Placental Site Trophoblastic Tumor of the Uterus: An Ultrastructural and Immunohistochemical Study and Immunohistochemical Study

Ultrastructural and immunohistochemical studies in a case of placental site trophoblastic tumor (PSTT) of the uterus were carried out in order to define the nature of the abnormal tissue. By electron microscopy, the large cells, whether mononuclear or syncytial, showed numerous ribosomes, prominent Golgi elements, and abundant rough endoplasmic reticulum (RER) filled with granular material. Pseudopods and microvilli were found on the cell surfaces. By immunofluorescence, the well-developed filamentous cyto-skeleton proved to be actin-rich. (3-HCG (human chorionic gonadotropin) and SP, (0,-specific pregnancy glycoprotein) were detected in only a few tumor cells, whereas most of them stained for HPL (human placental lactogen). The present results show the secretory nature of most of the tumor cells, which resemble the intermediate trophoblast of the placental bed. Together with previous studies, they suggest that a varying spectrum of syncytiotrophoblastic differentiation exists in PSTT. Decidual, myometrial, or histiocytic cells do not seem involved in the histogenesis of the tumor tissue.     

Coexisting epithelioid trophoblastic tumor and placental site trophoblastic tumor of the uterus following a term pregnancy: report of a case and review of literature

Gestational trophoblastic neoplasms are a group of fetal trophoblastic tumors including choriocarcinomas, epithelioid trophoblastic tumors (ETTs), and placental site trophoblastic tumors (PSTTs). Mixed gestational trophoblastic neoplasms are extremely rare. The existence of mixed gestational trophoblastic neoplasms that were composed of choriocarcinoma and/or PSTT and/or ETT was also reported. Herein, we present a case of uterine mixed gestational trophoblastic neoplasm which is ETT admixed with PSTT, and reviewed 9 cases of mixed gestational trophoblastic neoplasms reported in English literature available. The most common combination was a choriocarcinoma admixed with an ETT and/or PSTT. Mixed gestational trophoblastic neoplasms present in women of reproductive age and rare in postmenopausal, Abnormal vaginal bleeding is the most common presenting symptom, serum β-HCG levels are elevated, mostly below 2500 mIU/ml, the tumor was limited to uterus in 7 cases, the rest of 3 with pulmonary metastases at the time of diagnosis. Mixed gestational trophoblastic neoplasms have more similar clinical features with intermediate trophoblastic tumors (ITTs). Total hysterectomy with lymph node dissection is recommended treatment for mixed gestational trophoblastic neoplasms, and chemotherapy should be used in patients with metastatic disease and with nonmetastatic disease who have adverse prognostic factors.     

中间型滋养细胞肿瘤的临床病理特征

目的 探讨上皮样滋养细胞肿瘤(ETT)和胎盘部位滋养叶细胞肿瘤(PSTY)的临床病理特征.方法 结合临床表现、形态学特征、发病机制和免疫表型,对4例PSTT及1例ETT病例进行分析,并对鉴别诊断、治疗和预后进行分析.结果 PSTT和ETT临床表现为阴道不规则流血,伴HCG轻一中度升高.PSTT瘤细胞呈片块状或条索状穿插于子宫肌层平滑肌束间,常浸润血管壁;ETT瘤细胞排列成巢团状,位于玻璃样物或肿瘤坏死物中,呈地图样外观.免疫表型表达上皮性、滋养细胞性标志物,但对HPL、Mel-CAM、PLAP及p63的表达有差异.治疗手段以全子宫切除术和术后化疗为主,预后较好.结论 PSTT与ETT是罕见的中间型滋养细胞肿瘤(ITT),二者具有不同的形态学特征和免疫表型,但临床表现及惰性生物学行为相似.     

A typical postcesarean epithelioid trophoblastic lesion with placenta increta: Case report and literature review

We report an extremely rare case of unusual atypical epithelioid trophoblastic lesion from placenta increta. A 25-year-old Chinese woman with a history of 1 cesarean delivery was admitted to the hospital at 37 weeks’ gestation. Magnetic resonance imaging (MRI) showed the feature of placenta increta. An elective primary cesarean section was scheduled and a healthy baby was born. The patient was suggestive of placenta increta and implantation site was resected. Histology indicated a lesion consisting of epithelioid trophoblastic cells with an intermediate pattern between a classical placental site nodule and an epithelioid trophoblastic tumor. This may be linked to her previous cesarean delivery, which supports the relationship between atypical epithelioid trophoblastic lesion formation and surgical interventions. Her serum human chorionic gonadotropin (hCG) was 352.4 IU/L after delivery and gradually decreased to normal level.     

