Case Of Uterine Carcinosarcoma Research Articles

Non-Metastatic Uterine Carcinosarcoma: A Tailored Approach or One Size Fits All?

Purpose: Uterine carcinosarcomas are highly aggressive tumors of the endometrium and are associated with a poor prognosis. The optimal adjuvant treatment for both early and advanced-stage patients remains unclear. Methods: Cases of uterine carcinosarcoma were identified in our institution’s pathology database between 2000 and 2022. Kaplan–Meier estimates were calculated for the local and distant recurrence-free, disease-free and overall survival; hazard ratios were calculated using Cox proportional hazards modelling for independent prognostic factors including the stage and treatment. Results: A total of 48 patients were identified as having uterine carcinosarcoma, of whom 70.8% were surgically staged. In total, 43 patients had pelvic-confined disease, while five had positive omental or peritoneal biopsies at surgery. There were 10 pelvic (20.8%) and 19 (39.6%) distant recurrences. None of the patients with stage IA disease who received chemotherapy and brachytherapy experienced disease recurrence. The local recurrence-free survival was 54.95%, the distant recurrence-free survival was 44.7%, and the overall survival was 59.6% at 5 years. Local recurrence-free survival and overall survival were inversely associated with advanced-stage OR 1.23 (p = 0.005) and OR 1.28 (p = 0.017), respectively, and no chemotherapy was associated with OR 1.96 (p = 0.06) and OR 2.08 (p = 0.056), respectively. Conclusion: The local and distant recurrence rates were high for advanced=stage patients even when treated with aggressive adjuvant therapy regimens. Chemotherapy may improve recurrence and survival. Early-stage patients may perform well with vaginal vault brachytherapy and chemotherapy. Further prospective comparisons are required between sequential, sandwich, and concurrent approaches to chemotherapy and radiotherapy, to optimize outcomes in this high-risk population.

Clinicopathological and gene mutation characteristics of uterine carcinosarcoma

To explore the clinicopathological characteristics, immunophenotype, diagnosis and differential diagnosis of uterine carcinosarcoma (UCS), and to explore the gene mutation characteristics and tumor mutation burden (TMB) of UCS. The clinical imaging, pathomorphological data and immunohistochemical expression of 4 cases of UCS, which were archived in the Department of Pathology of the Second Affiliated Hospital of Soochow University from January 2021 to May 2022 were retrospectively analyzed. All exon groups of 4 cases of UCS were sequenced. All the 4 patients were female, aged 47-81 years. The maximum diameter of the tumor was 4.0-13.0 cm, and the boundary was unclear. Microscopically, the tumor was composed of malignant epithelium and sarcoma. Immunohistochemistry showed that the epithelial components of 4 patients expressed broad-spectrum cytokeratin (AE1/E3), the sarcoma components expressed Vimentin, PAX8, ER, PR were expressed to varying degrees, and Ki-67 positive index was high (60%-90%). There were 3 p53 missense mutations, 1 nonsense mutation, 4 MLH1, PMS2, MSH2, MSH6 were positive and PD-L1 was negative. The sequencing results of the whole exon group of 4 UCS patients showed that TP53, BCL9L, BRD4, CLTCLI, PSMD1I, PLEC genes showed a high mutation ratio, which was 3/4, 2/4, 2/4, 2/4, 2/4, 2/4, respectively. TMB analysis showed that the TMB of 4 cases of UCS was<5 mut/Mb. UCS is a rare and highly malignant endometrial tumor. The sequencing results of the whole exon group suggested that TP53, BCL9L, BRD4 and other genes had high mutation rates, suggesting that the occurrence and development of UCS may be closely related to Wnt signaling pathway. Molecular typing indicated that 3 cases of UCS were of high copy number type/p53 mutation type, and 1 case had POLD1 mutation. Microsatellite stability, low PD-L1 expression and TMB results suggested that UCS patients have no obvious advantage in immunotherapy.

A case of uterine carcinosarcoma with scalp metastasis

A case of uterine carcinosarcoma with scalp metastasis

Uterine cavity evacuation as a novel approach for uterine size reduction during minimal invasive surgery for uterine carcinosarcoma: a report of two cases

Background: Uterine carcinosarcoma often presents with significant uterine distention. This makes it difficult to perform minimally invasive surgery, which is preferred for uterine cancer given the significant recovery benefits. Cases: We present two cases of uterine carcinosarcoma in which we performed uterine evacuation intraoperatively to decompress the uterine volume to facilitate specimen removal through the vagina. The first patient ultimately had stage IA disease. She received adjuvant chemotherapy and radiation and has remained disease-free for 2 years. The second patient had stage IVB disease on final pathology report. She received adjuvant chemotherapy but had disease recurrence 4 months after completion of treatment. Conclusion: Intraoperative uterine evacuation during surgery for uterine carcinosarcoma may make possible a minimally invasive procedure in patients with large, distended uteri.

