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.

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.

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.

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.

Prognostic factors in patients with uterine sarcoma: the SARCUT study.

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.

[Uterin adenosarcoma: French Guidelines of the French Sarcoma Group and the Rare Gynecologic Tumor Group]. / Adénosarcomes mullériens de l'utérus ­ référentiels de prise en charge du GSF-GETO/NETSARC+ et du groupe TMRG.

Uterine adenosarcoma is a very rare malignancy defined as a biphasic tumor composed of both benign epithelial component and a malignant sarcoma component. The stage of the disease is determined by the presence of myometrial invasion and the extent of extra-uterine disease. The most important histopronostic factors are the existence of a sarcomatous overgrowth defined by a sarcomatous contingent occupying more than 25 % of the volume of the tumor (directly correlated to the grade of the disease), the presence of a heterologous and/or a high-grade component. Stage I adenosarcomas without sarcomatous overgrowth have a good prognosis, with an overall 5-year survival of up to 80 %. In localized disease, complete surgical removal is recommended. The role of hormone therapy, chemotherapy and adjuvant radiotherapy is not established. If possible, relapses should be re-treated surgically, with the aim of achieving complete resection. In the advanced inoperable or metastatic setting, hormone therapy is an option for low-grade adenosarcomas with estrogen receptor (ER) and progesterone receptor (PR) overexpression. For high-grade tumors, the standard chemotherapies are doxorubicin-based combinations, although an integrated approach of surgery and medical treatment should also be considered in this setting.

Differential diagnosis of uterine adenosarcoma: identification of JAZF1-BCORL1 rearrangement by comprehensive cancer genomic profiling.

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.

Microsatellite Instability Status and the Expression of p16 and Cyclin D1 Proteins in Uterine Adenosarcoma and Their Clinicopathological Significance.

OBJECTIVE: Uterine adenosarcoma has low malignant potential, except in cases with sarcomatous overgrowth (SOG) and a high-grade morphology. We here point out the prognostic clinicopathological and immunohistochemical features as well as the microsatellite instability (MSI) status of high- and low-grade adenosarcomas. MATERIAL AND METHOD: In this study, DNA mismatch repair proteins, p16, cyclin D1, ER, PR, and CD10 were examined in uterine adenosarcoma cases using immunohistochemistry. The association between these proteins and clinicopathological parameters was also evaluated. RESULTS: ER, PR and CD10 expressions were lower and weaker in high-grade adenosarcomas with SOG compared to low-grade adenosarcomas without SOG (p < 0.05). p16 positivity was more frequent in high-grade adenosarcomas than low-grade adenosarcomas (p < 0.05). There was no statistically significant difference between cyclin D1 positivity, MSI, and other clinicopathological parameters (p ≥ 0.05). Cyclin D1 positivity and loss of CD10 expression were associated with shorter disease-free survival (DFS). Loss of ER and CD10 expression was associated with shorter overall survival (OS) (p < 0.05). MSI was not associated with DFS or OS (p ≥ 0.05). CONCLUSION: These results suggested that p16 positivity, and loss of ER, PR, and CD10 expression were predictors of high-grade morphology. Additionally, the current study showed that cyclin D1-positive tumors had high recurrence rates; however, no significant relationships were found between MSI and DFS or OS in patients with uterine adenosarcoma. Further investigations are required to determine the importance of p16, cyclin D1, and MSI in uterine adenosarcomas.

Malignant Mixed Mullerian Tumor Arising from Endometriosis in the Groin: A Case Report and Literature Review.

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.

The Overexpression of Programmed Death-Ligand 2 in Uterine Adenosarcoma: Correlation with High-Grade Morphology, Mutant Type TP53 Expression and Clinical Outcomes.

