Interobserver variation in the classification of thymic tumours--a multicentre study using the WHO classification system.
ABSTRACT To test the reproducibility of the current World Health Organization (WHO) classification of thymic epithelial tumours and to determine the level of interobserver variation within a group of pathologists, all with experience and expertise in thoracic pathology.
Ninety-five thymic tumours were circulated to a group of 17 pathologists in the UK and The Netherlands over a 1-year period. Participants were asked to classify them according to WHO criteria. The diagnoses were subjected to statistical analysis and kappa values calculated. The overall level of agreement was moderate (kappa 0.45). When the categories were reduced in number by creating two groups, (A + AB + B1 + B2 and B3 + C), the level of agreement increased to 0.62. An alternative grouping (A + AB + B1 and B2 + B3 + C) increased it slightly further. The best agreement was in tumour types A and AB. Difficulties arose in distinguishing B1 tumours from B2 tumours and B2 tumours from B3 tumours.
Although the WHO system describes a number of well-defined tumour types with clear diagnostic criteria, the overall level of agreement was moderate and improved if some groups were amalgamated.
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ABSTRACT: Thymic carcinoma is a rare and aggressive thymic neoplasm. The European Society of Thoracic Surgeons developed a retrospective database collecting patients undergoing resection for thymic tumors from 1990 to 2010. Of 2265 patients with thymic tumors, there were 229 thymic carcinomas. Clinicopathological characteristics were analyzed including age, associated paraneoplastic diseases, stage (Masaoka-Koga), World Health Organization histologic subtypes, type of resection (total/subtotal/biopsy/no resection), tumor size, pre/postoperative treatments, and recurrence. Outcome measures included overall survival (OS), freedom from recurrence, and cumulative incidence of recurrence. A complete resection was achieved in 140 patients (69%). Recurrence occurred in 54 patients (28%). Five- and 10-year OS rates were 0.61 and 0.37. Five- and 10-year freedom from recurrence rates were 0.60 and 0.43. Cumulative incidence of recurrence was 0.21 (3 yr), 0.27 (5 yr), and 0.32 (10 yr). Survival was better after surgical resection versus biopsy/no resection (p < 0.001), after complete resection versus subtotal resection (p < 0.001), and when using Masaoka-Koga system (stages I-II versus III versus IV) (p < 0.001). The use of multidisciplinary treatments resulted in a survival advantage which was significant in the surgery + radiotherapy group (p = 0.02). Incomplete resection (p < 0.0001) and advanced stage (Masaoka-Koga III-IV) (p = 0.02) had a negative impact on OS at multivariable analysis. Administration of adjuvant radiotherapy was beneficial in increasing OS (p = 0.02). The results of our study indicate that patients with thymic carcinoma should undertake surgical resection whenever possible; a complete resection and early Masaoka-Koga stage are independent predictors of improved survival; our results also suggest that postoperative radiotherapy is beneficial in improving survival.Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 04/2014; 9(4):541-8. · 4.55 Impact Factor
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ABSTRACT: We analyzed 28 thymic epithelial tumors (TETs) using next-generation sequencing and identified a missense mutation (chromosome 7 c.74146970T>A) in GTF2I at high frequency in type A thymomas, a relatively indolent subtype. In a series of 274 TETs, we detected the GTF2I mutation in 82% of type A and 74% of type AB thymomas but rarely in the aggressive subtypes, where recurrent mutations of known cancer genes have been identified. Therefore, GTF2I mutation correlated with better survival. GTF2I β and δ isoforms were expressed in TETs, and both mutant isoforms were able to stimulate cell proliferation in vitro. Thymic carcinomas carried a higher number of mutations than thymomas (average of 43.5 and 18.4, respectively). Notably, we identified recurrent mutations of known cancer genes, including TP53, CYLD, CDKN2A, BAP1 and PBRM1, in thymic carcinomas. These findings will complement the diagnostic assessment of these tumors and also facilitate development of a molecular classification and assessment of prognosis and treatment strategies.Nature genetics. 06/2014;
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ABSTRACT: The 2004 version of the World Health Organization classification subdivides thymic epithelial tumors into A, AB, B1, B2, and B3 (and rare other) thymomas and thymic carcinomas (TC). Due to a morphological continuum between some thymoma subtypes and some morphological overlap between thymomas and TC, a variable proportion of cases may pose problems in classification, contributing to the poor interobserver reproducibility in some studies. To overcome this problem, hematoxylin-eosin-stained and immunohistochemically processed sections of prototypic, "borderland," and "combined" thymomas and TC (n = 72) were studied by 18 pathologists at an international consensus slide workshop supported by the International Thymic Malignancy Interest Group. Consensus was achieved on refined criteria for decision making at the A/AB borderland, the distinction between B1, B2, and B3 thymomas and the separation of B3 thymomas from TCs. "Atypical type A thymoma" is tentatively proposed as a new type A thymoma variant. New reporting strategies for tumors with more than one histological pattern are proposed. These guidelines can set the stage for reproducibility studies and the design of a clinically meaningful grading system for thymic epithelial tumors.Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 05/2014; 9(5):596-611. · 4.55 Impact Factor