肾上腺髓质内、外嗜铬细胞瘤181例与多发性内分泌肿瘤的临床病理资料分析

Pheochromocytomas in adrenal medulla or extra-adrenal and multiple endocrine neoplasms： a clinicopathologic analysis of 181 cases

目的分析肾上腺髓质内、外嗜铬细胞瘤与多发性内分泌肿瘤2型（MEN2）的发病变化，探讨它仃J在临床症状、体征、病理变化方面的异同点和相互关系。方法运用游程检验、方差分析、t检验、χ2检验，对天津医科大学总医院病理科1993—2008年181例肾上腺髓质内、外嗜铬细胞瘤（根据世界卫生组织《内分泌器官肿瘤病理学和遗传学2004年版》分别将其分为良性、恶性倾向、恶性病变3组）及伴MEN2的检出率、构成比、平均诊断年龄、性别比例及临床表现、病理变化进行统计学分析。结果16年外检总数167702例，肾上腺疾病、肾上腺髓质内、外嗜铬细胞瘤的例数（外检率）分别是910例（0．54％）、139例（0．08％）、42例（0．03％），其中嗜铬细胞瘤的良性、恶性倾向、恶性3组的例数（构成比）在肾上腺髓质内分别是102例（73．4％）、29例（20．9％）、8例（5．7％），102例良性病变中伴MEN2者共8例（7．8％）；在肾上腺髓质外分别是18例（42．8％）、12例（28．6％）、12例（28．6％）。16年间肾上腺疾病、肾上腺髓质内、外嗜铬细胞瘤及良性病变伴MEN2的检出率和构成比及嗜铬细胞瘤的良性、恶性倾向、恶性3组的构成比均无变化趋势（P〉0．05），并随病变恶性度的增加逐渐由女性多见转变为男性多见的发病规律。嗜铬细胞瘤患者总平均诊断年龄存髓质内良性组、恶性倾向组分别为42．7和40．1岁，均低于恶性组患者的51．6岁。髓质外良性组、恶性倾向组分别为43．1和45．2岁，均高于恶性组的37．8岁（P〈0．05）。恶性病变患者中，髓质内的发病年龄（51．6岁）明显高于髓质外（37．8岁，P〈0．05）；伴MEN2患者只见于患肾上腺髓质内良性嗜铬细胞瘤的女性，其平均诊断年龄（38．9岁）低于良性病变（42．7岁），而且甲状腺髓样癌的发生均早于肾上腺髓质内嗜铬细胞瘤。肾上腺髓质内、外嗜铬细胞瘤患者均显示恶性病变伴有高血压症状者的比例较良性、恶性倾向者明显下降（P〈0．05）。仪肾上腺髓质内嗜铬细胞瘤发生双侧病变，其中恶性病变（2／8）的发生率明显高于良性（15．7％）、恶性倾向（6．9％）。复发病变在肾上腺髓质内、外嗜铬细胞瘤的比例均随良性（11．8％，0）、恶性倾向（13．8％，25％）、恶性（33．3％，37．5％）的病变恶性度的上升l而逐渐增加。肾上腺髓质内、外嗜铬细胞瘤体积平均直径亦随良性（4．2、4．0cm）、恶性倾向（5．3、5．6cm）、恶性病变（7．3、6．9cm）的恶性度上升而逐渐增大（P〈0．05）。结论肾上腺髓质内、外嗜铬细胞瘤良性、恶性倾向、恶性病变3组的临床表现与病理变化密切相关，确切的病变类型和肿瘤性质仍要由病理学检查确定。

Objective To analyze the change in the incidence of pheochromocytomas in adrenal medulla or extra-adrenal and multiple endocrine neoplasm type 2 （ MEN2 ）, to summarize the clinical characteristics of benign, potentially malignant and malignant pheochromocytomas and to investigate the correlation between clinical raanifestations and pathological changes. Methods Statistic analysis was performed to detect the incidence, constituent ratio, mean diagnostic age, sex proportion and correlation hetween clinical manifestions and pathologic： changes in pheochromocytomas in adrenal medulla or extraadrenal gland and MEN2 from 1993 to 2008 in the Department of Pathology, the General Hospital of Tianjin Medical University with Runs test, ANOVA, t test and chi-square test. Results The total number of biopsies within the 16 years was 167 702 cases （average 10 481 eases per year）. The numbers （detectable rate） of total adrenal diseases, pheoehromocytomas in adrenal medulla and extra-adrenal glands were 910 （0. 54% ）, 139（0. 08% ） , and 42 （0. 03% ） cases, respectively. The numbers （ constituent ratio） of benign, potentially malignant and nmlignant of pheochromocytomas in adrenal medulla were 102 cases （73.4%）, 29 cases （20. 9% ） and 8 cases （5.7%）, respectively; in the 102 cases of benign tumors, patients with MEN2 were 8 （7. 8% ） ; the three groups of the tumors in extra-adrenal sites were 18（42. 8% ） cases, 12 （28.6%） cases and 12 （28.6%） cases. There were no changes in the detectable rate and constituent ratio of adrenal diseases, benign, potential malignant and malignant pheochromocytomas in adrenal medulla or extra-adrenal glands and patients with MEN2 during the past 16 years （P 〉 0.05 ） , but there was a tendency that malignant transformation was gradually increased with age, which was more commonly found in male patients than females. The mean age at diagnosis of patients with benign and potentially malignant pheochromocytomas was 42.7 years （ranged from 10-74 years）, and 40. 1 years （13- 66 years）, respectively, which were younger than patients with malignant pheochromocytomas （51.6 years, P 〈 0.05 ） ; the mean age of patients with benign and potentially malignant pheochromocytomas in extraadrenal sites was 43.1 years （ranged from 20-75 years） and 45.2 years （28-65 years） that were older than those with malignant （37.8 years, ranged from 14-58 years,P 〈 0. 05 ）. It was spectacular that patients with malignant pheochromocytoma in adrenal medulla （51.6 years） were older than that in extra-adrenal sites （37.8 years） ; all the patients with MEN2 were female benign pheochromocytoma in adrenal medulla, whose age （38.9 years ） was younger than that of benign lesions （ 42.7 years, P 〈 0. 05 ）, in which thyroid medullaly carcinoma appeared early than pheochromocytomas in adrenal medulla. The detectable rate of hypertension in patients with malignant pheochromocytomas in adrenal medulla and in extra-adrenal sites were less than that in benign and potentially malignant ones （ P 〈 0.05 ）. The bilateral lesions more commonly found in malignant pheochromocytoma （25.0%） than benign （15.7%） and potentially malignant pheochromocytomas （6. 9% ） only in adrenal medulla. Relapse rates in both adrenal and extra-adrenal tumors were rising from benign （ 11.8%, 0）, potentially malignant （ 13.8%, 25.0% ）, to malignant （33.3%, 37.5% ） groups; the average diameter of pheochromocytomas in both adrenal and extra-adrenal sites was increasing from benign （4. 2 era, 4. 0 cm）, potentially malignant （5.3 cm, 5.6 cm） to malignant （7.3 cm, 6.9 cm） groups （ P 〈 0.05 ）. Conclusions The diagnostic criteria of benign, potentially malignant and malignant pheochromoeytomas in adrenal medulla and in extra-adrenal sites are well established according to the WHO classification of endocrine tumors （2004）. The closer relationship is found between clinical manifestations and pathologic changes. The definite type and nature of pheochromocytomas are mainly rested upon the pathologic examination.