Immunotherapy involving the programmed death-1 (PD-1)/the programmed death-ligand (PD-1/PD-L) blockade is an understudied tumor therapy approach in cases of adenosarcoma. PD-L1 and PD-L2, and tumor protein p53 (p53) were examined in 20 uterine adenosarcoma cases, and tumor-infiltrating lymphocytes and tumor-associated macrophages were counted in tumor tissue using immunohistochemistry. While CPS PD-L1 positivity with 1% and 10% cut-off values was observed in 40% and 10% of tumors, respectively, CPS PD-L2 positivity with 1%, 10% and 50% cut-off values was observed in 100%, 85% and 50% of the tumors, respectively. The CPS PD-L2 positivity with a 50% cut-off value was positively correlated with tumor grade and the presence of sarcomatous overgrowth and lymphovascular invasion (LVI) (p = 0.025, p = 0.025, and p = 0.025, respectively). Nine of 11 high-grade adenosarcomas and none of the low-grade adenosarcomas showed mutant type p53 expression (p = 0.000). However, PD-L1 expression and tumor-infiltrating immune cells did not correlate with clinicopathological parameters. The CPS PD-L2 positivity with a 50% cut-off value was also positively correlated with mutant type p53 expression (p = 0.024) and tumor-associated macrophages density (p = 0.024). The CPS PD-L2 positivity with a 50% cut-off value and mutant type p53 expression were associated with shorter disease-free survival and shorter overall survival. The high density of tumor-associated macrophages and low density of tumor-infiltrating lymphocytes were also associated with shorter disease-free survival and overall survival (p < 0.05).These results suggested that the CPS PD-L2 positivity with a 50% cut-off value, p53 mutation and tumor microenvironment played an essential role in the progression of uterine adenosarcomas.

Epidemiology of adenosarcoma and the inverse probability of treatment weighting (IPTW) adjusted survival analysis of lymph node dissection in uterine adenosarcoma.

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.

Mullerian adenosarcoma: clinicopathologic and molecular characterization highlighting recurrent BAP1 loss and distinctive features of high-grade tumors.

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.

Embryonal Rhabdomyosarcoma of the Uterine Cervix: A Clinicopathologic Study of 94 Cases Emphasizing Issues in Differential Diagnosis Staging, and Prognostic Factors.

Embryonal rhabdomyosarcoma of the uterine cervix (cERMS) is rare and frequently associated with DICER1 mutations. We report 94 tumors that arose in patients aged 7 to 59 (median=23) years and presented with vaginal bleeding (52), protruding vaginal mass (17), cervical polyp (8), or expelled tumor fragments per vagina (5). Nine had DICER1 syndrome, 8 of whom had other syndromic manifestations including ovarian Sertoli-Leydig cell tumor (7), multinodular goiter (3), pleuropulmonary blastoma (2), pineoblastoma (1), and osteosarcoma (1). Syndromic patients were younger than nonsyndromic patients (16 vs. 24 y). Tumor size ranged from 2 to 24 (median=4.5) cm. Ninety-two tumors were polypoid, most being grape-like (77 of 92). They were characterized by aggregates of primitive cells, almost always exhibiting a cambium layer, within a variably myxoedematous stroma and were hypocellular (63), moderately cellular (22), or hypercellular (9). Entrapped glands, typically scant, were present in 84 tumors. Primitive hyperchromatic ovoid to spindled cells with minimal cytoplasm predominated but differentiated rhabdomyoblasts with abundant eosinophilic cytoplasm (having cross-striations in 30) were seen in 83 tumors; they were often sparse but predominated in three. Nine tumors showed areas of intersecting fascicles and 4 zones with densely cellular (solid) growth. Cartilage was present in 38. Anaplasia was seen in 15 tumors, as was necrosis. Mitotic activity ranged from 1 to 58/10 high-power fields (median=8). The varied microscopic features resulted in a spectrum of differential diagnostic considerations, mainly typical and cellular forms of fibroepithelial polyps, Mullerian adenosarcoma, and other sarcomas. Follow-up was available for 79 patients ranging from 6 to 492 (median=90) months. Treatment information was available in 62 and included polypectomy in 6 patients (2 also received chemotherapy), limited resection in 26 (14 also received chemotherapy), hysterectomy in 29 (15 with adjuvant chemotherapy), and biopsies only in 1 (with chemotherapy). Staging was possible in 56 tumors; according to the "uterine sarcoma" system (tumor size and extent) they were: stage I (10/56; could not be further subclassified as size not available), IA (22/56), IB (18/56), IIA (2/56), IIB 3/56), IIIC (1/56). According to the "adenosarcoma" system (depth of invasion and extent) they were: stage IA (26/56), IB (14/56), IC (10/56), IIA (2/56), IIB (3/56), IIIC (1/56). Eight patients had local recurrence following incomplete excision (10%). Eleven of 79 patients had extrauterine recurrences (14%) and 9 died of disease (11%). Older age was associated with extrauterine recurrence (median 44 vs. 22; P =0.002) and decreased disease-specific survival (median 44 vs. 22; P =0.02). For patients with tumors initially confined to the cervix, the adenosarcoma staging system was superior to the uterine sarcoma staging system for predicting survival ( P =0.02). Three patients with DICER1 syndrome who underwent fertility-preserving surgery developed a second primary cERMS 7, 7, and 12 years after their primary tumor. All 9 patients with DICER1 syndrome had tumors confined to the cervix and none died of disease. This study highlights the intriguing clinical aspects of cERMS including its long-known tendency to occur in the young but also more recently appreciated association with DICER1 syndrome. Establishing the diagnosis may still be difficult because of the hazard of sampling a neoplasm which in areas may appear remarkably bland and also because of its potential confusion with other neoplasms. This study indicates that this tumor has a good prognosis at this site and in selected cases a conservative surgical approach is a realistic consideration.

