Search

Uterine adenosarcoma coexisting with endometrial carcinoma is a very rare disease. Herein, we reported the case of uterine adenosarcoma coexisting with endometrioid endometrial carcinoma. Transvaginal ultrasound, computed tomography, and magnetic resonance imaging examinations all indicated a space-occupying lesion in the uterine cavity, and initially was considered endometrial carcinoma. Subsequently, total hysterectomy combined with bilateral salpingo-oophorectomy, pelvic lymphadenectomy, and para-aortic lymphadenectomy were performed. The coexistence of uterine adenosarcoma and endometrioid endometrial carcinoma was histologically confirmed postoperatively. The patient recovered well after surgery and was discharged on postoperative day 7. At a follow-up examination 10 months after surgery, we found no evidence of discomforting symptoms and recurrence or metastasis. Since the coexistence of uterine adenosarcoma and endometrial carcinoma is rare, it is easy to be overlooked the presence of uterine adenosarcoma on imaging or morphology, and thus be misdiagnosed as a more common disease, namely endometrial carcinoma. Observing the cystic structure within the lesion on magnetic resonance imaging is helpful for the diagnosis of uterine adenosarcoma. This article summarizes the imaging characteristics, clinicopathological features, molecular correlation, treatment, and prognosis of the disease., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Uterine sarcoma is a rare and heterogeneous gynecological malignancy characterized by aggressive progression and poor prognosis. The current study aimed to investigate the relationship between clinicopathological characteristics and the prognosis of uterine sarcoma in Chinese patients., Methods: In this single-center retrospective study, we reviewed the medical records of 75 patients with histologically verified uterine sarcoma treated at the First Affiliated Hospital of Xi'an Jiaotong University between 2011 and 2020. Information on clinical characteristics, treatments, pathology and survival was collected. Progression-free survival (PFS) and overall survival (OS) were visualized in Kaplan-Meier curves. Prognostic factors were identified using the log-rank test for univariate analysis and Cox-proportional hazards regression models for multivariate analysis., Results: The histopathological types included 36 endometrial stromal sarcomas (ESS,48%), 33 leiomyosarcomas (LMS,44%) and 6 adenosarcomas (8%). The mean age at diagnosis was 50.2 ± 10.7 years. Stage I and low-grade accounted for the majority. There were 26 recurrences and 25 deaths at the last follow-up. The mean PFS and OS were 89.41 (95% CI: 76.07-102.75) and 94.03 (95% CI: 81.67-106.38) months, respectively. Univariate analysis showed that > 50 years, post-menopause, advanced stage, ≥ 1/2 myometrial invasion, lymphovascular space invasion and high grade were associated with shorter survival (P < 0.05). Color Doppler flow imaging positive signals were associated with shorter PFS in the LMS group (P = 0.046). The ESS group had longer PFS than that of the LMS group (99.56 vs. 76.05 months, P = 0.043). The multivariate analysis showed that post-menopause and advanced stage were independent risk factors of both PFS and OS in the total cohort and LMS group. In the ESS group, diagnosis age > 50 years and high-grade were independent risk factors of PFS, while high-grade and lymphovascular space invasion were independent risk factors of OS., Conclusion: In Chinese patients with uterine sarcoma, post-menopause and advanced stage were associated with a significantly poorer prognosis. The prognosis of ESS was better than that of LMS. Color Doppler flow imaging positive signals of the tumor helped to identify LMS, which needs to be further tested in a larger sample in the future., (© 2024. The Author(s).)

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., Competing Interests: C.H.W. is an NCI K12 clinician scientist fellowship awardee. The remaining authors declare conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

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., (Copyright © 2024 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Mesonephric-like adenocarcinoma (MLA) of the ovary is a recently recognized, rare malignancy with aggressive clinical behavior, and is thought to originate from Mullerian epithelium with mesonephric transdifferentiation. Emerging evidence suggests that MLA may be classified as an endometriosis-associated neoplasm. The presence of a sarcomatous component within MLA is extremely rare, with common differential diagnoses including the spindle cell component of MLA, carcinosarcoma, as well as mixed Mullerian adenocarcinoma and adenosarcoma. Herein, we report a 58-year-old Chinese woman with bilateral ovarian solid-cystic masses. The left ovarian mass comprised a biphasic tumor with a predominantly high-grade sarcomatous component displaying heterologous mesenchymal differentiation, including liposarcoma, rhabdomyosarcoma and chondrosarcoma-like areas, with a null-type p53 expression. The epithelial component ranged from a bland appearance in areas diagnostic of adenosarcoma to a clearly invasive carcinoma, both with mesonephric-like phenotype, being negative for estrogen receptor, progesterone receptor, and Wilms' tumor 1, variably positive for paired box gene 8, GATA binding protein 3, and thyroid transcription factor 1, with a wild-type p53 expression. The differing p53 expression between the epithelial and sarcomatous elements mitigated against a diagnosis of carcinosarcoma. The right ovarian mass showed endometriosis with focal direct evidence of the development of malignancy within a benign endometriotic cyst, exhibiting the identical immunoprofile of MLA but originating as another malignancy. To the best of our knowledge, this case represents the first reported case of synchronous bilateral ovarian MLAs with separate origins, from high-grade Mullerian adenosarcoma and endometriosis respectively, which broadens the morphologic spectrum of MLA and provides further evidence supporting the Mullerian origin theory., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 by the International Society of Gynecological Pathologists.)

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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

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., (© 2024. The Author(s).)

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., (© 2024. The Author(s).)

Objective: Uterine sarcomas are a rare and heterogeneous group of malignancies that include different histological sub-types. The aim of this study was to identify and evaluate the impact of the different prognostic factors on overall survival and disease-free survival of patients with uterine sarcoma., Methods: This international multicenter retrospective study included 683 patients diagnosed with uterine sarcoma at 46 different institutions between January 2001 and December 2007., Results: The 5-year overall survival for leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma, and adenosarcoma was 65.3%, 78.3%, 52.4%, and 89.5%, respectively, and the 5-year disease-free survival was 54.3%, 68.1%, 40.3%, and 85.3%, respectively. The 10-year overall survival for leiomyosarcoma, endometrial stromal sarcoma, undifferentiated sarcoma and adenosarcoma was 52.6%, 64.8%, 52.4%, and 79.5%, respectively, and the 10-year disease-free survival was 44.7%, 53.3%, 40.3%, and 77.5%, respectively. The most significant factor associated with overall survival in all types of sarcoma except for adenosarcoma was the presence of residual disease after primary treatment. In adenosarcoma, disease stage at diagnosis was the most important factor (hazard ratio 17.7; 95% CI 2.86 to 109.93)., Conclusion: Incomplete cytoreduction, tumor persistence, advanced stage, extra-uterine and tumor margin involvement, and the presence of necrosis were relevant prognostic factors significantly affecting overall survival in uterine sarcoma. The presence of lymph vascular space involvement and administration of adjuvant chemotherapy were significantly associated with a higher risk of relapse., Competing Interests: Competing interests: None declared., (© IGCS and ESGO 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

This was a 57-year-old woman who presented with mild discomfort in the right groin. Physical examination revealed a mass in the right groin, and by ultrasound, the mass was hypoechoic and solid with some internal vascularity. The clinical differential diagnosis included lymphoma and others. The mass was excised for pathologic evaluation. Gross examination of the specimen revealed a 3 × 2.4 × 2 cm, solid and cystic mass. Microscopically, it was a biphasic tumor consisting of carcinomatous and sarcomatous components. The tumor was seen contiguous with endometriosis and atypical endometrioid hyperplasia. The histologic findings were consistent with malignant mixed Mullerian tumor (MMMT) arising from endometriosis in the right groin. The tumor involved the resection margin. Subsequent chest/abdominal/pelvic computed tomography did not reveal evidence of tumors, and diagnostic peritoneal/pelvic laparoscopy did not show diseases. Postoperatively, the patient received 6 cycles of chemotherapy consisting of carboplatin and paclitaxel, followed by radiation in the right groin. Malignant transformation from endometriosis occurs in less than 1% of endometriosis cases, and about 80% of the transformed tumors occur in the ovaries. The most commonly transformed malignant tumors are endometrioid and clear cell carcinomas, with rare adenosarcoma and endometrial stromal sarcoma reported. To our knowledge, we are reporting the first case of MMMT arising from endometriosis in the groin.

