Uterine Adenosarcoma Research Articles

The Impact on Survival of an Extensive Sex Cord-like Component in Mullerian Adenosarcomas: A Study Comprising 6 Cases.

Mullerian adenosarcomas are uncommon tumors of the female genital tract characterized by a synchronous proliferation of benign glands and sarcomatous stroma. In general, uterine Mullerian adenosarcomas are associated with a low risk of recurrence. The presence of "stromal overgrowth" (SO), historically defined by an estimate of the volume of sarcoma growing independently of epithelium, is associated with deep myometrial invasion, presence of heterologous elements, and poor outcomes. Very rarely, the stromal component can harbor foci resembling ovarian sex cord tumors (FROSCT). The aim of this study was to determine whether the presence of an extensive FROSCT component in Mullerian adenosarcomas has an impact on survival, akin to more typical types of SO. Six patients were included in this study. Age ranged from 39 to 71 yr. Five patients presented with uterine lesions (4 intracavitary, 1 isthmic), and 1 was located in the ovary. Tumors ranging in size from 2.5 to 19 cm were all diagnosed as Stage I. Morphologically, all had prominent FROSCT-like components that comprised 60% to 90% of tumor volume. Immunohistochemically, the FROSCT component was positive for CAM 5.2, vimentin, WT1, CD56, α-inhibin, calretinin, androgen and progesterone receptors, α-actin, and desmin. All patients are alive without disease at 26 to 102 mo. Compared with adenosarcomas with typical forms of SO, FROSCT overgrowth is low grade and not associated with recurrence or metastasis in this small series. Therefore, Mullerian adenosarcoma with extensive FROSCT should not be equated with SO.

A Case of Solitary Brain Metastasis from Uterine Mullerian Adenosarcoma with Sarcomatous Overgrowth.

Uterine adenosarcoma (AS) are rare tumors and have more favorable outcomes than the aggressive uterine carcinosarcomas. Uterine adenosarcoma with sarcomatous overgrowth (ASSO) is a variant form of AS and exhibits aggressive growth of tumor and the prognosis is relatively poor compared with typical AS. Usually patterns of metastasis have been known to behave like endometrial carcinoma and spread through the lymphatics. Brain metastasis from uterine AS is extremely rare. Herein, we report a case of successfully surgically removed solitary brain metastasis without any extracranial recurrence from uterine ASSO after 4 years of primary treatment.

Uterine adenosarcomas are mesenchymal neoplasms.

Uterine adenosarcomas (UAs) are biphasic lesions composed of a malignant mesenchymal (ie stromal) component and an epithelial component. UAs are generally low-grade and have a favourable prognosis, but may display sarcomatous overgrowth (SO), which is associated with a worse outcome. We hypothesized that, akin to breast fibroepithelial lesions, UAs are mesenchymal neoplasms in which clonal somatic genetic alterations are restricted to the mesenchymal component. To characterize the somatic genetic alterations in UAs and to test this hypothesis, we subjected 20 UAs to a combination of whole-exome (n = 6), targeted capture (n = 13) massively parallel sequencing (MPS) and/or RNA sequencing (n = 6). Only three genes, FGFR2, KMT2C and DICER1, were recurrently mutated, all in 2/19 cases; however, 26% (5/19) and 21% (4/19) of UAs harboured MDM2/CDK4/HMGA2 and TERT gene amplification, respectively, and two cases harboured fusion genes involving NCOA family members. Using a combination of laser-capture microdissection and in situ techniques, we demonstrated that the somatic genetic alterations detected by MPS were restricted to the mesenchymal component. Furthermore, mitochondrial DNA sequencing of microdissected samples revealed that epithelial and mesenchymal components of UAs were clonally unrelated. In conclusion, here we provide evidence that UAs are genetically heterogeneous lesions and mesenchymal neoplasms.

Mullerian adenosarcoma of the uterus associated with tamoxifen treatment for breast cancer

Mullerian adenosarcoma following tamoxifen therapy is a rare condition. Our aim was to report the youngest patient in the literature with uterine mullerian adenosarcoma who was undergoing tamoxifen therapy for breast cancer. A premenopausal woman aged 38 years who was undergoing tamoxifen therapy for breast cancer, was admitted with symptoms of lower abdominal pain and irregular vaginal bleeding and malodorous vaginal discharge that had continued for at least 6 months. A pelvic examination revealed a large and malodorous polypoid mass protruding through the cervix and an enlarged uterus. A biopsy from the protruding polypoid mass was reported as a large area of necrosis with neoplastic mesenchymal cells. The patient underwent a total abdominal hysterectomy, bilateral salpingo-oopherectomy, pelvic-paraaortic lymph node dissection, and omentectomie. The histologic diagnosis was Mullerian adenosarcoma. As a result, she was discharged to the oncology department. The woman is alive and her chemoradiotherapy treatment is ongoing.The role of tamoxifen therapy in the development of endometrial neoplasms remains unclear, but all cases of endometrial thickening and vaginal bleeding must be investigated for Mullerian adenosarcoma in tamoxifen users.

