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1.
Medicine (Baltimore) ; 103(19): e38147, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38728484

ABSTRACT

RATIONALE: Sarcomatoid carcinoma of the small intestine is an exceedingly rare and aggressive malignancy, often diagnosed at advanced stages with a poor prognosis. This study documents a detailed case of sarcomatoid carcinoma of the small intestine, highlighting the diagnostic challenges and treatment approaches, underscored by a comprehensive review of related literature. Given the rarity of this condition, our report aims to enrich the existing diagnostic and treatment frameworks for this malignancy, emphasizing the necessity for early detection and intervention strategies. By presenting this case in conjunction with a literature review, we seek to shed light on the elusive nature of sarcomatoid carcinoma in the small intestine and propose avenues for improving patient outcomes. PATIENT CONCERNS: Case presentation A 61-year-old male patient initially presented with recurrent abdominal pain and gastrointestinal symptoms. Initial abdominal computed tomography (CT) scans and gastrointestinal endoscopy revealed only inflammatory and hyperplastic changes in the duodenum and jejunum, with a diagnosis of intestinal obstruction. Two years later, due to gastrointestinal perforation, the patient was hospitalized again. DIAGNOSES: CT scans and other examinations revealed small intestinal lesions. Four small intestinal lesions were surgically removed, and pathology and immunohistochemistry confirmed sarcomatoid carcinoma of the small intestine. A short time later, enhanced CT scans revealed metastatic lesions in the hepatic portal and adrenal glands. INTERVENTIONS: After surgery, the gastrointestinal function gradually recovered, and the patient was discharged from the hospital on a semiliquid diet. No further treatment such as radiotherapy or chemotherapy was administered postoperatively. OUTCOMES: Five months after the surgery, the patient died due to brain metastasis. LESSONS: The study outcomes reveal the aggressive nature of sarcomatoid carcinoma of the small intestine, characterized by rapid progression and poor prognosis despite surgical interventions. The patient condition rapidly deteriorated, leading to metastasis and death within 5 months postsurgery. These findings underscore the critical need for early detection and possibly innovative treatment approaches to improve survival rates. This case also highlights the potential for gastrointestinal sarcomatoid carcinoma to metastasize to distant organs, including the brain, suggesting a propensity for hematogenous spread.


Subject(s)
Intestinal Perforation , Humans , Male , Middle Aged , Intestinal Perforation/etiology , Intestinal Perforation/surgery , Intestine, Small/pathology , Intestinal Neoplasms/pathology , Intestinal Neoplasms/complications , Carcinosarcoma/pathology , Carcinosarcoma/diagnosis , Carcinosarcoma/complications , Tomography, X-Ray Computed
2.
Front Immunol ; 15: 1374270, 2024.
Article in English | MEDLINE | ID: mdl-38650938

ABSTRACT

Pulmonary sarcomatoid carcinoma (PSC) represents a rare and highly aggressive variant of lung cancer, characterized by its recalcitrance to conventional therapeutic modalities and the attendant dismal prognosis it confers. Recent breakthroughs in immunotherapy have presented novel prospects for PSC patients; nevertheless, the utility of neoadjuvant/conversional immunotherapy in the context of PSC remains ambiguous. In this report, we present a middle-aged male presenting with Stage III PSC, notable for its high expression of the programmed death-ligand 1 (PD-L1), initially deemed as non-resectable for sizeable tumor mass and multiple lymph nodes metastases. The patient underwent a transformation to a resectable state after a regimen of three cycles of platinum-based chemotherapy plus immunotherapy. Following definitive surgical resection, the individual realized a pathological complete response (pCR), culminating in a significant prolongation of event-free survival (EFS). This case underscores the viability of employing immunochemotherapy as a neoadjuvant/conversional strategy for chosen cases of PSC.


