Serous ovarian carcinoma recurring as a heterologous carcinosarcoma

Only two cases of recurrence of heterologous carcinosarcoma from adenocarcinoma of the ovary have been documented in the published literature. We report a case of serous ovarian carcinoma recurring as a heterologous carcinosarcoma. The immunohistochemical analysis of several biological parameters in primary ovarian adenocarcinoma and recurrent carcinosarcoma has been also performed.     

Wilms tumor gene immunoreactivity in primary serous carcinomas of the fallopian tube, ovary, endometrium, and peritoneum.

Wilms tumor gene (WT-1) expression has been reported in many human cancers, including most ovarian and peritoneal serous carcinomas, but has not been studied in carcinomas of the fallopian tube. In this study, the authors evaluated the immunohistochemical expression of WT-1 in serous carcinomas of the fallopian tube and compared their reactivity with that of ovarian, peritoneal, and endometrial serous carcinomas. All primary serous carcinomas of the fallopian tube (13 cases), ovaries (25 cases), and peritoneum (3 cases) were reactive with the WT-1 antibody, whereas all five primary endometrial serous carcinomas were nonreactive. WT-1 reactivity in an unknown primary serous carcinoma is therefore suggestive of an extrauterine site. The marked difference in WT-1 staining raises the possibility of genetic differences between serous carcinomas arising in the endometrium compared with those arising in the ovaries, fallopian tubes, and peritoneum.     

Differences of chemoresistance assay between invasive micropapillary/low-grade serous ovarian carcinoma and high-grade serous ovarian carcinoma

The objective of this study was to evaluate the pattern of chemoresistance in invasive micropapillary/low-grade serous ovarian carcinoma (invasive MPSC/LGSC) and high-grade serous ovarian carcinoma (HGSC) according to extreme drug resistance (EDR) assay testing. Surgical specimens of 44 recurrent ovarian cancer patients harvested at the time of cytoreductive surgery between August 1999 and February 2004 were identified retrospectively from the tumor registry database. Thirteen patients (29.5%) had recurrent invasive MPSC/LGSC and 31 (70.5%) patients had recurrent HGSC. Eight drugs were evaluated; EDR assay results were compared between LGSC and HGSC groups using Fisher exact tests and exact logistic regression models. Compared to HGSC, invasive MPSC/LGSC were more likely to manifest EDR to the drugs paclitaxel (69% vs 14%, P < 0.001), carboplatin (50% vs 17%, P= 0.05), cyclophosphamide (40% vs 23%, P= 0.41), gemcitabine (36% vs 19%, P= 0.40), and cisplatin (33% vs 28%, P= 0.72) and less likely to be resistant to etoposide (0% vs 44%, P= 0.007), doxorubicin (8% vs 45%, P= 0.03), and topotecan (8% vs 21%, P= 0.65). Exact logistic regression estimates revealed that invasive MPSC/LGSC patients had significantly increased probabilities of paclitaxel resistance odds ratio (OR) = 12.5 (95% CI: 2.3-100.0), P= 0.001 and carboplatin resistance OR = 4.8 (95% CI: 0.9-25.0), P= 0.07, while the HGSC cases were more likely to be resistant to etoposide OR = 12.1 (95% CI: 1.7-infinity), P=0.009 and doxorubicin OR = 8.6 (95% CI: 1.0-413.7), P= 0.05. In this retrospective analysis, patients with recurrent invasive MPSC/LGSC were more likely to manifest EDR to standard chemotherapy agents (platinum and paclitaxel). These observations may help to guide chemotherapeutic decision making in these patients if confirmed in a large-scale study.     