Neoplastic and non-neoplasti mediate trophoblasts: An immunohistochemical an structural study

Five cases of non-molar trophoblastic disease including one placental site trophoblastic tumor (PSTT), two exaggerated placental sites and two choriocarcinomas were compared with each other and with normal chorionic villi and placental site. This involved light microscopic, immunohistochemical and ultrastructural studies. Comparison of PSTT with choriocarcinoma suggested that the former represented a neoplastic transformation of placental site intermediate trophoblast. The PSTT showed a characteristic immunohistochemical distribution of human placental lactogen and human chorionic gonadotropin, resembling that of the placental site intermediate trophoblast. Placental site trophoblastic tumor cells were also characterized ultrastructurally by prominent perinuclear filaments, abundant rough endoplasmic reticulum, or both. Infiltrating intermediate trophoblasts in exaggerated placental sites were similar to PSTT cells rather than normal placental site intermediate trophoblasts. However cells with vacuolated cytoplasm or spindle-shaped intermediate trophoblastic ceils were observed more frequently in the PSTT than the exaggerated placental sites. The intermediate trophoblastic cells in the choriocarcinomas showed a morphologically transitional form from cytotrophoblastic cell to syncytiotrophoblastic cell, but did not share unique ultra-structural similarities with placental site intermediate trophoblasts.     

中间型滋养细胞肿瘤的临床病理分析

目的探讨中间型滋养细胞（IT）源性肿瘤即胎盘部位滋养叶细胞肿瘤（PSTT）及上皮样滋养细胞肿瘤（ETT）临床病理特征及免疫表型表达特点、诊断与预后。方法北京妇产医院1959-2005年中,因恶性滋养叶疾病住院治疗患者共1012例,从中筛选6例PSTT及1例ETT,对其临床特征、病理诊断要点及免疫组织化学（SP法）结果进行分析,抗体包括CK18、胎盘催乳素（hPL）、人绒毛膜促性腺激素（hCG）、Mel—CAM（CDl46）及胎盘碱性磷酸酶（PLAP）。对照组为20例附有底蜕膜的早期绒毛及20例见有着床部位反应的葡萄胎。结果平均年龄PSTT为32．4岁,ETT为36岁;症状主要为阴道不规则出血和闭经;术前检查hCG呈正常→轻度→中度增高趋势,1例睾酮明显增高。5例PSTT术前行刮宫及宫腔镜切取标本之确诊率为3／5。镜下PSTT瘤细胞呈单个、条索状或片状浸润于肌纤维间,将单个或一束肌纤维分离;ETT则显示岛屿状细胞群位于玻璃样物及坏死物中,呈地图样结构。治疗手段以子宫切除术或术后辅以化疗为主。随访时间14个月至19年,其中1例PSTT术后5个月发生胰腺转移,单纯化疗PSTT患者疗效尚不能肯定,其余均无复发。结论PSTT与ETT分别为发生于着床部位IT及绒毛膜类型IT,二者有不同病理形态学,免疫组织化学特征性表达可辅助诊断和鉴别诊断;术前诊断性刮宫病理诊断具有重要临床意义;PSTT与ETT显示相同的生物学行为和预后。     

胎盘部位滋养细胞肿瘤的临床病理特点及鉴别诊断

目的了解胎盘部位滋养细胞肿瘤（ＰＳＴＴ）的临床病理特点及其鉴别诊断要点。方法对５例ＰＳＴＴ进行临床,光镜,电镜及免疫组化研究,并同时对比观察１０例绒癌及２例过度的胎盘部位反应（ＥＰＳ）。结果ＰＳＴＴ见于育龄妇女,前次妊娠多为足月产,常见症状为闭经及／或阴道出血。血清绒毛膜促性腺激素（ｈＣＧ）可有轻～中度升高。光镜下瘤细胞组成单一,仅见中间型滋养细胞,成片状,条索状穿插浸润于子宫平滑肌束间。血管浸润明显,却少有出血或坏死。分裂相少见。电镜下瘤细胞核周有丰富的中间丝。免疫组化表现为胎盘催乳素（ｈＰＬ）阳性而ｈＣＧ多为阴性。结论ＰＳＴＴ为一少见的滋养细胞肿瘤,具有独特的光镜,电镜及免疫组化特点,这些特点可与其它滋养细胞疾病鉴别     

