Current trend in the diagnosis and management of malignant pheochromocytoma: Clinical and prognostic factors

Table 1 Clinical factors and biomarkers assessing the risk of malignancy and prognosis of pheochromocytoma and paraganglioma

Ref.	Study duration and type	Study population	Study protocol/objective	Study outcome
Choi et al[10], 2015	1997-2013, retrospective	345 pts	Prognostic factors associated with survival for PPGL	Poor survival: Older age and synchronous metastasis
De Wailly et al[11], 2012	1993-2009, retrospective	53 pts	New immunohistologic elements correlating to malignant PPGL	Risk of malignancy/recurrence: Tumor necrosis, Ki-67 index > 4% and pS100
Hamidi et al[12], 2017	1960-2016, retrospective	272 pts	Epidemiology and survival outcome of malignant PPGL	MOS: 24.6 years, DSS: 33.7 years; poor survival: Older age at diagnosis, male sex, synchronous metastasis, larger tumor size, elevated dopamine
Mei et al[13], 2019	1973-2013, retrospective	1014 pts	Survival pattern of malignant PPGL	Survival advantage: Younger age, female sex, surgical resection and origin from of aortic/carotid bodies
Ruff et al[14], 2019	Prospective	35 pts	Serum miR-210 levels as a biomarker of malignancy	Lower serum miR-210 expression level and larger primary tumor size strongly correlated with malignant disease
Zelinka et al[15], 2011	Retrospective	41 pts	Biochemical and clinical outcome of malignant PPGL	Metastatic pheochromocytoma presented at a significantly younger age, with larger tumor, tumor necrosis and more frequent secreted norepinephrine
Hamidi et al[16], 2017	Systemic review and meta-analysis of 20 studies	1338 pts	Baseline characteristics and outcome of patients with malignant PPGL	5-year and 10-year mortality rates of 37% (95%CI: 24%-51%) and 29% (95%CI: 17%-42%), respectively; male sex and synchronous metastases were associated with higher mortality
Saffar et al[17], 2011	1986-2006, retrospective	51 pts	Galectin-3, COX-2, and nm-23 to discriminate benign disease from malignancy	Negative nm-23, along with positive galectin-3 or COX-2 were predictive of malignancy, with a sensitivity of 100%
Suh et al[18], 2017	1988-2013, retrospective	176 pts	Variations in genomic expressions and mutations of malignant PPGL	mRNA expression of malignant PPGL was up-regulated in five pathways; disease-free survival rates were closely related the presence or absence of mutations
Szalat et al[19], 2011	1980-2008, retrospective	16 pts	Predictive features of malignancy in PPGL	High levels of chromogranin A at the time of diagnosis were associated with malignancy; 10-year survival rate after initial diagnosis was 50% and 25% after metastasis
Zhong et al[20], 2017	2002-2014, retrospective	414 pts	Clinical significance of biomarker nomogram in detecting malignancy and rate of metastasis	Tumor size, tumor location, vascular invasion, ERBB-2 overexpression and SDHB mutation were independent predictors of malignancy and metastasis

DSS: Disease-specific survival; MOS: Median overall survival; PPGL: Pheochromocytoma and paraganglioma; SDHB: Succinate dehydrogenase subunit B.