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.

To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma (MM). Cytopathologists involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC), who have an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists, who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in cape town. During the previous IMIG biennial meetings, thorough discussions have resulted in published guidelines for the pathologic diagnosis of MM. However, previous recommendations have stated that the diagnosis of MM should be based on histological material only.[12] Accumulating evidence now indicates that the cytological diagnosis of MM supported by ancillary techniques is as reliable as that based on histopathology, although the sensitivity with cytology may be somewhat lower.[345] Recognizing that noninvasive diagnostic modalities benefit both the patient and the health system, future recommendations should include cytology as an accepted method for the diagnosis of this malignancy.[67] The article describes the consensus of opinions of the authors on how cytology together with ancillary testing can be used to establish a reliable diagnosis of MM.

Objective: To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma. Data Sources: Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks. Rationale: This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.

The guidelines for the cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma produced by the International Mesothelioma Interest Group and which are endorsed by the International Academy of Cytology and the Papanicolaou Society of Cytopathology are reviewed and discussed. This (predominantly) evidence-based document provides a robust and useful framework for diagnosticians and guideline producers to emphasise and promote the value, power and role of cytology in mesothelioma diagnosis and management with comments and suggestions about how the guidelines can be updated and improved in the future.

To provide practical guidelines for the cytopathologic diagnosis of malignant mesothelioma. Cytopathologists with an interest in the field involved in the International Mesothelioma Interest Group (IMIG) and the International Academy of Cytology (IAC) contributed to this update. Reference material includes peer-reviewed publications and textbooks. This article is the result of discussions during and after the IMIG 2012 conference in Boston, followed by thorough discussions during the 2013 IAC meeting in Paris. Additional contributions have been obtained from cytopathologists and scientists who could not attend these meetings, with final discussions and input during the IMIG 2014 conference in Cape Town.

Introduction: Cytology provides crucial window for early diagnosis of malignant mesothelioma (MM) since it is often the first and easily available material for evaluation, resulting in early treatment. Still, its role is overlooked in the current treatment guidelines. The aim of this study is to determine the sensitivity of cytomorphology and role of subsequent ancillary techniques in diagnosing MM. Methods: This is a 5-year retrospective analysis of MM in the tertiary oncology center to determine sensitivity of cytomorphology and subsequent role of immunohistochemistry (IHC) in final diagnosis of MM according to the guidelines for cytopathologic diagnosis of epithelioid and mixed-type malignant mesothelioma (GCDMM) laid by International Mesothelioma Interest Group. Cytomorphology and immunocytochemistry from effusions and fine needle aspirations were analyzed. Results: Sixty-two of 128 cases of MM had cytology and cytomorphological criteria described in GCDMM were fulfilled in 61.3% cases. Architectural atypia was useful in identifying cases with low cytological atypia. Overall sensitivity of cytomorphology was 73.01%. Sensitivity of effusion cytology was 77.8%. Subsequent IHC on cell blocks revealed the sensitivity as 100% for mesothelin, calretinin, and cytokeratin 5/6; 87.5% for thrombomodulin; and 50% for WT1, while CEA and TTF1 showed 100% specificity. Treatment was given based on final diagnosis of MM given after IHC on cytology material in only 25.8% cases. However, it was possible in additional 35.5% cases. Mean survival was 10 months when diagnosed by cytology, compared to 7 months by histology. Conclusions: Rather than ignoring the role of cytology in the diagnosis and treatment guidelines for MM, it is important to understand its strengths and limitations. Standardized guidelines in future can play an important role in more streamlined communication between cytopathologist and clinician.

Erratum: 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.

Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. To provide updated practical guidelines for the pathologic diagnosis of MM. Pathologists involved in the International Mesothelioma Interest Group and others with an interest in the field contributed to this update. Reference material includes peer-reviewed publications and textbooks. There was consensus opinion regarding (1) distinction of benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiation of epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. It is recommended that immunohistochemical markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.

A conclusive diagnosis of malignant mesothelioma (MM) can be based on effusion cytology using the guidelines for the cytopathologic diagnosis of epithelioid and mixed-type MM. Briefly, the diagnosis is obtained when the mesothelial phenotype of malignant cells is established by ancillary techniques. This study is based on the comparison of the overall survival rates of patients with MM when diagnosed by effusion cytology, histopathology, or a combination of both. A total of 144 patients were diagnosed with epithelioid and mixed-type pleural MM at Karolinska University Hospital between 2004 and 2013. The diagnosis was obtained by histopathology in 74 cases and by cytological examination of pleural effusion in 70 cases. In 29 of the latter cases, a diagnostic biopsy was obtained simultaneously. A total of 104 patients received chemotherapy. All diagnoses were supported by clinical findings, including computer tomography scans. The median time between first symptoms and diagnosis was similar for cytology and histopathology. However, a delay of more than 6 months after first symptoms was seen in many patients in the histopathology group, resulting in late onset of treatment. The overall survival and proportion of long-term survival were significantly better for cases diagnosed by cytology. Similarly, a better survival, following a cytological diagnosis, was also seen in patients who were only provided the best supportive care. Accurate cytological diagnosis enables conclusive diagnosis of MM. Our finding enables the initiation of treatment as soon as the cytological diagnosis is established, avoiding further delay and deterioration of patient survival and possibilities for treatment.

- Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. - To provide updated, practical guidelines for the pathologic diagnosis of MM. - Pathologists involved in the International Mesothelioma Interest Group and others with an interest and expertise in the field contributed to this update. Reference material included up-to-date, peer-reviewed publications and textbooks. - There was discussion and consensus opinion regarding guidelines for (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) recognition of the key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas, and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid MM, (7) use of molecular markers in the diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels employed is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Depending on the morphology, immunohistochemical panels should contain both positive and negative markers for mesothelial differentiation and for lesions considered in the differential diagnosis. Immunohistochemical markers should have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic and membranous markers). Selected molecular markers are now being used to distinguish benign from malignant mesothelial proliferations. These guidelines are meant to be a practical diagnostic reference for the pathologist; however, some new pathologic predictors of prognosis and response to therapy are also included.

Malignant mesothelioma (MM) is an uncommon tumor that can be difficult to diagnose. To develop practical guidelines for the pathologic diagnosis of MM. A pathology panel was convened at the International Mesothelioma Interest Group biennial meeting (October 2006). Pathologists with an interest in the field also contributed after the meeting. There was consensus opinion regarding (1) distinguishing benign from malignant mesothelial proliferations (both epithelioid and spindle cell lesions), (2) cytologic diagnosis of MM, (3) key histologic features of pleural and peritoneal MM, (4) use of histochemical and immunohistochemical stains in the diagnosis and differential diagnosis of MM, (5) differentiating epithelioid MM from various carcinomas (lung, breast, ovarian, and colonic adenocarcinomas and squamous cell and renal cell carcinomas), (6) diagnosis of sarcomatoid mesothelioma, (7) use of molecular markers in the differential diagnosis of MM, (8) electron microscopy in the diagnosis of MM, and (9) some caveats and pitfalls in the diagnosis of MM. Immunohistochemical panels are integral to the diagnosis of MM, but the exact makeup of panels used is dependent on the differential diagnosis and on the antibodies available in a given laboratory. Immunohistochemical panels should contain both positive and negative markers. The International Mesothelioma Interest Group recommends that markers have either sensitivity or specificity greater than 80% for the lesions in question. Interpretation of positivity generally should take into account the localization of the stain (eg, nuclear versus cytoplasmic) and the percentage of cells staining (>10% is suggested for cytoplasmic membranous markers). These guidelines are meant to be a practical reference for the pathologist.

Malignant pleural mesothelioma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up☆