10例胎盘部位滋养层细胞肿瘤临床,病理免疫组化及超微结构研究

报告10例胎盘部位滋养层细胞肿瘤,平均年龄28.8岁,都有生育史。临床表现为阴道不规则流血或闭经。病理组织学特征为多边形或梭形胞浆丰富的瘤细胞弥漫或片状、索条状浸润于子宫肌纤维间。电镜下瘤细胞表面有少量微绒毛,瘤细胞间可见桥粒。免疫组化染色显示良性病例HPI强阳性,恶性病例HCG明显阳性。病人血HCG值明显升高,瘤细胞核分裂增多,HCG染色阳性增强似可作为提示生物学行为的参考。     

Epithelioid trophoblastic tumor after induced abortion with previous broad choriocarcinoma: a case report and review of literature

Epithelioid trophoblastic tumor (ETT) is a rare trophoblastic tumor originating from chorionic-type intermediate trophoblasts (ITs). It is usually associated with a prior gestational event. We present a 44-year-old woman who had unusual pregnancy related history. The patient received her second spontaneous abortion at the age of 25 years and had suffered from choriocarcinoma in left board ligament at the age of 29 years. She admitted no more treatment after 3 courses of multiagent chemotherapy when serum β-hCG returned to normal. Then she had Full-term delivery, induced abortion at the ages of 32, 33 years. The patient had high serum levels of beta-human chorionic gonadotropin (6587 IU/L). Microscopically, the tumor was composed of mainly mononuclear tumor cells, grew in cords, nests, and sheets within which were aggregates of hyaline material. Most were with distinct cell borders, eosinophilic cytoplasm. Immunohistochemical staining revealed strong diffuse reactivity for cytokeratins (AE1/AE3, CK18), P63, focal reactivity for beta-human chorionic gonadotropin, human placental lactogen, and inhibin-alpha. The Ki-67 index was 77%. The histological and immunohistochemical features were characteristic of epithelioid trophoblastic tumor. This is the first reported case of these two gestational trophoblastic tumor happened on one person with the intervening normal pregnancy.     

Extrauterine placental site trophoblastic tumour in association with a lithopedion

AIM: We describe an unusual case of extrauterine placental site trophoblastic tumour located in pouch of Douglas in association with a lithopedion. METHODS AND RESULTS: A 35-year-old female presented with acute abdomen and peritonitis following rectal perforation. The patient gave a history of 5 months amenorrhoea followed by vaginal bleeding 5 years prior to admission. At laparotomy, a lithopedion was found in pouch of Douglas with rectal perforation and peritonitis. The lithopedion was removed, rectal perforation was sutured and a colostomy was performed. The colostomy was closed later and tumour was seen in the colostomy wound as well as attached to the lithopedion removed previously. The patient presented with a repeated episode of rectal perforation and the tumour had spread to colon, small intestine, omentum, mesentery and right ovary. CONCLUSION: A high-grade malignant placental site trophoblastic tumour with aggressive clinical course occurred at an extrauterine site. It complicated calcified abdominal pregnancy and resulted in repeated rectal perforation and peritonitis.     

Gestational trophoblastic tumours and non-neoplastic trophoblastic lesions: morphology and immunocytochemistry to refine the diagnosis

Gestational trophoblastic disease (GTD) is generally subclassified into hydatidiform moles (HM), Gestational trophoblastic tumours (GTTs) and non-neoplastic trophoblastic lesions. GTT represent a spectrum of neoplasms that originate from the extravillous trophoblast and have variable malignant potential. These include choriocarcinoma (CC), Placental site trophoblastic tumour (PSTT) and Epitheloid trophoblastic tumour (ETT). Among tumour like conditions exaggerated placental site reaction (EPSR) and placental site nodule (s)/plaque (s) are included. The morphological appearances of GTT can be mimicked both by non-malignant tumour-like conditions and also non-gestational tumours with trophoblastic differentiation, adding to the diagnostic dilemma of these already rare tumours. GTT have a favourable prognosis and better response to specific chemotherapeutic regimens when compared to non-gestational malignant genital tract neoplasms, and thus their recognition is important. This article discusses the morphological appearances and immunocytochemistry of these rare tumours along with recent developments in the form of targeted immunotherapy.     

