Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma

    1. The Phaeochromocytoma Study Group in Japan
    1. Pathology Division, Department of Clinical Research, National Hospital Organization, Hakodate Hospital, Postal cord 041-8512, 18-16 Kawahara, Hakodate, Hokkaido, Japan
      1Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
      2Department of Urology and Andrology, Kansai Medical University, Osaka, Japan
      3Third Department of Internal Medicine (Diabetes Endocrine and Metabolism), School of Medicine, Kyorin University, Tokyo, Japan
      4Department of Medicine, Metabolism and Endocrinology, School of Medicine, St Marianna University, Kawasaki, Japan
      5Department of Urology, Miyagi Cancer Center, Natori, Japan
      6Department of Geriatric Medicine and Nephrology, Graduate School of Medicine, Osaka University, Osaka, Japan
      7Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University Itabashi Hospital, Tokyo, Japan
      8Department of Endocrinology and Metabolism, Tokyo Women's Medical University, Tokyo, Japan
      9Department of Endocrinology and Metabolism, School of Medicine, Hirosaki University, Hirosaki, Japan
      10Division of Nephrology, Endocrinology and Vascular Medicine, Department of Medicine, School of Medicine, Tohoku University, Sendai, Japan
      11Council Member Examination Committee of Social Insurance, Ministry of Health, Labour and Welfare, Tokyo, Japan
      12Department of Endocrinology, Metabolism, and Hypertension, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan
    1. Correspondence should be addressed to N Kimura; Email: kimura-path{at}


    Phaeochromocytomas (PHEO) and paragangliomas are rare catecholamine-producing tumours. Although 10–30% of these tumours metastasise, histopathological criteria to discriminate malignant from benign tumours have not been established; therefore, reliable histopathological markers predicting metastasis are urgently required. A total of 163 tumours, including 40 metastatic tumours, collected by the Phaeochromocytoma Study Group in Japan (PHEO-J) were analysed using a system called grading system for adrenal phaeochromocytoma and paraganglioma (GAPP). The tumours were scored based on GAPP criteria as follows: histological pattern, cellularity, comedo-type necrosis, capsular/vascular invasion, Ki67 labelling index and catecholamine type. All tumours were scored from 0 to 10 points and were graded as one of the three types: well-differentiated (WD, 0–2 points), moderately differentiated (MD, 3–6 points) and poorly differentiated (PD, 7–10 points). GAPP scores of the non-metastatic and metastatic groups were 2.08±0.17 and 5.33±0.43 (mean±s.e.m., P<0.001) respectively. There was a significant negative correlation between the GAPP score and the interval until metastasis (r=−0.438, P<0.01). The mean number of years until metastasis after the initial operation was 5.5±2.6 years. The study included 111 WD, 35 MD and 17 PD types. The five-year survival of these groups was 100, 66.8 and 22.4% respectively. In addition, negative immunoreactivity for succinate dehydrogenase gene subunit B (SDHB) was observed in 13 (8%) MD or PD tumours and ten of the 13 (77%) had metastases. Our data indicate that a combination of GAPP classification and SDHB immunohistochemistry might be useful for the prediction of metastasis in these tumours.

    • Revision received 12 February 2014
    • Accepted 12 February 2014
    • Made available online as an Accepted Preprint 12 February 2014
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