Subject(s)
Lung Neoplasms , Humans , Male , Lung Neoplasms/therapy , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Middle Aged , Neoplasm Staging , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Neoadjuvant Therapy/methods , Immunotherapy/methods , Treatment Outcome , B7-H1 Antigen/antagonists & inhibitors , Carcinosarcoma/therapy , Carcinosarcoma/pathology , Carcinosarcoma/drug therapy
3.
World J Surg Oncol ; 22(1): 104, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38637834

ABSTRACT

OBJECTIVES: To investigate the clinicopathological characteristics and prognosis of patients with primary sarcoma of the uterine cervix. METHODS: We identified all patients with primary cervical sarcomas treated at our institution from 2002 to 2020 and analyzed the clinicopathological characteristics and prognosis. RESULTS: 34 patients were identified, 7 (20.6%) patients had leiomyosarcoma, 6 (17.6%) had carcinosarcoma, 5 (14.7%) had Ewing sarcoma, 4 (11.8%) had rhabdomyosarcoma, 4 (11.8%) had undifferentiated sarcoma, 2 (5.9%) had adenosarcoma, 2 (5.9%) had endometrial stromal sarcoma, 1 (2.9%) had dermatofibrosarcoma protuberans, 1 (2.9%) had alveolar soft tissue sarcoma and 2 (5.9%) had sarcoma not otherwise specified. The median age of the whole patients was 43.5 years (range, 13-63). The median age of patients with Ewing sarcoma or rhabdomyosarcoma was 22 years (range, 13-39) and 17 years (range, 13-36 years), respectively. The distribution by stage was: stage I in 21 (61.8%) patients, stage II in 4 (11.8%), stage III in 6 (17.6%) and stage IV in 3 (8.8%). Overall, 30 patients (88.2%) received surgical treatment. The median follow-up was 33.3 months (range 3.6-187.3 months). 11 patients died within 2 years after diagnosis, most of them were patients with carcinosarcoma or undifferentiated sarcoma (45.5%, 5/11). In the entire cohort, 2- and 5-year OS were 67.2% and 56.9%, respectively. 5-year OS was 25.0% for undifferentiated sarcoma, 50.0% for rhabdomyosarcoma, 50.0% for carcinosarcoma, 53.3% for Ewing sarcoma, 57.1% for leiomyosarcoma. CONCLUSION: Cervical sarcomas are rare neoplasms with multiple histological subtypes and follow an aggressive course. Prognosis may be associated with tumor histology and stage.


Subject(s)
Carcinosarcoma , Leiomyosarcoma , Rhabdomyosarcoma , Sarcoma, Ewing , Sarcoma , Uterine Cervical Neoplasms , Uterine Neoplasms , Female , Humans , Adolescent , Young Adult , Adult , Middle Aged , Leiomyosarcoma/pathology , Sarcoma, Ewing/surgery , Uterine Cervical Neoplasms/surgery , Uterine Neoplasms/diagnosis , Sarcoma/surgery , Sarcoma/diagnosis , Carcinosarcoma/pathology , Rhabdomyosarcoma/surgery , Prognosis
4.
Medicina (B Aires) ; 84(2): 337-341, 2024.
Article in Spanish | MEDLINE | ID: mdl-38683520

ABSTRACT

Primary hepatic sarcomatoid carcinoma is a very aggressive tumor, representing 0.4-0.7% of all primary hepatic neoplasms. The disease is associated with liver disease due to hepatotropic viruses and is more prevalent in Asians. Histology shows sarcomatous and carcinoma components. It does not have pathognomonic clinical or imaging characteristics and its diagnosis is based on the pathological and immunohistochemistry findings. Surgery could prolong survival in localized stages. We report the case of a 72-year-old Korean patient with a history of chronic liver disease due to B virus, who was diagnosed with primary hepatic sarcomatoid carcinoma with bone and lymph node metastases.


El carcinoma sarcomatoide primario hepático es un tumor agresivo que representa el 0.4-0.7% de todas las neoplasias primarias hepáticas. Se asocia a hepatopatía por virus hepatotropos, es más prevalente en la población asiática y en su histología se evidencian componentes de carcinoma y sarcoma. No posee características clínicas ni imagenológicas patognomónicas y su diagnóstico se realiza en base a los hallazgos de la anatomía patológica e inmunohistoquímica. La cirugía en estadio localizado representa la única modalidad terapéutica con impacto en la sobrevida. Reportamos el caso de una paciente de 72 años, coreana, con antecedentes de hepatopatía crónica por virus B, a quien se le diagnosticó un carcinoma sarcomatoide hepático primario con metástasis ósea y ganglionares.


