Pathological grading for predicting metastasis in phaeochromocytoma and paraganglioma

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 2.08G0.17 and 5.33G0.43 (meanGS.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 5.5G2.6 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.

Efficacy and safety of metyrosine in pheochromocytoma/paraganglioma: a multi-center trial in Japan

“…ber of Japanese patients is 2,920: 2,600 with benign and 320 with malignant disease [3]. Although most of the patients with PPGL show benign lesions, a considerable portion of these patients show metastatic lesions [2,3].…”

“…Although most of the patients with PPGL show benign lesions, a considerable portion of these patients show metastatic lesions [2,3].…”

Biomarker, Molecular, and Technologic Advances in Urologic Pathology, Oncology, and Imaging

“…[44][45][46][47] One study showed negative immunoreactivity (loss) with the SDHB antibody in 8% (n ¼ 13) of moderately or poorly differentiated pheochromocytomas or paragangliomas, and 10 of those 13 patients (77%) had developed metastases, suggesting that routine IHC staining with SDHB might be useful for prediction of metastasis in these tumors. 48 In another study detailing 33 bilateral adrenal pheochromocytomas and 26 abdominal, but extra-adrenal sympathetic paragangliomas, no SDHB mutations were found in any of the bilateral pheochromocytomas; however, 3 SDHB mutations were found in the 26 sympathetic paragangliomas, of which, 1 was metastatic at the time of the study.…”

Recurrent, bilateral, and metastatic pheochromocytoma in a young patient with Beckwith-Wiedemann syndrome: A genetic link?

“…The grading system for adrenal pheochromocytoma and paraganglioma (GAPP) can be used to predict metastasis, 2,3 and is helpful because metastatic disease is required for malignancy and 60% of metastases are asynchronous. Points are scored for the histological pattern, tumour cellularity, comedonecrosis, vascular or capsular invasion, Ki-67 labeling, and catecholamine subtype.…”