子宫内膜间质肿瘤35例临床病理分析

目的 探讨子宫内膜间质肿瘤(endometrial stromal tumours, ESTs)的临床病理学特征,以期提高对ESTs的诊断和治疗水平.方法 回顾性分析35例子宫内膜间质肿瘤患者的临床及病理资料,部分辅以免疫组织化学染色分析.结果 患者平均年龄45岁,临床主要表现为子宫占位和阴道出血,35例ESTs中子宫内膜间质结节(endometrial stromal nodule, ESN)4例、低级别子宫内膜间质肉瘤(low-grade endometrial stromal sarcoma,ESS)26例、未分化子宫内膜肉瘤(undifferentiated endometrial sarcoma,UES)5例.ESN和ESS均由类似增生期子宫内膜间质的肿瘤细胞构成,并伴有丰富的螺旋小动脉,UES则具有明显的细胞异型性并缺乏螺旋动脉.18例辅以免疫组化标记的病例中17例CD10阳性,7例SMA局灶阳性,4例desmin局灶阳性.结论 ESTs是一组诊断可能具有困难的子宫间叶肿瘤,确诊依靠组织病理和一组免疫组化抗体标记,诊断上应与平滑肌肿瘤、PEComa等肿瘤相鉴别.     

子宫内膜间质肿瘤病理诊断的实用策略

<正>子宫内膜间质肿瘤(endometrial stromal tumors, EST)是第二大常见的子宫间质肿瘤，与平滑肌肿瘤相比，其发病率较低，年发病率约为0.30/10万^[1]。EST分为4类：子宫内膜间质结节(endometrial stromal nodule, ESN)、低级别子宫内膜间质肉瘤(low-grade endometrial stromal sarcoma,LGESS)、高级别子宫内膜间质肉瘤(high-grade endometrial stromal sarcoma, HGESS)和未分化子宫肉瘤(undifferentiated uterine sarcoma, UUS)。     

子宫内膜间质肉瘤:从Ⅰ期低级别转化为Ⅳ期高级别肿瘤的临床病理分析

目的探讨子宫内膜间质肉瘤(endometrial stromal sarcoma,ESS)从Ⅰ期低级别子宫内膜间质肉瘤(low grade endometrial stromal sarcoma,LGESS)转化为Ⅳ期高级别子宫内膜间质肉瘤(high grade endometrial stromal sarcoma,HGESS)的临床病理学特征、诊断及治疗。方法分析1例由LGESS转化为HGESS患者的临床资料、病理学特征(包括组织学、免疫表型、超微结构)及全景癌基因检测,并对相关文献进行复习。结果患者女性,52岁,初次宫腔镜下肿瘤电切的病理诊断为LGESS,Ki-67增殖指数为1%,全子宫+双侧附件切除术证实无肿瘤浸润转移。宫腔镜术后12个月患者出现复发、转移,屡次切除的复发肿瘤标本Ki-67增殖指数不断上升,最终达40%;至宫腔镜术后26个月转化为Ⅳ期,31个月转化为HGESS,临床出现腹腔、胸腔、肺、骨骼及皮肤等多处转移,于初次手术后48个月死亡。历次手术标本的CD10均(3+);ER及PR在初次标本中呈(2+),初次复发的标本中呈(1+),此后的手术标本均(-);p53在初次标本中呈(-),逐渐转变为在HGESS标本中(3+)。cKit(9,11,13,17)、EGFR(18,19,20,21)、PDGFRa(12,18)基因外显子均无突变。结论尽管LGESS多为早期、临床预后好,即便复发也多为晚期复发,但仍有LGESS转化为HGESS的情况出现,应引起临床和病理医师的高度重视。     

