Mullerian Tumor Research Articles

GHRH Receptor Expression in Malignant Mixed Müllerian Tumors: A Potentially Targetable Biopredictor.

Malignant mixed Müllerian tumors (MMMTs) are aggressive malignant neoplasms with a high recurrence rate and poor prognosis. Despite advances in adjuvant therapies in recent years, the prognosis of these tumors has not improved. Growth hormone-releasing hormone (GHRH) is produced by a variety of malignant tumors and acts as a growth factor in an autocrine/paracrine manner. Its function requires the presence of its receptors to exert its effects on neoplastic cells. In this study, we evaluated the expression of GHRH receptors (GHRH-R) in a group of MMMTs. Thirty-one examples of MMMTs from endometrium, ovary, uterine tube, and pelvic peritoneum were retrieved from the files of Department of Pathology at the University of Miami, Jackson Memorial Hospital. Immunohistochemistry for GHRH-R was performed on paraffin sections and the staining results were evaluated separately in both epithelial and mesenchymal components of each tumor. The presence of pituitary type growth hormone-releasing hormone receptor mRNA and that of its biologically active splice variant were also evaluated by RT-PCR in 6 of the tumors. Positive immunohistochemical reaction for GHRH-R was detected in 30 tumors (96%). The epithelial and sarcomatous components were positive in 30 (96%), whereas one endometrial tumor was negative in both components. The mRNA for GHRH-R and its splice variant was found in all 6 tested tumors. This study shows that GHRH-R is expressed by the majority of MMMTs in both epithelial and mesenchymal components. This finding could potentially serve as a basis for therapeutic approaches using synthetic peptide antagonists of GHRH-R that have shown significant efficacy with minimal side effects in experimental models.

Morphological and Immunohistochemical Reevaluation of Tumors Initially Diagnosed as Ovarian Endometrioid Carcinoma With Emphasis on High-grade Tumors.

Ovarian endometrioid carcinomas (OEC) of low grade have characteristic morphologic features, but high-grade tumors can mimic high-grade serous and undifferentiated carcinomas. We reviewed tumors initially diagnosed as OEC to determine whether a combination of pathologic and immunohistochemical features can improve histologic subclassification. Tumors initially diagnosed as OEC were reviewed using World Health Organization criteria. We also noted the presence of associated confirmatory endometrioid features (CEFs): (i) squamous metaplasia; (ii) endometriosis; (iii) adenofibromatous background; and (iv) borderline endometrioid or mixed Mullerian component. A tissue microarray was constructed from 27 representative tumors with CEF and 14 without CEF, and sections were stained for WT-1, p16, and p53. Of 109 tumors initially diagnosed as OEC, 76 (70%) tumors were classified as OEC. The median patient age was 55 years, and 75% of patients were younger than 60 years. Ninety-two percent presented with disease confined to the pelvis, and 87% of tumors were unilateral. The median tumor size was 11.8 cm. Only 3% of tumors were high grade (grade 3of 3). Eighty percent of cases had at least 1 CEF, and 59% had at least 2 CEFs. Eleven percent overexpressed p16, 0% overexpressed p53, and 3% expressed WT-1. Only 10% of patients died of disease at last follow-up. Thirty-three (33) tumors, or 30% of tumors originally classified as endometrioid, were reclassified as serous carcinoma (OSC). The median patient age was 54.5 years, and 59% of patients were younger than 60 years of age. Only 27% had disease confined to the pelvis at presentation, 52% of tumors were unilateral, and the median tumor size was 8 cm. Associated squamous differentiation, endometrioid adenofibroma, and endometrioid or mixed Mullerian borderline tumor (CEFs) were not present in any case, but 6% of patients had endometriosis. Approximately one half of the reclassified OSC demonstrated SET-pattern morphology (combinations of glandular, cribriform, solid, and transitional cell-like architecture) and were immunophenotypically indistinguishable from OSCs with papillary architecture. Sixty percent of OSC overexpressed p16, 50% overexpressed p53, and 82% expressed WT-1. At last follow-up, 52% had died of disease. Compared with OSC, OEC patients more frequently presented below 60 years of age (P=0.046), had low-stage tumors (P<0.001), were more frequently unilateral (P<0.001), more frequently had synchronous endometrial endometrioid carcinomas (P<0.001); and had no evidence of disease at last follow-up (P<0.001). Their tumors were of lower grade (P<0.001), had more CEFs (P<0.001), and less frequently overexpressed p16 and p53 (P=0.003 and P<0.001, respectively) and less frequently expressed WT-1 (P<0.001). This analysis emphasizes the diagnostic value of CEFs, the presence of a low-grade gland-forming endometrioid component, and WT-1 negativity, as valid, clinically relevant criteria for a diagnosis of OEC. Glandular and/or cribriform architecture alone may be seen in both OECs and OSCs and are therefore not informative of diagnosis. Further study is needed to elaborate the characteristics of the exceedingly rare high-grade OEC.