Subject(s)
Liver Neoplasms , Humans , Aged , Liver Neoplasms/pathology , Liver Neoplasms/diagnostic imaging , Male , Lymphatic Metastasis/pathology , Carcinosarcoma/pathology , Carcinosarcoma/diagnostic imaging
5.
Clin Oncol (R Coll Radiol) ; 36(6): e137-e145, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38565457

ABSTRACT

AIMS: Sinonasal teratocarcinosarcomas (SNTCS) are rare sinonasal malignancies, the incidence of which is less than 1% of all tumors. There is limited data available on SNTCS's, often as case reports and small case series. The management of SNTCS is complicated because of its location, locally aggressive biology, difficulty in achieving complete resection, and limited data on chemotherapy in these malignancies. This audit was performed to understand the role of neoadjuvant chemotherapy (NACT) in SNTCS's, its ability to downstage the disease, achieve complete resection, and impact on long-term survival outcomes. METHODS: This was a retrospective analysis of a prospectively maintained database approved by the Institutional Ethics Committee (IEC). The baseline characteristics, the extent of tumor, Kadish stage, NACT regimen, and adverse events were extracted from the Electronic Medical Records and the patient's case file. Patients with baseline extensive/inoperable disease were referred for NACT from the multidisciplinary joint clinic followed by response assessment (RECIST v1.1). Patients underwent skull-base surgery if respectable post-completion of NACT, however, if deemed unresectable were treated with non-surgical modalities or palliative therapies. RESULTS: The data of 27 patients were evaluated from the year 2015-2022. The median age was 42 years (IQR:30-56) and 85.2% (n = 23) were males. The ECOG-PS was 0-1 in 88.8% (n = 24) patients. All 27 patients received NACT in view of extensive disease at presentation. 74.1% (n = 20) patients received Cisplatin-Etoposide and 25.9% (n = 7) received other chemotherapy regimens. The median number of chemotherapy cycles was 2(IQR:2-3). 96.3% patients (n = 26) completed the planned NACT cycles. 70.4% (n = 19) patients achieved a partial response in post-NACT imaging. 77.8% (n = 18) underwent surgery, 18.5% (n = 5) received CTRT, and 7.4% (n = 2) received definitive-RT alone. The median PFS and OS of the cohort was 19months (95%CI:12.0-25.6) and 23months (95%CI:5.94-40.06) respectively. CONCLUSION: NACT is safe, feasible, and effective with significant response rates, leading to effective downstaging, resectability and improved survival in patients with locally advanced SNTCS's.


Subject(s)
Carcinosarcoma , Neoadjuvant Therapy , Nose Neoplasms , Tertiary Care Centers , Humans , Male , Female , Retrospective Studies , India , Adult , Middle Aged , Neoadjuvant Therapy/methods , Carcinosarcoma/drug therapy , Carcinosarcoma/therapy , Carcinosarcoma/pathology , Paranasal Sinus Neoplasms/drug therapy , Paranasal Sinus Neoplasms/therapy , Paranasal Sinus Neoplasms/pathology , Teratoma/drug therapy , Teratoma/therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Aged , Chemotherapy, Adjuvant/methods
6.
Zhongguo Fei Ai Za Zhi ; 27(2): 157-160, 2024 Feb 20.
Article in Chinese | MEDLINE | ID: mdl-38453449

ABSTRACT

Pulmonary sarcomatoid carcinoma (PSC) is a rare and highly malignant tumor, which includes the following five pathologic types: pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, carcinosarcoma and pulmonary blastoma. The onset of PSC is occult with non-specific clinical symptoms and signs. The clinical manifestations include irritating cough, bloody sputum, dyspnea, chest pain and so on, which are closely related to the growth and invasion site of the tumor. PSC tends to metastasize early, so most patients are already in local advanced stage or advanced stage with a median survival of 9 months at the time of hospital visit. A patient with primary PSC which led to 90% stenosis in central airway was treated by combined method of vascular and tracheoscopic intervention in our respiratory center. This treatment prolonged the patient's survival time and got a satisfactory effect at 19-month follow-up after surgery. Herein we report the case for clinical reference.
.


