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.     

Myogenous phenotype of epithelial-like areas in endometrial stromal sarcomas

Approximately 25% of low-grade endometrial stromal sarcomas of the uterus contain areas of epithelial-like differentiation, which are often reminiscent of ovarian sex-cord tumors. It has been suggested that these areas may represent attempted differentiation toward either uterine glands or smooth muscle. To investigate these two possibilities, we examined the histologic and immunohistochemical features of 26 low-grade endometrial stromal sarcomas. Eight tumors had epithelial-like differentiation, which in some tumors was so prominent as to suggest a purely epithelial neoplasm. Areas typical of endometrial stromal sarcoma were vimentin positive, whereas epithelial-like differentiation expressed vimentin and the muscle markers muscle-specific actin and desmin, as well as cytokeratin, but not the epithelial marker epithelial membrane antigen. Epithelial-like differentiation in low-grade endometrial stromal sarcoma is not uncommon and, based on our immunohistochemical results after comparison with normal controls, epithelial-like differentiation has a myogenous rather than an epithelial phenotype.     

Uterine mesenchymal tumours: recent advances

Almost all uterine mesenchymal tumours have been historically classified as either smooth muscle or endometrial stromal neoplasms. Recent application of molecular techniques has identified numerous lesions with distinctive genetic abnormalities and clinicopathological characteristics. Newly discovered uterine sarcoma subtypes include high-grade endometrial stromal sarcomas with BCOR genetic abnormalities, fibrosarcoma-like uterine sarcomas with NTRK rearrangements and COL1A–PDGFRB fusions, as well as undifferentiated uterine sarcomas with SMARCA4 mutations. Novel PLAG1 and PGR fusions have been identified in subsets of myxoid and epithelioid leiomyosarcomas. Some uterine tumours resembling ovarian sex-cord tumour harbour GREB1 and ESR1 rearrangements. Histological and immunophenotypical features as well as underlying genetic abnormalities defining these lesions are discussed.     

Inhibin and CD99 (MIC2) expression in uterine stromal neoplasms with sex-cord-like elements.

Uterine mesenchymal neoplasms with sex-cord-like elements are designated as endometrial stromal tumor with sex-cord-like elements (ESTSCLE) or uterine tumor resembling ovarian sex-cord tumor (UTROSCT), depending on the extent of sex-cord-like differentiation. Occasionally, sex-cord elements similar to those in ESTSCLE and UTROSCT occur in uterine adenosarcomas. To determine whether the sex-cord-like elements in these tumors show immunohistological evidence of sex-cord differentiation, we studied a series of uterine neoplasms for expression of inhibin, a peptide hormone expressed by normal ovarian granulosa cells and ovarian sex-cord neoplasms, and CD99, a protein also expressed by granulosa cells, Sertoli cells, and some ovarian sex-cord tumors. Thirty uterine mesenchymal neoplasms (five epithelioid or plexiform smooth muscle tumors, three endometrial stromal tumors, two mixed endometrial stromal and smooth muscle tumors, 10 ESTSCLE, five UTROSCT, and five miscellaneous stromal processes) and five epithelial neoplasms were evaluated for expression of CD99 (clone 12E7) and inhibin (clone R1) in formalin-fixed, paraffin-embedded tissue. Three of 10 (30%) ESTSCLE and five of five (100%) UTROSCT were inhibin and CD99 immunoreactive. Inhibin staining was confined to the areas with sex-cord-like differentiation, and staining was generally much stronger and more extensive in areas featuring prominent foam cells. There were no differences in the degree or intensity of staining for inhibin in premenopausal and postmenopausal women. CD99 expression tended to correlate with inhibin and was typically confined to similar cell types in the individual neoplasms. Weak CD99 immunoreactivity was seen in one additional epithelioid smooth muscle tumor, whereas all other mesenchymal and epithelial neoplasms studied for inhibin and CD99 were negative. These results provide further immunohistological support for true sex-cord differentiation within uterine mesenchymal proliferations and suggest that the degree of sex-cord differentiation may correlate with the expression of these markers.     

