Uterine Mesenchymal Tumors Research Articles

A Case of Endometrial Stromal Sarcoma with Synchronous Bilateral Adenocarcinoma of Ovary

Endometrial stromal tumor is a rare mesenchymal uterine tumor. We report the case of a patient with endometrial stromal sarcoma and concomitant bilateral endometrioid adenocarcinoma of the ovary in the context of pelvic endometriosis. The patient underwent a complete cytoreduction including total hysterectomy and bilateral adnexectomy, pelvic lymphadenectomy, appendicectomy, infracolic omentectomy, and pelvic peritonectomy. This is the first report to our knowledge that describes a synchronous endometrial stromal sarcoma and bilateral endometrioid adenocarcinoma of the ovary.

Tumeurs mésenchymateuses myxoïdes du corps utérin : tumeurs du stroma endométrial et tumeurs musculaires lisses, dans leur variante myxoïde

Four myxoid variant of uterine mesenchymal tumors are reported. One was a low grade stromal sarcoma with infiltrative margins and the others were well circumscribed tumors corresponding to an endometrial stromal nodule and two leiomyomas. They were hypocellular neoplasms composed of stellated cells with an abundant Alcian Blue positive myxoid matrix. The myxoid nature of the neoplasms obscured their cellular nature and made the distinction between smooth muscle and endometrial stromal tumors difficult. Endometrial stromal tumors, showed very focal areas of small basophilic cells, characteristic of endometrial stroma. The diagnosis was based on the presence of a spiral arteriolar network, a CD10 positivity as well as the absence of h-caldesmon and desmin expression. The two myxoid leiomyomas showed more spindle cells and a desmin expression while h-caldesmon was negative and CD10 focally positive in both cases. Myxoid variant of endometrial stromal tumors does not necessarily exhibit the typical morphology of endometrial stroma. They may demonstrate morphological features of smooth muscle tumors in the uterus. Also, myxoid changes in uterin smooth muscle tumors may modify the classical immunoreactivity of smooth muscle markers in these tumors and make it difficult to distinguish between benign and malignant neoplasms. An immunohistochemical panel of antibodies including CD10, h-caldesmon and desmin may help in establishing the correct diagnosis.

Low-Grade Endometrial Stromal Tumors of the Uterus

AbstractEndometrial stromal tumors are uncommon uterine mesenchymal neoplasms that are occasionally discovered in endometrial biopsy/curettage specimens or in hysterectomies. Typical examples are composed of cells that resemble proliferative-phase endometrial stromal cells. The tumor cells have mono

Cytogenetic and molecular aberrations in endometrial stromal tumors

Endometrial stromal tumors (ESTs) are rare uterine mesenchymal tumors, comprising <10% of all uterine mesenchymal neoplasms. The latest World Health Organization classification divides endometrial stromal tumors into 3 categories based on morphologic features: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma, and undifferentiated endometrial sarcoma. Specific cytogenetic aberrations and molecular genetic alterations have recently been identified in endometrial stromal tumors, providing insights into their molecular biology, potential diagnostic markers, and possible therapeutic targets. Currently, recurrent chromosomal rearrangements resulting in gene fusion play a substantive role in the pathogenesis of endometrial stromal nodules, endometrial stromal sarcomas, and a small subset of undifferentiated endometrial sarcomas. Loss of heterozygosity of tumor suppressor genes and deregulation of the Wnt signaling pathway have also been implicated in EST tumorigenesis. In this review, we summarize the recent advances in the molecular pathology of endometrial stromal tumors.

Uterine mesenchymal tumors

Uterine mesenchymal tumors are a heterogeneous group of neoplasms that can frequently be diagnostically challenging. Differentiation between the benign and malignant counterparts of mesenchymal tumors is significant due to differences in clinical outcome, and the role of the surgical pathologist in making this distinction (especially in the difficult cases) cannot be underestimated. Although immunohistochemical stains are supportive toward establishing a final diagnosis, the morphologic features trump all the other ancillary techniques for this group of neoplasms. This review therefore emphasizes the key morphologic features required to diagnose and distinguish uterine mesenchymal tumors from their mimics, with a brief description of the relevant immunohistochemical features.

