Thymoma and thymic carcinoma

Thymoma and thymic carcinoma are two most common tumors of thymic gland. Along with thymic neuroendocrine tumours, they constitute thymic epithelial tumours (TETs). Differentiation is important from the prognostic point of view. Spectrum varies from a largely benign thymoma to virulent thymic carcinoma. Thymoma, though largely benign, can transform into malignant variant either de novo or through natural progression.

Staging of TETs has always been a subject matter of much debate worldwide. Rarity of these tumours make staging system and its relationship with outcome difficult. Fifteen unique staging classifications had been proposed for thymic tumours [1]. Widely used Masaoka-Koga system of staging based on 96 patients is giving way to tumour node metastasis (TNM) system (based on international database of 10,000 patients) despite obvious challenges because of unique characteristics of TETs such as slow growth, local spread and non-availability of specific tumor markers. Currently, there are no specific immunohistochemical markers for thymic tumours. Normal thymic gland stains similarly as squamous cell carcinoma [2]. Previously, thymic tumours were considered benign or malignant depending upon absence or presence of adjacent tissue invasion/infiltration. Surgeon, rather than pathologist, was the person to label a thymic tumor malignant or otherwise. This is reflected in TNM classification for TETs wherein “T” does not mean tumour size, as in TNM staging of other malignancies, but invasion [3].

What concerns patient and the surgeon alike is overall prognosis, i.e. disease-free survival (DFS) and overall survival (OS). Regardless of the tumour histology, local spread does influence DFS and OS, be it thymoma or thymic carcinoma. Later in this issue, Bayram et al. present “Clinical Features and Prognostic Factors in Thymoma and Thymic Carcinoma” [4]. Despite the retrospective nature of the study, some important conclusions have emerged. In a study of 45 cases of thymoma and 15 cases of thymic carcinoma, complete curative resection (R0) was found to be associated with better DFS and OS in both entities. In addition, thymoma patients with Eastern Cooperative Oncology Group (ECOG) 0–1 had better prognosis. Even with thymic carcinoma, patients with ECOG 0–1 had more than four times better median OS (mOS).

History of smoking and alcohol intake and age more than 45 years also decreased mOS to almost half even in thymoma patients. So is the case with other comorbid conditions. It is a known fact that tumour biology is altered with smoking, alcohol intake, advancing age and other comorbid conditions resulting in less favourable outcome. Delicate balance between antitumour and protumour cytokines shifts unfavourably when associated with these comorbidities. According to Truffi et al. (2020), “Tumour microenvironment is not just a silent bystander, but rather an active promoter of cancer progression” [5].

The study is silent on the impact of tumour size on median DFS (mDFS) or mOS but then so is TNM classification. Patients of thymoma with myasthenia gravis had better mOS, most likely because of early diagnosis in these patients. In the absence of symptoms, the diagnosis is usually delayed in TETs. Major vessel invasion was found to be a negative prognostic factor, presumably because of difficulty in achieving R0 resection in these patients, be it thymoma or thymic carcinoma.

There is lot of fundamental research available on tumour biology and behavior. But how to translate and correlate this basic research into clinical relevance is important. We all are aware about the negative impact of smoking, alcohol, advancing age, obesity and comorbidities on the general health of the person. All these are probably altering the immune status and immune competency resulting in unfavorable outcome, once a tumorous stage develops. Cancer immune editing, as first proposed by Burnet, involves 3 distinct stages viz. elimination, equilibrium and escape [6]. There is also interplay of anti-tumour and pro-tumour cytokines which determines tumour biology and behavior in any patient [7, 8]. Each organ is immunologically distinct and so is the tumour. This may explain why similar patients with same stage of tumour have widely different outcomes. Recent surge in strengthening immune system by various immune-modulating agents is a logical approach to address this issue.

Nonetheless, this study does throw more light on various demographic and clinical features that impact DFS and OS. More robust prospective randomized controlled trials are needed to have better understanding of these tumours. However, rarity of these tumours coupled with indolent growth, heterogenicity and no specific tumour markers make this goal very difficult if not impossible. Translating fundamental research to clinical pathways is probably the way forward.

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The authors declare no competing interests.