Uterine Adenosarcoma in a Teen Ager.

Uterine adenosarcoma is a rare tumor composed of benign epithelium in combination with malignant mesenchymal components. Misdiagnosis is common due to the lack of specific clinical manifestations and the rarity of such tumors in young age groups. The mean age at diagnosis is 58.6 years, and <10% of patients are younger than 40 years. Herein, we describe a case of a 19-year girl who presented with worsening menorrhagia. Her ultrasound revealed multiple heterogeneous masses in the uterine cavity. Intraoperatively, a small piece of grayish-white tumor tissue was sent for the frozen section, but the results did not confirm malignancy. She underwent hysteroscopy, laparoscopic hysterectomy, and bilateral salpingo-oophorectomy. Histopathologic examination finally confirmed uterine adenosarcoma. The patient had no evidence of residual tumor or recurrence during six months of follow-up. Key Words: Uterus, Adenosarcoma, Mixed tumor.

The first successful treatment and genetic sequencing of primary hepatic adenosarcoma with sarcomatous overgrowth: a case report.

Adenosarcoma is a rare type of tumor with a mixture of epithelial and stromal components and often occurs in the female reproductive system. Primary hepatic adenosarcoma (PHAS) is extremely rare, with only two cases reported so far. Both patients had poor outcomes. Here, we report the case of a 36-year-old man with pain under the xiphoid process who was diagnosed with a bile duct tumor. He was treated with adjuvant radiotherapy when surgery was performed on him. Pathologically, the tumor contained benign epithelial tissue, and the submucosa of the bile duct in the liver showed infiltrating growth of spindle cell components. The cells were dense, mildly heterotypic, and occasionally mitotic, and the patient was diagnosed with PHAS. Whole-exome sequencing results showed that a total of 12 mutations were shared by the two tissues. The patient received adjuvant radiotherapy and he was tumor-free until 31 months postoperatively. This case will provide some references of the disease to other researchers.

Primary Fallopian Tube Mullerian Adenosarcoma With Sarcomatous Overgrowth and a Previously Unreported MEIS1-NCOA2 Gene Fusion.

Extrauterine Mullerian adenosarcomas (MA) are rare and often associated with endometriosis. We report a 55-yr-old patient seen in consultation for abdominal pain and bloating. Imaging was suggestive of a left adnexal mass and "peritoneal carcinomatosis". Pathological examination of the specimen revealed a MA arising in the left fallopian tube, with sarcomatous overgrowth, diffuse peritoneal involvement and omental "caking". Next-generation sequencing identified a MEIS1-NCOA2 gene fusion, previously unreported in MA.

Atypical uterine polyps show morphologic and molecular overlap with mullerian adenosarcoma but follow a benign clinical course.

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.

Unusual uterine cervical polypoid mass presenting during pregnancy.

The authors encountered a case of uterine cervical adenosarcoma with sarcomatous overgrowth during pregnancy. Cytological images of atypical stromal cells in sarcoma components were obtained in this case.