Endometrial stromal tumors: Diagnostic updates and challenges

Endometrial stromal tumors are rare uterine mesenchymal tumors of endometrial stromal origin. They are classified into endometrial stromal nodule, low-grade endometrial stromal sarcoma, high-grade endometrial stromal sarcoma, and undifferentiated uterine sarcoma by the current (2020) WHO classification. Correct diagnosis of endometrial stromal tumors is critical for proper patient management. However, due to infrequent encounters, overlapping morphological features and immunohistochemical profiles, the differential diagnoses among endometrial stromal lesions and their morphologic mimics are often challenging. Partially with our own experience, here we review and summarize the tumor morphology, immunohistochemical phenotype, as well as molecular feature of endometrial stromal tumors and key differential diagnoses, emphasizing the newest developments and their utilization in daily practice.     

Role of Electron Microscopy in Metastatic Endometrial Stromal Tumors

Endometrial stromal tumors may pose a problem in diagnosis when they appear as metastatic lesions without a known primary tumor. To determine the usefulness of electron microscopy in identifying them in these situations, optimally fixed low-grade stromal sarcomas (five), normal endometrial specimens (six), and malignant mesodermal mixed tumors (four) were studied. The endometrial stromal sarcomas had a general resemblance to normal proliferative endometrial stroma, being composed of undifferentiated cells, fibroblasts, and myofibroblasts. One stromal tumor showed evidence of partial epithelial differentiation. One of the four malignant mesodermal mixed tumors had a fibrosarcomalike component, but there was insufficient resemblance to normal endometrial stroma to indicate a relationship between the two. Together with a review of the literature, this study indicates that electron microscopy is useful in the diagnosis of low-grade endometrial stromal tumors by demonstrating characteristic cellular findings as well as a lack of features specific for other round cell and spindle cell neoplasms.     

Mesenchymal tumours of the uterus: selected topics emphasizing diagnostic pitfalls

Smooth muscle tumours and endometrial stromal tumours represent the two main categories of mesenchymal tumours of the uterus. Although their diagnosis is straightforward in most cases, difficulties arise with particular leiomyoma variants, especially highly cellular leiomyoma (often confused with an endometrial stromal tumour) and leiomyoma with bizarre nuclei, mitotically active leiomyoma, and leiomyomas with hydropic or myxoid change, which may cause concern for leiomyosarcoma. Endometrial stromal tumours including several recently described variants, those with smooth muscle, sex-cord-like or glandular differentiation, or a fibrous-myxoid background are responsible for their own subset of diagnostic problems as are two other entities considered here: high-grade endometrial sarcomas and uterine tumours resembling ovarian sex-cord tumours. This review highlights useful morphologic features as well as immunohistochemical findings that may help in the classification of these often confusing tumours.     

Myxoid mesenchymal tumors of uterus: endometrial stromal and smooth muscle tumors, myxoid variant

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.     

Uterine tumors resembling ovarian sex-cord tumors producing parathyroid hormone-related protein of the uterine cervix

A case of uterine tumors resembling ovarian sex-cord tumors (UTROSCT) producing parathyroid hormone-related protein (PTH-rP) of the uterine cervix is reported. A 66-year-old woman underwent total hysterectomy with bilateral salpingo -oophorectomy due to the possibility of a malignant uterine tumor. A fairly well-circumscribed tumor, measuring 8 x 5 x 7 cm, was present in the myometrium of the cervix and extended into the endocervical mucosa. Histologically, the tumor showed predominantly sex-cord-like differentiation and the features of conventional endometrial low-grade stromal sarcoma were observed in part. Immunohistochemically, the tumor cells were negative for CD10. From these findings, we diagnosed the present case as Clement and Scully's group II UTROSCT arising from the uterine cervix. To our knowledge, this is the first report of the cervical occurrence of UTROSCT. Furthermore, in this tumor, production of PTH-rP was demonstrated by normalization of serum PTH-rP after the tumorectomy and immunoreactivity for PTH-rP in the tumor cells.     

Distinction of endometrial stromal sarcomas from 'hemangiopericytomatous' tumors using a panel of immunohistochemical stains.