Transition of epithelial toward mesenchymal differentiation during ovarian carcinosarcoma tumorigenesis

BACKGROUND: It was the purpose of this study to test the monoclonal theory in ovarian carcinosarcoma. METHODS: Twenty-six women with a diagnosis of ovarian carcinosarcoma were subjected to a clinicopathologic analysis. Biopsies from metastatic lesions obtained at primary surgery and surgery for recurrent disease were reviewed. Special attention was paid to the composition of metastatic lesions and to florid desmoplastic reaction as a potential pitfall for the detection of sarcomatous areas. RESULTS: Biopsies derived from metastatic disease at primary surgery (n = 107) consisted of carcinoma cells only (n = 71, 66%), >50% carcinoma cells (n = 21, 20%), >50% sarcoma cells (n = 13, 12%), or sarcoma cells only (n = 2, 2%). The microscopic analysis demonstrated a preponderance of epithelial cells in the primary setting and suggested the epithelial component to drive the tumor, a finding consistent with the monoclonal theory. Biopsies derived from surgery for recurrent disease (n = 8) consisted of carcinoma cells only (0%), >50% carcinoma cells (n = 1, 13%), >50% sarcoma cells (n = 4, 50%), or sarcoma cells only (37%). Since sarcomatous cells dominated the tumorigenic cell population in the recurrent setting, this analysis revealed a change of the composition of metastatic lesions in time when compared to the data in the primary setting. This change was supported by the observation of a threefold higher incidence of sarcoma-dominated metastatic lesions at interval debulking when compared to primary debulking (24 vs 8%, respectively). The potential of a phenotypic change during ovarian cancer progression was further highlighted by the detection of two cases of carcinosarcoma that presented as a recurrence of epithelial ovarian carcinoma. CONCLUSION: Our results are consistent with the monoclonal theory of ovarian carcinosarcoma histogenesis, but suggest that there is a tendency toward a sarcomatous differentiation during disease progression. These data are important to understand the tumor biology and might have implications for a tailored treatment of ovarian carcinosarcoma.     

卵巢上皮性癌血清肿瘤标志物谱变化的临床意义

目的 探讨卵巢上皮性癌(卵巢癌)患者化疗后肿瘤标志物谱的变化及其潜在的临床意义.方法 选择1999年1月至2007年7月期间经肿瘤细胞减灭术及规范化疗的卵巢癌患者102例,对其术前、术后、每次化疗前、随访期间和复发前后的血清肿瘤标志物CA125、CA19-9和CP2的水平进行检测、分析,其中48例患者的肿瘤标志物记录完整而纳入分析,复发患者为28例,初治化疗患者20例(均为耐药病例).根据肿瘤标志物谱变化与否,分别将复发和初治化疗患者分为肿瘤标志物谱变化组与未变化组.平均随访时间为25个月.结果 (1)肿瘤标志物谱的主要变化表现为标志物的数最变化和(或)标志物的种类改变.28例复发患者中肿瘤标志物谱发生变化者占46%(13/28),20例初治化疗患者中标志物谱发生变化者占45%(9/20).(2)肿瘤标志物谱变化的复发患者中,病理类型以浆液性癌所占比例最高,为77%(10/13),而初治化疗患者中,以黏液性癌所占比例最高,为4/9.(3)复发患者肿瘤标志物谱变化组的无疾病进展期和中位总生存时间分别为22.2、60.0个月,较未变化组(分别为17.4、46.0个月)明显延长(P均<0.05);初治化疗患者肿瘤标志物谱变化组的中位总生存时间较未变化组(分别为15.9、25.0个月)明显缩短(P<0.05).结论 卵巢癌化疗期间和复发后肿瘤标志物谱可发生变化,化疗及随访期间应对肿瘤标志物进行联合检测.     

Recurrent clear cell carcinoma of the ovary changing into producing parathyroid hormone-related protein (PTH-rP) with hypercalcemia

We experienced the case of a clear cell carcinoma of the ovary arising from an endometrial cyst, which started to produce parathyroid hormone-related protein (PTH-rP) in a recurrent tumor, thus inducing hypercalcemia. Using immunohistochemical analysis, we demonstrated that the primary carcinoma was immunonegative for PTH-rP, but that the recurrent carcinoma was strongly immunopositive for PTH-rP.     

