In this issueThymoma: a clinicopathological correlation of 1470 cases☆
Introduction
The classification and staging of thymomas have generated significant interest and controversy over the last 2 decades. Of note, some earlier publications have also shed important light on the pathology of the thymus. In 1955, in the first series of fascicles of the Armed Forces Institute of Pathology [1], under the designation of Atlas of Tumor Pathology, Section V—Fascicle 19, the author stated, “Many attempts have been made to classify thymomas on the basis of cell type.” In addition, the author stated, “… it is both difficult and hazardous to classify tumors of such cell derivatives,… there are so many variations within a given tumor … no attempt is made to give a special name to any particular variant.” Interestingly, only recently has such a statement been proven in a study of 630 thymomas evaluated for the impact on histologic heterogeneity [2]. In 1975, in the second series of fascicles from the Armed Forces Institute of Pathology [3], the authors stated, “… once the term thymoma is restricted to the tumor of epithelial thymic cells, with or without lymphocytic component, all further subdivisions are artificial.”
In 1961, Bernatz et al [4] put forward a classification system based on the proportion of lymphocytes and separated thymomas into lymphocyte rich, epithelial rich, and mixed thymomas in which the tumor shows approximately equal proportion of lymphocytes and epithelial cells. In a subsequent publication of 181 thymomas, Bernatz et al [5] clearly stated that all histological variants might become invasive neoplasms. In 1985, Marino and Müller-Hermelink [6] proposed a new histological classification so-called histogenetic classification, separating thymomas by “cell of origin” into cortical and medullary types. However, contrary to the system of Bernatz et al [4], which predicts clinical outcome based on tumor stage at the time of diagnosis, this so-called histogenetic classification bases its prediction of clinical outcome on histology—cortical or medullary type.
With the lack of an official classification for thymomas, the World Health Organization (WHO) organized a panel of experts who in 1999 produced their first official publication on the Histological Typing of Tumours of the Thymus [7]. However, this initial WHO classification was a compromised approach comparing the Bernatz et al [4] and the Marino and Müller-Hermelink [6] classification schemas. In the WHO proposal, a system of letters and numbers was put forth as a “facilitator” of those schemas. Two important statements, quoted below, emerged as a highlight of this initial WHO schema [7]:
“… the terminology chosen here is a non-committal one based on a combination of letters and numbers. It is not proposed as a new classification, but mainly to facilitate comparison among the many terms and classification schemes.”
“… the committee wishes to stress the importance of independently evaluating thymic epithelial tumours on the basis of their presence and degree of invasiveness and their cytoarchitectural features.”
Furthermore, the committee offered an additional statement: “It will be appreciated, of course, that the classification reflects the present knowledge and that modifications are almost certain to be needed as experience accumulates.” The last 2 publications from the WHO (2004 and 2015) [8], [9] have ignored the advice from the members of the 1999 committee and the abundant evidence on the subjectivity of this schema. In addition, the authors have also perpetuated a schema that was clearly not intended as a new classification.
The current study of 1470 resected thymomas represents the largest series of these tumors and clearly demonstrates that a simplified histological schema [10] and a more recently proposed pathological staging system [11] offer an excellent predictor for clinical outcome, which, in turn, will aid in determining who is best treated with surgery alone or who is best to be followed with additional treatment such as radiation and/or chemotherapy.
Section snippets
Materials
All of the cases correspond to surgical resections identified by the Thymic International Group in the files of their respective departments of pathology, following approved Institutional Review Board guidelines. The patient records were evaluated for additional significant clinical history specifically myasthenia gravis (MG), other autoimmune disorders, or associated neoplasia. In addition, all hematoxylin-eosin sections were reviewed. Clinical follow-up information was obtained in 1339
Clinical features
Tables 1 and 2 depict the most important clinical findings in this cohort. The cohort includes 1470 patients, 720 men and 750 women between the ages of 12 to 86 years (average, 54.8 years); 127 patients are younger than 35 years (8.6%). Clinical information regarding the presence of MG, other autoimmune disorders, or other neoplasia obtained in 807 patients shows that 137 patients (17%) had MG, 31 patients (3.8%) had another autoimmune disease, and 55 patients (6.8%) had another neoplastic
Discussion
The histological classification and the staging system of thymomas are subjects that have been debated for some time and continue to pose many challenges. Prior to the 1999 WHO schema of thymomas, there were numerous clinicopathological correlations that emphasized the importance of tumor invasion [12], [13], [14], [15], [16], [17], [18], including the incidence of recurrence in previously diagnosed “encapsulated tumors” [12], which was estimated to occur in less than 2% of all thymomas. In
Supplementary data
The following are the Supplementary data to this article.
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Disclosures: None of the authors has any conflict of interest regarding the elaboration of this manuscript. In addition, no specific funding was provided in the preparation of this manuscript.