Mesothelioma: Marchevsky AM

Marchevsky AM, Wick MR. · Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Appl Immunohistochem Mol Morphol. · Pubmed #17525624 No free full text.

Abstract: There are no firmly established guidelines for the use of antibodies in immunohistology as individual tests or panels. Practicing pathologists must rely on information available in individual publications, review articles, books, and internet-based databases to develop diagnostic immunohistochemical algorithms for their individual practices. In contrast, other medical specialties have crafted many evidence-based practice guidelines (EBG) that are widely used; these have helped to augment standardization and cost effectiveness. In particular, the use of several "epithelial" and "mesothelial" antibodies has been proposed to distinguish epithelioid malignant mesothelioma from metastatic pulmonary adenocarcinoma. Other authors have previously done systematic literature reviews of this subject up through 2004 and integrated the results of 88 publications into summarized test-performance values for 15 preselected immunohistochemical markers. The results suggested that 7 tests provide optimal sensitivity and specificity (MOC-31, BG8, CEA, TTF-1, CK5/6, WT-1, and HBME-1), but they provide no guidance for integration of such data into EBG. Odds ratios (ORs) were employed to compare the effectiveness of any single test, and chosen combinations thereof, in the differential diagnosis of malignant mesothelioma and metastatic pulmonary adenocarcinoma. Surprisingly, selected single immunostains or antibody pairs yielded ORs (varying from 96.34 to 1233.19) that were equal or better in efficacy when compared with more comprehensive panels. These results support the potential value of systematic reviews, meta-analysis, and OR calculations for development of EBG in diagnostic immunohistology.

Marchevsky AM. · Department of Anatomic Pathology, Cedars-Sinai Medical Center, 8700 Beverly Blvd, Room 8712, Los Angeles, CA 90048-1865, USA. · Arch Pathol Lab Med. · Pubmed #18318582 No free full text.

Abstract: CONTEXT: The diagnosis of malignant mesothelioma (MM) is rendered with the aid of immunohistochemistry to demonstrate the presence of "mesothelial," "epithelial," or "sarcomatous" differentiation. Antibody panels that have been proposed for the distinction between MM and other neoplasms usually include 2 or more epithelial markers used to exclude the diagnosis of a carcinoma, such as monoclonal and polyclonal carcinoembryonic antigen, Ber-EP4, B72.3, CD15, MOC-31, thyroid transcription factor 1, BG8, and others, and 2 or more mesothelial markers used to confirm the diagnosis of MM, such as cytokeratin 5/6, calretinin, HBME-1, thrombomodulin, WT-1, mesothelin, D2-40, and podoplanin. In general, most antibody panels provide excellent sensitivity and specificity for the differential diagnosis between MM epithelial variant and adenocarcinoma, particularly of lung origin. However, the accuracy of these markers is lower for the diagnosis of sarcomatous MM and for the differential diagnosis between MM and squamous cell carcinoma and carcinomas of renal, ovarian, and other origin. OBJECTIVE: To identify optimal antibody panels for the diagnosis of MM. DATA SOURCES: Literature review to determine how many and which mesothelial and epithelial markers need to be included in differential diagnosis antibody panels. CONCLUSIONS: Various antibody panels have been recommended for the diagnosis of MM, with no overall consensus about how many and which markers should be used. A recent study with Bayesian statistics has demonstrated that the use of many markers does not provide higher diagnostic accuracy than the use of selected single antibodies or various combinations of only 2 markers. There is a need for the development of evidence-based or consensus-based guidelines for the diagnosis of MM in different differential diagnosis situations.

Marchevsky AM, Harber P, Crawford L, Wick MR. · Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Ann Diagn Pathol. · Pubmed #16844568 No free full text.

Abstract: The specific parameters of nonoccupational asbestos exposures (NOAE) that can distinguish an idiopathic from an asbestos-caused malignant mesothelioma (MM) are controversial. A systematic literature review yielded 1028 cases with this putative association. Only 287 of those reports had a defined single exposure to a household, building occupant, or neighborhood/community asbestos source. The available "evidence" was used to develop semiarbitrary evidence-based causation guideline rules for the assessment of putative associations between MM and NOAE. The rules are classified into class A (tissue burden analysis shows asbestos body counts or fiber counts in lung tissues comparable to MM caused by occupational exposure to asbestos) and classes B to D based on whether certain combinations of NOAE features and MM (evidence) have been described in over 15% (class B), 5% to 15% (class C), and less than 5% (class D) of the patients reviewed. The proposed 4 classes of evidence-based causation guidelines provide a semiarbitrary framework to evaluate the causation of individual MM patients by NOAE based on decreasing levels of currently available evidence. The neoplasms in classes A to C patients are probably caused by NOAE, with decreasing weight of evidence in the 3 groups. There is minimal evidence to support the causation of MM by NOAE in class D patients. There is no evidence or only anecdotal evidence to support a causal association between MM and NOAE in individuals who cannot be classified into any of the 4 classes. Future studies are needed to provide more comprehensive data regarding the association between MM and NOAE.

Marchevsky AM, Wick MR. · Departments of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA. · Ann Diagn Pathol. · Pubmed #14571437 No free full text.

Abstract: Asbestos is a group of fibrous silicate minerals that includes two mineralogic groups: amphiboles and serpentines. While the carcinogenic role of amphiboles (eg, crocidolite and amosite) is well established, medical "experts" that tend to strongly advocate their views currently argue in medicolegal cases multiple specific issues regarding the carcinogenicity of asbestos fibers. For example, it is controversial whether chrysotile causes malignant mesothelioma (MM); what are the specific carcinogenic thresholds for amphiboles and chrysotile; what occupations are truly at risk to develop MM as a result of asbestos exposure; what is the role of chrysotile in the development of peritoneal MM; how to assign causation in individuals exposed to multiple industrial products containing variable concentrations of various asbestos fibers; and, what criteria should be used to accept causation in household exposure cases and others. The causation criteria currently acceptable in U.S. courts are surprisingly flexible and subject to variable interpretation by medical "experts." At a time where thousands of individuals are claiming causation of MM by asbestos exposure, there is a need to develop more specific causation guidelines based on scientific evidence. Evidence-based medicine has been proposed as a new approach to the study, teaching, and the practice of medicine and has been used as a process of systematically reviewing the relevant studies in the literature to assess their scientific validity and development of guidelines. This article summarizes some of the current controversies regarding the role of asbestos exposure in the causation of MM and suggests the need for future evidence-based medicine-type studies to develop causation guidelines that could be used consistently during litigation.

Marchevsky AM, Varshney D, Fuller C. · Department of Pathology and Laboratory Medicine, Cedars-Sinai Medical Center, Los Angeles, Calif 90048, USA. · Arch Pathol Lab Med. · Pubmed #12683905 No free full text.

Abstract: We describe the case of a 74-year-old man with a mediastinal tumor composed predominantly of epithelioid cells exhibiting histopathologic and immunohistochemical features intermediate between those of a solitary fibrous tumor and those of a cellular adenomatoid tumor. We discuss the differential diagnosis and possible histogenesis of this unusual neoplasm, and we propose the term epithelioid solitary fibrous tumor for this entity.