Demopoulos R I, Jones K Y, Mittal K R, Vamvakas E C
Department of Ob-Gyn Pathology, New York University Medical Center, NY 10016, USA.
Int J Gynecol Pathol. 1997 Apr;16(2):131-7. doi: 10.1097/00004347-199704000-00008.
This study examined the histologic changes associated with administration of leuprolide acetate, a gonadotropin-releasing hormone agonist, in leiomyomata. Thirty-seven women treated with leuprolide acetate who subsequently underwent myomectomy or hysterectomy were matched by age (+/- 3 years), race, and uterine size (+/- 2 weeks) with untreated controls. Tissue samples of leiomyomata (four to 10 slides per patient) were examined "blinded" by two pathologists and evaluated for cellularity, edema, myxoid change, hyalinization, fibrosis, inflammation, infarction, and vascular changes (thrombosis, intimal fibrosis, thickening of the vessel wall with narrowing of the lumen, perivascular fibrosis). A matched case-control analysis was conducted for each morphologic characteristic. Cellularity, hyalinization, and fibrosis were graded as 1(+) versus 2(+); all other characteristics were graded as present or absent. The analysis showed that leuprolide acetate-treated leiomyomata had significantly increased hyalinization (p < 0.005) and decreased cellularity (p < 0.10) as compared with controls; there was also thickening of blood vessel walls with narrowing of the lumen (p < 0.01). A subgroup of leuprolide acetate-treated patients categorized as clinical responders (having > 30% reduction in tumor size) more frequently had thickening of vessel walls (p < 0.05) and vascular thrombosis (p < 0.10) than did nonresponders. Our data suggest that a leuprolide acetate-induced hypoestrogenic state may cause vasoconstriction, thickening of blood vessel walls, and thrombosis, leading to ischemia, hyalinization, and atrophy of the leiomyoma.
本研究检测了促性腺激素释放激素激动剂醋酸亮丙瑞林给药后在平滑肌瘤中所产生的组织学变化。37名接受醋酸亮丙瑞林治疗随后接受肌瘤切除术或子宫切除术的女性，在年龄（±3岁）、种族和子宫大小（±2周）方面与未治疗的对照组进行匹配。平滑肌瘤组织样本（每位患者4至10张玻片）由两名病理学家“盲法”检查，并评估细胞密度、水肿、黏液样变、玻璃样变、纤维化、炎症、梗死以及血管变化（血栓形成、内膜纤维化、血管壁增厚伴管腔狭窄、血管周围纤维化）。针对每种形态学特征进行匹配的病例对照分析。细胞密度、玻璃样变和纤维化分为1（+）与2（+）；所有其他特征分为存在或不存在。分析显示，与对照组相比，醋酸亮丙瑞林治疗的平滑肌瘤玻璃样变显著增加（p<0.005），细胞密度降低（p<0.10）；血管壁也有增厚伴管腔狭窄（p<0.01）。在醋酸亮丙瑞林治疗的患者亚组中，被归类为临床反应者（肿瘤大小缩小>30%）比无反应者更频繁地出现血管壁增厚（p<0.05）和血管血栓形成（p<0.10）。我们的数据表明，醋酸亮丙瑞林诱导的低雌激素状态可能导致血管收缩、血管壁增厚和血栓形成，进而导致平滑肌瘤缺血、玻璃样变和萎缩。
