Application of hysteroscopy in the treatment of Mullerian adenosarcoma of the cervix in an adolescent girl with 7 years of follow-up.

BACKGROUND: Mullerian adenosarcoma of the cervix is a rare biphasic tumor composed of a benign epithelial component and a malignant stromal component. Here, we report a rare case of Mullerian adenosarcoma of the cervix in an adolescent girl treated with hysteroscopic resection. CASE PRESENTATION: A 16-year-old girl presented to the Affiliated Hospital of North Sichuan Medical College in April 2017 with a one-year history of a painless vaginal mass. 10 hours prior to presentation, she had experienced rapid enlargement of the vaginal mass and mild vaginal bleeding. 16 hours after hospitalization, a mass measuring 14 × 10 × 4 cm was spontaneously expelled from the vagina. Histopathological examination of the mass confirmed a diagnosis of Mullerian adenosarcoma. On May 10, 2017, the patient underwent hysteroscopic resection of a cervical lesion and partial cervical resection. After nearly 7 years of follow-up, the tumor has not recurred. CONCLUSIONS: Mullerian adenosarcoma of the cervix is difficult to diagnose in adolescents. For young women affected by low-risk early-stage Mullerian adenosarcoma of the cervix, fertility preserving treatment using hysteroscopic resection with robust follow-up is a reasonable management option.

Survival Trends for Uterine Sarcomas from a Tertiary Center: The Oxford Experience.

Uterine sarcomas are rare and aggressive gynecological malignancies. We evaluated the epidemiology, treatment outcomes and survival rates in uterine sarcoma patients managed in our institute. The medical records of women with histology proven uterine sarcoma, including leiomyosarcoma (LMS), adenosarcoma (ADS), and endometrial stromal sarcoma (ESS), treated at our institution from February 2010 to February 2022, were analyzed. In total, 41 patients were identified. In detail, LMS, ADS, and high-grade and low-grade ESS were identified, respectively, in 60.9%, 19.5%, 12.1%, and 7.3% of the cases. The majority of women affected by LMS (72%) underwent primary surgery and 40% of them also received adjuvant chemotherapy. A surgical approach was the preferred mode of treatment in 83% of the recurrences. The median OS (overall survival), DFS (disease free survival), and PFS (progression free survival) for the LMS group were 25, 44.5, and 8 months, respectively. The 5-year survival rates for LMS, ADS, and ESS groups were 30.5%, 100% and 37.5%, respectively. The 5-year survival for LMS was found to be significantly worse than for other histology types (p = 0.016). Our study provides valuable data for the evaluation of treatment strategies and survival trends among these rare cancers. The management and follow-up planning of each subtype requires a thorough patient-focused multidisciplinary discussion.

Müllerian adenosarcoma with sarcomatous overgrowth and heterologous elements: A case report and literature review.

Uterine mullerian adenosarcoma (MA) is a rare biphasic tumour that accounts for less than 0.5% of uterine neoplasms. The age range of presentation is wide, with the median age in the 5th decade of life. It usually has a good prognosis; however, it worsens when it presents with sarcomatous overgrowth, heterologous elements or infiltrates the myometrium. We report the case of a 63-year-old woman presenting with abnormal vaginal bleeding and a sensation of solid material coming out of the cervical canal who was diagnosed with mullerian adenosarcoma with sarcomatous overgrowth (MASO) and presence of heterologous elements after performing a mass biopsy and subsequent hysterectomy. We reviewed the literature, focusing especially on the differential diagnoses to be evaluated, as well as the differences in prognosis and treatment according to whether or not they present histologic features of poor prognosis.

A rare case report of endometrial adenosarcoma in the cesarean scar diverticulum.

Background: Endometrial adenosarcoma is an unusual type of uterine tumor that features a seemingly benign epithelial component, paired with a low-grade sarcomatous component, usually similar in appearance to endometrial stromal sarcoma. To our knowledge, no image of endometrial adenocarcinoma in the cesarean scar diverticulum has been reported previously. Case Description: We present a rare case of endometrial adenocarcinoma located in the cesarean scar diverticulum of a 44-year-old patient. The patient was admitted to our hospital complaining of irregular vaginal bleeding that had lasted for over two months. Both B-ultrasound and magnetic resonance imaging confirmed a mass at the junction of the corpus uteri and cervix. After the initial curettage failed to confirm the disease, a hysteroscopy was subsequently performed. Upon further pathological analysis, a diagnosis of endometrial adenosarcoma was confirmed. The patient underwent hysterectomy and salpingo-oophorectomy. The patient was discharged home four days after the surgery and remained recurrence-free for one year after follow-up. Conclusions: Hysteroscopy can serve as a valuable diagnostic tool to identify the lesion in this unique scenario, particularly when curettage fails to diagnose this uncommon condition. We hope that this case would bring awareness of this potential scenario, enabling clinicians in the future to identify similar cases more readily.

