pleura or the lung), but they seldom extend to nearby lymph nodes or extrathoracic locations. It is possible to develop superior vena cava (SVC) syndrome if the tumor is damaging the primary blood vessel, the superior vena cava, that runs between the brain and the heart. The most typical signs and symptoms of SVC syndrome are face/neck edema, dilated neck veins, cough, dyspnea, orthopnea, proptosis, swelling of the upper extremities, and dilated chest vein collaterals. ^2 , 4

Diagnosis

• •Patients who have thymoma in its early stages are usually asymptomatic, and the tumor is frequently discovered inadvertently on a chest x-ray examination or computed tomography (CT) scan.
• •Due to the substantial correlation between myasthenia gravis and thymoma, regular chest CT scans are performed on myasthenia gravis patients as part of their diagnostic evaluation. ⁴

Differential Diagnosis

The thymoma is the most prevalent type of tumor that can be seen in the anterior mediastinum region. ^{2 , 6 , 7}

• •Primary anterior mediastinal mass following by thymoma in adults
  • 1.Substernal goiter
  • 2.Lymphoma
  • 3.Germ cell tumor (teratoma)
  • 4.Carcinoma
• •Primary anterior mediastinal mass following by thymoma in children
  • 1.Lymphoma
  • 2.Germ cell tumor (teratoma)
  • 3.Thymic cyst

Workup

In patients presenting with anterior mediastinal mass, workup is aimed at differentiating between thymic tumors (the most common type) and nonthymic tumors for further management planning.

Laboratory Tests

In cases when myasthenia gravis is suspected, investigations may involve showing antibodies (such as antiacetylcholine receptors or muscle-specific kinase. ⁵

Imaging Studies

Contrast-enhanced CT is the imaging modality of choice for imaging thymic tumors because of its excellent spatial and temporal resolution, ease of access, and convenience; nonetheless, chest radiographs are the most often performed imaging examination and may be the first modality to suggest a thymic mass. Typical characteristics are a well-defined anterior mediastinal mass in the thymic bed, the absence of tumor markers, the absence of additional adenopathy, and the absence of continuity with the thyroid. ⁶⁷⁸

MRI is not frequently utilized in the examination of thymic tumors, although it is beneficial in specific situations, such as evaluating for regions of modest local invasion such as in mediastinal organs. ⁷

• •The importance of PET/CT is particularly evident in aggressive tumors, such as thymic carcinoma, due to a greater total tumor metabolism demonstrated by a much higher absorption of fluorodeoxyglucose in thymic carcinomas compared to thymomas. ⁹

Biopsy

• •If a resectable thymoma is firmly suspected based on clinical and radiologic symptoms (e.g., patients with myasthenia gravis and a distinctive mass on CT), surgical biopsy is not required due to the possibility of tumor seeding when the tumor capsule is breached. In fact, using a transpleural approach to get a thymoma biopsy should be avoided due to the high risk of spreading the tumor within the pleural space, which could result in a stage I thymoma evolving into a stage IV thymoma. ⁴
• •Small biopsies (fine-needle or core needle biopsies) may not necessarily reveal the presence of invasion. However, if the lesion is sampled using a CT-guided needle biopsy, biopsies are accompanied by a low risk of pneumomediastinum or mediastinitis and an even lower risk of heart or large blood vessel injury.
• •Histologically, thymic tumors can be classified according to the World Health Organization (WHO) categories. These classifications are based on the appearance of tumor cells under a microscope as follows ¹⁰

World Health Organization (WHO) Classification of Thymoma and Thymic Carcinoma ²⁰

WHO Type	Histologic Terminology
A	Spindle cell, medullary
AB	Mixed
B1	•Lymphocyte-rich, lymphocytic•Predominantly cortical•Organoid
B2	Cortical
B3	•Epithelial, atypical•Squamoid•Well-differentiated thymic carcinoma
Thymic carcinomas	•Epidermoid keratinizing (squamous cell) carcinoma•Epidermoid nonkeratinizing carcinoma•Lymphoepithelioma-like carcinoma•Sarcomatoid carcinoma (carcinosarcoma)•Clear cell carcinoma•Basaloid carcinoma•Mucoepidermoid carcinoma•Papillary carcinoma•Undifferentiated carcinoma

Masaoka Clinical Staging of Thymoma ²¹

Stage	Description
I	Macroscopically and microscopically completely encapsulated (tumor can invade into but not through the capsule)
IIA	Microscopic invasion through capsule
IIB	Macroscopic invasion into surrounding fatty tissue or mediastinal pleura
IIIA	Macroscopic invasion into neighboring organs (e.g., pericardium or lung)
IIIB	Macroscopic invasion of great vessels
IVA	Pleural or pericardial dissemination
IVB	Lymphogenous or hematogenous metastases

How is this condition treated?

