The size of the primary tumor and age at initial diagnosis are independent predictors of the metastatic behavior and survival of patients with SDHB-related pheochromocytoma and paraganglioma: a retrospective cohort study

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.

SDHB mutation status and tumor size but not tumor grade are important predictors of clinical outcome in pheochromocytoma and abdominal paraganglioma

“…7,16 The association of the primary tumor size with locoregional recurrence and distant metastases is also consistent with other studies. 9,17 Our finding that SDHB mutation status and primary tumor size are more predictive of patient outcomes than Ki67% or MI suggests that histologic-based grading systems may not be as useful. We found that Ki67% and MI are not associated with locoregional recurrence or distant metastases, nor were they associated with SDHB mutation status and shorter DFI.…”

“…Studies on prognostic factors associated with PC/PGL have shown the presence of SDHB mutation, primary tumor size, and age at diagnosis to be significant prognostic factors. 9 Previously described staging systems based on pathologic data, such as the pheochromocytoma of the adrenal gland scaled score (PASS), have been shown to be associated with patient outcome in small cohort studies but have not been validated. 10–14 The grading system for adrenal PC and PGL (GAPP), utilizing pathology findings to create a scoring system, has also been proposed, as it was associated with patient outcome in one study.…”

Leptomeningeal dissemination of a low-grade lumbar paraganglioma: case report

“…20 The most commonly mutated susceptibility gene associated with pheochromocytomas and paragangliomas is succinate dehydrogenase subunit B (SDHB), which also carries the highest risk of malignancy. 20,22 In patients with SDHB mutations, primary tumor size has been found to be an age-independent predictor of patient survival and metastasis. 22 Age at diagnosis has also been found in these patients to be a size-independent predictor of patient survival.…”

“…20,22 In patients with SDHB mutations, primary tumor size has been found to be an age-independent predictor of patient survival and metastasis. 22 Age at diagnosis has also been found in these patients to be a size-independent predictor of patient survival. 22 Thus, in order to achieve the best possible clinical outcome, patients discovered to have any SDHB mutation are recommended to undergo genetic counseling 24 and early and regular evaluations for the development of PCC/PGL.…”

18F-FLT PET/CT in the Evaluation of Pheochromocytomas and Paragangliomas: A Pilot Study

“…Classical indicators of poor prognosis include: SDHB mutation, tumor size > 5 cm, tumor location (extra-adrenal), age < 30 years at first presentation, and metastatic disease (9-11). Recently, some new studies have proposed to predict metastatic potential and/or tumor aggressiveness using characteristics such as a dopaminergic phenotype (i.e.…”