49例卵巢子宫内膜异位症恶变的临床病理分析

背景与目的:卵巢子宫内膜异位症是常见妇科良性疾病,异位的子宫内膜与原位的子宫内膜一样,都具有恶性潜能.本研究探讨49例卵巢子宫内膜异位症恶变的临床病理学特征.以及雌激素受体(estrogen receptor,ER)和孕激素受体(progesterone receptor,PR)在卵巢子宫内膜异位症恶变和无恶变卵巢子宫内膜异位症之间的表达差异.方法:对49例卵巢子宫内膜异位症恶变(恶变组)的临床病理学特征进行回顾性研究,应用ER、PR抗体对恶变组及49例无恶变卵巢子宫内膜异位症(对照组)进行免疫组织化学染色和统计学分析.结果:49例卵巢子宫内膜异位症恶变患者为29～70岁,中位年龄49岁.首发症状多为发现盆腔包块,B超检查提示盆腔混合性囊实性包块.术后肉眼检查见包块呈囊实性,直径4.0 cm～20.0 cm,囊内壁粗糙呈棕或黄色,内有咖啡色粘稠液体,实性区呈菜花样或乳头状的增生物,质脆或嫩,直径0.5 cm～15.0 cm.镜下见恶变组中的异位宫内膜腺上皮发生不典型增生及恶变.恶变组和对照组ER阳性率分别为20.4%(10/49)和95.9%(47/49),PR阳性率分别为14.3%(7/49)和95.9%(47/49),两者之间都有统计学意义(P＜0.05).结论:卵巢子宫内膜异位症恶变多发于围绝经期妇女,结合患者临床表现、B超结果以及病理检查都有助于疾病诊断.异位子宫内膜ER、PR抗体的表达阴性可作为诊断的依据之一.     

子宫内膜异位症恶变的研究现状

子宫内膜异位症（内异症）是良性疾病，但可以发生恶变。约809，6的内异症恶变发生在卵巢（endometriosis—associated ovariancancer，EAOC），主要的细胞类型为透明细胞癌和子宫内膜样癌。目前卵巢内异症恶变的诊断标准为：（1）在同一卵巢中，内异症和癌并存；（2）内异症和癌的组织学关系相类似；（3）除外转移性恶性肿瘤;（4）有良性内异症向恶性组织过渡的组织形态。内异症与肿瘤在临床病理、分子生物学以及遗传学方面均有相似之处，两者的发生有着相同的生物学基础。     

子宫内膜和卵巢原发性双癌合并子宫颈内膜异位症伴不典型增生1例并文献复习

目的:探讨子宫内膜和卵巢原发性双癌合并子宫颈内膜异位症伴不典型增生的临床病理特征及鉴别诊断.方法:分析1例子宫内膜和卵巢原发性双癌合并子宫颈内膜异位症伴不典型增生的组织病理学、免疫表型资料并复习文献.结果:患者左侧附件可见5cm×4cm×3cm大囊状肿物一个,囊内壁附着约直径3cm大实性结节;子宫腔宫底可见3cm×2.5cm×1 cm大菜花状肿物;境下两者均为高分化子宫内膜样腺癌伴左侧卵巢子宫内膜异位;同时,子宫颈局部表面见灰褐色出血点,镜下示子宫颈子宫内膜异位伴腺上皮不典型增生.3处肿瘤细胞ER-α、ER-β、PTEN及Bcl-2表达一致.结论:子宫内膜和卵巢原发性双癌合并子宫颈内膜异位症伴不典型增生多发生于绝经前女性,少见肿瘤,一般发现早,预后较好.子宫内膜异位与此类病例发病有一定关系,取材时应考虑到多部位子宫内膜异位的可能,尽量减少漏诊率.     

