A Large Thymoma Resected via Left Antero-lateral Thoracotomy
1Department of Thoracic Surgery, “Marius Nasta” National Institute of Pneumology, Bucharest, Romania
2Department of Thoracic Surgery, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
3Department of Internal Medicine, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
4Department of Internal Medicine, Clinical Emergency Hospital of Bucharest, Bucharest, Romania
5Department of Marketing and Medical Technology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
6Department of Public Health and Management University of Medicine and Pharmacy "Carol Davila", Bucharest, Romania
7Department of Urology, “Prof. Dr. Th. Burghele” Clinical Hospital, Bucharest, Romania
8Department of Urology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
9Department of Surgery, “Ponderas” Academic Hospital, Bucharest, Romania
10Department of Obstetrics and Gynecology, “Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania
11Department of Visceral Surgery, Center of Excellence in Translational Medicine “Fundeni” Clinical Institute, Bucharest, Romania
Thymomas are rare tumors and, along with thymic carcinomas, make up the epithelial tumors originating in the thymus. Literature states that thymomas, out of the entire mediastinal masses, have an incidence of 20-30% in adults and only 1% in children (1,2). Thymomas, although rare, represent the most frequent type of anterior mediastinal mass (50% of cases) (3). According to some authors, the incidence of thymomas is 2.5/1,000,000 people/year with a median age between 50 and 60 years and an even distribution between genders (4), while other authors have stated an incidence rate of 0.13-0.15/100,000 people/year (3). Thymomas are more frequent in the Asian population and pacific islanders, followed by black people and then Caucasians. This indicates that genetics may be a part in the development of this disease (4). Also, smoking and spirits consumption are a risk factor (5).
Other studies claim that radiation exposure or aging are linked to thymomas (5). The most recent classification of thymomas (2015) according to World Health Organization (
We present the case of a 67-year-old male, non-smoker. He presented in our clinic for a persistent cough accentuated by dorsal decubitus position, thoracic pain and retrosternal pressure, dyspnea, physical weakness, loss of appetite and weight loss of 1 kg in the previous month. The patient noticed the symptoms in the last three weeks before admission. Blood tests revealed mild anemia, hemoglobin (Hb) 10.5 g/dl, with a slightly elevated partial pressure of carbon dioxide (pCO2). Biochemical and coagulation profiles were within normal limits. Antero-posterior chest x-ray revealed an increase in size of the mediastinal shadow in both hemithoraces, more accentuated towards the left hemithorax, with well-defined margins of subcostal intensity, suggesting the presence of a mediastinal mass. There was also a minimal pleural effusion in the cardio-diaphragmatic sinus.
A standard and contrast thoracic computed tomography (CT) scan (
Surgery was performed by left antero-lateral thoracotomy through the fourth intercostal space due to the growth of the mass in the left hemithorax. Intraoperatively, we discovered a well-defined encapsulated tumor, with no invasion in the adjacent anatomical structures (
Pathological examination revealed a tumor mass (
Very large, giant thymic tumors are rare cases. Thymomas are tumors with slow growth, well tolerated by the patient. Advanced cases with secondary pleural or pericardial lesions are sometimes found (9). In 15-30% of cases, thymomas are discovered by accident, while symptoms of mediastinal suffering are only present in 10% of cases. Alongside clinical symptoms, such as persistent cough, dyspnea and chest pain, other clinical signs may present due to the compression of mediastinal organs including the superior vena cava, venous brachiocephalic trunk, esophagus, phrenic and recurrent nerve. A case of type B3 thymoma with esophageal invasion was reported, with the tumor being visible during esophagoscopy; the first case reported so far (10).
Although superior vena cava syndrome is more frequently found in pulmonary cancer or lymphomas, it has also been described in thymomas (11). A case of thymoma with invasion of the right atrium and superior vena cava has been reported and successfully operated under cardio-pulmonary bypass (12). More so, 30% of thymomas have been found to invade the local mediastinal organs, pleura or pericardium (13). Superior vena cava syndrome in thymomas is very rare, found in only 4% of cases. The extrinsic compression of the superior vena cava or the brachiocephalic trunk is more common (14).
