Abstract
BackgroundSuccinate dehydrogenase subunit B (SDHB) mutations are associated with aggressive pheochromocytoma (PHEO)/paraganglioma (PGL) behavior, often resulting in metastatic disease and fatal outcomes. These tumors are often larger, extra-adrenal, and contain lower catecholamine concentrations than other hereditary PHEOs/PGLs. This study evaluated the size and age at diagnosis of primary SDHB-related PHEOs/PGLs as independent predictors of their metastatic behavior and outcome (survival).MethodsOne hundred six patients with SDHB mutation-related PHEO/PGL were included in this retrospective study. The recorded largest diameters, locations, and patient ages at initial diagnosis of SDHB-related primary tumors were analyzed in the context of time to metastasis and patient survival.ResultsFirst, the development of metastatic disease in patients with primary tumors ≥4.5 cm was significantly earlier than in patients with smaller tumors (P = 0.003). Second, patients with primary tumors larger than 5.5 cm also had worse overall survival than patients with smaller tumors (P = 0.008). Third, age at initial diagnosis was found to be an independent predictor of patient survival (PHEOs: P = 0.041; PGLs: P < 0.001). Fourth, we did not observe a significant difference in survival based on the specific SDHB mutations or patient sex.ConclusionReceiver operating characteristic curves established 4.5 cm as the best value to dichotomize the primary SDHB-related PHEO/PGL in order to evaluate the development of metastatic disease and 5.5 cm as the best value for survival prediction. Subsequently, the size of the primary tumor was found as an age-independent predictor of patient survival and metastases development in PGL. In both PHEO and PGL, age at diagnosis was found to be a size-independent predictor of patient survival. No significant difference was found in metastases development or patient survival between males and females or among specific SDHB mutations. This data further extends and supports previous recommendations that carriers with SDHB mutations must undergo early and regular evaluations to detect PHEO/PGL in order to achieve the best clinical outcome.
Highlights
Succinate dehydrogenase subunit B (SDHB) mutations are associated with aggressive pheochromocytoma (PHEO)/paraganglioma (PGL) behavior, often resulting in metastatic disease and fatal outcomes
The number of males in the present study was significantly higher than the number of females (P = 0.008), but these two groups did not differ in any of these following parameters: size of the primary tumor (P = 0.13); percentage of patients with synchronous metastases (P = 0.36); time to metastasis (P = 0.94); or overall survival (P = 0.36) (Figure 1A)
In the present study of 106 patients with pathogenic SDHB germline mutations, we found that the size of the primary tumor is an age-independent predictor of patient survival and metastases development in PGL
Summary
Succinate dehydrogenase subunit B (SDHB) mutations are associated with aggressive pheochromocytoma (PHEO)/paraganglioma (PGL) behavior, often resulting in metastatic disease and fatal outcomes. These tumors are often larger, extra-adrenal, and contain lower catecholamine concentrations than other hereditary PHEOs/PGLs. This study evaluated the size and age at diagnosis of primary SDHB-related PHEOs/PGLs as independent predictors of their metastatic behavior and outcome (survival). Mutations in succinate dehydrogenase subunit B (SDHB), first described by the pioneering work of Astuti et al in 2001 [3], have been linked to more aggressive tumor behavior, presenting with a higher metastatic rate than other PHEOs/PGLs [3,4,5,6,7]. In their study, the genetic background was not considered [12]
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