[Multimodal treatment of malignant mixed Müllerian tumor]. / Malignus kevert Müller-cso-eredetu tumor komplex kezelése.

INTRODUCTION AND AIM: The aim of our study was to evaluate the prognostic factors and treatment options of a very rare and highly aggressive type of uterine neoplasms, the malignant mixed Müllerian tumor, known as carcinosarcoma. METHOD: Between 2009 and 2017, 29 patients were treated with malignant mixed Müllerian tumor. At stage I, surgery and postoperative radiotherapy were performed. At stages II-IV, trimodal treatment (surgery, chemotherapy and radiotherapy) was administered. RESULTS: The average age of patients was 68.51 (49-90) years, mean body mass index was 30.22 (20.90-37.22). We have experienced recurrence of disease after complete resection in 6 cases (4 of 6 patients did not accept radiation therapy). Local recurrence has occurred after an average 15.52 (6-36) months, distant metastasis with an average 19.2 (8-32) months. Overall survival was 11.92 (1-75) months. Six patients are free of tumours at the moment. CONCLUSIONS: As overall survival has not increased in recent decades by using combined chemotherapy, there is no congruent consensus associated with the optimal treatment. The standard surgical treatment is total abdominal hysterectomy with bilateral oophorectomy, although due to high rates of recurrence and metastases, the necessity of lymphadenectomy and postoperative treatment is in the focus of recent studies. Though postoperative irradiation improves local control, the beneficial effect on overall survival is still not proven. Adjuvant chemotherapy decreases the rate of both pelvic and extrapelvic recurrence at the same time, although there is no recommendation for the optimal chemoterapeutic agent. Multimodal therapy should lead to better outcomes. Recently there are many ongoing studies with biologic and target therapies to improve efficiency, however, the relevant results will be disclosed in many years only, due to the small number of patients. Orv Hetil. 2018; 159(19): 741-7747.

Malignant Mixed Müllerian Tumour of the Uterus: Analysis of 44 Cases.

OBJECTIVES: The aim of our study was to evaluate the clinicopathological features and prognostic factors of uterine carcinosarcoma. PATIENTS AND METHODS: In this retrospective study, the clinical characteristics of 44 patients with uterine MMMT were evaluated. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. RESULTS: Forty-four patients with uterine carcinosarcoma were referred to our unit between 1995 and 2015. Their median age was 66.5 years. All women underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Twenty-five percent had omental resection. Pelvic lymphadenectomy was performed in 18.2% of the cases. Twenty-six of the patients presented with stage I/II disease, 17 with advanced stages. In 20.5% of the cases there were metastases at diagnosis. Forty women received adjuvant chemotherapy, with complete remission in 67.9% of the cases. Recurrences were observed in 27.3% of the women. Disease-free and overall survival was 27 and 103 months, respectively. The FIGO stage, histological type, tumour size, chemotherapy regimen, pelvic lymphadenectomy, and myometrial invasion did not affect survival. CONCLUSIONS: Uterine MMMT is an aggressive tumour, often diagnosed at an advanced stage and with a high rate of metastases or recurrences. Because of its rarity, its management is controversial and fixed prognostic factors cannot be defined.

Outcome and prognosis in uterine sarcoma and malignant mixed Mullerian tumor.

