Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma

Noriko Kimura, Ryoichi Takayanagi, Nae Takizawa, Eiji Itagaki, Takayuki Katabami, Narihiko Kakoi, Hiromi Rakugi, Yukihiro Ikeda, Akiyo Tanabe, Takeshi Nigawara, Sadayoshi Ito, Itaru Kimura, Mitsuhide Naruse

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179 Citations (Scopus)


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 (rZK0.438, 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.

Original languageEnglish
Pages (from-to)405-414
Number of pages10
JournalEndocrine-Related Cancer
Issue number3
Publication statusPublished - 2014 Jun


  • Histopathological diagnosis
  • Immunohistochemistry
  • Metastasis
  • Paraganglioma
  • Phaeochromocytoma
  • Succinate dehydrogenase gene subunit B
  • Survival

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Oncology
  • Endocrinology
  • Cancer Research


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