Division of Anatomic Pathology, Mayo Clinic, Rochester, MN, USA.
Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic, Rochester, MN, USA.
Pituitary. 2021 Apr;24(2):192-206. doi: 10.1007/s11102-020-01096-2. Epub 2020 Oct 19.
Growth hormone-producing pituitary adenomas are divided into two clinically relevant histologic subtypes, densely (DG-A) and sparsely (SG-A) granulated. Histologic subtype was evaluated in a large cohort of patients with acromegaly, separating DG-A and SG-A, and correlated with clinicopathological characteristics.
Patients with acromegaly undergoing surgery as initial therapy between 1995 and 2015 were identified. Histologic subtype was determined by keratin expression pattern with CAM5.2 and correlated with clinical and imaging parameters, somatostatin receptor subtype 2 (SST2) expression, post-surgical remission rate, and application of a prognostic scoring system incorporating proliferation and invasiveness.
One hundred thirty-one patients were included. Tumors were classified as DG-A (75, 57.3%), SG-A (29, 22.1%), intermediate (I-A) (9, 6.9%), and unclassified (18, 13.7%) when CAM5.2 was negative. DG-A and I-A were combined for analysis (DG/I-A) and compared to SG-A. Age, gender, proliferation, and post-surgical remission did not differ. SG-A were larger [2 vs. 1.5 cm (median), p = 0.03], more frequently invasive [65.5% vs. 32.9%, p = 0.004], associated with higher MRI T2-weighted signal ratio [1.01 vs. 0.82 (median), p = 0.01], showed lower SST2 expression (p < 0.0001), and scored higher in the prognostic classification (p = 0.004). Surgical remission occurred in 41.7% DG/I-A and 41.4% SG-A (p = 1.0). On multivariate analysis, absence of invasion (p = 0.009) and lower pre-operative IGF-1 index (p = 0.0002) were associated with post-surgical remission.
CAM5.2 allowed distinction between DG/I-A and SG-A in most but not all cases. Histologic subtype did not predict surgical outcome. Absence of invasion and lower pre-operative IGF-1 index were the only significant predictors of post-surgical remission in this cohort.
生长激素分泌型垂体腺瘤分为两种具有临床意义的组织学亚型，致密颗粒（DG-A）和稀疏颗粒（SG-A）。本研究在一组大型肢端肥大症患者中评估了组织学亚型，将 DG-A 和 SG-A 分开，并与临床和影像学特征相关联。
确定了 1995 年至 2015 年间接受初始手术治疗的肢端肥大症患者。通过 CAM5.2 检测角蛋白表达模式来确定组织学亚型，并将其与临床和影像学参数、生长抑素受体亚型 2（SST2）表达、术后缓解率以及应用包含增殖和侵袭性的预后评分系统相关联。
共纳入 131 例患者。当 CAM5.2 为阴性时，肿瘤被分为 DG-A（75 例，57.3%）、SG-A（29 例，22.1%）、中间型（I-A）（9 例，6.9%）和未分类（18 例，13.7%）。当将 DG-A 和 I-A 合并分析（DG/I-A）时，与 SG-A 相比，两者的年龄、性别、增殖和术后缓解率均无差异。SG-A 更大[2 厘米与 1.5 厘米（中位数），p=0.03]，侵袭性更高[65.5%与 32.9%，p=0.004]，MRI T2 加权信号比值更高[1.01 与 0.82（中位数），p=0.01]，SST2 表达更低（p<0.0001），预后分类评分更高（p=0.004）。DG/I-A 和 SG-A 的手术缓解率分别为 41.7%和 41.4%（p=1.0）。多变量分析显示，无侵袭性（p=0.009）和较低的术前 IGF-1 指数（p=0.0002）与术后缓解相关。
CAM5.2 可在大多数但并非所有情况下将 DG/I-A 与 SG-A 区分开来。组织学亚型与手术结果无关。无侵袭性和较低的术前 IGF-1 指数是该队列中术后缓解的唯一显著预测因素。