Use of Myocardin in the Classification of Mesenchymal Tumors of the Uterus

It can sometimes be difficult to distinguish between the 2 main types of uterine mesenchymal neoplasms; uterine smooth muscle tumors (SMTs) and endometrial stromal sarcomas (ESSs), particularly when the ESSs show smooth muscle differentiation or the SMTs are highly cellular. The aim of this study was to investigate myocardin expression in normal uterus myometrium, in SMTs, and in ESSs and to determine whether myocardin can be used as a useful diagnostic tool in the classification of problematic uterine mesenchymal tumors. Immunohistochemical staining was performed in each group. Besides myocardin, all cases were also stained for other smooth muscle markers (h-caldesmon, desmin, smooth muscle actin) and for CD10. All tested markers were analyzed in 21 conventional leiomyomas (LMs), 21 highly cellular leiomyomas (HCLs), 12 leiomyosarcomas (LMSs), 3 endometrial stromal nodules (ESNs), 11 ESSs, and 15 normal uterus myometrium. Myocardin was expressed in all normal uterine myometrium and in SMTs (even in the regions with epithelioid features) moderately or strongly, at least topically, whereas in endometrium, in ESNs and in ESSs, except in the regions of smooth muscle differentiation, it was negative. All ESNs, 11 of 11 ESSs and 14 of 15 endometrium were negative for h-caldesmon, but all SMTs and normal uterine myometrium were positive for h-caldesmon except for 2 LMSs, 2 HCLs, and for the regions with epithelioid features in 2 LMs. Desmin was stained in all normal uterine myometrium and in SMTs (except those of the regions with epithelioid features), but it was negative in 1 HCL and 1 LMS. One of 3 ESNs and 2 of 11 ESSs were expressed in desmin. Smooth muscle actin was negative in all ESNs, 2 LMSs, and 2 HCLs, and positive in all myometriums, LMs (except for the regions with epithelioid features), 1 ESSs, and 1 proliferative phase endometrium. Eight of 11 ESSs and all ESNs were positive for CD10, as was 1 HCL, and 2 LMSs. All uterine myometrium, 3 ESSs, and 3 endometriums were negative for CD10. Our study indicates that the myocardin is expressed in normal and neoplastic uterine smooth muscle cells sensitively and that the evaluation of myocardin expression is useful in distinguishing SMTs from ESSs.

Uterine Composite Tumor Composed of Leiomyosarcoma and Embryonal Rhabdomyosarcoma With Immature Cartilage

We report a rare composite uterine mesenchymal neoplasm in a 66-year-old woman composed of approximately equal amounts of leiomyosarcoma and embryonal rhabdomyosarcoma, the latter containing foci of immature cartilage. Immunohistochemically, both components were positive with desmin. The leiomyosarcomatous element was positive with alpha smooth muscle actin and h-caldesmon and the rhabdomyosarcomatous component with myogenin and myo-D1. In a review of the literature, we have identified only a single example of a similar case. This is likely to represent rhabdomyosarcomatous differentiation in a leiomyomatous neoplasm or alternatively bidirectional differentiation from an uncommitted mesenchymal stem cell.

MRI appearance of mesenchymal tumors of the uterus

Purpose Uterine leiomyomas are the most common uterine neoplasms. Statistically, a uterine mass with unusual imaging features is more likely to represent a leiomyoma than other uncommon uterine mesenchymal neoplasms such as leiomyosarcoma or endometrial stromal tumors. Several prior studies have attempted to identify objective imaging characteristics that differentiate these entities. The purpose of this study was to test these criteria on our patient population. Methods and materials This retrospective study was approved by the institutional Human Investigations Committee and was performed in compliance with HIPAA regulations. Four patients with uterine leiomyosarcoma, two with stromal tumors of uncertain malignant potential (STUMP), one with endometrial stromal sarcoma, and two with mixed endometrial stromal and smooth muscle tumors were included in the study. Seventeen additional control cases of leiomyomas were selected as controls. Cases were blindly evaluated by two experienced readers. Objective criteria included T1 and T2 signal characteristics, enhancement pattern, the presence of cystic changes, and ill defined margins. Subjective criteria included individual reader gestalt. All cases had pathologic correlation. Results None of the objective criteria were associated with the presence or absence of uterine mesenchymal neoplasm. Ill defined margins came closest to having statistical significance ( p = 0.06). Reader gestalt was statistically associated with the presence of mesenchymal neoplasm for one of our readers ( p = 0.02) but not for the other ( p = 0.07). Conclusion We found poor accuracy for objective imaging criteria in distinguishing leiomyomas with atypical imaging features from more clinically significant uterine mesenchymal neoplasms.