Background: Uterine adenosarcoma is a rare malignant tumor that accounts for 8% of all uterine sarcomas, and less than 0.2% of all uterine malignancies. However, it is frequently misdiagnosed in clinical examinations, including pathological diagnosis, and imaging studies owing to its rare and non-specific nature, which is further compounded by the lack of specific diagnostic markers., Case Presentation: We report a case of uterine adenosarcoma for which a comprehensive genomic profiling (CGP) test provided a chance to reach the proper diagnosis. The patient, a woman in her 60s with a history of uterine leiomyoma was diagnosed with an intra-abdominal mass post presentation with abdominal distention and loss of appetite. She was suspected to have gastrointestinal stromal tumor (GIST); the laparotomically excised mass was found to comprise uniform spindle-shaped cells that grew in bundles with a herringbone architecture, and occasional myxomatous stroma. Immunostaining revealed no specific findings, and the tumor was diagnosed as a spindle cell tumor/suspicious adult fibrosarcoma. The tumor relapsed during postoperative follow-up, and showed size reduction with chemotherapy, prior to regrowth. CGP was performed to identify a possible treatment, which resulted in detection of a JAZF1-BCORL1 rearrangement. Since the rearrangement has been reported in uterine sarcomas, we reevaluated specimens of the preceding uterine leiomyoma, which revealed the presence of adenosarcoma components in the corpus uteri. Furthermore, both the uterine adenosarcoma and intra-abdominal mass were partially positive for CD10 and BCOR staining., Conclusion: These results led to the conclusive identification of the abdominal tumor as a metastasis of the uterine adenosarcoma. The JAZF1-BCORL1 rearrangement is predominantly associated with uterine stromal sarcomas; thus far, ours is the second report of the same in an adenosarcoma. Adenosarcomas are rare and difficult to diagnose, especially in atypical cases with scarce glandular epithelial components. Identification of rearrangements involving BCOR or BCORL1, will encourage BCOR staining analysis, thereby potentially resulting in better diagnostic outcomes. Given that platinum-based chemotherapy was proposed as the treatment choice for this patient post diagnosis with adenosarcoma, CGP also indirectly contributed to the designing of the best-suited treatment protocol., (© 2023. The Author(s).)

Mullerian adenosarcoma is an uncommon mesenchymal tumor of the gynecologic tract. Most cases are low-grade, while high-grade adenosarcomas are rare and not well studied. Herein, we characterize the clinicopathologic and molecular features of 27 adenosarcomas of gynecologic origin, enriched for high-grade tumors subjected to targeted panel sequencing. Sarcomatous overgrowth was more frequently seen in high-grade compared to low-grade tumors (12/17, 71%, vs 1/10, 10%, p = 0.004) and heterologous elements were exclusive to high-grade cases (n = 7, p = 0.03). All deaths were from high-grade disease (advanced primary, n = 2, or recurrence, n = 5). Genetic alterations specific to high-grade adenosarcomas have known associations with chromosome instability, including TP53 mutations (n = 4) and amplifications of MDM2 (n = 2) and CCNE1 (n = 2). Somatic ATRX frameshift mutations were found in 2 patients with high-grade recurrences following a primary low-grade adenosarcoma and ATRX deletion in 1 high-grade adenosarcoma with an adjacent low-grade component. The fraction of genome altered by copy number alterations was significantly higher in high-grade compared to low-grade adenosarcomas (P = 0.001). Other recurrent genetic alterations across the entire cohort included BAP1 homozygous deletions (n = 4), DICER1 mutations (n = 4), ARID1A mutations (n = 3), TERT promoter mutations (n = 2) and amplification (n = 1), as well as alterations involving members of the PI3K and MAPK signaling pathways. One tumor harbored an ESR1-NCOA3 fusion and another had an MLH1 homozygous deletion. Immunohistochemical analysis for BAP1 revealed loss of nuclear expression in 6/24 (25%) cases, including all four tumors with BAP1 deletions. Notably, out of 196 mesenchymal neoplasms of gynecologic origin, BAP1 homozygous deletion was only found in adenosarcomas (P = 0.0003). This study demonstrates that high-grade adenosarcomas are heterogeneous at the molecular level and are characterized by genomic instability and TP53 mutations; ATRX loss may be involved in high-grade transformation of low-grade adenosarcoma; and BAP1 inactivation appears to be a specific pathogenic driver in a subset of adenosarcomas., (© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

The objective for the study was to analysis the epidemiology of adenosarcoma, and independent prognostic factors and impact of lymph node dissection (LND) of uterine adenosarcoma. Cases of patients with primary adenosarcoma were obtained from the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2016. Overall survival was analyzed by the Kaplan-Meier method and log-rank test. The differences in baseline covariates between the 2 groups were adjusted by inverse probability of treatment weighting method. The prognostic factors were identified by univariate and multivariate Cox regression analysis and hazard ratio and 95% confidence interval (CI) of covariates were also estimated. 1129 patients with pathological primary adenosarcoma between 2000 and 2016 were identified from the surveillance, epidemiology, and end results database. The only 4 patients were male. 1027 patients with primary uterine adenosarcoma, and 53.1% underwent LND and only 3.5% patients were with positive lymph node. Age, marital status, largest tumor size, tumor grade, T stage and chemotherapy were significantly correlated with survival. Race, tumor number, LND, and radiotherapy did not affect overall survival in patients. Inverse probability of treatment weighting-adjusted K-M curve showed that LND did not improve survival and lymph node metastasis (LNM) did not affect survival. The majority of primary adenosarcoma patients are female with high incidence of uterus and rare incidence of distant metastasis. Age, marital status, tumor size, T stage, grade, and chemotherapy are independent prognostic factors of uterine adenosarcoma. LNM was not a significant prognostic risk factor, and LND did not benefit survival., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

