Carcinosarcoma

Carcinosarcoma (CS) of the uterus or ovary is a rare, aggressive and biphasic neoplasm composed of carcinoma and sarcoma elements. Previous genomic studies have identified the driver genes and genomic properties associated with CS. However, there is still no molecular subtyping scheme with clinical relevance for this disease. Here, we sequence 109 CS samples, focusing on 596 genes. We identify four molecular subtypes that resemble those observed in endometrial carcinoma: POLE-mutated, microsatellite instability, copy number high, and copy number low subtypes. These molecular subtypes are linked with DNA repair deficiencies, potential therapeutic strategies, and multiple clinicopathological features, including patient outcomes. Multi-regional comparative sequencing reveals genomic alteration-independent CS cell differentiation. Transcriptome and DNA methylome analyses confirm epithelial-mesenchymal transition as a mechanism of sarcoma differentiation. The current study thus provides therapeutic possibilities for CS as well as clues to understanding the molecular histogenic mechanism of its development.

BackgroundPulmonary sarcomatoid carcinoma is a diagnostically challenging group of tumors. It's a rare histologic subtype of non-small cell lung cancer.There are five subgroups of pulmonary sarcomatoid carcinoma, they are identified as pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma, and pulmonary blastoma. We explored the clinicopathologic features and prognostic factors of this tumor.MethodsWe analyzed retrospectively the clinicopathological data of 51 patients with pulmonary sarcomatoid carcinoma who were treated in the First Affiliated Hospital of Zhengzhou University, Henan Cancer Hospital and Henan People Hospital from January 2005 to December 2012. The correlation between prognosis and age, sex, smoking history, tumor size, TNM staging, and treatment modality was analyzed by the statistical software SPSS 17.0. The survival analysis was conducted using the Kaplan-Meier method. The factors influencing survival were analyzed using univariate (Log-rank) and multivariate (Cox) models.ResultsThe overall survival rates at 1, 2, 3 and 5 years were 45.5%, 35.8%, 28.2% and 20.1%, respectively. Cox univariate analyses revealed that age, tumor size, T stage, M stage, surgery or not, and postoperative chemotherapy or not, were prognostic factors. Cox multivariate analysis found that tumor size and M stage were independent prognostic factors for PSC.ConclusionsDue to its rarity and the lack of large-scale clinical trial evidence, few studies about PSC have been reported, its clinical and pathological characteristics remain unclear, and its preoperative diagnosis and investigation of novel treatment approaches are imperative. In our study, the main factors affecting the prognosis of tumor size and M staging are the crucial prognostic factors for PSC. Surgical resection and postoperative adjuvant chemotherapy might result in better prognosis.

BackgroundIn endometrial cancer (EMCA), indocyanine green (ICG) sentinel lymph node (SLN) mapping has been reported, mainly in conjunction with robotic surgery.ObjectiveWe aimed to evaluate detection rates, sensitivity, and false negative (FN) rate of laparoscopic ICG SLN mapping in EMCA, and to evaluate differences in surgical outcomes between patients subjected to SLN biopsy only versus lymphadenectomy.MethodsA retrospective analysis of EMCA patients undergoing ICG SLN mapping ± pelvic (PLND) and/or para-aortic lymphadenectomy (PALND) was performed. Detection rates were calculated for the entire cohort. Sensitivity and FN rates were calculated for patients undergoing lymphadenectomy after SLN mapping, and surgical outcome was compared among patients undergoing SLN mapping only versus lymphadenectomy.ResultsOf 75 patients, 33 underwent SLN mapping and 42 underwent SLN mapping followed by PLND/PALND. Overall and bilateral detection rates were 96 % (72/75) and 88 % (66/75), respectively, and the median number of removed SLNs, pelvic non-SLNs (NSLN) and para-aortic NSLNs was 3, 27, and 19, respectively. With a FN rate of 8.3 %, only one patient had bilateral FN SLNs and a metastatic para-aortal NSLN. Estimated blood loss (EBL) and operative (OR) time were significantly lower in patients undergoing SLN mapping only. No differences in complication rates between patients undergoing SLN mapping only and patients undergoing lymphadenectomy were recorded.ConclusionsLaparoscopic ICG SLN mapping has excellent overall and bilateral detection rates and a low FN rate. Compared with lymphadenectomy, SLN biopsy is associated with significantly lower EBL and shorter OR time.

BackgroundOvarian carcinosarcoma (OCS) is a rare, aggressive tumor composed of both carcinomatous and sarcomatous components, typically associated with poor prognosis. Due to its rarity, the molecular characteristics, immune microenvironment, and optimal treatment of OCS remain unclear. This study aimed to characterize the genomic profiles, Trop-2 expression, and immune microenvironment of the carcinomatous and sarcomatous components of OCS separately, and to explore candidate therapeutic targets for this rare and aggressive tumor.CaseThis retrospective, single-institution study analyzed nine cases of ovarian or fallopian tube carcinosarcoma treated between 2013 and 2023. Targeted next-generation sequencing of 160 cancer-related genes was performed in eight cases, and immunohistochemistry for p53, Trop-2, CD8, and PD-L1 was performed in nine cases, with the carcinomatous and sarcomatous components evaluated separately whenever they were separable. All tumors contained high-grade serous carcinoma components. Targeted sequencing revealed TP53 mutations in all samples. Most genetic alterations were shared by both components, supporting the role of epithelial-mesenchymal transition in OCS pathogenesis. Amplifications in CCND1, CCNE1, PRKCI, and GNAS (37.5%), and ERBB2 (12.5%) were detected, and whole genome duplication was observed in two cases (25%). One case (12.5%) showed high microsatellite instability and was associated with Lynch syndrome. Immunohistochemistry showed Trop-2 positivity in all carcinomatous components, with a trend toward higher expression compared with sarcomatous areas (p = 0.0625). CD8 and PD-L1 levels were low, consistent with a relatively non-inflamed, immune-cold-like microenvironment.ConclusionThese findings suggest molecular similarities between OCS and high-grade serous carcinoma and highlight the role of epithelial-mesenchymal transition. The low immune marker expression suggests limited benefit from immune checkpoint inhibitors, except in select Lynch syndrome cases. In contrast, the consistently high Trop-2 expression in the carcinomatous component may warrant further investigation of Trop-2-targeted antibody-drug conjugates as a hypothesis-generating therapeutic candidate for OCS.