Endometrial stromal sarcomas are low-grade malignant tumors that may pose a diagnostic challenge, especially when they are present in an extrauterine site. Owing to the presence of an arborizing vasculature and cells with an undifferentiated appearance, endometrial stromal sarcomas can be confused with several soft-tissue neoplasms. We studied 17 endometrial stromal sarcomas, eight hemangiopericytomas, 14 solitary fibrous tumors, and 16 synovial sarcomas immunohistochemically, detecting the following antigens: CD10, estrogen receptor, progesterone receptor, bcl-2, CD34, smooth muscle antigen, epithelial membrane antigen and cytokeratin (AE1/AE3). Most endometrial stromal sarcomas stained positively for CD10 (16/17), estrogen receptor (17/17), progesterone receptor (15/17), and bcl-2 (17/17). Staining with antismooth muscle antigen was seen in 11 of 17 cases of endometrial stromal sarcoma, with more intense staining seen in areas showing smooth muscle differentiation. Staining with AE1/3 was seen in four of 17 endometrial stromal sarcomas, with two of the positive cases containing epithelioid cells. None of the endometrial stromal sarcomas expressed epithelial membrane antigen or CD34. More than half of the hemangiopericytomas (4/8) and solitary fibrous tumors (9/14) cases demonstrated CD10 expression either focally or in a patchy cytoplasmic and membranous pattern. Hemangiopericytomas, solitary fibrous tumors, and synovial sarcomas did not express estrogen receptor. Four of eight hemangiopericytomas and seven of 14 solitary fibrous tumors also showed patchy progesterone receptor expression. CD34 expression was identified in six of eight hemangiopericytomas and 13 of 14 solitary fibrous tumors, but we did not find expression of CD34 in synovial sarcoma. Differences between endometrial stromal sarcoma and other soft-tissue tumors were detected for all of the immunohistochemical markers (P<0.05), except anti-bcl-2 and AE1/3. Antibodies against CD10 mark a substantial number of hemangiopericytomas and solitary fibrous tumors (albeit not diffusely) and should always be combined with antiestrogen receptor and CD34 when the differential diagnosis includes endometrial stromal sarcoma. Unlike estrogen receptor antibodies, progesterone receptor antibodies show at least focal nuclear staining in most hemangiopericytomas, solitary fibrous tumors and rare synovial sarcomas, and are not useful for this differential diagnosis. All endometrial stromal sarcomas expressed bcl-2, mostly in a diffuse pattern, but this did not distinguish between endometrial stromal sarcoma and mimics. We therefore recommend the use of a small antibody panel comprising anti-CD10, anti-estrogen receptor, and anti-CD34 to distinguish endometrial stromal sarcomas from tumors with a predominant hemangiopericytomatous growth pattern.     

Uterine epithelioid endometrial stromal sarcoma presenting as a "cervical polyp"

Although appearance of conventional uterine endometrial stromal sarcoma is easily recognized on histology, it may uncommonly assume unusual appearances such as uterine tumor resembling ovarian sex-cord tumor, thereby hindering its diagnosis. Recently, its manifestation as an epithelioid neoplasm was described. In this report, we detail yet another instance where this tumor adopted an epithelioid morphology, presenting itself as a polyp extruding from the cervical os in a 41-year-old Chinese woman. Both the polypectomy and subsequent hysterectomy specimens revealed a predominant proliferation of CD10-negative, caldesmon-negative, and CD117-positive epithelioid cells set within a stroma containing vascular proliferation resembling endometrial stromal tumor. Areas of typical low-grade endometrial stromal sarcoma containing spindle cells that were focally positive for CD10 and negative for CD117 were present in close association with the epithelioid areas. The differential diagnoses and possible implication of CD117 positivity are discussed.     