Rare Mullerian adenosarcoma of the uterine cervix arising on a background of endometriosis: A diagnostic challenge with risk of malignant transformation-A case report and review of the current literature.

Endometriosis may contribute to Mullerian adenosarcoma development but makes diagnosis challenging given similar symptoms. Survival benefit has not been definitively shown for chemotherapy, hormonal therapy, or radiotherapy, consolidating surgery as the mainstay treatment. Local excision may be a treatment option for patients with confined tumors wishing to preserve their fertility.

Prognostic factors in uterine adenosarcoma: subanalysis of the SARCUT study.

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; p = 0.004) and FIGO stage II-III (HR 17.75, 95% CI 2.87-109.93; p = 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.

Management of endometrial cancer in Latin America: raising the standard of care and optimizing outcomes.

Molecular characterization of endometrial cancer is allowing for increased understanding of the natural history of tumors and paving a more solid pathway for novel therapies. It is becoming increasingly apparent that molecular classification is superior to histological classification in terms of reproducibility and prognostic discrimination. In particular, the Proactive Molecular Risk Classifier for Endometrial Cancer allows classification of endometrial cancer into groups very close to those determined by the Cancer Genome Atlas Research Network-that is, DNA polymerase epsilon-mutated, mismatch repair-deficient, p53 abnormal, and non-specific molecular profile tumors. The transition from the chemotherapy era to the age of targeted agents and immunotherapy, which started later in endometrial cancer than in many other tumor types, requires widespread availability of specialized pathology and access to novel agents. Likewise, surgical expertise and state-of-the-art radiotherapy modalities are required to ensure adequate care. Nevertheless, Latin American countries still face considerable barriers to implementation of international guidelines. As we witness the dawn of precision medicine as applied to endometrial cancer, we must make continued efforts towards improving the quality of care in this region. The current article discusses some of these challenges and possible solutions.

Mullerian adenosarcoma of the uterus with MASO: a case report of cervical adenosarcoma in a young female that never had sexual behavior.

BACKGROUND: Cervical mullerian adenosarcoma is a rare uterine sarcoma, especially in young women. Its pathological features are low-grade malignant tumors with bidirectional differentiation, and the degree of malignancy is similar to that of low-grade endometrial stromal sarcoma. This paper reports the case of a young asexual patient who has been closely followed up after tumor resection and has not had any recurrences. CASE PRESENTATION: A 20-year-old, young asexual woman was diagnosed with cervical mullerian adenosarcoma with sarcomatous overgrowth (MASO). Cervical tumor resection was performed after admission, and the resection margin was negative. After the operation, she refused to undergo secondary surgery due to fertility requirements and did not receive adjuvant treatment. The patient was closely followed up after the operation and has not yet relapsed. CONCLUSION: A young woman with cervical MASO did not receive adjuvant treatment after cervical tumor resection. For women with fertility requirements, close follow-ups should be conducted after the operation to guard against tumor recurrence and radical tumor resection should be performed as early as possible after the patient no longer requires their fertility.

Nonpuerperal uterine inversion caused by an adenosarcoma: A case report.

INTRODUCTION: Eighty-five per cent of uterine inversions are puerperal. Non-puerperal uterine inversion is usually caused by tumours that exert a traction force on the fundus of the uterus. This causes the uterus to be partially or completely inverted. It is commonly related to benign tumours like submucosal leiomyomas. Nevertheless, malignancies are an infrequent association. CASE PRESENTATION: We report a case of a 35-year-old female patient, medically and surgically free, gravida0 para0, complaining of menometrorrhagia associated with pelvic pain for 2 years. A suprapubic ultrasound scan showed an enlarged, globular uterus with a heterogeneous, undefined mass of 49 mm in size. MRI scan showed the appearance of a U-shaped uterine cavity and a thickened inverted uterine fundus with an endometrial infiltrating mass of 25 mm. Intraoperative exploration showed uterine inversion involving the ovaries; the fallopian tubes and the round ligaments and a necrotic intracavitary mass. The malignancy of the tumor was confirmed through anatomopathological examination as Adenosarcoma. CONCLUSIONS: Uterine inversion is rare outside the puerperal period, and malignant etiology must not be overlooked. Therefore, comprehensive care with meticulous etiological investigation is crucial.

