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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Article: Thymoma and thymic carcinoma[Show abstract] [Hide abstract]
ABSTRACT: Thymoma and thymic carcinoma are an extremely heterogeneous group of neoplastic lesions with an exceedingly wide spectrum of morphologic appearances. They show different presentations with a variable and unpredictable evolution ranging from an indolent non-invasive attitude to a highly infiltrative and metastasising one. Prognosis can be predicted on the basis of a number of variables, mainly staging, the WHO histological pattern and diameter of the tumour. Complete surgical resection is certainly the gold standard to achieve cure. However, especially in patients with lesions at advanced stage, complete resection may be difficult and recurrence often occurs; at these stages, disease-free long-term survival may be difficult to be accomplished. Chemo- and radiotherapy protocols have been designed to complete surgical treatment and improve results in inoperable patients as well, based on the reported sensitivity of thymic tumours to these treatment modalities. The integration of clinical staging and histology, with the new histogenetic morphological classification, has contributed to design multimodality treatment protocols that help to improve prognosis. Induction therapy can now be applied before surgery in patients with tumours considered inoperable, improving resectability and outcome without adding morbidity and mortality to the surgical procedure. This newly developed approach helps to reduce the recurrence rate and to ameliorate disease-free survival. New therapies are now being evaluated as for many other tumours; however, they still need confirmation in prospective randomised studies. In the future, integrated treatment modality should be incorporated in a standardised approach that goes from a careful assessment of histology, staging and lymph node status, and a constructive and non-empirical co-operation between medical and radiation oncologists, pathologists and thoracic surgeons.European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 08/2009; 37(1):13-25. DOI:10.1016/j.ejcts.2009.05.038 · 2.81 Impact Factor
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ABSTRACT: Some of the numerous examples that can be quoted are those on dysplasia in Barrett's esophagus, 6 grading of prostatic carcinoma, 7 grading of breast carcinoma, 8 diagnosis of hydatidiform mole, 9 and classification of thymic tumors. 10 On first sight, these results make surgical pathology look like a subjective, arbitrary, unscientific discipline, and therefore many surgical pathologists don't like them. I still get occasional snotty remarks about a study of the kind I did many years ago on proliferative ductal lesions of the breast. 11 Yet, I doubt whether burying our head in the sand is the solution. Perhaps it is the nature of the beast, and nothing can be done about it. 12 As Vickery 13 stated, some of the criteria on which we base those distinctions "may be indefinite and vulnerable to subjective morphologic interpretation." Or perhaps some of these studies will identify a specific problem that can be addressed. The various thyroid studies above quoted mainly deal with the diagnostic significance of certain morphologic nuclear features (herein referred to as PTC-type nuclei) in the diagnosis of papillary thyroid carcinoma (PTC). It is obvious from the results obtained that some experts have a much lower threshold for the identification and/or diagnostic significance of PTC-type nuclei than others. It may be of some interest to briefly recount the evolution that PTC-type nuclei have had in thyroid pathology until reaching their presently exalted status. Originally, and for the many decades that followed its description, PTC was diagnosed primarily on the basis of the presence of papillae, hence its name. Then people began noticing that these tumors had peculiar nuclei, which looked empty or optically clear. Ronald DeLellis 14 gave credit to Nancy Warner for drawing the amusing analogy between these nuclei and the eyes of Harold Gray's comic strip character, "Little Orphan Annie". Thus, the expression "Orphan Annie's eyes nuclei" became popular when referring to PTC, although the presence of papillae and other cytoarchitectural features (carefully listed and discussed in Vickery's authoritative review on the subject 13 ) were still regarded as important criteria for the diagnosis of PTC. However, with the passing of the years, PTC-type nuclei rose through the ranks, so to speak, to become the paramount criterion for the diagnosis of PTC. At present, a thyroid tumor can have a papillary, follicular, solid, trabecular or cribriform pattern of growth; it can be composed of large, small, oncocytic, clear, round, spindle or columnar cells; it can be encapsulated, minimally invasive or widely invasive; in sum, it can have any of those features and more, but as long as it has PTC-type nuclei it is thought to be a PTC or one of its innumerable variants.
Conference Paper: Proof strategies for hardware verification[Show abstract] [Hide abstract]
ABSTRACT: Ascertaining correctness of digital hardware designs through simulation does not scale-up for large designs because of the sheer combinatorics of the problem. Formal verification of hardware designs holds promise because its computational complexity is of the order of number of different types of components (and not number of components in the design). This approach requires the specification of the behavior and the design in a formal language, and reason with them using a theorem prover. In this paper we attempt to develop a methodology for writing and using these specifications for some important classes of hardware circuits. We examine digital hardware verification in the HOL-90 environment. (HOL-90 is a proof checker written in Standard ML which assists in mechanically checking a formal proof of hardware correctness.) In particular, we analyze proofs for a variety of circuits, and develop proof strategies for combinational circuits and restricted sequential circuits. Overall, this approach makes the theorem proving task less tedious and provides guidance to the user in carrying out proofsAerospace and Electronics Conference, 1996. NAECON 1996., Proceedings of the IEEE 1996 National; 06/1996