IA05.02 Mesothelioma Cases

It is with mixed emotions that I say goodbye to our Associate Editor, Gladwyn Leiman, MBBCh, FIAC, FRCPath, professor and director of cytopathology and the Cytopathology Fellowship Program at the University of Vermont College of Medicine in Burlington, who is retiring from practice this year. We will miss her very much at Cancer Cytopathology. Gladwyn joined Cancer Cytopathology as an editorial board member in 2001 and was appointed Associate Editor in 2011. She has been a wellspring of ideas and vision and an amazing colleague. Those of us fortunate enough to have worked with her during her tenure as a cytopathologist have experienced firsthand her enthusiasm and dedication to our specialty. Gladwyn's distinguished career began in Johannesburg, South Africa. After her medical and postgraduate training at the University of Witwatersrand Medical School, she was appointed medical officer and subsequently an associate professor in the Cytology Unit in the Department of Anatomical Pathology in the School of Pathology of the South African Institute for Medical Research. A large part of her academic life was spent as an educator both at home and internationally, bringing cytology workshops, tutorials, and seminars to 5 continents. She was quickly recognized as a leader in this evolving field, and over the next 30 years she brought her knowledge, insight, and collegiality to numerous international committees such as the International Academy of Cytology, the American Society of Cytopathology, the Papanicolaou Society of Cytopathology, the International Academy of Pathology, the British Society for Clinical Cytology, and the International Congress of Cytology. Within cytopathology, Gladwyn was actively involved as an Associate Editor for Acta Cytologica and served on several editorial boards, including those for Diagnostic Cytopathology and Advances in Anatomic Pathology. Notably, in 1996, she was named as a Light Source Personality of Cytopathology in South Africa by the International Academy of Cytology “CYTOPATHS” newsletter. And in 1999, the refurbished laboratory at the South African Institute for Medical Research was renamed the Gladwyn Leiman Cytopathology Centre. At the beginning of the new millennium, Gladwyn traveled to the United States as a professor of pathology to assume the directorships of the Laboratory and Fellowship Program at the University of Vermont College of Medicine in Burlington. She continued to expand her affiliations to include the United States and Canadian Academy of Pathology, the International Society of Breast Pathology, and the Australian Society of Cytology, all the while retaining her dedication to cytopathology in South Africa. During the International Congress of Cytology in Paris in 2013, Gladwyn received the 2012 Maurice Goldblatt Award. An excerpt from this recognition epitomizes Gladwyn: “For her lifelong love and dedication to clinical cytology; for her very special relationship to underserved areas of the world and her willingness to bring knowledge and expertise to people deserving improved medical care; for her academic rigor and achievements in publishing and teaching; to her loyal support of Acta Cytologica and the International Academy of Cytology for many years.” Gladwyn's accomplishments cannot be summarized in this short editorial. It suffices to say that she has had a measurable impact on the evolution of our discipline. In this issue, Gladwyn authors one of Cancer Cytopathology's 20th anniversary editorials reflecting on the seminal articles and changes in the field of pulmonary cytopathology. One reason for the success of Cancer Cytopathology is the effort exhibited by our Associate Editors in the selection and critical review of articles received for publication. Undoubtedly, we have benefited immensely from Gladwyn's wisdom and expertise in this regard. On behalf of myself, the Associate Editors, and the American Cancer Society, I would like to thank Dr. Gladwyn Leiman for her remarkable contribution to the journal. It is with deep personal gratitude that I say she has been a reliable source of inspiration and wisdom that I have tapped regularly. I am highly appreciative of her service and partnership. Thank you, Gladwyn. As a postscript, Gladwyn will be relocating to North Carolina's Raleigh-Durham area. When asked what comes next, Gladwyn replied, “My future plans are to resurrect my right brain, and reenter the worlds of literature, music, and history, which were my major interests before I deviated to medical school. In particular, I want to reengage in Holocaust studies and genealogy, which have been constant unofficial pursuits throughout my life.” For those who would like to extend their congratulations to Gladwyn on her amazing career and send best wishes for her retirement, you can contact her through Cancer Cytopathology at [email protected]. All correspondence will be forwarded to her.

A group of international experts in breast fine needle aspiration biopsy (FNAB) cytopathology, supported by the International Academy of Cytology (IAC), drafted a comprehensive system for reporting breast FNAB cytopathology in 2017-2018. The editorial team produced a survey to assess the international response to the proposed category structure, definitions, and management recommendations in this draft. A web-based survey of 186 questions was generated using the Qualtrics software package (Provo, Utah) supported by the Division of Information Technology at the University of Wisconsin-Madison. The survey was advertised widely-including through the IAC, American Society of Cytopathology, Japanese Society of Clinical Cytology, Papanicolaou Society of Cytopathology, and Australian Society of Cytology and to audiences at national and international meetings-and was available from April to June 2018. The data obtained from the 265 respondents was assessed by the editorial team. The survey provided a snapshot of the current role and use of breast FNAB and the international variations. Demographic questions were followed by specific questions based on the draft category definitions and statements and focused on issues that had generated discussion among the authors, including the FNAB diagnosis of ductal carcinoma in situ. The survey results strongly supported the development of the IAC Yokohama System and informed subsequent discussions among the authors regarding the final text.

An international panel of experts in the field of salivary gland cytology (SGC), supported by the American Society of Cytopathology (ASC) and the International Academy of Cytology, conducted a survey to seek evidence and practice patterns regarding SGC. Results were used to provide focus for the proposed Milan System for Reporting Salivary Gland Cytopathology. The study group, formed during the 2015 European Congress of Cytology held in Milan, Italy, generated a survey that included 49 specific questions related to the taxonomies, practices, and diagnostic entities of salivary cytology. Qualtrics software was used as the study platform. Software and server support were provided by the division of information technology at the University of Wisconsin. The survey was available online from November 2015 until February 2016. Participants were invited through the Web sites of the ASC, the International Academy of Cytology, and the Papanicolaou Society of Cytopathology as well as by the ASC e-mail "ListServe"; responses were evaluated by the Milan System editors. Responses from a total of 515 participants were collected and reviewed. A total of 347 participants provided demographic data information. Responses revealed variations in diagnostic practice and subsequent management. Participants believed that the acceptable rate for nondiagnostic samples should not be higher than 10%. There were varied opinions regarding the approach to neoplastic lesions of uncertain malignant potential, those that may or may have not local invasion and distant spread. Results of the survey demonstrated strong support for the development of a unified system for reporting SGC. Cancer Cytopathol 2017;125:757-66. © 2017 American Cancer Society.