Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma

Endocr Relat Cancer. 2014 May 6;21(3):405-14. doi: 10.1530/ERC-13-0494. Print 2014 Jun.

Abstract

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.

Keywords: histopathological diagnosis; immunohistochemistry; metastasis; paraganglioma; phaeochromocytoma; succinate dehydrogenase gene subunit B; survival.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Gland Neoplasms / metabolism
  • Adrenal Gland Neoplasms / mortality
  • Adrenal Gland Neoplasms / pathology*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / metabolism*
  • Case-Control Studies
  • Catecholamines / metabolism
  • Female
  • Follow-Up Studies
  • Humans
  • Immunoenzyme Techniques
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Metastasis
  • Paraganglioma / metabolism
  • Paraganglioma / mortality
  • Paraganglioma / pathology*
  • Pheochromocytoma / metabolism
  • Pheochromocytoma / mortality
  • Pheochromocytoma / secondary*
  • Prognosis
  • Succinate Dehydrogenase / metabolism*
  • Survival Rate
  • Young Adult

Substances

  • Biomarkers, Tumor
  • Catecholamines
  • SDHB protein, human
  • Succinate Dehydrogenase