Subject(s)
Carcinoma , Carcinosarcoma , Lung Neoplasms , Humans , Lung Neoplasms/diagnosis , Prognosis , Carcinoma/pathology , Carcinosarcoma/surgery , Carcinosarcoma/pathology , Lung/pathology
10.
J Med Case Rep ; 18(1): 24, 2024 Jan 20.
Article in English | MEDLINE | ID: mdl-38243328

ABSTRACT

BACKGROUND: Carcinosarcoma of the parotid gland is an extremely rare malignancy comprising of 0.04-0.16% of all salivary gland tumors. This is the first case of an adenoid cystic carcinoma with chondrosarcoma to the best of our knowledge. They consist of distinct carcinomatous and sarcomatous components and may arise de novo or from a preexisting pleomorphic adenoma. CASE PRESENTATION: Herein we present a case of an 80-year-old white female who presented with progressively increasing left facial swelling over 6 weeks. Magnetic Resonance Imagining revealed a mass (3.4 cm) in the parotid gland with a predominant cystic/necrotic component. The cytology was atypical (Milan3) and a total parotidectomy and selective lymph node dissection was done. The resection showed extensive necrosis with high grade sarcomatous (chondrosarcoma) areas. The epithelial component was adenoid cystic carcinoma with perineural invasion. The patient is currently undergoing radiotherapy of the tumor bed and skull base due to propensity of perineural invasion of the adenoid cystic component. The most common carcinomas in carcinosarcomas of salivary glands are adenocarcinoma and squamous cell carcinoma. CONCLUSION: Carcinosarcoma is a high-grade aggressive lesion with a poor prognosis and should be treated aggressively. More studies are needed to understand the origin of these tumors.


Subject(s)
Bone Neoplasms , Carcinoma, Adenoid Cystic , Carcinosarcoma , Chondrosarcoma , Parotid Neoplasms , Humans , Female , Aged, 80 and over , Parotid Gland/pathology , Parotid Neoplasms/diagnostic imaging , Parotid Neoplasms/surgery , Carcinoma, Adenoid Cystic/diagnostic imaging , Carcinoma, Adenoid Cystic/surgery , Carcinoma, Adenoid Cystic/pathology , Carcinosarcoma/diagnosis , Carcinosarcoma/surgery , Carcinosarcoma/pathology , Chondrosarcoma/pathology , Bone Neoplasms/pathology
11.
J Gynecol Oncol ; 35(2): e11, 2024 Mar.
Article in English | MEDLINE | ID: mdl-37914528

ABSTRACT

OBJECTIVE: This study aimed to evaluate mesothelin (MSLN) expression and determine its clinical significance and correlation with human epidermal growth factor receptor 2 (HER2) expression in gynecological carcinosarcoma. METHODS: We retrospectively evaluated patients with uterine carcinosarcoma (UCS) and ovarian carcinosarcoma (OCS) who underwent surgery between 1997 and 2019. Immunohistochemical staining of formalin-fixed, paraffin-embedded specimens for MSLN (clone SP74) and HER2 (clone 4A5) was also performed. MSLN was scored using the H-score and 4-tired scoring system (0-3+). MSLN positivity was defined as any positive cell at any intensity, while high MSLN expression was defined as an intensity of ≥2+ in ≥30% of tumor cells. HER2 expression was scored according to modified 2018 American Society of Clinical Oncology/College of American Pathologists criteria. RESULTS: A total of 128 patients were recruited, including 119 with UCS and 9 with OCS. All cases in UCS exhibited MSLN positivity, and 33.9% showed high-MSLN expression. Clinicopathological characteristics were not significantly associated with high or low-MSLN expression. However, the high-MSLN group showed more prolonged overall survival (OS) than the low-MSLN group (not assessed vs. 36.8 months; hazard ratio=0.48, 95% confidence interval=0.26-0.89, p=0.016). HER2-high patients had higher MSLN expression than HER2-negative patients. In high-MSLN and low-MSLN expression groups, HER2 status did not affect OS. OCS showed 100% MSLN positivity, with 66.6% high-MSLN. CONCLUSION: MSLN expression is widely observed in gynecological carcinosarcomas. Moreover, high-MSLN expression is a favorable prognostic factor for UCS. MSLN could be a promising therapeutic target for UCS, even in the era of anti-HER2 therapy.