A subset of clinically benign uterine polyps shows atypical morphologic features worrisome for, but not diagnostic of, Mullerian adenosarcoma. We report clinicopathologic data for 63 polyps from 58 women with atypical morphologic features including abnormal architecture, abnormal periglandular stroma, stromal atypia, and mitoses >2 per 10 hpf. Four (11%) of 36 women with follow-up tissue sampling had residual/recurrent atypical polyp. Twelve (27%) of 44 women underwent hysterectomy subsequent to a diagnosis of atypical polyp. No patient developed adenosarcoma over median follow-up of 150 months. Twenty-one primary atypical polyps underwent molecular profiling. Five (24%) harbored chr 12q13-15 gain or amplification, 9/20 (45%) harbored chr 6q25.1 gain, and 7/21 (33%) had no significant copy number alterations. Gains of chr 1q, chr 8p12, and chr 10q11.21-23, amplifications of chr 12q24.12-13, chr 15p24.1-26.1, and chr 18q21.33, and loss of chr 7 and chr 11q21 were each seen in a single polyp. Mean tumor mutational burden was 3.1 (range, 0.76-8.365) mutations/Mb. Pathogenic point mutations were identified in 12/20 (60%) primary atypical polyps. We propose the term "atypical uterine polyps" for these lesions, which show biologic overlap with early Mullerian adenosarcoma but lack molecular alterations characteristic of clinically aggressive adenosarcoma and appear to follow a benign clinical course. Conservative management with close clinical follow-up and repeat sampling can be considered for these lesions, when clinically appropriate., (© 2021. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)

Background: Adenosarcoma is classified as a mixed epithelial and mesenchymal tumor composed of a benign epithelial component and a malignant stromal component. The stromal component in adenosarcoma is usually low grade, and consequently the prognosis is relatively favorable. While, adenosarcoma with sarcomatous overgrowth (SO) is defined as an adenosarcoma in which the sarcomatous component constitutes more than 25% of the tumor. The stromal component is also high-grade sarcoma showing greater nuclear pleomorphism and mitotic activity, thus, it is associated with worse prognosis. MRI findings of adenosarcoma without SO have been described in previous literatures but the imaging findings in adenosarcoma with SO may be poorly defined. Therefore we present two cases of uterine adenosarcoma with SO., Case Presentation: Patient 1 was a 76-year-old woman referred to our hospital with complaint of abdominal distension and postmenopausal bleeding. Patient 2 was a 57-year-old woman with complaint of lower abdominal pain and abnormal uterine bleeding. On magnetic resonance imaging (MRI), T2 weighted imaging showed a large, heterogeneous high-intensity mass with hyperintense tiny cysts that expanded the uterine cavity and extended into the cervical canal for both patients. On diffusion-weighted imaging (DWI), both masses appeared as high signal intensity. Patient 2 also had a right ovarian adult granulosa cell tumor that may have contributed to development of the adenosarcoma. Patient 1 recurred with peritoneal sarcomatosis 6 months after surgery and died of the disease. Patient 2 also recurred with a left upper lung metastasis 3 months after surgery., Conclusions: DWI may depict pathological changes produced by SO of adenosarcoma as high signal intensity, even though SO does not seem to change MRI findings of adenosarcoma on other sequences. Therefore, DWI could potentially predict SO in presumptive adenosarcoma on MRI and the patient's prognosis. It is also important for pathologists to know if SO can arise in adenosarcoma because they need to examine the tumor thoroughly to determine the percentage of SO component in the tumor volume when SO is present., (© 2021. The Author(s).)

Uterine sarcomas represent a clinical challenge because of their difficult diagnosis and the poor prognosis of certain subtypes. The aim of this study was to evaluate the expression of the special AT-rich sequence-binding protein 2 (SATB2) in endometrial stromal sarcoma (ESS) and other types of uterine sarcoma by immunohistochemistry. We studied the expression of SATB2 on 71 full tissue sections of endometrial stromal nodule, low-grade ESS, uterine leiomyomas and leiomyosarcoma, undifferentiated uterine sarcoma, adenosarcoma, and carcinosarcoma samples. Nuclear SATB2 expression was then evaluated in an extended sample set using a tissue microarray, including 78 additional uterine tumor samples. Overall, with a cut-off of ≥10% of tumor cell staining as positive, the nuclear SATB2 score was negative in all endometrial stromal nodule samples (n=10) and positive in 83% of low-grade ESS samples (n=29/35), 40% of undifferentiated uterine sarcoma (n=4/10), 13% of leiomyosarcoma (n=2/16), 14% of adenosarcoma (n=3/22), and 8% carcinosarcoma (n=2/25) samples. Furthermore, in ESS patients, direct comparison of nuclear SATB2 scores with clinicopathologic parameters and other reported biomarkers such as progesterone receptor and estrogen receptor showed that nuclear SATB2 was associated with PR expression and a decreased risk of disease-specific death (odds ratio=0.06, 95% confidence interval=0.04-0.81, P=0.04). Our data suggest that SATB2 could be a marker with relative sensitivity (83%) for distinguishing between endometrial stromal nodule and ESS with potential prognostic value., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 by the International Society of Gynecological Pathologists.)

Müllerian adenosarcoma is an uncommon biphasic malignant tumor most often occurring in the uterine corpus and derived from native surface endometrium. We report a case of intramural uterine adenosarcoma arising in association with adenomyosis, in the absence of tumor involving the surface endometrium. This is an extremely rare phenomenon, with only 8 other published cases of uterine corpus adenosarcoma in the absence of surface endometrial involvement, 5 originating in adenomyosis and 3 in adenomyomas. We review these cases. The current FIGO staging system for uterine adenosarcoma assumes origin from the surface endometrium and does not address the rare occurrence of intramural tumors without a surface endometrial component. Such tumors are problematic to stage and could potentially be overtreated, particularly if there is deep myometrial involvement., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 by the International Society of Gynecological Pathologists.)

Mullerian adenosarcoma is a biphasic neoplasm composed of benign or atypical Müllerian epithelium and a malignant mesenchymal component that is usually, but not always, of low grade. Focal architectural or cytologic atypia of the epithelial component resembling atypical hyperplasia may uncommonly be present and foci of adenocarcinoma have been rarely reported. Whether the coexistence of these 2 tumor components is a result of independent primaries (collision tumor), adenocarcinoma arising from the epithelial component of the adenosarcoma, an unusual form of carcinosarcoma or some other mechanism is uncertain. To establish the diagnostic criteria and clinical significance of the coexistence of adenocarcinoma in close association with Müllerian adenosarcoma, we conducted a multi-institutional study of these rare tumors. Twenty-six patients were identified with "mixed" adenosarcoma and adenocarcinoma; they ranged in age from 43 to 87 years (median: 66 y). Tumors occurred in the uterine corpus (n=22), ovary (n=2), and the pelvis (n=2). All but 6 had International Federation of Gynecology and Obstetrics (FIGO) stage I disease. All extrauterine tumors were associated with endometriosis. The tumor size ranged from 2 to 25 cm (median: 7.9 cm). The sarcomatous component was of low grade in 18 and high grade in 8 (the majority demonstrating rhabdomyoblastic differentiation); 9 had stromal overgrowth. Twenty-five carcinomas were endometrioid in type (23 FIGO grade 1; 3 FIGO grade 2) and 1 carcinoma was dedifferentiated with FIGO grade 1 endometrioid adenocarcinoma component; 33% of the uterine neoplasms were associated with adjacent endometrial hyperplasia. Next-generation sequencing in 2 tumors identified similar molecular abnormalities in the sarcomatous and carcinomatous components supporting a clonal relationship. Of 10 patients with available follow-up (median: 18 mo), 8 had no evidence of disease and 2 died of recurrent sarcoma at 7 and 8 months. Endometrioid adenocarcinomas that arise in close spatial association with Müllerian adenosarcoma appear to be clonally related to the sarcoma. Unlike carcinosarcomas, these tumors are usually early stage at presentation. The prognosis appears to be driven by the sarcomatous component. These tumors should be distinguished from carcinosarcomas, dedifferentiated endometrial carcinomas, and corded and hyalinized endometrioid carcinomas., Competing Interests: Conflicts of Interest and Source of Funding: D.I.L. reports current full-time employment at Foundation Medicine which is a whole subsidiary of Roche. The remaining authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Gynecologic sarcomas are uncommon neoplasms, the majority occurring in the uterus. Due to the diverse nature of these, the description of "new" morphological types and the rarity of some of them, pathological diagnosis and treatment is often challenging. Finding genetic alterations specific to, and frequently occurring, in a certain type can aid in the diagnosis. DICER1 is a highly conserved ribonuclease crucial in the biogenesis of microRNAs and mutations in DICER1 (either somatic or germline) have been detected in a wide range of sarcomas including genitourinary embryonal rhabdomyosarcomas (ERMS) and adenosarcomas. Importantly, DICER1-associated sarcomas share morphological features irrespective of the site of origin such that the pathologist can strongly suspect a DICER1 association. A review of the literature shows that almost all gynecologic ERMS reported (outside of the vagina) harbor DICER1 alterations, while approximately 20% of adenosarcomas also do so. These two tumor types exhibit significant morphological overlap and DICER1 tumor testing may be helpful in distinguishing between them, because a negative result makes ERMS unlikely. Given that germline pathogenic DICER1 variants are frequent in uterine (corpus and cervix) ERMS and pathogenic germline variants in this gene cause a hereditary cancer predisposition syndrome (DICER1 syndrome), patients diagnosed with these neoplasms should be referred to medical genetic services. Cooperation between pathologists and geneticists is crucial and will help in improving the diagnosis and management of these uncommon sarcomas., (© 2020 Wiley Periodicals LLC.)