PURPOSE: There is low evidence regarding the optimal treatment in patients with uterine sarcomas and malignant mixed Mullerian tumors (MMMTs). This study provides an overview of experience at our center with patients diagnosed with uterine sarcoma and MMMT, in relation to the clinical management and outcome. METHODS: The medical records for 143 patients with low-grade endometrial stromal sarcoma (ESS), leiomyosarcoma (LMS), and high-grade (undifferentiated) endometrial sarcoma (UES) and MMMT were reviewed. All available clinical and pathological data were collected and analyzed. Putative prognostic factors were entered into a multivariate analysis using a Cox proportional hazards ratio model, and survival data were calculated. RESULTS: The 5-year overall survival rates were significantly different between patients with ESS, LMS, and UES and MMMT (86 vs. 40 vs. 57 vs. 45 %; P < 0.001). The multivariate analysis showed that the patients' age, higher FIGO stage (III-IV), a history of smoking, prior pelvic radiation, diabetes, and residual tumor after surgery were associated with a poorer overall survival. Histological subtypes of LMS (HR 4.68; 95 % CI 1.35-16.17), UES (HR 1.21; 95 % CI 0.26-5.77) and MMMT (HR 1.63; 95 % CI 0.42-6.43) were also associated with a poorer overall survival than ESS (P = 0.008). Adjuvant therapies showed no associations with overall survival. CONCLUSIONS: Adjuvant therapy has so far not shown any overall survival benefit, and the focus is therefore on primary surgery. In future studies, the entities should be investigated separately in relation to prognostic factors and effective therapeutic management.

The Growing Burden of Endometrial Cancer: A Major Racial Disparity Affecting Black Women.

BACKGROUND: In contrast with the decreasing incidence seen for most cancers, endometrial cancer has been increasing in the United States. We examined whether the increasing incidence and mortality from endometrial cancer are equally distributed by race/ethnicity and tumor histologic subtype. METHODS: Surveillance, Epidemiology, and End Results (SEER) endometrial cancer incidence and mortality data were obtained from 2000 to 2011. Age-adjusted incidence and incidence-based mortality rates, 95% confidence intervals, and annual percent changes (APC) were calculated. Rate ratios were calculated to compare racial/ethnic groups. Five-year relative survival rates were presented to explore survival by stage at diagnosis. RESULTS: Incidence rates for endometrial cancers are rising across all racial/ethnic groups, with the greatest APC seen among non-Hispanic black (NHB) and Asian women (APC, 2.5 for both). NHB women have significantly higher incidence rates of aggressive endometrial cancers (clear cell, serous, high-grade endometrioid, and malignant mixed Mullerian tumors) compared with non-Hispanic white (NHW) women. Hispanic and Asian women have incidence rates equal to or lower than NHW women for all tumor subtypes. For nearly every stage and subtype, the 5-year relative survival for NHB women is significantly less than NHW women, whereas Hispanic and Asian women have the same or better survival. CONCLUSIONS: Endometrial cancer incidence is increasing for all women, particularly the aggressive subtypes. The disparity associated with excess incidence for these aggressive histologic subtypes and poorer survival is limited to NHB women. IMPACT: Increasing rates of aggressive endometrial cancers may widen the survival disparity between NHW and NHB women.

Role of p53 pathway alterations in uterine carcinosarcomas (malignant mixed Müllerian tumors).

Carcinosarcomas (CSs; malignant mixed Müllerian tumors) of the uterus are highly malignant neoplasms characterized by an unfavorable outcome. They represent less than 5% of all uterine malignancies, and the median patient survival rate is only 21 months. p53 pathway alterations have been studied in CSs originating from the uterus, supporting the monoclonal nature of most but not all of these neoplasms. This paper gives an overview of the current knowledge of p53 pathway distortions in patients with uterine CSs. The survival of patients with uterine CSs in relation to p53 pathway alterations is also briefly summarized.

Clinico-pathological spectrum of primary ovarian malignant mixed mullerian tumors (OMMMT) from a tertiary cancer institute: A series of 27 cases.