Subject(s)
Carcinosarcoma , Ovarian Neoplasms , Uterine Neoplasms , Humans , Female , Mesothelin , Retrospective Studies , Uterine Neoplasms/pathology , Ovarian Neoplasms/pathology , Carcinosarcoma/pathology
12.
Gynecol Oncol ; 180: 1-5, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38029652

ABSTRACT

OBJECTIVE: Investigate the prevalence of ERBB2/HER2 gene amplification among patients with gynecologic malignancies. METHODS: The American Association of Cancer Research (AACR) Genomics Evidence of Neoplasia Information Exchange (GENIE) (version 13.1) database was accessed and patients with endometrial, ovarian, and cervical cancer were identified. Patients with available data on the presence of copy-number gene alterations were selected for further analysis. Incidence of ERBB2 amplification following stratification by tumor site and histology was evaluated. Data from the OncoKB database, as provided by cBioPortal, was utilized to determine presence of pathogenic genomic alterations. RESULTS: A total of 6961 patients who met the inclusion criteria were identified: 49.1% with ovarian cancer, 45.2% with endometrial cancer and 5.7% with cervical cancer respectively. Overall incidence of ERBB2 amplification was 3.8%. Highest incidence of ERBB2 amplification was observed among patients with mucinous ovarian (14.4%), uterine serous (13.2%), uterine clear cell (9.4%), and uterine carcinosarcoma (7.9%). ERBB2 amplification was rare among patients with TP53 wild-type endometrioid endometrial cancer (0.4%). High incidence of mutations in genes of the PI3K pathway was observed among patients with ERBB2 amplified tumors. CONCLUSION: ERBB2 amplification is frequently encountered among patients with uterine serous carcinoma, and mucinous ovarian carcinoma. In addition, a high incidence was also observed among those with uterine clear cell carcinoma, and uterine carcinosarcoma. For patients with endometrioid endometrial carcinoma, incidence of ERBB2 amplification is low, especially in the absence of TP53 mutations.


Subject(s)
Carcinoma, Endometrioid , Carcinosarcoma , Endometrial Neoplasms , Genital Neoplasms, Female , Ovarian Neoplasms , Uterine Cervical Neoplasms , Uterine Neoplasms , Humans , Female , Genital Neoplasms, Female/genetics , Gene Amplification , Uterine Cervical Neoplasms/genetics , Phosphatidylinositol 3-Kinases/metabolism , Mutation , Ovarian Neoplasms/pathology , Uterine Neoplasms/genetics , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Carcinoma, Endometrioid/pathology , Carcinosarcoma/pathology , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism
13.
Jpn J Clin Oncol ; 54(2): 111-120, 2024 Feb 07.
Article in English | MEDLINE | ID: mdl-37861097

ABSTRACT

Esophageal cancer is common worldwide, including in Japan, and its major histological subtype is squamous cell carcinoma. However, there are some rare esophageal cancers, including neuroendocrine neoplasm, gastrointestinal stromal tumor, carcinosarcoma and malignant melanoma. The biological and clinical features of these cancers differ from those of esophageal squamous cell carcinoma. Therefore, different treatment strategies are needed for these cancers but are based on limited evidence. Neuroendocrine neoplasm is mainly divided into neuroendocrine tumor and neuroendocrine carcinoma by differentiation and the Ki-67 proliferation index or mitotic index. Epidemiologically, the majority of esophageal neuroendocrine neoplasms are neuroendocrine carcinoma. The treatment of neuroendocrine carcinoma is similar to that of small cell lung cancer, which has similar morphological and biological features. Gastrointestinal stromal tumor is known to be associated with alterations in the c-KIT and platelet-derived growth factor receptor genes and, if resectable, is treated in accordance with the modified Fletcher classification. Carcinosarcoma is generally resistant to both chemotherapy and radiotherapy and requires multimodal treatments such as surgery plus chemotherapy to achieve cure. Primary malignant melanoma is resistant to cytotoxic chemotherapy, but immune checkpoint inhibitors have recently demonstrated efficacy for malignant melanoma of the esophagus. This review focuses on the current status and future perspectives for rare cancer of the esophagus.