Extraskeletal Ewing sarcoma presenting as intra-abdominal or pelvic disease in adult female patients is very rare and may lead to diagnostic difficulty due to clinical and histologic overlap with Mullerian adenocarcinomas, which are far more common. We report a case of an intra-abdominal Ewing sarcoma in a postmenopausal female patient whose clinical and radiological presentation closely resembled that of peritoneal carcinomatosis. Biopsy of an omental nodule revealed numerous histologic features suggestive of a Mullerian carcinoma, including gland-like rosettes, strong, diffuse PAX8 immunoreactivity and cytokeratin expression. After excluding other differential diagnostic considerations, the possibility that this might represent an intra-abdominal Ewing sarcoma was entertained. Reverse transcriptase polymerase chain reaction testing demonstrated the presence of an EWSR1-ERG fusion transcript, confirming the diagnosis. The differential diagnostic considerations when dealing with this unusual clinical scenario and the uncommon yet important pitfall of PAX8 immunoreactivity in Ewing sarcoma are discussed., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 by the International Society of Gynecological Pathologists.)

Background: Uterine sarcomas are very rare tumours with different histotypes, molecular features and clinical outcomes; therefore, it is difficult to carry out prospective clinical trials, and this often results in heterogeneous management of patients in the clinical practice., Aim: We planned to set up an Italian consensus conference on these diseases in order to provide recommendations on treatments and quality of care in our country., Results: Early-stage uterine sarcomas are managed by hysterectomy + bilateral salpingo-oophorectomy according to menopausal status and histology; lymphadenectomy is not indicated in patients without bulky nodes, and morcellation must be avoided. The postoperative management is represented by observation, even though chemotherapy can be considered in some high-risk patients. In early-stage low-grade endometrial stromal sarcoma and adenosarcomas without sarcomatous overgrowth, hormonal adjuvant treatment can be offered based on hormone receptor expression. In selected cases, external beam radiotherapy ± brachytherapy can be considered to increase local control only. Patients with advanced disease involving the abdomen can be offered primary chemotherapy (or hormonal therapy in the case of low-grade endometrial stromal sarcoma and adenosarcoma without sarcomatous overgrowth), even if potentially resectable in the absence of residual disease in order to test the chemosensitivity (or hormonosensitivity); debulking surgery can be considered in patients with clinical and radiological response. Chemotherapy is based on anthracyclines ± ifosfamide or dacarbazine. Palliative radiotherapy can be offered for symptom control, and stereotactic radiotherapy can be used for up to five isolated metastatic lesions., Conclusions: Treatment of uterine sarcoma should be centralised at referral centres and managed in a multidisciplinary setting., Competing Interests: Conflict of interest statement On behalf of all the authors, there are no conflicts of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Aims: Tumours of the female genital tract with a combination of malignant Mullerian and germ cell or trophoblastic tumour (MMGC/T) components are usually diagnosed in postmenopausal women, and pursue an aggressive clinical course characterised by poor response to therapy and early relapses. These clinical features suggest that MMGC/T are somatic in origin, but objective molecular data to support this interpretation are lacking. This study evaluates the molecular features of nine MMGC/T, including seven tumours containing yolk sac tumour (YST), one tumour containing choriocarcinoma and one tumour containing epithelioid trophoblastic tumour. The objectives were to: (i) investigate whether MMGC/T show a distinct genetic profile and (ii) explore the relationship between the different histological components., Methods and Results: Next-generation sequencing of paired samples demonstrated that the mutational profile of the Mullerian and non-Mullerian components of the tumour were almost identical in all cases. Moreover, the driver mutations identified were those expected in the specific subtype of Mullerian component present in each case. In contrast, variants expected in postpubertal germ cell tumours and gestational trophoblastic tumours were not identified, and FISH for i(12p) was negative in all cases tested. In this study, mismatch repair-proficient MMGC/T (eight of nine) were characterised by a complex copy-number variant profile, including numerous focal, regional, arm-level and chromosome-level events., Conclusions: Comparison of paired samples supports that the YST and trophoblastic tumour components of MMGC/T have a somatic origin and often show numerous copy-number variants, suggestive of underlying genomic instability., (© 2020 John Wiley & Sons Ltd.)

Background: Uterine adenosarcoma, a rare uterine tumor subtype, is a biphasic tumor consisting of epithelial and mesenchymal elements. To date, there is no research comparing the histopathological features and immunohistochemistry of primary and recurrent tumors; furthermore, the relationship between pathology and the clinical course remains unclear. We reviewed the pathology and immunohistochemical features of patients with adenosarcoma and investigated the relevance of the histomorphological features to the clinical course. We also compared the immunohistochemical features of the primary and recurrent tumors., Methods: The data of seven patients with adenosarcoma who underwent surgery in our hospital were evaluated. We performed immunohistochemical staining for the progesterone receptor, estrogen receptor, p53, and two Switch/Sucrose Non-Fermentable chromatin remodeling proteins (SMARCA4, BCOR), which were recently developed for the undifferentiated sarcoma diagnosis in addition to conventional staining methods., Results: All patients had International Federation of Gynecology and Obstetrics stage IB-IC diseases. All tumors were polypoid and every patient presented with abnormal uterine bleeding. Six patients aged over 50 years and were menopausal; one patient aged under 50 years and was non-menopausal (average age: 59.1 years). Histologically, the sarcomatous components were homologous and heterogenous in six and one patient, respectively. Four and three cases were recurrent and non-recurrent, respectively. The recurrent patients showed high-grade morphology with sarcomatous overgrowth and were negative for ER and PR. Three recurrences could be evaluated by imaging, showing recurrence only in a distant area; biopsy specimens from these tissues revealed the identical mesenchymal component found in the primary tumor without a benign epithelial component. Immunohistochemical staining results were also similar to the corresponding of the original tumor, except for the p53 expression in one patient. At the primary site, p53 was overexpressed in two recurrent patients and had a wild-type level in one recurrent patient; however, all three recurrent tissues showed p53 overexpression. None of our patients showed SMARCA4 loss, and BCOR expression was positive in one case., Conclusions: Initial pathological adenosarcoma analysis with appropriate immunohistochemical staining is vital for prognostic assessment. p53 expression might increase at recurrence. SMARCA4 and BCOR might not be an index of malignancy.