AIMS AND OBJECTIVES: To study the clinico-pathological characteristics of primary ovarian malignant mixed mullerian tumor (OMMMT) and assess the prognostic factors associated with treatment outcome and survival. MATERIALS AND METHODS: The pathology database was searched for primary ovarian carcinosarcoma diagnosed and/or managed at our institute from period of January 2004 to July 2010. The histological sections were reviewed, with emphasis on type and grade of epithelial and sarcomatous components. The medical records were retrospectively analyzed for clinical details and follow up. RESULTS: A total of 27 cases of primary ovarian carcinosarcoma were identified. The median age at diagnosis was 51 years. Fourteen patients had advanced stage (stage III and IV) at presentation. Cytoreductive surgery was done in 18 cases, and 7 had received upfront chemotherapy. Histologically, 10 cases had epithelial predominance (> 50% epithelial component) and 11 had sarcoma predominance. The most frequent epithelial component was endometroid type, and most common sarcoma component was rhabdomyosarcomatous. Hyaline droplets within sarcomatous stroma were seen prominently in 15 cases. Three cases showed germ cell /yolk sac-like areas. Eighteen cases had follow up with a median of 15 months (4-40 months). The recurrence-free survival in advanced stage and sarcoma predominant was 10.5 months in comparison to 13 months in early stage and epithelial predominant OMMMT. CONCLUSION: Primary ovarian carcinosarcoma is a rare biphasic malignancy with variable proportions of epithelial and spindle elements. Presence of hyaline droplets within spindle sarcoma in a biopsy from ovarian mass should alert the pathologists regarding MMMT. Advanced stage, suboptimal cytoreduction, and sarcoma predominant tumors are likely to have a worse outcome in ovarian MMMT.

Prognostic factors and treatment outcomes in 93 patients with uterine sarcoma from 4 centers in Turkey.

INTRODUCTION: Uterine sarcomas are a group of heterogenous and rare malignancies of the female genital tract and there is a lack of consensus on prognostic factors and optimal treatment. OBJECTIVE AND METHODOLOGY: To perform a retrospective evaluation of clinicopathological characteristics, prognostic factors and treatment outcomes of 93 patients with uterine sarcomas who were diagnosed and treated at 4 different centers from November 2000 to October 2010. RESULTS: Of the 93 patients, 58.0% had leiomyosarcomas, 26.9% malignant mixed Mullerian tumors, 9.7% endometrial stromal sarcomas, and 5.4% other histological types. According to the last International Federation of Gynecology and Obstetrics (FIGO) staging, 43.0% were stage I, 20.4% were stage II, 22.6% were stage III and 14.0 % were stage IV. Median relapse free survival (RFS) was 20 months (95% confidence interval (CI), 12.4-27.6 months), RFS after 1, 2, 5 years were 66.6%, 44.1%, 16.5% respectively. Median overall survival (OS) was 56 months (95% CI, 22.5-89.5 months), and OS after 1, 2, 5 years was 84.7%, 78%, 49.4% respectively. Multivariate analysis showed that age≥60 years and high grade tumor were significantly associated with poor OS and RFS; patients administered adjuvant treatment with sequential chemotherapy and radiotherapy had longer RFS time. Among patients with leiomyosarcoma, in addition to age and grade, adjuvant treatment with sequential chemotherapy and radiotherapy after surgery had significant effects on OS. CONCLUSION: Uterine sarcomas have poor progrosis even at early stages. Prognostic factors affecting OS were found to be age and grade.

Presence of a sarcomatous component outside the ovary is an adverse prognostic factor for primary ovarian malignant mixed mesodermal/mullerian tumors: a clinicopathologic study of 47 cases.

