Hormonal therapy of endometrial stromal sarcoma

PURPOSE OF REVIEW: Low-grade endometrial stromal sarcomas are steroid receptor positive tumors with slow tumor progression and high recurrence rates, which lack established treatment protocols. We present an update on hormonal therapy options. RECENT FINDINGS: In the past, hormonal therapy consisted of progestins for advanced/recurrent/metastatic low-grade endometrial stromal sarcomas. Aromatase inhibitors and gonadotropin-releasing hormone analogues have become new effective alternatives for first and second line treatment. The high recurrence rates after short disease free intervals in low-grade endometrial stromal sarcoma patients were partly due to inadvertent growth stimulation during estrogen-containing hormone replacement therapy and tamoxifen treatment, which - according to current knowledge - are contraindicated. Recently, hormonal therapy has been introduced for the prevention of recurrences. Aromatase inhibitors are becoming the treatment of choice, since progestins are poorly tolerated due to side effects. The effective duration of preventive hormonal therapy is still undetermined. SUMMARY: Hormonal therapy with progestins, aromatase inhibitors and gonadotropin-releasing hormone analogues has become an effective treatment alternative to radiation and chemotherapy for low-grade endometrial stromal sarcoma patients. Preventive hormonal therapy is of particular interest in the setting of concomitant endometriosis.     

子宫内膜间质肉瘤和低分化子宫内膜样腺癌的病理特征及鉴别诊断

目的:探讨子宫内膜间质肉瘤和低分化子宫内膜样腺癌临床病理特征和鉴别诊断,以期提高诊断准确性.方法:回顾性分析2010年1月-2013年1月12例子宫内膜间质肉瘤和12例低分化子宫内膜样腺癌患者,分别从巨检、镜检、免疫组化三方面进行总结.结果:子宫内膜间质肉瘤肿块切面大部分灰白、灰黄色、无明显出血坏死.低分化子宫内膜样腺癌表面内膜增厚、粗糙、质脆,表面凹凸不平,子宫切面有些肉眼可见肌层浸润.镜检子宫内膜间质肉瘤呈不规则舌状或岛状浸润肌层,有突人淋巴管、血管内生长、肿瘤细胞密集.肿瘤内可见较薄壁螺旋小血管,血管周围肿瘤细胞同心圆样排列,缺乏子宫内膜间质细胞分化特点和典型生长方式,无螺旋小血管,伴盆腔淋巴结转移.子宫内膜间质肉瘤ER阳性率为25％,PR阳性率为8.33％,而低分化子宫内膜样腺癌ER阳性率为100％,PR阳性率为100％,两组比较差异显著(P＜0.05).结论:子宫内膜间质肉瘤和低分化子宫内膜样腺癌在镜检和免疫组化上可予区分.     

免疫组织化学标记在子宫内膜间质肉瘤诊断和治疗中的价值

 目的 探讨免疫组织化学标记在子宫内膜间质肉瘤（ESS）中的表达及其在诊断和治疗中的价值。方法 用免疫组织化学EnVision二步法对15例原发及3例转移复发ESS进行CD10、SM-MHC、h-caldesmon、AE1／3、CD99、Ki-67、CD34、c-kit、ER、PR的检测，并与其病理组织形态、临床并发症、鉴别诊断及预后对照。结果 17例CD10阳性，其中13例强阳性，7例伴平滑肌分化，3例伴上皮样分化，7例伴性索样分化；ER13例阳性，PR16例阳性； Ki-67 36 %～78 %。结论 子宫内膜间质肿瘤可伴多方向分化，主要为平滑肌和性索样分化；CD10是诊断子宫间质肿瘤的特异抗体，结合组织形态及SM-MHC、h-caldesmon等标记可增加其特异性；ER、PR常规检测主要用于指导孕激素辅助治疗。     

