Article

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

Department of Pathology, Leeds Teaching Hospital NHS Trust, Leeds, UK.
Histopathology (Impact Factor: 3.3). 09/2008; 53(2):218-23. DOI: 10.1111/j.1365-2559.2008.03088.x
Source: PubMed

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.

0 Followers
 · 
92 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Normal thymic architecture is essential for the proper development of T-lymphocytes. Immature T-cell progenitors enter the thymus where through interactions with cortical and medullary thymic epithelial cells (TECs) they undergo positive and negative selection and become competent cells that do not react with self-antigens. This process requires normal thymic architecture, expression of major histocompatibility complex (MHC) class II, and normal expression of the autoimmune regulator (AIRE) gene. Thymomas are rare neoplasms of the TECs that often generate lymphocytes that mature into CD4+ and CD8+ T-lymphocytes. However, several abnormalities have been described in thymomas that may affect normal T-cell development: the tumor architecture is distorted, neoplastics expresses less MHC class II, most thymomas do not express AIRE, and production of T-regulator cells is decreased. Thymomas are associated with a variety of autoimmune disorders often linked to T-cell-mediated autoimmunity. Myasthenia gravis, the most common autoimmune disorder associated with thymoma patients, is present in 30% of patients with thymoma. Several theories attempt to explain the association of immune disorders with thymomas. These different theories are based on failure of positive and negative selection of T-lymphocytes and on autoimmunizing mechanisms in an AIRE-poor environment in the thymus. The finding that immunosurveillance against cancer may be impaired before the diagnosis of thymoma may challenge current theories and suggest a more complex defect in T-lymphocyte maturation. It is likely that a combination of mechanisms is responsible for immune disorders in patients with thymoma. More investigation is needed to clarify the basic mechanisms responsible for immune disorders in patients with thymoma.
    Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2014; 9(9 Suppl 2):S137-S142. DOI:10.1097/JTO.0000000000000299 · 5.80 Impact Factor
  • [Show abstract] [Hide abstract]
    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; 46(8). DOI:10.1038/ng.3016 · 29.65 Impact Factor
  • Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2014; 9(9 Suppl 2):S125-S130. DOI:10.1097/JTO.0000000000000297 · 5.80 Impact Factor