CHARACTERISTICS AND OUTCOMES OF METASTATIC SDHB AND SPORADIC PHEOCHROMOCYTOMA/PARAGANGLIOMA: AN NATIONAL INSTITUTES OF HEALTH STUDY

Abstract

Objective: Overall about 10 to 20% of pheochromocytomas/paragangliomas (PHEOs/PGLs) are metastatic, with higher metastatic potential observed in succinate dehydrogenase subunit B/fumarate hydratase (SDHB/FH)-related tumors. Due to the improved availability of biochemical and genetic testing and the frequent use of anatomical/functional imaging, there is currently a higher detection rate of metastatic PHEO/PGL.

Methods: A retrospective analysis of 132 patients (27 children, 105 adults) with metastatic PHEO/PGL diagnosed and treated from 2000 to 2014 was conducted.

Results: Seventy-seven (58%) males and 55 (42%) females were included; 39 (30%) have died, with no sex preference. Seventy-three (55%) patients had SDHB mutations; 59 (45%) patients had apparently sporadic tumors (AST). SDHB patients had an average age at primary tumor diagnosis of 31 ± 16 years compared to 40 ± 15 years in AST patients (P<.001). The average metastatic interval (MI) decreased with increasing age in both SDHB and AST patients (P = .013 for both). Only 16% of all primary tumors were smaller than 4.5 cm. Eleven percent of patients had biochemically silent disease, more with SDHB. Of SDHB patients, 23% had metastatic tumors at first diagnosis, compared to 15% of AST patients. Five- and 10-year survival rates were significantly better for metastatic AST than SDHB patients (P = .01). Overall survival was significantly different between children and adults (P = .037); this was mostly attributed to the SDHB patients, in whom children had statistically significantly longer survival than adults (P = .006). The deceased patients all died due to the PHEO/PGL and mainly had noradrenergic phenotypes.

Conclusion: In children, metastatic PHEOs/PGLs are mainly due to SDHB mutations; in adults they are equally distributed between in SDHB mutations and AST, with better 5- and 10-year survival rates for ASTs. In SDHB patients, children survive longer than adults. Primary metastatic tumors, most presenting as noradrenergic PGLs, are larger than 4.5 cm in >80% of patients. The frequency of metastatic tumors from primary AST increases with age, including a decreased MI compared to SDHB tumors. These results support several recommendations that are summarized in the Discussion.

Fig. 1.

(A) Kaplan-Meier survival curves of 73 patients with SDHB mutations and 59 patients with AST; there was a statistically significant difference in survival between patients with SDHB mutations and those with AST (P = .006). (B) Kaplan-Meier survival curves for SDHB versus AST patients, divided by sex. No statistically significant difference in survival probability was seen between males and females in either the AST or SDHB groups (AST: P = .349, SDHB: P = .272) (C) Kaplan-Meier survival curves for children (0–19 years) versus all adults (age 20 or older). Overall survival was significantly different between children and adults (P = .037). AST = apparently sporadic tumors; SDHB = succinate dehydrogenase subunit B. D. Kaplan-Meier survival curves for children (0-19 years) versus all adults (age 20 or older).

Fig. 1.

(A) Kaplan-Meier survival curves of 73 patients with SDHB mutations and 59 patients with AST; there was a statistically significant difference in survival between patients with SDHB mutations and those with AST (P = .006). (B) Kaplan-Meier survival curves for SDHB versus AST patients, divided by sex. No statistically significant difference in survival probability was seen between males and females in either the AST or SDHB groups (AST: P = .349, SDHB: P = .272) (C) Kaplan-Meier survival curves for children (0–19 years) versus all adults (age 20 or older). Overall survival was significantly different between children and adults (P = .037). AST = apparently sporadic tumors; SDHB = succinate dehydrogenase subunit B. D. Kaplan-Meier survival curves for children (0-19 years) versus all adults (age 20 or older).

Fig. 1.

(A) Kaplan-Meier survival curves of 73 patients with SDHB mutations and 59 patients with AST; there was a statistically significant difference in survival between patients with SDHB mutations and those with AST (P = .006). (B) Kaplan-Meier survival curves for SDHB versus AST patients, divided by sex. No statistically significant difference in survival probability was seen between males and females in either the AST or SDHB groups (AST: P = .349, SDHB: P = .272) (C) Kaplan-Meier survival curves for children (0–19 years) versus all adults (age 20 or older). Overall survival was significantly different between children and adults (P = .037). AST = apparently sporadic tumors; SDHB = succinate dehydrogenase subunit B. D. Kaplan-Meier survival curves for children (0-19 years) versus all adults (age 20 or older).

Fig. 1.

(A) Kaplan-Meier survival curves of 73 patients with SDHB mutations and 59 patients with AST; there was a statistically significant difference in survival between patients with SDHB mutations and those with AST (P = .006). (B) Kaplan-Meier survival curves for SDHB versus AST patients, divided by sex. No statistically significant difference in survival probability was seen between males and females in either the AST or SDHB groups (AST: P = .349, SDHB: P = .272) (C) Kaplan-Meier survival curves for children (0–19 years) versus all adults (age 20 or older). Overall survival was significantly different between children and adults (P = .037). AST = apparently sporadic tumors; SDHB = succinate dehydrogenase subunit B. D. Kaplan-Meier survival curves for children (0-19 years) versus all adults (age 20 or older).