Thymic epithelial tumors: still enigmatic neoplasms!

Thymic epithelial tumors comprising thymomas and thymic carcinomas, are quite fascinating tumors due to their specific location in the mediastinum, their association with several paraneoplastic syndromes, and different clinical behavior (1). In contrast to lung cancer and pleural mesothelioma, thymic epithelial tumors usually have a good prognosis when a complete resection is obtained. Operative morbidity and mortality are low unless extended resections are necessary and recurrences occur at a lower frequency compared to the other thoracic tumors. Specific tumor characteristics related to recurrent disease have not been firmly established.

In the present study 235 cases originating from the National Yang Ming University in Taipei, Taiwan were analyzed (2). Long-term survival and recurrence rate were studied. All patients underwent surgical resection with a complete resection rate of 97.02% as mentioned in table 1 of the manuscript (and not 93.44% as mentioned in the text). Surgical procedures included extended thymothymectomy (removal of the entire thymic gland including thymoma) by median sternotomy, or thymomectomy (removal of the thymoma only) by thoracotomy or video-assisted thoracic surgery (VATS). Overall mortality was 5.6% (13 patients). Median follow-up time was 105 months (8.8 years). During follow-up recurrences were detected in 25 patients (10.7%). These were subdivided into local recurrence (6 patients), regional recurrence (12 patients) and distant recurrence (10 patients). Distant metastatic disease included bone metastasis (3 patients), liver metastasis (1 patient) and intraparenchymal pulmonary nodules (6 patients). Overall survival rate was 94.4%. In univariate analysis Masaoka stage, histological type, tumor size, adjuvant therapy and margin status were related to tumor recurrence (2). The authors conclude that due to the indolent behavior of thymoma, tumor recurrence appears to be the best parameter to study oncological outcome.

This retrospective study includes a large series of patients with thymic epithelial tumors. However, it expands over an almost 16-year time period during which diagnostic and therapeutic algorithm most probably have changed substantially. Patients who had neoadjuvant chemoradiation were excluded which is unfortunate as they represent a challenging group of patients with more advanced disease. Overall, a detailed survival analysis is presented and recurrence studied according to specific clinical factors for which the authors are to be commended. Although the title mentions outcome of thymic carcinoma, no such patients are enlisted in the first table where all 235 patients were categorized as having thymoma. This means that the recurrence rate which is higher in thymic carcinoma compared to thymoma, was in fact not studied (3). Regarding staging itself in the first table, only Masaoka stage (or was it Masaoka-Koga?) and World Health Organization (WHO) histological type are listed although the authors state in the Materials and Methods section that they used the new, 8th edition of the Tumor-Node-Metastasis (TNM) staging system (4-6). In the figures overall and disease-free survival were not depicted according to this new edition of the TNM-classification, although for recurrence rate (the third table) this TNM stage was included, which is rather confusing. In total, 43.4% of patients had adjuvant radiotherapy or chemoradiation which is surprising as 97.0% had a complete R0 resection. Indications for adjuvant therapy are not clearly mentioned by the authors.

Factors related to recurrence of thymoma which is the main objective of this study, are as can be expected. Patients with more advanced stage, larger tumors, unfavorable histology, adjuvant therapy and doubtful margins presented a high risk of recurrence. Regarding the type of resection, the authors performed as well a thymomectomy as an extended thymothymectomy. This is still a controversial issue in literature, but as also mentioned by the authors, in case of myasthenia gravis extended resection is necessary, not only to remove the tumor but also all possible sources of antibody production (7,8).

Although the authors provide details on risk of recurrence, they do not detail specific therapy and outcome in these patients with recurrent thymoma. In literature there are no clear recommendations but repeat resection of recurrent disease, whether it be purely local or locoregional, seems to provide the best long-term results (9-11).

The present study highlights the specific problems and possible bias encountered with retrospective studies associated with a low number of events. As also mentioned by the authors, they were only able to perform a univariate analysis. A detailed multivariate analysis was not possible due to the limited number of patients with recurrent disease. Single-institution experiences are not able to resolve completely the specific question of which factors significantly determine long-term survival and recurrence rate. Only joint efforts with creation of large prospective databases as initiated by the International Thymic Malignancies Interest Group (ITMIG) are able to collect enough data to provide more definite answers (12). All thoracic surgeons and thoracic oncologists are encouraged to participate in this worldwide effort and include as many patients as possible. In this way, thymic epithelial tumors will become less enigmatic in the near future.

Acknowledgments

Funding: None.

Footnote

Provenance and Peer Review: This article was commissioned and and reviewed by Section Editor Dr. Zhuoqi Jia (Thoracic Department, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/med.2017.09.05). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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