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Background: Uterine carcinosarcomas (UCS) constitute 3–4% of all uterine malignancies and 16% of deaths caused due to uterine neoplasms. Aim: In this study, we aimed to perform DNA-based mutation analysis in 12 genes (KRAS, NRAS, EGFR, C-KIT, BRAF, PDGFRA, ALK, ERBB2, ERBB3, ESR1, RAF1, PIK3CA) to determine the molecular subtypes of UCS using next-generation sequencing (NGS) in patients with aggressive UCS and poor prognosis. We aimed to compare the results of our analysis with clinicopathological data to contribute to the development of targeted therapy approaches related to the molecular changes of UCS. Materials and Methods: In this study, we included 12 cases diagnosed with uterine carcinosarcomas and examined the changes in oncogenes that play a role in UCS pathogenesis. For the analysis of mutation, the clinicopathological data were compared with the variations in the DNA-based gene panel consisting of 12 genes and 1237 variants in the UCS using the NGS method. Results: EGFR mutation was found in 91.7% of the cases, mutation in 41.7%, PDGFRA mutation in 25%, KRAS and PIK3CA mutation in 16.7%, and C-KIT mutation in 8.3% of the cases. Although no statistical significance was found between the detected mutation and clinicopathological data, it was concluded that PDGFRA mutation might be associated with advanced-stage disease development. Conclusion: This study's findings regarding different molecular types of UCS and information on oncogenesis of UCS can provide inferences for targeted therapies in the future by identifying targetable mutations representing early oncogenic events and thereby contribute toward further studies on this subject.
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Background: Evaluation was done in 100 women presenting with postmenopausal bleeding, (PMB), to discuss the utility of hysteroscopy combined guided endometrial curettage in the diagnosis of uterine cancer and endometrial hyperplasia, and, treat benign lesions, like polyps, synechiae at the same sitting. At MGMH during the years, 2002 to 2006, there were 57 women, and at care, 40 women with PMB during 2011 to 2013, and three in a nursing home, Hyderabad, were investigated.Methods: Evaluation was done in 100 women presenting with PMB by hysteroscopy and curettage to diagnose the cause of PMB and benign lesions like polyps, synechiae were managed by operative hysteroscopy. Bettocchi 5 mm hysteroscope, monopolar instruments and glycine was used for excision of polyps.Results: In one hundred women with PMB, 19% had cancer. Endometrial adenocarcinoma in 14, endocervical carcinoma in 2, uterine carcinosarcoma in 3 cases. All 3 cases of uterine carcinosarcoma on hysteroscopy were large polyps measuring 5×5-6 cm size. Atypical hyperplasia endometrium in 7% and simple hyperplasia in 17%, was reported on histopathology, in cases with hyperplastic endometrium on hysteroscopy. Benign polyps in 41% were managed at the same sitting by operative hysteroscopy.Conclusions: Women with postmenopausal bleeding must have USG, trans vaginal sonography (TVS), endometrial thickness (ET) measurement, preferably endometrial echo complex (EEC). In women with PMB, the risk of uterine cancer would be 19%, i.e., 1 out of 5 women. Atypical hyperplasia in 7%. Hysteroscopy guided curettage, with histopathology, is the gold standard protocol in cases of PMB.
