Erik Thunnissen1, Alain C Borczuk2, Douglas B Flieder3, Birgit Witte4, Mary Beth Beasley5, Jin-Haeng Chung6, Sanja Dacic7, Sylvie Lantuejoul8, Prudence A Russell9, Michael den Bakker10, Johan Botling11, Elisabeth Brambilla12, Erienne de Cuba13, Kim R Geisinger14, Kenzo Hiroshima15, Alberto M Marchevsky16, Yuko Minami17, Andre Moreira18, Andrew G Nicholson19, Akihiko Yoshida20, Ming-Sound Tsao21, Arne Warth22, Edwina Duhig23, Gang Chen24, Yoshihiro Matsuno25, William D Travis26, Kelly Butnor27, Wendy Cooper28, Mari Mino-Kenudson29, Noriko Motoi20, Claudia Poleri30, Giuseppe Pelosi31, Keith Kerr32, Seena C Aisner33, Yuichi Ishikawa34, Reinhard H Buettner35, Naoto Keino36, Yasushi Yatabe37, Masayuki Noguchi17. 1. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: e.thunnissen@vumc.nl. 2. Deptartment of Pathology, Weill Cornell Medicine, New York, New York. 3. Department of Pathology, Fox Chase Cancer Center, Philadelphia, Pennsylvania. 4. Department of Epidemiology and Biostatistics, VU University Medical Centre, Amsterdam, The Netherlands. 5. Department of Pathology, Mount Sinai Medical Center, New York, New York. 6. Department of Pathology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Republic of Korea. 7. Department of Pathology University of Pittsburgh, Pittsburgh, Pennsylvania. 8. Department of Biopathology, Centre Léon Bérard UNICANCER, Lyon, France. 9. St. Vincent's Pathology and The University of Melbourne, Melbourne, Australia. 10. Department of Pathology, Maasstad Ziekenhuis, Rotterdam, the Netherlands. 11. Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. 12. CHU Albert Michallon-Institut de Biologie, Département d'Anatomie et Cytologie Pathologiques, Grenoble, France. 13. Department of Pathology, VU University Medical Center, Amsterdam, The Netherlands. 14. Department of Pathology, The University of Mississippi Medical Center, Jackson, Mississippi. 15. Department of Pathology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan. 16. Department of Pathology, Cedars Sinai Medical Center, Los Angeles, California. 17. Department of Pathology, Institute of Basic Medical Sciences, University of Tsukuba, Tsukuba, Japan. 18. Pulmonary Pathology, New York University Center for Biospecimen Research and Development, New York University, New York, New York. 19. Department of Histopathology, Royal Brompton and Harefield Hospitals National Health Service Foundation Trust and National Heart and Lung Institute, Imperial College, London, United Kingdom. 20. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital, Tokyo, Japan. 21. Department of Pathology, University Health Network-Princess Margaret Hospital and University of Toronto, Toronto, Ontario, Canada. 22. Institute of Pathology, Heidelberg University, Heidelberg, Germany. 23. Sullivan Nicolaides Pathology, The John Flynn Hospital, Tugun, Queensland, Australia. 24. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai, People's Republic of China. 25. Department of Surgical Pathology, Hokkaido University Hospital, Sapporo, Japan. 26. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York. 27. Department of Pathology, University of Vermont, Burlington, Vermont. 28. Tissue Pathology and Diagnostic Oncology, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia. 29. Department of Pathology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. 30. Laboratorio de Patología Torácica, Buenos Aires, Argentina. 31. Department of Oncology and Hemato-Oncology, Università degli Studi di Milano, Milan, Italy. 32. Department of Pathology, Aberdeen Royal Infirmary, Aberdeen, United Kingdom. 33. Department of Pathology and Laboratory Medicine at Rutgers New Jersey Medical School, Rutgers University, Newark, New Jersey. 34. Division of Pathology, The Cancer Institute, Japan Foundation Cancer Research, Tokyo, Japan. 35. Cologne Institute for Pathology, Köln, Germany. 36. Tsukuba Clinical Research and Development Organization, University of Tsukuba, Tsukuba, Japan. 37. Department of Pathology and Molecular Diagnostics, Aichi Cancer Center, Nagoya, Japan.
Abstract
INTRODUCTION: The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin-stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise κ scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC. METHODS: Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3). RESULTS: For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, κ scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64. CONCLUSIONS: Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided.
INTRODUCTION: The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin-stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise κ scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC. METHODS: Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3). RESULTS: For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, κ scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64. CONCLUSIONS: Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided.
Authors: Marina K Baine; Christopher A Febres-Aldana; Jason C Chang; Achim A Jungbluth; Shenon Sethi; Cristina R Antonescu; William D Travis; Min-Shu Hsieh; Mee Sook Roh; Robert J Homer; Marc Ladanyi; Jacklynn V Egger; W Victoria Lai; Charles M Rudin; Natasha Rekhtman Journal: J Thorac Oncol Date: 2022-06-24 Impact factor: 20.121
Authors: Bingnan Zhang; C Allison Stewart; Qi Wang; Robert J Cardnell; Pedro Rocha; Junya Fujimoto; Luisa M Solis Soto; Runsheng Wang; Veronica Novegil; Peter Ansell; Lei He; Luisa Fernandez; Adam Jendrisak; Cole Gilbertson; Joseph D Schonhoft; Jiyun Byun; Joshua Jones; Amanda K L Anderson; Ana Aparicio; Hai Tran; Marcelo V Negrao; Jianjun Zhang; Wei-Lien Wang; Ignacio I Wistuba; Jing Wang; Rick Wenstrup; Lauren A Byers; Carl M Gay Journal: Br J Cancer Date: 2022-04-19 Impact factor: 9.075
Authors: Jules L Derks; Robert Jan van Suylen; Erik Thunnissen; Michael A den Bakker; Harry J Groen; Egbert F Smit; Ronald A Damhuis; Esther C van den Broek; Ernst-Jan M Speel; Anne-Marie C Dingemans Journal: Eur Respir J Date: 2017-06-01 Impact factor: 16.671