Mesothelioma: Wick MR

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.

Wick MR, Mills SE. · No affiliation provided · Am J Clin Pathol. · Pubmed #10800393 links to  free full text

This publication has no abstract.

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.

Wick MR, Moran CA, Mills SE, Suster S. · University of Virginia Medical Center, Charlottesville, Virginia, USA. · Curr Opin Pulm Med. · Pubmed #11470972 No free full text.

Abstract: The immunohistochemical diagnosis of atypical epithelial proliferations in pleural fluid is a challenging topic in cytopathology and surgical pathology. Mesothelioma may be simulated clinically and radiologically by several other nonneoplastic and neoplastic disorders, mandating that strict histologic, histochemical, immunohistochemical, and ultrastructural guidelines be followed for its diagnosis. Because of its availability to most laboratories, immunohistochemistry has emerged as the most commonly used procedure for the diagnosis of pleural malignancies. This review considers the current status of that investigative modality, with particular attention to lesions that are suspected to be mesothelial.

Moran CA, Wick MR, Suster S. · Department of Pathology, The University of Alabama at Birmingham, 35294, USA. · Semin Diagn Pathol. · Pubmed #10968703 No free full text.

Abstract: The immunohistochemical diagnosis of mesothelioma is perhaps one of the most perplexing and controversial issues in surgical pathology. A tumor that in essence is extremely rare has managed to captivate the attention not only of pulmonologists and thoracic surgeons but also of pathologists. Throughout its history, mesothelioma has emerged as one of the tumors that has evaded definitive characterization; hence, the numerous attempts at trying to establish not only histological criteria but also histochemical, immunohistochemical, and ultrastructural guidelines for its diagnosis. Perhaps as we enter an era of more sophisticated technology, molecular biology will have an opportunity to make inroads into the diagnosis and characterization of this peculiar neoplasm. Despite the many difficulties involved in the diagnosis of malignant mesothelioma, we have recently gained significant knowledge of this entity in many respects, several decades after its description. From a morphological point of view, several variations of the histological appearances that these tumors may exhibit have been described. Traditional histochemistry and electron microscopy continue to play an important role in the evaluation of these neoplasms, with ultrastructural analysis in particular representing the most reliable technique for making this diagnosis in equivocal cases. However, because of its speed, cost-effectiveness, and general availability, immunohistochemistry has emerged as the most commonly used procedure for the diagnosis of mesotheliomas. We herein present a review of the current status of immunohistochemical evaluation of malignant lesions that are suspected of having a mesothelial lineage.

Padgett DM, Cathro HP, Wick MR, Mills SE. · Department of Pathology, University of Virginia Health System, Charlottesville, VA 22908, USA. · Am J Surg Pathol. · Pubmed #18162779 No free full text.

Abstract: Immunohistochemistry using a broad panel of markers is an invaluable tool for diagnosing sarcomatoid mesothelioma. Membranous podoplanin staining has been proposed as a specific and sensitive marker to distinguish epithelioid mesothelioma from adenocarcinoma. We found that cytoplasmic podoplanin staining was present in sarcomatoid mesotheliomas, and wanted to explore the reproducibility and specificity of this staining pattern. Immunohistochemistry for podoplanin, using 2 podoplanin antibodies (antipodoplanin and D2-40), was performed in 55 mesotheliomas (24 epithelioid, 18 sarcomatoid, and 13 biphasic), 80 pulmonary adenocarcinomas, 8 synovial sarcomas, and 16 sarcomatoid carcinomas. Expression of calretinin, vimentin, MOC31, and TTF-1 was also examined in all adenocarcinomas, sarcomatoid carcinomas, 7 synovial sarcomas, and 21 of the mesotheliomas. Calretinin staining performed previously on an additional 31 mesotheliomas was reviewed. Using membranous or cytoplasmic staining as indicative of positivity, we found that antipodoplanin and D2-40 each stained 84% of mesotheliomas (antipodoplanin: 46/55; D2-40: 38/44), including 72% of sarcomatoid mesotheliomas (antipodoplanin: 13/18; D2-40: 11/14). With antipodoplanin antibody, no staining was seen in the pulmonary adenocarcinomas (0/80, 0%) or the synovial sarcomas (0/8, 0%), and weak cytoplasmic staining was seen in only 1 sarcomatoid carcinoma (1/15, 7%). D2-40 showed similar results, staining 3% (2/80) of pulmonary adenocarcinomas, 13% (1/8) of synovial sarcomas, and 8% (1/13) of sarcomatoid carcinomas. Overall sensitivities and specificities were 84% and 99% for antipodoplanin, and 86% and 96% for D2-40. These findings suggest that cytoplasmic podoplanin expression may be useful in the diagnosis of sarcomatoid mesothelioma, although it should be used with caution on biopsy material.

Allen TC, Cagle PT, Churg AM, Colby TV, Gibbs AR, Hammar SP, Corson JM, Grimes MM, Ordonez NG, Roggli V, Travis WD, Wick MR. · Department of Pathology, Baylor College of Medicine, Houston, TX, USA. · Am J Surg Pathol. · Pubmed #15958850 No free full text.

Abstract: Localized malignant mesotheliomas are uncommon sharply circumscribed tumors of the serosal membranes with the microscopic appearance of diffuse malignant mesothelioma but without any evidence of diffuse spread. Little is known about their behavior. We report 23 new cases. The mean age at presentation was 63 years, and the sex ratio was approximately 2:1 (male/female). Twenty-one tumors were pleural and 2 were peritoneal. Sixteen tumors reproduced microscopic patterns of diffuse epithelial mesotheliomas, 6 had mixed epithelial and sarcomatous patterns, and 1 was purely sarcomatous. After surgical excision of the tumor, 10 of 21 patients with follow-up data were alive without evidence of disease from 18 months to 11 years after diagnosis. Patients who died had developed local recurrences and metastases, but none had diffuse pleural spread. Localized malignant mesotheliomas should be separated from diffuse malignant mesotheliomas because of their localized presentation, quite different biologic behavior, and far better prognosis.