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Objectives: The objective of the study is to understand the impact of adjuvant radiotherapy (RT) and prognostic factors for patients diagnosed with uterine carcinosarcoma. Materials and Methods: The records of 31 patients receiving adjuvant RT between the dates of September 2003–January 2013 in our clinic were evaluated retrospectively. Surgery was performed in 27 (87%) patients as staging laparotomy, for 4 patients as total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pelvic external beam radiotherapy (EBRT) was 4500–5040 cGy in 25–28 fractions. In addition, 23 patients received brachytherapy following EBRT, 12 patients received adjuvant, and 1 patient received neoadjuvant chemotherapy (CT). Results: The median age was 63 (between 30 and 78). The stage distribution of the patients was as follows: Stage I, 20 (64%); Stage II, 7 (23%), and Stage III, 4 (13%) patients. Five-year locoregional control (LRC) rate was 100%, disease-free survival (DFS) and overall survival (OS) rates were 65.5% and 66.2%, respectively. Stage I or II patients have a tendency for better 5-year OS and DFS rates than Stage III patients (73.1% vs. 42.9% and 72.7% vs. 42.9%; P = 0.065 and 0.051). Regarding lymph node dissection was performed or not, 5-year OS (64.7% vs. 75.0%) was not statistically different between groups (P = 0.77). Five-year OS and DFS rates were 69.2% and 61.5% for patients receiving CT (adjuvant or neoadjuvant) versus 63.7% and 68.8% for patients not receiving CT; P = 0.63 and P = 0.89, respectively. Based on the analysis of peritoneal washings, 5-year OS was 0% for patients with malignant or suspicious cytology whereas 89% for patients with benign cytology (P = 0.000). A negative correlation was observed between mitotic count of sarcomatous component and DFS time (rs = −0.812 and P = 0.05). Conclusions: Surgery and adjuvant RT seem beneficial for excellent LRC rate. However, survival rates are low due to distant metastases. Thus, there is a great need for better systemic therapies
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PURPOSE: This study aimed to compare the diagnostic value of ¹⁸F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) and magnetic resonance imaging (MRI) in the preoperative evaluation of uterine carcinosarcoma.METHODS: Fifty-four women with pathologically confirmed uterine carcinosarcoma who underwent preoperative FDG PET/CT and MRI from June 2006 to November 2016 were included. Pathologic findings from primary tumor lesions, para-aortic and pelvic lymph node (LN) areas, and peritoneal seeding lesions were compared with the FDG PET/CT and MRI findings. The maximum standardized uptake value (SUVmax) of the primary tumor and LN was obtained. The tumor-to-liver ratio (TLR) was calculated by dividing the SUVmax of the primary tumor or LN by the mean SUVof the liver.RESULTS: For detecting primary tumor lesions (n = 54), the sensitivity and accuracy of FDGPET/CT (53/54) andMRI (53/54) were 98.2%. The sensitivity, specificity, and accuracy of FDG PET/CT versus MRI were as follows: 63.2% (12/19) versus 26.3% (5/19), 100% (35/35) versus 100% (35/35), and 87.0% versus 74.0%, respectively, for pelvic LN areas (p = 0.016); 85.7% (12/14) versus 42.9%(6/14), 90%(36/40) versus 97.5%(39/40), and 88.9%versus 83.3%, respectively, for para-aortic LN areas (p = 0.004); and 59.4% (19/32) versus 50% (16/32), 100% (22/22) versus 100% (22/22), and 75.9% versus 70.4%, respectively, for peritoneal seeding lesions (p = 0.250). For distant metastasis, the sensitivity, specificity, and accuracy of FDG PET/CTwere 100 (8/8), 97.8 (45/46), and 98.2%, respectively.CONCLUSION: FDG PET/CT showed superior diagnostic accuracy compared to MRI in detecting pelvic and para-aortic LN metastasis in patients with uterine carcinosarcoma. Moreover, FDG PET/CT facilitated the identification of distant metastasis.
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Female , Humans , Carcinosarcoma , Electrons , Liver , Lymph Nodes , Magnetic Resonance Imaging , Neoplasm Metastasis , Positron-Emission Tomography , Positron Emission Tomography Computed Tomography , Sensitivity and SpecificityABSTRACT
@#Uterine carcinosarcoma, also known as malignant mixed mullerian tumor (MMMT) is a rare and aggressive malignancy. It is the only type of uterine carcinoma with both an epithielial-derived carcinoma and a mesodermal-derived sarcoma. Classically, they have been considered as a soft tissue sarcoma, however, recent studies ascertain the pathogenesis of carcinosarcomas as to that of a metaplastic transformation of a carcinoma to give rise to a sarcomatous component. With the paradigm shift on the pathogenesis of disease, treatments have been aligned to follow protocols used in aggressive uterine carcinomas and are in further evaluation for its applicability to the aforementioned carcinosarcoma. This paper presents three cases of MMMT diagnosed in a Private Tertiary Hospital from October 2015 to February 2017. Among the three cases, two cases underwent endometrial sampling with results suggestive of MMMT and one case with an intraoperative frozen section done revealing carcinosarcoma. All cases underwent extrafascial hysterectomy with bilateral salpingo-oophorectomy (EHBSO) and bilateral lymph node dissection (BLND). Post-operatively, two of the cases underwent adjuvant chemotherapy and are currently alive. The one case that did not receive adjuvant chemotherapy succumbed to the disease eight months after diagnosis. With the high propensity of MMMT to metastasis, relapse and recurrence, it is then imperative that all cases are properly managed.
