青年妇女子宫内膜癌刮宫活检的病理分析

目的 探讨青年妇女子宫内膜癌刮宫活检的病理特点.方法 回顾分析16例40岁以下子宫内膜癌患者临床病理资料.结果 子宫内膜样腺癌14例,腺鳞癌(腺癌伴鳞状上皮分化)1例,浆液性乳头状癌并透明细胞癌1例.子宫内膜样腺癌的组织学特点是子宫内膜腺体失去极性:细胞核变大、变圆、核仁突出,染色质粗或呈空泡状,同时子宫内膜间质消失,代之为肉芽组织或纤维组织,常有炎性反应.多累及浅肌层、无转移.结论 青年妇女子宫内膜癌多为高分化子宫内膜样腺癌.应注意与子宫内膜不典型增生及不典型息内状肌瘤鉴别.     

浅谈妇产科病理诊断

2．8．1卵巢浆液性囊腺癌与宫内膜样囊腺癌前者囊壁常分布大小不等乳头、簇状结节，光镜下除衬覆1～3层不等异型浆液性上皮外，及1～3级乳头状分枝或筛状结构，常伴砂砾体沉着，后者往往呈钝、粗、宽乳头状结构，及大小不等腺腔为主，衬覆异型子宫内膜型上皮，高分化者常伴有鳞状分化，或伴发透明细胞癌，若同时伴发子宫体子宫内膜样腺癌，     

血清CA125及CA19-9水平诊断子宫内膜癌的价值

ＣＡ１２５是卵巢上皮性癌的相关抗原,作为卵巢癌的肿瘤标志物已被广泛应用于临床诊断、化疗疗效观察和疾病复发的监测〔１〕,尤其对尚缺乏理想肿瘤标志物的子宫内膜癌可协助诊断。为此,我们检测了子宫内膜癌患者血清ＣＡ２５及ＣＡ１９９的含量,以探讨子宫内膜癌评估和监测的价值与临床预后因素的关系。１材料和方法１．１材料１９９４０１～１９９８０５,经手术和病理确诊为子宫内膜癌的患者１４９例,其中浆液性乳突状囊腺癌４８例,粘液性囊腺癌２７例,交界性浆液性囊腺癌６例,子宫内膜样癌１７例,库肯勃氏肿瘤７例,腺鳞癌８例,透明细胞癌…     

子宫浆液性癌及其前期病变

子宫内膜癌是常见的女性生殖道恶性肿瘤 ,根据组织学形态、病因因素、临床表现和生物学行为 ,大体上可分为两类 ,第一类即子宫内膜样癌 ,第二类中最具代表性的为子宫浆液性癌 (或称子宫浆液性乳头状癌 ,简称ＵＳＣ)。子宫内膜样癌占子宫内膜癌的大多数 ,其发生与子宫内膜增殖有关 ,临床上总伴有无拮抗的雌激素刺激 ,是雌激素依赖性肿瘤 ,相当于ＢｏｈｋｍａｎⅠ型子宫内膜癌 ;ＵＳＣ发生于老年妇女萎缩的子宫内膜 ,较少有典型的子宫内膜癌危险因素 ,如肥胖、高血压或糖尿病 ,无高雌激素症 ,是非雌激素依赖性肿瘤 ,相当于ＢｏｈｋｍａｎⅡ型…     

Ⅱ型子宫内膜癌的前驱病变及其发生模式

子宫内膜癌可分两型,Ⅰ型以子宫内膜样癌为代表,Ⅱ型以子宫浆液性乳头状癌为代表。本文旨在阐述Ⅱ型子宫内膜癌的前驱病变及其可能的发生发展模式。子宫浆液性乳头状癌又称子宫内膜浆液性癌,是一种侵袭性子宫内膜癌,预后不良。由于病因不清,人们一直努力试图找出该病的前驱病变,以便通过早期发现来改善其治疗效果。     

