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Gynecologic Oncology Oct 2023Investigate the incidence of homologous recombination DNA damage response (HR-DDR) genomic alterations among patients with uterine sarcoma.
OBJECTIVE
Investigate the incidence of homologous recombination DNA damage response (HR-DDR) genomic alterations among patients with uterine sarcoma.
METHODS
The American Association for Cancer Research GENIE v13.0 database was accessed and patients with uterine leiomyosarcoma, adenosarcoma, undifferentiated uterine sarcoma, high-grade endometrial stromal sarcoma, low-grade endometrial stromal sarcoma, and endometrial stromal sarcoma not otherwise specified were identified. We determined the incidence of pathogenic alterations in the following genes involved in HR-DDR: ATM, ARID1A, ATRX, BAP1, BARD1, BLM, BRCA2, BRCA1, BRIP1, CHEK2, CHEK1, FANCA, FANCC, FANCD2, FANCE, FANCF, FANCG, FANCL, MRE11, NBN, PALB2, RAD50, RAD51, RAD51B, RAD51C, RAD51D, WRN. Data from the OncoKB database, as provided by cBioPortal, was utilized to determine the presence of pathogenic genomic alterations.
RESULTS
A total of 509 patients contributing with 525 samples were identified. Median patient age at sample collection was 56 years while the majority were White (80.7%). The most common histologic subtype was leiomyosarcoma (63.8%) followed by adenosarcoma (12.3%). The overall incidence of HR-DDR genomic alterations was 28.2%. The most commonly altered genes were ATRX (18.2%), BRCA2 (4%), and RAD51B (2.6%). The highest incidence of HR-DDR genomic alterations was observed among patients with leiomyosarcoma (35.4%), adenosarcoma (27%) and undifferentiated uterine sarcoma (30%), while those with low-grade endometrial stromal sarcoma had the lowest (2.9%) incidence.
CONCLUSIONS
Approximately 1 in 3 patients with uterine sarcoma harbor a pathogenic alteration in HR-DDR genes. Incidence is high among patients with uterine leiomyosarcoma and adenosarcoma.
PubMed: 37611378
DOI: 10.1016/j.ygyno.2023.07.020 -
Frontiers in Oncology 2024The purpose of the study was to analyse the role of prognostic factors on the risk of recurrence and overall survival of patients with uterine adenosarcoma.
OBJECTIVE
The purpose of the study was to analyse the role of prognostic factors on the risk of recurrence and overall survival of patients with uterine adenosarcoma.
METHODS
A retrospective international multicentre study involving 46 centres collected 32 cases of uterine adenosarcoma, and these cases were included in the present subanalysis. Clinical and demographic features and tumour characteristics were gathered, as well as information on treatment and relapse. Disease-free and overall survival were analysed.
RESULTS
The 5-year disease-free survival (DFS) was 85.3% and the 5-year overall survival (OS) rate was 89.5%. The risk factors significantly associated with overall survival were age (HR 1.09, 95% CI 1.03-1.15; = 0.004) and FIGO stage II-III (HR 17.75, 95% CI 2.87-109.93; = 0.002). Patients who experienced early relapse (within 12 months) had a tumour size >30 mm and advanced stage. The majority of recurred cases were treated with radiotherapy or surgery and obtained a good response rate.
CONCLUSION
The most significant prognostic factors in uterine adenosarcoma were age and FIGO stage and, indirectly, tumour size at diagnosis. The use of secondary surgery and/or radiotherapy could help in prolonging the disease-free status of the patients.
PubMed: 38835369
DOI: 10.3389/fonc.2024.1393707 -
Radiologic Clinics of North America Jul 2023Uterine sarcomas are a group of rare uterine tumors comprised of multiple subtypes with different histologic characteristics, prognoses, and imaging appearances.... (Review)
Review
Uterine sarcomas are a group of rare uterine tumors comprised of multiple subtypes with different histologic characteristics, prognoses, and imaging appearances. Identification of uterine sarcomas and their differentiation from benign uterine disease on imaging is of critical importance for treatment planning to guide appropriate management and optimize patient outcomes. Herein, we review the spectrum of uterine sarcomas with a focus on the classification of primary sarcoma subtypes and presenting the typical MR imaging appearances.
Topics: Female; Humans; Leiomyosarcoma; Sarcoma; Uterine Neoplasms; Prognosis; Magnetic Resonance Imaging
PubMed: 37169428
DOI: 10.1016/j.rcl.2023.02.008 -
Ginekologia Polska Jul 2023Cervical adenofibroma is a rare form of mixed mesodermal tumor that can present as cervical polyps with a tendency for local recurrence and progression. Few cases...