Diagnosis and treatment of placental site trophoblastic tumor

Here we report a case of a placental site trophoblastic tumor in a 36 year old Chinese woman, 31 months following a prior normal pregnancy. Her clinical presentation and ultrasound findings were uncharacteristic; and the final definitive diagnosis was established based on histological examination in conjunction with immunohistochemistry studies and a normal beta human chorionic gonadotropin level. The tumor exhibited high grade histological features with tumor necrosis, nuclear atypia and high mitosis. The patient was successfully treated with hysterectomy with pre- and post-operative chemotherapy.     

Epithelioid trophoblastic tumor of the uterus: cytological and immunohistochemical observation of a case

Epithelioid trophoblastic tumor (ETT) is a new entity of trophoblastic tumor and 14 such cases were reported by Shih and Kurman in 1998. However, only three subsequent cases supporting ETT have been reported. Recently, we experienced a case of ETT in a 37-year-old woman whose preoperative endometrial brushings showed atypical mononucleate giant cells and who underwent hysterectomy with the diagnosis of a uterine fibroid. The specimens revealed a 2.5 x 3.0 cm yellow-tan intramural nodule located in the lower uterine segment, which was composed of a neoplastic proliferation of intermediate trophoblasts in epithelioid arrangements. Immunohistochemically, the tumor cells were diffusely positive for cytokeratin and inhibin-alpha, and focally positive for human chorionic gonadotropin and human placental lactogen. She presented an uneventful clinical course as of September 2001.     

层粘连蛋白和纤维粘连蛋白在正常绒毛膜葡萄胎、绒毛膜癌组织中的表达

目的探讨层粘连蛋白和纤维粘连蛋白在正常绒毛膜和滋养细胞肿瘤中的作用。方法用免疫组织化学方法观察层粘连蛋白和纤维粘连蛋白在正常绒毛膜、葡萄胎和绒毛膜癌组织中的表达。结果在正常绒毛膜组织中,二种蛋白有广泛表达,如绒毛上皮基膜、毛细血管内皮基膜、绒毛间质、滋养细胞柱和蜕膜。在葡萄胎,层粘连蛋白分布于绒毛上皮基膜和蜕膜组织,在基膜中表达强度有所不同;纤维粘连蛋白分布于绒毛和蜕膜内,呈弱阳性表达。在侵蚀性葡萄胎和绒毛膜癌,层粘连蛋白和纤维粘连蛋白在细胞质中均呈强阳性表达,在细胞间质内呈阳性或弱阳性表达。结论层粘连蛋白和纤维粘连蛋白与孕早期绒毛膜和蜕膜的形成及滋养细胞肿瘤的发生、侵润密切相关。     

Molecular genotyping in the diagnosis of trophoblastic tumours

Tumours showing trophoblastic differentiation in women with raised levels of serum human chorionic gonadotrophin may not always be a gestational trophoblastic neoplasia (GTN). A gestational origin can be confirmed by demonstrating the presence of paternally derived DNA in the tumour using molecular genotyping. Genotyping can also be used to identify the causative pregnancy in GTN, particularly important for women with placental site or epithelioid trophoblastic tumours where the time interval between the causative pregnancy and tumour diagnosis has prognostic significance. Molecular genotyping has confirmed that the antecedent pregnancy is not always the causative pregnancy in GTN and that tumours may have originated in a much earlier pregnancy in multiparous woman. Where tumour tissue is not available for investigation, cell free DNA isolated from patients' plasma can be used to facilitate diagnosis. Patients' plasma may also be used to investigate other molecules that might prove to be useful prognostic biomarkers in the future.     