Thirty-day postoperative mortality for endometrial carcinoma in England: a population-based study.

To quantify trends in 30-day mortality following surgery for endometrial carcinoma in England, and investigate hospital- and geographical-level variations. Retrospective population-based observational study using cancer registration and Hospital Episodes Statistics data. England. Women diagnosed with endometrial carcinoma (ICD10 C54-C55 excluding sarcomas and malignant mixed Mullerian tumours) between 2000 and 2009 who were treated surgically (n= 38332). Random effects logistic regression model of postoperative mortality rates, adjusting for patient- and/or tumour-level factors (namely age, income deprivation, year of diagnosis, FIGO stage and grade). Case-mix adjusted postoperative mortality rates for hospitals and cancer networks were derived from the model. Multiple imputation was used to account for missing stage and grade data. 30-day postoperative mortality rate. For 2000-2009, the percentage of women dying within 30days of surgery for endometrial carcinoma was very low at 0.61% (235 deaths), and decreased from 0.70% in 2000-2001 to 0.48% in 2008-2009. Postoperative mortality rates were lower for laparoscopic surgery, and higher for older women, those with advanced stage disease and high-grade tumours. Crude and case-mix adjusted results indicated that one hospital had a higher postoperative mortality rate than expected. The postoperative mortality rate for endometrial carcinoma in England is low and has improved since 2000, with increasing use of laparoscopic surgery. Postoperative mortality rates differed by surgical approach, patient age, disease stage and tumour grade. Only one hospital had a higher postoperative mortality rate than expected after adjusting for patient case-mix. More women with endometrial cancer but better 30-day survival after surgery since 2000.

An Unusual Site of Metastasis of Malignant Mixed Müllerian Tumor of the Uterus

Malignant mixed Mullerian tumors (carcinosarcomas) are biphasic tumors of the uterus and uterine cervix with carcinomatous and sarcomatous components. Malignant mixed Mullerian tumors (MMMT) are rare tumors, accounting for <5% of uterine cancers. They most commonly metastasize to the vagina, pelvic wall, lungs, and ovaries. We report a unique case of MMMT, which developed in a 69-year-old woman after she presented with hip and knee pain. Ultimately, her pain was found to be caused by metastatic tumor deposits in her psoas muscle. The primary tumor was found to be a MMMT of the uterine corpus. We recommend practitioners be aware of this entity and include it and other metastatic lesions in their differential diagnosis in difficult cases of non-resolving pain.

Abstract A69: The PAX8 cistrome in benign and malignant Mullerian epithelia.