Primary sarcoma of the liver (PSL) is a rare entity accounting for less than 1% of all liver cancers, with unknown aetiology. Several subtypes have been recognized, with histology playing an essential role in patient tailoring and management. We are about to report a case of an unusual PSL, with peculiar morphologic and immunohistochemical properties. A 65-year-old female with a multicystic hepatic lesion underwent surgery due to spontaneous rupture. Pathology revealed dilated bile duct-like structures lined by benign cuboidal/columnar epithelium surrounded by neoplastic proliferation of spindle and epithelioid cells with interspersed osteoclast-like multinucleated giant cells, loosely arranged in a storiform pattern, positive for CD10. The conjugation of morphology and immunohistochemistry results provided the diagnosis of primary biliary adenosarcoma of the liver, biliary type. The patient experienced tumour relapse and died of disease 2 years and 7 months later.

Aims: A unique fibrosarcoma-like tumour of the uterine cervix harbouring a rearrangement of a neurotrophic tyrosine kinase receptor (NTRK) gene (NTRK1 or NTRK3) has recently been described in 11 young women, some with recurrence and/or metastasis. The aims of this study were to expand the morphological spectrum of this tumour by reporting three additional cases that showed adenosarcoma-like features not previously described, one of which is the first reported to respond to targeted therapy, and to evaluate 19 conventional uterine adenosarcomas for evidence of NTRK rearrangement., Methods and Results: Three patients presented with a polyp or mass confined to the cervix. The constellation of polypoid growth, spindle cell morphology, entrapped endocervical glands and intraglandular stromal projections raised diagnostic consideration for adenosarcoma with stromal overgrowth. Deep cervical wall invasion was present in two cases at hysterectomy, and the third was removed by polypectomy. All three stained for S100 and pan-Trk, but were negative for a spectrum of other diagnostic markers. All three harboured NTRK rearrangements (TPM3-NTRK1, TPR-NTRK1, and SPECC1L-NTRK3). One patient developed pleural metastases at 16 months, received the NTRK inhibitor larotrectinib, and is free of disease 15 months later. Two others are alive without disease. None of the uterine adenosarcomas showed any S100 or pan-Trk staining, or rearrangement of NTRK1, NTRK2 or NTRK3 on next-generation sequencing., Conclusions: Unusual adenosarcoma-like spindle cell neoplasms of the cervix may represent an NTRK fusion sarcoma, which can be detected by S100 and pan-Trk staining and confirmed by NTRK molecular testing. Conventional uterine adenosarcomas do not harbour NTRK rearrangements., (© 2020 John Wiley & Sons Ltd.)

Adenosarcoma can mimic high-grade endometrial stromal sarcoma with ZC3H7B-BCOR fusion that may show entrapped glands and often exhibits diffuse BCOR expression. We encountered diffuse BCOR expression in rare adenosarcomas and sought to define its frequency among a larger cohort of these tumors. BCOR immunohistochemistry was performed on archival formalin-fixed paraffin-embedded tumor tissue in 13 of 14 adenosarcomas with and without stromal overgrowth arising in the uterus or ovary. The staining intensity and percentage of positive tumor nuclei in the mesenchymal component were evaluated. Eleven cases with sufficient tumoral tissue were subjected to fluorescence in situ hybridization for the detection of BCOR, BCORL1, NUTM1, ZC3H7B, and JAZF1 rearrangement. Three cases were subjected to targeted RNA sequencing. BCOR was expressed in 9 of 13 (70%) tumors, including 6 with and 3 without stromal overgrowth. Moderate to strong staining in >70% of cells was seen throughout in 1 low-grade and 6 high-grade tumors, 5 of which had stromal overgrowth. No staining was seen in 3 low-grade and 1 high-grade tumors with stromal overgrowth. One tumor demonstrating extensive sex cord-like differentiation and diffuse BCOR expression harbored JAZF1 and BCORL1 rearrangements. No BCOR or BCORL1 rearrangement was identified in the remaining tumors. BCOR expression is seen in most adenosarcomas with and without stromal overgrowth. BCORL1 rearrangement is seen in rare tumors with diffuse BCOR expression. Assessment of BCOR or BCORL1 rearrangement status is required in adenosarcomas demonstrating BCOR expression.

Embryonal rhabdomyosarcomas (ERMS) account for 2-3% of cancers in pediatric and adolescent populations. They are rarer in adults. We and others have reported that ERMS arising in the uterine cervix may harbor mutations in the gene encoding the microRNA biogenesis enzyme, DICER1, but a large series of cases has not been published. In the uterus, distinguishing ERMS from adenosarcoma can be very challenging, even for expert pathologists, and DICER1 alterations have been identified in a variable subset of uterine adenosarcomas. We hypothesized that DICER1 genetic testing may be useful in distinguishing between ERMS and adenosarcoma. We conducted a central pathology review-based study of 64 tumors initially thought to be uterine ERMS or adenosarcoma; 19 neoplasms had a consensus diagnosis of ERMS, 27 of adenosarcoma and for 18, no consensus diagnosis was reached. The median age at diagnosis was 30 years (range 2.5-69) for ERMS, 57.5 years (range 27-82) for adenosarcoma, and 65.5 years (range 32-86) for no consensus cases. In our series, the DICER1 mutation prevalence differed between the three groups: DICER1 alterations were present in 18/19 (95%) ERMS, 7/27 (26%) adenosarcomas (p < 0.001), and 4/18 (22%) no consensus cases. A germline alteration was present in 6/12 ERMS patients tested versus 0/6 adenosarcoma patients. Thus, although DICER1 mutations are near ubiquitous in uterine ERMS and are significantly less common in uterine adenosarcoma, DICER1 testing is only of value in distinguishing between the two neoplasms when a DICER1 mutation is absent, as this is helpful in excluding ERMS. On review of the clinical and radiological features of the single DICER1 wild-type cervical ERMS, this was thought most likely to be of vaginal origin. Given the significant prevalence of DICER1 germline pathogenic variants in uterine ERMS, all patients with this diagnosis should be referred to a genetics service.

Dedifferentiated carcinoma is defined as undifferentiated carcinoma coexisting with a second component of FIGO grade 1 or 2 endometrioid carcinoma. It is a rare entity with highly aggressive behavior. Dedifferentiated carcinoma combined with another primary uterine tumor is even rarer. We describe a case containing 3 different morphologies comprised of a dedifferentiated carcinoma associated with a low-grade endometrioid carcinoma coexisting with a low-grade Müllerian adenosarcoma. We also used targeted genomic analysis to show all 3 components arise from the same founding clone and identify novel mutations that drive tumor progression.

