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

Abstract

Background: A staging/prognostic system has long been desired to better categorize pheochromocytoma/paraganglioma which can be very aggressive in the setting of SDHB mutations.

Methods: A retrospective analysis was conducted of clinical characteristics and outcomes including results of genetic testing, tumor recurrence/metastasis, Ki67/MIB1% staining, and tumor mitotic index in patients with pheochromocytoma/paraganglioma.

Results: Patients with SDHB mutation presented at younger age (33.0 years old vs 49.6 years old, P < .001), had increased local recurrence and distant metastases (47.6% vs 9.1%, P < .001, and 56.3% vs 9.1%, P < .001, respectively), and lesser median disease-free interval (89.8 months, 95% confidence interval 36.0-96.4 vs not reached, P < .001). SDHB mutation, greatest tumor diameter, and open operative resection were associated with a greater rate of local recurrence and distant metastases (P < .006 each). SDHB mutation and tumor diameter were independent risk factors for local recurrence (P ≤ .04 each) and metastases. Ki67% and mitotic index were not associated with SDHB mutation (P ≥ .09 each), local recurrence (P = .48, P = .066, respectively), metastases (P ≥ .22 each), or disease-free interval (P ≥ .19 each).

Conclusion: SDHB status and primary tumor size are more predictive of patient outcome than Ki67% or mitotic index and should be part of any clinically relevant, prognostic scoring system.

Figure 1

Representative histologic images. (Hematoxylin and Eosin stain (A&C) and Ki67% stain (B&D) (X20). (A, B) Tumor sample from a patient with SDHB mutation and metastatic PGL, Ki67 1–3%. (C, D) Tumor from a patient with sporadic PC and no recurrence, Ki67% over 3%.

Figure 2

Prognostic factors associated with disease-free interval (DFI). SDHB mutation status, PGL, and requiring an open surgical approach were significantly associated with decreased DFI. (A) SDHB mutation vs. no mutation. Median time of 89.8 months (95% CI: 36.0 – 96.4) vs. median not reached (p<0.001). (B) PGL vs. PC. Median not reached vs. 91.8 months (95% CI: 38.4 – 96.4, p=0.044). C) Open vs. laparoscopic (lap) surgical approach. Median time of 48.5 months (95% CI: 16.0 – 103.0) vs. median not reached (p<0.001). D) Nonfunctional (NF) vs. functional (FUN) tumor. Median time of 89.8 months (95% CI: 2 – 89.8) vs. 103.0 months (95% CI: 51.0 – undefined, p=0.11).

Figure 3

DFI and clinical and pathologic variables. Tumor diameter was significantly associated with decreased DFI, but not Ki67% or Mitotic Index. (A) Tumor diameter (TD) < 3.0 cm, 3.1 – 6.0, over 6.1 cm. Median not reached, vs. 95.4 months (95% CI: 48.5 – undefined), vs. 38.4 months (95% CI: 6.8 – undefined, p<0.001). (B) Ki67% was not associated with decreased DFI (p=0.69). (C) Mitotic index (MI) was not associated with decreased DFI (p=0.19).