子宫浆液性乳头状癌24例临床病理分析

目的比较子宫浆液性乳头状癌(uterine papillary serous carcinoma,UPSC)和子宫内膜样癌(uterine endometrioid carcino-ma,UEC)的组织病理学和免疫组化表达,以了解两种肿瘤生物学行为的差异。方法对24例UPSC和54例UEC进行组织学复查和应用免疫组化SP法检测肿瘤的p53蛋白、ER和PR的表达。结果24例UPSC占子宫内膜癌的3·77%,平均年龄UP-SC组为60岁,UEC组为51·7岁(P<0·01),晚期癌(FIGOⅢ-Ⅳ)UPSC组占62·5%,UEC组占35·1%(P<0·025)。p53蛋白的表达UPSC组16例阳性(66·7%),UEC组10例阳性(18·5%),两组比较(P<0·01)。ER阳性表达UPSC组(8·3%),UEC组(42·5%),PR阳性表达UPSC组(12·5%),UEC组(35·2%),两组比较:ER(P<0·01),PR(P<0·05),差异有显著性。UPSC组p53蛋白表达与肿瘤分期、分级、及肌层浸润无明显关系,而UEC组Ⅲ~Ⅳ期肿瘤的p53蛋白的表达率高于Ⅰ-Ⅱ期(P<0·005)。UPSC的5年生存率为25%,UEC组5年生存率为80·9%(P<0.01),两组差异有显著性。结论UPSC为p53高表达,而缺乏雌激素和孕激素受体,为高度恶性的肿瘤。它的生物学行为不同于UEC,因而强调诊断时需和其他类型的子宫内膜癌相区别。     

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…     

子宫内膜间质肉瘤9例临床病理分析

目的 探讨子宫内膜间质肉瘤(endometrial stromal sarcoma,ESS)的临床病理特征、诊断、鉴别诊断及预后.方法 对9例ESS患者进行临床、病理资料分析、免疫组化检测及随访.结果 患者年龄39～64岁,中位46.3岁.临床主要表现为阴道流血及子宫增大/占位.肿瘤直径2.3～11 cm,平均4.6 cm.光镜下8例呈低度恶性子宫内膜间质肉瘤(low grade endometrial stromal sarcoma,LGESS),均由类似增殖期子宫内膜间质肿瘤细胞构成,细胞密集,异型性不明显,呈不规则舌状或岛状浸润肌层,并伴较多薄壁螺旋小血管;1例为高度恶性子宫内膜间质肉瘤/未分化子宫内膜肉瘤(high grade endometrial stromal sarcoma/undifferentiated endometrial sarcoma,HGESS/UES),肿瘤细胞直接替代子宫肌层,具有明显的细胞异型性,无LGESS常见的螺旋小血管.免疫组化检测显示肿瘤细胞CD10、vimentin均阳性,PR、ER大部分阳性,SMA和desmin及h-Caldesmon为极少数局灶阳性,S-100、CD34均阴性.术后随访7例(平均53个月),只有1例HGESS/UES死亡.结论 ESS是女性生殖道很少见的一种恶性肿瘤,恶性度相差很大.确诊主要依靠其临床病理特点,并辅以免疫组化标记综合分析.诊断时要与子宫内膜间质结节、平滑肌肿瘤、低分化癌等鉴别.     

子宫内膜增生与子宫内膜上皮内瘤变的临床病理分析

目的 探讨WHO1994有关子宫内膜增生(endometrial hyperplasia,EH)和子宫内膜上皮内瘤变(endometrial intraepithelial neoplasia,EIN)的形态学特点以及分类的优点.方法 观察474例刮宫标本HE切片中的EH性病变(包括子宫内膜单纯性增生、复杂性增生及两者伴有的不典型增生),根据新标准找出EIN,总结分析EH分类与EIN分类的关系,同时对部分EIN患者进行随访.结果 379例子宫内膜单纯性增生中EIN 11例(2.9%),16例伴有不典型增生的单纯性增生中EIN 1例(6.25%),48例子宫内膜复杂性增生中EIN 6例(12.5%),31例伴有不典型增生的复杂性增生中EIN 28例(90.3%).共随访到EIN患者13例,因恶变摘除子宫者3例(23.07%).结论 EIN为单克隆增生(肿瘤增生)性病变,恶变潜能较高,完全不同于良性的EH,具有其特殊的形态学特点和生物学行为,EIN的分类方法在诊断标准上和对恶变潜能的预判方面优于WHO 1994年分类,明确EIN的病理学诊断特点对今后的诊断及治疗都有极其重要的意义.     