Background: Uterine sarcomas are mesenchymal tumors; they are rare, representing less than 2-3% of all uterine malignancies. Among them, we can define four types: leiomyosarcoma (LMS), endometrial stromal sarcoma (ESS), Adenosarcoma and Carcinosarcoma. This last type was recently reclassified by FIGO as a Mullerian type of the endometrial adenocarcinoma. Therefore, today only the first three types are histologically considered., Methods: In this paper, we reported a case of simultaneous presence of three different rare neoplasms in the same surgical specimen, resulting from a hysterectomy of a premenopausal woman. The woman presented to the ED with a six-months history of vaginal bleeding. Given the complexity of the clinical picture, we suggested hospitalization in our Department of Gynecology, to perform appropriate diagnostic tests. Because of the persistent hemorrhage and the absence of required fertility preservation, a laparotomic hysterectomy with bilateral annessiectomy was performed., Results: The postoperative histology of the specimen described the myoma at the fundus as a leiomyosarcoma. The myoma of the uterine anterior wall appeared as an endometrial stromal sarcoma of low-grade. Moreover, an intramural cavernous hemangioma of 3 cm in diameter was reported at the uterine corpus., Conclusion: All these described pathologies have no specific clinic characteristics; the most common symptom is abnormal uterine bleeding. To date, hysterectomy and bilateral salpingo-oophorectomy are the standards of care in the management of all early stage uterine sarcomas. To our knowledge, cases of LMS, ESS and cavernous haemangioma coexisting in the same patient have not been reported in literature to date. The pathogenesis of this combination remains to be elucidated. Key words: Cavernous hemangioma, Endometrial stromal sarcoma, Leiomyosarcoma, Uterine sarcomas.

Rationale: Uterine adenosarcoma (UA) with sarcomatous overgrowth (ASSO) is a rare and aggressive disease. Herein, wereported the case of a young patient with advanced uterine ASSO., Patients Concerns: A 29-year-old woman with the diagnoses of endometrial polyp and adenomyosis underwent hysteroscopic endometrial polypectomy for the giant endometrial polyp. Postoperative regular ultrasound scan indicated thickened endometriumand an ill-defined mass with continuous enlargement in the myometrium of the posterior wall of the uterus, which was considered as an adenomyoma. Two years after hysteroscopy, she was re-admitted due to lower abdominal distension and large pelvic mass. At that time, she had taken oral short-acting contraceptives for 2.5 years., Diagnoses: Magnetic resonance imaging (MRI) of the pelvis revealed an irregular mass with the size of 12*56*107 mm in the right annex area, without distinct border with the rectum, moreover, an uneven intrauterine echo that has no obvious boundary with uterine wall. Right ovarian cancer and adenomyoma were initially considered., Interventions: The patient received transperitoneal retroperitoneal pelvic combined with total viscera resection, including uterus, bilateral appendages and rectum, omentectomy, appendectomy, lymphadenectomy, and ileostomy. Postoperative pathology confirmed ASSO in the uterine cavity and muscular layer, the whole cervical duct and the right adnexal. She underwent 2 systemic chemotherapy sessions after the surgery. The chemotherapy regimen was ifosfamide 2.5 g day 1 to 3, with liposomal doxorubicin 40 mg day 1., Outcomes: The final diagnosis was uterine ASSO, International Federation of Gynecology and Obstetrics stage IVa. The patient has been following-up so far, with no progression., Lessons: Review of the case indicated that history of long-term oral short-acting contraceptives and giant endometrial polyps may be the high-risk factors for UA. For patients with high-risk factors, the follow-up ultrasound scan should be more frequently conducted. Moreover, 3D-ultrasound, MRI and outpatient hysteroscopy are recommended for routine screening. Placement of levonorgestrel-releasing intra-uterine system after hysteroscopy may be an effective intervention for patients with a high risk of giant polyps. Cluster of Differentiation 10, Estrogen receptor, Progesterone receptor, and nuclear antigen may be predictors for prognosis and selection of individualized treatment program.

Background: Müllerian adenosarcoma is a rare malignancy. These tumors occur mainly in the uterus, but also in extrauterine locations, usually related to endometriosis. Because of their rarity, there is limited data on optimal management strategies., Case Presentation: We present a 44-year-old woman with a history of endometriosis who consults for chronic pelvic pain. In the imaging tests, a heterogeneous mass is observed that impresses endometriosis, encompassing the uterus and left appendage. Surgery is performed by finding an extrauterine adenosarcoma that affected the uterus, ovary and bladder wall., Conclusion: This is a rare case but should be considered in a patient with atypical clinical characteristics or preoperative pathology, so we show the diagnostic and therapeutic strategies carried out for the resolution of the case.

Background: The management of adenosarcoma is based on the limited available data. This study aimed to explore the characteristics and oncologic outcomes of patients with uterine and cervical adenosarcoma., Materials and Methods: A total of 21 and 32 cases of cervical and uterine adenosarcoma, respectively, were retrospectively reviewed in Peking Union Medical College Hospital between April 2006 and March 2019., Results: The median follow-up time was 37.5 months (range, 1-153 months). The disease progression rate (DPR) was significantly higher in patients with uterine adenosarcoma compared with those with cervical adenosarcoma (28.1% vs. 4.8%). The curve of progression-free survival significantly differed. For those with cervical adenosarcoma, the presence of a tumor stalk was a protective factor, whereas heterologous elements (HE) presented a risk factor for disease progression. For those with uterine adenosarcoma, the presence of a tumor stalk was an independent protective factor, whereas lymphovascular space invasion (LVSI) was an independent risk factor for disease progression. Moreover, HE was an independent risk factor for mortality. Fertility-sparing surgery (FSS) was performed in four and five patients with cervical and uterine adenosarcoma, respectively. Regarding FSS, combined with cases in previous studies, the DPR of patients with uterine adenosarcoma was relatively higher compared with those with cervical adenosarcoma., Conclusion: We found that cervical adenosarcoma had a better prognosis than uterine adenosarcoma. The presence of a tumor stalk was a protective factor, whereas HE and LVSI were risk factors for prognosis. For those with uterine adenosarcoma, if FSS was administered, robust evaluation would be necessary. The small sample size limits the ability to make any strong conclusions about FSS., Implications for Practice: Uterine cervical adenosarcoma had a better prognosis than uterine adenosarcoma. For patients with cervical adenosarcoma, the presence of a tumor stalk was a protective factor and the presence of heterologous elements (HE) was a risk factor for disease progression. For those with uterine adenosarcoma, the presence of a tumor stalk was a protective factor and lymphovascular space invasion was a risk factor for disease progression. Moreover, HE was a risk factor for mortality. Regarding fertility-sparing surgery (FSS), the disease progression rate was higher in patients with uterine adenosarcoma compared with those with cervical adenosarcoma. For patients with uterine adenosarcoma, if FSS was administered, hysteroscopy and robust imaging evaluation would be necessary., Competing Interests: Disclosures of potential conflicts of interest may be found at the end of this article., (© AlphaMed Press 2019.)

Mullerian adenosarcoma with sarcomatous overgrowth (MASO) of the uterine cervix is an extremely rare variant of adenosarcoma of the genital tract associated with aggressive clinical course. We searched the PubMed and Medline databases for MASO of the cervix and we identified and reviewed eleven cases published between years 2004 and 2017. The most common clinical picture includes abnormal vaginal bleeding, postcoital bleeding, pelvic pain and foul-smelling vaginal discharge. Therapeutic options for MASO are still undefined. Radical hysterectomy with sufficient tumour-free margins combined with adjuvant chemotherapy and radiotherapy should serve as an effective treatment tool with favourable outcome., (Copyright © 2018. Published by Elsevier Inc.)