Clinical and imaging features of carcinosarcoma of the uterus and cervix

AimThe purpose of our study was to analyze the clinical and imaging features of uterine carcinosarcoma (UCS) and cervical carcinosarcoma (CCS), and to explore the diagnostic and staging accuracy of computed tomography (CT) and magnetic resonance imaging (MRI) examinations.Methods41 patients including 37 with UCS and 4 with CCS from July 2011 to September 2020 were enrolled in the study. Of the 37 UCS cases, 7 had CT images, 27 had MRI images, and 3 had both CT and MRI images. The Clinical data, CT or MRI imaging findings were analyzed. Diagnosis and staging accuracy of CT and MRI images were also analyzed.ResultsCarcinosarcoma usually occurs in postmenopausal women (40/41), with the typical clinical symptom being vaginal bleeding (33/41). The CA125 degree was significantly different between the two invasion depth groups (p = 0.011). Most uterine carcinosarcomas showed unclear boundaries, uneven density, low or equal signal on T1WI, high or mixed signal on T2WI, uneven high signal on diffusion-weighted image (DWI), and mild enhancement. The diagnostic accuracies of CT and MRI for carcinosarcoma were 0% and 3.33%, respectively. The diagnostic accuracy for malignant tumors on CT and MRI was 50% and 83.33%, respectively.ConclusionsCarcinosarcoma lesions presented with huge mass filling in the cavity, and some presented with small polypoid lesions or endometrial thickening. Evaluation of lymph node metastasis is a significant challenge for imaging staging.

Does the histologic subtype of uterine carcinosarcoma correlate with outcomes?

<h3>Objectives:</h3> To evaluate uterine carcinosarcoma (UCS) by epithelial component subtype and compare clinicopathologic characteristics, recurrence patterns, and survival. <h3>Methods:</h3> We conducted a retrospective medical record review of patients diagnosed with UCS from January 2008 through March 2019 at one institution. Cases of UCS were classified based on carcinoma subtype-endometrioid versus non-endometrioid. Non-endometrioid included serous, clear cell, mixed cell, squamous, poorly differentiated and un-differentiated epithelial components. If a predominant histologic carcinoma subtype was not identified with initial review, the slides were classified by a pathologist. Recurrence sites were pelvic, nodal, or distant. Data are presented as percent, median (interquartile range) or mean ± standard deviation. We compared characteristics between UCS subtypes and calculated hazard ratios (HR) and 95% confidence intervals (CI) for overall survival. <h3>Results:</h3> We identified 77 patients with UCS, 18 (23%) with endometrioid subtype, 58 (75%) with non-endometrioid subtype, and one who could not be classified, as slides were unavailable. Median length of follow-up was 2 years[MRH1]; mean age at diagnosis was 70 years. The cohort was primarily White (66%) and African American (18%). Measured demographic variables, risk factors, symptoms at presentation, surgery, and adjuvant treatments were similar between epithelial subtypes. Most patients underwent surgery (96%) with nodal evaluation in 67%, 77% received chemotherapy, and 51% underwent radiation treatment. Forty percent of patients had mismatch repair protein immunohistochemistry, and 33% of patients with endometrioid subtype had loss of expression of at least one protein compared with 0% in the non-endometrioid group (p=0.02). Of patients with endometrioid subtype, 72% presented in stage I/II compared to only 46% of those with non-endometrioid subtype (p=0.06). The endometrioid subtype was more likely to recur in the pelvis (33%) than non-endometrioid (12%), but of the 32 (46%) patients whose disease recurred, there was no differences in nodal or distant recurrence by subtype. Median overall survival for stage I/II UCS was 6[MRH2] years; patients with stage I/II endometrioid subtype demonstrated poorer overall survival than stage I/II non-endometrioid subtype (HR 3.0, 95% CI 0.98-9.2). Median overall survival for stage III/IV was 2 years; data survival for stage III/IV did not meet assumptions to calculate an HR. <h3>Conclusions:</h3> In this single-institution review of patients with UCS, those with stage I/II endometroid subtype had worse overall survival than those with stage I/II non-endometrioid subtype. Deficiency in mismatch repair protein expression and pelvic site of recurrent disease was more common in endometrioid than non-endometrioid subtypes. These findings suggest that the epithelial subcomponent in UCS has implications for biologic behavior of the disease and therapeutic choice.