OBJECTIVES
Cervical adenofibroma is a rare form of mixed mesodermal tumor that can present as cervical polyps with a tendency for local recurrence and progression. Few cases progressing to adenosarcoma have previously been reported. We report a case of cervical adenofibroma progressing to adenosarcoma, and we seek to remind clinicians of the method and importance of the differential diagnosis of this disease. A fertile woman was admitted in our department for the eighth recurrence of a cervical polypoidal mass which for the past 10 years. Recurrence of cervical adenofibroma was confirmed by ultrasound and MRI. A wide local excision under hysteroscopy was performed due to her strong desire to preserve the uterus. Surgical pathology and immunohistochemical interpretation revealed cervical adenosarcoma. A hysterectomy with conservation of the ovaries was recommended, with regular follow-ups for evidence of disease recurrence.
CONCLUSIONS
Differential diagnoses of cervical adenofibroma are hard to prove. Adenosarcoma should be ruled out, especially in women presenting with recurrent cervical polypoidal masses. A combined histological/immunohistochemical investigation is mandatory.
PubMed: 37435916
DOI: 10.5603/GP.a2023.0069 -
Bulletin Du Cancer 2023Uterine adenosarcoma is a very rare malignancy defined as a biphasic tumor composed of both benign epithelial component and a malignant sarcoma component. The stage of...
Uterine adenosarcoma is a very rare malignancy defined as a biphasic tumor composed of both benign epithelial component and a malignant sarcoma component. The stage of the disease is determined by the presence of myometrial invasion and the extent of extra-uterine disease. The most important histopronostic factors are the existence of a sarcomatous overgrowth defined by a sarcomatous contingent occupying more than 25 % of the volume of the tumor (directly correlated to the grade of the disease), the presence of a heterologous and/or a high-grade component. Stage I adenosarcomas without sarcomatous overgrowth have a good prognosis, with an overall 5-year survival of up to 80 %. In localized disease, complete surgical removal is recommended. The role of hormone therapy, chemotherapy and adjuvant radiotherapy is not established. If possible, relapses should be re-treated surgically, with the aim of achieving complete resection. In the advanced inoperable or metastatic setting, hormone therapy is an option for low-grade adenosarcomas with estrogen receptor (ER) and progesterone receptor (PR) overexpression. For high-grade tumors, the standard chemotherapies are doxorubicin-based combinations, although an integrated approach of surgery and medical treatment should also be considered in this setting.
Topics: Female; Humans; Genital Neoplasms, Female; Adenosarcoma; Neoplasm Recurrence, Local; Uterine Neoplasms; Hormones
PubMed: 37202293
DOI: 10.1016/j.bulcan.2023.04.017 -
Revista Colombiana de Obstetricia Y... Sep 2023To report the case of a patient with a uterine collision tumor and to conduct a review of the literature.
OBJECTIVES
To report the case of a patient with a uterine collision tumor and to conduct a review of the literature.
MATERIAL AND METHODS
A 76-year-old patient who presented to the national cancer referral center in Bogota (Colombia), where she was diagnosed with a uterine collision tumor consisting of a seroustype endometrial adenocarcinoma and a cervical adenosarcoma. The patient underwent surgical treatment followed by chemotherapy and supplemental radiotherapy, and died 16 months later. A search was conducted in the Medline via PubMed and Embase databases, including reports and case series of women with a diagnosis of uterine collision tumor, with retrieval of information regarding diagnosis, treatment and prognosis. A narrative summary of the findings was made.
RESULTS
The search identified 36 titles, of which 14 studies with 17 patients were included. The most frequent histopathological diagnosis was endometrial adenocarcinoma and high and low grade endometrial sarcoma (47 %). Primary treatment was surgery and adjuvant treatment with chemotherapy and radiotherapy (15 %) was performed in close to 50 % of cases. One-year survival was 75 %.
CONCLUSIONS
No cases of uterine collision tumors with the histopathology or in the location of the reported case were found in the literature. If this reported case is taken into account, 2-year mortality is 28 %. Further studies to describe the immunohistochemistry, treatment and prognosis of this condition are needed.
Topics: Female; Humans; Adenocarcinoma; Colombia
PubMed: 37937912
DOI: 10.18597/rcog.4011 -
Annals of Clinical and Laboratory... Jul 2023A review of the clinical-pathologic characteristics and outcomes of biphasic polyps occurring in the female genital tract, not meeting the diagnostic criteria of... (Review)
Review
OBJECTIVE
A review of the clinical-pathologic characteristics and outcomes of biphasic polyps occurring in the female genital tract, not meeting the diagnostic criteria of Mullerian Adenosarcoma (MA).