Primary ovarian malignant mixed mesodermal tumors are uncommon. There exist few data in the literature on the significance of the sarcomatous component (SC) in these tumors. Here we investigated this aspect in 47 such tumors, with particular interest in whether the presence of SC outside the ovary confers a worse prognosis. We correlated various features of the SC (homologous vs. heterologous, type of heterologous SC, extent/percentage, mitotic count, necrosis, whether or not SC is present outside the ovary) with disease-specific survival (DSS) using the Kaplan-Meier method and log-rank test. We also correlated other clinicopathologic parameters with DSS: age, stage, tumor size, tumor laterality, type of the carcinomatous component (CC), lymph node status, vascular invasion, and degree of surgical debulking. The mean age was 69.0 years (range, 43 to 89 y). The tumor was located in the left and right ovary in 18 and 24 patients, respectively (laterality could not be determined in 5 cases). The mean tumor size was 13.6 cm. Surgical debulking was optimal in 28, suboptimal in 6, and unclear in 13 patients. FIGO stage was I in 1 patient, II in 5 patients, III in 40 (IIIA in 1, IIIB in 11, IIIC in 28), and IV in 1 patient. Node metastasis and vascular invasion were noted in 6/17 and 29/47 patients, respectively. The mean percentage of SC was 29% (median 20%; range, 1% to 90%). The SC was heterologous in 34 (72%) and homologous in 13 (28%) patients. The mitotic figures per 10 HPF in SC were 33 (0 to 128). Tumor necrosis was present in 45/47 cases (mean 10%; range, 1% to 40%, only in CC in 14, only in SC in 2, in both SC and CC in 29). The CC was high-grade serous in 27 patients, endometrioid in 2, mixed high-grade serous and endometrioid in 17, and mixed high-grade serous and clear cell carcinoma in 1 patient. The extraovarian tumor contained only CC in 17 cases, only SC in 1 case, and both SC and CC in 28 cases. The median follow-up was 29 months (range, 1 to 183 mo): 6 patients were lost to follow-up, 3 died postoperatively, 29 died from disease, 2 died from other causes, and 7 were still alive (14 to 183 mo). The DSS rate at 1, 2, and 5 years was 75%, 56%, and 21%, respectively. Presence of SC outside the ovary was a significant adverse prognostic factor (P=0.03), whereas other parameters were not. After adjusting for FIGO stage, presence of SC outside the ovary was still a significant adverse prognosticator for stage III patients (P=0.003), whereas others were not. Therefore, our findings showed that presence of SC outside the ovary was a significant adverse prognostic factor. We advocate listing the specific extraovarian tumor component (SC and/or CC) in the pathology report for primary ovarian malignant mixed mesodermal tumors.

The comparison of clinicopathological characteristics in primary malignant mixed mullerian tumour with epithelial endometrial carcinoma.

AIMS: We performed an age-matched case-control study to compare the clinical and pathology outcomes between histologically diagnosed primary malignant mixed mullerian tumour (MMMT) of the uterus and endometrial carcinoma. METHODS: Thirty-two women were treated for primary MMMT at seven tertiary medical centres in Korea from 2000 to 2006. For each woman with MMMT, four women with endometrioid and two with non-endometrioid endometrial carcinoma were selected as age-matched controls for analysis. Medical records were retrospectively reviewed to obtain outcome data. RESULTS: The incidence of MMMT was 2.57% (32/1244). In comparison with women with endometrioid endometrial cancer, those with MMMT were characterised by large tumour size, higher incidence of adnexal involvement and lymph node metastases, leading to advanced disease stage. Despite the frequent use of adjuvant treatment, the 5-year survival rate of women with MMMT was significantly poorer than those with endometrioid endometrial cancer. However, women with MMMT were not significantly different from those with non-endometrioid endometrial cancer in terms of important pathologic variables, apart from larger tumour size. In addition, the 5-year survival rate of women MMMT was poorer than that those with non-endometrioid endometrial cancer, but the difference was not statistically significant. CONCLUSIONS: Malignant mixed mullerian tumour is characterised by a high incidence of lymph node metastases and advanced stage at diagnosis, leading to poorer overall survival than other subtypes of endometrial carcinoma. Clinical trials for MMMT are critical for improving treatment strategies.

Comparison of survival outcomes between patients with malignant mixed mullerian tumors and high-grade endometrioid, clear cell, and papillary serous endometrial cancers.