Characterization of a newly established endometrial stromal sarcoma cell line

We describe a newly established human sarcoma cell line derived from an endometrial stromal sarcoma (ESS). The cell line has been maintained in long-term cell culture for more than 2 years. It has been repeatedly analyzed in terms of morphology, immunocytochemical features, ultrastructure and karyotypic characteristics. In contrast to uniform endometrial stromal differentiation in vivo, the tumor cells were shown to display distinct phenotypical heterogeneity in vitro. In addition to the predominant cell type, which retained sarcomatous differentiation, foci of epithelial-like cells were observed in the cell culture. Immunocytochemical and ultrastructural analysis demonstrated a mainly mesenchymal phenotype with signs of epithelial characteristics, such as expression of cytokeratins, and the presence of desmosomes and kinetocilia, respectively. Cytogenetic analyses in early and late passages revealed unbalanced translocations between chromosomes 3 and 6 and an additional i(19)(q10), as common karyotypic changes in all tumor cells, indicating a monoclonal origin. Our new cell line can be used as an in vitro model to study the mechanisms of heterogenous differentiation patterns in ESS. Int. J. Cancer 77:424–428, 1998. © 1998 Wiley-Liss, Inc.     

Detection of complete response to imatinib mesylate (Glivec/Gleevec) with 18F-FDG PET/CT for low-grade endometrial stromal sarcoma

Malignant mesenchymal tumors consist of approximately 10% of uterine tumors. The majority of uterine sarcomas are leiomyosarcoma and endometrial stromal sarcoma (ESS). Surgery, radiotherapy, chemotherapy, and hormonal therapy are used for the treatment of ESS. Imatinib mesylate is indicated in the management of gastrointestinal stromal tumor and chronic myelogeneus leukemia. There is an interest to use imatinib mesylate in the treatment of c-kit positive ESS. We reported a case of 42-year-old female low-grade ESS progressed on chemotherapy and presented with objective response to imatinib mesylate. The treatment response was evaluated with FDG PET/CT. Complete metabolic response was detected. FDG PET, a sensitive method for tumor response evaluation on the basis of tumor metabolism changes, is useful for the evaluation of imatinib treatment in low-grade ESS. An erratum to this article can be found at     

子宫内膜间质肉瘤保留生育功能治疗体会

Abstract  

The paper introduced the experience of a case of recurrence of endometrial stromal sarcoma with fertility conservation treatment after full-term delivery. A 24-year-old unmarried patient who, with her increasing amount of menstruation in the late six months, had a mass in her lower-abdominal which was confirmed by B-ultrasonic diagnosis as myometrium mixed mass, was given an enucleation of uterus tumor. The pathological examination of tumor sample revealed it as low-grade endometrial stromal sarcoma (LESS). And the patient underwent 6 cycles of chemotherapy over 8 months before she got pregnant and had a full-term delivery. But in 34 months after delivery, the disease recurred with metastatic of pelvic and peritoneal cavity and the patient had to receive comprehensive therapy.     

Malignant mixed müllerian tumors. An ultrastructural and immunohistochemical analysis with histogenetic considerations

In the female genital tract, malignant mixed müllerian tumors (MMTs) are uncommon neoplasms of uncertain histogenesis. We have examined 11 MMTs by both electron microscopy (EM) and immunoperoxidase techniques (IPX). Eight were of endometrial, two were of ovarian, and one of tubal origins. The IPX analysis included monoclonal antibodies to keratin (k) and vimentin (v) and a polyclonal antibody to myoglobin. Carcinomatous elements were always keratin positive (K+) and were focally positive for vimentin in six tumors. Homologous stromal sarcoma cells were vimentin positive (V+) and in three tumors were focally K+. Ultrastructurally, the epithelial cells were not highly differentiated and the sarcomatous elements generally resembled normal proliferative-phase stromal cells. The epithelial and stromal elements were separated by a thin basal lamina that only rarely and focally had discontinuities. No transitional cellular forms were identified. A definite positive myoglobin reaction was seen in two of the four neoplasms in which rhabdomyoblasts were identified by light microscopy. Myofilaments were identified by electron microscope in three neoplasms.     