未分化子宫内膜肉瘤6例临床病理观察

目的 探讨未分化子宫内膜肉瘤(undifferentiated endometrial sarcoma,UES)的临床病理特点、诊断及鉴别诊断.方法 对6例未分化子宫内膜肉瘤的临床资料、组织学形态及免疫组化结果进行观察分析.结果 患者年龄49～71岁,平均年龄59岁,临床主要表现为宫腔内占位和阴道出血;肿瘤大体呈息肉样,突入宫腔;镜下见肿瘤组织分化差,细胞异型明显,核分裂象丰富(＞10个/10 HPF),坏死常见;免疫组化标记,肿瘤细胞CD10、ER、PR、desmin、SMA、CK、EMA阴性,vimentin、EGFR阳性;6例随访6个月～4年,3例死于肺转移.结论 未分化子宫内膜肉瘤是一种少见的子宫内膜间质肿瘤,具有高度恶性.肿瘤组织分化差,细胞异型明显,常见坏死,免疫组化标记有助于诊断与鉴别.     

子宫内膜间质肉瘤5例临床病理分析

目的 探讨子宫内膜间质肉瘤(endometrial stromal sarcoma,ESS)的临床病理特点、诊断、鉴别诊断及免疫表型.方法 回顾性分析5例ESS患者的临床资料,探讨其病理特点、免疫表型及预后等相关因素.结果 5例ESS中,低度恶性4例,高度恶性1例,镜下见低度恶性密集排列的类似增殖期子宫内膜间质细胞围绕螺旋小动脉样的血管分布,核分裂少见,高度恶性瘤细胞大,异型性明显,小血管数量减少,核分裂多见,浸润明显,伴坏死,免疫表型:CD10、vimentin、ER、PR均阳性,CK、CD34、Melan-A均阴性.结论 ESS是女性生殖道少见肿瘤,术前常误诊为平滑肌瘤,确诊主要依靠组织病理学、免疫表型来判断肿瘤有无浸润及恶性程度的高低.CD10可作为ESS的鉴别诊断的重要标记之一.     

子宫乳头状浆液性癌3例

例１,５９岁,孕６产６。因绝经１９年、水样白带１年余伴阴道流血５月就诊。检查：血压２０／１１５ｋＰａ,体重５４ｋｇ,血糖４５ｍｍｏｌ·Ｌ－１。术中见子宫约２＋月孕大,双卵巢外观正常。行腹膜外盆腔淋巴结及腹主动脉旁取样,次广泛子宫切除＋双附件切除。病理检查：肿物突向宫腔,６ｃｍ×５ｃｍ×５ｃｍ,分叶状,侵犯肌层,切面灰白,有出血、坏死。镜下：瘤组织呈乳头状腺癌结构（图１）。乳头反复分支,部分呈簇状分布。表面上皮细胞异型性明显,部分细胞核体积大,深染,可见异常的有丝分裂象,并可见大量砂粒体（图２…     

腹膜浆液性乳头状腺癌4例并临床病理分析

目的探讨腹膜浆液性乳头状腺癌(peritoneal papillary serous carcinoma,PPSC)的临床病理学特征、免疫表型、鉴别诊断及预后。方法对4例PPSC行免疫组化SP法染色及HPV检测,并复习相关文献。结果 4例PPSC均为女性,年龄23~62岁,平均51岁。临床表现多为无特异性的腹部不适,CA125升高,影像学表现为腹腔肿块。镜下肿瘤细胞形成形态不一、大小不等的乳头状结构;肿瘤细胞为低柱状,核质比大,核圆形,核仁大,异型性明显,核分裂象易见。腺体及间质内可见砂砾体。免疫表型:肿瘤细胞CA125、WT1、CK7、p53、CEA、p16均呈阳性,部分肿瘤细胞表达CK5/6、ER、PR;不表达GCDFP-15、CR、D2-40、CK20、Villin、CDX2、TTF1;HPV检测阴性。结论 PPSC是一种少见的原发于腹膜的恶性肿瘤,临床误诊率高,依据其临床和病理组织学特点,结合免疫组化染色可以明确诊断。     