Uterine adenosarcoma: Clinical significance of histological classification and SNP array analysis.

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.

Uterine adenosarcoma presenting as uterine inversion: A case study.

•Non-puerperal uterine inversion can be associated with uterine sarcomas.•Adenosarcoma is a tumor composed of benign epithelium and malignant stroma.•If malignancy is suspected or confirmed treatment of uterine inversion with hysterectomy is advised.

Clinicopathological analysis of 22 Müllerian adenosarcomas and the sequencing of DICER1 mutation.

BACKGROUND: Müllerian adenosarcoma, a rare malignancy, presents diagnostic and therapeutic challenges. In this study, we conducted an analysis of the clinicopathological characteristics of 22 adenosarcomas, with a particular focus on screening for DICER1 hot mutations. METHODS: The cohort consisted of patients with adenosarcoma who were registered at the West China Second Hospital between the years 2020 and June 2022. Sanger sequencing was employed to screen for somatic Hotspot mutations in the RNase IIIb domain of DICER1 in the 22 adenosarcomas. RESULTS: Only one patient exhibited a DICER1 mutation that was not a DICER1 Hotspot mutation. Among the 22 patients, all underwent total hysterectomy with bilateral salpingo-oophorectomy, and 14 out of these 22 patients received adjuvant treatment. CONCLUSION: In summary, our study of 22 Müllerian adenosarcomas focused on the clinicopathological features and the presence of DICER1 Hotspot mutations. Although our findings did not reveal any DICER1 mutations in the studied samples, this negative result provides valuable information for the field by narrowing down the genetic landscape of adenosarcomas and highlighting the need for further research into alternative molecular pathways driving this malignancy.

Unveiling the intriguing grape-like mass: Uterine cervical adenosarcoma.

Key Clinical Message: Adenosarcoma of the uterine cervix should be considered in the evaluation of post-menopausal bleeding, as it can be a potential underlying cause. Timely diagnosis and appropriate management are essential to optimize patient outcomes. Abstract: Adenosarcoma is a biphasic neoplasm comprising both a benign epithelial component and a typically low-grade sarcomatous stromal component. Adenosarcoma mainly affects the endometrium (71%), with a lesser incidence in the cervix (2%). Herein, the authors report a case of adenosarcoma of the uterine cervix with distinct gross features.

Case report: An atypical case of uterine adenosarcoma with extensive bizarre stromal cells and amplification of MDM2.

Polypoid lesions in the uterus are very common. There are a lot of benign lesions and malignant tumor should be considered. Adenosarcoma, one of the differential diagnoses, is a rare mixed epithelial and mesenchymal tumor consisting of benign epithelial components and sarcoma stroma. Here, we present a case of atypical adenosarcoma that has never been reported. This tumor was composed of benign endometrial epithelium and hyperplastic stroma with extensive bizarre stromal cells. But the cleft-like spaces and papillary stomal fronds which were the typical histological images of adenosarcoma were absent. These stomal cells, including bizarre cells, were positive for vimentin, CD10, ER, PR, cyclin D1 and P16 but were immunonegative for caldesmon. Furthermore, this tumor harbored amplification of MDM2, as revealed by fluorescence in situ hybridization testing (FISH) and next-generation DNA sequencing (NGS).

A Case Report of Uterine Müllerian Adenosarcoma With Sarcomatous Overgrowth.

Uterine adenosarcoma remains a highly aggressive tumor and is less described in the literature, with an unfavorable prognosis and an increased risk of local and distant recurrence. However, surgery, chemotherapy, and radiotherapy offer local control of the disease, and overall survival remains reduced. We report the case of a 79-year-old patient with stage IIIB uterine adenosarcoma, confirmed by immunohistochemistry and initially diagnosed with postmenopausal metrorrhagia. The patient was managed through a multimodal treatment by conducting a multidisciplinary consultation.

[Diagnosis of uterine sarcomas and rare uterine mesenchymal tumours with malignant potential. Guidelines of the French Sarcoma Group and Rare Gynaecological Tumours]. / Diagnostic des sarcomes utérins et tumeurs mésenchymateuses utérines rares à potentiel de malignité. Référentiels du Groupe Sarcome Français et des Tumeurs Rares Gynécologiques.