Uterine sarcomas.

Uterine sarcomas.

Abstract 5257: Immunohistochemical analysis and comprehensive hormone receptor profiling of uterine adenosarcomas at a single institution

Abstract Uterine adenosarcomas (AS) are rare uterine tumors with benign epithelium and a sarcomatous component which is typically low-grade. Those displaying sarcomatous overgrowth (AS+SO) behave in a more aggressive fashion and are associated with worse clinical outcomes. Immunohistochemistry performed on AS and AS+SO have shown a greater preponderance for estrogen receptor alpha (ERα) and progesterone receptor (PR) positivity in those with a low-grade sarcomatous component. Further studies showed an increased proliferative index (Ki-67) in AS+SO and confirmed loss of expression in ER/PR in addition to loss of CD10. Expression of estrogen receptor beta (ERβ), a classic estrogen receptor as well as G protein-coupled estrogen receptor (GPER), a receptor that interacts with estrogen independently of the classic receptors, has been reported in uterine carcinosarcomas and they are associated with advanced stage disease. We conducted this study to analyze the receptor status of ERβ and GPER in cases of uterine AS. An H-score was calculated as the product of intensity and the percentage of cells staining positive (0-100%), higher scores indicate increased intensity and a greater number of positive cells. Unpaired t-test was used to compare the mean H-scores of receptor expression between low-grade AS (LG-AS) and high-grade AS (HG-AS). Mean age of diagnosis was 59.4 ± 11.9 years, mean BMI of 34.2 ± 8.5, and median disease free survival was 18 months (range 2-113 months). There were 7 cases of LG-AS and 3 cases of HG-AS, 2 cases displayed SO. Seven cases were stage IA, two were IB and one stage IV. There was a significant difference (p = 0.01) between the mean H-score for ERα between LG-AS (203) and HG-AS (1.7), There was also a significant difference (p = 0.04) in mean H-score for PR between LG-AS (188.6) and HG-AS (18.3). ERβ and GPER expression were retained in the HG-AS at similar levels as in the LG-AS, thus there was no difference in mean H-scores. In one patient with HG-AS and recurrent disease after 2 years, the recurrent tumor remained negative for ERα and PR, and showed somewhat decreased ERβ expression. Although the sample size is small, this is the first report of comprehensive estrogen receptor profiling in this uncommon uterine tumor. Citation Format: Jenna R. Zechmeister, Gloria S. Huang, Rouzan Karabakhtsian, Melissa Schwartz, Eric R. Prossnitz, Gary L. Goldberg, Merieme Klobocista. Immunohistochemical analysis and comprehensive hormone receptor profiling of uterine adenosarcomas at a single institution. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5257. doi:10.1158/1538-7445.AM2015-5257

Uterine adenosarcoma with omentum metastasis complicated by a rapidly progressing liver abscess

Uterine adenosarcoma with omentum metastasis complicated by a rapidly progressing liver abscess

Müllerian Adenosarcoma of the Uterus With Low-grade Sarcomatous Overgrowth Characterized by Prominent Hydropic Change Resulting in Mimicry of a Smooth Muscle Tumor

Müllerian Adenosarcoma of the Uterus With Low-grade Sarcomatous Overgrowth Characterized by Prominent Hydropic Change Resulting in Mimicry of a Smooth Muscle Tumor

MR Imaging Findings of Tamoxifen-associated Uterine Adenosarcoma: Report of Two Cases

Adenosarcoma of the uterus is a rare biphasic tumor containing benign glandular epithelial and malignant mesenchymal components. The tumor has been reported to be associated with antiestrogen therapy, particularly tamoxifen, but there have been a few case reports with MRI. We present two cases of MRI findings of uterine adenosarcoma after antiestrogen therapy, tamoxifen and toremifene in breast cancer patients. The tumor presents as a large polypoid mass occupying the endometrial cavity, and may protrude into the vagina. On MRI, the tumor typically shows solid components with scattered small cysts and heterogeneous enhancement. These findings are not significantly different from conventional adenosarcoma.

