Interobserver variation in the classification of thymic lesions including biopsies and resection specimens in an international digital microscopy panel

Abstract

Aims: Thymic tumours are rare in routine pathology practice. Although the World Health Organization (WHO) classification describes a number of well-defined categories, the classification remains challenging. The aim of this study was to investigate the reproducibility of the WHO classification among a large group of international pathologists with expertise in thymic pathology and by using whole slide imaging to facilitate rapid diagnostic turnover.

Methods and results: Three hundred and five tumours, consisting of 90 biopsies and 215 resection specimens, were reviewed with a panel-based virtual microscopy approach by a group of 13 pathologists with expertise in thymic tumours over a period of 6 years. The specimens were classified according to the WHO 2015 classification. The data were subjected to statistical analysis, and interobserver concordance (Fleiss kappa) was calculated. All cases were diagnosed within a time frame of 2 weeks. The overall level of agreement was substantial (κ = 0.6762), and differed slightly between resection specimens (κ = 0.7281) and biopsies (κ = 0.5955). When analysis was limited to thymomas only, and they were grouped according to the European Society for Medical Oncology Clinical Practice Guidelines into B2, B3 versus A, AB, B1 and B3 versus A, AB, B1, B2, the level of agreement decreased slightly (κ = 0.5506 and κ = 0.4929, respectively). Difficulties arose in distinguishing thymoma from thymic carcinoma. Within the thymoma subgroup, difficulties in distinction were seen within the B group.

Conclusions: Agreement in diagnosing thymic lesions is substantial when they are assessed by pathologists with experience of these rare tumours. Digital pathology decreases the turnaround time and facilitates access to what is essentially a multinational resource. This platform provides a template for dealing with rare tumours for which expertise is sparse.

Keywords: interobserver variation; thymoma; tumour classification; whole slide imaging.

Figure 1

Examples of thymomas from the thymoma panel; cases A–D were scored with high consensus rates, and for cases E–H there were split opinions. A, Encapsulated mediastinal mass scored by seven pathologists, with 100% consensus for type AB thymoma. B, Resected mediastinal tumour scored by 10 pathologists, with 100% consensus for type A thymoma. C, Resected thymic tumour scored by seven pathologists, with 99% consensus for type B3 thymoma. (1% type B2). D, Thymic resection unanimously scored by seven pathologists as thymic carcinoma. E, Biopsy specimen with a thymic epithelial tumour weakly staining for CD5 and strongly staining for p40. CD117 and terminal deoxynucleotidyl transferase were negative. The specimen was scored by nine pathologists, with an outcome of 55% type B3 thymoma and 45% thymic carcinoma. F, Resected encapsulated mediastinal tumour scored by nine pathologists, with an outcome of 74.7% type B3 thymoma, 22.2% thymic carcinoma, and 3.33% type B2 thymoma. G, Resected anterior mediastinal tumour. The tumour was positive for p40, cytokeratin (CK) 5, CK19, Pax8, and CD117, and negative for CK7, thyroid transcription factor‐1, napsin A, chromogranin, and synaptophysin. It was scored by nine pathologists, with an outcome of 77.78% thymic carcinoma and 22.22% type A thymoma. H, Resected multilobular tumour from the anterior mediastinum. The tumour was partly positive for CD5 and CD99, and negative for CD117. It was scored by 10 pathologists, with an outcome of 58% type B3 thymoma, 23% thymic carcinoma, 10% type AB thymoma, 8% type B2 thymoma, and 1% type A thymoma.