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

Abstract

Interobserver variation in the classification of thymic lesions including biopsies and resection specimens in an international digital microscopy panel 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 (j = 0.6762), and differed slightly between resection specimens (j = 0.7281) and biopsies (j = 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 (j = 0.5506 and j = 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.

Thymic epithelial tumours: histopathological classification and differential diagnosis

“…They rarely metastasize (in 1%–2% of cases) and if so, are associated with a poor prognosis. The histopathologic classification of TETs is subject to interobserver variability due to the wide variety of histopathological patterns found in various subtypes 9 . Many subtyping schemes have been introduced, 10‐16 but currently subtyping is performed according to the most recent WHO classification 1 .…”

“…This heterogeneity should be reflected in the bottom line of the pathology report by mentioning the presence of different subtypes in 10% increments 14 . Both the recognition and designation of different patterns, as well as the enumeration of their relative content can lead to significant interobserver variability 9,86,87 . This potential heterogeneity of thymomas also precludes confident subtyping of thymomas on biopsies (see below), which is best reserved for the resection specimen.…”

“…The histopathologic classification of TETs is subject to interobserver variability due to the wide variety of histopathological patterns found in various subtypes. 9 Many subtyping schemes have been introduced, 10-16 but currently subtyping is performed according to the most recent WHO classification. 1 This classification is based on "organotypical" features akin to those seen in the normal thymus, including growth pattern (encapsulation and a "lobular architecture") and cellular composition, but also on functional, genetic, and clinical evidence.…”

Juan Rosai as master of our comprehensive understanding of thymus and thymoma

“…It appears that the 4 th edition of the WHO classification was well received and used all around the world. Digital pathology consultations on the reproducibility of the classification gave positive results; training and discussions among pathologists and specific expertise in rare thoracic tumors provided a relevant increase in reproducibility 72 .…”

DNA-Methylation Analysis as a Tool for Thymoma Classification

“…Thymomas are classified based on variably pronounced “organo-typical” architectural features (e.g., the presence or absence of ‘medullary islands’ and ‘perivascular spaces’), tumor cell morphology (spindly versus polygonal), and the relative abundance of non-neoplastic immature T cells compared to neoplastic epithelial cells. Given this morphological complexity, it is not surprising that inter-observer reproducibility has remained an issue in real-life settings [ 10 , 11 , 12 ] and made some authors argue in favor of a simplified histological scheme [ 7 ]. On the other hand, meticulous immunohistochemical analysis of WHO-defined thymoma subtypes in terms of functional molecules of the cortical and medullary thymic epithelial cells [ 13 ] demonstrated the value of the historic classification by Marino and Müller-Hermelink [ 14 ], separating thymomas on the basis of the presumed “cell of origin” into two main categories, cortical and medullary thymomas.…”