妊娠期局限性子宫内膜增生4例临床病理学分析及文献复习

诊断学理论与实践››2025,Vol. 24››Issue (05): 529-533.doi:10.16150/j.1671-2870.2025.05.008

妊娠期局限性子宫内膜增生4例临床病理学分析及文献复习

黄素明¹^,², 张慧娟¹^,², 周峰¹^,²()

1.开云网页登录医学院附属国际和平妇幼保健院病理科，上海 200030
2.上海胚胎源性疾病重点实验室，上海 200030

收稿日期:2025-01-23修回日期:2025-06-19接受日期:2025-08-10出版日期:2025-10-25发布日期:2025-10-23
通讯作者:周峰 E-mail：pathozf@163.com
基金资助:
上海自然科学基金面上项目(25ZR1401367)

Clinicopathological analysis of four cases of localized endometrial proliferations of pregnancy and literature review

HUANG Suming¹^,², ZHANG Huijuan¹^,², ZHOU Feng¹^,²()

1. Department of Pathology, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
2. Shanghai Key Laboratory of Embryo Original Diseases, Shanghai 200030, China

Received:2025-01-23Revised:2025-06-19Accepted:2025-08-10Published:2025-10-25Online:2025-10-23

摘要/Abstract

摘要：

目的：探讨妊娠期局限性子宫内膜增生（localized endometrial proliferations of pregnancy， LEPP）的临床病理学特征变。方法：收集开云网页登录医学院附属国际和平妇幼保健院2014年至2024年间收治的4例LEPP患者的临床病理学资料，复习其HE染色的病理组织切片，并进行免疫组化检测，并结合文献复习，总结其临床病理特点。结果：4例患者的平均年龄为34.5岁（29~40岁），均在孕早期人流样本中发现LEPP。低倍镜下均见腺体扩张，腺体呈筛状或乳头状排列，上皮增生，细胞复层；高倍镜下细胞核轻度异型，核分裂象少见（0~1个/2 mm²）；其中1例背景可见钙化。免疫组化色示，4例患者均为雌激素受体（estrogen receptor，ER）、孕激素受体（progesterone receptor，PR）、配对盒基因2（paired box gene，PAX2）阳性，强于周围内膜；肿瘤蛋白53（protein 53，P53）野生型表达；错配修复蛋白阳性；同源性磷酸酶-张力蛋白（phosphatase and tensin homolog，PTEN）缺失。复习文献发现，LEPP具有腺上皮高度增生，细胞异型性小，生物学行为良性等特点。已报道的7例诊断为子宫内膜不典型增生或早期子宫内膜癌的病例，形态学描述更符合LEPP，随访均未见子宫内膜相关疾病复发。结论：LEPP是一类于妊娠期发生的病变，具有腺体内腺上皮高度增生、细胞异型性小、PTEN缺失、PAX2阳性等特点，目前认为其生物学行为良性。

关键词:妊娠期局限性子宫内膜增生,子宫内膜不典型增生,同源性磷酸酶-张力蛋白

Abstract:

ObjectiveTo investigate the clinicopathological features of localized endometrial proliferations of pregnancy (LEPP).MethodsClinicopathological data of 4 LEPP patients treated at the International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine from 2014 to 2024 were collected. Their hematoxylin and eosin (HE)-stained pathological sections were reviewed, immunohistochemical (IHC) testing was performed, and literature was reviewed to summarize clinicopathological characteristics.ResultsThe average age of the 4 patients was 34.5 years (range: 29-40). LEPP was identified in first-trimester abortion specimens in all cases. Microscopically, low-power examination revealed dilated glands arranged in cribriform or papillary patterns, with epithelial hyperplasia and cell stratification. High-power examination showed mild nuclear atypia, with rare mitotic figures (0-1/2 mm²). Calcification was observed in one case. IHC staining demonstrated that all 4 patients were positive for estrogen receptor (ER), progesterone receptor (PR), and paired box gene 2 (PAX2), with stronger expression than in surrounding endometrium. Tumor protein 53 (P53) showed wild-type expression. Mismatch repair proteins were positive. Phosphatase and tensin homolog (PTEN) expression was absent. Literature review indicated that LEPP was characterized by marked glandular epithelial hyperplasia, minimal cytological atypia, and benign biological behavior. Seven cases diagnosed as atypical endometrial hyperplasia or early endometrial carcinoma exhibited morphological features more consistent with LEPP, and no recurrence of endometrial-related diseases was observed during follow-up.ConclusionLEPP is a type of lesion occurring during pregnancy characterized by marked glandular epithelial hyperplasia, minimal cytological atypia, PTEN loss, and PAX2 positivity. It is currently considered biologically benign.