卵巢子宫内膜样癌与子宫内膜腺癌及子宫内膜异位症的关系

分析19例卵巢子宫内膜样癌的诊治情况。结果临床表现月经异常及绝经后阴道流血者占47．3％（9／19），高于其它类型上应性卵巢癌的14．5％（P＜0．01）。手术治疗后采取以化疗为主的综合治疗，I期病例全部存活，II期和巩期患者大部分死于肿瘤复发／转移，平均存活时间分别为7．5年、4年和2．7年。合并子宫内膜腺癌／及子官内膜异位症对预后无影响。作者还就卵巢子宫内膜样癌的临床表现特征，与子宫内膜癌的鉴别（原发抑或继发），与子宫内膜异位症的关系及治疗进行探讨。     

卵巢子宫内膜异位症恶变临床分析

目的 探讨卵巢子宫内膜异位症恶变的临床病理特征及预后.方法 回顾性分析入组的郑州大学第一附属医院2010年7月至2019年8月收治的27例卵巢子宫内膜异位症恶变患者的临床病理资料,包括临床症状和体征、盆腔影像学检查(包块直径)、发病年龄、孕产次、绝经状态、血清糖类抗原125(CA125)和人附睾蛋白4(HE4)水平、手...     

子宫内膜异位症相关性卵巢癌的临床病理特点

[目的]探讨子宫内膜异位症相关性卵巢癌(EAOC)的临床病理特点.[方法]分析2002至2012年收治的27例EAOC和184例未合并子宫内膜异位症的卵巢癌患者临床资料,比较两组患者的年龄分布、病理类型、细胞分化和临床病理分期.[结果] EAOC患者平均年龄(47±15)岁,较未合并子宫内膜异位症的卵巢癌小5岁;病理类型以卵巢子宫内膜样癌和卵巢透明细胞癌为主,未合并子宫内膜异位症的卵巢癌以浆液性癌为主;手术病理分期早于未合并子宫内膜异位症的卵巢癌患者.[结论]与未合并子宫内膜异位症的卵巢癌相比,EAOC患者年龄更小,分期更早,病理类型以内膜样癌和透明细胞癌为主.     

9例子宫内膜和卵巢同步癌的临床病理特征

目的 探讨子宫内膜和卵巢同步癌(SEOC)的临床病理特征。方法 回顾性分析2009年8月至2020年8月经手术切除并经病理组织学证实的9例SEOC患者的临床病理资料，分析其临床病理特征并复习相关文献。结果 患者年龄29～65岁，平均年龄47.44岁，首发症状以子宫异常出血为主。9例SEOC患者子宫内膜癌的病理类型均为子宫内膜样癌，以低级别、Ⅰ期肿瘤为主；8例伴子宫内膜非典型增生/子宫内膜上皮内瘤变(AH/EIN)。9例SEOC中，卵巢癌的病理类型为低级别子宫内膜样癌(G₁、G₂)8例，透明细胞癌1例；均为Ⅰ期肿瘤，多为单侧卵巢受累。6例存在卵巢子宫内膜异位症。均无淋巴脉管间隙浸润及输卵管受累。4例患者行腹水细胞学检查，仅1例发现癌性腹水。其中病例5既往有结肠腺癌病史，子宫内膜癌、卵巢癌及结肠腺癌免疫组化结果显示MLH1、PMS2表达缺失；病例8卵巢癌病理类型为透明细胞癌，子宫内膜癌及卵巢癌免疫组化结果显示MSH2、MSH6表达缺失。所有患者均接受手术治疗及术后辅助治疗。结论 SEOC通常发生于年轻女性。以低级别子宫内膜样癌、早期肿瘤为主。治疗...     

卵巢透明细胞癌18例临床分析

目的:分析18例卵巢透明细胞癌的临床特点、预后及与子宫内膜异位症的关系.方法:对18例原发性卵巢透明细胞癌患者回顾性分析其治疗方法、对化疗的敏感性和生存率,以及合并子宫内膜异位症患者对化疗的敏感性和生存率.结果:卵巢透明细胞癌患者常发生月经紊乱或绝经后出血,Ⅰ期患者比例较高,多发生于单侧卵巢,常伴发卵巢子宫内膜异位症,是否合并子宫内膜异位症对化疗的敏感性和生存率无统计学差异.结论:卵巢透明细胞癌临床特点不同于其他的卵巢上皮性恶性肿瘤,其临床分期早,对化疗不敏感,易复发,预后差.伴有子宫内膜异位症与否与预后无相关性.本病预后与临床分期直接相关,与肿瘤体积、有/无腹水、肿瘤扩散程度、肿瘤侵犯单侧或双侧卵巢等因素密切相关.     