伴有特殊形态子宫内膜间质肉瘤10例临床病理特征分析

目的探讨低级别子宫内膜间质肉瘤(low grade endometrial stromal sarcoma,LGESS)变异形态的临床病理特点。方法回顾性分析10例LGESS的临床病理特征、免疫表型特征并对患者进行随访。采用免疫组化En Vision两步法检测CD10、vimentin、ER、PR、SMA、desmin、H-caldesmon、α-inhibin和Ki-67的表达,并复习相关文献。结果10例LGESS平均发病年龄47. 5岁,肿块最大径4. 1～12. 2 cm;镜下除经典形态外,8例见黏液变,4例伴平滑肌分化,3例呈印戒细胞样形态,2例伴纤维化,2例间质出现石棉样纤维,2例微囊性变,1例伴广泛玻璃样变性,1例同时出现性索样、腺管样、腺瘤样瘤样、梁状、囊性变、伴横纹肌分化等形态,1例子宫内膜间质肉瘤(endometrial stromal sarcoma,ESS)卵巢转移灶见蜕膜样形态。10例LGESS均表达CD10、vimentin,1例ER、PR阴性,ESS瘤细胞中Ki-67增殖指数均10%,1例伴性索样分化ESS局部α-inhibin阳性,在伴有平滑肌分化的区域H-caldesmon阳性(4/10)、desmin(4/10)阳性、SMA(6/10)阳性。结论 LGESS特殊变异形态给病理医师带来病理诊断上的挑战,联合应用免疫组化及基因检测可为临床提供更精准的病理诊断。     

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.     

子宫内膜间质肉瘤55例临床病理特点和预后分析

目的 了解子宫内膜间质肉瘤(ESS)的病理形态特征并分析影响预后的相关指标.方法 收集该院55例ESS患者的临床和病理资料,所有病例重新阅片,参照文献分类为低级别子宫内膜间质肉瘤(LGESS)、不伴核多形的未分化子宫内膜肉瘤(UES-U)、伴有核多形的未分化子宫内膜肉瘤(UES-P);同时观察肿瘤细胞的形态特点,包括纤维样、肌样、黏液样、上皮样分化,并计数核分裂象等.对所有病例进行临床资料的收集并随访.结果 LGESS、UES-U、UES-P型病例分别为39、9、7例.病理形态上,ESS有多种形态分化并存的特点,LGESS、UES-U及UES-P型病例中分别有12.8%(5/39)、5/9及5/7伴有两种以上混合的形态学分化;同一病例的不同区域核分裂象计数和组织学类型亦存在较大差异.临床上肿瘤复发比例分别为51.6%(16/31)、5/6、2/3;LGESS无死亡病例,UES-U和UES-P中各有2例死亡,且UES-U的死亡病例均有局灶UES-P区域.按核分裂象最高计数进行预后分析,≥10/10 HPF的病例复发率显著高于＜10/10 HPF的复发率(P=0.009),在LGESS病例中亦存在这种统计学差异,所有死亡病例的核分裂象最高计数均＞30/10 HPF.结论 ESS常见不同程度分化重叠及多向分化的特点,尤以UES-U和UES-P中更为常见,因此应充分取材以寻找诊断线索.肿瘤中伴有UES-P图像,同时伴核分裂象计数高度活跃可能会增加死亡风险.在LGESS病例中,核分裂象最高计数≥10/10 HPF的肿瘤复发率显著增高,在诊断时应引起重视.