Abstract Background: PAX8 is a highly evolutionarily conserved transcription factor with essential roles in both Mullerian development as well as high grade serous ovarian cancer. While PAX8 has emerged as a common clinical tool to identify Mullerian primary tumors, the transcriptional network directed by PAX8 in Mullerian epithelia is unknown. In this study, we sought to understand how PAX8 interacts with chromatin in the context of both benign fallopian tube secretory epithelial cells as well as in high grade serous carcinomas. Methods: This study examined PAX8 using six cell lines: three immortalized fallopian tube secretory cell lines (FT33TAg, FT194, FT246) generated by our laboratory and three high grade serous ovarian cancer cell lines (KURAMOCHI, OVSAHO, and JHOS4) with high genomic fidelity to human tumors according to The Cancer Genome Atlas. First, we used chromatin immunoprecipitation combined with DNA sequencing (ChIP-Seq) to map PAX8 binding sites along the genome. Overlapping peaks among the cell lines were aligned to define a minimum consensus binding motif for PAX8. Unsupervised hierarchical clustering then segregated the peaks into groups. The nearest gene within 50000 base pairs to each peak was identified. Next, we used a series of RNAi experiments to knockdown PAX8 in all six cell lines using three independent siRNA sequences plus a pool and examined the effect on the transcriptome in each cell line using RNA-seq. Finally, we used pathway analysis software and gene ontology tools to map the signaling networks directed by PAX8. Results: Among the six cell lines, there were 11,361 unique PAX8 peaks by ChIP-seq. Approximately half of all PAX8 binding sites were located in intergenic sequences and about a 40% were in intronic sequences. The consensus DNA binding motif was almost identical between benign and malignant cell lines and was consistent with a predicted PAX homology motif. Unsupervised clustering identified 3 sets of peaks: 1) a highly conserved set of peaks among all six cell lines comprised of 558 peaks; 2) a common set of peaks common to benign cell lines but absent in cancer cell lines comprised of 3013 peaks; and 3) a very heterogeneous pattern of DNA binding unique to each cancer cell line ranging from few PAX8 peaks (JHOS4) to more than 3000 PAX8 peaks (both KURAMOCHI and OVSAHO). By gene ontology analysis, the common set of peaks for all six cell lines clustered around apoptosis and programmed cell death. Using the combination of RNAi with RNA-seq, few genes (ranging from 1 – 32 genes) were affected by loss of PAX8 in the fallopian tube cell lines or JHOS4, while more than 200 genes were altered in KURAMOCHI and OVSAHO. While in KURAMOCHI these genes were more likely to involve metabolic processes, in OVSAHO these genes were more likely to involve cell cycle regulation. Conclusions: PAX8 expression is shared among benign fallopian tube secretory cells and high grade serous carcinoma, but PAX8 function appears to be context dependent. While there is a shared set of PAX8 binding sites in benign and malignant Mullerian epithelia, PAX8 appears to be essential for the expression of very few targets in benign cells compared to cancer. In addition, PAX8 appears to have greater access to chromatin in the setting of cancer as evidenced by an increase in the number of PAX8 binding sites, while at the same time losing affinity for a set of binding sites seen only in benign fallopian tube cells. Together, these data suggest a dynamic reorganization of chromatin in the process of malignant transformation. Citation Format: Kevin M. Elias, Megan Emori, Myles Brown, Ronny Drapkin. The PAX8 cistrome in benign and malignant Mullerian epithelia. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Ovarian Cancer Research: Exploiting Vulnerabilities; Oct 17-20, 2015; Orlando, FL. Philadelphia (PA): AACR; Clin Cancer Res 2016;22(2 Suppl):Abstract nr A69.

Malignant Mixedmullerian Tumor of Uterus: Rare Case &amp; Rarer Diagnosis

Carcinosarcoma or malignant mixed mullerian tumor (MMMT) of uterus is a rare tumor, representing only 1-2 % of all uterine neoplasm. The pre-operative diagnosis of MMMT can be a challenge as no preoperative diagnostic test including endometrial biopsy, CT or MRI has enough sensitivity or specificity. We are reporting one such case of MMMT where endometrial biopsy failed to make a pre-operative diagnosis to highlight the fact that a definitive pre-operative diagnosis can only be made in a small proportion of such cases thus precluding optimal surgery in such cases. Keywords: Carcinosarcoma, Malignant mixed mullerian tumor, Endometrial biopsy.

Large retroperitoneal malignant mixed Mullerian tumor

A 57-year-old asymptomatic lady had come for a master health check-up with a report of fibroid uterus diagnosed on ultrasound at a private hospital. Intraoperatively, a large retroperitoneal tumor was found with the uterus and adnexae being normal. The mass was removed in toto, and its pathological examination revealed a malignant mixed Mullerian tumor (MMMT). Immunohistochemistry also supported the diagnosis of MMMT. The postoperative period was uneventful, and the patient was discharged with the advice of oncology referral.