Uterine tumor resembling ovarian sex-cord tumor--a case report and review of the literature

A uterine tumor resembling an ovarian sex-cord tumor (UTROSCT) is a very rare lesion with only 38 cases reported in the literature so far. Here, we show an additional case of a pure UTROSCT with a DNA stemline at 1c in a 49-year-old woman presenting with abnormal vaginal bleeding. Problems in differential diagnosis arise mainly due to the variable histological picture of UTROSCT. Immunohistochemically, these tumors express cytokeratin, epithelial membrane antigen, vimentin, and smooth muscle actin. Moreover, in some cases, CD99 and alpha-inhibin are detectable. Although 36% of UTROSCT have infiltrative margins, almost all of them behave benignly. It is thus questionable whether the same prognostic criteria apply for these tumors as for endometrial stromal sarcomas. However, in the so-called mixed UTROSCT, the endometrial stromal sarcoma component determines the outcome.     

From Krukenberg to today: the ever present problems posed by metastatic tumors in the ovary. Part II

This is the second of a two-part consideration of metastatic tumors to the ovary. Here, the matter is considered in 16 categories, largely site-specific. The first tumor discussed is gastric carcinoma of intestinal-type whose ovarian manifestations have been the subject of a recent paper which emphasized its differences from the Krukenberg tumor. Coverage of intestinal adenocarcinoma emphasizes the landmark 1987 paper of RH Lash and WR Hart. The section on pancreatic neoplasms reemphasizes the problems caused by metastatic ductal carcinoma, considered primarily in Part I, and discusses less common issues such as spread of neuroendocrine and acinar cell carcinomas. The limited information on spread of tumors of the gallbladder and extrahepatic bile ducts is then reviewed before more detailed consideration of hepatic neoplasms, prompted by recent contributions on hepatocellular carcinoma and intrahepatic cholangiocarcinoma, the latter based on significant experience with this problem in Thailand. The section on appendiceal neoplasms highlights ovarian spread of diverse tumors ranging from typical intestinal-type adenocarcinoma to signet-ring cell carcinomas with various patterns which in the ovary may prompt diagnoses such as a goblet cell (mucinous) carcinoid tumor, but whose ovarian features place them in the category of a Krukenberg tumor. The diverse problems in differential diagnosis of carcinoid tumor (provoked by nested, acinar, and other patterns, including folliclelike spaces) are then reviewed. The section on breast cancer emphasizes that, although usually a manifestation of late stage disease and often not bulky in the ovaries, metastatic breast cancer may form large masses which can represent the clinical presentation. That patients with breast cancer have an increased risk of primary ovarian cancer and that the latter is more common than secondary spread of breast cancer is noted. The section on lung tumors largely reflects information in a recent paper that small cell carcinoma and adenocarcinoma are the lung cancers that spread to the ovary most commonly. The extremely broad differential diagnosis posed by metastatic malignant melanoma ranging from that of an oxyphilic tumor, to a small cell tumor, to a follicle-forming neoplasm, is then considered. The sections on renal cell carcinoma and other urinary tract neoplasms emphasize the differential diagnosis of metastatic clear cell carcinoma and primary clear cell carcinoma, an issue usually resolvable by an awareness of the various features of the ovarian variant, rarely or never seen in the renal variant. The section on metastatic sarcomas discusses endometrial stromal sarcomas, gastrointestinal stromal neoplasms, and miscellaneous other sarcomas. The endometrial stromal tumors are problematic largely because the history of a primary tumor may be remote, in the ovaries the typical growth and vascular pattern of endometrial stromal neoplasms is not always conspicuous, and some endometrial stromal sarcomas in the ovary show sex cordlike patterns of growth. Recent information has indicated that gastrointestinal stromal tumors may rarely have significant ovarian manifestations and if the primary neoplasm is overlooked, the ovarian tumor may be misdiagnosed, usually as an ovarian fibromatous tumor, but potentially as another primary neoplasm. The sections on ovarian spread of uterine carcinomas emphasize the problems owing to cervical adenocarcinomas, which have a greater tendency to involve the ovaries than squamous cell carcinomas and can simulate primary mucinous or endometrioid cancers. The final neoplasms considered are malignant mesothelioma and the desmoplastic small round cell tumor. The microscopic features of malignant mesothelioma are so different from those of primary ovarian carcinoma in most instances that the diagnosis should be readily established on routine microscopic evaluation. The differential diagnosis of the desmoplastic small round cell tumor is more complex because of the greater overlap with the many other small cell malignant tumors that may involve the ovaries primarily or secondarily. Nonetheless, differences exist in most cases and awareness of the entity should lead to consideration of the desmoplastic neoplasm, particularly in a young female. In this area, as in a number of others considered in the review, immunohistochemistry may play a significant, sometimes crucial, role. However, as pointed out in brief concluding remarks, despite the aid of that modality, as in surgical pathology overall, careful consideration of the clinical background, distribution of disease, gross characteristics and spectrum of routine microscopic findings, will lead to the correct diagnosis in the majority of cases and at the very least lead to formulation of a considered differential diagnosis such that use of special techniques may be judicious and those results placed in context of the time-honored clinical and pathologic features.     