Abstract：

Objective To investigate the clinicopathologic features and the prognostic factors of endometrial stromal sarcoma (ESS). Methods 55 cases of endometrial stromal sarcoma were reviewed and categorized into 3 pathologic types based on the related literatures, i.e. , low grade endometrial stromal sarcoma (LGESS), undifferentiated endometrial sarcoma with nuclear uniformity (UES-U) and undifferentiated endometrial sarcoma with nuclear pleomorphism (UES-P). Meanwhile, the pathologic features were reviewed, including fibroid, myoid, mucoid, and epithelioid differentiation and mitotic index.Clinical and follow-up data were collected. Results In endometrial stromal sarcoma, two or three pathologic types co-existed in one case, including 12. 8% (5/39) of LGESS, 5/9 of UES-U, and 5/7 of UES-P.Mitotic index varied in different regions of one tumor from rare to high. Multi-differentiation was also commonly seen in ESS. The numbers of cases in LGESS, UES-U and UES-P were 39, 9 and 7, with recurrence rate of 51.6% ( 16/31 ), 5/6 and 2/3, respectively. There was no death case in LGESS, and 2 cases were died in UES-U and UES-P, respectively. In the 2 death cases of UES-U, both had focus of UES-P. There was a significant difference in the recurrence rate between cases with different mitotic index ( ≥ 10/10 HPF and ＜ 10/10 HPF, P = 0. 009), especially in LGESS group. All death cases had high mitotic index ( ＞ 30/10 HPF). Conclusions It is a common phenomenon in ESS that two or three pathologic types may exist in one case, especially in UES-U and UES-P. And multi-differentiation is also commonly seen in ESS. So adequate pathologic sampling is important for pathologists to make a correct diagnosis of ESS in daily work. The recurrence rates are significantly higher in cases with high mitotic index,especially in LGESS. In addition, the presence of UES-P and high mitotic index may increase the risk of death in the patients.     

子宫内膜间质肉瘤中BCOR、CD10和Cyclin D1的诊断意义

目的探讨子宫内膜间质肉瘤(endometrial stromal sarcoma, ESS)中BCOR、CD10和Cyclin D1的表达及其诊断意义。方法收集38例ESS,其中低级别子宫内膜间质肉瘤(low-grade endometrial stromal sarcoma, LG-ESS)23例、高级别子宫内膜间质肉瘤(high-grade endometrial stromal sarcoma, HG-ESS)12例和未分化子宫肉瘤(undifferentiated uterine sarcoma, UUS)3例,另收集6例子宫平滑肌肉瘤(包括2例黏液性平滑肌肉瘤)和20例子宫富于细胞性平滑肌瘤作为对照组,采用免疫组化EnVision法检测BCOR、CD10和Cyclin D1在不同子宫组织中的表达,分析三者的差异表达并复习相关文献。结果 BCOR在HG-ESS、LG-ESS、UUS、平滑肌肉瘤和富于细胞性平滑肌瘤中的表达分别为7、1、0、0和0例,CD10在HG-ESS、LG-ESS、UUS、平滑肌肉瘤和富于细胞性平滑肌瘤中的表达分别为8、21、1、2和4例,Cyclin D1在HG-ESS、LG-ESS、UUS、平滑肌肉瘤和富于细胞性平滑肌瘤中的表达分别为5、4、1、1和0例。结论 BCOR在HG-ESS中具有较高的敏感性与特异性,特别是在Cyclin D1阴性和伴黏液样背景的HG-ESS中,可联合CD10和Cyclin D1用于HG-ESS的诊断及鉴别诊断。     

子宫内膜间质肉瘤及双侧卵巢内膜样间质肉瘤1例

患者,41岁.2006年1月因阴道不规则出血伴腹痛2个月行诊刮术,病理报告为少量增生期子宫内膜伴子宫内膜间质增生,可见丰富的螺旋动脉,核分裂5～6个/10 HPF,由于组织破碎,与周围结构不清,目前难以判断良、恶性.术后患者常出现阴道不规则出血,多次B超及宫腔镜检查均见宫腔后壁占位,病理检查示子宫内膜间质细胞增生,但不能明确与周围组织的关系.近2个月出现下腹痛,2009年8月B超示宫腔占位,右侧附件混合型包块.2009年9月行手术治疗,术中切除右侧卵巢肿块送快速病理检查,诊断为子宫内膜间质肉瘤(endometrial stromal sarcoma,ESS).遂予扩大全子宫切除术+双侧附件切除术.     