A novel germline mutation in hMLH1 in three Korean women with endometrial cancer in a family of Lynch syndrome: case report and literature review

BackgroundEndometrial cancer is often the sentinel cancer in women with Lynch syndrome, among which endometrioid endometrial cancer is the most common. We found a Korean case of uterine carcinosarcoma associated with Lynch syndrome. And we reviewed 27 Korean women with endometrial cancer associated with Lynch syndrome already released in case report so far.Case presentationThe proband, a 45-year-old Korean woman received treatment for endometrioid adenocarcinoma. Her older sister and niece were treated for endometrioid adenocarcinoma and carcinosarcoma, respectively. Family history met the Amsterdam II criteria and immunohistochemical analysis revealed a loss of MLH1 and PMS2. They all harbored a previously unreported germline likely pathogenic variant in c.1367delC in MLH1. They underwent staging operations including total hysterectomy, bilateral salpingo-oophorectomy, pelvic/paraaortic lymph node dissection, and washing cytology. All three women were healthy without evidence of relapse for over 4 years.ConclusionThis report indicates a novel germline c.1367delC variant in MLH1, and presents a Korean case of uterine carcinosarcoma associated with Lynch syndrome. Furthermore, the c.1757_1758insC variant in MLH1 was suggested as a founder mutation in Lynch syndrome in Korean women.

Carcinosarcomas of the Uterus: Prognostic Factors and Impact of Adjuvant Treatment.

BackgroundUncertainties remain about the most effective treatment for uterine carcinosarcoma (UCS), a rare but aggressive uterine cancer, due to the limited scope for randomized trials. This study investigates whether nodal excision or adjuvant therapies after hysterectomy offer a survival benefit, using multi-institutional clinical registry data from South Australia.MethodsData for all consecutive cases of UCS from 1980 to 2019 were extracted from the Clinical Cancer Registry. Clinical and treatment-related factors associated with disease-specific mortality (DSM) and all-cause mortality (ACM) were determined using multivariable Cox proportional hazards regression, with subgroup analyses by stage.ResultsMedian follow-up for the 140 eligible cases was 21 months. 94% underwent hysterectomy, and 72% had an additional pelvic lymph node dissection (PLND). Furthermore, 16% received adjuvant chemotherapy; 11% adjuvant radiotherapy and 16% multimodal chemoradiotherapy, with an increase in the latter two modalities over time. DSM was reduced among those who underwent PLND (HR: 0.41; 95%CI: 0.23–0.74), adjuvant chemotherapy (HR: 0.39; 95%CI: 0.18–0.84) or multimodality treatment (HR: 0.11; 95%CI: 0.06–0.30) compared with hysterectomy alone for the whole cohort and for late stage disease (FIGO III/IV) but not for earlier stage disease, except for reduced DSM with multimodal therapy. Findings were similar for ACM.ConclusionOur findings indicate better survival among those who received PLND, chemotherapy and multimodal adjuvant therapy, with the latter applying to early and late stage disease. However, cautious interpretation is warranted, due to potential “indication bias” and limited power. Further research into effective treatment modalities, ideally using prospective study designs, is needed.

Mismatch Repair Deficiency in Uterine Carcinosarcoma: A Multi-institution Retrospective Review.

Immunohistochemistry (IHC) for mismatch repair (MMR) proteins is recommended in endometrial carcinomas as a screening test for Lynch syndrome, and mismatch repair deficiency (MMRd) is reported in ∼30% of cases. However, few studies have evaluated the rate of MMR loss in uterine carcinosarcomas. A 5-year retrospective database search of uterine carcinosarcomas was performed at 3 academic institutions. The histologic diagnoses, type of carcinoma present, and MMR IHC interpretations were confirmed by a gynecologic pathologist. One hundred three cases of uterine carcinosarcomas with available MMR IHC results were identified. Ninety-nine cases (96%) showed intact expression and 4 cases (4%) showed loss of MLH1/PMS2. All MMRd carcinosarcomas identified in this series had an endometrioid carcinomatous component and wild-type p53 expression. In contrast, the majority of MMR intact carcinosarcomas had a serous morphology and aberrant p53 expression. Three additional cases initially diagnosed as carcinosarcoma also revealed MMRd; however, given the lack of clear mesenchymal differentiation, these cases were reclassified as dedifferentiated endometrial carcinomas and were subsequently excluded from the carcinosarcoma category. No cases of Lynch syndrome were identified among carcinosarcoma patients, as all 4 MMRd cases were due to somatic MLH1 hypermethylation. In summary, we found that the rate of MMRd is markedly lower in uterine carcinosarcoma when compared with endometrial carcinoma. In the setting of MMR loss, a diagnosis of dedifferentiated carcinoma should be considered as almost half of the MMRd tumors which were called carcinosarcomas initially were reclassified as dedifferentiated on review. However, given the interobserver variability in the classification of carcinosarcoma versus dedifferentiated carcinoma a universal screening approach that includes uterine carcinosarcoma is still recommended.