A Rare Case of Mullerian Adenosarcoma of Uterus in a 14-year-old Girl

Background: Mullerian Adenosarcoma, a rare tumor, is composed of mixed mesenchymal and epithelial elements. The epithelial component is typically benign and admixed with malignant Sarcomatous Stroma. This tumor can be distinguished in approximately 8% of all uterus sarcomas and commonly originates in the endometrium as a growing polypoid mass in the uterine cavity. All age groups are affected but the average age of uterine Adenosarcoma is about 58. Case report: We aim to introduce a 14-year-old case of uterine Adenosarcoma as a rare occurrence, presenting with menometrorrhagia and formation of uterine fragile polypoid mass which extends into vagina. Total Abdominal Hysterectomy (TAH) and staging were performed. She had been clinically disease-free in a 40-month post operation follow-up. Distant metastasis is a very rare phenomenon, albeit the necessity of long-term follow-up seems necessary.Conclusion: Data accumulation of individual cases with such unusual neoplasm is essential for further experience provision.[GMJ.2014;3(4):256-9]

Gynecologic Cancer InterGroup (GCIG) consensus review for mullerian adenosarcoma of the female genital tract.

Mullerian adenosarcomas of the female genital tract are rare malignancies, originally described in the uterus, the most common site of origin, but they may also arise in extrauterine locations. Uterine adenosarcomas make up 5% of uterine sarcomas and tend to occur in postmenopausal women. They are usually low-grade tumors and are characterized by a benign epithelial component with a malignant mesenchymal component, which is typically a low-grade endometrial stromal sarcoma but can also be a high-grade sarcoma. Tumors that exhibit a high-grade sarcomatous overgrowth have a worse outcome. Adenosarcomas have been described as being midway along the spectrum between benign adenofibromas and carcinosarcomas. They generally have a good prognosis with the exception of deeply invasive tumors or those with high-grade sarcomatous overgrowth. Extrauterine adenosarcomas also have a higher risk for recurrence. In view of their rarity, there have not been any clinical trials in mullerian adenosarcomas and relatively little research. This article reviews the current knowledge and provides recommendation for the management of mullerian adenosarcomas.

Uterine adenosarcoma: An analysis on management, outcomes, and risk factors for recurrence

ObjectivesUterine adenosarcoma is a rare malignancy with little data on optimal management. We aimed to clarify the impact of adjuvant therapy in patients with uterine adenosarcoma and identify risk factors for recurrence and death. MethodsWe performed a retrospective review of patients undergoing primary evaluation and treatment for uterine adenosarcoma at a single institution from July 1982 through December 2011. Univariate and multivariate analyses were used to identify prognostic factors for progression-free survival (PFS) and overall survival (OS). ResultsWe identified 100 patients with uterine adenosarcoma, and 74 patients met the inclusion criteria. On multivariate analysis, sarcomatous overgrowth (SO) and lymphovascular space invasion (LVSI) were predictors of worse PFS and OS. Median PFS and OS were 29.4 and 55.4months for patients with SO, compared to 105.9 and 112.4months for patients without SO (PFS HR 2.58, 95% CI 1.37–4.84, p=0.003; OS HR 2.45, 95% CI 1.26–4.76, p=0.008). Among patients with stage I disease, 17 of 22 patients (77%) with SO and 8 of 37 patients (22%) without SO had a recurrence (p<0.001). Among patients with stage I disease with SO, adjuvant therapy appeared to be associated with longer PFS and OS, but these differences were not statistically significant (PFS, 46.7 vs. 29.4months, p=0.28; OS, 97.3 vs. 55.4months, p=0.18). ConclusionIn patients with uterine adenosarcoma, the presence of SO or LVSI confers a higher risk of recurrence. We did not identify an optimal treatment strategy for patients with SO, but adjuvant therapy may be associated with prolonged PFS.

