A histological grading system of chromophobe renal cell carcinoma (chRCC) is highly desirable to identify approximately 5-10% of tumors at risk for progression. Validation studies failed to demonstrate a correlation between the four-tiered WHO/ISUP grade and outcome. Previous proposals with three-tiered chromophobe grading systems could not be validated. In this study, the presence of sarcomatoid differentiation, necrosis, and mitosis was analyzed in a Swiss cohort (n = 42), an Italian cohort (n = 103), a German cohort (n = 54), a Japanese cohort (n = 119), and The Cancer Genome Atlas cohort (n = 64). All 3 histological parameters were significantly associated with shorter time to tumor progression and overall survival in univariate analysis. Interobserver variability for identification of these parameters was measured by Krippendorff's alpha coefficient and showed high concordance for the identification of sarcomatoid differentiation and tumor necrosis, but only low to medium concordance for the identification of mitosis. Therefore, we tested a two-tiered tumor grading system (low versus high grade) based only on the presence of sarcomatoid differentiation and/or necrosis finding in the combined cohorts (n = 382). pT stage, patient's age (> 65 vs ≤ 65), lymph node and/or distant metastasis, and the two-tiered grading system (low versus high grade) were significantly associated with overall survival and were independent prognostic parameters in multivariate analysis (Cox proportional hazard). This multi-institutional evaluation of prognostic parameters suggests tumor necrosis and sarcomatoid differentiation as reproducible components of a two-tiered chromophobe tumor grading system.
Virchows Archiv : an international journal of pathology. 2019 Nov 23 [Epub ahead of print]
Riuko Ohashi, Guido Martignoni, Arndt Hartmann, Anna Caliò, Diego Segala, Christine Stöhr, Sven Wach, Franziska Erlmeier, Wilko Weichert, Michael Autenrieth, Peter Schraml, Niels J Rupp, Chisato Ohe, Yoshiro Otsuki, Takashi Kawasaki, Hiroshi Kobayashi, Kazuhiro Kobayashi, Tatsuhiko Miyazaki, Hiroyuki Shibuya, Hiroyuki Usuda, Hajime Umezu, Fumiyoshi Fujishima, Bungo Furusato, Mitsumasa Osakabe, Tamotsu Sugai, Naoto Kuroda, Toyonori Tsuzuki, Yoji Nagashima, Yoichi Ajioka, Holger Moch
Histopathology Core Facility, Niigata University Faculty of Medicine, 1-757 Asahimachi-dori, Chuo-ku, Niigata, 951-8510, Japan., Department of Diagnostic and Public Health, University of Verona, Piazzale Ludovico Antonio Scuro 10, 37134, Verona, Italy., Institute of Pathology, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Krankenhausstrasse 8-10, 91054, Erlangen, Germany., Department of Pathology, Pederzoli Hospital, Via Monte Baldo 24, 37019, Peschiera del Garda, Italy., Department of Urology and Pediatric Urology, University Hospital Erlangen, Friedrich Alexander-University Erlangen-Nürnberg, Krankenhausstrasse 12, 91054, Erlangen, Germany., Institute of Pathology, Technical University Munich, Trogerstrasse 18, 81675, Munich, Germany., Department of Urology, Technical University Munich, Klinikum rechts der Isar, Ismaninger Strasse 22, 81675, Munich, Germany., Department of Pathology and Molecular Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland., Department of Pathology and Laboratory Medicine, Kansai Medical University, 2-5-1 Shin-machi, Hirakata, 573-1010, Japan., Department of Pathology, Seirei Hamamatsu General Hospital, 2-12-12 Sumiyoshi, Naka-ku, Hamamatsu, 430-8558, Japan., Department of Pathology, Niigata Cancer Center Hospital, 2-15-3 Kawagishi-cho, Chuo-ku, Niigata, 951-8566, Japan., Department of Pathology, Tachikawa General Hospital, 1-24 Asahioka, Nagaoka, 940-8621, Japan., Department of Pathology, Gifu University Hospital, 1-1 Yanagido, Gifu, 501-1194, Japan., Department of Pathology, Niigata City General Hospital, 463-7 Shumoku, Chuo-ku, Niigata, 950-1197, Japan., Department of Diagnostic Pathology, Nagaoka Red Cross Hospital, 2-297-1 Sensyu, Nagaoka, 940-2085, Japan., Division of Pathology, Niigata University Medical & Dental Hospital, 1-754 Asahimachi-dori, Chuo-ku, Niigata, 951-8520, Japan., Department of Anatomic Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi, 980-8575, Japan., Cancer Genomics Unit, Clinical Genomics Center, Nagasaki University Hospital, 1-7-1, Sakamoto, Nagasaki, 852-8501, Japan., Department of Molecular Diagnostic Pathology, School of Medicine, Iwate Medical University, 2-1-1, Idai-dori, Yahaba-cho, Shiwa-gun, Iwate, 028-3695, Japan., Department of Diagnostic Pathology, Kochi Red Cross Hospital, 1-4-63-11 hadaminamimachi, Kochi, Kochi, 780-8562, Japan., Department of Surgical Pathology, Aichi Medical University Hospital, 1-1 Yazakokarimata, Nagakute, 480-1195, Japan., Department of Surgical Pathology, Tokyo Women's Medical University Hospital, 8-1 Kawada-cho, Shinjuku-ku, Tokyo, 162-8666, Japan., Department of Pathology and Molecular Pathology, University and University Hospital Zurich, Schmelzbergstrasse 12, CH-8091, Zurich, Switzerland. .