The spectrum of mesenchymal neoplasia in the uterus has expanded in recent years. First, the identification of prevalent, recurrent molecular alterations has led to a more biologically and clinically congruent classification of endometrial stromal tumors. Likewise, the diagnostic criteria of several rare and miscellaneous tumor types have been refined in recent case series (Perivascular Epithelioid Cell tumor, inflammatory myofibroblastic tumor). Pure mesenchymal tumors are still broadly classified based on morphology according to the tumor cell phenotype. Smooth muscle tumors predominate in frequency, followed by tumors of endometrial stromal derivation; the latter are covered in depth in this article with an emphasis on defining molecular alterations and their morphologic and clinical correlates. The remaining entities comprise a miscellaneous group in which cell derivation does not have a normal counterpart in the uterus (eg, rhabdomyosarcoma) or is obscure (eg, undifferentiated uterine sarcoma). This article discusses their clinical relevance, recent insights into their molecular biology, and the most important differential diagnoses. Regarding the latter, immunohistochemistry and (increasingly) molecular diagnostics play a role in the diagnostic workup. We conclude with a few considerations on intraoperative consultation and macroscopic examination, as well as pathologic staging and grading of uterine sarcomas as per the most recent American Joint Cancer Commission and the Fédération Internationale de Gynécologie et d'Obstétrique staging systems., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: To present the case of a patient diagnosed with high grade adenosarcoma of the endocervix and the endometrial cavity, with a heterologous component, and to conduct a review of the literature focusing on the diagnosis and therapeutic management of this disease condition., Materials and Methods: We present the case of a 31-year-old female patient who came to Virgen Macarena University Hospital of Seville, a Level III regional institution, complaining of genital bleeding arising from an endocervical polypoid mass. The biopsy of the mass revealed a high grade, poorly differentiated leiomyosarcoma of the endocervix. The patient was taken later to total abdominal hysterectomy. The study of the surgical specimen provided the following result: adenosarcoma of the endocervix and endometrial cavity with a heterologous rhabdomyosarcoma component. A search was conducted in the Medline database via Pubmed using the terms "adenosarcoma," "endocervical," "cervix," "uterus," "heterologous." The search in- cluded literature review articles, case reports and clinical case series describing aspects of cervical adenosarcoma and the heterologous rhabdomyosar- coma component, published in English and Spanish since 1974., Results: Six articles corresponding to literature reviews, case reports or case series in which the most relevant aspects of the diagnosis and treatment of this disease condition are described were retrieved., Conclusions: This condition is characterized, on occasions, by rapid and aggresive growth, hence the importance of early diagnosis and optimal treatment based on a combination of surgery, radiation therapy and chemotherapy. However, due to its low prevalence, further studies are needed in order to confirm these data., Competing Interests: None declared, (Copyright© 2019 This is an open-access article distributed under the terms of the Creative Commons Attribution License by-nc-nd/4.0.)

Müllerian adenosarcomas are biphasic epithelial-mesenchymal tumors with benign epithelial and malignant mesenchymal components. The sarcoma component may be low or high grade; the latter is often seen in the presence of stromal overgrowth, which correlates with worse clinical outcome. Heterologous differentiation may also occur, usually in association with stromal overgrowth. DICER1 mutations have been reported primarily in a small subset of adenosarcomas with rhabdomyosarcomatous elements, but whether these are specific to the rhabdomyosarcomatous phenotype is unclear. In this study, we examined the clinical, pathologic, and genomic features of 19 müllerian adenosarcomas enriched for tumors with rhabdomyosarcomatous differentiation, as well as eight uterine carcinosarcomas with a rhabdomyosarcoma component. Somatic hotspot mutations in the RNase IIIb domain of DICER1 were identified in 8/19 (42%) adenosarcomas, of which four showed rhabdomyosarcomatous differentiation. DICER1 mutations were detected in 4/6 (67%) cases with a rhabdomyosarcoma component and in 4/11 (36%) cases without rhabdomyosarcoma. At least two DICER1 mutations were identified in 7/8 (88%) tumors, of which four had a truncating mutation. The hotspot DICER1 mutation in the remaining tumor was hemizygous and associated with loss of heterozygosity. Other less frequent recurrent somatic pathogenic alterations included Ras or PI3K/PTEN pathway aberrations (5/19 each, 26%), CDK4/MDM2 amplifications (3/19, 16%), and mutations in TP53 (3/19) and ARID1A (3/19). Two tumors demonstrated homozygous BAP1 deletion. One tumor harbored an ESR1-NCOA3 fusion gene. Carcinosarcomas with rhabdomyosarcomatous differentiation showed frequent mutations in TP53 (7/8, 88%) and the PI3K/PTEN pathway (6/8, 75%) but lacked DICER1 mutations. The findings highlight the importance of DICER1 mutations in müllerian adenosarcoma tumorigenesis and show that these alterations are not exclusive to heterologous rhabdomyosarcomatous differentiation.

Mullerian adenosarcoma is a rare biphasic malignant neoplasm of cervix characterized by an admixture of benign epithelial elements and a malignant sarcomatous stromal component, which may be either homologous or heterologous. Mullerian adenosarcoma with stromal overgrowth (MASO) in an aggressive variant of adenosarcoma, which is extremely rare with only two such cases reported till date. In this report, we present a case of MASO of cervix with heterologous elements in a 55/F presenting with postmenopausal bleeding. As it commonly simulates clinically and radiologically as benign cervical polyp, the gynecologists and pathologists should be aware of this extremely rare entity presenting with aggressive clinical course., Competing Interests: None

In this study, we summarize the clinical role of magnetic resonance imaging (MRI) in the diagnosis of patients with malignant uterine neoplasms, including leiomyosarcoma, endometrial stromal sarcoma, adenosarcoma, uterine carcinosarcoma, and endometrial cancer, with emphasis on the challenges and disadvantages. MRI plays an essential role in patients with uterine malignancy, for the purpose of tumor detection, primary staging, and treatment planning. MRI has advanced in scope beyond the visualization of the many aspects of anatomical structures, including diffusion-weighted imaging, dynamic contrast enhancement-MRI, and magnetic resonance spectroscopy. Emerging technologies coupled with the use of artificial intelligence in MRI are expected to lead to progressive improvement in case management of malignant uterine neoplasms., Competing Interests: Conflicts of Interest: The authors have no financial conflicts of interest.

Introduction: Uterine adenosarcoma is a rare tumor with both epithelial and stromal components. Standard treatment is total abdominal hysterectomy and bilateral salpingo-oophorectomy. There is no defined role for adjuvant or neoadjuvant chemotherapy or radiation. There is a misconception that this is an indolent, low-grade sarcoma. In fact, at least 50% of patients will develop disease recurrence. Establishing prognostic factors is of paramount importance. Areas covered: This article reviews the current literature regarding adenosarcoma prognostic factors from case reports, case series, and retrospective series. An extensive review of the literature was undertaken via PubMed and Medline searches, relevant articles are included in this review. Expert commentary: The most important prognostic factors of uterine adenosarcoma are age, presence of sarcomatous overgrowth, presence of myometrial invasion, presence of lymphovascular invasion, and lymph node involvement. These factors can be used to accurately prognosticate for uterine adenosarcoma patients. Patients at low risk of disease recurrence can be identified. These patients require observation alone. Patients at high risk of disease recurrence can be identified and are candidates for aggressive therapy with adjuvant chemotherapy to reduce the risk of disease recurrence.