METHODS
An archival database search was run, after IRB approval, between 2001 and 2019, using terminology such as "Mullerian adenofibroma," "atypical Mullerian adenofibroma," "polypoid adenofibroma," and "atypical polyp with increased stromal cellularity." Two pathologists (JW and MRQ) reviewed all the retrieved cases and documented the morphologic features with particular emphasis on the presence of any features of Mullerian adenosarcoma. Follow-up data were also abstracted.
RESULTS
Twenty-one cases, 12 cervical and 9 endometrial lesions, constituted the study cohort. Patients ranged from 26 to 64 years (median 49 years). On review, 20 of 21 of those cases showed Phyllodes-like architectural patterns. However, only one case showed all four features of MA, all of which were focal and inconspicuous. Follow-up (median duration of 5 years) did not document any recurrences in any of the 21 cases after excision.
CONCLUSION
This series adds to the growing body of literature affirming the existence of benign biphasic Mullerian polyps encountered in the endometrium and cervix that fall short of the Mullerian adenosarcoma diagnosis.
Topics: Humans; Female; Phyllodes Tumor; Adenosarcoma; Stromal Cells; Adenofibroma; Breast Neoplasms
PubMed: 37625832
DOI: No ID Found -
Ultrasound features using MUSA terms and definitions in uterine sarcoma and leiomyoma: cohort study.Ultrasound in Obstetrics & Gynecology :... May 2024Timely and accurate preoperative diagnosis of uterine sarcoma will increase patient survival. The primary aim of this study was to describe the ultrasound features of...
OBJECTIVES
Timely and accurate preoperative diagnosis of uterine sarcoma will increase patient survival. The primary aim of this study was to describe the ultrasound features of uterine sarcoma compared with those of uterine leiomyoma based on the terms and definitions of the Morphological Uterus Sonographic Assessment (MUSA) group. A secondary aim was to assess the interobserver agreement for reporting on ultrasound features according to MUSA terminology.
METHODS
This was a retrospective cohort study of patients with uterine sarcoma or uterine leiomyoma treated in a single tertiary center during the periods 1997-2019 and 2016-2019, respectively. Demographic characteristics, presenting symptoms and surgical outcomes were extracted from patients' files. Ultrasound images were re-evaluated independently by two sonologists using MUSA terms and definitions. Descriptive statistics were calculated and interobserver agreement was assessed using Cohen's κ (with squared weights) or intraclass correlation coefficient, as appropriate.
RESULTS
A total of 107 patients were included, of whom 16 had a uterine sarcoma and 91 had a uterine leiomyoma. Abnormal uterine bleeding was the most frequent presenting symptom (69/107 (64%)). Compared with leiomyoma cases, patients with uterine sarcoma were older (median age, 65 (interquartile range (IQR), 60-70) years vs 48 (IQR, 43-52) years) and more likely to be postmenopausal (13/16 (81%) vs 15/91 (16%)). In the uterine sarcoma cohort, leiomyosarcoma was the most frequent histological type (6/16 (38%)), followed by adenosarcoma (4/16 (25%)). On ultrasound evaluation, according to Observers 1 and 2, the tumor border was irregular in most sarcomas (11/16 (69%) and 13/16 (81%) cases, respectively), but regular in most leiomyomas (65/91 (71%) and 82/91 (90%) cases, respectively). Lesion echogenicity was classified as non-uniform in 68/91 (75%) and 51/91 (56%) leiomyomas by Observers 1 and 2, respectively, and 15/16 (94%) uterine sarcomas by both observers. More than 60% of the uterine sarcomas showed acoustic shadows (11/16 (69%) and 10/16 (63%) cases by Observers 1 and 2, respectively), whereas calcifications were reported in a small minority (0/16 (0%) and 2/16 (13%) cases by Observers 1 and 2, respectively). In uterine sarcomas, intralesional vascularity was reported as moderate to abundant in 13/16 (81%) cases by Observer 1 and 15/16 (94%) cases by Observer 2, while circumferential vascularity was scored as moderate to abundant in 6/16 (38%) by both observers. Interobserver agreement for the presence of cystic areas, calcifications, acoustic shadow, central necrosis, color score (overall, intralesional and circumferential) and maximum diameter of the lesion was moderate. The agreement for shape of lesion, tumor border and echogenicity was fair.
CONCLUSIONS
A postmenopausal patient presenting with abnormal uterine bleeding and a new or growing mesenchymal mass with irregular tumor borders, moderate-to-abundant intralesional vascularity, cystic areas and an absence of calcifications on ultrasonography is at a higher risk of having a uterine sarcoma. Interobserver agreement for most MUSA terms and definitions is moderate. Future studies should validate the abovementioned clinical and ultrasound findings on uterine mesenchymal tumors in a prospective multicenter fashion. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Humans; Female; Uterine Neoplasms; Leiomyoma; Middle Aged; Retrospective Studies; Sarcoma; Ultrasonography; Aged; Observer Variation; Uterus; Terminology as Topic; Adult
PubMed: 37970762
DOI: 10.1002/uog.27535 -
International Journal of Gynecological... Jul 2024SMARCA4 gene encodes BRG1 , a member of the SWItch/sucrose non-fermentable protein family involved in epigenetic transcriptional regulation of important cellular...