Alpha-fetoprotein producing ovarian clear cell carcinoma with a neometaplasia to hepatoid carcinoma arising from endometriosis: a case report

We present a rare case of alpha-fetoprotein (AFP) producing ovarian clear cell carcinoma. This is the first report of a clear cell ovarian carcinoma with hepatoid carcinoma arising from endometriosis. A 54-year-old menopausal woman had a primary ovarian carcinoma of International Federation of Gynecology and Obstetrics stage IIIc. Serum level of AFP was 4195 ng/mL. Histological examination revealed clear cell adenocarcinoma arising from endometriosis with hepatoid carcinoma. Metastatic liver and lymph node tumors were found after 25 months from the first surgery. However, the patient's serum AFP was within normal limits. The recurrent and metastatic tumors disappeared in response to combined liposomal doxorubicin and carboplatin chemotherapy. She has had a disease-free survival of 4 years. In conclusion, the patient had a clear cell ovarian carcinoma with hepatoid carcinoma arising clearly from endometriosis. The recurrent tumors did not show a component of hepatoid carcinoma. Therefore, it is possible to expect better survival with good sensitivity to chemotherapy.     

Ovarian cystic teratoma with primary epithelial cell melanoma

We report a rare case of malignant melanoma arising in a cystic teratoma of the ovary occurring in a 60-year-old woman who died in four months despite the combined treatment administrated (surgery and chemotherapy). Diagnosis of ovarian melanoma was confirmed by immunohistochemical positivity to S-100 protein and HMB 45. There was no evidence of extra-ovarian primary melanoma on clinical examination; therefore the diagnosis was primary ovarian melanoma. Melanoma metastases were detected on the uterus, the right ovary, the omentum and in one of the three excised left external iliac lymph nodes. A review of the literature is analyzed and discussed.     

卵巢上皮性癌组织中DNA甲基转移酶亚型mRNA的表达及其意义

目的 探讨DNA甲基转移酶（DNMT）亚型mRNA在卵巢上皮性癌组织中的表达及其临床意义。方法 采用半定量RT-PCR技术测定55例卵巢上皮性癌组织（其中原发性40例、复发性15例）及20例正常卵巢组织中DNMT亚型1、3A及3BmRNA的表达水平,并对其相关临床病理指标进行分析。结果 正常卵巢、原发性及复发性卵巢上皮性癌组织中,DNMT1 mRNA的表达水平分别为1．15、3．11、2．85,3者之间比较,差异有统计学意义（P〈0．05）;DNMT3A mRNA的表达水平分别为1．32、0．71、1．24,3者之间比较,差异无统计学意义（P〉0．05）;DNMT3B mRNA表达水平分别为0．25、0．60、2．12,复发性卵巢上皮性癌组织显著高于其他两者（P〈0．01）。原发性卵巢上皮性癌组织中DNMT1 mRNA表达水平,中低分化、手术病理分期为Ⅲ～Ⅳ期、淋巴结转移阳性者明显高于高分化、Ⅰ～Ⅱ期及淋巴结转移阴性者（分别为4．92和1．38,6．02和2．13,8．25和2．40;P均〈0．05）。原发性卵巢上皮性癌组织中,浆液性癌和透明细胞癌组织中DNMT1、3A、3BmRNA表达水平（分别为5．64、1．00、0．78）均明显高于其他病理类型（分别为1．76、0．44、0．23;P均〈0．05）。COX回归分析发现,卵巢上皮性癌组织中DNMT3B mRNA表达水平可能是影响患者生存期的惟一因素。结论 原发性及复发性卵巢上皮性癌组织中,DNMT1、3BmRNA高表达与其疾病进展及预后有关。     

Endometriosis-associated epithelial ovarian cancer is a more complicated disease than we suspected before

ObjectiveEndometriosis-associated epithelial ovarian cancer (EOC) often includes clear cell carcinoma and endometrioid-type carcinoma. Due to the low incidence of primary mucinous EOC and absence of association between endometriosis and primary mucinous EOC, we present an unusual endometriosis-associated mixed mucinous and endometrioid adenocarcinoma arising from the same ovary.Case reportA 54-year-old woman had an abdominal palpable mass for months. Medical and surgical history, as well as preoperative surveys was unremarkable, except of presence of a pelvic mass. She underwent an exploration laparotomy, and a 22-cm right ovarian tumor was found. Grossly, right ovarian tumor containing brownish cloudy cystic fluid 2450 ml and an apparent 4 × 4 × 2 cm-sized papillary growth. Microscopically, a confluent glandular and infiltrative pattern presented endometrioid adenocarcinoma, and cells with intracytoplasmic mucin and stratified elongated epithelial cells presented mucinous adenocarcinoma. Surgico-pathological stage was FIGO IIIA due to tumor invading to the peritoneum above the pelvis. Postoperatively, the dose-dense chemotherapy was applied with uneventful outcome.ConclusionThis is a rare case, composed with mixed mucinous and endometrioid adenocarcinoma of the same ovary, suggesting that careful pathological diagnosis of endometriosis-associated EOC is needed.     