Molecular characterization of a population-based series of endometrial stromal sarcomas in Kuwait

Endometrial stromal sarcomas (ESSs) frequently harbor genetic fusions, including JAZF1-SUZ12 and equivalent fusions in low-grade ESS (LGESS) and YWHAE-NUTM2 in high-grade ESS (HGESS). This study aims to classify a population-based series of ESSs in Kuwait based on the 2014 World Health Organization classification system and to assess the diagnostic use of interferon-induced transmembrane protein 1 (IFITM1) immunomarker for ESSs. Twenty ESSs including 19 LGESSs and 1 HGESS treated during the period between 2002 and 2013 were identified, and the cases were reviewed and characterized using fluorescence in situ hybridization and immunohistochemical studies. Thirteen (81.3%) of 16 LGESSs with interpretable results showed JAZF1 and/or PHF1 genetic rearrangements by fluorescence in situ hybridization, and the only HGESS in the series showed YWHAE genetic rearrangement. All LGESSs with interpretable results showed positive immunostaining for CD10 compared with 11 (61%) of 18 that showed positive immunostaining for IFITM1; 4 of 7 IFITM1-negative LGESSs showed JAZF1 and/or PHF1 rearrangements. A series of uterine leiomyomas, leiomyosarcomas, adenosarcomas, and carcinosarcomas were included for comparison, and positive IFITM1 staining was found in 1 of 10 leiomyomas, 3 of 13 leiomyosarcomas, 3 of 4 adenosarcomas, and 3 of 8 carcinosarcomas, compared to 0 of 10 leiomyomas, 9 of 13 leiomyosarcomas, 3 of 4 adenosarcomas, and 5 of 8 carcinosarcomas that were positive for CD10. Our results demonstrated characteristic genetic rearrangements in a high percentage of LGESSs in this Middle Eastern population, and IFITM1 antibody appears to be less sensitive than CD10 for LGESS.

Uterine adenosarcomas: A dual-institution update on staging, prognosis and survival

ObjectiveUterine adenosarcomas (AS) are rare tumors thought to have a favorable prognosis. The aim of this study was to evaluate clinicopathological characteristics and treatment outcome in women with uterine AS. MethodsPatients with uterine AS were identified from the institutional databases at two regional cancer centers, Princess Margaret Hospital, Toronto and Vancouver General Hospital. All cases underwent specialist pathological review and were re-staged according to FIGO criteria (2009). Patient demographics, treatment data and outcomes were evaluated. ResultsBetween 1984 and 2010, 64 patients with confirmed AS were identified: 30 exhibited sarcomatous overgrowth (AS+SO). 47 patients presented with stage I disease: 27 IA and 18 IB. 57 of the 58 patients with known surgical management underwent hysterectomy: 55 having bilateral salpingo-oophorectomy, 12 having lymph node dissection. 14 patients received adjuvant treatment: 10 radiotherapy, 3 chemotherapy and 1 both. Sixteen of the 45 patients (35.6%) with follow-up recurred; median time to recurrence 21.2months, range 2.1–87.8months. Recurrence was associated with myometrial invasion (p=0.05). Two of the 10 women (20%) with AS+SO receiving adjuvant treatment recurred compared to 9 of the 14 (64%) who did not. One of the 5 women (20%) with stage IB disease who received adjuvant treatment recurred (20%) compared to 6 of the 7 (85.6%) who did not. ConclusionsLong term surveillance is required given the variable time to recurrence. For those with AS+SO and myometrial invasion adjuvant treatment should be considered and further investigation of adjuvant strategies is warranted.

Uterine adenosarcoma: A closer look at a rare disease

Objective: Uterine adenosarcoma (AS) is a rare disease and standard therapy remains elusive. We aimed to review treatment and outcomes for patients diagnosed with uterine AS with high-risk features, including heterologous elements and sarcomatous overgrowth (SO).

Adenosarcoma mülleriano de útero: un tumor infrecuente de difícil diagnóstico

Uterine adenosarcoma is a rare neoplasm constituting only around 8% of all uterine sarcomas. This tumor is associated with tamoxifen therapy and pelvic radiation. The most characteristic clinical feature is a recurrent cervical polypoid lesion. Patients have often had previous biopsies for the same reason, but without an accurate diagnosis. Furthermore, a mistaken diagnosis may have been made, the most common being cervical polyp. Uterine adenosarcoma consists of neoplastic glands with a benign appearance and a sarcomatous stroma.We report the case of a 53-year-old woman with a uterine polypoid lesion. After macroscopic, microscopic and immunohistochemical studies, the diagnosis was a uterine Müllerian adenosarcoma, which is a low-grade neoplasm with good prognosis, but with a high percentage of recurrences (25%-40%).Treatment is simple hysterectomy with double adnexectomy, with the option of subsequent postoperative radiotherapy. However, because this tumor is a low-grade neoplasm, a more conservative approach has sometimes been adopted in some young patients without children.This tumor is malignant, however, and mortality from abdominal or other types of metastases has been reported. Therefore, we believe that the most appropriate and safest therapeutic option is hysterectomy.