肺穿刺活检转移性低级别子宫内膜间质肉瘤临床病理分析

目的探讨肺穿刺活检转移性低级别子宫内膜间质肉瘤(low-grade endometrial stromal sarcoma, LG-ESS)的临床病理特点、免疫表型及鉴别诊断。方法收集2例肺穿刺活检转移性LG-ESS,分析其临床资料、病理组织学、免疫表型特点,并复习相关文献。结果 2例均为原位复发且发生肺多发转移患者,临床行肺穿刺活检。镜下肿瘤细胞均呈短梭形弥漫排列,间质见螺旋小动脉,例2可见平滑肌样细胞。免疫表型:瘤细胞CD10、ER、PR均弥漫阳性,Ki-67增殖指数5%,例2平滑肌样细胞SMA、h-caldesmon均阳性。子宫原发肿瘤病理切片形态一致,且均见脉管内瘤栓。结论 LG-ESS发生肺转移非常罕见,肺穿刺活检诊断困难,需充分了解病史,结合组织病理学和免疫表型,排除肺原发肿瘤后可确诊。     

Endometrial stromal neoplasms of the uterus. A clinicopathologic study.

A clinicopathologic study of uterine endometrial stromal tumors (EST) has been performed with special emphasis on histologic and immunohistochemical differential criteria and prognostic factors. The material comprised three stromal nodules (SN), twelve low grade stromal sarcomas (LGESS) and five high grade stromal sarcomas (HGESS). Previously unreported endolymphatic growth was found within one SN. EST showed an association of mitotic index (IM) with atypia, degree of stromal differentiation, additional non-stromal differentiation and venous invasion. IM was the best criterion in the differential diagnosis of LGESS and HGESS and the most significant histologic prognosticator. The present study shows that a histologic grade of stromal sarcoma was a more significant prognostic factor than pTNM stage. The results suggested that clinicopathologic classification of EST could be supplemented by including the following subgroups: a) SN--without intravascular growth, and potentially malignant SN--with endolymphatic growth within the tumor; b) LGESS with IM < 2 and no atypia, and LGESS with 2 > IM < 10 and mild atypia; c) HGESS with 10 > IM < 20 and moderate atypia, and HGESS with IM > 20 and marked atypia. Contrary to common view these observations indicate that the distinction of some SN and LGESS from stromal hyperplasia is possible in an endometrial curretage material.     

Low-grade endometrial stromal sarcoma presenting as multiple pulmonary nodules: A potential pitfall in fine needle aspiration and core biopsy specimens - A Cytological - Pathological Correlation

Low-grade endometrial stromal sarcoma (LGESS) is the second most common malignant mesenchymal tumor of the uterus. The most common location is the uterine corpus, but it can also primarily arise in a variety of extrauterine locations such as pelvis, ovary, abdominal cavity, vagina, and vulva. We are reporting a case of a 47-year-old female with no significant medical history who presented with multiple pulmonary nodules. Fine needle aspiration (FNA) specimen revealed spindle cell neoplasm consistent with the diagnosis of LGESS. The differential diagnosis included neuroendocrine tumor, synovial sarcoma, solitary fibrous tumor, smooth muscle tumors, and peripheral nerve sheath tumors. The clinical, cytological, and histopathologic details of this case, as well as a discussion of the potential pitfalls and differential diagnosis of spindle cell lesions of the lung are described.     

Endometrial stromal tumor with limited infiltration and probable extrauterine metastasis: report of a case