Primary ovarian carcinosarcoma: a case report and review of the literature

Primary ovarian carcinosarcoma is characterized by an admixture of malignant epithelial and stromal elements. This neoplasm is extremely rare with fewer than 400 cases reported in the English literature. Its histogenesis, clinical features and optimal treatment remain unclear because of the rarity of primary ovarian carcinosarcoma. This study focuses on the clinical, pathological, immunohistochemical features and survival of a 73-year-old patient with primary ovarian carcinocarcoma. The patient was treated with surgery followed by combined chemotherapy with carboplatin and taxol and assigned to FIGO Stage IIIc. She died from the disease 17 months after surgery. In conclusion, ovarian carcinosarcoma is a very aggressive tumor, especially when it is diagnosed at advanced stage.     

Low-grade and high-grade serous Mullerian carcinoma: Review and analysis of publicly available gene expression profiles

ObjectiveMullerian low grade serous carcinoma (LGSC) and high grade serous carcinoma (HGSC) have distinct molecular profiles, clinical behavior and treatment response. Our objective was to study the biological profiles of these carcinomas.MethodsThis study examines publicly available gene expression profiles of LGSC and HGSC to identify differentially expressed genes and key pathways involved in carcinogenesis and chemotherapy response.ResultsOur analysis supports the hypothesis that serous mullerian carcinoma develop through two different pathways yielding two distinct malignancies, namely LGSC and HGSC. Furthermore, genes potentially involved in chemotherapeutic resistance of LGSC were identified. Suppressing the levels of these genes/proteins may increase clinical response to standard chemotherapy in patients with LGSC.ConclusionIn summary, this review shows the molecular profile of LGSC and HGSC through multi-center analysis of gene expression profiles of these tumors. The gene signatures of these neoplasms may potentially be used to develop disease-specific, targeted therapy for LGSC and HGSC.     

Carcinosarcoma arising from atypical endometriosis in a cesarean section scar

Malignant change of endometriosis in a cesarean scar (CS) is rare. We report a case of carcinosarcoma arising from atypical endometriosis in a CS scar, which was successfully treated with complete excision of the lesion and repair of the abdominal wall defect with autologous skin-muscle flap graft. A 41-year-old woman presented with a recurrent endometriosis in a CS scar. Within 16 years it changed from benign to atypical endometriosis and finally to carcinosarcoma after three operations. Complete excision of the tumor was performed, with a big defect of abdominal wall successfully repaired by autologous pedicle skin-muscle graft. The diagnosis of carcinosarcoma arising from atypical endometriosis was confirmed histologically. The lesion recurred 6 months after the fourth operation. She died of disease 15 months after the fourth operation. This case demonstrated that long-standing recurrent scar endometriosis could undergo malignant changes and should be made aware. The primary treatment is complete surgical excision.     

子宫内膜和卵巢原发性双癌的诊治和预后

目的探讨子宫内膜和卵巢原发性双癌的临床病理特点及预后。方法回顾性分析自1995年1月至2006年9月北京大学第一医院诊治的6例子宫内膜和卵巢原发性双癌病例资料。结果6例患者平均年龄为44.7岁,其中3例发生在绝经前。所有患者均接受手术治疗,术后3例病理报告子宫内膜和卵巢均为内膜样癌。5例患者术后接受化疗。全部患者随访3～112个月,1例术后60个月复发,再次接受化疗后病灶消失,所有患者均存活。结论子宫内膜和卵巢原发性双癌不同于单纯子宫内膜癌和卵巢癌,发病年龄早,以内膜和卵巢同为内膜样癌为主要病理类型,首选手术治疗,根据患者情况辅以化疗,预后良好。     