原发性子宫内膜浆液性癌17例临床病理观察

目的探讨子宫内膜浆液性癌(uterine serous carcinoma,USC)的临床病理学特征、诊断与鉴别诊断。方法对17例USC进行临床病理分析、组织形态学及免疫组化En Vision法染色,结合文献对其临床表现、病理形态特点及鉴别诊断进行探讨。结果患者年龄46~75岁,肿瘤位于子宫宫腔,浸润深度从内膜至子宫肌壁全层,累及子宫颈管7例,双侧附件未见累及,盆腔及腹主动脉旁淋巴结转移各1例。肿瘤组织呈腺管状或实性排列,乳头状结构常见,细胞核异型性明显,核分裂象易见,部分病例可见砂粒体形成。免疫表型:瘤细胞表达p53、p16、PTEN,不表达WT1,较少表达ER、PR,Ki-67增殖指数40%~90%。结论原发性USC临床罕见,侵袭性高,预后差,其组织形态复杂多样,需与子宫内膜样腺癌、透明细胞癌等子宫内膜恶性肿瘤鉴别。     

卵巢浆液-黏液性癌：一种罕见的新分类的肿瘤报道

浆液-黏液性肿瘤是新版世界卫生组织女性生殖器官肿瘤分类中有关卵巢上皮性肿瘤增加的一个新肿瘤。目前,交界性肿瘤已经得到了很好的描述,然而很少有浆液-黏液性癌的报道。该文报道19例卵巢浆液-黏液性癌,患者年龄16~79岁,平均47岁;其中16例单侧发生,3例双侧发生;瘤体直径1．8~18 cm,平均10．5 cm;肿瘤分期：Ⅰ期15例,Ⅱ期1例,Ⅲ期3例。12例以乳头状结构为主,含有少量腺管状、微管状和实性成分;6例以腺管状结构为主,1例以实性生长成分为主。典型的特征是两种细胞类型的混合。15例以子宫颈样黏液细胞为主,4例以子宫内膜样细胞为主;另外一些细胞类型,包括鞋钉样细胞、嗜酸性细胞、鳞状细胞、透明细胞及印戒样细胞,可以以不同的比例出现。多数病例中以嗜中性粒细胞浸润为显著特征。大多数病例呈现伴透明胞质和腔内多形性改变的微管状结构区域,这一特征与子宫颈微腺性增生相似。少数病例可出现间质玻璃样变区、腺纤维瘤样结构和砂粒体。10例卵巢发现了子宫内膜异位症,并且同时有浆液-黏液性交界性肿瘤的成分。采用FIGO分级系统关于子宫的子宫内膜样腺癌的标准对其进行分级：1级13例,2级5例,3级1例。1例同时伴有子宫的子宫内膜样腺癌。免疫表型：CK7(17/17)、ER (16/16)、PR(6/7)、CA125(15/15)、Pax-8(8/8)、CEA (8/13)、CA19．9(8/9)、WT1(2/13)、野生型p53(4/4)阳性;p16局灶阳性(5/5);CK20和CDX2在所有检测的病例中均阴性。8例患者获得随访信息,7例无病生存(随访3~74个月),1例ⅡB期肿瘤患者术后192个月死亡。鉴于两型细胞混合的特性及其与低级别浆液性肿瘤、黏液性肿瘤及子宫内膜样肿瘤在形态学重叠的特性,对浆液-黏液性癌的最适合的分类仍然未明确。尽管形态学与子宫内膜样腺癌相似,本文认为最好将其视作与卵巢上皮性恶性肿瘤不同的肿瘤,由于其与卵巢子宫内膜样癌生物学行为相似,推荐将该肿瘤重新分类。     