Some thymomas, such as the cystic ones can present with intracystic hemorrhage, having an effect of “acute” mediastinal compression (15). Others may present together with a hemorrhagic pericardial effusion, which may lead to cardiac tamponade (16). Ectopic localizations of thymomas have also been reported, in the left or right hemithorax or posterior to the left innominate vein (17-20). Giant thymomas with intrathoracic development (left or right) are often confused with solitary pleural fibromas (21). Particular cases of thymoma have also been described, such as an ectopic hamartomatous thymoma, with genetic testing revealing it to be a neoplastic disease with changes in the histidyl-transfer ribonucleic acid (tRNA) ligase (
Thymomas tend to have local recurrences and are associated with a series of autoimmune diseases such as autoimmune necrotising myopathy and severe multi-autoimmune syndrome (acute chronic inflammatory demyelinating polyneuropathy, Graves disease, leukocytoclastic vasculitis) (23). Pure white cell aplasia is a rare manifestation in type A+B2 mixed thymomas, associated with neutropenia and severe immunodeficiency (24). However, the most frequent autoimmune manifestation associated with thymoma is myasthenia gravis. It is present in almost 50% of patients with thymoma. Genetic studies revealed approximately 140 genes related to myasthenia gravis, pointing out that hypoxia-inducible factor 3 subunit alpha (HIF3A) is significantly increased in patients with myasthenia gravis. In this regard, itmay play a role in the development of myasthenia gravis (25).
Some authors consider that the presence of a large intrathoracic tumoral mass associated with symptoms of myasthenia gravis should point towards a thymoma diagnosis (18). A series of histological and biological parameters have been identified in patients with thymoma susceptible to developing myasthenia gravis: anti acetylcholine receptor antibodies, type B1 or B2 thymoma, presence of ectopic germinal thymic cells, local invasion by the thymoma, female sex with an age less than 50 (26).
Histopathologically, thymomas are made of different proportions of epithelial cells and lymphocytes. A characteristic of thymomas is that the histological types do not correlate with the clinical presentation, prognosis or survival. Regarding this, there have been cases described, such as a type A thymoma with vertebral metastases, diagnosed using positron emission tomography (PET) scans, having an increased reactivity to 18F-Fluorodeoxyglucose (18F-FDG) (27). Because of such cases, the Masaoka–Koga staging required modifications (28). Immunohistochemistry (IHC) is used for an accurate diagnosis of the thymoma type. This type of epithelial tumor is positive for cytokeratin, vimentin, epithelial membrane antigen and, in most cases, the presence of cells in string-of-pearls or streaming pattern.
For our patient we utilized IHC tests and found positive lymphocytes expressing cluster of differentiation (CD) 1a, terminal deoxynucleotidyl transferase (TdT) and CD5 and negative for CD34, cytokeratin (CK) and epithelial membrane antigen (EMA), leading to a diagnosis of type AB thymoma. Some authors noticed that in type A to B3 thymomas, a series of genetic mutations are more frequent, such as:
Regarding imaging studies, a thoracic CT scan is the main investigation used in identifying thymomas. Studies have been realized which correlate CT findings, Masaoka–Koga staging and the
Recent studies have underlined that in the Masaoka–Koga classification, tumor size was not included as a criterium. However, there has been evidence showing a correlation between tumor size and rate of recurrence in complete thymic resections (32). Other authors consider that the size of the thymoma represents a significant prognostic factor: ≥5 cm points to a high risk of local recurrence and ≥8 cm modifies disease-specific survival (33,34). Similarly, other studies consider patients with tumors larger than 4 cm to have a worse prognosis than those with smaller tumors (34). This correlation was observed in patients with stage I thymoma (35). Risk factors for local recurrence of thymoma after surgery are: histological form according to the
Surgical resection represents the gold standard in treatment of thymomas in both invasive and non-invasive cases (18). Giant encapsulated thymomas tend to have an expansive evolution, but without invading nearby organs or blood vessels. That is why surgical resection, independently of tumor size, must be taken into consideration (37). However, there are other authors that consider radiotherapy as an alternative to surgical treatment in recurrent thymoma. Using high doses of radiation with advanced techniques of precision and focus, results have been favorable, providing evidence towards the fact that recurrent thymomas are radiosensitive (38).