Expression of androgen receptors in benign and malignant endometrial stromal neoplasms

Several studies have shown that endometrial stromal neoplasms express estrogen and progesterone receptors (ER, PR). To our knowledge, the presence or absence of androgen receptors (AR) in these rare uterine neoplasms has not been investigated. Tumors (n=20)—3 endometrial stromal nodules, 14 low-grade endometrial stromal sarcomas (ESS, low grade), and 3 high-grade endometrial sarcomas (undifferentiated endometrial sarcoma, UES)—were studied. Immunohistochemical analyses for ER, PR, and AR were performed on formalin-fixed, paraffin-embedded archival material. Positive immunoreactions for ER and PR were observed in 14 (70%) and 17 (85%) cases, respectively. Furthermore, 9 cases (45%) were positive for AR. Among 17 ESS and UES cases, 7 (41%) revealed positivity for AR. Two of three benign stromal nodules were also positive for AR. Moreover, one of the three high-grade sarcomas (undifferentiated endometrial sarcoma) was negative for both ER and PR, but showed positive reaction for AR. In summary, ARs are expressed in 45% of endometrial stromal neoplasms. In addition to determination of ER and PR, the results of immunohistochemical examination of AR in these rare uterine tumors may have some impact on the postoperative management of the patients.     

Uterine tumour resembling an ovarian sex cord tumour

Endometrial stromal sarcomas account for 0.25% of all uterine malignancies. These tumours were originally divided into low grade and high grade stromal sarcomas, but the recent World Health Organisation classification (2003) recognises low grade stromal sarcoma and undifferentiated endometrial sarcoma. Low grade sarcomas may exhibit other forms of differentiation, including smooth muscle and sex cord differentiation. In the latter form, the tumour contains epithelial-like or sex cord-like elements often with epithelioid appearance, arranged in nests, cords, trabeculae, solid, or tubular structures. If this element predominates, the tumour is considered to be a uterine tumour resembling ovarian sex cord tumour, and may cause diagnostic difficulties. This case report describes the histological and immunohistochemical features of a uterine stromal sarcoma showing exclusively a pattern reminiscent of ovarian sex cord tumour.     

New developments in endometrial stromal sarcoma

Endometrial stromal tumours have been recently reclassified in the WHO 2014 Classification due to the discovery of new genetic fusions. This has enabled the subdivision of previously described undifferentiated endometrial sarcomas into the molecularly-defined high grade endometrial stromal sarcoma (HG ESS) and undifferentiated uterine sarcoma (UUS). In this review, we discuss the discoveries behind the 2014 Classification and its rationale, and give practical tips for diagnosis of these neoplasms, as well as discussing the differential diagnoses that one may consider.     

Myxoid mixed low-grade endometrial stromal sarcoma and smooth muscle tumor of the uterus. Case report

We report the case of a 73-year-old female with myxoid mixed low-grade endometrial stromal sarcoma and smooth muscle tumor of the uterus. Grossly, the tumor sized 130 x 130 x 100 mm involved the uterine corpus almost in its entirety. Histologically, the tumor consisted of two cell types. In some areas, the tumor cells showed typical features of endometrial stromal tumors and resembled stromal cells of proliferative endometrium. In other areas, however, the tumor showed smooth muscle features and consisted of larger mostly epitheloid cells with a moderate amount of cytoplasm. In all areas, myxoid changes and multiple hyalinizing giant rosettes were present. The tumor infiltrated the myometrium in a pattern typical of low-grade endometrial stromal sarcoma. Immunohistochemically, the tumor cells showed expression of vimentin, estrogen and progesterone receptors and variable expression of CD10, α-smooth muscle actin, desmin, h-caldesmon, and cytokeratin AE1/AE3. Other markers examined including CD99, α-inhibin, cytokeratin CAM5.2, S-100 protein, and HMB45 were negative. To the best of our knowledge, mixed low-grade endometrial stromal and smooth muscle tumor with myxoid changes has not been described to date.     