Key words:Localized endometrial proliferations of pregnancy,Atypical endometrial hyperplasia,Phosphatase and tensin homolog

中图分类号:

黄素明, 张慧娟, 周峰. 妊娠期局限性子宫内膜增生4例临床病理学分析及文献复习[J]. 诊断学理论与实践, 2025, 24(05): 529-533.

HUANG Suming, ZHANG Huijuan, ZHOU Feng. Clinicopathological analysis of four cases of localized endometrial proliferations of pregnancy and literature review[J]. Journal of Diagnostics Concepts & Practice, 2025, 24(05): 529-533.

图/表3

表1

4例LEPP病变的临床病理特征

Indice	Case
Indice	1	2	3	4
Clinical features
Age (years)	39	30	40	29
Gestational period (weeks)	7	7	7	8
Gravidity and parity	G2P1	G1P0	G2P1	G2P1
Pathological features	15	5	10	15
Maximum diameter (mm)
Microscopic structure	Papillary, cribriform	cribriform	cribriform	cribriform
Mitosis (/2mm²)	1	1	0	0
Nuclear atypia	mild-mode-rate	mild	mild	mild-moderate
Calcification	yes	no	no	no
Arias-Stella	focal	focal	focal	focal
IHC
ER	70%+	90%+	50%+	70%+
PR	20%+	70%+	10%+	10%+
P53	wild	wild	wild	wild
Ki-67	5%	5%	3%	3%
MSH2	+	+	+	+
MSH6	+	+	+	+
MLH1	+	+	+	+
PMS2	+	+	+	+
PAX2	80%+	80%+	95%+	80%+
PTEN	-	-	-	-
ARID1A	+	+	+	+
β-catenin	membrane+	membrane+	membrane+	membrane+
P40	-	-	-	-

表1

图1

表2

文献报道妊娠期AH和EC

Reference	Age	Gestational age (wk)	Diagnosis	FIGO stage	Follow-up(mo)	Status
Bayoglu, et al^{[ 5 ]}	36	<13	EC, grade 1	Ⅰ	12	NED
Carinelli, et al^{[ 6 ]}	40	Unknown	AH	Ⅰ	6	NED
Hannuna, et al^{[ 7 ]}	39	<13	EC, grade 2	Ⅰ	18	NED
Sandstrom, et al^{[ 8 ]}	37	10	EC, grade 1	ⅠA	30	NED
Shiomi, et al^{[ 9 ]}	35	35	EC, grade 1	ⅠA	48	NED
Terada^{[ 10 ]}	29	8	EC, grade 2	Ⅰ	Unknown	Unknown
Zhou, et al^{[ 11 ]}	33	9	EC, grade 1	Ⅰ	4	NED