卵巢上皮性包涵体的起源与低级别卵巢浆液性癌的发病机制

目的 探讨卵巢上皮性包涵体的起源与低级别卵巢浆液性癌的发病机制.方法 收集山东大学齐鲁医院和美国亚利桑那大学附属医院病理科自2000年5月至2010年4月间收治的卵巢浆液性肿瘤患者及行预防性附件切除术患者的手术标本共198份.其中,卵巢肿瘤标本138份,包括卵巢浆液性囊腺瘤53份、卵巢交界性浆液性肿瘤44份、低级别卵巢浆液性癌41份;无明显病理学变化的同侧卵巢及输卵管标本116份(卵巢及输卵管分别为60、56份),取自60例行预防性附件切除术患者的一侧附件.HE染色后镜下观察所有标本的病理学形态特点;并采用免疫组化单染色法检测其免疫表型配对盒基因8抗原( PAX8)、钙结合蛋白(calretinin)、微管蛋白(tubulin)、核增殖相关抗原(Ki-67)的表达,免疫组化双染色法检测其免疫表型PAX8/calretinin的表达.结果 免疫组化PAX8、calretinin单染色法检测显示,90％( 54/60)的卵巢表面生发上皮细胞的免疫表型为PAX8阴性(-)、calretinin阳性(+),HE染色后镜下观察符合间皮组织的形态特点,为间皮型上皮;但有10％(6/60)的卵巢表面生发上皮细胞的免疫表型为PAX8(+)、calretinin(-),HE染色后镜下观察其与输卵管上皮组织的形态相似,为输卵管型上皮.60份正常卵巢中共有921个卵巢上皮性包涵体,表现出两种免疫表型,79％( 728/921)为PAX8(+)、calretinin(-),HE染色后镜下观察其与输卵管上皮组织的形态相似,为输卵管型包涵体;21％(193/921)为PAX8(-)、calretinin(+),HE染色后镜下观察其与间皮组织的形态相似,为间皮型包涵体.免疫组化PAX8/calretinin双染色法进一步验证了卵巢上皮性包涵体的这两种免疫表型.免疫组化PAX8、calretinin、tubulin单染色法检测显示,免疫表型为PAX8(+)、calretinin(-)、tubulin(+)的卵巢表面生发上皮和卵巢上皮性包涵体均包含纤毛型细胞和分泌型细胞2种柱状细胞,形态上接近输卵管黏膜上皮;而免疫表型为PAX8(-)、calretinin(+)、tubulin(+)的卵巢表面生发上皮和卵巢上皮性包涵体则为单层扁平或立方形细胞,与间皮组织的细胞形态类似.免疫组化tubulin、Ki-67单染色法检测显示,分泌型细胞与纤毛型细胞数的比值和细胞增殖指数在卵巢上皮性包涵体及卵巢浆液性囊腺瘤、卵巢交界性浆液性肿瘤、低级别卵巢浆液性癌中呈明显递增趋势(P＜0.05).结论 免疫表型为PAX8(+)、calretinin(-)的卵巢上皮性包涵体可能起源于输卵管,低级别卵巢浆液性癌的发生可能与分泌型细胞的克隆扩增有关.     

青春期卵巢型子宫内膜异位症保守手术后复发9例临床分析

目的: 探讨青春期卵巢型子宫内膜异位症（endometriosis,EMs）患者术后复发的可能原因。方法: 回顾性分析经保守性手术治疗后复发的9例青春期卵巢型EMs患者的临床病例资料。 结果: 9例患者中,Ⅰ期1例,Ⅲ期1例,Ⅳ期7例;7例患者于停止药物治疗后3~4个月痛经复发;7例患者初次手术后1年内病灶复发,另外2例分别为手术后3年及4年后复发。病灶复发可见于对侧卵巢3例,初次手术病灶较小一侧卵巢3例,同侧卵巢2例,双侧卵巢复发1例。5例患者初次手术后复发1次,3例患者复发2次,1例患者复发3次。2例患者术后妊娠并足月分娩。9例患者术后药物治疗2~6个周期。结论: 青春期卵巢型EMs患者保守手术后复发患者初次手术时临床分期高,病灶及痛经复发多在手术后1年内。临床分期高、痛经史、术后药物长期管理依从性差及妊娠意愿低等可能是手术后复发原因。     