Endometrial stromal nodule (ESN) is a tumor composed of cells closely resembling those of the endometrial stroma with minimal cytologic atypia. The most important criterion for the differential diagnosis from the endometrial stromal sarcoma (ESS) is a well-defined noninfiltrative expansile border. However, the definition of the ESN also includes a tumor with the presence of focal irregularities or fingerlike projections of the margin into the adjacent myometrium, none of which exceeds 2 to 3 mm. In some cases, however, it is difficult to differentiate marginal irregularities of ESN from "true invasion" of ESS. We described a case of extrauterine ESS that was associated with small intramyometrial stromal lesions with limited infiltration. The intramyometrial lesion could be definitionally categorized as ESNs. However, peritumoral fibroblastic band and inflammatory stromal reactions, irregular fingerlike projections, and multiple concurrent extrauterine ESS strongly suggested that these were small primary focus of ESS mimicking ESN. We propose that the patient with endometrial stromal tumor with limited infiltration should be more carefully followed than the usual ESN for possible metastasis and that a hysterectomy with meticulous histological examination of the specimen be performed before a diagnosis of primary extrauterine ESS is made, even in a case showing a grossly or radiologically normal uterus.     

Myxoid endometrial stromal sarcoma of the uterus

A rare case of a myxoid type of endometrial stromal sarcoma of the uterus in a 41-year-old woman is reported. A tumor was found in the myometrium and was well circumscribed, measuring 9 x 7 x 7 cm in size. The tumor was mainly composed of a hypocellular area with tumor cells separated by prominent myxoid stroma. The tumor cells were spindle-shaped and resembled endometrial stromal cells. Numerous small thin-walled vessels were seen throughout the tumor. Immunohistochemically, the tumor cells were diffusely stained for estrogen and progesterone receptors and CD10, and focally and weakly for HHF35, alpha-smooth muscle actin and desmin, but not stained for h-caldesmon. These results indicated that the tumor originated from endometrial stromal cells. The tumor had an increased mitotic activity (MIB-1 labeling index: 1-10%), and focally showed nuclear pleomorphism. Thus, this tumor had a malignant potential and was diagnosed as a myxoid type of low-grade endometrial stromal sarcoma. The patient is currently well with no evidence of local recurrence or metastasis 21 months after the operation. This case indicates a wide morphological spectrum of endometrial stromal tumor. A myxoid endometrial stromal sarcoma should be considered in the different diagnosis of the intramural myxoid tumors in the uterus.     

The diagnosis of uterine leiomyosarcoma and endometrial stromal sarcoma]

The diagnostic problems in uterine smooth muscle tumors and endometrial stromal tumors are reviewed and discussed with analysis of 14 selective cases collected from the affiliated hospital. Data suggested that, in the differential diagnosis of benign and malignant uterine smooth muscle tumors, it is not comprehensive to use mitotic activity as the only criterion. Nuclear atypia and some other clinico-pathological features should be considered together, and, it is important to recognize the "mitotic active" leiomyoma which runs a benign course despite a high mitotic rate. In endometrial stromal sarcoma, the growth pattern and the extent of tumor spreading seem not closely correlated with the mitotic activity, nor the atypia, and, the clinical stage was considered as a significant reference in the prognosis. Thus, it is suggested that the differentiation of endometrial stromal sarcoma into low and high malignancy according to the mitotic rate alone is not the best reliable guide in evaluating the tumor behavior. It is emphasized that the extent of spreading of the tumor should be stated in the diagnosis. Immunohistochemical study revealed that the sex cord element in endometrial stromal sarcoma and other uterine tumors expressed a myogenous rather than an epithelial phenotype.     

Endometrial stromal sarcoma of the uterus with rhabdoid features

A case of endometrial stromal sarcoma of the uterus with rhabdoid features, occurring in a 57 year old woman is reported. Electron microscopy and immunohistochemistry revealed that the rhabdoid cells contained intermediate filaments which were positive for vimentin, cytokeratin, alpha-smooth muscle actin, and muscle specific actin, but not for myoglobin and desmin. This indicated that the tumor in this case differed somewhat from the three rhabdoid tumors and an endometrial stromal sarcoma with rhabdoid differentiation previously reported and that, therefore, these tumors were heterogeneous.     