Malignant mixed Mullerian tumor: A rare case report

Malignant mixed Mullerian tumor of the uterus, also called carcinosarcoma, is a very rare and aggressive type of malignancy with epithelial and mesenchymal components. Therefore, it is considered a metaplastic carcinoma. Predominantly these carcinomas are found in postmenopausal women presenting with uterine bleeding and uterine enlargement. We represent a case of a 60-year-old female with complaints of pain in the abdomen and bleeding per vaginum. Hysterectomy with bilateral salpingo-oophorectomy was performed and a diagnosis of malignant mixed Mullerian tumor of the uterus was made.

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

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. 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. 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. 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.

Uterine Carcinosarcoma Associated with Tamoxifen Use in a Menopausal Patient: A Case Report

BACKGROUND AND OBJECTIVE: Uterine carcinosarcoma, also known as malignant mixed Mullerian tumor, is a rare uterine malignancy. Although the origin and prognosis of this cancer remain undetermined, the Mullerian ducts are believed to be the main origin. This tumor has the ability to change into epithelial and mesenchymal components and is more common among black and postmenopausal women. Prior history of radiation therapy and use of tamoxifen also contribute to this condition. The clinical characteristics of uterine carcinosarcoma, including postmenopausal bleeding, are similar to those of endometrial cancer. This condition with a poor prognosis and aggressive nature may be overcome by a combination of therapies including surgery, chemotherapy, and radiotherapy. Herein, we present a case of uterine carcinosarcoma associated with tamoxifen use in a menopausal patient. CASE REPORT: The patient was a 67-year-old menopausal woman (G9, P5, L5, Ab4), who underwent lumpectomy and chemoradiotherapy ten years ago due to estrogen receptor-positive breast cancer (ductal carcinoma). The patient received 40 mg of tamoxifen on a daily basis, and after six years of tamoxifen use, she experienced postmenopausal bleeding. Increased endometrial thickness appeared in the ultrasound, and uterine carcinosarcoma was diagnosed, based on pathologic evaluations. The patient received multi-modal therapy, and after a year of follow-up, no specific problems were reported. CONCLUSION: According to the results, symptoms of uterine cancer should be taken into account in menopausal patients consuming tamoxifen.

Uterine Malignant Mixed Mullerian Tumour - Revisited In Newer Lights : A Case Report From A Tertiary Care Centre

Carcinosarcoma of the uterus, also known as malignant mixed mullerian tumour (MMMT) is a very rare and aggressive gynaecological neoplasm, having an overall poor prognosis. They can arise in any organ of the female genital tract but are most commonly found in uterus. They are histologically biphasic having malignant epithelial and mesenchymal components. We report a case of uterine MMMT, clinically presenting as uterine polyp, in a postmenopausal female.

Abstract B62: Racial disparities in endometrial cancer incidence and mortality are limited to non-Hispanic black women