胰腺浆液性微囊性腺瘤11例临床病理分析

目的探讨胰腺浆液性微囊性腺瘤(serous microcystic adenoma of pancreas,SMAP)临床病理学特征及鉴别诊断。方法采用免疫组化En Vision两步法对11例SMAP进行检测,回顾性分析其临床病理学特征,并复习相关文献。结果 11例SMAP患者均为女性,发病年龄41~68岁,平均55岁,伴右上腹疼痛、恶心、呕吐、消瘦等临床症状。肿物位于胰腺头部5例(45.5%)。11例SMAP中10例为单发,1例为多发,肿瘤界清,切面呈蜂窝状。镜下见肿瘤由大小不一的小囊构成,囊壁内衬单层扁平或立方上皮细胞,胞质透亮,细胞核小、无异型。免疫表型:11例SMAP均表达CK、CK7、CK18、CK19、EMA,3例表达NSE、α-ACT,Cg A、Syn、vimentin、TG、Calretinin均阴性,Ki-67增殖指数﹤1%,D2-40、CD34血管阳性,二者在肿瘤细胞中阴性。结论 SMAP是一种少见的胰腺良性肿瘤,需与胰腺寡囊型囊腺瘤、假性囊肿、黏液性囊腺瘤、淋巴管瘤和毛细血管瘤、间皮瘤鉴别。     

GLUT1 and p63 expression in endometrial intraepithelial and uterine serous papillary carcinoma

AIMS: To analyse the expression patterns of GLUT1, p63 and p53 and the possible correlation between these markers in uterine serous papillary carcinoma (USPC) and endometrial intraepithelial carcinoma (EIC). METHODS AND RESULTS: Fourteen cases of USPC, 12 of which also showed EIC, were examined for GLUT1, p63 and p53 immunoreactivity. Four-micrometre sections from formalin-fixed paraffin-embedded tissue were immunostained using commercially available primary antibodies and Dako Envision Plus reagents for visualization. Membranous GLUT1 immunoreactivity was observed in all cases, including all 14 invasive tumours (100%) and 11 of 12 associated EICs (92%), and was confined to neoplastic cells. In USPC, staining tended to be strongest in superficial antistromal regions. p63 positivity was found in 8/14 (57%) USPCs and 9/12 (75%) associated EICs. In 11 cases p53 was overexpressed in both invasive USPC (11/14; 79%) and EIC (11/12; 92%). p53+ USPCs tended to be positive for p63, whereas p53- USPCs were also negative for p63. CONCLUSIONS: GLUT1 is expressed in the vast majority of USPC and EIC, suggesting a biological role during the early steps of carcinogenesis in endometrial serous neoplasms. GLUT1 expression may be induced by hypoxia-related as well as other mechanisms.     

Minimal uterine serous carcinoma: current concepts in diagnosis and prognosis

Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer with a propensity to have extra-uterine spread at diagnosis, in some cases despite limited involvement of the uterus. Serous endometrial intra-epithelial carcinoma (EIC) is a recently recognised entity with the same cytological features and p53 mutations as USC, but it does not demonstrate stromal or myometrial invasion. In addition to representing the putative precursor to USC, the pure form of serous EIC may also be associated with extra-uterine tumour at the time of diagnosis and with risk for recurrence, spread, and eventual death from tumour. Current evidence indicates that serous EIC is a form of minimal USC with behaviour that is stage dependent, thereby necessitating complete surgical staging despite limited disease in the uterus. We review the diagnostic criteria for minimal USC, pitfalls in the differential diagnosis, and discuss a practical approach to evaluating biopsies, polypectomies, or hysterectomies containing minimal USC.     