子宫内膜浆液性腺癌

我院１９８２－１９９２年间诊断为子宫内膜癌的９４例中，９例为子宫内膜浆液性腺癌。这９例均为临床Ⅰ期。切除的子宫标本中，浸润肌层８例，侵入肌层内淋巴管７例，侵及宫颈４例，部分播散至卵巢，输卵管，盆壁，大网膜，腹主动脉旁和／或盆腔淋巴结及肝内等。另１０例亦为临床Ⅰ期的乳头状子宫内膜样腺癌均无子宫外播散，仅４例有肌层浸润。结果表明，子宫内膜浆液性腺癌不仅形态上具有特性性，而且易发生早期的浸润和播散。     

结合组织形态学及分子检测回顾性诊断子宫内膜KRAS突变型中肾样腺癌

子宫内膜中肾样癌是一类罕见的子宫内膜癌亚型,其组织形态和分子标记与中肾管腺癌相似,存在KRAS基因突变和缺乏微卫星不稳定性。该亚型还具有独特的免疫表型特征,即GATA-3、CD10和TTF-1阳性,ER和PR阴性。该文通过形态学和分子学相结合方法对子宫内膜中肾样腺癌进行回顾性分析。作者从经大规模测序的570例子宫内膜癌数据库中选择KRAS突变的微卫星稳定(MSS)子宫内膜癌病例,并对典型KRAS突变且缺乏诊断子宫内膜样癌特征(包括鳞状或黏液分化)的MSS肿瘤进行中肾样腺癌的形态学特征复查。     

血浆VEGF水平在维吾尔族妇女子宫内膜癌中表达及意义

目的探索血浆血管内皮生长因子（VEGF）在子宫内膜癌中的表达。方法收集新疆地区50例维吾尔族子宫内膜样腺癌患者血浆,收集40例健康维吾尔族妇女血浆为正常对照。用酶联免疫法测血浆VEGF含量,分析子宫内膜癌同血管内皮生长因子的相关性。分析子宫内膜癌各临床分期及分化程度血浆VEGF的变化状况。结果子宫内膜样腺癌血浆VEGF水平同正常对照血浆相比差异有统计学意义（P〈0．01）;晚期（Ⅲ期、Ⅳ期）子宫内膜样腺癌血浆VEGF增高的水平与早期（Ⅰ期、Ⅱ期）子宫内膜样腺癌相比差异有统计学意义（P〈0．01）,在不同分化程度的子宫内膜样腺癌中,随着分化程度的加重,血浆VEGF水平增高,各组相比差异有统计学意义（P〈0．05）。结论子宫内膜癌与血浆VEGF水平增高相关,血浆VEGF水平与临床分期、分化程度相关,临床分期晚的和分化程度低的血浆VEGF水平增高更加明显。     

Expression of nm23 in normal, hyperplastic and neoplastic endometrial tissues

This study evaluated the expression of nm23 in curettage specimens from 63 cases of normal, hyperplastic and neoplastic endometrial tissues by immunohistochemistry. The histological diagnoses were as follows: normal proliferative (N = 5) or secretory (N = 5), simple hyperplasia (N = 11), complex hyperplasia (N = 9), atypical hyperplasia (N = 8) and adenocarcinoma (N = 25), consisting of endometrioid adenocarcinoma (N = 15), clear cell (N = 7) and serous papillary adenocarcinoma (N = 3). There was no immunostaining for nm23 protein in the 10 cases of normal endometria and in the 28 cases of endometrial hyperplasia. In contrast, 52% of the adenocarcinomas displayed a cytoplasmic staining pattern which was moderate to strong. This difference was statistically significant (p < 0.0001, chi-square test). nm23 expression in curettage specimens had no predictive value for determining the FIGO stage in the hysterectomy specimens (p = 0.2709, chi-square test). No significant difference for nm23 immunoreactivity was found between the histologic subtypes of endometrial adenocarcinoma (endometrioid versus serous papillary and clear cell, p = 0.1413, chi-square test). In this study, there was no immunostaining of normal endometria or of endometrial hyperplasia (including atypical endometrial hyperplasia) to support the hypothesis that expression of the nm23 gene product is related to the development of endometrial adenocarcinoma. In contrast, nm23 expression was upregulated in many cases of endometrial adenocarcinomas irrespective of the histologic subtype.     

