目的2004年,WHO将非典型垂体腺瘤分类为独特的腺瘤亚型。然而,这种区别的临床意义仍未确定。作者试图定义患者特征,肿瘤特征,以及与非典型垂体腺瘤相关的治疗结果。方法作者回顾了加州大学垂体腺瘤切除术患者的记录。旧金山,2007年至2014年。根据机构协议,表现出有丝分裂活性的腺瘤接受了所有3个非典型标记物的评估(有丝分裂指数,广泛的p53染色,MIB-1指数≥3%)。使用χ2、Fisher精确检验进行统计分析,t检验,log-rank,和逻辑回归。结果2007年至2014年,701例患者接受了垂体腺瘤切除术。在这些患者中,122腺瘤表现出有丝分裂活性,因此对所有3个非典型标记进行了评估,36个肿瘤(5%)被证明是不典型的。非典型队列中有21名女性患者(58%)和15名男性患者(42%),在非非典型队列中,313名女性患者(47%)和352名男性患者(53%)(p=0.231)。非典型队列中患者的平均年龄为37岁(范围为10-65岁),显著低于非非典型队列患者的平均年龄49岁(范围10-93岁)(p<0.001)。非典型腺瘤患者最常见的症状是头痛(42%)和视觉变化(33%)。与非非典型腺瘤(42%;p<0.001)相比,非典型腺瘤更可能是功能性的(78%)。功能性非典型腺瘤明显大于功能性非非典型腺瘤(平均直径2.2vs1.4cm;p=0.009),非功能性非典型腺瘤与非功能性非非典型腺瘤相比(平均直径3.3vs2.3cm;p=0.01)。在整个腺瘤队列中,较大的肿瘤大小与海绵窦浸润有关(p<0.001),在二项多变量回归分析中,次全切除与海绵窦侵犯(p<0.001)和较大体积(p<0.001)相关。非典型腺瘤的中位复发时间为56个月,功能性非非典型腺瘤129个月,非功能性非非典型腺瘤204个月(p<0.001)。功能性非典型腺瘤比功能性非非典型腺瘤复发更频繁且明显更早(p<0.001)。考虑到切除的程度,海绵窦侵入,尺寸,年龄,性别,和功能亚型,在功能性腺瘤中,非典型性仍是早期复发的重要预测因子(p=0.002).结论与非非典型垂体腺瘤相比,非典型腺瘤更可能出现在年龄较大的患者中,更常见的是荷尔蒙分泌过多,并与早期复发有关。除了离散的病理诊断外,这些特征还使非典型垂体腺瘤成为独特的临床实体。
OBJECTIVE In 2004, the WHO classified atypical pituitary adenoma as a distinct adenoma subtype. However, the clinical significance of this distinction remains undetermined. The authors sought to define patient characteristics, tumor features, and treatment outcomes associated with atypical pituitary adenoma. METHODS The authors reviewed records of patients who underwent resection of pituitary adenoma at the University of California, San Francisco, between 2007 and 2014. Per institutional protocol, adenomas exhibiting mitotic activity underwent evaluation for all 3 markers of atypicality (mitotic index, extensive p53 staining, and MIB-1 index ≥ 3%). Statistical analyses were performed using χ2, Fisher\'s exact test, t-test, log-rank, and logistic regression. RESULTS Between 2007 and 2014, 701 patients underwent resection for pituitary adenoma. Among these patients, 122 adenomas exhibited mitotic activity and therefore were evaluated for all 3 markers of atypicality, with 36 tumors (5%) proving to be atypical. There were 21 female patients (58%) and 15 male patients (42%) in the atypical cohort, and 313 female patients (47%) and 352 male patients (53%) in the nonatypical cohort (p = 0.231). The mean age of patients in the atypical cohort was 37 years (range 10-65 years), which was significantly lower than the mean age of 49 years (range 10-93 years) for patients in the nonatypical cohort (p < 0.001). The most common presenting symptoms for patients with atypical adenomas were headaches (42%) and visual changes (33%). Atypical adenomas were more likely to be functional (78%) than nonatypical adenomas (42%; p < 0.001). Functional atypical adenomas were significantly larger than functional nonatypical adenomas (mean diameter 2.2 vs 1.4 cm; p = 0.009), as were nonfunctional atypical adenomas compared with nonfunctional nonatypical adenomas (mean diameter 3.3 vs 2.3 cm; p = 0.01). Among the entire adenoma cohort, larger presenting tumor size was associated with cavernous sinus invasion (p < 0.001), and subtotal resection was associated with cavernous sinus invasion (p < 0.001) and larger size (p < 0.001) on binomial multivariate regression. The median time until recurrence was 56 months for atypical adenomas, 129 months for functional nonatypical adenomas, and 204 months for nonfunctional nonatypical adenomas (p < 0.001). Functional atypical adenomas recurred more frequently and significantly earlier than functional nonatypical adenomas (p < 0.001). When accounting for extent of resection, cavernous sinus invasion, size, age, sex, and functional subtype, atypicality remained a significant predictor of earlier recurrence among functional adenomas (p = 0.002). CONCLUSIONS When compared with nonatypical pituitary adenomas, atypical adenomas are more likely to present in younger patients at a larger size, are more often hormonally hypersecretory, and are associated with earlier recurrence. These features lend credence to atypical pituitary adenomas being a distinct clinical entity in addition to a discrete pathological diagnosis.