INTRODUCTION: Malignant mixed mullerian tumors (MMMTs) are an aggressive subtype of endometrial cancer (EC). Previous studies compare survival between high-grade endometrioid (EM), clear cell (CC), and papillary serous (PS) ECs; yet few studies compare MMMTs to these aggressive subtypes. The goal of this study was to compare recurrence-free survival (RFS), disease-specific survival (DSS), and overall survival (OS) among EC subtypes. METHODS: We conducted a retrospective cohort study of EC cases treated at Magee-Women's Hospital between 1996 and 2008. Kaplan-Meier estimates of RFS, DSS, and OS as well as and log-rank tests were used to compare survival distributions between histologic subtypes. Cox regression was used to estimate hazard ratios for histologic subtypes, adjusted for other significant prognostic factors. Interactions between histologic subtype and prognostic factors were examined to assess effect modification. RESULTS: This cohort included 81 MMMT (15%), 254 high-grade EM (46%), 73 CC (13%), and 147 PS (26%) cases. Compared to high-grade EM (6%) and CC (7%) cases, relatively more MMMT (12%) and PS (12%) cases were nonwhite. Stage differed significantly among the subtypes, with 36%, 34%, 37%, and 51% of MMMT, high-grade EM, CC, and PS cases, respectively, diagnosed at advanced late stage (P<0.001). Kaplan-Meier curves and log-rank tests showed similar RFS, DSS, and OS between MMMT, high-grade EM, CC, and PS cases stratified by stage. In adjusted Cox regression models, RFS and DSS were not significantly different between MMMT and other subtypes. High-grade EM cases had a significantly better OS compared to MMMT cases (HR, 0.63; 95% confidence interval [CI], 0.41-0.98). CONCLUSIONS: This is the first retrospective study to suggest that certain survival outcomes are similar among MMMT, high-grade EM, CC, and PS subtypes. Other large-scale studies are needed to confirm these findings.

Systematic pelvic lymphadenectomy vs. no lymphadenectomy in early-stage endometrial carcinoma: randomized clinical trial.

BACKGROUND: Pelvic lymph nodes are the most common site of extrauterine tumor spread in early-stage endometrial cancer, but the clinical impact of lymphadenectomy has not been addressed in randomized studies. We conducted a randomized clinical trial to determine whether the addition of pelvic systematic lymphadenectomy to standard hysterectomy with bilateral salpingo-oophorectomy improves overall and disease-free survival. METHODS: From October 1, 1996, through March 31, 2006, 514 eligible patients with preoperative International Federation of Gynecology and Obstetrics stage I endometrial carcinoma were randomly assigned to undergo pelvic systematic lymphadenectomy (n = 264) or no lymphadenectomy (n = 250). Patients' clinical data, pathological tumor characteristics, and operative and early postoperative data were recorded at discharge from hospital. Late postoperative complications, adjuvant therapy, and follow-up data were collected 6 months after surgery. Survival was analyzed by use of the log-rank test and a Cox multivariable regression analysis. All statistical tests were two-sided. RESULTS: The median number of lymph nodes removed was 30 (interquartile range = 22-42) in the pelvic systematic lymphadenectomy arm and 0 (interquartile range = 0-0) in the no-lymphadenectomy arm (P < .001). Both early and late postoperative complications occurred statistically significantly more frequently in patients who had received pelvic systematic lymphadenectomy (81 patients in the lymphadenectomy arm and 34 patients in the no-lymphadenectomy arm, P = .001). Pelvic systematic lymphadenectomy improved surgical staging as statistically significantly more patients with lymph node metastases were found in the lymphadenectomy arm than in the no-lymphadenectomy arm (13.3% vs 3.2%, difference = 10.1%, 95% confidence interval [CI] = 5.3% to 14.9%, P < .001). At a median follow-up of 49 months, 78 events (ie, recurrence or death) had been observed and 53 patients had died. The unadjusted risks for first event and death were similar between the two arms (hazard ratio [HR] for first event = 1.10, 95% CI = 0.70 to 1.71, P = .68, and HR for death = 1.20, 95% CI = 0.70 to 2.07, P = .50). The 5-year disease-free and overall survival rates in an intention-to-treat analysis were similar between arms (81.0% and 85.9% in the lymphadenectomy arm and 81.7% and 90.0% in the no-lymphadenectomy arm, respectively). CONCLUSION: Although systematic pelvic lymphadenectomy statistically significantly improved surgical staging, it did not improve disease-free or overall survival.

Uterine sarcoma: clinicopathological characteristics, treatment and outcome in Iran.