Evaluation of Archival Time on Shotgun Proteomics of Formalin-Fixed and Paraffin-Embedded Tissues

There is increasing acceptance of the critical importance of correlating the morphologic features of tissue with the data obtained from various molecular analytic techniques. Access to archived formalin-fixed and paraffin-embedded (FFPE) tissue specimens via shotgun-based proteomic analyses may, therefore, open new avenues for both prospective and retrospective translational research. However, one of the remaining issues in performing comparative proteomic measurements among FFPE tissues relates to potential variability in protein composition and retrieval based on length of storage periods. Optimized protein extraction and digestion procedures for handling FFPE tissues are coupled with the capillary isotachophoresis-based proteome technology to evaluate the effects of length of storage period on archival tissue proteome analysis across 10 archived uterine mesenchymal tumor tissue blocks, including 9 uterine leiomyomas dating from 1990 to 2002 and a single case of alveolar soft part sarcoma (ASPS) from 1980. Several statistical measures, including the Pearson correlation coefficient, coefficient of variance, k-means clustering, and ANOVA, are employed to evaluate the possibility of an archival effect on individual proteins or groups of proteins within nine leiomyomas. Low abundance proteins may be more susceptible to the long-term storage as these proteins are more difficult to be retrieved and extracted as the tissue block ages in paraffin. Despite using tissue blocks stored for as many as 28 years, high confidence and comparative proteome analysis between the leiomyomas and the sarcoma is achieved. Though sharing over 1800 common proteins in a core set, a total of 80 proteins unique to the sarcoma are identified distinguishing the ASPS from the leiomyomas. Vacuolar proton translocating ATPase 116 kDa subunit isoform a3, one of the unique proteins expressed in the ASPS, is further validated by immunohistochemistry (IHC). Although IHC is highly sensitive and provides the subcellular resolution, mass spectrometry-based proteome profiling enables global identification and quantification of thousands of proteins without a priori knowledge of individual proteins being analyzed or the need of validated antibodies.

Uterine mesenchymal tumors: a review of selected topics

Uterine mesenchymal tumors are unusual neoplasms that frequently give rise to diagnostic difficulties. I have chosen to review the clinical and histopathologic features of three interesting lesions – low-grade endometrial stromal sarcoma, leiomyosarcoma and carcinosarcoma (malignant mixed Mullerian tumor) – and have also provided information about ancillary diagnostic techniques and strategies for sorting between entities featured in the differential diagnosis.

C‐kit protein expression in uterine and ovarian mesenchymal tumours

The protooncogene c-kit encoding transmembrane tyrosine kinase receptor protein plays an important role in the signal transduction pathway that regulates cellular growth and repair. Gene product KIT overexpression has been shown in a number of different neoplasms, particularly in mastocytosis and gastrointestinal stromal tumours (GIST). The morphologic similarity of uterine mesenchymal tumours and GIST, and the presence of KIT protein in normal uterine tissue, suggests that uterine sarcomas may have the same c-kit overexpression. The purpose of this study was to determine the overexpression of c-kit protein in uterine and ovarian sarcomas. Immunohistochemical staining using a polyclonal anti-c-kit antibody was performed on tissue blocks from 12 carsinosarcomas, 14 leiomyosarcomas, 8 endometrial stromal sarcomas, 2 adenosarcomas, 1 atypical leiomyoma, 1 leiomyoma with limited experience, and 10 leiomyomas. The slides were evaluated by a semiquantitative method. C-kit was positive in 10 of 12 (83%) carcinosarcomas, 10 of 14 (71%) leiomyosarcomas, 6 of 8 75(%) endometrial stromal sarcomas, 1 of 2 (50%) adenosarcomas, 1 leiomyoma with limited experience, and 1 of 10 (10%) leiomyomas. The uterine sarcomas express c-kit, like GISTs. It seems that KIT may have a significant role in the oncogenesis of mesenchymal tumours of the uterus and ovary.