Abstract Background: Unlike the decreasing incidence seen for most cancers, incidence rates of endometrial cancer have been increasing in the United States over the last decade. Earlier studies have shown that mortality rates from endometrial cancer are significantly higher for non-Hispanic black women compared to non-Hispanic white women, but this has not been established for other racial/ethnic groups. Our objective was to determine whether the increasing incidence and mortality from endometrial cancer are equally distributed by race/ethnicity and tumor histologic subtype. Methods: Data from the Surveillance, Epidemiology and End Results (SEER) registry were used to identify women diagnosed with endometrial cancer from 2000-2011. A total of 120,513 women, including 90,621 non-Hispanic white (NHW) women (75.2%), 11,386 Hispanic women (9.4%), 10,365 non-Hispanic black women (NHB) (8.6%) and 8,141 Asian women (6.8%) comprised the study population. Age-adjusted incidence and incidence-based mortality rates, with 95% confidence intervals and annual percent changes (APC), were calculated by race/ethnicity (4 groups) overall and for 7 histologic subtypes (low grade endometrioid, high grade endometrioid, clear cell, mixed, MMMT, serous, and other), along with rate ratios to compare racial/ethnic groups, using NHW as the referent group. In addition, 5-year survival rates were calculated by race/ethnic group, histologic subtype, and stage at diagnosis (localized, regional, distant). Differences between NHW and NHB women in the percentage surviving 5 years were described by calculating (%NHW-%NHB)/%NHW) overall and for each histologic subtype and each stage at diagnosis (21 comparisons). Results: Incidence rates for endometrial cancers are rising across all racial/ethnic groups, with the greatest annual percent change (APC) seen among NHB and Asian women (APC=2.5 for both). Low-grade endometrioid endometrial cancers are the most commonly diagnosed subtype among all women, with highest rates in NHW women, but these rates have stabilized or decreased over the last decade for all women with the exception of NHB women (APC=1.0). High grade endometrioid endometrial cancers have significantly decreased incidence rates over the last decade, particularly among NHW women (APC=-2.5). NHB women have the highest incidence rates of this and other aggressive subtypes of endometrial cancers (clear cell, serous, and malignant mixed Mullerian tumors) compared to NHW women. Hispanic and Asian women had incidence rate ratios equal to or lower than NHW women for all tumor subtypes. For every subtype and stage of disease, the 5-year survival for NHB women is lower than for NHW women, and significantly lower for nearly each comparison. The smallest percent difference seen is for women with localized endometrioid cancers, where NHB women have 6% lower survival, and the largest is 59% lower survival for distant stage clear cell cancers. Hispanic and Asian women have the same or slightly better survival rates compared to NHW women across all stages and subtypes. Conclusions: The lower survival rates among NHB women with endometrial cancer persist at nearly every stage and histologic subtype examined. Various factors, including socioeconomic status (SES), comorbid conditions, access to care, and treatment decisions may all impact this disparity to some extent, yet Hispanic women who have many of the same challenges are at lower risk of occurrence and have outcomes similar to NHW women after diagnosis. Additionally, the most aggressive types of endometrial cancer are also more common among NHB women, and are among the endometrial cancer subtypes with largest increasing incidence rates. We have yet to fully account for these disparities seen primarily in NHB women and, without intervention, they are likely to persist and potentially widen as endometrial cancer emerges as a significant cause of morbidity and mortality in the decades to come. Citation Format: Michele L. Cote, Julie J. Ruterbusch, Sara H. Olson, Karen H. Lu, Rouba Ali-Fehmi. Racial disparities in endometrial cancer incidence and mortality are limited to non-Hispanic black women. [abstract]. In: Proceedings of the Seventh AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 9-12, 2014; San Antonio, TX. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2015;24(10 Suppl):Abstract nr B62.

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

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. 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. 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. 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. Increasing rates of aggressive endometrial cancers may widen the survival disparity between NHW and NHB women.

Membrane associated cancer-oocyte neoantigen SAS1B/ovastacin is a candidate immunotherapeutic target for uterine tumors.

The metalloproteinase SAS1B [ovastacin, ASTL, astacin-like] was immunolocalized on the oolemma of ovulated human oocytes and in normal ovaries within the pool of growing oocytes where SAS1B protein was restricted to follicular stages spanning the primary-secondary follicle transition through ovulation. Gene-specific PCR and immunohistochemical studies revealed ASTL messages and SAS1B protein in both endometrioid [74%] and malignant mixed Mullerian tumors (MMMT) [87%] of the uterus. A MMMT-derived cell line, SNU539, expressed cell surface SAS1B that, after binding polyclonal antibodies, internalized into EEA1/LAMP1-positive early and late endosomes. Treatment of SNU539 cells with anti-SAS1B polyclonal antibodies caused growth arrest in the presence of active complement. A saporin-immunotoxin directed to SAS1B induced growth arrest and cell death. The oocyte restricted expression pattern of SAS1B among adult organs, cell-surface accessibility, internalization into the endocytic pathway, and tumor cell growth arrest induced by antibody-toxin conjugates suggest therapeutic approaches that would selectively target tumors while limiting adverse drug effects in healthy cells. The SAS1B metalloproteinase is proposed as a prototype cancer-oocyte tumor surface neoantigen for development of targeted immunotherapeutics with limited on-target/off tumor effects predicted to be restricted to the population of growing oocytes.