Subject(s)
Carcinoma, Neuroendocrine , Carcinosarcoma , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Gastrointestinal Stromal Tumors , Melanoma , Humans , Esophageal Neoplasms/pathology , Carcinosarcoma/pathology
14.
Br J Cancer ; 130(2): 327-335, 2024 02.
Article in English | MEDLINE | ID: mdl-38097740

ABSTRACT

BACKGROUND: Ovarian carcinosarcoma (OCS) is an exceptionally aggressive and understudied ovarian cancer type harbouring distinct carcinomatous and sarcomatous compartments. Here, we seek to identify shared and compartment-specific events that may represent potential therapeutic targets and candidate drivers of sarcomatous compartment formation through epithelial-to-mesenchymal transition (EMT). METHODS: We performed multiomic profiling (exome sequencing, RNA-sequencing, microRNA profiling) of paired carcinomatous and sarcomatous components in 12 OCS cases. RESULTS: While paired sarcomatous and carcinomatous compartments demonstrate substantial genomic similarities, multiple loci are recurrently copy number-altered between components; regions containing GNAS and SRC are recurrently gained within the sarcomatous compartment. CCNE1 gain is a common event in OCS, occurring more frequently than in high grade serous ovarian carcinoma (HGSOC). Transcriptomic analysis suggests increased MAPK activity and subtype switching toward poor prognosis HGSOC-derived transcriptomic subtypes within the sarcomatous component. The two compartments show global differences in microRNA profiles, with differentially expressed microRNAs targeting EMT-related genes (SIRT1, ZEB2) and regulators of pro-tumourigenic pathways (TGFß, NOTCH); chrX is a highly enriched target of these microRNAs and is also frequently deleted across samples. The sarcomatous component harbours significantly fewer CD8-positive cells, suggesting poorer immune engagement. CONCLUSION: CCNE1 gain and chrX loss are frequent in OCS. SRC gain, increased GNAS expression and microRNA dysregulation represent potential mechanisms driving sarcomatous compartment formation.


Subject(s)
Carcinosarcoma , MicroRNAs , Ovarian Neoplasms , Sarcoma , Female , Humans , Multiomics , Carcinosarcoma/genetics , Carcinosarcoma/metabolism , Carcinosarcoma/pathology , Ovarian Neoplasms/pathology , MicroRNAs/genetics , Epithelial-Mesenchymal Transition/genetics , Chromogranins/genetics , GTP-Binding Protein alpha Subunits, Gs/genetics
16.
Med Sci Monit ; 29: e941562, 2023 Dec 07.
Article in English | MEDLINE | ID: mdl-38058118

ABSTRACT

BACKGROUND Uterine sarcomas and carcinomas are rare tumors and treatment outcomes are far from expected. We investigated the prognostic significance of selected serum biomarkers and the impact of some clinical and tissue factors on overall survival (OS) at 10-year follow-up. MATERIAL AND METHODS The material for analysis was a group of 34 patients with uterine sarcomas and 18 with carcinomas. Immunohistochemistry was performed to determine Ki 67, p53 and ER and PR. Concentrations: CA 125, IL8, VEGF, SFTL1, VEGF R2, sTNFRI and MMP-9 were determined in the serum of patients before treatment and in the control group. RESULTS The most frequently elevated levels observed of sTNF RI in 94% and VEGF in 62%. On the ROC curve analysis, sTNF RI and VEGF concentrations showed the highest sensitivity. Patients with striated cell sarcoma, smooth cell sarcoma and high-grade rhabdomyosarcoma had the worst prognosis. Patient age, FIGO stage and expression of Ki67, p53, ER and PR, CA 125 (p<0.038) and IL-8 (p<0.024) were statistical prognostic factors for OS. However, in multivariate analysis, serum levels of: CA 125 concentration (p<0.045), age (p<0.010) and p53 expression (p<0.014) were found to be significant independent prognostic factors. CONCLUSIONS A 10-year follow-up of patients with uterine sarcoma indicates that age above 60 years at diagnosis and high p53 expression and elevated CA125 levels before treatment can be independent prognostic factors. The high diagnostic sensitivity of sTNF RI and VEGF suggests the possibility of using these biomarkers in the early diagnosis of uterine sarcomas.