卵巢子宫内膜样间质肉瘤临床病理分析(附2例报道)

目的:探讨卵巢子宫内膜样间质肉瘤的临床病理特征、诊断与鉴别诊断以及治疗和预后。方法:对2例卵巢子宫内膜样间质肉瘤进行光镜、免疫组化检测,并复习有关文献。结果:肿瘤组织由形似增殖期子宫内膜间质细胞的小细胞组成,卵圆形或梭形,胞浆稀少,其间满布厚壁小血管类似子宫内膜螺旋小动脉,肿瘤细胞呈漩涡状围绕小血管。免疫组化CD10( ),CD99( ),ER( ),PR( ),α-inhibin(-),SMA(-)。网状纤维染色:网状纤维密布于肿瘤细胞之间。结论:卵巢子宫内膜样间质肉瘤是一种非常罕见的恶性肿瘤,组织学形态需与卵巢性索-间质肿瘤和卵巢肉瘤等鉴别。     

子宫内膜异位症恶变3例报告

目的探讨子宫内膜异位症恶变的临床特点。方法回顾性分析1995年1月至2006年4月收治的3例子宫内膜异位症恶变病例的临床、病理资料并结合复习文献。结果子宫内膜异位症恶变3例占同期盆腔子宫内膜异位病例的1.82%;常见症候为盆腔包块、腹部不适或疼痛和痛经;手术切除病灶经病理检查才能确诊;3例中1例失访、1例已生存42个月、另1例已生存55个月。结论子宫内膜异位症恶变罕见;术前难以诊断、切除病检才能确诊;治疗以手术切除为主综合化疗、放疗及激素治疗;早期病例预后较好。     

Comparative immunohistochemical studies of bcl-2 and p53 proteins in benign and malignant ovarian endometriotic cysts

BACKGROUND: A number of histologic and epidemiologic studies have suggested an association between endometriosis and ovarian carcinoma. Some reports have described a transition from endometriosis to atypical endometriosis to carcinoma. Using immunohistochemistry, the authors compared staining patterns in benign endometriotic cysts with ovarian tumors and the endometriotic cyst lining from which they arose, in an attempt to identify sequential or etiologic correlations. METHODS: One hundred thirteen formalin-fixed, paraffin-embedded sections were studied (30 benign ovarian endometriotic cysts, 24 endometriotic cysts containing endometrioid carcinomas, 19 endometriotic cysts harboring clear cell carcinomas, and 40 ovarian papillary serous cystadenocarcinomas). All sections were immunostained with anti-bcl-2 and anti-p53 antibodies using the streptavidin-biotin method. RESULTS: bcl-2 was reported to stain 23% of benign endometriotic cysts, 67% of endometrioid carcinomas, 73% of clear cell carcinomas, and 50% of papillary serous carcinomas. Approximately 42% of benign endometriotic lesions adjacent to the endometrioid carcinoma and 73% adjacent to clear cell carcinomas were found to stain for bcl-2 (p = 0.274 [not significant (NS)] and P = 0.008, respectively). p53 staining was negative in the benign endometriotic cyst group and was positive in 37-55% of the group with tumors. p53 staining was positive in 25% of the benign endometriotic lesions next to the endometrioid carcinoma and in 9% of the benign endometriotic lesions next to clear cell carcinoma (P = 0.014 and P = 0.239 [NS], respectively). CONCLUSIONS: The results of the current study suggest that alterations in bcl-2 and p53 may be associated with the malignant transformation of endometriotic cysts.     