Median sternotomy is the gold standard regarding the surgical approach in favor of minimally invasive surgery used in thymomas. The completeness of resection is an important prognostic factor in the evolution of patients with thymoma (39). However, median sternotomy is not used much in large or giant tumors. It is used more frequently for cases with local extension of the tumor where complete excision is key for the therapeutic success.
Several studies comparing video-assisted thoracoscopic surgery (VATS) with classic surgery in thymoma treatment were performed and they concluded that the outcomes are similar, especially in cases associated with myasthenia gravis. VATS resection can be used for thymomas that only extend to the mediastinal pleura. For large encapsulated thymomas, with compression signs of the mediastinum, open surgery is preferred (40). Some authors compared the postoperative results of patients that underwent VATS and robotic surgery for the treatment of stages I and II thymomas and observed similar results, with both techniques having the same viability (41). In order to obtain proper access to both the mediastinum as well as the superior thoracic cavity, some authors prefer using a hemi-clamshell incision, especially for giant thymomas (42). For large thymomas developing towards either thoracic cavity, some surgeons prefer using a median sternotomy along with a splitting of the sternum along the intercostal space (19).
Giant encapsulated thymomas, with no local extension can be resected using an antero-lateral thoracotomy, preferred by most authors. In our case, the surgical resection was performed using a left antero-lateral thoracotomy through the fourth intercostal space, due to the tumor development being mostly in the left hemithorax and no presence of mediastinal invasion on the CT scan. This type of approach has the advantage of being less invasive and much more versatile due to the ability to extend it. The surgical approach was safe, giving enough visibility in order to perform a complete resection of the tumor along with lymph node dissection.
Histological diagnosis along with IHC confirmed a stage I, type AB thymoma, in which case we considered complementary treatment not to be necessary. Patient follow up was done after one, three, six months and one year, with no signs of local recurrence (patient received surgical treatment 14 months ago). Even so, postoperative radiotherapy in thymomas is still a controversial theme. Although it does not increase relapse free survival or overall survival for stage II or III thymomas, it has a proven beneficial effect for stage II and III thymic carcinoids (43).
Some authors have suggested alternative treatments, such as CT-guided radiofrequency ablation for small stage I thymomas, observing the benefits of this method as it has a minimal rate of complications, removal is complete and costs are reduced (34). Although induction therapy is used especially in pulmonary neoplastic disease, it has also been used in thymic neoplastic disease (44). Comparative studies performed on patients that underwent surgery for thymic tumors with or without induction chemotherapy concluded that it may improve resectability, influencing the result in stage III and IV thymomas (45).
On the other hand, for invasive thymomas or unresectable stage IV thymic carcinoma an association between Tegafur, Gimeracil and Oteracil is recommended. Results obtained are similar to immunotherapy, but with much lower costs (46). Studies following the role of surgery depending on the stage of the disease show a smaller survival rate for patients with type B3 compared to those with types A, B1 or B2 thymomas. Long-term survival was increased in patients that also underwent surgical treatment for recurrences (47).
Local tumor extension remains the most important prognostic factor. In stage I, surgical treatment alone is recommended as treatment whereas, in stages II and III, adjuvant radiotherapy should be performed. Although each histological type is associated with different rates of recurrence and survival, a multicentre analysis revealed that age, stage as well as resectability are the main prognostic factors. The histological type is important in appreciating the chances of recurrence but not for survival (48,49).
So far, in the literature, there is no consensus regarding the surgical approach of giant thymomas. Complete resection can be performed for large stage I and II thymomas using an antero-lateral thoracotomy. This type of approach has the advantage of being less invasive and much more versatile due to the ability to extend it. Surgical treatment is still the main therapeutic method used for thymomas, no matter their size, local extension or recurrence.
Conflicts of Interest
The Authors have no conflicts of interest to declare regarding this study.
CS, AM, AG, IG, AZ performed the surgical procedure; VAT, NB, IB reviewed literature data; CD, FG performed preoperative investigation of the patient; CD, FG, FF performed perioperative and postoperative follow up of the patient; IB, FG FF, DR prepared the draft of the manuscript; IC was the advisor of the surgical procedures; CS, NB reviewed the final version of the manuscript. All Authors read and approved the final version of the manuscript.