Endometrioid adenocarcinoma of the ovary arising in atypical endometriosis

Ovarian endometriosis can transform into malignant tumors, and ovarian carcinomas relatively frequently contain foci of endometriosis. In this study, the author reviewed 15 cases of endometrioid adenocarcinoma of the ovary in the last 15 years of our pathology laboratory in search for the presence of endometriosis within the tumor. Six (40%) of the 15 endometrioid adenocarcinoma were found to have endometriosis in the tumor. All of the endometriosis were atypical. The age of the 6 patients ranged from 44 year to 78 year with a median of 59 years. Grossly, the endometrial adenocarcinomas with endometriosis were characterized by unilocular cystic tumors in 5 cases and multilocular cystic tumor in one case. Histologically, the grade of endometrioid carcinoma was grade I in 3 cases, grade II in 2 cases and grade III in 1 case. Endometriosis was mixed with the tumors or was present adjacent to the tumor. The endometriosis was composed of a layer of atypical epithelium (atypical endometriosis), and gradual merges between endometriosis and carcinoma were present in 3 cases. These findings suggest that atypical endometriosis can transform into endometrioid carcinoma.     

Image cytometry DNA ploidy correlates with histological subtypes in endometrial carcinomas.

Image cytometric DNA ploidy analysis of endometrial carcinomas was performed to determine whether ploidy status and ploidy-related parameters like DNA index, percentage of cells exceeding 5c and 9c, correlate with histologic subtype. This is a prospective study of 391 patients with stage I endometrial carcinoma which included 331 (85%) endometrioid adenocarcinoma, 22 (6%) serous adenocarcinoma, 7 (2%) clear cell adenocarcinoma, 2 (0.5%) small cell carcinoma, 1 (0.3%) undifferentiated carcinoma, and 28 (7%) unclassifiable adenocarcinoma. Twenty-five percent of endometrioid adenocarcinomas were non-diploid. In contrast, all clear cell adenocarcinomas and 21/22 (95%) of serous adenocarcinomas were non-diploid. Hyperdiploidy (25 cases) was found only in endometrioid adenocarcinomas. Mean DNA index of the stemline in serous adenocarcinoma (1.72) and clear cell adenocarcinoma (1.81) was higher than in endometrioid adenocarcinoma (1.1). The difference in ploidy-related parameters between endometrioid adenocarcinoma and serous adenocarcinoma was highly significant (P<0.001). In addition, Grade 3 endometrioid adenocarcinoma showed significant difference in all ploidy-related parameters compared with grade 1 and grade 2 tumors (P<0.001). Our results show that DNA ploidy-related parameters may be valuable in subtyping histologically difficult cases of endometrial carcinomas.     

The pathogenesis of endometrial carcinomas at menopause: facts and figures

Almost a third of the life of a woman is now postmenopausal, and during this period over 80% of endometrial carcinomas develop. This is by far the most common gynaecological malignancy in the industrialised world and, probably, the less completely understood with regard to its pathogenesis after the menopause. For while it is generally thought that these neoplasms are non-oestrogen-induced, we are, at the same time, informed that oestrogenic stimulation is continuous during menopause through increases to oestrone formation in the adipose tissue from androgens of adrenal and ovarian origin. Furthermore, the postmenopausal endometrium has been typified as atrophic, which is indeed true, but is also implied as being inactive, which in fact it is not; in most cases, the postmenopausal endometrium appears to be weakly proliferative with potential to give rise to an endometrial carcinoma. It is also assumed that postmenopausal endometrial tumours are predominantly of serous papillary and clear cell type, and, in general, they are not well-differentiated endometrioid carcinomas; in reality, no more than 15% are serous papillary and clear cell carcinomas, and no less than 55% are well-differentiated endometrioid neoplasms. The overall prognosis is presumed to be poor, yet postmenopausal patients harbouring well-differentiated endometrioid carcinomas have the same excellent prognosis as those premenopausal women having endometrioid tumours of similar grade and stage. This brief account of endometrial carcinogenesis at menopause re-evaluates these issues and, in the light of new and old evidence, proposes the separation of G1 endometrioid adenocarcinomas (low-grade tumours) from all others (high-grade tumours).     