The landscape of uterine sarcomas is becoming more complex with the description of new entities associated with recurrent driver molecular alterations. Uterine sarcomas, in analogy with soft tissue sarcomas, are distinguished into complex genomic and simple genomic sarcomas. Leiomyosarcomas and undifferentiated uterine sarcomas belong to complex genomic sarcomas group. Low-grade and high-grade endometrial stromal sarcomas, other rare tumors associated with fusion transcripts (such as NTRK, PDGFB, ALK, RET ROS1) and SMARCA4-deficient uterine sarcoma are considered simple genomic sarcomas. The most common uterine sarcoma are first leiomyosarcoma and secondly endometrial stromal sarcomas. Three different histological subtypes of leiomyosarcoma (fusiform, myxoid, epithelioid) are identified, myxoid and epithelioid leiomyosarcoma being more aggressive than fusiform leiomyosarcoma. The distinction between low-grade and high-grade endometrial stromal sarcoma is primarily morphological and immunohistochemical and the detection of fusion transcripts can help the diagnosis. Uterine PEComa is a rare tumor, which is distinguished into borderline and malignant, according to a risk assessment algorithm. Embryonal rhabdomyosarcoma of the uterine cervix is more common in children but can also occur in adult women. Embryonal rhabdomyosarcoma of the uterine cervix is almost always DICER1 mutated, unlike that of the vagina which is wild-type DICER1, and adenosarcoma which can be DICER1 mutated but with less frequency. Among the emerging entities, sarcomas associated with fusion transcripts involving the NTRK, ALK, PDGFB genes benefit from targeted therapy. The integration of molecular data with histology and clinical data allows better identification of uterine sarcomas in order to better treat them.

Clear Cell Carcinoma Arising in Low-Grade Mullerian Adenosarcoma: First Reported Case with Insight into Molecular Profile.

Uterine adenosarcoma (AS) is a rare biphasic neoplasm composed of a malignant, usually low-grade stromal component and benign epithelial component, usually endometrioid. Pathogenesis is unknown; some cases are undoubtably associated with tamoxifen use. Endometrial clear cell carcinoma (CCC) is an aggressive subtype of endometrial cancer, accounting for less than 10% of all uterine carcinomas. The etiology is unknown but can rarely be associated with Lynch syndrome and tamoxifen administration. The development of a composite neoplasm consisting of adenocarcinoma in AS is extremely rare. Endometrioid carcinoma typically represents the epithelial component of the composite tumor. Here we present the very first case of composite tumor, namely, AS with CCC in which next-generation sequencing was performed. Patient was an 85-year-old woman treated with tamoxifen for 5 years. To better understand the pathobiology of two tumors, a targeted genomic analysis of both components was performed. We found seven identical somatic variants in the samples of both tumors, indicating that the tumors have a high probability of having the same origin. Dual amplification of CDK4 and MDM2 was the most likely primary cause of tumor formation, but also one driver variant in the DHX15 gene that was present in both tumor components, suggesting that DHX15 may play an important role in the initiation and development of sarcoma and carcinoma. The patient is followed by regular clinical controls and is alive without signs of disease recurrence 18 months after surgery.

Next generation sequencing reveals a high prevalence of pathogenic mutations in homologous recombination DNA damage repair genes 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.

The uterine adenosarcoma with postoperative residual in a woman treated by total abdominal hysterectomy/bilateral salpingo-oophorectomy: A case report and review of literature.

BACKGROUND: In patients with uterine adenosarcoma, a total abdominal hysterectomy (TAH) with bilateral salpingo-oophorectomy (BSO) is typically recommended as an initial treatment. There is no consensus on adjuvant therapies. CASE: We report the case of a patient with uterine adenosarcoma with postoperative residual disease. We performed four courses of adjuvant chemotherapy, including Ifosfamide, Mesna, and Adriamycin, and whole pelvic radiation with a dose of 50.4 Gy/28 Fr. CONCLUSION: A combination of chemotherapy and radiotherapy may be a promising treatment option for uterine adenosarcoma with postoperative residual disease.

Benign Biphasic Tumors of the Mullerian Tract - a Mimic of Phyllodes Tumor. A Clinical-Pathologic Description of 21 Cases.

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.