Uterine serous carcinoma and endometrial intraepithelial carcinoma arising in endometrial polyps: report of 5 cases, including 2 associated with tamoxifen therapy

Uterine serous carcinoma (USC) is the prototype of type II endometrial cancer. Endometrial intraepithelial carcinoma (EIC) is the precursor lesion of USC, Rarely, USC and EIC may arise within and be largely confined to otherwise benign endometrial polyps. This report describes 5 such cases. The patients ranged in age from 67 to 89 years, with a mean age of 75 years. In 2 of the cases there was a history of tamoxifen therapy. In 2 cases USC or EIC was confined to the endometrial polyp, and in 3 cases there was focal involvement of nonpolypoid endometrium. In 1 case there was a single small focus of extrauterine tumor within an ovarian vascular channel. In 2 cases the invasive tumor within the polyp also contained areas of endometrioid adenocarcinoma, and in 2 cases there was a component of clear cell carcinoma. In all cases USC and EIC were strongly reactive for p53 and showed a high proliferation index with MIB1. Two cases were negative with estrogen receptor, and 3 cases exhibited positive staining. The cases reported herein show that USC and EIC may rarely arise in benign endometrial polyps and that extrauterine involvement may be present without myometrial infiltration. Because 2 of the patients had been taking tamoxifen, this raises the possibility of an association between tamoxifen and the development of USC and EIC in the endometrial polyps that are characteristic of this medication.     

WT-1 assists in distinguishing ovarian from uterine serous carcinoma and in distinguishing between serous and endometrioid ovarian carcinoma

AIMS: It has been suggested that WT-1 is helpful in distinguishing a primary ovarian serous carcinoma (OSC) from a primary uterine serous carcinoma (USC). Since both neoplasms are often disseminated at diagnosis and since USC often spreads to the ovary and vice versa, it may be difficult to ascertain the primary site. This is important, since adjuvant therapies for OSC and USC may differ. WT-1 staining patterns also differ between OSC and ovarian endometrioid carcinoma and so it is possible that WT-1 may assist in the distinction of these two neoplasms, which is sometimes problematic, especially with poorly differentiated tumours. This study aims to document the value of WT-1 in these settings. Cases of ovarian borderline serous tumour, primary peritoneal serous carcinoma (PPSC) and uterine endometrioid carcinoma were also studied. METHODS AND RESULTS: Cases of OSC (n = 38), USC (n = 25) (in five of these cases there was also a component of endometrioid adenocarcinoma), ovarian endometrioid carcinoma (n = 13), uterine endometrioid carcinoma (n = 7), ovarian borderline serous tumour (n = 16) and PPSC (n = 6) were stained with WT-1. Cases were scored on a scale of 0-3, depending on the percentage of positive cells. The intensity of staining was scored as weak, moderate or strong. There was positive nuclear staining of 36 of 38 (94.7%) OSC with WT-1. In most OSC (68.4%), >50% of cells stained positively and staining was usually strong. Five of 25 (20%) USC were positive with only two cases exhibiting staining of >50% of cells. All primary ovarian and uterine endometrioid carcinomas were negative. All PPSC were positive, usually with diffuse strong immunoreactivity. Fourteen of 16 borderline serous tumours exhibited positivity with WT-1. CONCLUSIONS: WT-1 is useful in distinguishing OSC (characteristically diffuse strong nuclear positivity) from USC (characteristically negative). However, rarely OSC is negative and occasional cases of USC are positive. WT-1 may also be helpful in differentiating poorly differentiated OSC from poorly differentiated ovarian endometrioid carcinoma.     

