嗜铬细胞瘤/副神经节瘤2017版WHO肾上腺肿瘤分类下临床病理再评价的单中心研究

Reevaluation of Clinicopathology of Pheochromocytoma and Paraganglioma Based on Update on Adrenal Tumours in 2017 World Health Organization(WHO) of Endocrine Tumours:A Single Center Study

目的:探讨在2017版世界卫生组织肾上腺肿瘤新分类标准下嗜铬细胞瘤(pheochromocytoma,PHEO)/副神经节瘤(paraganglioma,PGL)的临床病理特点等方面的差异,为提高临床上对PHEO/PGL的认识提供相关参考,进一步评价新版分类标准下肾上腺嗜铬细胞瘤和副神经节瘤分级系统(the grading system for adrenal phaeochromocytoma and paraganglioma,GAPP)评分系统的临床应用价值。方法:回顾性收集2008年7月至2018年12月青岛大学附属医院泌尿外科收治的行手术治疗并经术后病理确诊的PHEO/PGL患者306例,将306例PHEO/PGL患者按照2017版WHO肾上腺肿瘤新分类标准进行重新分类,比较PHEO/PCL的临床表现、病理特点、实验室检查等方面的差异。采用Spearman秩相关分析苯乙醇胺N-甲基转移酶(phenylethanolamine N-methyltransferase,PNMT)免疫组化染色定性结果与GAPP评分之间的相关性。结果:306例PHEO/PGL患者中,有高血压症状者244例(79. 74%),具有典型三联征(头痛、心悸、多汗)表现者76例(24. 84%);PGL患者持续性高血压症状的比例和体重减轻的发生率高于PHEO患者(均P <0. 05)。PGL患者的去甲肾上腺素水平高于PHEO患者,差异有统计学意义(P <0. 05)。306例PHEO/PGL患者的GAPP评分为(3. 3±1. 8)分,其中高分化74例(24. 18%)、中分化189例(61. 76%)、低分化43例(14. 05%)。PGL患者的GAPP评分高于PHEO患者[(3. 5±1. 7)分vs(3. 0±1. 9)分],差异有统计学意义(P <0. 05);肾上腺病理评估方面,PGL患者的血管/包膜侵犯率(18. 9%vs 3. 9%)、分泌去甲肾上腺素的比例(44. 6%vs30. 2%)明显高于PHEO患者,分泌肾上腺素的比例更低(18. 9%vs 37. 9%),差异有统计学意义(均P <0. 05)。PHEO及PGL患者的GAPP评分均与PNMT免疫组化定性评分之间存在负相关。结论:PHEO/PGL患者多数伴有高血压症状,PGL的去甲肾上腺素水平高于PHEO,PGL的GAPP评分高于PHEO,PHEO、PGL患者的GAPP评分与PNMT免疫组化定性评分之间均存在负相关关系。

Objective: To discuss clinicopathological differences between pheochromocytoma(PHEO) and paraganglioma(PGL) based on findings for the adrenal tumours in the fourth edition of the World Health Organization(WHO) classification of endocrine tumours,provide relevant references for the improvement in the clinical understanding of PHEO or PGL,and evaluate the clinical application value of the grading system for adrenal phaeochromocytoma and paraganglioma(GAPP)based on new classification criteria. Methods: Data of 306 patients with PHEO or PGL admitted to the Department of Urology at the Affiliated Hospital of Qingdao University from July 2008 to December 2018 were collected retrospectively. Patients with PHEO or PGL were reclassified according to update on adrenal tumours in 2017 World Health Organization(WHO) of Endocrine Tumours. Differences between PHEO and PGL were compared in terms of clinical manifestations,pathological features,laboratory examination. Spearman rank correlation was used to analyze the correlation between qualitative scores of immunohistochemical staining of phenylethanolamine N-methyltransferase(PNMT) and GAPP scores. Results: Among 306 patients with PHEO or PGL,244(79. 74%) had hypertension symptoms,76(24. 84%) had three typical signs and symptoms of Whipple’s disease(headache,palpitation,hyperhidrosis). Proportion of persistent hypertension symptoms and incidence of weight loss in patients with PGL were higher than those in patients with PHEO(P < 0. 05). Norepinephrine(NE)levels in patients with PGL were higher than those in patients with PHEO(P < 0. 05). The average GAPP score of 306 patients with PHEO or PGL was(3. 3 ± 1. 8). Among them,74(24. 18%) were highly differentiated,189(61. 76%) were moderately differentiated and 43(14. 05%) were poorly differentiated. The average GAPP score of patients with PGL was significantly higher than that of patients with PHEO [(3. 5 ± 1. 7) vs(3. 0 ± 1. 9),P < 0. 05]. Pathological results of adrenal gland showed that incidence of vascular/capsular invasion rate(18. 9% vs 3. 9%) and that of NE secretion(44. 6% vs30. 2%) in patients with PGL were significantly higher than those in patients with PHEO,and incidence of adrenaline secretion in the former was significantly lower than that in the latter(18. 9% vs 37. 9%,P < 0. 05). There was a negative correlation between GAPP scores and qualitative scores of immunohistochemical staining of PNMT in patients with PHEO or PGL(P < 0. 05). Conclusion: Most of PHEO or PGL patients had hypertension symptoms. NE levels and the average GAPP score in patients with PGL was higher than those in patients with PHEO. There was a negative correlation between GAPP scores and qualitative scores of immunohistochemical staining of PNMT in patients with PHEO or PGL.