Use of Histone Deacetylase 8 (HDAC8), a New Marker of Smooth Muscle Differentiation, in the Classification of Mesenchymal Tumors of the Uterus

Uterine smooth muscle tumors (SMTs) are usually recognized on the basis of their routine morphologic features; however, their distinction from endometrial stromal tumors (ESTs), the second most common mesenchymal tumor of the uterus, is sometimes problematic. Histone deacetylases (HDACs) were originally identified as nuclear enzymes regulating histone acetylation. We have recently shown that in normal human tissues, HDAC8 is exclusively expressed in the cytoplasm of cells showing smooth muscle differentiation. In this study, we examined HDAC8 expression in SMTs and ESTs of the uterus to determine whether HDAC8 may be a useful diagnostic tool in the classification of problematic uterine mesenchymal tumors. HDAC8 immunohistochemical staining was performed in 15 leiomyomas (LMs), 9 highly cellular leiomyomas (HCLs), 8 epithelioid SMTs, 13 leiomyosarcomas (LMSs), and 17 ESTs, including 3 with sex-cord differentiation and 5 with smooth muscle differentiation. All tumors were also stained for other smooth muscle markers (desmin, h-caldesmon, smooth muscle actin [SMA], smooth muscle myosin heavy chain) and for CD10. All LMs had moderate to strong expression of all smooth muscle markers. HDAC8 was detected in 8 of 9 HCLs and in all epithelioid SMTs (8 of 8); however, it was weak in 4 epithelioid SMTs. In contrast, desmin, h-caldesmon and smooth muscle myosin were positive in only 2 of 8, 1 of 8 and 4 of 8 epithelioid SMTs, respectively. All smooth muscle markers had similar frequency of staining in LMSs; however, HDAC8 showed overall moderate intensity compared with other smooth muscle markers, which showed stronger staining. HDAC8, h-caldesmon, and smooth muscle myosin did not stain conventional areas of ESTs or ESTs with sex-cord differentiation, whereas SMA and desmin were positive in those areas in 4 of 12 and 3 of 12 ESTs, respectively. Areas of smooth muscle differentiation in ESTs were positive for HDAC8 in all cases, but they were less constantly positive for the other smooth muscle markers. CD10 was expressed in most ESTs (14 of 17), but it was also positive in 15 of 45 SMTs. 1) HDAC8 seems to be a specific marker of SM differentiation because conventional ESTs and ESTs with sex-cord differentiation are negative for HDAC8, whereas areas of smooth muscle differentiation in these tumors are consistently positive; 2) HDAC8 gives similar results to those obtained with desmin, h-caldesmon, and smooth muscle myosin in both LMs and LMSs, although the staining for HDAC8 in LMSs tends to be less intense; 3) HDAC8 may be a more sensitive marker than desmin and h-caldesmon in epithelioid SMTs. Thus, HDAC8 detection may be useful in helping the differential diagnosis of uterine mesenchymal tumors.