Synchronous granular cell tumor of the bladder, endometrial carcinoma and endometrial stromal sarcoma

We describe a very rare case of synchronous granular cell tumor of the bladder, endometrial carcinoma and endometrial stromal sarcoma. A 55‐year‐old woman with a 4‐month history of genital bleeding was cytologically diagnosed with endometrial carcinoma. Imaging studies suggested concomitant bladder tumor with the possibility of direct invasion from endometrial carcinoma. Total abdominal hysterectomy with bilateral salpingo‐oophorectomy and transurethral resection of bladder tumor was performed. The bladder tumor comprised polygonal cells with abundant eosinophilic, finely granular cytoplasm, separated by collagenous tissue. Neither nuclear pleomorphism nor tumor necrosis was found. Immunohistochemical expression of neural markers of neuron‐specific enolase and S‐100 allowed the diagnosis of granular cell tumor (GCT) of the bladder. Microscopic examination of endometrium revealed endometrioid adenocarcinoma with squamous differentiation (EAC). Ill‐defined nodular lesion comprising endometrial stromal sarcoma (ESS) was accidentally found in myometrium. Postoperatively, the patient underwent radiotherapy. This is the first well‐documented case of synchronous triple tumors comprising GCT of the bladder, uterine EAC and ESS.     

低度恶性子宫内膜间质肉瘤的临床病理特点

目的探讨低度恶性子宫内膜间质肉瘤(LGESS)的临床及病理特点.方法回顾性分析10例LGESS的临床及病理资料,部分病例辅以免疫组织化学染色.结果患者年龄35～61岁,平均为46.5岁.LGESS临床上多表现为不规则阴道出血.大体类型有宫内型、壁间型、弥漫型及混合型.肿瘤切面呈典型的鱼肉状、淡黄色或部份淡黄色、松软.2例有囊性变.镜下肿瘤细胞类似增殖期子宫内膜间质细胞,螺旋小血管多见.肿瘤细胞呈舌状浸润肌层或弥漫浸润.4例伴有不同程度的平滑肌分化,1例伴有性索样分化.8例获随访2～8年,1例绝经后患者术后4年复发,其余无复发.结论 LGESS临床少见,术前诊断困难,预后较好.大体病理检查有其特征性,镜下特点显示多样性,平滑肌分化常见.     

低级别子宫内膜间质肉瘤的治疗进展

低级别子宫内膜间质肉瘤是一种罕见的妇科恶性肿瘤,临床表现与一般妇科疾病相似,无特异性,因此,术前诊断困难,容易误诊或漏诊。目前最佳的治疗方式仍存在争议,本文主要就低级别子宫内膜间质肉瘤的治疗进展作一综述。     

A case of Müllerian adenosarcoma of the uterus

A case of Müllerian adenosarcoma of the uterus is reported. This is a low-grade malignant tumor situated between fibroadenomas and carcinosarcomas in the mixed mesodermal tumors. A 69-year-old woman complaining of an abdominal mass, underwent surgical resection of a tumor of the uterus. The tumor was divided into two parts, i.e. polypoid tumor in the endometrial cavity and nodular tumor in the myometrium. The 2 tumor types showed continuity. Microscopically, it was a so-called mixed tumor consisting of a glandular element of benign epithelial cells and an undifferentiated sarcoma; it was diagnosed as adenosarcoma.     

A case of mixed mesodermal tumor of the uterus with alpha-fetoprotein production

A case of mixed mesodermal tumor of the uterus with alpha-fetoprotein (AFP) production in a postmenopausal woman is reported, with special reference to its histogenesis. Judging from the serum AFP levels, the AFP content of the tumor and immunohistochemical localization of AFP in the tumor, AFP was produced by the tumor. The observation that in this patient AFP existed exclusively in carcinoma cells strongly supports the hypothesis that malignant transformation of Müllerian epithelial and stromal cells in mixed mesodermal tumors of the uterus occurs independently after the primitive mesenchymal cells have differentiated towards epithelial and stromal components.     

Müllerian adenosarcoma of the uterus: an ultrastructural study of four cases.