低度恶性子宫内膜间质肉瘤临床病理分析

目的 探讨低度恶性子宫内膜问质肉瘤(LESS)的临床病理学特征、诊断和鉴别诊断。方法 分析17例LESS的临床病理特点,通过网织纤维染色、免疫组化染色和电镜观察来研究其病理学特征。结果 LESS临床上主要表现为阴道不规则流血。HE染色见肿瘤组织成巢团样浸润,肿瘤细胞圆形、卵圆形或梭形。肿瘤内有大量的小血管。网织纤维染色见网状纤维丰富,围绕瘤细胞生长。肿瘤细胞14例CD10阳性,12例ER阳性,13例PR阳性,3例actin阳性,C1934、CDll7、Melan—A肿瘤细胞均阴性。电镜观察见肿瘤细胞胞质内的中间丝呈杂乱无序的排列。结论 LESS易误诊,确诊主要依靠组织病理学和免疫组织化学;病理形态上看似良好的低度恶性子宫内膜间质肉瘤,预后不一定好。     

Mixed endometrial stromal and smooth muscle tumor: Report of a case with focal anaplasia and early postoperative lung metastasis

A rare case of a mixed endometrial stromal and smooth muscle tumor arising in the uterus of a 74‐year‐old woman is reported. The patient underwent hysterectomy for an enlarging uterine mass, and a large intramural tumor, showing marked central hyaline necrosis with calcification, was found. The tumor consisted of an admixture of a low‐grade endometrial stromal sarcoma (ESS) and a fascicular proliferation of spindle cells suggesting smooth muscle differentiation, and a characteristic ‘star‐burst’ appearance was found. In the ESS region, there were a few small foci of anaplasia where large polygonal cells with atypical nuclei and abundant eosinophilic cytoplasm proliferated, and the proliferative activity was locally increased in these foci. A small metastatic nodule appeared in the lung nine months after the hysterectomy, and the resected metastatic lesion showed features of anaplastic spindle cell sarcoma which was immunoreactive for CD10 but not for smooth muscle markers. Mixed endometrial stromal and smooth muscle tumors should be regarded as malignant neoplasms with the potential for hematogenous metastasis, particularly when they contain foci of cellular anaplasia.     

Inverse correlation of secreted frizzled-related protein 4 and beta-catenin expression in endometrial stromal sarcomas

Endometrial stromal sarcomas are rare uterine tumours. Whereas the histology and immunohistochemistry of these tumours are well documented, almost nothing is known about the molecular mechanisms involved in their pathogenesis. To characterize the genes altered in these malignancies, a genome-wide cDNA library was generated by suppression subtractive hybridization and a set of differentially expressed clones was isolated. These were then used to produce custom-spotted cDNA arrays. Genes deregulated in endometrial stromal sarcomas were identified by cDNA array hybridization and were confirmed by quantitative real-time PCR analyses and in situ hybridization. Following cDNA array analysis, more than 300 genes deregulated in endometrial stromal sarcoma were selected and sequenced. Among the most significantly deregulated genes were those of secreted frizzled-related proteins (SFRPs), in particular secreted frizzled-related protein 4 (SFRP4). SFRPs are putative modulators of the Wnt-signalling pathway and play a role in different cellular events including cell proliferation. Compared with normal endometrium, the expression of SFRP4 was decreased in both low-grade endometrial stromal sarcoma (ESS; n = 10) and undifferentiated endometrial sarcoma (UES; n = 4), being lower in the latter more aggressive form. These results were verified on paraffin wax-embedded tissue by quantitative real-time PCR analysis and in situ hybridization. Furthermore, the expression of beta-catenin, an important component of the Wnt-signalling pathway, was regulated in an opposite manner to SFRP4, being particularly increased in undifferentiated sarcomas. The activation of the Wnt-signalling pathway was additionally supported by the immunohistochemical demonstration that beta-catenin was translocated to the nucleus in UES. SFRP4 may therefore be a putative tumour suppressor involved in deregulation of the Wnt pathway and in the pathogenesis of ESS and UES.