Inflammatory Myofibroblastic Tumor of the Uterus

Inflammatory myofibroblastic tumor (IMT) is an indolent spindle cell proliferation that can histologically resemble various malignant mesenchymal neoplasms; however, it generally behaves as a benign or locally recurrent tumor. Most IMTs involve the lung, mesentery, omentum, or retroperitoneum. We report the clinical and pathologic features of six IMTs of the uterus, one of which was included in a previous report, and emphasize the histologic and immunohistochemical features that distinguish IMTs from uterine spindle cell neoplasms that require aggressive treatment. Recently, translocations of the anaplastic lymphoma kinase (ALK) gene and immunohistochemical expression of ALK have been reported in IMTs of various anatomic sites. We compared ALK expression in uterine IMTs with that in uterine mesenchymal neoplasms with which it may be confused. Patients with IMT were between 6 and 46 years of age. None had a history of abdominal surgery; three were multiparous. The IMTs ranged from 1 to 12 cm in maximum dimension. Three grew as polypoid masses that arose in the lower uterine segment, and two of these prolapsed through the cervical os. The three other tumors grew as bulky myometrial masses with focally irregular borders and infiltrated the endometrium, parametrium, or cervical stroma. There were three main microscopic patterns: a hypocellular pattern, a fascicular pattern, and a hyalinized pattern. A lymphoplasmacytic infiltrate was present in all of the tumors, and most had a myxoid background. Mitotic activity ranged from 0 to 2 mitotic figures per 10 high power fields (HPF) except in one tumor that focally had up to 8 mitotic figures per 10 HPF. No nuclear atypia or necrosis was present. Immunohistochemical expression of ALK was present in a cytoplasmic pattern in all IMTs tested. No ALK expression was identified in uterine leiomyoma (n = 7), leiomyosarcoma (n = 6), carcinosarcoma (n = 4), endometrial stromal sarcoma (n = 4), or normal uterine tissues. Follow-up ranging from 1.5 years to 5 years in 4 patients with uterine IMTs revealed no recurrence or metastasis. IMTs should be differentiated from aggressive uterine mesenchymal tumors because they can be treated conservatively and have a more favorable prognosis. ALK expression appears to be of diagnostic value in conjunction with other immunohistochemical stains.

Endometrial Stromal Sarcomas Frequently Express Epidermal Growth Factor Receptor (EGFR, HER-1)

Endometrial stromal sarcomas are rare malignant mesenchymal uterine tumors. The expressions of different epidermal growth factor receptors such as EGFR (HER-1), HER-2, HER-3, and HER-4 have not yet been examined in these tumors. Twenty-three cases of endometrial sarcomas consisting of 20 low-grade endometrial stromal sarcomas and 3 undifferentiated endometrial sarcomas were examined immunohistochemically for EGFR (HER-1), HER-2, HER-3, and HER-4. EGFR (HER-1) was positive in 17 of 23 (74%) cases. While the three undifferentiated endometrial sarcomas were positive for EGFR, 14 of 20 (70%) low-grade endometrial stromal sarcomas showed positive reactions for EGFR. All examined cases were negative for HER-2, HER-3, and HER-4. This study is the first to show common expression of EGFR (HER-1) in endometrial stromal sarcomas. This finding may provide the basis for a new therapeutic strategy using monoclonal antibodies against EGFR (such as cetuximab) or small molecule inhibitors of EGFR (such as gefitinib) in patients with endometrial sarcomas.

Diagnosis of malignant mesenchymal uterine tumors by hysteroscopic excisional biopsy

To emphasize the need for histologic evaluation of intrauterine lesions. Six cases of unexpected mesenchymal uterine tumors were diagnosed following pathologic review of specimens obtained during hysteroscopy to evaluate intrauterine lesions. Retrospective chart review (Canadian Task Force classification II-3). Large tertiary care medical center. Four postmenopausal and two perimenopausal women with uterine mesenchymal tumors. Hysteroscopy and staging laparotomy. Mean age of the patients was 57.5 +/- 19.5 years (mean +/- 2SD). Four women (67%) were postmenopausal. Three patients had abnormal uterine bleeding, one had a cervical mass, and the other two were asymptomatic and referred for evaluation of thick endometrium detected by routine ultrasound, which had been preformed as part of their annual check-up. In all cases, the initial hysteroscopic diagnosis was endometrial polyp or submucous myoma. Following the pathologic review, all six women underwent complete staging laparotomy. In two women, there was no residual disease in the surgical specimen. None of the patients had extrauterine spread of the disease. At mean follow-up of 21.5 +/- 9.7 months (mean +/- 2SD), all women were asymptomatic. Intrauterine lesions erroneously considered to be benign endometrial polyps or myomas can turn out to be malignant mesenchymal uterine tumors. Hysteroscopic evaluation and biopsy might offer early diagnosis and treatment to these patients.