表2

参考文献21

[1]	ARIAS-STELLA J. The Arias-Stella reaction: facts and fancies four decades after[J].Adv Anat Pathol,2002,9(1):12-23. pmid:11756756
[2]	GENEST D R, BRODSKY G, LAGE J A. Localized endometrial proliferations associated with pregnancy: clinical and histopathologic features of 11 cases[J].Hum Pathol,1995,26(11):1233-1240. pmid:7590698
[3]	WEPY C, CHAPEL D B, MUTTER G L, et al. Localized endometrial proliferations of pregnancy are clonal glandular outgrowths characterized by PTEN loss and PIK3CA pathogenic variants[J].Mod Pathol,2023,36(8):100213.
[4]	SINGH N, PISKORZ A M, BOSSE T, et al. p53 immunohistochemistry is an accurate surrogate for TP53 mutational analysis in endometrial carcinoma biopsies[J].J Pathol,2020,250(3):336-345.
[5]	BAYOGLU TEKIN Y, GUVENDAG GUVEN E S, SEHITOGLU I, et al. Tubal pregnancy associated with endometrial carcinoma after in vitro fertilization attempts[J].Case Rep Obstet Gynecol,2014,2014:481380.
[6]	CARINELLI S G, CEFIS F, MERLO D. Epithelial neoplasia of the endometrium in pregnancy. A case report[J].Tumori,1987,73(2):175-180.
[7]	HANNUNA K Y, PUTIGNANI L, SILVESTRI E, et al. Incidental endometrial adenocarcinoma in early pregnancy: a case report and review of the literature[J].Int J Gynecol Cancer,2009,19(9):1580-1584. doi:10.1111/IGC.0b013e3181a841a7pmid:19955941
[8]	SANDSTROM R E, WELCH W R, GREEN T H JR. Adenocarcinoma of the endometrium in pregnancy[J].Obstet Gynecol,1979,53(3 Suppl):73S-76S.
[9]	SHIOMI M, MATSUZAKI S, KOBAYASHI E, et al. Endometrial carcinoma in a gravid uterus: a case report and literature review[J].BMC Pregnancy Childbirth,2019,19(1):425.
[10]	TERADA T. Endometrial adenocarcinoma in spontaneous abortion[J].Pathology,2009,41(7):694-695.
[11]	ZHOU F, QIAN Z, LI Y, et al. Endometrial adenocarcinoma in spontaneous abortion: two cases and review of the literature[J].Int J Clin Exp Med,2015,8(5):8230-8233. pmid:26221400
[12]	WHO Clsaaification of Female Genital Tumours[M]. 5 ed. Lyon: IARC Press,2020.
[13]	MOTE P A, BALLEINE R L, MCGOWAN E M, et al. Heterogeneity of progesterone receptors A and B expression in human endometrial glands and stroma[J].Hum Reprod,2000,15(Suppl 3):48-56.
[14]	HOWITT B E, MONTE N M, ELVIN J, et al. Dyssynchronous secretory endometrial glands often show sporadically acquired progesterone nonresponsiveness[J].Int J Gynecol Pathol,2015,34(3):239-244. doi:10.1097/PGP.0000000000000157pmid:25844547
[15]	NIU S, MOLBERG K, CASTRILLON D H, et al. Biomar-kers in the diagnosis of endometrial precancers. Molecular characteristics, candidate immunohistochemical mar-kers, and promising results of three-marker panel: current status and future directions[J].Cancers (Basel),2024,16(6):1159.
[16]	CANCER GENOME ATLAS RESEARCH N, KANDOTH C, SCHULTZ N, et al. Integrated genomic characterization of endometrial carcinoma[J].Nature,2013,497(7447): 67-73.
[17]	MAO T L, ARDIGHIERI L, AYHAN A, et al. Loss of ARID1A expression correlates with stages of tumor progression in uterine endometrioid carcinoma[J].Am J Surg Pathol,2013,37(9):1342-1348.
[18]	CHEUNG L W, HENNESSY B T, LI J, et al. High frequency of PIK3R1 and PIK3R2 mutations in endometrial cancer elucidates a novel mechanism for regulation of PTEN protein stability[J].Cancer Discov,2011,1(2):170-185. doi:10.1158/2159-8290.CD-11-0039pmid:21984976
[19]	SALVESEN H B, MACDONALD N, RYAN A, et al. PTEN methylation is associated with advanced stage and microsatellite instability in endometrial carcinoma[J].Int J Cancer,2001,91(1):22-26. pmid:11149415
[20]	ABD EL-MAQSOUD N M, EL-GELANY S. Differential expression patterns of pten in cyclic, hyperplastic and malignant endometrium: Its relation with ER, PR and clinicopathological parameters[J].J Egypt Natl Canc Inst,2009,21(4):323-331.
[21]	ROBERT J. KURMAN L H E A B M R.Blaustein's pathology of the female genital tract[M]. 7 ed. Switzerland AG: Springer,2019.