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NeoplasmsABSTRACT
Objective To investigate the relationship between MRI and pathological features of uterine carcinosarcoma(UCS).Methods 13 cases of UCS which were confirmed by surgery and pathology were collected,MRI plain scan and enhanced scan were carried on all of the patients,the pathological tissue was got after operation for conventional HE and immunohistochemical staining.The MRI representation and pathological tissue composition of all the 13 cases were analyzed and summarized.Results 8 cases were occurred in uterine body,3 cases were in the cervix and 2 were involving the uterine body and cervix at the same time.The MRI manifestations of them were enlarged uterine size with irregular masses showed,intermediate or hypointensity intensity signal on T1 weighted and hyperintensity or intermediate intensity signal on T2 weighted,necrosis and cystic lesions were showed in 5 cases,2 cases hemorrhage were displaied which showed hyperintensity signal on T1 weighted,4 cases were endometrial thickening,all of the cases were heterogeneous enhancement;the pathological showed different proportion of carcinorma and sarcoma were visible in all the 13 cases of UCS.Conclusion UCS has complex components histopathologically,including both carcinoma tissue and sarcoma tissue.The heterogeneous signal of cystic degeneration,necrosis and hemorrhage within tumor in MRI could help the diagnosis of UCS.
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Objective To explore the clinical value of color Doppler ultrasonography in the diagnosis of uterine carcinosarcoma (UCS).Methods The clinical data and ultrasonographic manifestations of 63 cases of UCS proved by operation and pathology in Obstetrics and Gynecology Hospital of Fudan University from January 2003 to December 2014 were retrospectively analyzed.The clinical features and characteristics of ultrasound images in UCS were summarized and classified according to their ultrasonographic features.Results It mostly occurred in postmenopausal women (77.8％).The average age of the 63 patients of UCS was (57.7 ± 11.5) years old.The most common symptoms of UCS were postmenopauseal vaginal bleeding (57.1％),menstrual disorders (20.6％),vaginal discharge (11.1％),uterine mass or thickened endometrium (11.1％).Tumor marker CA125 was evaluated in 36 women and found to be elevated in 15 women (41.7％),60％ of which (9/15) was less than 200 U/mL.Six cases (16.7％) of relative higher level of serum CA125 (＞ 200 U/mL) were at advanced stage or with malignant ovarian tumors.The sonographic findings of UCS had three types:Uterine cavity type (71.4％),endometrium type (14.3％),and myometrium type (14.3％).The ultrasonographic characteristics of uterine cavity type and myometrium type were fuzzy boundary,irregular shape,and internal uneven echo.Color doppler flow image showed rich blood signals and low resistance index (0.55 + 0.11) of the surrounding and internal artery of the lesions.The large volume of lesion was the characteristic of myometrium type.Conclusions UCS is a very aggressive and extremely rare tumor with the symptoms of postmenopauseal vaginal bleeding,menstrual disorders,vaginal discharge,et al.There are three types of sonographic findings of UCS:uterine cavity type,endometrium type and myometrium type.To strengthen the understanding of UCS and combined with clinical manifestations,the transvaginal color Doppler ultrasound was helpful to early detection,early diagnosis and making the appropriate treatment.
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We report a case of port-site metastasis after laparoscopic surgery for early stage uterine carcinosarcoma (UCS) and review the related literature. A 53-year-old woman with suspected uterine malignance underwent a total laparoscopic hysterectomy with bilateral salpingo-oophorectomy, infra-colic omentectomy, and pelvic lymphadenectomy resulting pathologically in a stage IA UCS. Twelve months later she developed a palpable abdominal-wall mass at the trocar site without other synchronous metastases. A mass resection was performed and it was pathologically diagnosed with port-site metastasis of UCS. When performing surgery for UCS, specimens should be carefully removed in case small pieces of the occult disseminated metastatic tissues are trapped between the outer surface of the trocar sleeve and the abdominal wall incisional canal. Despite the low incidence, a laparotomy might be considered rather than laparoscopy to prevent port-site metastasis and more gynecological oncology clinical practices might be relevant to the management of port-site metastasis.
