As reported in the literature worldwide, the frequency of thymic tumors in both Latin America and Colombia is low; in fact, only 105 patients with thymomas were included in the multicenter study CLICaP-LATimus,[9] which was carried out from 1997 to 2018 in 7 Latin American countries (Mexico, Costa Rica, Colombia, Ecuador, Brazil, Peru and Argentina). In Colombia, a recent publication by Buitrago et al reported 31 patients with thymic tumors who were treated at the National Institute of Cancerology (INC) between 2006 and 2017.[10]
The population described in this article was mainly masculine, unlike what was reported in the CLICaP-LATimus and the INC studies, were the proportion was inverted (40% men and 60% woman).[9, 10] However, the mean age (52.7 years) was similar to the previous studies, unlike what has been reported in international cohorts, such as the European RARECAREnet projects (2000–20007)[11] or the Japanese publication by Kanemura et al,[12] in which patients were on average a decade older at diagnosis.
Unlike what its usually reported, 83.4% of patients were symptomatic at diagnosis, being dyspnea the most frequent manifestation. In this study, we found that 27.7% of patients presented with paraneoplastic syndromes, consistent with the frequency reported in the literature of 30–50%.[6] Furthermore, paraneoplastic neuromuscular syndromes (myasthenia gravis, Eaton-Lambert syndrome, myotonic dystrophy, myositis, neuromyotonic, limbic encephalitis and stiff-person syndrome) are the most common similar to our findings, but hematological (RBC aplasia and pancytopenia), endocrine, dermatological and rheumatological disorders are also prevalent.[6]
Symptomatic patients are more likely to have a chest image, facilitating diagnosis. Although a contrast enhanced chest computed tomography (CT) is the image of choice (Fig. 1),[7] cardiac or chest nuclear magnetic resonance imaging (NMRI) is useful in distinguishing compression from vascular invasion, in large lesions were this could be difficult to determine by CT. NMRI also allows the evaluation of the phrenic nerves and gives additional information about the involvement of the chest wall.[13, 14, 15]
National Comprehensive Cancer Network (NCCN) guidelines divide thymic cancers into three categories, according to the possibility of surgical resection. A total thymectomy and complete excision of the tumor without further treatment is the recommendation for TNM stage I tumors. When capsular invasion is present (stage II-IV) postoperative radiotherapy should be considered. For locally advanced tumors, the possibility of resection should be carefully considered by an experienced multidisciplinary team, and multimodal treatment with chemotherapy and/or radiotherapy is warranted.[16] In our study 89% patients were managed with surgery alone, leaving no residual tumor, including 13 patients with stage I cancer, 1 patient with stage II (T2N0M0) and 1 patient with stage IVB (T3N2M0). The 2 remaining patients, who had separate pleural metastasis (T4N2M1a) and extrathoracic metastasis (T4N2M1b) affecting the brain, also underwent surgery but were offered additional oncologic treatment.
There are different surgical approaches to radical thymectomy, including cervicotomy, thoracotomy, sternotomy and video-assisted thoracoscopic surgery (VATS) (Fig. 9). All soft tissue should be removed in the anterior mediastinum between the phrenic nerves, which is key to control patients who present with myasthenia gravis and positively impact in mortality.[17, 18]. Thoracoscopy was the most utilized approach in our patients (66.6%), as it is minimally invasive and significantly reduces complication rate. VATS is considered to have equal oncologic efficacy than open surgery, with less blood less and complication rate, although there is a higher risk for phrenic nerve injury.[17] In our experience there were no intra or post operatory complications, even in patients who underwent sternotomy and thoracotomy.
Definitive diagnosis was made after surgical intervention in most cases, as in our patients, since the use of biopsy is only contemplated when there is suspicion of a differential diagnosis such as germ cell tumor or goiter.[19] The World Health Organization (WHO) described a histopathological classification for thymomas, thymic carcinomas, thymic neuroendocrine tumors, among others. Specifically for thymomas, which are the most frequent, they are classified as type A, atypical type A variant, type AB, type B1-B3, micronodular thymoma with lymphoid stroma (MNT), metaplastic thymoma and other rare thymomas such as microscopic thymoma, sclerosing thymoma and lipofibroadenoma (Table 3).[20] In our experience, thymomas were the most common histopathological finding (72.2%), similar to the INC study which reported thymomas in 70.9% of cases.[10] Our most frequent subtype was B1 (46.1%) followed by type A (30.8%).
Table 3. World Health Organization (WHO) histological classification of thymomas
Thymoma subtype
|
Obligatory criteria
|
Optional criteria
|
Type A
|
Occurrence of bland, spindle shaped epithelial cells (at least focally); paucitya of absence of immature (TdT+) T cells throughout the tumor
|
Polygonal epithelial cells CD20+ epithelial cells
|
Atypical type A variant
|
Criteria of type A thymoma; in addition: comedo-type tumor necrosis; increased mitotic count (>4/2 mm2); nuclear crowding
|
Polygonal epithelial cells CD20+ epithelial cells
|
Type AB
|
Occurrence of bland, spindle shaped epithelial cells (at least focally); abundance of immature (TdT+) T cells focally or throughout the tumor
|
Polygonal epithelial cells CD20+ epithelial cells
|
Type B1
|
Thymus-like architecture and cytology: abundance of immature T cells, areas of medullary differentiation (medullary islands); paucity of polygonal or dendritic epithelia cells without clustering (< 3 contiguous epithelial cells)
|
Hassall’s corpuscles; perivascular spaces
|
Type B2
|
Increased numbers of single or c lustered polygonal or dendritic epithelial cells intermingled with abundant immature T cells
|
Medullary islands; Hassall’s corpuscles; perivascular spaces
|
Type B3
|
Sheets of polygonal slightly to moderately atypical epithelial cells; absent or rare intercellular bridges; paucity or absence of intermingled TdT+ T cells
|
Hassall’s corpuscles; perivascular spaces
|
MNTb
|
Nodules of bland spindle or oval epithelial cells surrounded by an epithelial cell free lymphoid stroma
|
Lymphoid follicles; monoclonal B cells and/or plasma cells (rare)
|
Metaplastic thymoma
|
Biphasic tumor composed of solid areas of epithelial cells in a background of bland-looking spindle cells; absence of immature T cells
|
Pleomorphism or epithelial cells; actin, keratin or EMA-positive spindle cells
|
Rare othersc
|
|
|
aPaucity versus abundance: any area of crowded immature T cells or moderate numbers of immature T cells > 10% of the investigated tumor are indicative of “abundance.”
bMNT, micronodular thymoma with lymphoid stroma.
cMicroscopic thymoma; sclerosing thymoma; lipofibroadenoma.
Marx A, Chan JK, Coindre JM, et al. The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes. J Thorac Oncol. 2015;10(10):1383‐1395. doi:10.1097/JTO.0000000000000654
Long-term survival of thymic tumors, particularly thymomas, tends to be favorable after radical resection. A retrospective analysis of 62 patients with thymomas who underwent thymectomy, reported an overall 5- and 10-year survival rate of 85.36% and 78.20%, respectively. In this cohort, patients < 50 years old, early Masaoka stages (I and II), histological type (type A, AB, B1) and lack of recurrence were independent prognostic factors of survival.[21] In our experience, survival rate at 5 years was 81%, similar to the study cited earlier. We had three mortalities, of which 2 had disseminated disease.