Hague K, Post K D, Morgello S
Department of Pathology, Mt. Sinai School of Medicine, New York, New York 10029, USA.
Surg Neurol. 2000 Jan;53(1):77-81. doi: 10.1016/s0090-3019(99)00159-7.
Pituitary surgery is the standard treatment for Cushing's disease but is complicated by a recurrence rate that ranges from 5.9 to 27%. Whereas some recurrences may be due to technical or anatomical factors resulting in subtotal resection of adenoma, clinical relapse after total tumor resection is a well-documented occurrence. The factors leading to such recurrences are unknown.
With the hypothesis that the pathology of the nontumoral adenohypophysis is important in predicting relapse, we undertook a study to determine if the absence of Crooke's change (CC), thought to be an indicator of nontumoral corticotroph inhibition, was associated with unexpected clinical recurrence. Twenty-one patients with Cushing's disease, with gross total resection of intrasellar corticotroph microadenoma, were reviewed independently by 2 neuropathologists for the presence of CC in adjacent adenohypophysis. All tumors were stained with H&E, PAS/orange-G and immunohistochemistry for ACTH. Clinical relapse was determined by chart reviews and defined as serum ACTH > 15 pg/ml, clinically Cushingoid, and/or radiographic evidence of recurrent tumor.
Seven of 21 patients recurred; 3 did not have CC in their initial resection specimen. All 3 of these patients had unexpected recurrences at 6 to 48 months post-op. Two patients with CC recurred at one year follow-up, 1 after 4 years and 1 after 5 years. All specimens from patients with long-term cure (follow-up from 9-72 months) contained CC. In this study, the absence of CC in peritumoral adenohypophysis was associated with unexpected recurrence of Cushing's disease (p = 0.0214).
We conclude that absence of CC in peritumoral adenohypophysis may be of some assistance in predicting recurrence of Cushing's disease after adequate resection of intrasellar microadenoma.
垂体手术是库欣病的标准治疗方法，但存在5.9%至27%的复发率，这使其变得复杂。虽然一些复发可能是由于技术或解剖因素导致腺瘤次全切除，但肿瘤全切除后临床复发也是有充分记录的情况。导致这种复发的因素尚不清楚。
基于非肿瘤性腺垂体的病理在预测复发中很重要这一假设，我们开展了一项研究，以确定被认为是非肿瘤性促肾上腺皮质激素细胞抑制指标的克鲁克改变（CC）缺失是否与意外的临床复发相关。21例库欣病患者，其蝶鞍内促肾上腺皮质激素细胞微腺瘤已进行了大体全切，由2名神经病理学家独立检查相邻腺垂体中CC的存在情况。所有肿瘤均用苏木精和伊红染色、过碘酸雪夫氏/橘黄G染色以及促肾上腺皮质激素免疫组化染色。通过查阅病历确定临床复发，定义为血清促肾上腺皮质激素>15 pg/ml、临床库欣样表现和/或肿瘤复发的影像学证据。
21例患者中有7例复发；其中3例患者的初始切除标本中没有CC。这3例患者均在术后6至48个月出现意外复发。2例有CC的患者在1年随访时复发，1例在4年后复发，1例在5年后复发。所有长期治愈患者（随访9至72个月）的标本均含有CC。在本研究中，肿瘤周围腺垂体中CC的缺失与库欣病的意外复发相关（p = 0.0214）。
我们得出结论，肿瘤周围腺垂体中CC的缺失可能有助于预测蝶鞍内微腺瘤充分切除后库欣病的复发。