Subject(s)
Carcinoma , Carcinosarcoma , Sarcoma , Uterine Neoplasms , Female , Humans , Middle Aged , Follow-Up Studies , Prognosis , Vascular Endothelial Growth Factor A , Tumor Suppressor Protein p53 , Sarcoma/diagnosis , Sarcoma/pathology , Carcinosarcoma/diagnosis , Carcinosarcoma/pathology , Uterine Neoplasms/diagnosis , Uterine Neoplasms/pathology , Biomarkers , Retrospective Studies
17.
BMJ Case Rep ; 16(12)2023 Dec 28.
Article in English | MEDLINE | ID: mdl-38154864

ABSTRACT

A carcinosarcoma is a rare form of cancer characterised by the presence of both carcinomatous and sarcomatous components. Here, we present our experience with an extremely rare case of an uterine carcinosarcoma with immature teratoid-like differentiation. The patient was a woman in her 60s. She was referred for the evaluation of a uterine tumour. She underwent total abdominal hysterectomy with bilateral adnexectomy and received postoperative treatment with paclitaxel and carboplatin. On microscopic examination, the tumour had a heterogeneous appearance with a combination of carcinomatous and sarcomatous elements, and teratoid features. The tumour included immature squamous epithelial cells and immature epithelial glands, and focal atypical fused glands, which are consistent with endometrioid carcinoma, were identified in the endometrium. Pathological differentiation from extrarenal Wilms' tumour and teratocarcinosarcoma was challenging. The final pathological diagnosis was uterine carcinosarcoma with immature teratoid-like differentiation. At 14 months after the surgery, the patient has not experienced recurrence.


Subject(s)
Carcinosarcoma , Uterine Neoplasms , Female , Humans , Uterine Neoplasms/surgery , Uterine Neoplasms/pathology , Hysterectomy , Carboplatin , Paclitaxel , Carcinosarcoma/diagnosis , Carcinosarcoma/surgery , Carcinosarcoma/pathology
18.
Adv Sci (Weinh) ; 10(32): e2303134, 2023 11.
Article in English | MEDLINE | ID: mdl-37749866

ABSTRACT

Phosphatase and TENsin homolog (Pten) and p53 are two of the most frequently mutated tumor suppressor genes in endometrial cancer. However, the functional consequences and histopathological manifestation of concomitant p53 and Pten loss of function alterations in the development of endometrial cancer is still controversial. Here, it is demonstrated that simultaneous Pten and p53 deletion is sufficient to cause epithelial to mesenchymal transition phenotype in endometrial organoids. By a novel intravaginal delivery method using HIV1 trans-activator of transcription cell penetrating peptide fused with a Cre recombinase protein (TAT-Cre), local ablation of both p53 and Pten is achieved specifically in the uterus. These mice developed high-grade endometrial carcinomas and a high percentage of uterine carcinosarcomas resembling those found in humans. To further demonstrate that carcinosarcomas arise from epithelium, double Pten/p53 deficient epithelial cells are mixed with wild type stromal and myometrial cells and subcutaneously transplanted to Scid mice. All xenotransplants resulted in the development of uterine carcinosarcomas displaying high nuclear pleomorphism and metastatic potential. Accordingly, in vivo CRISPR/Cas9 disruption of Pten and p53 also triggered the development of metastatic carcinosarcomas. The results unfadingly demonstrate that simultaneous deletion of p53 and Pten in endometrial epithelial cells is enough to trigger epithelial to mesenchymal transition that is consistently translated to the formation of uterine carcinosarcomas in vivo.