Outcome of neoadjuvant chemotherapy in BRCA1/2 mutation positive women with advanced-stage Müllerian cancer

ObjectivesTo investigate whether patients with germline BRCA1/2 mutations who received neoadjuvant chemotherapy (NAC) for advanced-stage Müllerian cancer (MC) have an improved outcome compared to patients who did not undergo genetic testing. MethodsThree hundred and two patients who received NAC for stage III–IV MC were identified from a multi-institutional study involving Cleveland Clinic and Brigham and Women's Hospital for 2000–2014 and 2010–2014 respectively. Patients were divided into 3 cohorts: patients with germline BRCA1/2 mutations (BRCA_mut+; N=30), patients with no genetic testing (BRCA_mut_unk; N=166) and patients with negative genetic testing (BRCA_mut−, N=106). ResultsThere were no differences in the clinical characteristics and rates of complete cytoreduction and bowel resection between the three groups. BRCA_mut+ had longer PFS compared to BRCA_mut_unk and BRCA_mut− (19.1 vs. 15.1 vs. 15.7months respectively. However, this difference was not statistically significant (p=0.48). Patients with BRCA2 mutation had non-significant trend toward longer PFS compared to patients with unknown BRCA or BRCA1 mutation (20.2 vs. 15.1 vs. 14.8months respectively, p=0.58). BRCA_mut+ and BRCA_mut− had longer overall survivals (OS) compared to BRCA_mut_unk patients (50.5 vs. 54.1 vs. 36.5months respectively, p=0.009). In multivariable analyses, controlling for age, stage and complete cytoreduction, BRCA_mut_unk was associated with worse PFS (HR 1.44, 95% CI 1.01–2.05, p=0.045) and OS (HR 2.67, 95% CI 1.33–5.36, p=0.006). ConclusionsPatients with germline BRCA mutations had improved outcomes with NAC compared to patients with unknown BRCA status. These outcomes were more favorable compared to the outcome of NAC in prior studies.

Primary Chondroblastic Osteosarcoma of the Uterus: Immunohistochemical Examination and Differential Diagnosis with Malignant Mixed Mullerian Tumor

Primary Chondroblastic Osteosarcoma of the Uterus: Immunohistochemical Examination and Differential Diagnosis with Malignant Mixed Mullerian Tumor

UTERİN KARSİNOSARKOMLAR: 18 OLGUDA HİSTOPATOLOJİK GÖZDEN GEÇİRME

Objective: Uterine carcinosarcomas are relatively rare tumors with poor prognosis. These tumors were considered as a subset of uterine sarcomas; however currently they are classified within the carcinoma group. Recent studies have revealed that these tumors behave according to the characteristics of the epithelial component. The aim of the study was to discuss the histopathological characteristics of these quite aggressive tumors, which were diagnosed in our clinic, in the light of the literature. Materials and Methods: We performed a retrospective analysis of 18 patients with uterine sarcoma, who were operated at our oncology department between 2004 and 2014. Cases with a pathology result of either carcinosarcoma or malignant mixed Mullerian tumor were included in the study pathologically. Tumor size, presence of myometrial invasion and pelvic lymph node metastases were reviewed. Demographic data were recorded. Staging was performed according to FIGO (1988) protocol. Results: 18 patients were diagnosed with carcinosarcoma. 95% of the patients were in postmenopausal period. The mean age was 64.6 . 13 patients underwent comprehensive surgical staging (total hysterectomy + bilateral salpingo-oophorectomy + pelvic para-aortic lymphadenectomy + omentectomy + appendectomy). 5 patients with advanced stage disease underwent suboptimal debulking. 7 patients were stage I and 11 patients were stage II-IV. Myometriyal invasion was present in 17 patients and for 9 of these patients the invasion was observed in more than ½ of the myometrium. Lymphovascular invasion was observed in 11 patients. Conclusion: Uterine carcinosarcomas are extremely aggressive neoplasms. Although they used to be categorized under the group of sarcoma, recent studies have shown that uterine carcinosarcomas are high-grade endometrial carcinomas, which include sarcomatous metaplasia. First-line treatment for uterine carcinosarcomas is surgery. Adjuvant chemotherapy and radiation therapy combinations are used as complementary therapies