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Female , Humans , Middle Aged , Abdominal Wall , Carcinosarcoma , Hysterectomy , Incidence , Laparoscopy , Laparotomy , Lymph Node Excision , Neoplasm Metastasis , Surgical InstrumentsABSTRACT
OBJECTIVE: Uterine carcinosarcoma (UCS) shared the same staging system with endometrial carcinoma in the International Federation of Gynecology and Obstetrics 2009. The aim of the present study was to compare the clinicopathological and prognostic characteristics between UCS and grade 3 endometrioid endometrial carcinoma (G3EC). METHODS: A retrospective analysis of 60 UCS and 115 G3EC patients with initial treatment at the Department of Gynecology in the Fudan University Shanghai Cancer Center between February 2006 and August 2013. Chi-square analysis was used to compare differences between variables. Prognostic factors were determined using univariate/multivariate analysis, and the survival rates were assessed using the Kaplan-Meier method. The Cox regression model was used to assess the independent prognostic factor. RESULTS: UCS had significantly worse overall survival (OS) compared with G3EC. Carcinosarcoma subtype was an independent factor (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.0 to 5.8; p=0.039), stratified based on stage. Compared with G3EC, UCS patients had a greater incidence of ascites fluid (55.0% vs. 15.7%, p<0.001) and adnexal involvement (20.0% vs. 8.7%, p=0.048) and larger median tumor volume (4.6 cm vs. 4.0 cm, p=0.046). Subgroup analysis of the prognostic factors revealed that UCS patients exhibited worse OS than G3EC patients in such specific subgroups as patients at younger ages, with postmenopausal status, without ascites fluid, with early stage diseases, without vagina invasion, without lymph node metastases and receiving adjuvant chemo/radiotherapy. Adjuvant radiotherapy with chemotherapy was predictive of better survival in UCS patients compared with chemotherapy or radiotherapy alone (5-year OS, 71.0% vs. 35.8%, p=0.028). Multivariate Cox regression revealed that tumor mesenchymal component (HR, 4.6; 95% CI, 1.4 to 15.8; p=0.014) was an independent prognostic factor for UCS, whereas advanced stages (HR, 5.9; 95% CI, 1.0 to 33.9; p=0.046) and ascites fluid (HR, 5.1; 95% CI, 1.1 to 22.7; p=0.032) were independently correlated with poor prognosis for G3EC patients. CONCLUSION: The distinctions in both clinicopathological and prognostic characteristics between UCS and G3EC suggest that this subtype should be treated separately from high-risk epithelial endometrial carcinoma.
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Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Adnexa Uteri/pathology , Age Factors , Aorta , Ascites/etiology , Carcinoma, Endometrioid/secondary , Carcinosarcoma/secondary , Chemotherapy, Adjuvant , Cytoreduction Surgical Procedures , Endometrial Neoplasms/pathology , Hysterectomy , Lymph Node Excision , Lymphatic Metastasis , Neoplasm Grading , Neoplasm Invasiveness , Neoplasm Staging , Pelvis , Postmenopause , Radiotherapy, Adjuvant , Retrospective Studies , Survival Rate , Tumor Burden , Vagina/pathologyABSTRACT
OBJECTIVE: To investigate the role of radiotherapy (RT) in patients who underwent hysterectomy for uterine carcinosarcoma (UCS). METHODS: Patients with the International Federation of Gynecology and Obstetrics stage I–IVa UCS who were treated between 1990 and 2012 were identified retrospectively in a multi-institutional database. Of 235 identified patients, 97 (41.3%) received adjuvant RT. Twenty-two patients with a history of previous pelvic RT were analyzed separately. Survival outcomes were assessed using the Kaplan-Meier method and Cox proportional hazards model. RESULTS: Patients with a previous history of pelvic RT had poor survival outcomes, and 72.6% of these patients experienced locoregional recurrence; however, none received RT after a diagnosis of UCS. Univariate analyses revealed that pelvic lymphadenectomy (PLND) and para-aortic lymph node sampling were significant factors for locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS). Among patients without previous pelvic RT, the percentage of locoregional failure was lower for those who received adjuvant RT than for those who did not (28.5% vs. 17.5%, p=0.107). Multivariate analysis revealed significant correlations between PLND and LRRFS, distant metastasis-free survival, and DFS. In subgroup analyses, RT significantly improved the 5-year LRRFS rate of patients who did not undergo PLND (52.7% vs. 18.7% for non-RT, p<0.001). CONCLUSION: Adjuvant RT decreased the risk of locoregional recurrence after hysterectomy for UCS, particularly in patients without surgical nodal staging. Given the poorer locoregional outcomes of patients previously subjected to pelvic RT, meticulous re-administration of RT might improve locoregional control while leading to less toxicity in these patients.
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Middle Aged , Carcinosarcoma/mortality , Chemotherapy, Adjuvant , Hysterectomy , Kaplan-Meier Estimate , Lymph Node Excision , Lymphatic Metastasis , Neoplasm Recurrence, Local/prevention & control , Proportional Hazards Models , Radiotherapy, Adjuvant/adverse effects , Retrospective Studies , Survival Rate , Uterine Neoplasms/mortalityABSTRACT
Los carcinosarcomas uterinos (anteriormente denominados tumores müllerianos mixtos malignos - TMMM) son neoplasias poco frecuentes y altamente agresivas. Se describe un caso de rápida progresión de un carcinosarcoma de útero y se discute su diagnóstico diferencial y el planteamiento terapéutico.