Subject(s)
Carcinosarcoma , Endometrial Neoplasms , Uterine Neoplasms , Humans , Female , Mice , Animals , Tumor Suppressor Protein p53/genetics , Tumor Suppressor Protein p53/metabolism , Epithelial-Mesenchymal Transition , CRISPR-Cas Systems/genetics , Endometrial Neoplasms/genetics , Endometrial Neoplasms/metabolism , Endometrial Neoplasms/pathology , Uterine Neoplasms/genetics , Uterine Neoplasms/pathology , Carcinosarcoma/genetics , Carcinosarcoma/pathology
19.
Indian J Pathol Microbiol ; 66(3): 449-455, 2023.
Article in English | MEDLINE | ID: mdl-37530323

ABSTRACT

Background: Uterine carcinosarcomas (UCS) constitute 3-4% of all uterine malignancies and 16% of deaths caused due to uterine neoplasms. Aim: In this study, we aimed to perform DNA-based mutation analysis in 12 genes (KRAS, NRAS, EGFR, C-KIT, BRAF, PDGFRA, ALK, ERBB2, ERBB3, ESR1, RAF1, PIK3CA) to determine the molecular subtypes of UCS using next-generation sequencing (NGS) in patients with aggressive UCS and poor prognosis. We aimed to compare the results of our analysis with clinicopathological data to contribute to the development of targeted therapy approaches related to the molecular changes of UCS. Materials and Methods: In this study, we included 12 cases diagnosed with uterine carcinosarcomas and examined the changes in oncogenes that play a role in UCS pathogenesis. For the analysis of mutation, the clinicopathological data were compared with the variations in the DNA-based gene panel consisting of 12 genes and 1237 variants in the UCS using the NGS method. Results: EGFR mutation was found in 91.7% of the cases, mutation in 41.7%, PDGFRA mutation in 25%, KRAS and PIK3CA mutation in 16.7%, and C-KIT mutation in 8.3% of the cases. Although no statistical significance was found between the detected mutation and clinicopathological data, it was concluded that PDGFRA mutation might be associated with advanced-stage disease development. Conclusion: This study's findings regarding different molecular types of UCS and information on oncogenesis of UCS can provide inferences for targeted therapies in the future by identifying targetable mutations representing early oncogenic events and thereby contribute toward further studies on this subject.


Subject(s)
Carcinosarcoma , Uterine Neoplasms , Female , Humans , Proto-Oncogene Proteins p21(ras)/genetics , Uterine Neoplasms/genetics , Uterine Neoplasms/pathology , Mutation , Receptor Protein-Tyrosine Kinases/genetics , Carcinosarcoma/genetics , Carcinosarcoma/pathology , High-Throughput Nucleotide Sequencing/methods , DNA
20.
Gynecol Oncol ; 176: 115-121, 2023 09.
Article in English | MEDLINE | ID: mdl-37506533

ABSTRACT

OBJECTIVE: Folate receptor alpha (FRα), which is expressed in various cancers, is a potential therapeutic target. However, its expression and clinical significance in uterine (UCS) and ovarian carcinosarcoma (OCS) remain to be elucidated. METHODS: This retrospective study included patients with gynecologic carcinosarcoma who underwent primary surgery between 1997 and 2019 at our institution. Immunohistochemical staining of surgical FFPE specimens was performed for FRα and HER2. FRα was evaluated using the H-score and the 4-tired scoring system (0 to 3+). Subsequently, FRα expression (≥5% of tumor cells with ≥1+ intensity) and FRα-high (score 2+ and 3+) were evaluated. HER2 was scored according to the modified ASCO/CAP criteria. The association between FRα-high and clinicopathological features, HER2 expression, and survival was assessed in UCS. RESULTS: A total of 120 patients with UCS and nine patients with OCS were included. In UCS, FRα expression was observed in all patients, whereas FRα-high status was present in 20% of patients. Among HER2-negative UCS, 34% exhibited FRα-high. No significant association was observed between clinicopathological characteristics and FRα status. During the follow-up period (median 34.5 mo), FRα-high was not strongly associated with progression, free survival, and overall survival. All the OCS tumor specimens showed FRα-high expression. CONCLUSIONS: FRα expression was observed in all the UCS and OCS specimens, including HER2-negative UCS patients. This widespread FRα expression suggests that FRα-targeted therapies may hold promise for the treatment for gynecologic carcinosarcoma. However, in uterine carcinosarcoma, no significant relationship was observed between FRα expression and clinicopathological features or prognosis.


Subject(s)
Carcinosarcoma , Ovarian Neoplasms , Uterine Neoplasms , Female , Humans , Carcinosarcoma/pathology , Folate Receptor 1 , Ovarian Neoplasms/pathology , Prognosis , Retrospective Studies , Uterine Neoplasms/pathology
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