Metastatic collision tumour: A case report

Abstract Background Collision tumours are extremely rare. They are defined by the presence of two tumours of different histological origin in the same organ. Clinical case A 71-year-old female with history of a carcinoid tumour removed 20 years ago without any recurrence. The patient was admitted with intestinal occlusion symptoms secondary to a right flank abdominal tumour. An exploratory laparotomy was performed, removing the tumour and applying optimal debulking. The histopathological study reported bilateral ovary adenocarcinoma, as well as metastatic collision tumour of two histological types: well differentiated adenocarcinoma and a mixed malignant mesodermic Mullerian tumour. The patient was treated with adjuvant chemotherapy with poor results (death in 24 months). Conclusions The presence of collision tumours is extremely rare. There are no statistics or specific treatment reported. Diagnosis is made with histopathology. At the moment, no similar cases have been reported.

Primitive Fallopian Tube Carcinosarcoma: Three Cases with Immunohistochemical Profiling

in the endometrium or in the ovary in elderly women. This tumor type is rarely observed in the Fallopian tube. We report here three cases of primitive Fallopian tube MMMT. The immunophenotypic profile was based on the analysis of epithelial (cytokeratin AE1/AE3) and stromal (CD10) markers. The search of heterologous mesenchymal component was performed using anti- S100, desmin, myogenin, smooth actin, cKit antibodies and that of sex-cord component with anti-inhibin antibody. P53 status was also documented as frequently altered in high grade serous carcinoma. Cases Case 1 Abstract Most carcinosarcoma, formerly designed as Malignant Mixed Mullerian Tumors are found in the uterus or the ovary, but rarely in the fallopian tube. The histogenesis of this type of tumor and its place regarding serous or poorly differentiated carcinoma are discussed. We document here three typical cases primarily developed in the fallopian tube. The patients were 69, 70 and 82 years old. They all presented with abdominal pain and large unilateral adnexal mass apparently confined to the ovary. Bilateral salpingo-oophorectomy was performed in all cases. Macroscopically, the tumors were located on the fimbriae in two cases and on the fallopian tube in one. They presented cystic and solid components. In addition, in one case, vegetations were present on the serosal surface of the homolateral ovary whereas both ovaries were normal in the two other cases. Microscopically, tumors were classified as carcinocarcoma with heterologous component in two cases and as homologous carcinosarcoma in one. All tumors showed immunoreactivity for cytokeratins, p53, and CD10 and, in two cases, immunoreactivity for S100 was also observed. The tumor located in the fallopian tube was associated with p53 positive intra-epithelial neoplasia in the contralateral fimbriae. The vegetations observed on the surface of the homolateral ovary in one case corresponded to a focus of high grade serous carcinoma. As high grade serous carcinoma, carcinosarcoma can derive from the fimbria of the Fallopian tube.

Advanced Mesodermal (Müllerian) Adenosarcoma of the Ovary: Metastases to the Lungs, Mouth, and Brain.

Background. A malignant mixed Müllerian tumor (MMMT) is a malignant neoplasm found in the uterus, the ovaries, the fallopian tubes, and other parts of the body that contains both carcinomatous (epithelial tissue) and sarcomatous (connective tissue) components. Outcome of MMMTs is determined primarily by depth of invasion and stage. The metastatic background of these lesions is controversial and unknown. Case Report. A 75-year-old woman was admitted to the hospital with anorexia, weakness, and persistent coughing. The imaging exams revealed a solid, promiscuous lesion of 16 × 14 cm in dimensions located into the small pelvis, surrounding the uterus and the ovaries. The patient underwent exploratory laparotomy. The mass was removed and the histological examination of the specimen revealed an advanced mesodermal adenocarcinoma of the ovary (MMMT). Nine days after the operation the patient presented with metastatic lesions in the mouth as well as the lungs. Within a month after the discharge from the hospital metastatic lesions of the MMMT were also depicted in the CT brain scan. Conclusion. Despite the fact that sarcomas have a long-term metastatic potential, to our knowledge this is the first case of Müllerian adenosarcoma presenting with such extraperitoneal metastases.