• Surgery, including total thymectomy and complete tumor removal, is suggested for all resectable thymomas in surgically appropriate patients.
• •The term “resectability” refers to a complete resection (R0). Indeed, resection completeness is the most significant outcome predictor. ^13 , 14
• •The pericardium, phrenic nerve, pleura, lung, and even significant vascular structures may need to be excised in order to perform a complete resection. The pleural surfaces should be evaluated for pleural metastases during thymectomy. If feasible, pleural metastases should be eradicated to accomplish complete gross resection. However, bilateral phrenic nerve resection should be avoided due to severe respiratory morbidity. ¹⁵
• •Adjuvant therapy is not indicated for stage I thymomas that have been totally resected (R0); however, postoperative radiation therapy is recommended for incompletely resected thymomas and patients with thymomas that have capsular invasion after an R0 resection. ¹⁴
• •Postoperative radiation is recommended for patients with stage II and stage III thymoma (with macroscopic invasion into adjacent organs) due to the increased risk of disease recurrence. Since thymomas frequently do not disseminate to local lymph nodes, intensive nodal irradiation is rarely a viable option. Postoperative chemotherapy is also not helpful in this situation. The presence of encapsulation has very little impact on the prognosis since all thymomas are classified as malignant when the tumor disrupts the capsule. ¹⁶¹⁷¹⁸

Prognosis

Significance prognostic factors related to shorter overall survival include incomplete tumor resection (R1, R2), increased age, and high staging. ¹⁴

Surveillance

• •Following the primary treatment for resectable thymomas, surveillance for recurrence should comprise chest CT scans every 6 mo for the first 2 yr, followed by yearly screenings for the next 10 yr for thymoma.
• •MRI may be utilized for surveillance, including (1) when patients cannot tolerate contrast and (2) when patients are young and will be evaluated for many years to reduce radiation exposure. ¹⁹

References

1.Engels E.A.: Epidemiology of thymoma and associated malignancies . J Thorac Oncol 2010; 5 (10 Suppl 4): pp. S260-S265.

2.Strollo D.C., et al.: Primary mediastinal tumors. Part 1: tumors of the anterior mediastinum . Chest 1997; 112 (2): pp. 511-522.

3.Engels E.A., Pfeiffer R.M.: Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies . Int J Cancer 2003; 105 (4): pp. 546-551.

4.Detterbeck F.C., Zeeshan A.: Thymoma: current diagnosis and treatment . Chin Med J (Engl) 2013; 126 (11): pp. 2186-2191.

5.Bernard C., et al.: Thymoma associated with autoimmune diseases: 85 cases and literature review . Autoimmun Rev 2016; 15 (1): pp. 82-92.

6.Juanpere S., et al.: A diagnostic approach to the mediastinal masses . Insights Imaging 2013; 4 (1): pp. 29-52.

7.Araki T., et al.: Anterior mediastinal masses in the Framingham Heart Study: prevalence and CT image characteristics . Eur J Radiol Open 2015; 2: pp. 26-31.

8.Benveniste MF et al: Role of imaging in the diagnosis, staging, and treatment of thymoma, Radiographics 31(7):1847-1861; discussion 61-63, 2011.

9.Kim K., et al.: Diagnostic test accuracy of 18F-FDG PET or PET/CT for characterization of histologic type of thymic epithelial tumor: a meta-analysis . Clin Nucl Med 2022; 47 (1): pp. 36-42.

10.Marx A., et al.: The 2021 WHO classification of tumors of the thymus and mediastinum: what is new in thymic epithelial, germ cell, and mesenchymal tumors? . J Thorac Oncol 2022; 17 (2): pp. 200-213.

11.Masaoka A., et al.: Follow-up study of thymomas with special reference to their clinical stages . Cancer 1981; 48 (11): pp. 2485-2492.

12.Masaoka A.: Staging system of thymoma . J Thorac Oncol 2010; 5 (10 Suppl 4): pp. S304-S312.

13.Falkson C.B., et al.: The management of thymoma: a systematic review and practice guideline . J Thorac Oncol 2009; 4 (7): pp. 911-919.

14.Ruffini E., et al.: Tumours of the thymus: a cohort study of prognostic factors from the European Society of Thoracic Surgeons database . Eur J Cardiothorac Surg 2014; 46 (3): pp. 361-368.

15.Ye B., et al.: Surgical techniques for early-stage thymoma: video-assisted thoracoscopic thymectomy versus transsternal thymectomy . J Thorac Cardiovasc Surg 2014; 147 (5): pp. 1599-1603.

16.Basse C., et al.: Multidisciplinary tumor board decision making for postoperative radiotherapy in thymic epithelial tumors: insights from the RYTHMIC prospective cohort . J Thorac Oncol 2017; 12 (11): pp. 1715-1722.

17.Hamaji M., et al.: A meta-analysis of postoperative radiotherapy for thymic carcinoma . Ann Thorac Surg 2017; 103 (5): pp. 1668-1675.

18.Attaran S., et al.: Which stages of thymoma benefit from adjuvant chemotherapy post-thymectomy? . Interact Cardiovasc Thorac Surg 2012; 15 (2): pp. 273-275.

19.Marom E.M.: Imaging thymoma . J Thorac Oncol 2010; 5 (10 Suppl 4): pp. S296-S303.

20.Travis W.D., Harris C.: Pathology and genetics of tumours of the lung, pleura, thymus and heart . Lyon, France . 2004 . IARC Press ,

21.Masaoka A.: Staging system of thymoma . J Thorac Oncol 2010; 5: pp. S304-S312.