OBJECTIVE: Uterine sarcomas are rare and heterogeneous tumors with histopathological diversity characterized by rapid clinical progression and a poor prognosis. The aim of this study was to investigate clinical and histopathological characteristics together with treatment and outcome of Iranian patients with uterine sarcomas. MATERIALS AND METHODS: Records of 57 patients with histologically verified uterine sarcoma treated at the Vali-e-Asr Hospital were reviewed (1999-2004). RESULTS: The lesions were 19 leomyosarcoma (LMSs), 17 malignant mixed Mullerian tumors (MMMT), 16 endometrial stromal sarcomas (ESSs), 3 unspecified sarcomas, 2 rabdomyosarcomas. Median age at diagnosis was 50 (17-81) years. Clinical stages (based on FIGO) were 30 with stage I disease, 9 with stage II, 12 with stage III and 6 with stage IV. Only one patient did not undergo surgery and most cases with LMS and ESS were treated with simple total hysterectomy (STH). Forty patients (out of 57) received adjuvant radiotherapy. The median follow-up period was 19 (2-96) months and median disease free period was 16 (1-86) months. The overall survival rates after 1, 2, and 5 years were 71%, 58% and 52%, respectively. Survival was related to histological type of ESS (p=0.0018), grade I (p=0.0032) and early stage (p=0.045) significantly, but was not linked to postoperative irradiation. However, local recurrence rate was significantly improved after adjuvant radiotherapy. Twenty-one patients had relapse, 16 in the pelvic and 5 in extrapelvic sites. CONCLUSION: Based on the findings in this series, prognosis is dependent on histopathological subtype, grade and tumor stage. Adjuvant radiotherapy decreases local recurrence rate, but without significant impact on survival.

Advanced primary peritoneal carcinoma: clinicopathological and prognostic factor analyses.

OBJECTIVE: To investigate the factors favoring a positive prognosis for advanced primary peritoneal carcinoma (PPC). METHODS: Twenty-four cases meeting the criteria for PPC were analyzed retrospectively for the clinicopathologic profiles. Immunohistochemistry was used to determine the expressions of p53, Top2alpha, Ki-67 and Her-2/neu. Then all these clinicopathological factors and molecular markers were correlated with the prognosis. RESULTS: There were 15 cases of primary peritoneal serous papillary carcinoma (PPSPC), 6 cases of mixed epithelial carcinoma (MEC) and 3 cases of malignant mixed Mullerian tumor (MMMT). All patients underwent cytoreductive surgery with optimal debulking achieved in 3 cases. Among those receiving first-line chemotherapy, 13 patients received the TP regimen (paclitaxel-cisplatin or carboplatin) and 7 patients received the PAC regimen (cisplatin-doxorubicin-cyclophosphamide). The median overall survival of all patients was 42 months, while the breakdown for survival time for patients with PPSPC, MMT and MEC was 44, 13 and 19 months, respectively. The expressions of p53, Top2alpha and Ki-67 were all demonstrated in 11 cases respectively. None showed the expression of Her-2/neu. There were significant differences in the median survival between patients with PPSPC and those with MMMT (44 months vs 13 months, P<0.05), also between patients receiving TP combination and those receiving the PAC regimen (75 months vs 28 months, P<0.05). Another significant difference in the median progression-free survival (PFS) was identified between patients with positive p53 immunostaining and those with negative p53 immunostaining (15 months vs 47 months, P<0.05), whereas age, menopausal status, residual tumor size and the other molecular factors did not significantly impact survival. CONCLUSION: Patients with PPC should be treated with a comprehensive management plan including appropriate cytoreductive surgery and responsive chemotherapy. Overestimating an optimal debulking surgery may not benefit survival. The pathologic subtype, chemotherapy regimen and p53 overexpression were significant prognostic factors.

Retrospective analysis of 105 cases with uterine sarcoma.