Atypical epithelial changes and mutant p53 gene expression in ovarian endometriosis

It has been reported that cases of ovarian endometriosis those with epithelial cytological atypia have potential for malignant transformation. This study was planned to determine the incidence of atypical endometriosis and its cytological criteria, to evaluate the malignant potential of atypical endometriosis via immunohistochemical methods (p53). In this study we evaluated 140 samples obtained from 120 cases of ovarian endometriosis and 10 ovarian endometrioid carcinomas that have been previously diagnosed histopathologically. We re-evaluated endometriosis cases with respect to their epithelial and stromal features, existence of acute or chronic inflammatory cells in endometriotic epithelium or stroma and other accompanying histological findings. We observed atypia in 7 (5.8%) cases; reactive atypia in 37 (30.8%) cases, no atypia in 76 (63.4%) cases. We evaluated immunohistochemical p53 expression in 7 atypical cases, 37 reactive atypical cases, and in 10 of those without atypia and in 10 endometrioid carcinoma cases. We noted no staining in cases with atypia, reactive atypia and without atypia while 3 cases of endometrioid carcinoma had positive staining for p53. We concluded that prominent nucleolus and angulation of nuclear contour could be added to criteria of atypia that were mentioned before in the literature. In our study, even though p53 expression could not be shown with immunohistochemical methods in atypical endometriotic cases; it can not be determined that atypical endometriosis lesions are not premalignant. Still, endometriosis cases should be evaluated carefully by the pathologist for foci of cytological atypia and it should be kept in mind that malignant transformation might occur in these atypical endometriosis cases.     

子宫内膜异位症与卵巢癌相关性临床分析

目的:探讨子宫内膜异位症(内异症)与卵巢癌的相关性。方法:收集199例卵巢癌患者,分内异症组(n=32),非内异症组（n=167）,回顾性分析两组患者一般情况、临床表现、病理特征、实验室检查及预后。结果:内异症组平均年龄明显小于非内异症组(P＜0.05),年龄<50岁、未生育患者构成比明显高于非内异症组;内异症组患者临床症状以月经改变和下腹痛、腹胀为主（P＜0.05）;内异症组肿瘤直径通常小于20cm,且主要在10-20cm之间,非内异症组肿瘤直径大部分为10-20cm;内异症组患者血CA125主要在200-1000kU/L之间,非内异症组大部分在200kU/L以下;内异症组患者以透明细胞癌、宫内膜样癌为主,非内异症组以浆液性囊腺癌为主(P＜0.05);内异症组患者分期较早,I期 、Ⅱ期占合并卵巢癌患者68.8%,非内异症组分期多处于Ⅱ期、Ⅲ期,占原发卵巢癌患者70.1%（P＜0.05）;内异症组患者病灶部位多位于左侧卵巢,非内异症组病灶部位在左侧、右侧、双侧分布较接近 (P＜0.05);内异症组5年生存率为59.4%,非内异症组5年生存率为34.7%,两组差异具有统计学意义(P＜0.05)。结论:应充分了解内异症恶变的临床症状及病理特征,提高早期诊断率。     

Possible involvement of hMLH1, p16(INK4a) and PTEN in the malignant transformation of endometriosis

Endometriosis is a common gynecologic disease, which generally follows a benign course. Notwithstanding, several clinical and histologic studies as well as molecular data show that endometriosis could be a precursor of sporadic endometrioid and clear cell carcinomas at extrauterine loci. Several reports have implicated alterations of the hMLH1 and p16(ink4a) (p16) genes, in particular hypermethylation of the promoter region, and of the PTEN gene, principally genetic mutations, in endometrial and ovarian cancers and have indicated that these alterations are already present in precancer conditions. In this report, we analyzed the methylation status of hMLH1 and p16 and the protein expression of PTEN and hMLH1 in 46 cases of endometriosis stages III and IV to better define the possible involvement of these genes in the malignant transformation of endometriosis. We found abnormal methylation of hMLH1 in 4 of the 46 cases (8.6%). In addition, these cases had no detectable hMLH1 protein expression. Regarding patients with hMLH1 alterations, 2 were classified as stage IV and 2 showed coexistent endometriosis and carcinoma. Only 1 case of endometriosis (2.17%), classified as atypical, showed abnormal methylation of p16. Reduced PTEN protein expression was detected in 7 of 46 cases (15.21%): 5 were clinically classified as stage IV, and the other 2 presented both cancer and hypermethylated hMLH1. Our preliminary study suggests that reduced expression of both hMLH1 and PTEN may be involved in the malignant evolution of endometriosis and should be used as markers of neoplastic transformation in aggressive endometriosis with elevated tumor markers.     

