Clinico-pathologic study of 252 resected thymomas with emphasis on atypical A and AB group: a single institution experience.

Abstract

Background: World Health Organization (WHO) classification defines subdivision of type B group (B1, B2, and B3) based on proportion of neoplastic epithelial cells and non-neoplastic lymphocytes, and a number of studies have demonstrated correlation between the subtype and prognosis, with type B3 being unfavorable. Type A and AB tumors share similar clinico-pathological features, with generally indolent behavior, and both are characterized by GTF2I mutation. A subset of type A and AB tumors shows atypical features such as increased mitotic activity, cytologic atypia and necrosis, and the term atypical type A has been proposed; however, the atypical category is not well-defined. Aim of the study is to establish criteria for atypical type A thymoma.

Methods: A total of 252 thymomas resected from 247 patients were retrieved and reviewed. A variety of clinical and histopathologic parameters were recorded and analyzed, and prognostic factors in type A and AB group were investigated in order to better define the atypical category.

Results: Median age was 63 years (range, 14-84 years), equal male:female ratio (121:129), median tumor size 65 mm (range, 10-300 mm). There were 46 tumors (type A), 105 (AB), 22 (B1), 47 (B2), and 32 (B3). The majority of patients with A/AB subtypes were above 63 years old, whereas the majority of patients with B group were below 63 years old. Type B group was more often of advanced stage compared to A/AB. Vascular invasion was shown more often in subtype A and necrosis in subtype B1. AB group included larger tumors than the other subtypes. Paraneoplastic syndromes were reported in 71 (28.4%) patients and were more frequently seen in subtypes B2 and B3. In A/AB group, multivariate Cox proportional hazard models demonstrated that mitotic count was the only independent prognostic factor as continuous variable [hazard ratio (HR) 1.15, 95% confidence interval (CI): 1.07-1.24, P<0.001]. A/AB cases were further classified by mitotic count in 4 groups (1-4, 5-9, 10-19 and ≥20 mitotic figures per 2 mm²). Patients with mitotic count 1-4, 5-9 and 10-19 had similarly favorable progression free survival (PFS), while those with ≥20 mitotic figures per 2 mm² had remarkably worse outcomes. Therefore, A/AB patients were classified as typical if mitotic count was 0-19/2 mm² and atypical if ≥20 mitotic figures per 2 mm². Multivariate Cox proportional hazard models were performed in the entire population. The strongest prognostic factors were the new subtype classification, the presence of necrosis, the status of surgical margins and neoadjuvant treatment.

Conclusions: Our results suggest atypical type A and AB could be defined as tumors with ≥20 mitotic figures per 2 mm².