OBJECTIVETo 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 manifestations and pathological changes.

METHODSStatistic analysis was performed to detect the incidence, constituent ratio, mean diagnostic age, sex proportion and correlation between clinical manifestions and pathologic changes in pheochromocytomas in adrenal medulla or extra-adrenal 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.

RESULTSThe total number of biopsies within the 16 years was 167 702 cases (average 10 481 cases per year). The numbers (detectable rate) of total adrenal diseases, pheochromocytomas 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 malignant 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 extra-adrenal 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 medullary 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 cm, 4.0 cm), potentially malignant (5.3 cm, 5.6 cm) to malignant (7.3 cm, 6.9 cm) groups (P < 0.05).

CONCLUSIONSThe diagnostic criteria of benign, potentially malignant and malignant pheochromocytomas 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.