Genomic imbalance and onco-protein expression of ovarian endometrioid adenocarcinoma arisen in an endometriotic cyst

BACKGROUND: Malignant transformation in endometriosis is a rare but well known complication. However, detailed mechanisms of malignant transition and tumourigenesis in endometriosis remain unknown. We here describe the case of an endometrioid carcinoma arisen in endometriotic ovarian cyst fulfilling Sampson's criteria for malignant transformation of endometriosis. We compared genetic alterations and oncoprotein expression in the endometriotic ovarian cyst and the associated endometrioid adenocarcinoma. MATERIALS AND METHODS: Genomic instability was evaluated by comparative genomic hybridization (CGH). Onco-protein expression was analysed by immunohistochemistry with antibodies against bcl-2, c-MYC, cyclin D1, p53, HER-2 and KIT protein. RESULTS: CGH revealed a gain of 8q, including the locus of the oncogene c-MYC at 8q24. Immunohistochemistry disclosed a differing protein expression profile between the epithelia of the pre-existing cyst and adenocarcinoma. Apart from HER-2, all onco-proteins were more strongly expressed in epithelial cells of the adenocarcinoma than of the endometriotic cyst. CONCLUSION: The solitary genomic imbalance of chromosome 8 possibly reflects the importance for initiation and/or progression of endometrioid carcinoma. Overexpression of onco-proteins then may occur subsequently in the malignant transformation of ovarian endometriosis. However, the exact mechanisms of malignant transition in ovarian endometriosis remain to be elucidated in future studies with a higher number of cases.     

The shifting landscape of genetic alterations separating endometriosis and ovarian endometrioid carcinoma

Ovarian cancer is one of the most common cancers worldwide, and is associated with a prior diagnosis of endometriosis in several cases. Our aim was to correlate genetic and methylation profile of ovarian endometrioid ovarian cancer and endometriosis patients. We evaluated the genetic profile of 50 ovarian endometriosis and 20 ovarian endometrioid carcinoma samples using next generation sequencing technology. In addition, the DNA methylation profile was evaluated for both cohorts of patients. We observed several mutated genes that were common for both types of patients, but we also identified mutated genes that were characteristic for each group: JAK3, KRAS and RB1 for endometriosis; and ATM, BRAF, CDH1, EGFR, NRAS, RET and SMO for ovarian endometrioid cancer. Also we idenfied genes that are highly methylated only in endometriosis samples (PYCARD, RARB, RB1, IL2, CFTR, CD44 and CDH13) and MLH3 gene was methylated only in endometrioid ovarian carcinoma samples. Also, BRCA1, CADM1, PAX6 and PAH genes are mainly methylated in endometrioid ovarian carcinoma patients. We identified a correlation for the cancer group between tumor stage, copy number aberrations and the presence of metastases; more specifically, the presence of BRCA1 pathogenic variants was correlated with tumor differentiation degree, TP53 variants and copy number aberrations. This study was able to demonstrate the presence of similar pathways being altered in both endometriosis and ovarian endometrioid carcinoma, which could mean that a diagnosis of endometriosis could be an early marker for cancer diagnosis. In addition, we showed that GATA2 hypomethylation, ATM hypermethylation, CREM hypomethylation, higher tumor differentiation degree or higher tumor stage is associated with a poor prognosis in patients with ovarian endometrioid carcinoma.     

Endometriosis and Ovarian Cancer: an Integrative Review (Endometriosis and Ovarian Cancer)

Despite being initially considered a benign disease, it is widely thought nowadays that endometriosis and especially ovarian endometriomas are neoplastic conditions with the potential to become malignant. This review was conducted to summarize, in a concise and systematic manner, the available scientific data relating endometriosis to ovarian cancer, published in the past five years. After reading abstracts and applying our predefined inclusion and exclusion criteria, a final list of 11 scientific papers was obtained and subjected to review. Endometriosis is associated with an increased risk of developing epithelial ovarian cancer (EOC), mainly of endometrioid and clear cell subtypes. This might be by virtue of the high estrogen concentration with the disease, which leads to malignant proliferation of endometriotic cysts, or be due to mutations in the ARID1A gene and consequent loss of BAF250a expression. The iron produced in the fluid of endometriotic cysts promotes oxidative stress, which in turn may cause genetic mutations and malignant progression of ovarian cysts.     