To evaluate the role of adjuvant therapy in survival and to identify important prognostic factors in uterine sarcoma. One hundred five patients with uterine sarcoma have been retrospectively researched to evaluate the results in this tumor group. 43.8% had leiomyosarcoma, 28.6% had endometrial stromal sarcoma and 27.6% had a malign Mullarian mixed tumor while the distribution according to the histological subgroups were found to be 42.6,16.2 and 41.2% in grade I, II and III tumors respectively. 38.1% of the patients had Radiotherapy, 18.1% had chemotherapy and 12.4% had chemoradiotherapy in addition to surgery. The distant metastases rate is 30% and the local recurrence is 16.2%. All the local recurrences and 90% of the distant metastases have occurred within the first two years. The disease free survival and overall survival rates at 3rd and 5th years are 54.46, 49.88, 54.63 and 51.09% all respectively. In our series, univariate analysis for overall survival demonstrated statistical significance for radical surgery, grade, stage, age, menopausal status and presence of RT in treatment modality, but; histology, number of mitosis, tumor size demonstrated no significance. Our data favors treatment for uterine sarcoma with radical surgery plus radiotherapy alone over 54 Gy or with chemotherapy.

Tumores müllerianos mixtos de cuello uterino / Mullerian mixed tumors of the uterine cervix

Objetivo: Presentar 3 casos clínicos de tumores müllerianos mixtos de cuello uterino más revisión de la literatura. Método: Análisis retrospectivo de fichas clínicas desde noviembre de 1997 hasta enero de 2005 y revisión de las placas histológicas. Resultados: El rango de edad de las pacientes fue de 36 a 56 años (promedio: 48,3 años). El principal motivo de consulta fue la genitorragia. Al examen clínico presentaban un cuello uterino tumoral de gran volumen (5 a 7 cm). En dos pacientes se identificó un carcinosarcoma, en la otra paciente se diagnosticó un adenosarcoma. Al momento del diagnóstico no presentaban enfermedad extrapelviana evidente. Se realizó histerectomía radical y radioterapia pelviana más braquiterapia postoperatoria en todas ellas. Dos pacientes fallecen con enfermedad extrapelviana a los 11 y 20 meses de seguimiento. La otra paciente esta libre de enfermedad a los 48 meses de seguimiento. Conclusión: Los tumores müllerianos mixtos de cuello uterino son raros, de mal pronóstico cuyo tratamiento principal es la cirugía radical con radioterapia adyuvante en caso de enfermedad localmente avanzada. En casos confinados al cuello uterino se puede lograr una mayor sobrevida libre de enfermedad.

Objective: 3 clinical cases of mixed müllerian tumors of uterine cervix and a literature review are presented. Method: Retrospective analysis of clinical charts and pathological reports between November 1997 and January 2005. Results: Patients' ages ranged from 36 to 56 years (mean: 48,3 years). Abnormal vaginal bleeding was the most common presenting symptom. Pelvic examination revealed a large cervical mass (5 to 7 cm) in all cases. Two patients presented a carcinosarcoma, the other one an adenosarcoma tumor. At the initial diagnosis there were not evidence of extrapelvic disease. Radical hysterectomy and external beam radiation therapy and brachytherapy was performed in all cases. Two patients died with extrapelvic metasta-ses at 11 and 20 months of follow-up. The other one remains without evidence of recurrence 48 months after her treatment. Conclusion: Cervical mixed müllerian tumors are rare and poor prognosis neoplasms, radical surgery and adjuvant radiation therapy for local bulky disease are the optimal therapy. Long-term survival is possible in cervix confined early stage disease.

Prognostic features of surgical stage I uterine carcinosarcoma.

