Clinicopathological Features,the Expression Of SDHx And Prognostic Factors Of Paraganglioma

Objective Paraganglioma(PGL)is a rare neuroendocrine tumor derived from the paraganglion.The clinical symptoms are atypical and the preoperative diagnosis rate is low in this tumor.The biological behavior of the tumor can not be judged by a single index,and the recurrence and metastasis can still occur a few years or even more after the operation.SDH germline mutation is the most common gene mutation in pheochromocytoma and paraganglioma(PPGL),but the relationship between the expression of succinate dehydrogenase(SDHx)and the prognosis of PGL is not completely clear.The purpose of this study is to comprehensively analyze the relationship between the clinical characteristics,pathological characteristics,expression of SDHx and Ki-67 index and the prognosis of paraganglioma(PGL).This study aims to improve the understanding of PGL and provide evidence for clinical treatment and prognosis evaluation.Methods The clinical and pathological characteristics of 96 cases of PGL diagnosed pathologically from the Affiliated Hospital of Qingdao University between January 2008 and December 2018 were retrospectively reviewed,including age,sex,symptoms,blood pressure,location,maximum diameter of tumor,necrosis,invasion of surrounding tissues,metastasis,recurrence or death,and other pathological descriptions.The patients were followed up and the follow-up date was as of December 30,2021.The expression of SDHAF2,SDHB,SDHD and Ki-67 in PGL were detected by immunohistochemistry,For SDH deletion cases,we further studied the expression of the main signal molecules of hypoxia signal pathway or kinase activation pathway,including FH,PTEN,p53 and so on.The operation cases were judged by modified GAPP score.Analyzing the differences in various factors of PGL between abdomen and head and neck.Univariate and multivariate survival analysis was used to test the relationship between gender,age,history of hypertension,intraoperative sudden rise of blood pressure,clinical symptoms,maximum diameter of the tumor,modified GAPP score,mitosis number / 10 HPF,expression status of SDHx,invasion of envelope or vascular,invasion of surrounding tissue,necrosis,Ki-67 index and progression-free survival.Results Of the 96 patients,49 was male and 47 was female,The age ranged from 10 to 77 years,with an average age of 49.9 ± 12.6 years.57 was located in the abdomen,22 was located in head and neck and 17 was located in other parts.38 cases were found by health examination and 58 cases had symptoms and signs,of which 4 cases had typical "triple sign",29 cases were accompanied by hypertension,intraoperative blood pressure increased sharply in 15 cases.PGL showed round or quasi-round soft tissue shadows in the imaging manifestations,30 cases were diagnosed by imaging,and the diagnostic rate was 31.3%.91 cases were surgical specimens and 5 cases were biopsy specimens,The maximum diameter of the tumor was 0.5～18.5cm,with a median of 4.5cm.Pathologically,the tumor cells showed typical zellballen pattern composed of main cells and sustentacular cells,in some cases,irregular zellballen pattern,pseudorosette pattern,comedo necrosis,invasion of vascular or capsular and invasion of surrounding tissue could be seen.of the 91 surgical specimens,the modified GAPP score was≤4 in 57 cases and>4 in 34 cases.SDHAF2-negative immunoreactivity were 2 cases,SDHB-negative immunoreactivity were 10 cases,SDHD-negative immunoreactivity were 8 cases and SDHx-negative immunoreactivity were 19 cases in total,there were 55 cases with low expression of Ki-67.The 19 cases with defective expression of SDHx were all FH(+),p53(-)and PTEN(-).5 cases recurred,2cases metastasized and 7 cases died after the operation,the progression-free survival time was 3～153 months,with a median of 60 months.It was found significant differences between PGL in abdomen and head and neck in size,hypertension symptoms,suggestive effect of imaging on tumor,necrosis,invasion of vascular or capsule,invasion of surrounding tissue and modified GAPP score(X~2=3.881～36.085,P<0.05～0.001)by statistical treatment,univariate analysis showed that modified GAPP score>4,defective expression of SDHx and necrosis(X~2=4.355～14.976,P<0.05～0.001)were essential factors in the progression-free survival of patients with PGL.Age≤40 years old,modified GAPP score > 4,defective expression of SDHx,necrosis and Ki-67 index ≥ 3%(X~2=4.216～22.334,P<0.05～0.001)were essential factors in the progression-free survival of patients with abdominal PGL.multivariate analysis showed that SDHx expression deficiency was independent risk factors for progression-free survival of patients with PGL(P=0.007)and abdominal PGL(P=0.020).Conclusion The clinical and pathological characteristics and biological behavior are different in different parts of PGL,abdominal PGL is more prone to happen hypertension,large tumor volume,necrosis,invasion of blood vessels or capsule and surrounding tissues and high modified GAPP score than PGL of head and neck.Defective SDHx expression and necrosis are independent risk factors for the progression-free survival of patients with PGL.Immunohistochemical detection of the expression of SDHx may play an essential role in evaluating the prognosis of PGL.