Evaluation of the Pathogenesis of Tumor Development from Endometriosis by Estrogen Receptor,P53 and Bcl-2 Immunohistochemical Staining

Objective: Endometriosis, one of the most common estrogen dependent gynecological disorders, can present as both benign and malignant disease. The prevalence of tumoral transformation is 0.7-1.6% and the most common tumors are clear cell and endometrioid carcinomas. Unfortunately, the pathogenesis of transformation is unknown. For this purpose, we examined molecular alterations in ovarian endometriosis and endometriosis-associated tumors. Methods: Using the data bank of Alzahra hospital pathology department and paraffin blocks from appropriate cases were identified. Sections were cut and stained for 3 markers: estrogen receptor, P53 and bcl2. Correlations between findings were investigated. Results: Nineteen cases of endometriosis-associated tumor and 19 cases of endometriosis were identified. Staining for bcl2 was documented in 14 of 19 (73.7%) of endometriosis-associated tumor cases and also 7 of 19 (36.8%) endometriosis cases (P=0.02). Only 3 of the 19 (15.8%) endometriosis-associated tumors exhibited positive staining for estrogen receptors, compared with 14 of 19 (73.7%) endometriosis cases (P<0.001). Positive staining for P53 was noted in 5 of 19 (31.6%) endometriosis-associated ovarian tumor samples but was absent in endometriosis samples (0%), (P =0.008). Conclusions: Endometriosis-associated tumors appear to be associated with overexpression of bcl2 and P53 and reduced expression of Estrogen receptor. These finding may help to diagnose tumoral transformation with a background of endometriosis.     

Molecular genetic evidence that endometriosis is a precursor of ovarian cancer

Histopathology and epidemiology studies have consistently demonstrated a strong link between endometriosis and endometriosis-associated ovarian cancers (EAOCs)--in particular, the endometrioid and clear cell subtypes. However, it is still unclear whether endometriosis is a precursor to EAOCs, or whether there is an indirect link because similar factors predispose to both diseases. In order to search for evidence of clonal progression, we analyzed 10 EAOCs (endometrioid=4; clear cell=6) with coexisting endometriosis for common molecular genetic alterations in both the carcinoma and corresponding endometriosis. We used 82 microsatellite markers spanning the genome to examine loss of heterozygosity (LOH) in the coexisting carcinoma and endometriosis samples. A total of 63 LOH events were detected in the carcinoma samples; twenty two of these were also detected in the corresponding endometriosis samples. In each case, the same allele was lost in the endometriosis and cancer samples. Interestingly, no marker showed LOH in the endometriosis alone. These data provide evidence that endometriosis is a precursor to EAOCs.     

KLF4与S100A14在子宫内膜异位症相关性卵巢癌中的表达及临床意义

目的:探求子宫内膜异位症相关性卵巢癌中Krüppel样因子4（KLF4）与钙离子结合蛋白14（S100A14）的表达情况及临床意义。方法:免疫组化判定KLF4及S100A14分别在36例正常/良性卵巢组织（对照组）、30例卵巢子宫内膜异位症组织（ovarian endometriosis，OE）和49例子宫内膜异位症相关性卵巢癌组织(endometriosis associated ovarian carcinoma，EAOC)中的表达情况，并分析二者与EAOC患者相关临床参数的关系。结果:KLF4在对照组、OE组以及EAOC组中的阳性表达率分别为72.2%（26/36）、63.3%（19/30）、32.7%（16/49），差异有统计学意义（P＜0.01）。S100A14在三组中表达的阳性率分别为61.1%（22/36）、63.3%（19/30）、87.8%（43/49），差异有统计学意义(P＜0.05)。在EAOC中，KLF4表达与淋巴结转移有显著相关性（P＜0.05）。KLF4与S100A14呈负相关(r=-0.138)。结论:KLF4低表达和S100A14高表达可能参与了卵巢子宫内膜异位症恶变，同时KLF4可能促进了EAOC的转移。