Abstract：
Gestational endometrium can demonstrate a spectrum of atypical but benign changes. One such lesion is localized endometrial proliferation of pregnancy (LEPP), first described in a series of 11 cases. To understand its biological and clinical importance, we explore the pathologic, immunophenotypic, and molecular features of this entity. Nine cases of LEPP identified in 15 years were retrieved from departmental archives and reviewed. Immunohistochemistry and next-generation sequencing using a comprehensive 446-gene panel were performed when the material was available. Eight cases were identified in curettage specimens performed after first-trimester pregnancy loss, and 1 in the basal plate of a mature placenta. The mean patient age was 35 (range 27-41) years. The mean lesion size was 6.3 (range 2-12) mm. Architectural patterns, often coexisting in the same case, included cribriform (n = 7), solid (n = 5), villoglandular (n = 2), papillary (n = 2), and micropapillary (n = 1). Cytologic atypia was mild in 7 cases and moderate in 2. Mitotic activity was low (up to 3 per 2.4 mm2). All lesions were associated with neutrophils. Background Arias-Stella phenomenon was present in 4 cases. Immunohistochemistry was performed in 7 LEPP, all of which demonstrated wildtype p53, retained MSH6 and PMS2, membranous beta-catenin, and positive estrogen receptor (mean 71%) and progesterone receptor (mean 74%). All were negative for p40 except 1 case (focal weak positivity). PTEN was markedly reduced in background secretory glands in all cases; in 5/7, LEPP foci showed a complete absence of PTEN expression. PIK3CA pathogenic variants were identified in 4/4 cases sequenced; 3/4 had inactivating PTEN mutations. Follow-up, available in 8 patients (mean length = 51 months, range 7-161), was conservative with observation only and showed no persistence or adverse outcomes. LEPP is characterized by intraglandular cribriform/solid architecture, positive estrogen receptor/progesterone receptor, PTEN loss, and PIK3CA and PTEN mutations. Although our findings indicate that LEPP is neoplastic, for now, we advise against diagnosing LEPP as endometrial carcinoma or hyperplasia because LEPP has a particular clinicopathologic context (concurrent gestation), distinct morphology (purely intraepithelial complex growth), and indolent outcome. Thus, it should be distinguished from endometrial intraepithelial neoplasia and carcinoma for which therapeutic interventions are indicated.
摘要：
妊娠子宫内膜可以表现出一系列非典型但良性的变化。一个这样的病变是妊娠局部子宫内膜增生（LEPP），首先描述了一系列11个案例。了解其生物学和临床重要性，我们探索病理，该实体的免疫表型和分子特征。从部门档案中检索并审查了15年内发现的9例LEPP。当材料可用时,使用全面的446基因组进行免疫组织化学和下一代测序。在妊娠早期流产后进行的刮宫标本中发现了8例，一个在成熟胎盘的底板上.患者平均年龄为35岁（范围27-41岁）。平均病变大小为6.3（范围2-12）mm。建筑模式,通常在同一情况下共存，包括筛状(n=7)，固体（n=5），滑膜腺体（n=2），乳头状（n=2）和微乳头状（n=1）。细胞学异型性轻度7例，中度2例。有丝分裂活性低（每2.4mm2高达3）。所有病变均与中性粒细胞相关。背景4例患者存在Arias-Stella现象。在7LEPP中进行免疫组织化学，所有这些都证明了野生型p53，保留了MSH6和PMS2，膜β-catenin，ER阳性（平均71%）和PR阳性（平均74%）。除1例（局灶性弱阳性）外，所有p40均为阴性。在所有情况下，背景分泌腺中的PTEN均显着减少；在5/7中，LEPP病灶显示完全没有PTEN表达。在4/4测序的病例中鉴定出PIK3CA致病变体；3/4具有失活的PTEN突变。后续行动,8例患者(平均身长=51个月，范围7-161)，只对观察是保守的，并显示无持续性或不良结局。LEPP的特点是颗粒内筛状/固体结构，ER/PR阳性，PTEN丢失,和PIK3CA和PTEN突变。虽然我们的发现表明LEPP具有肿瘤性质，目前，我们建议不要将LEPP诊断为子宫内膜癌或增生，因为LEPP具有特定的临床病理背景（并发妊娠），独特的形态（纯粹的上皮内复合体生长）和惰性结局。因此，应将其与子宫内膜上皮内瘤变和需要治疗干预的癌区分开来.