Proposal for a Risk-Based Categorization of Uterine Carcinosarcoma.

To propose a categorization model of uterine carcinosarcoma (UCS) based on tumor cell types (carcinoma and sarcoma) and sarcoma dominance. This secondary analysis of a prior multicenter retrospective study examined 889 cases of UCS with available histologic evaluation. Based on survival outcome, cases were clustered into three groups: low-grade carcinoma with nondominant homologous sarcoma [type A, n = 96 (10.8%)], (1) low-grade carcinoma with heterologous sarcoma or any sarcoma dominance and (2) high-grade carcinoma with nondominant homologous sarcoma [type B, n = 412 (46.3%)], and high-grade carcinoma with heterologous sarcoma or any sarcoma dominance [type C, n = 381 (42.9%)]. Tumor characteristics and outcome were examined based on the categorization. Women in type C category were more likely to be older, obese, and Caucasian, whereas those in type A category were younger, less obese, Asian, and nulligravid (all P < 0.01). Type C tumors were more likely to have metastatic implants, large tumor size, lymphovascular space invasion with sarcoma cells, and higher lymph node ratio, whereas type A tumors were more likely to be early-stage disease and small (all P < 0.05). On multivariate analysis, tumor categorization was independently associated with progression-free survival (5-year rates: 70.1% for type A, 48.3% for type B, and 35.9% for type C, adjusted P < 0.01) and cause-specific survival (5-year rates: 82.8% for type A, 63.0% for type B, and 47.1% for type C, adjusted P < 0.01). Characteristic differences in clinicopathological factors and outcomes in UCS imply that different underlying etiologies and biological behaviors may be present, supporting a new classification system.

Sarcomatous Component in Uterine Carcinosarcomas Correlates With Advanced Stage and Poorer Prognosis.

Uterine carcinosarcomas, also known as malignant-mixed mullerian tumors, are rare and highly aggressive tumors whose prognostic factors remain controversial. The stage at the time of presentation is the most important prognostic factor thus far, but little information exists on the prognostic impact of the sarcomatous component (SC) in these tumors. We reviewed 21 cases of uterine carcinosarcomas and estimated the volume of the SC in each case. This information was correlated with the stage of the tumor at presentation. The percentage of the SC was also used to stratify the patients into 2 cohorts (high percentage of SC and low percentage of SC), and the 2 patient cohorts were compared based on the available follow-up data to identify prognostic differences. Patients with a lower concentration of SC (<30%) typically presented with low stage of disease when compared with their counterparts. Although not statistically significant (P=0.1966), our data suggest a correlation between a lower concentration of SC with longer follow-up and longer survival rates when compared with those of patients presenting with higher volumes of the SC (≥30%). Greater volume of the SC is seen in advanced stage tumors, which could serve as an indicator of prognosis.

Fascin Is Associated With Aggressive Behavior and Poor Outcome in Uterine Carcinosarcoma.

The mechanisms underlying the histogenesis and aggressiveness of uterine carcinosarcoma (UCS) are poorly understood; however, previous studies implicate epithelial-mesenchymal transition (EMT). Fascin is a proinvasive, actin-bundling protein and an important component of EMT. It is associated with poor outcomes in human carcinoma, especially in estrogen receptor (ER)-negative tumors arising in organs normally expressing ER. We sought to evaluate fascin expression in UCS and its relationship to ER status, clinicopathologic indicators of tumor aggressiveness, and survival outcomes. Forty-four surgically staged cases of UCS were immunohistochemically evaluated for fascin and estrogen receptor-α expression and correlated with clinicopathologic parameters derived from electronic medical records and pathology reports. Fascin was only expressed in malignant epithelium and mesenchyma and was uniformly absent in background benign counterparts. Increased expression was associated with extrapelvic disease (P = 0.028), higher stage (P = 0.021), larger tumor size (P = 0.032), shorter progression-free interval (P = 0.035), and reduced estrogen receptor-α expression (P = 0.04). Fascin is aberrantly expressed in both elements of UCS and is associated with aggressive behavior and worse outcome. As a component of EMT and mediator of invasion, fascin may serve as a target in future therapies.