SMARCA4 / BRG1 -deficient Uterine Neoplasm With Hybrid Adenosarcoma and Carcinoma Features: Expanding the Molecular-morphologic Spectrum of SMARCA4 -driven Gynecologic Malignancies.
SMARCA4 gene encodes BRG1 , a member of the SWItch/sucrose non-fermentable protein family involved in epigenetic transcriptional regulation of important cellular processes. In the uterine corpus, SMARCA4 / BRG1 deficiency is associated with a novel class of undifferentiated uterine sarcomas, characterized by younger age onset, rhabdoid histology, focal phyllodiform architecture, high-risk pathologic findings, and dismal prognosis. Herein, we report a case of a 34-year-old Asian woman with a SMARCA4 / BRG1 -deficient uterine tumor fulfilling the clinicopathologic features of an undifferentiated uterine sarcoma. However, the tumor exhibited several unique features that have not been previously emphasized, including (1) conspicuous phyllodiform architecture recapitulating conventional adenosarcoma, (2) rhabdoid tumor cells forming cords and keratin-positive cohesive epithelial islands, and (3) cooccurrence with a spatially distinct and discrete endometrial complex atypical hyperplasia from the rest of the proliferation. By immunohistochemistry, the tumor cells were diffusely positive for synaptophysin, whereas BRG1 was lost. Pertinent molecular findings included frameshift mutations in the SMARCA4 gene, mutations in histone modification and chromatin remodeling genes, including KMT2C , ARID1B , KAT6A , and NCOR1 , and mutations in Wnt signaling involving APC and CTNNB1 . Copy number gain in MDM2 and CDK4 were also identified. The tumor mutation burden was intermediate (6.8/MB) and it was microsatellite stable. On balance, our case exhibited morphologic and molecular features that overlap with (1) an undifferentiated uterine sarcoma, (2) an adenosarcoma with sarcomatous overgrowth, and (3) a mixed adenosarcoma and undifferentiated endometrial carcinoma. These hybrid features further expand the molecular-morphologic spectrum of SMARCA4 / BRG1 -deficient uterine neoplasms.
Topics: Humans; Female; DNA Helicases; Transcription Factors; Nuclear Proteins; Adult; Adenosarcoma; Uterine Neoplasms; Immunohistochemistry; Carcinoma
PubMed: 38113031
DOI: 10.1097/PGP.0000000000000996 -
Human Pathology Jun 2024Mullerian adenosarcoma is a rare malignant biphasic tumor. The mesenchymal component may be low or high grade, with or without sarcomatous overgrowth (SO). Little is...
Mullerian adenosarcoma is a rare malignant biphasic tumor. The mesenchymal component may be low or high grade, with or without sarcomatous overgrowth (SO). Little is known about the molecular heterogeneity of these tumors. In this study, we aim to reclassify a large retrospective monocentric cohort of uterine adenosarcomas according to tumor grade and SO, to evaluate the clinical significance of pathological classification and to correlate with copy-number variations inferred from single nucleotide polymorphism array. Of the 67 uterine adenosarcomas, 18 (26.9%) were low grade without SO, 7 (10.4%) low grade with SO, 8 (11.9%) high grade without SO and 34 (50.7%) high grade with SO. SO, necrosis and RMS were more frequent in high grade than low grade adenosarcomas (p < 0.001). Low-rank test showed that recurrence-free survival was significantly shortened in high grade than low grade adenosarcomas (p = 0.035) and SO was associated with shortened overall and recurrence-free survival (p = 0.038 and p = 0.009, respectively). High-grade tumors displayed complex genomic profiles with multiple segmental losses including TP53, ATM and PTEN genes. The median genomic index was significantly higher in high grade than low grade tumors (27 [3-60] vs 5,3 [0-16], p < 0.0001) and was significantly higher in presence of SO in low grade tumors (12,8 [10-16] vs 2,6 [0-10], p = 0.0006). We propose to report sarcomatous overgrowth with the tumor grade for prognostication in adenosarcoma and representative sampling is crucial for evaluation of these histological criteria.
Topics: Humans; Adenosarcoma; Female; Uterine Neoplasms; Polymorphism, Single Nucleotide; Middle Aged; Retrospective Studies; Aged; Adult; Neoplasm Grading; DNA Copy Number Variations; Aged, 80 and over; Biomarkers, Tumor; Clinical Relevance
PubMed: 38688412
DOI: 10.1016/j.humpath.2024.04.016