Interobserver variation in the classification of thymic tumours - A multicentre study using the WHO classification system

ArticleinHistopathology 53(2):218-23 · September 2008with6 Reads
DOI: 10.1111/j.1365-2559.2008.03088.x · Source: PubMed
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.


    • "Thymomas comprise a spectrum of unique thymic epithelial tumors that generally show intratumoral thymopoiesis. They are subdivided into WHO type A, AB, B1, B2, and B3 thymomas (1, 2), but this classification has been challenged by some authors (3, 4). Thymic carcinoma also show a spectrum subtypes that resemble analogously called extrathymic carcinomas (TCs) (2, 5). "
    [Show abstract] [Hide abstract] ABSTRACT: The molecular pathogenesis of thymomas and thymic carcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important. This made us re-analyze historic expression data obtained in a spectrum of thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.
    Full-text · Article · Dec 2013
    • "Our results support previous interobserver agreement studies, although only a few have addressed this issue in thymic epithelial neoplasms [4, 5, 18]. For instance, Verghese et al. [5] reported a κ value of only 0.48 (moderate agreement) for type B3 vs thymic carcinomas when a panel of 17 pathologists reviewed thymic epithelial neoplasms according to the current WHO classification. Furthermore, a meta-analysis of 15 publications by Marchevsky et al. [19] revealed a high variability of the proportions of different subtypes of thymomas. "
    [Show abstract] [Hide abstract] ABSTRACT: Objectives: Thymic carcinomas have wide ranges of reported survival. Interobserver agreement on diagnosis might affect prognostical studies. Clinicopathological features of thymic carcinomas were compared with thymic epithelial neoplasms in which pathologists disagreed upon. Methods: Patients treated with thymic epithelial neoplasms were reviewed. Three thoracic pathologists independently classified all cases according to the World Health Organization classification. The study group comprised cases in which all pathologists agreed independently on thymic carcinomas. A disagreement group included cases in which pathologists disagreed upon the diagnosis. Tumours were staged according to the modified Masaoka and tumour-node metastasis (TNM) stages. Time-to-death was estimated with the Kaplan-Meier method. Survival outcomes were assessed with the Cox proportional-hazards regression. Results: In the study group, 25 of 29 patients presented with symptoms but no autoimmune diseases. Masaoka stage III (18 of 29) and TNM stage III (13 of 24) were most common. Complete tumour resection was achieved in 17 of 29. Four patients had metastasis at diagnosis, and 12 developed metastasis/recurrence post-treatment. The estimated 5-year survival was 35.6%, and recurrence/metastasis-free survival was 34.2%. Overall survival was associated with weight loss (P = 0.02) and metastasis/recurrence with morphology (P = 0.009). In the disagreement group, most disagreements occurred between type B3 thymomas and carcinomas (21 of 29). Twenty-four of the 29 patients presented with symptoms, including autoimmune disorders (12 of 29). Masaoka stage III (10 of 29) and TNM stage IV (10 of 17) were most common. Twenty-one of the 29 underwent complete tumour resection. The estimated 5-year survival was 64.9%. Two patients had metastasis at diagnosis and eight developed metastasis/recurrence post-treatment. The study group had significantly more patients with chest pain and additional treatment than the disagreement group (P = 0.005 and 0.044, respectively). The disagreement group had more patients with myasthenia gravis and a higher TNM stage (P = 0.0003 and 0.025, respectively). The risks of death and recurrence/metastasis were significantly higher in the study group than the disagreement group [P = 0.025, hazard ratio (HR) = 2.44 and P = 0.012, HR = 3.23, respectively]. Conclusions: Thymic carcinomas were diagnosed at high stages and the overall prognosis appeared relatively poor. Autoimmune disease was not a manifestation of thymic carcinomas. Weight loss was associated with survival. The disagreement group in contrast had more patients with autoimmune syndrome and, despite a higher stage, had a better survival, suggesting that interobserver variability in the histopathological classification of thymic carcinomas vs thymomas leads to prognostical variability.
    Full-text · Article · Oct 2012
    • "In the same way, there are hints for an underlying sequence in carcinogenesis for some thymic carcinomas and some thymomas since there are several reports regarding combined subtypes of thymic tumours as, e.g. type B2/B3 thymomas or combined type B3 thymomas/ thymic carcinomas [17]. Furthermore, cluster analysis of genomic imbalances detected by CGH as well as oncogenetic tree models indicate that such a molecular sequence may exist for some of these tumours [5, 9]. "
    [Show abstract] [Hide abstract] ABSTRACT: Carcinoma showing thymus-like elements (CASTLE) is a rare neoplasm of the thyroid gland resembling lymphoepithelioma-like and squamous cell carcinoma of the thymus and is thought to arise from ectopic thymic tissue within the thyroid gland or rudimentary branchial pouches along the thymic line. Using comparative genomic hybridization (CGH), chromosomal imbalances have been detected in several types of thymomas and thymic carcinomas. To evaluate whether there are hints of an underlying sequence in the pathogenesis of CASTLE analogue to those found in thymomas and thymic carcinomas, we evaluated four of these rare neoplasms for chromosomal imbalances using CGH. The most frequent gains were seen on chromosomal arm 1q (3/4), and losses were most frequently detected on 6p (4/4), 6q (3/4) and 16q (3/4). These CGH data show that CASTLE is characterized by chromosomal imbalances similar to those found in thymomas and thymic carcinomas and indicate a similar sequence in tumour development.
    Full-text · Article · Aug 2011
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