Four cases of uterine müllerian adenosarcoma, a distinctive form of mixed müllerian tumor, were studied by light and electron microscopy. All tumors showed the characteristic histologic pattern of benign neoplastic glands within sarcomatous stroma. Ultrastructurally, both mesenchymal and epithelial cells were seen. The mesenchymal cells showed some features of endometrial stromal cells, including the presence of intracytoplasmic collagen fibers. The epithelial cells formed glands, which resembled benign endometrial glands and were separated from the stroma by a well-defined basal lamina. No transitional cells between the epithelial and mesenchymal cells were seen. The ultrastructural features of these tumors suggest that the sarcomatous portion is of endometrial stromal origin. The glandular portion may arise, along with the stroma, from multipotential stem cells, or the glands may be non-neoplastic entrapped endometrial glands stimulated by the stroma and thus appearing to form an integral part of the tumor.     

Conditional immortalization of human endometrial stromal cells with a temperature-sensitive simian virus 40

The study of immortalization and other alterations associatedwith neoplastic transformation of endometrial stromal cellsis important to understanding the development of uterine sarcomasand mixed tumors. Because stromal cells are important regulatorsof associated epithelial cells, alterations in the regulationof stromal cell proliferation that influence epithelial cellsmay also contribute to the development of endometrial carcinomas.To study immortalization and associated phenotypic and geneticalterations of human endometrial stromal cells, cultures weretransfected with a plasmid containing an ori-, temperature-sensitivemutant SV40, A209 (tsSV40). Morphologically transformed colonieswere selected and propagated at the permissive temperature untilthey entered ‘crisis’. In contrast to human fibroblasts,every clone tested was immortalization competent. The frequencyof immortalization was     

卵巢子宫内膜样间质肉瘤临床病理观察

目的探讨卵巢子宫内膜样间质肉瘤的发生机制、临床病理特征、诊断与鉴别诊断及预后。方法 对1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 肿瘤组织由形似增生期子宫内膜间质细胞的小细胞组成, 瘤细胞呈卵圆形或短梭形, 胞浆稀少, 肿瘤细胞呈漩涡状围绕似子宫内膜螺旋小动脉的厚壁小血管。免疫组化示瘤细胞表达Vimentin和CD10, 不表达Calretinin, α-inhibin, H-caldesmon, CD99, CD117, CD34, desmin, SMA and CK(AE1/AE3)。结论 卵巢子宫内膜样间质肉瘤在临床为一惰性生长的恶性肿瘤, 非常罕见。其鉴别诊断主要包括子宫内膜间质肉瘤累及卵巢(直接侵犯或转移)和卵泡膜细胞-纤维瘤。     

低级别子宫内膜间质肉瘤的临床诊治探讨

为了探讨低级别子宫内膜间质肉瘤(LESS)的临床病理学特征、诊断和鉴别诊断,分析10例LESS的临床病理特点、网织纤维染色和免疫组化染色研究其病理学特征。结果显示,LESS临床上主要表现为阴道不规则流血;瘤细胞类似于增生期子宫内膜间质细胞,形态较一致,圆形或卵圆形,少数为短梭形,胞质较少,胞核圆形或不规则形,核染色质较细;肿瘤内有大量丛状生长的分支状小的、薄壁的血管,类似于子宫内膜的螺旋动脉,部分肿瘤血管透明变性呈星状或放射状结构;网织纤维染色见网状纤维丰富,围绕瘤细胞生长。肿瘤细胞8例CD10阳性,6例ER阳性,6例PR阳性,2例Actin阳性,CD34、CD117和Melan-A肿瘤细胞均阴性。初步研究结果提示,LESS易误诊为子宫内膜间质结节、未分化子宫内膜间质肉瘤、富于细胞性平滑肌瘤、静脉内平滑肌瘤病及血管周上皮样细胞肿瘤,确诊主要依靠组织病理学和免疫组织化学。     

胃肠道间质瘤58例临床病理分析

 分析胃肠道间质瘤（GIST）的形态特点和免疫组织化学特征，探讨肿瘤的组织来源和分型。方法 对58例GIST进行光镜观察，用EnVision二步法免疫组织化学方法检测波形蛋白、CD117（c-Kit）、CD34等抗原标记物在肿瘤中的表达情况。结果 58例GIST占同期消化系统间叶性肿瘤的86.6 %（58／67）；其中梭形细胞为主者41例，伴有上皮样细胞者12例，单纯由上皮样细胞组成者5例，瘤细胞呈长、短梭形和圆形，胞质弱嗜酸，常见核端空泡，有时呈印戒样或透明细胞样；排列呈漩涡状、栅栏状或弥漫性巢状。免疫组织化学显示肿瘤组织中抗原标记物表达阳性率波形蛋白为100 %（58／58），CD117 94.8 %（55／58），CD34 79.3 %（46／58）。结论 GISTs是消化道最常见的间叶性肿瘤，光镜形态与真性肌源性和神经源性肿瘤极为相似，CD117、CD34等免疫标记物可对其作出正确诊断，GIST可能起源于多潜能的、卡哈尔间质细胞样的前体细胞。     