Uterine carcinosarcomas (CSs) are aggressive neoplasms, with 5-year overall survival (OS) rates of less than 35%. They are customarily separated into types harboring either heterologous or homologous mesenchymal elements, but the prognostic significance of this finding is controversial. Our goal was to study clinicopathologic features of possible prognostic relevance in surgical stage I uterine CS. A retrospective clinical and histopathologic review was performed for all women diagnosed with surgical stage I uterine CS. These tumors were compared with stage I high-grade endometrial (HGEm) carcinomas for clinical outcomes. There were 42 cases of surgical stage I uterine CS identified between January 1990 and January 2004. The disease-free survival and OS rates for patients with stage I CS were significantly worse compared with stage I HGEm (P=0.001; P=0.01). The median disease-free survival for patients with heterologous CS was 15 months and had not been reached for women with homologous CS (P=0.001). The 3-year OS rates were 45% versus 93% in women with heterologous compared with homologous stage I CS (P<0.001). The 3-year OS rates for homologous CS and HGEm were both >90%. Homologous stage I CSs have survival outcomes that are similar to HGEm. This further supports the concept that homologous stage I CSs are carcinomas with sarcomatoid features, not sarcomas. More importantly, the presence of heterologous sarcomatous elements is a powerful negative prognostic factor in surgical stage I uterine CS.

[Morphological structure and classification of Muller mixed uterine tumors].

A review of the literature is presented which deals with modern aspects of Muller mixed tumors (MMT) classification and problems of their histo- and morphogenesis, immunohistochemical, ultrastructural and molecular-genetic peculiarities. Prognostic factors and survival rates are considered. Further study of MMT is necessary for verification of their histo- and morphogenesis and for development of their classification.

Malignant mixed müllerian tumors of the ovary: experience with cytoreductive surgery and platinum-based combination chemotherapy.

This study reviews the clinical outcome and prognosis of patients with malignant mixed müllerian tumors (MMMTs) of the ovary treated with optimal cytoreductive surgery, leaving no residual disease, and platinum-based chemotherapy. Ten patients diagnosed with MMMT of the ovary after complete surgical staging from February 1993 to February 2004 at Asan Medical Center in Korea were studied retrospectively. All ten patients were treated with optimal cytoreductive surgery, leaving no gross residual disease. Seven patients received ifosfamide/cisplatin chemotherapy, and the remaining three patients received other platinum-based combination chemotherapy. Demographic data, pathologic findings, treatments, and survival time were reviewed. Of the ten patients, two were scored at FIGO stage IIC, seven were at stage IIIC, and one was at stage IV. The median survival time of all ten patients was 46 months. The overall survival rate was 60.0% at 1 year, 40.0% at 2 years, and 20.0% at 5 years. Platinum-based combination chemotherapy after optimal cytoreductive surgery may be effective in the treatment of ovarian MMMT.

On the apparent failure of adjuvant pelvic radiotherapy to improve survival for women with uterine sarcomas confined to the uterus.

Despite numerous studies documenting reduction of pelvic relapses after adjuvant pelvic radiotherapy stage I and II uterine sarcomas, improved survival remains unproven. This retrospective report analyzes patterns of failure, survival, and toxicity in 42 women with stage I and 7 patients with stage II uterine sarcomas treated from 1972 through 1998 to identify patients likely to benefit from pelvic or abdominal radiotherapy and chemotherapy. Four of these patients also received adjuvant chemotherapy. There were 20 leiomyosarcomas, 18 homologous mixed mullerian tumors, and 11 heterologous mixed mullerian tumors. Disease-free survivals for mixed mullerian tumors were 65% at 5 years and 61% at 15 years. Disease-free survivals for leiomyosarcomas were 40% at 5 years and 40% at 15 years. There were 14 distant only, 5 distant and abdominal, 1 abdominal, 1 distant and pelvic, and 2 unknown initial sites of failure. Acute toxicity was acceptable as measured by a median 1-kg weight loss from radiotherapy and a 2% rate of failure to complete therapy. Chronic toxicity consisted of 3 small bowel obstructions and 1 sigmoid colon obstruction. In conclusion, the efficacy of adjuvant pelvic radiation is demonstrated by the absence of any isolated pelvic failures. Although the frequent occurrence of peritoneal failures suggests a role for prophylactic abdominal radiation for mixed mullerian tumors, more effective systemic therapy is necessary to substantially increase the chance of cure for women with early-stage uterine sarcomas.