Clinical and Functional Significance of WHO Classification on Human Thymic Epithelial Neoplasms

Abstract

We examined the clinical and functional significance of histologic classification of thymic epithelial neoplasms proposed by the World Health Organization (WHO), based on an analysis of 146 consecutive tumors derived from 141 patients and 47 normal thymuses derived from children ranging in age from 1 to 9 years. Invasive tumors were seen in 12.5%, 38.6%, 40.0%, 69.4%, 80.0%, and 100% of type A, AB, B1, B2, B3, and C primary tumors, respectively. All of six recurrent or metastatic lesions were type B2 tumors. Myasthenia gravis was associated in 0%, 6.8%, 40.0%, 55.6%, 10.0%, and 0% in patients with type A, AB, B1, B2, B3, and C tumors, respectively. The average number (x10(6)) of tumor-associated CD4+CD8+ cells present in 1 g of tumor tissue was 1.5, 391.1, 1041.7, 333.9, 24.5, and 0.2 in type A, AB, B1, B2, B3, and C, respectively, and it was 1168.2 in the normal thymuses. Thus, type B1 tumor retained the function to induce CD4+CD8+ double-positive cells at a level comparable to that of the normal thymic cortical epithelial cells, followed by type AB and type B2 tumors. Type A and B3 tumors had this function at a barely detectable level, and type C tumor was nonfunctional. WHO histologic classification was shown to reflect the clinical features and the T-cell-inducing function of thymic epithelial tumors.

The World Health Organization histologic classification system reflects the oncologic behavior of thymoma

“…21 Our previous study showed that the WHO histologic classification system reflects the invasive nature of thymoma. 22 That observation was reconfirmed by the current study, which included greater numbers of patients with longer follow-up, as shown in Tables 4 and 5. Furthermore, the current study suggested that type B2 and B3 tumors had more malignant nature in terms of prognosis and tumor recurrence compared with type A, AB, and B1 tumors (Fig.…”

“…Our previous study revealed that type B3 tumors have significant numbers (although fewer than type B1 and B2 tumors) of CD4 positive/CD8 positive, double-positive cells inside the tumor, whereas type C tumors do not. 22 Furthermore, type B3 tumors often were associated with myasthenia gravis (Table 3), whereas any type C tumors were not. For these reasons, type B3 tumors are supposed to be related functionally more to type B1 and B2 tumors than to type C tumors.…”

“…Although we recently reported that the WHO histologic classification system reflects the immunologic function as well as the invasive nature of thymomas, 22 the significance of this novel histologic classification as a prognostic factor remains to be elucidated. In this study, which was based on our 44 years of experience, we examined postoperative survival with reference to WHO histologic classification and evaluated its relation with other prognostic factors.…”

WHO types A and AB thymomas: not always benign

“…6 Their potential for recurrent behavior has been reported in several previous studies. 19,30,35,[40][41][42][43][44] In our study, 16 of 29 patients had invasive tumors. In follow-up, we observed metastatic events from as early as 1 year to as late as 11 years (mean: 62.25 months) from diagnosis.…”

“…Studies have shown that patients with type AB thymoma are at an increased risk of relapse between 2 and 8 years (Table 4). 30,42 In some series, tumor recurrences were more frequent in type AB compared with type A thymoma. 41,44 Masaoka stage is a good predictor of aggressive behavior, 10,35,38,44 although recurrences have been documented even with early stage disease.…”