Endometrial carcinomas: a review emphasizing overlapping and distinctive morphological and immunohistochemical features

This review focuses on the most common diagnostic pitfalls and helpful morphologic and immunohistochemical markers in the differential diagnosis between the different subtypes of endometrial carcinomas, including: (1) endometrioid versus serous glandular carcinoma, (2) papillary endometrioid (not otherwise specified, villoglandular and nonvillous variants) versus serous carcinoma, (3) endometrioid carcinoma with spindle cells, hyalinization, and heterologous components versus malignant mixed müllerian tumor, (4) high-grade endometrioid versus serous carcinoma, (5) high-grade endometrioid carcinoma versus dedifferentiated or undifferentiated carcinoma, (6) endometrioid carcinoma with clear cells versus clear cell carcinoma, (7) clear cell versus serous carcinoma, (8) undifferentiated versus neuroendocrine carcinoma, (9) carcinoma of mixed cell types versus carcinoma with ambiguous features or variant morphology, (10) Lynch syndrome-related endometrial carcinomas, (11) high-grade or undifferentiated carcinoma versus nonepithelial uterine tumors. As carcinomas in the endometrium are not always primary, this review also discusses the differential diagnosis between endometrial carcinomas and other gynecological malignancies such as endocervical (glandular) and ovarian/peritoneal serous carcinoma, as well as with extra-gynecologic metastases (mainly breast and colon).     

Fallstricke bei der histopathologischen Diagnostik des Endometriumkarzinoms und seiner Vorstufen

Making an incorrect histopathological diagnosis of an endometrial lesion may lead to unwanted loss of fertility and therapy-associated morbidity; therefore, endometrial carcinomas need to be correctly typed and differentiated from hyperplastic precursors, benign lesions and artifacts. Typical diagnostic pitfalls are described in this article. Misdiagnosing endometrial lesions can be avoided by paying thorough attention to gross as well as microscopic features and by taking crucial differential diagnoses into consideration. These are, in particular, well-differentiated endometrioid adenocarcinoma of the endometrium versus atypical endometrial hyperplasia, myoinvasive endometrioid adenocarcinoma versus atypical polypoid adenomyoma and endometrioid carcinoma versus serous carcinoma of the endometrium with a predominantly glandular pattern. It is also important to consider the possibility of a false positive diagnosis of atypical endometrial hyperplasia or carcinoma in cases of biopsy-induced artifacts.     

Beta-catenin and E-cadherin expression patterns in high-grade endometrial carcinoma are associated with histological subtype.