Uterine carcinosarcomas (previously called malignant Müllerian mixed tumors) are rare malignant and highly aggressive neoplasias. A case of a rapid progression uterine carcinosarcoma is reported, and differential diagnosis and treatment are discussed.
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Objetivos: Evaluar los factores pronósticos para sobrevida en pacientes con carcinosarcoma uterino. Diseño: Estudio retrospectivo de cohortes. Institución: Instituto Nacional de Enfermedades Neoplásicas, Lima, Perú. Participantes: Pacientes con carcinosarcoma uterino. Intervenciones: Se revisó las historias clínicas y resultados de anatomía patológica en pacientes con diagnóstico de carcinosarcoma uterino tratadas durante el periodo 2005 a 2011. El análisis estadístico fue desarrollado usando el SPSS 19,0 para Windows, con frecuencias y medidas resumen. La sobrevida fue estimada con el método de Kaplan-Meier. Todas las pruebas tuvieron una significancia de 95%, p< 0,05. El análisis multivariado se realizó con el modelo de Cox proportional hazards para efectos de las variables pronóstico. Principales medidas de resultados: Factores pronósticos de sobrevida. Resultados: Se identificó 37 pacientes con carcinosarcoma uterino. La edad media fue 63 años; la mayoría de los pacientes (67%) se presentó en estadio avanzado. En 33 pacientes (89%), la cirugía inicial fue desarrollada de manera no estandarizada. Solo siete pacientes tuvieron linfadenectomía pélvica (19%), lo que no influyó en la sobrevida global. Quince pacientes tuvieron omentectomía (40%), de las cuales ocho tenían metástasis a epiplón, lo cual influyó en la sobrevida global. El tiempo mediano de seguimiento fue cuatro meses (rango 0,5 a 59 meses). La sobrevida global estimada a tres años para todos los estadios fue 48,9%. Hubo ocho (21,6%) pacientes con recurrencia. Conclusiones: El tratamiento quirúrgico y adyuvante fue realizado de manera no estandarizada. El estadio al momento del diagnóstico y la metástasis a epiplón fueron los únicos factores que influyeron en la sobrevida. La terapia adyuvante no mejoró la sobrevida. Se debe considerar omentectomía como parte del estadiaje.
Objectives: To determine survival prognostic factors in patients with uterine carcinosarcoma. Design: Retrospective cohort study. Setting: Instituto Nacional de Enfermedades Neoplasicas, Lima, Peru. Participants: Patients with uterine carcinosarcoma. Interventions: A review of medical histories and pathology reports in patients with uterine carcinosarcoma treated from 2005 through 2011 was performed. Statistical analysis used SPSS 19.0 for Windows, with frequencies and summary measures. Survival was estimated using Kaplan-Meier method. Significance was 95%, p< 0.05. Multivariate analysis for prognostic variables was done with Cox proportional hazards model. Main outcome measures: Survival prognostic factors. Results: In 37 patients with uterine carcinosarcoma mean age was 63 years, most of them (67%) presented advanced stages. Non-standardized initial surgery was performed in 33 patients (89%). Only seven patients had pelvic lymphadenectomy (19%) that did not influence overall survival. Omentectomy was done in 15 patients (40%), and eight had metastases to omentum influencing overall survival. Conclusions: Surgical and adjuvant treatments were developed in a non-standardized way. Only factors influencing survival were stage at diagnosis and omentum metastasis. Adjuvant therapy did not improve survival. Omentectomy should be considered in staging.
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Uterine carcinosarcomas are rare and highly aggressive tumors with a poor prognosis. Due to early metastasis and disease progression, it is known to be far more aggressive than matched grade 3 endometroid endometrial carcinomas. Five-year survival for stage IV is reported to be 10% and overall survival for stage IVB is expected to be very poor. The authors report one case after experiencing long-term survival (over 5 years) for stage IVB carcinosarcoma of uterus. Total abdominal hysterectomy and bilateral salpingo-oophorectomy was performed to 56 year old patient for uterine myoma. On pathology report, uterine carcinosarcoma was diagnosed and image studies were performed. With the impression of stage IVB uterine carcinosarcoma, 6 cycles of chemotherapy (ifosfamide and cisplatin) was conducted as adjuvant. Up to recently (over 5 years), she maintains good performance scale without evidence of tumor recurrence or disease progression.