Increased expression of neurotensin in high grade serous ovarian carcinoma with evidence of serous tubal intraepithelial carcinoma

High grade serous ovarian carcinoma (HGSC) without identifiable serous tubal intraepithelial carcinoma (STIC) within the fallopian tube (FT) occurs in approximately 50% of patients. The objective of this study was to use a multisite tumor sampling approach to study HGSC with and without STIC. RNAseq analysis of HGSC samples collected from multiple sites e.g. ovary, FT and peritoneum, revealed moderate levels of intrapatient heterogeneity in gene expression that could influence molecular profiles. Mixed-model ANOVA analysis of gene expression in tumor samples from patients with multiple tumor sites (n = 13) and patients with a single site tumor sample (n = 11) to compare HGSC-STIC to HGSC-NOSTIC identified neurotensin (NTS) as significantly higher (> two-fold change, False Discovery Rate (FDR) < 0.10) in HGSC-STIC. This data was validated using publicly available RNA-Seq datasets. Concordance between higher NTS gene expression and NTS peptide levels in HGSC-STIC samples was demonstrated by immunohistochemistry. To determine the role of NTS in HGSC, five ovarian cancer (OvCa) cell lines were screened for expression of NTS and its receptors, NTSR1 and NTSR3. Increased expression of NTS and NSTR1 was observed in several of the OvCa cells, whereas the NTSR3 receptor was lower in all OvCa cells, compared to immortalized FT epithelial cells. Treatment with NTSR1 inhibitor (SR48692) decreased cell proliferation, but increased cell migration in OvCa cells. The effects of SR48692 were receptor mediated, since transient RNAi knockdown of NTSR1 mimicked the migratory effects and knockdown of NTSR3 mimicked the anti-proliferative effects. Further, knockdown of NTSR1 or NTSR3 was associated with acquisition of distinct morphological phenotypes, epithelial or mesenchymal, respectively. Taken together, our results reveal a difference in a biologically active pathway between HGSC with and without STIC. Furthermore, we identify neurotensin signaling as an important pathway involved in cell proliferation and epithelial–mesenchymal transition in HGSC-STIC which warrants further study as a potential therapeutic target. © 2019 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.     

Advances in serous tubal intraepithelial carcinoma: correlation with high grade serous carcinoma and ovarian carcinogenesis

Early serous carcinoma in fallopian tube or serous tubal intraepithelial carcinoma (STIC), an early lesion limited to the epithelium of the fallopian tube and firstly identified from specimen obtained by prophylactic salpingo-oophorectomy, has provided insight into pelvic high grade serous carcinoma (HGSC). Increasing evidence indicates that STIC is a likely precursor for HGSC and several studies have focused on this lesion and its clinical significance. This review addresses recent advances in recognizing STIC and its correlation with HGSC and ovarian carcinogenesis. It also describes evidence regarding the fallopian tube as a source of some HGSCs, the protocol for optimizing histological evaluation of the tubes, the spectrum of tubal lesions from benign to noninvasive carcinoma, changes in diagnostic criteria from purely morphologic characteristics to a combination of morphologic features and molecular biomarkers, and new studies about potential biomarkers. However, the direct evidence regarding STIC as the precursor of HGSC is still tantalizing due to other possibilities that may also explain the origin of pelvic HGSC. Further molecular genetic studies are required to address this important question.     

子宫峡部内膜腺癌14例临床病理分析

目的探讨子宫峡部内膜腺癌（uterine isthmic endometrial adenocarcinoma,UIE）的临床病理特征、生物学行为及预后。方法回顾性分析14例UIE临床病理资料,总结其大体、组织学、免疫组化及预后特点,并与63例子宫体内膜腺癌（uterine corpus endometrial adenocarcinoma,UCE）相比较。结果UIE病灶中心在子宫峡部,仅有局部宫颈上端及宫体下端的蔓延。子宫峡部肿块呈外生性息肉状或内生浸润性生长,直径1.5～4cm;9例（64．3％）UIE浸润深肌层（〉50％）,其中4例浸润达浆膜。组织学上,1例为透明细胞型,2例为鳞腺癌,11例为子宫内膜样型;11例（78.6％）UIE为高级别（7例G2、4例G3）。UIE患者的临床分期,Ⅰ期1例（7．1％）,Ⅱ期8例（57.2％）、Ⅲ期4例（28,6％）及Ⅳ期1例（7.1％）。UIE与UCE在浸润深肌层、组织级别、临床分期及淋巴管浸润上差异有显著性;而ER、PR及p53的表达在UIE与UCE之间差异无显著性。结论子宫峡部内膜腺癌是少见的,临床病理及生物学行为与UCE不同。UIE是独立的预后差的子宫内膜腺癌。