The pathology of gestational trophoblastic disease: recent advances

When inundated with numerous specimens of products of conception as the consequence of miscarriage, it is all too easy for histopathologists to forget that the biology of trophoblast and the events of early placental implantation continue to fascinate because of the inherently invasive properties of the non-villous (extravillous) trophoblast. However, unlike the invasion of a malignant tumour, the invasion of trophoblast is controlled. The failure of adequate conversion of maternal uteroplacental arteries is a major pathogenetic phenomenon of important disorders of pregnancy including pre-eclampsia. However, it is in the field of gestational trophoblastic disease that diagnostic acumen is most called for. There are several problematic areas that give rise to diagnostic error; e.g., the diagnosis of early complete mole as partial mole, the over-diagnosis of hydatidiform mole in tubal pregnancy and the diagnosis of placental site non-villous trophoblast as placental site trophoblastic tumour or choriocarcinoma, particularly if associated with atypia, as frequently observed in complete mole. The chorionic villi of early diploid complete mole show characteristic features of villous profile, stromal mucin and stromal nuclear debris. The distinction between complete mole and triploid partial mole can be facilitated by ploidy analysis and immunohistochemistry for the product of the paternally imprinted, maternally expressed gene, p57kip2. Persistent trophoblastic disease (PTD) is a clinical not a histopathological diagnosis and the role of the histopathologist once a diagnosis of PTD has been made is limited. Invasive mole and choriocarcinoma are encompassed by PTD. Tumours of the non-villous trophoblast are placental site trophoblastic tumour and the more recently recognised epithelioid trophoblastic tumour. The role of immunohistochemistry in the elucidation of trophoblastic lesions is discussed pragmatically.     

p57(KIP2) immunohistochemical staining of gestational trophoblastic tumours does not identify the type of the causative pregnancy

AIM: To determine whether immunohistochemical staining for p57(KIP2), the product of the maternally expressed gene CDKN1C, can be used to differentiate between gestational trophoblastic tumours arising from a complete hydatidiform mole and those originating from non-molar pregnancies. METHODS: The immunohistochemical expression of p57(KIP2) was investigated in 23 cases of choriocarcinoma and 17 placental site trophoblastic tumours. Fourteen of the tumours examined were shown by DNA analysis to have arisen from complete hydatidiform moles and 26 from non-molar pregnancies. RESULTS: Five of 11 (45%) post-complete hydatidiform mole choriocarcinomas and two of three (67%) post-complete hydatidiform mole placental site trophoblastic tumours were found to be p57(KIP2)+ and showed similar immunostaining characteristics to tumours that developed from non-molar pregnancies. Although there was a statistically significant reduction in the proportion of cases showing positive p57(KIP2) staining in post-complete hydatidiform mole tumours compared with those originating in non-molar pregnancies [proportion difference 0.35 [95% confidence interval (CI) 0.05, 0.61], P = 0.02], immunostaining did not provide diagnostically useful information to differentiate between these tumours in clinical practice. There was no significant difference between the extent of staining in choriocarcinoma versus placental site trophoblastic tumours [proportion difference 0.17 (95% CI - 12, 42), P = 0.19]. The majority of both types of gestational trophoblastic tumour were positive for the presence of the p57(KIP2) protein irrespective of their genetic origin. CONCLUSION: Immunostaining for p57(KIP2) fails to discriminate between gestational trophoblastic tumours that have arisen from complete hydatidiform moles and those that have originated from other types of pregnancy.     

Sensitivity and specificity of finding of multinucleate trophoblastic giant cells in decidua in placentas from high-risk pregnancies

This is a retrospective analysis of sensitivity and specificity of clustered placental basal plate multinucleate trophoblastic giant cells for various clinical conditions and placental lesions associated with fetal and placental hypoxia. Selected clinical and placental parameters of 375 consecutive cases of placentas with clusters of multinucleate trophoblastic giant cell (at least 3 cells with at least 3 nuclei) in the decidua (study group) were compared with all remaining 2674 placentas concurrently studied (control group) in 20-week-or-more high-risk pregnancies. Multinucleate trophoblastic giant cell was found in 12.3% of placentas. The study group had statistically significantly more cases of preeclampsia, abnormal Dopplers, induction of labor, and cesarean sections, with its placentas lighter and with more common other hypoxic lesions than in the control-group placentas. The multinucleate trophoblastic giant cell prevalence negatively correlated with gestational age (R = -0.56), peaking at the turn of the second and the third trimesters of pregnancy and declining afterward, and most strongly correlated with the excessive amount of extravillous trophoblasts in the chorionic disc (R = +0.33). The sensitivity of multinucleate trophoblastic giant cells was, on average, 3 times lower than the specificity, the latter averaging greater than 90%. In conclusion, finding of multinucleate trophoblastic giant cells is not exclusively limited to uteroplacental malperfusion of preeclampsia but is also seen in other types of high-risk pregnancy and in association with other placental hypoxic lesions and patterns. Multinucleate trophoblastic giant cells most likely reflect a premature fusion of extravillous trophoblasts because of several factors, likely including also hypoxia. Being highly specific, finding the multinucleate trophoblastic giant cells is unlikely to give a false-positive result and therefore has high value in retrospectively explaining the perinatal morbidity and mortality.