Both beta-catenin and E-cadherin are epithelial cell adhesion molecules. In addition, beta-catenin is an important element of the Wnt signal transduction pathway, which has been implicated in embryogenesis and carcinogenesis, including the development of endometrial and ovarian endometrioid carcinomas. We hypothesized that the expression pattern of these two adhesion molecules may depend upon the histological subtype of endometrial carcinomas. Therefore, we compared the immunohistochemical expression of beta-catenin and E-cadherin in a set of uterine adenocarcinomas matched for high histologic grade, that is, poorly differentiated (International Federation of Gynecology and Obstetrics [FIGO] Grade III) uterine endometrioid carcinomas and uterine serous carcinomas. Seventeen FIGO Grade III endometrioid adenocarcinomas and 17 serous carcinomas were evaluated histologically and immunohistochemically with commercially available monoclonal antibodies against beta-catenin and E-cadherin. Nuclear expression of beta-catenin was observed in 8 of 17 (47%) endometrioid adenocarcinomas but in none of the serous carcinomas (P = .003). Moderate or strong E-cadherin expression was identified in 7 of 17 (41%) serous carcinomas as opposed to in only 1 of 17 (6%) endometrioid adenocarcinomas (P = .02). The majority of endometrioid adenocarcinomas showed strong beta-catenin expression coupled with weak E-cadherin expression; serous carcinomas did not exhibit a comparable trend. Our results indicate that the expression of beta-catenin and E-cadherin in high-grade endometrial cancers is strongly associated with histological subtype. These data provide further support for the distinct molecular profiles of endometrioid adenocarcinoma and serous carcinoma. Notably, differences in cell adhesion molecule expression could account for variations in patterns of tumor dissemination. The immunohistochemical staining pattern may also be useful for diagnostic purposes.     

Neues in der WHO-Klassifikation 2014 der Tumoren des Corpus uteri

The 2014 World Health Organization (WHO) classification of uterine tumors revealed simplification of the classification by fusion of several entities and the introduction of novel entities. Among the multitude of alterations, the following are named: a simplified classification for precursor lesions of endometrial carcinoma now distinguishes between hyperplasia without atypia and atypical hyperplasia, the latter also known as endometrioid intraepithelial neoplasia (EIN). For endometrial carcinoma a differentiation is made between type 1 (endometrioid carcinoma with variants and mucinous carcinoma) and type 2 (serous and clear cell carcinoma). Besides a papillary architecture serous carcinomas may show solid and glandular features and TP53 immunohistochemistry with an “all or null pattern” assists in the diagnosis of serous carcinoma with ambiguous features. Neuroendocrine neoplasms are categorized in a similar way to the gastrointestinal tract into well differentiated neuroendocrine tumors and poorly differentiated neuroendocrine carcinomas (small cell and large cell types). Leiomyosarcomas of the uterus are typically high grade and characterized by marked nuclear atypia and lively mitotic activity. Low grade stromal neoplasms frequently show gene fusions, such as JAZF1/SUZ12. High grade endometrial stromal sarcoma is newly defined by cyclin D1 overexpression and the presence of the fusion gene YWHAE/FAM22 and must be distinguished from undifferentiated uterine sarcoma. Carcinosarcomas (malignant mixed Mullerian tumors MMMT) show biological and molecular similarities to high-grade carcinomas.     

Molecular genetic pathways in various types of endometrial carcinoma: from a phenotypical to a molecular-based classification

Two types of endometrial carcinoma are distinguished with respect to biology and clinical course. Type-I carcinoma is related to hyperestrogenism by association with endometrial hyperplasia, frequent expression of estrogen and progesterone receptors and younger age, whereas type-II carcinoma is unrelated to estrogen, associated with atrophic endometrium, frequent lack of estrogen and progesterone receptors and older age. Histologically, endometrioid and mucinous carcinomas are considered type I, serous and clear cell carcinomas type II. Molecular data from multiple studies support the hypothesis of different genetic pathways in the development of endometrioid and serous carcinoma. The most frequent genetic alteration in endometrioid carcinoma is PTEN inactivation by mutation, followed by microsatellite instability (MIN) and mutations of K-ras and -catenin. PTEN and K-ras mutations and MIN are considered early events, occurring in a subset of atypical endometrial hyperplasia, whereas p53 mutation is considered a late event, during progression of about 10–20% of endometrioid carcinomas. In serous carcinoma, p53 mutation is the most frequent genetic alteration, followed by inactivation of p16 and e-cadherin and amplification of her2/neu. p53 mutation occurs in endometrial intraepithelial carcinoma, the putative precursor of serous carcinoma. Considering these genetic pathways, the current histological classification of endometrial carcinoma is molecular based.