Proceedings of the American Society of Cytopathology companion session at the 2019 United States and Canadian Academy of Pathology Annual meeting, part 2: effusion cytology with focus on theranostics and diagnosis of malignant mesothelioma

Our plain-English summary of Proceedings of the American Society of Cytopathology companion session at the 2019 United States and Canadian Academy of Pathology Annual meeting, part 2: effusion cytology with focus on theranostics and diagnosis of malignant mesothelioma, by M.T. Siddiqui, F. Schmitt, A. Churg (Journal of the American Society of Cytopathology, 2019).

The study

• Authors: M.T. Siddiqui, F. Schmitt, A. Churg
• Journal: Journal of the American Society of Cytopathology
• Published: 2019;8(6):352-361
• Cited by: 22 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

We live in the "era" of minimally invasive procedures, molecular testing, and personalized care. Effusions have a high sensitivity and will often yield diagnostic cytological material. The companion session presented by the American Society of Cytopathology at the 2019 United States and Canadian Academy of Pathology meeting outlined our current and future projected practices in characterizing, managing, and diagnosing serous cavity fluids. In this second part, the role of theranostics and the diagnosis of malignant mesothelioma, as was discussed at the meeting, have been highlighted. In theranostics, a vast amount of data has been reported regarding the epidermal growth factor receptor and related molecules. Some studies have also reported on HER2 immunohistochemistry and fluorescence in situ hybridization. This follows the most active areas of research in targeted therapy. Furthermore, during this session, malignant mesothelioma was extensively discussed. The cytologic diagnosis of malignant mesothelioma in effusion specimens has been controversial; however, a definitive diagnosis will be possible in many cases. Radiologic information should be sought, because the radiologist can often provide a definite or very likely diagnosis of malignancy. Microscopically, high cellularity and/or numerous balls of cells or papillary groups will favor the diagnosis of mesothelioma. It is important to exclude metastatic carcinoma with a broad-spectrum carcinoma marker, of which claudin-4 has been the best, because it will not cross react with mesothelioma. BAP1 and MTAP immunohistochemistry and CDKN2A fluorescence in situ hybridization are very useful adjunctive techniques for separating benign from malignant mesothelial proliferations. The use of 2 of these approaches together will produce a sensitivity of 80% to 90% for epithelial mesotheliomas in the pleura, although the sensitivity has been lower in the peritoneal cavity.

Copyright © 2019 American Society of Cytopathology. Published by Elsevier Inc. All rights reserved.

In plain English

This article records part of a 2019 pathology meeting session. It is a narrative review, not a new study: the authors summarized published research on testing fluid that collects around the lungs, heart or abdomen (effusions). It did not study asbestos exposure. The first part reviewed molecular tests used to select targeted cancer drugs, such as EGFR, ALK and HER2 testing. The second part covered diagnosing malignant mesothelioma from effusion fluid. The authors wrote that sarcomatous mesothelioma, as a rule, does not shed into effusions. They wrote that highly cellular samples, or many balls or papillary groups of atypical mesothelial cells, favor mesothelioma. They also wrote that claudin-4 is probably the best marker for ruling out metastatic carcinoma. They reported that combining two of three tests (BAP1, MTAP, CDKN2A) gives a sensitivity of 80% to 90% for epithelial mesotheliomas in the pleural cavity. They added that CDKN2A loss is much less frequent in peritoneal mesothelioma. The authors concluded that diagnosis from effusions is accurate and reliable when the microscopic findings are typical.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review written as the proceedings of a meeting companion session; no new data collected
• Who was studied: No study population. The authors reviewed published studies on serous effusion (pleural, pericardial, peritoneal fluid) cytology. One illustrative case in a figure: a woman in her 50s with peritoneal malignant mesothelioma diagnosed from an effusion specimen.
• Exposure: Not applicable: the article is about diagnostic and molecular testing of effusion fluid; asbestos and fiber types are not discussed
• Main results:
  • The authors stated that effusion cytology is considered by most to be equivalent to tissue specimens in its adequacy for molecular testing (based on studies they reviewed)
  • A previously published survey of 55 laboratories, cited by the authors, found about two thirds will make a definitive mesothelioma diagnosis from an effusion specimen and one third never will
  • The authors wrote that sarcomatous mesothelioma, as a rule, does not shed into effusions, so cytologic diagnosis almost always concerns epithelial tumors
  • The authors described two generally accepted features favoring mesothelioma in effusions: a highly cellular specimen and/or innumerable balls or papillary groups of atypical mesothelial cells
  • On imaging, the authors wrote that thickening of the mediastinal pleura almost always indicates malignancy, and that bilateral effusions are a strong indication against mesothelioma
  • The authors described claudin-4 as probably the best broad-spectrum carcinoma marker for separating mesothelioma from metastatic carcinoma. They recommended 2 mesothelial markers plus a broad-spectrum carcinoma marker.
  • Running 2 of the tests BAP1, MTAP and CDKN2A gives a sensitivity of 80% to 90% for epithelial mesotheliomas in the pleural cavity. The authors suggested BAP1 plus MTAP immunohistochemistry as probably the most efficient approach.
  • The authors stated that CDKN2A loss is much less frequent in peritoneal mesothelioma, and that this is probably also true for MTAP loss
  • The authors stated that specimens fixed only in formalin give much more reliable immunohistochemistry than alcohol-fixed specimens
• The authors' conclusion: The authors concluded that diagnosing malignant mesothelioma from effusion specimens is accurate and reliable when the morphologic findings are typical. In equivocal cases, BAP1 and MTAP immunohistochemistry and CDKN2A FISH can help separate mesothelioma from reactive mesothelial proliferations.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: Cytology, Pathology, Mesothelioma, Molecular Profiling, HER2, Immunohistochemistry, Fluorescence In Situ Hybridization (FISH), Targeted Therapy.

Related studies

• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma. Complementary statement from the International Mesothelioma Interest Group, also endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary Statement from the International Mesothelioma Interest Group, Also Endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology — A. Hjerpe, V. Ascoli, et al. (2015)
• Guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma: Complementary statement from the international mesothelioma interest group, also endorsed by the international academy of cytology and the papanicolaou society of cytopathology. A proposal to be applauded and promoted but which requires updating — M. Sheaff (2020)
• Summary of presentations from the 46th Annual Meeting of the American Society of Clinical Oncology (2010) focus on tumor biology and biomarkers related to lung cancer — J. Subramanian, L. Corrales, et al. (2011)
• An update on pleuro-pulmonary cytopathology: Part i: Cytological diagnosis of mesothelioma and molecular cytology of lung cancer with an historical perspective — C.W. Bedrossian (2015)
• 2015 American Society of Clinical Oncology annual meeting — S. Cleghorn (2015)

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