Uterine sarcomas account for approximately 3%-7% of all uterine cancers. Since carcinosarcomas are currently classified as metaplastic carcinomas, leiomyosarcomas remain the most common subtype. Exclusion of several histologic variants of leiomyoma, as well as atypical smooth muscle tumors (so-called "smooth muscle tumors of uncertain malignant potential"), has highlighted that the vast majority of leiomyosarcomas are high-grade tumors associated with poor prognosis even when apparently confined to the uterus. Low-grade endometrial stromal sarcomas are indolent tumors associated with long-term survival. High-grade endometrial stromal sarcomas and undifferentiated endometrial sarcomas behave more aggressively than tumors showing nuclear uniformity. Adenosarcomas have a favorable prognosis except for tumors showing myometrial invasion or sarcomatous overgrowth. The prognosis for carcinosarcomas (which are considered here in a postscript fashion) is usually worse than that for grade 3 endometrial carcinomas. Tumor stage is the single most important prognostic factor for uterine sarcomas., (© 2018 The Authors. International Journal of Gynecology & Obstetrics published by John Wiley & Sons Ltd on behalf of International Federation of Gynecology and Obstetrics.)

Objective: This retrospective study examined the clinicopathologic features of adenosarcoma patients to determine potential prognostic factors and retrospectively evaluated overall survival (OS), disease-free survival (DFS), and local recurrence-free survival (LRFS) after primary treatment of adenosarcoma including surgery, radiation, and chemotherapy., Methods: One hundred sixty-five patients with adenosarcoma were identified from the MD Anderson Cancer Center tumor registry between 1982 and 2014. Clinical data were collected retrospectively. Pathologic characteristics were examined by sarcoma pathologists. We used the Kaplan-Meier method to estimate OS, DFS, and LRFS. The log-rank test was performed to test the difference in survival between groups. Multivariate regression analyses of survival data were conducted using the Cox proportional hazards model., Results: Median OS and DFS for all patients were 8.5 and 4.7 years, respectively. Pathologic characteristics that influence OS and DFS were sarcomatous overgrowth (SO), myometrial invasion (MI), lymphovascular invasion (LVI), tumor size, number of mitosis, estrogen receptor, progesterone receptor, International Federation of Gynecology and Obstetrics (FIGO) stage, age, and resection status. Median OS for adenosarcoma patients with SO was 5.2 versus 14.5 years for patients without SO (P < 0.0001). Median OS for adenosarcoma patients with MI was 5.8 years versus not reached for patients without MI (P = 0.0005). Median OS for adenosarcoma patients with LVI was 1.0 versus 8.9 years for patients without LVI (P = 0.0021). On Cox analysis for OS and DFS and LRFS, only SO, MI, LVI, age, resection status, and FIGO stage remained significant. There was no difference in OS or LRFS for adjuvant radiation versus no adjuvant radiation (P = 0.17, P = 0.076)., Conclusions: This study highlights the importance of LVI as a prognostic factor and confirms the prognostic significance of SO, MI, age, resection status, and FIGO stage for adenosarcoma. Furthermore, this study suggests that there is no additional benefit to adjuvant radiation. The standard-of-care treatment for adenosarcoma should remain total abdominal hysterectomy bilateral salpingo-oophorectomy +/- lymphadenectomy and no adjuvant radiation.

Objective: To assess the clinicopathological characteristics and clinical management of patients diagnosed with mullerian adenosarcoma of the uterine cervix., Materials and Methods: Records of six patients surgically treated for cervical mullerian adenosarcoma were reviewed., Results: The median age of the patients was 50 years (range, 17-74). Four patients presented with vaginal bleeding and two of them had watery discharge as the primary symptoms. Three nulliparous patients who hoped to preserve their uterus were included in this study and only one of the three patients received fertility-preservation surgery. Five patients underwent hysterectomy (simple in 3, modified radical in 2) with bilateral salpingo-oophorectomy or bilateral salpingectomy. One patient underwent conization of the cervix to preserve her fertility as there was no sarcomatous overgrowth, heterologous elements, or deep cervical stromal invasion. A recurrence of cervical mullerian adenosarcoma with sarcomatous overgrowth was observed in one patient who underwent simple hysterectomy., Conclusion: The presence of sarcomatous overgrowth and deep cervical stromal invasion are associated with poor prognosis. Along with adequate counseling, fertility-preservation surgery may be an acceptable option for exophytic cervical mullerian adenosarcoma in the cases that do not show sarcomatous overgrowth and deep cervical stromal invasion., (Copyright © 2018. Published by Elsevier B.V.)

Mullerian adenosarcoma (MA) of ovary with sarcomatous (rhabdomyoblastic) overgrowth is an extremely rare malignant type of female genital tract neoplasm. These tumours are highly aggressive and presence of heterologous elements is associated with worse prognosis. A 44 year old female presented with lower abdominal pain and distension. She had history of removal of tumour from pouch of Douglas in 2006 for which she did not receive any additional treatment nor did she keep continuous follow up. Current preoperative radiological examination revealed bilateral ovarian masses. She underwent abdominal hysterectomy with bilateral oophorectomy. Microscopic examination revealed biphasic tumours exhibiting sarcomatous overgrowth with rhabdomyoblastic differentiation. Review of the previous biopsy revealed low grade Mullerian adenosarcoma without sarcomatous overgrowth. Hence the current tumour was considered recurrent. This report highlights the aggressive nature of MA even with low grade morphological features and emphasizes the importance of continuous follow up and additional treatment.

Aim: Uterine adenosarcoma is a rare malignancy with limited cohort data in Asian countries. This study evaluated the clinicopathologic features of Japanese patients with uterine adenosarcoma and their potential treatment challenges., Methods: A retrospective chart review was performed at the National Cancer Center Hospital, Japan from 2000 to 2016. A literature search for Japanese cases of uterine adenosarcoma was conducted using PubMed, Japanese Central Review of Medicine, and the Annual of Pathological Autopsy Cases in Japan. Only histologically confirmed cases of uterine adenosarcoma were included. All collected data were analyzed., Results: A total of 110 cases was identified (6 from our hospital and 104 from the literature review). Most baseline characteristics were similar to those reported in western countries. Death due to the disease was observed in 34% (29/86) of patients, whereas patients with stage IA disease showed a 13% (4/30) recurrence rate and a 3.3% (1/30) mortality rate. Preoperative radiological and pathological examinations occasionally failed to help reach the correct diagnosis. In cases of sarcomatous overgrowth, the recurrence and mortality rates were 45% (9/20) and 35% (7/20), respectively. Distant recurrence occurred in 44% (12/27) of cases, 75% of which included lung metastasis., Conclusions: This study showed the clinicopathologic features of Japanese patients with uterine adenosarcoma and suggested potential solutions for improving prognosis including early treatment based on a timely diagnosis, the development of effective adjuvant therapy for patients at high risk of recurrence, and optimal follow-up focusing on late recurrence and lung metastasis., (© 2018 John Wiley & Sons Australia, Ltd.)