Clinical benefit of trabectedin in uterine adenosarcoma

Uterine adenosarcoma is an extremely rare uterine malignancy, and the utility of chemotherapy in this disease is not well defined. This study assessed the safety and efficacy of trabectedin in patients with recurrent/metastatic uterine adenosarcoma with sarcomatous overgrowth. A retrospective search of a prospectively maintained database was performed to identify patients with adenosarcoma treated with trabectedin between 2010 and 2012, within a compassionate use trial. Three patients with recurrent/metastatic uterine adenosarcoma treated with trabectedin were identified. All three patients tolerated the drug well. Two patients obtained prolonged clinical benefit from treatment, one having received 17 cycles and another 11 cycles of therapy. Trabectedin is well tolerated and has clinical activity in recurrent/metastatic uterine adenosarcoma.

30. Adenosarcoma of the uterus responsive to hormonal therapy: a case report

Aims To review a case of a rare tumour, adenosarcoma of the uterus, and its response to hormonal therapy. Methods Adenosarcoma of the uterus is a rare tumour and there are very limited reports of the use of hormonal therapy in its treatment. One case of mullerian adenosarcoma occurring in the uterus of an 82-year-old woman was reviewed from our institution. We compared routine H&E stained slides and oestrogen and progesterone immunohistochemical stains of the initial biopsy of the tumour with slides of the excision specimen. The excision was made after a period of 3 months of treatment with an aromatase inhibitor, le-trozole. She was deemed unsuitable for other forms of therapy due to her other medical conditions. Results Following the 3 months of treatment with letrozole a repeat MRI revealed a significant decrease in size of the tumour (9.5×4.3×3.7 cm to 4.9×4.2×3.1 cm). The extent of parametrial extension had also decreased. The immunohistochemical stains showed increased intensity and more diffuse expression of oestrogen receptor antigen and possibly progesterone receptor antigen in the post-treatment sample compared to the initial biopsy. Observations There was a noticeable decrease in the size of the adenosarcoma of the uterus and expression/intensity of oestrogen and possibly progesterone receptor antigen following treatment with hormonal therapy. There is only very limited data relating to this method of treatment in the literature. This case highlights the need for further studies on the use of hormonal therapy as a possible therapy in these rare tumours.

Synchronous occurrence of primary malignant mixed müllerian tumor in ovary and uterus

Malignant mixed müllerian tumor (MMMT) arising from female internal genitalia is rare with the uterine corpus being the most prevalently affected site. It is even more rare when it occurs on both uterus and ovary at the same time. We describe a case of synchronized occurrence of MMMT on ovary and uterine adenosarcoma with review of literature.

Management of uterine adenosarcomas with and without sarcomatous overgrowth

ObjectivesUterine adenosarcomas (AS) are rare tumors composed of malignant stromal and benign epithelial components. We sought to evaluate the role of primary surgery, adjuvant treatments, and salvage therapies for patients with uterine adenosarcomas. MethodsWe identified all patients diagnosed with AS from 1990 to 2009 at our institution. Patient demographics, surgical procedures, sites of metastatic disease, and histologic features (e.g., presence of sarcomatous overgrowth, and heterologous elements) were collected. Treatment regimens and survival outcomes were evaluated. ResultsThirty-one patients were evaluable for this study: 19 (61%) received up-front treatment at our institution and 12 (39%) received treatment for recurrent disease. Most of the up-front treated patients (15, 79%) were diagnosed with stage I disease and underwent hysterectomy (100%) with bilateral salpingo-oophorectomy (84%). Of the 19 patients treated at our institution from time of initial diagnosis, 5 (26%) patients recurred (median follow-up, 72.9months; range, 3–154). In 5 patients with sarcomatous overgrowth (AS+SO), the 2-year progression-free and overall survival rates were both 20% versus 100% for 14 patients without sarcomatous overgrowth. Responses to systemic treatment of measurable disease were observed in patients with and without sarcomatous overgrowth, but no optimal treatment strategy could be identified for either groups. ConclusionsUnlike AS without sarcomatous overgrowth, AS+SO is an aggressive disease with a high recurrence rate. In our series, no optimal adjuvant or systemic treatment strategy was identifiable but standard sarcoma chemotherapy regimens appear to have efficacy in both AS and AS+SO.