Abstract
BACKGROUND: Morphologic heterogeneity in thymomas depends on histopathological patterns and sampling techniques. There is a lack of knowledge about the incidence and potential impact of heterogeneous thymomas on the disease burden. The primary aim of this study is to investigate the incidence and patient characteristics of thymomas with heterogeneous histopathology. METHODS: All patients who underwent a thymomectomy between 2012 and 2024 in the Maastricht University Medical Center (MUMC) were included and retrospectively analyzed. Thymomas were histologically classified by the 5th edition of the World Health Organization of thymic epithelial tumors. The Masaoka-Koga staging system and 9th TNM classification reported tumor invasion. All thymomas were postoperatively evaluated by the same senior pathologist. After fixation, regular sampling of the specimen is performed, with at least one block per cm of tumor and generous sampling of close margins. The definition of heterogeneous thymoma is based on histologically proven heterogeneity in resected thymoma. Components of mixed histopathology were noted in percentages. Patients with a biopsy were excluded from this study. Pearson’s Chi-squared test was considered statistically significant in case P<0.05. RESULTS: Morphological heterogeneity was observed in 81 of the 206 included patients (39.3%). The majority of the heterogeneous thymomas were type A–B2 (43.2%) and type B2–B3 (30.9%). Heterogenic thymomas were more frequently observed in non-steroid using patients (34.2% vs. 1.8%, P<0.001). The B3-component was ≥50% in 100% of A–B3 thymomas. The B2 component was ≥50% in 68.6% of A-B2 thymomas. Adjuvant postoperative radiotherapy (PORT) was performed less in heterogeneous thymomas compared to homogenous thymomas (12.3% vs. 25.6%, P=0.02), and most diverse in heterogeneous B3-thymomas compared to homogeneous B3-thymomas (29.0% vs. 73.0%, P<0.001). No significant differences in gender, age, tumor size, or presence of myasthenia gravis were found in patients with homogeneous versus heterogeneous thymomas. CONCLUSIONS: Morphological tumor heterogeneity was found in 39.3% of the resected thymomas. Neglecting the involvement of aggressive thymoma subtypes might have an impact on decisions regarding treatment, such as PORT. Future research is necessary to analyze the consequences of thymoma heterogeneity on recurrence and survival rates. Development of guidelines with sampling recommendations may help identify heterogeneous thymomas.