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery.

Abstract 2359: Inhibition of the ATR kinase enhances therapeutic efficacy of cisplatin in ATM low uterine carcinosarcoma cells

Abstract Objective: Uterine carcinosarcoma (UCS) is an aggressive malignancy, making up less than 5% of uterine cancers. Pharmacologic inhibition of ATR kinase synergistically enhances the ability of cisplatin to kill carcinoma cells of many solid tumor types and is further enhanced in ATM low carcinoma cells. It is unknown whether ATR inhibition (ATRi) offers a therapeutic opportunity in UCS. The goal of this study was to evaluate ATM expression in UCS tumors and determine the response of an ATM low UCS model to ATRi + cisplatin combination. Methods: ATM expression was evaluated in full tissue sections from 74 UCS tumors by immunohistochemistry (IHC) with an ATM specific monoclonal antibody (clone Y170, Abcam), and was categorized as negative vs any positive staining in the carcinomatous (C) vs sarcomatous (S) components. In vitro models of UCS: SK-UT-1, SK-UT-1B, KLE, and RL95-2 cell lines were treated with an ATRi (AZD6738), cisplatin, and ATRi + cisplatin. ATM low models were generated in RL95-2 cells using short hairpin RNA (shRNA) lentivirus targeting ATM and a non-target control. Cells were subjected to cisplatin and ATRi dose response analyses. Results: Negative IHC expression of ATM protein was observed in 24% of the C vs 31% of the S components of the 74 UCS cases (Table 1). ATRi increased the sensitivity of uterine carcinosarcoma cell line models to cisplatin. Western blot confirmed a 57% knockdown in ATM in RL95-2 cells infected with shRNA for ATM and treatment with ATRi +cisplatin therapy showed ~20% increase in cell death in ATM low vs control cells lines, p=0.02. Conclusions: IHC analyses of UCS tumors showed an average of ~27% of tumors have loss of ATM in C and S components. Preliminary evidence shows that ATRi increases the sensitivity of UCS cell models to cisplatin therapy, which is further increased in ATM low uterine carcinoma cells. These findings suggest a novel therapeutic opportunity for ATRi + cisplatin therapy in UCS patients with low ATM expressing tumors. Immunohistochemistry-based quantification of ATM expression in uterine carcinosarcoma tumorsATMUterine CarcinosarcomaIntensityCarcinomatous ComponentSarcomatous component0-131 (41.9%)33 (44.6%)018 (24.3%)23 (31.1%)113 (17.6%)10 (13.5%)2-343 (58.1%)41 (55.4%)211 (14.9%)10 (13.5%)332 (43.2%)31 (41.9%)TOTAL7474 Citation Format: Emily R. Penick, Paulette Mhawech-Fauceglia, Nicholas Bateman, Kelly Conrads, Tracy Litzi, Chunqiao Tian, Chad A. Hamilton, Kathleen Darcy, George Maxwell, Thomas Conrads. Inhibition of the ATR kinase enhances therapeutic efficacy of cisplatin in ATM low uterine carcinosarcoma cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 2359. doi:10.1158/1538-7445.AM2017-2359

Impact of adjuvant therapy on recurrence patterns in stage I uterine carcinosarcoma