不同类型上皮性卵巢癌中卵巢与输卵管病变累及关系的研究

目的:研究不同病理类型上皮性卵巢癌的输卵管累及情况,探讨浆液性卵巢癌起源于输卵管上皮的可能性。方法:回顾分析2008年10月至2013年2月在同济大学附属第一妇婴保健院进行初次手术治疗的146例上皮性卵巢癌患者的临床病理资料,比较不同病理类型对输卵管的累及,并比较高级别浆液性癌(HGSC)和低级别浆液性癌(LGSC)的临床病理资料。结果:上皮性卵巢癌中,浆液性癌有69.9%累及输卵管,高于其余病理类型;输卵管累及的病例中,卵巢的病理类型为浆液性癌者占90.6%。浆液性癌中,HGSC组的晚期病例(FIGOⅢ、Ⅳ期)数、累及双侧卵巢、累及输卵管、累及腹膜及大网膜的情况均高于LGSC组,差异有统计学意义(P0.05)。结论:高级别浆液性卵巢癌较其他病理类型,同时发生输卵管病变的情况更多见,提示输卵管可能为浆液性卵巢癌的起源之一。     

A case of rapidly growing ovarian squamous cell carcinoma successfully controlled by weekly paclitaxel-carboplatin administration

BACKGROUND: Primary squamous cell carcinoma of the ovary is uncommon and has a poor prognosis. Because of its rarity, the effective postoperative treatment is unknown. We describe a remarkable response of this tumor to weekly paclitaxel-carboplatin administration. CASE: A 53-year-old woman had rapidly growing primary squamous cell carcinoma of the ovary that metastasized to the abdominal wall and transverse colon after maximum cytoreductive surgery. The tumor was resistant to primary chemotherapy with cisplatin, vincristine, mitomycin C, and bleomycin. A combination of paclitaxel and carboplatin was used for second-line chemotherapy and was repeated every week. The patient tolerated the chemotherapy well and demonstrated a pathological complete response in the abdominal metastases following the five courses of chemotherapy. CONCLUSION: Weekly paclitaxel-carboplatin administration may be a safe and effective treatment for advanced and rapidly growing ovarian squamous cell carcinoma with primary resistance to chemotherapy.     

A case report of recurrent epithelial ovarian cancer metastatic to the sternum,diaphragm, costae,and bowel managed by aggressive secondary cytoreductive surgery without postoperative chemotherapy

BACKGROUND: Ovarian epithelial cancer typically presents in advanced stage and has been traditionally managed by a combination of cytoreductive surgery followed by adjuvant systematic chemotherapy. The management of recurrent ovarian cancer has been individualized: surgical resection of intraabdominal and/or pelvic disease has been performed when technically feasible and usually followed with chemotherapy. CASE: This case describes aggressive surgical management of recurrent ovarian cancer metastatic to the lower ribs, sternum, and diaphragm. A clear cell, Stage IIIA ovarian cancer was successfully resected in a 73-year-old female. The patient had total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy followed by six cycles of adjuvant chemotherapy, consisting of cyclophospamide and carboplatinum. A period of 8 years elapsed before recurrent disease was detected; there were two separate metastatic sites. A secondary cytoreductive surgery without further chemotherapy has been the mainstay of treatment. A combination of exploratory laparotomy and en bloc resection revealed the metastatic deposits, a 5-cm mass involving the diaphragm, the lower aspect of the manubrium sternum, and four right lower ribs. The second deposit was identified in the left paracolic gutter invading the sigmoid colon. CONCLUSION: At 47 months of follow-up, the patient is alive and without any evidence of measurable disease by exam and confirmed by CT scans of chest, abdomen, and pelvis. To our knowledge, this is one of the few reported cases managed successfully by surgical approach and is recommended in selected patients with metastatic ovarian cancer.