Introduction: Pheochromocytoma and paraganglioma (PPGL), a relative rare neuroendocrine tumor, was re-classified as a malignant tumor according to WHO Classification of Endocrine Organs in 2017 due to its metastatic potential. The review article in 2019 from New England Journal of Medicine stated succinate dehydrogenase B (SDHB) mutation was associated with metastasis. Grading System for Adrenal Pheochromocytoma and Paraganglioma (GAPP) was proposed in 2014, with Ki-67 index of 1% and 3% as scoring parameters for predicting metastasis. However, the cut-off value differs across studies and remains questionable. Furthermore, there is no other demographic variable reported for metastasis prediction. Therefore, we aimed to analyze the disease and to find predictive factors for metastasis.
Methods: Patients diagnosed with PPGL from 2010 to 2019 were reviewed retrospectively in single institute. Demographic data, including classical symptoms of sympathetic nervous system hyperactivity were recorded, together with biochemistry related to pheochromocytoma (vanillylmandelic acid, catecholamine) and pathological features including tumor size, Ki-67 proliferation index, SDHB mutation and disease metastasis. Both descriptive and comparative statistical analyses were performed.
Results: Among total 89 patients included, 47 (52.8%) were male, with the mean age of 52.6 ± 12.8 and BMI of 23.9 ± 3.9 kg/m2 at diagnosis. The mean follow-up duration was 34.2 months, and 12 (13.5%) patients were observed with disease metastasis. Comparing metastasis group with non-metastasis group, most of the demographic data, clinical presentation, vanillylmandelic acid, catecholamine and tumor characteristics were not statistically different. But in gender, male appears as a risk for develop metastasis (p=0.03). In pathological features, tumor size and SDHB mutation (n=1, p=0.140) did not reach statistical significance. As for Ki-67 index, significantly higher value was noted in metastasis group (2.2 ± 2.1 vs. 8.6 ± 6.2, p<0.001). By multivariate logistic regression, Male gender (OR = 7.674, 95% CI = 1.286 - 45.797; p=0.025) and Ki-67 index with cutoff at 5% (OR = 17.275, 95% CI = 3.786 - 78.834, p<0.001) were independent risk factors for metastasis.
Conclusions: In contrast to previous literature and scoring parameters, our results showed higher Ki-67 index in PPGL patients, with greater cutoff value of 5% as a significant predictor for metastasis. Moreover, male gender could also be an independent risk factor for metastatic potential in patients with PPGL.