子宫内膜间质肉瘤的MRI表现

目的:探讨子宫内膜间质肉瘤的MRI表现特点。方法:回顾性分析7例经手术及病理证实的子宫内膜间质肉瘤患者的临床和MRI资料。所有病例均行MRI平扫。结果:本组7例患者子宫体积均增大。6例病变位于宫腔内,呈息肉状突向宫腔或弥漫性填充宫腔;1例位于子宫肌壁间,类似囊性变性子宫肌瘤。2例囊实混合性占位,5例实性占位。7例ESS病变直径范围为2.5cm-15cm,平均8.8cm。肿瘤在MRI平扫上5例T1WI 呈等信号或低信号,T2WI呈稍高信号;2例T1WI呈等及低信号,T2WI呈稍高为主的混杂信号,伴有出血或坏死囊变,其中1例位于子宫肌壁间。6例可见向子宫肌层侵润性生长,子宫T2WI结合带低信号中断或消失,其中1例可见宫颈、双侧输卵管壁、卵巢及膀胱受侵,1例子宫肌层及宫旁可见扭曲条点状流空信号影。4例合并少量盆腔积液,2例合并子宫肌瘤,1例合并卵巢滤泡囊肿,3例合并增殖期子宫内膜。病理示低度恶性ESS 6例,未分化ESS 1例。结论:子宫内膜间质肉瘤好发于宫腔内,也可见于子宫肌壁间,多向子宫肌层浸润性生长,于T1WI呈等或低信号,T2WI呈稍高信号,伴出血或坏死囊变时呈T2WI稍高信号为主的混杂信号,其在MRI上具有一定的信号特点,能为该病的诊断提供帮助。     

Granulosa cell tumor arising in the ovary irradiated 22 years earlier for endometrial stromal sarcoma

We encountered a rare case of metachronous tumors in a 57-year-old Japanese housewife who presented with an ovarian granulosa cell tumor 22 years after receiving treatment for endometrial stromal sarcoma. Treatment consisted of a total abdominal hysterectomy and left salpingo-oophorectomy followed by 40 Gy whole abdominal irradiation. Since the second tumor occurred in the ovary that had been previously irradiated to treat the first metachtonous neoplasm, the present case can help to improve our understanding of the histogenesis of granulosa cell tumors.     

A malignant mixed mesodermal tumor of the ovary

We report a primary malignant mixed mesodermal tumor in the right ovary of 75-year-old woman. She was admitted to Kobe West Municipal Hospital because of an abdominal fullness and an upper abdominal pain. A laparotomy yielded yellowish-clear ascites (2,000 ml) a tumor located in the right ovary, an upper abdominal mass the size of a child's head between the stomach and the transverse colon, and disseminating small tumors of the peritoneum. The left ovary and uterus showed no particular change. Four months after the onset of her symptoms, the patient died of carcinomatous cachexia and dyspnea. On microscope examination, the tumor of right ovary showed combined features of an adenocarcinoma, an adenosquamous carcinoma and a serous cystadenocarcinoma with foci of a heterologous stromal differentiation, that is an area of immature, striated muscle cells, bone, and cartilage and undifferentiated spindle cells. Immunohistochemical stains were useful for determining elements of the tumor cells. Epithelial tumor cells were positive for cytokeratin, epithelial membrane antigen, and CEA, while mesenchymal tumor cells were generally positive for vimentin and the immature muscle cells were especially positive for desmin, actin, and myosin. Additionally, myoglobin was identified in the rhabdomyoblast. Finally, S-100 protein was present in cartilage area and partially present in the adenocarcinomatous element.