BackgroundTo examine recurrence patterns in women with stage I uterine carcinosarcoma (UCS) stratified by adjuvant therapy pattern. MethodsWe examined 443 cases of stage I UCS derived from a retrospective cohort of 1192 UCS cases from 26 institutions. Adjuvant therapy patterns after primary hysterectomy-based surgery were correlated to recurrence patterns. ResultsThe most common adjuvant therapy was chemotherapy alone (41.5%) followed by chemotherapy/radiotherapy (15.8%) and radiotherapy alone (8.4%). Distant-recurrence was the most common recurrence pattern (5-year cumulative rate, 28.1%) followed by local-recurrence (13.3%). On multivariate analysis, chemotherapy but not radiotherapy remained an independent prognostic factor for decreased risk of local-recurrence (5-year cumulative rates 8.7% versus 19.8%, adjusted-hazard ratio [HR] 0.46, 95% confidence interval [CI] 0.25–0.83, P=0.01) and distant-recurrence (21.2% versus 38.0%, adjusted-HR 0.41, 95%CI 0.27–0.62, P<0.001). The chemotherapy/radiotherapy group had a lower 5-year cumulative local-recurrence rate compared to the chemotherapy alone group but it did not reach statistical significance (5.1% versus 10.1%, adjusted-HR 0.46, 95%CI 0.13–1.58, P=0.22). Radiotherapy significantly decreased local-recurrence when tumors had high-grade carcinoma, sarcoma component dominance, and deep myometrial tumor invasion (all, P<0.05); and combining radiotherapy with chemotherapy was significantly associated with decreased local-recurrence compared to chemotherapy alone in the presence of multiple risk factors (5-year cumulative rates, 2.5% versus 21.8%, HR 0.12, 95%CI 0.02–0.90; P=0.013) but not in none/single factor (P=0.36). ConclusionAdjuvant chemotherapy appears to be effective to control both local- and distant-recurrences in stage I UCS; adding radiotherapy to chemotherapy may be effective to control local-recurrence when the tumor exhibits multiple risk factors.

Rare case of an ovarian vein tumor thrombosis identified on fluorodeoxyglucose positron emission tomography/computed tomography.

Fludeoxyglucose positron emission tomography/computed tomography is valuable in the identification of tumor thrombus and differentiating it from bland thrombus which has implications in initiating anticoagulation. We present a rare case of tumor thrombosis in ovarian vein, in a recurrent case of uterine carcinosarcoma.

“A Rare Case of Uterine Carcinosarcoma in a Patient who had Received Radiotherapy 14 Years Back for Carcinoma Cervix”

“A Rare Case of Uterine Carcinosarcoma in a Patient who had Received Radiotherapy 14 Years Back for Carcinoma Cervix”

Molecular characterization of 361 cases of uterine carcinosarcomas reveal alterations in the DNA repair and PI3K pathways as potential therapeutic targets

Molecular characterization of 361 cases of uterine carcinosarcomas reveal alterations in the DNA repair and PI3K pathways as potential therapeutic targets

Expression and localization of E-cadherin and β-catenin in uterine carcinosarcoma

This study was designed to analyze the subcellular localization of E-cadherin and β-catenin both of which play a critical role in cell-cell adhesion in uterine carcinosarcoma (UCS). We performed an immunohistochemical reaction analysis of the subcellular localization of E-cadherin and β-catenin proteins in 46 cases of UCSs consisting of 28 UCSs with heterologous sarcoma and 18 UCSs with homologous sarcoma and compared their clinicopathological features. In most UCSs, membranous expression of E-cadherin and β-catenin was completely lost in sarcomatous components, but it was preserved in carcinomatous components. Nuclear β-catenin expression was observed significantly more frequently in sarcomatous components (31/46, 67.4%) than in carcinomatous components (22/46, 47.8%; P = 0.0025). In sarcomatous components, nuclear β-catenin expression was found significantly more frequently in heterologous sarcoma (23/28, 82.1%) than in homologous sarcoma (8/18, 44.4%; P = 0.0279). The stage was the only independent prognostic significant factor. These results suggest that reduced membranous expression of E-cadherin and β-catenin may contribute to the biphasic morphology of UCS. Furthermore, although the precise mechanism is unclear, nuclear β-catenin expression in sarcomatous components may also be associated with biphasic morphology and heterologous sarcomatous differentiation.

Uterine carcinosarcoma metastatic to the lung as large-cell neuroendocrine carcinoma with synchronous sarcoid granulomatosis

A 58-year-old woman underwent a curative total abdominal hysterectomy with bilateral salpingo-oophorectomy for a uterine carcinosarcoma. Fifteen months later, PET and CT scan revealed three pulmonary nodules and multiple lymphadenopathy. An atypical lung segmentectomy with dissection of the regional lymph nodes was performed. Two of the three nodules showed morphological and immunohistochemical profiles consistent with the diagnosis of large-cell neuroendocrine carcinoma (LCNEC). The third nodule, the surrounding pulmonary parenchyma and lymph nodes showed diffuse sarcoid granulomatosis. Re-review of the histology of the uterine carcinosarcoma revealed LCNEC morphology with immunohistochemical and genetic profiles identical to the lung cancers, finally deemed as metastatic deposits. Systemic sarcoidosis was ruled out. To our knowledge this is the first case of uterine carcinosarcoma with LCNEC features metastatic to the lung and occurring in association with sarcoid reaction.