子宮平滑筋肉腫（LMS）と癌肉腫（CS）の画像診断

子宮平滑筋肉腫（LMS）と癌肉腫（CS）の画像診断

Immunohistochemistry in gynaecological pathology: a review

This paper reviews some aspects of the application of immunohistochemistry in gynaecological pathology. The use of cytokeratins 7 and 20 are discussed with reference to applications in ovarian pathology, including metastatic disease to the ovaries. Developments in utilising MIB-1 and p16 in cervical squamous and glandular lesions are discussed. Recent assertions regarding the differential diagnosis between endocervical and endometrial carcinomas are also reviewed. Antibodies that may be of use in the diagnosis of uterine mesenchymal and ovarian tumours are highlighted, as are antibodies of use in trophoblastic lesions including the use of p57 in evaluating hydatidiform moles.

Treatments and results of uterine mesenchymal tumor

Treatments and results of uterine mesenchymal tumor

The proto-oncogene c-kit is expressed in leiomyosarcomas of the uterus

Objective The proto-oncogene c-kit encodes for a 145-kDa transmembrane tyrosine kinase receptor. Interaction with its ligand, stem cell factor, is essential in the development of hematopoietic stem cells, mast cells, gametocytes, melanocytes, and interstitial cells of Cajal. C-kit expression has been identified in a number of different neoplasms that includes mastocytosis/mast cell leukemia, acute myeloblastic leukemia, seminoma/dysgerminoma, and gastrointestinal stromal tumors. This study examines c-kit expression in uterine endometrial stromal sarcomas, leiomyomas, and leiomyosarcomas using immunohistochemistry. Methods Archival tissue from 38 patients with the uterine mesenchymal tumors (16 leiomyosarcomas, 8 leiomyomas, 11 low-grade endometrial stromal sarcomas, and 3 high-grade endometrial stromal sarcomas) was stained with polyclonal antibody for c-kit. Modified avidin biotin (ABC) immunoperoxidase method was employed for antibody detection. Individual tumors were considered positive if more than 10% of the cells comprising the neoplasm displayed immunoreactive staining. Staining intensity was graded 1+ to 3+ and distribution graded as focal (10–30% of the cells), intermediate (30–60% of the cells), or diffuse (>60% of the cells). Results C-kit was positive in 12 (75%) of the 16 leiomyosarcomas. The staining was 3+ and diffuse in the majority of the positive tumors. C-kit expression was not detected in any of the 8 leiomyomas. Two of the 3 high-grade endometrial stromal sarcomas displayed c-kit positivity. Staining was diffuse and 3+ in both of these tumors. Expression of c-kit was observed in only 3 of the 11 low-grade endometrial stromal sarcomas. Conclusions C-kit is expressed in uterine leiomyosarcomas and endometrial stromal sarcomas. Adjunctive diagnostic studies using c-kit may be useful in distinguishing leiomyosarcomas from benign leiomyomas in uterine tumors that offer uncharacteristic features. Furthermore, studies should investigate the prospect of treating these malignant tumors with tyrosine kinase inhibitors.

Sonographic evaluation of a uterine angiolipoleiomyoma.

We report the case of a 51-year-old postmenopausal woman with an angiolipoleiomyoma, a rare mesenchymal uterine tumor, and describe its sonographic appearance. The clinical presentation of these invariably benign tumors often mimics that of uterine leiomyomas, making angiolipoleiomyomas difficult to diagnose correctly before histopathologic evaluation. In this case, sonography performed to determine the cause of the patient's vaginal bleeding showed a sharply marginated, brightly echogenic solid mass adjacent to the echogenic endometrium, without associated shadowing. Histopathologic examination revealed that this tumor was composed of smooth muscle, adipose tissue, fibrous connective tissue, and blood vessels. These sonographic findings, which are unusual for tumors of the uterus, suggest the diagnosis of angiolipoleiomyoma. Accurate diagnosis of these benign tumors could prevent patients from undergoing surgery and would allow appropriate counseling of patients.