Reproducibility of 3 Histologic Classifications and 3 Staging Systems for Thymic Epithelial Neoplasms and Its Effect on Prognosis

Abstract

Data regarding the prognostic significance of the histopathologic classifications of thymic epithelial neoplasms are contradictory, perhaps reflecting issues in reproducibility. We studied the effect of reproducibility of 3 histopathologic classifications on prognosis and investigated the interobserver agreement on invasion and its effect on staging and prognosis. A total of 456 patients who underwent surgery for thymic epithelial neoplasm at Mayo Clinic Rochester (1942 to 2008) were staged (modified Masaoka, proposed Moran, proposed IASLC/ITMIG) and independently classified by 3 thoracic pathologists (World Health Organization, proposed Suster & Moran [S&M], and Bernatz). Interobserver agreement was moderate to substantial for all histopathologic classifications (κ values: 0.65, 0.52, 0.74 for World Health Organization, Bernatz, and S&M, respectively). All histopathologic classifications were significant for overall survival (OS) and disease-free survival (DFS) (all reviewers). If adjusted for Masaoka, only Bernatz classification for one reviewer and all histopathologic classifications for another reviewer were significant for OS. Interobserver agreement for invasion was substantial (κ=0.61) and almost perfect for Masaoka, Moran, and IASLC/ITMIG stage (κ values: 0.85, 0.81, and 0.92, respectively). The correlation coefficient for Masaoka and Moran staging was 0.93. Masaoka and IASLC/ITMIG staging were significant for OS and DFS (all reviewers). If adjusted for any histopathologic classification, Masaoka was significant for OS and DFS (all reviewers). In conclusion, reproducibility of histopathologic classifications has some effect on outcome. S&M is the most reproducible classification. Reproducibility of invasion has no effect on the prognostic value of staging. Masaoka, Moran, and IASLC/ITMIG staging are almost perfectly reproducible. The strong correlation between Masaoka and Moran staging suggests similar prognostic strength.

Evolution of Classification of Thymic Epithelial Tumors in the Era of Dr Thomas V. Colby

“…In that study, the agreement among 3 thoracic pathologists from the same institution was almost perfect for the modified Masaoka staging system (j ¼ 0.85, n ¼ 315) and the proposed Moran staging system (j ¼ 0.81, n ¼ 290) and substantial for the proposed IASLC/ITMIG staging system (j ¼ 0.75, n ¼ 81). 4 If evaluating only the T component of the proposed IASLC/ITMIG (n ¼ 297), the agreement was also substantial (j ¼ 0.75). Most common disagreements occurred between encapsulated and minimally invasive tumors, which would correspond to stage I and IIA tumors of the modified Masaoka staging system (15.8% of cases).…”

“…Moreover, this study showed that the only moderate to substantial reproducibility of histomorphologic classifications indeed plays a role in determining the prognostic significance of TET, with differences in prognosis between the 3 reviewers in multivariate analysis. 4 Therefore, Roden et al 40 evaluated the prognostic significance of thymoma using cases in which all 3 thoracic pathologists independently agreed upon a diagnosis. Univariate analysis confirmed that all histomorphologic classifications studied, including Bernatz, Suster and Moran, and WHO (2004), are of prognostic significance for overall and disease-free survival.…”

“…There is no sex predilection in TETs. 1,[4][5][6] Thymic epithelial tumors can be classified according to their histopathologic features or staged based on the presence and extent of invasion, implants, lymph node involvement, and/or distant metastases. At least 24 histomorphologic classifications and 14 staging systems have been proposed within the last century (Table 1).…”

Radiologic Response to Neoadjuvant Treatment Predicts Histologic Response in Thymic Epithelial Tumors

“…First, the histologic classification of posttreatment TETs was difficult because the histologic type might be biased on account of treatment effect as well as heterogeneity of TETs and interobserver variability, which we have shown previously. 19 Second, differences in neoadjuvant treatment occurred not only between studies but also within studies, including ours. Given the rarity of the tumor, these differences were unavoidable because to achieve a larger number of cases, these had to be collected over many years.…”

“…Because of interobserver variability in the morphologic classification of TETs, 19 all pre-and postneoadjuvant treatment specimens were reviewed by three thoracic pathologists (A. C. R., M. C. A., and E. S. Y.).…”