Mesenchymale Uterustumoren

Uterine stromal neoplasms are classified into endometrial stromal nodules and stromal sarcomas, as well as undifferentiated sarcomas. The two former groups demonstrate identical histological composition, consisting of small monomorphous cells with scant cytoplasm and round nuclei and typically contain numerous arteriolar-type vessels. Stromal tumors are distinct from stromal nodules by virtue of their myometrial and vascular invasion. Undifferentiated sarcomas consist of polymorphic cells and lack any cytological similarity to the stroma of normal proliferative endometrium. There is no smooth or striated muscle differentiation. Adenosarcomas are mixed neoplasms with a low grade stromal sarcoma component containing benign glands, which are surrounded by condensed neoplastic stroma. Typical uterine tumors resembling ovarian sex cord tumors (UTROSCT Type2) show predominant sex cord differentiation in a well circumscribed nodule. Focal sex cord differentiation may occur in stromal nodules and stromal sarcomas (UTROSCT Type2).     

Fibromyxoid variant of endometrial stromal sarcoma with atypical bizarre nuclei

Endometrial stromal sarcoma (ESS) is the second most common malignant uterine mesenchymal tumor. It affects women primarily in the perimenopausal age group. ESSs are morphologically heterogeneous. The distinction between uterine smooth muscle tumors such as cellular leiomyoma and myxoid leiomyosarcoma and low-grade ESS can be problematic when stromal sarcomas show prominent smooth muscle differentiation and abundant myxoid stroma, respectively. We herein present a rare case of fibromyxoid variant of ESS, which was misdiagnosed as hydropic leiomyoma on intraoperative frozen section examination. Grossly, the uterine mass consisted of intracavitary and intramural portions. The intracavitary portion with extensive hydropic degeneration mimicked a hydropic leiomyoma. In contrast, the intramural portion displayed an obvious tongue-like myometrial invasion. Histologically, the tumor consisted of both cellular (20%) and myxoid (80%) areas. In the cellular areas, oval to spindle-shaped tumor cells with bland nuclear features were found to surround concentrically a rich vascular network of arterioles, a characteristic of ESS. In addition, two relatively well-circumscribed nodular lesions showing atypical bizarre nuclei were identified in the myxoid area. Immunohistochemically, the tumor cells were diffusely and strongly positive for CD10. The present case indicates a wide morphological spectrum of ESS. Fibromyxoid variant of ESS should be considered in the differential diagnosis of intracavitary and/or intramural uterine mesenchymal tumors with myxoid differentiation. It is important to avoid confusion between fibromyxoid ESS and myxoid leiomyosarcoma because of the differences in their clinical course, treatment, and prognosis.     

Uterine stromal neoplasms: a clinicopathologic and DNA flow cytometric correlation

Twenty-five uterine stromal neoplasms (five stromal nodules and 12 low-grade and eight high-grade stromal sarcomas) were studied to determine the correlation between clinicopathologic features, flow cytometric tumor DNA content and proliferative fraction, and patient outcome. Fifteen of the 20 sarcomas (five of them high grade) were confined to the uterus (stages I and II); the other five (two low grade and three high grade) extended outside the uterus (stages III and IV). Stromal nodules and low-grade sarcomas manifested diploid DNA content and low proliferative index. All stromal nodules and the majority of low-grade sarcomas pursued a benign clinical course. Two cases of low-grade sarcoma ran a malignant course; both patients had high-stage disease. Three of the high-grade sarcomas were diploid and five were aneuploid. All eight neoplasms demonstrated high proliferative index and seven ran a malignant course (four of five were stage I and three of three were stage IV). Three high-grade stage I tumors had a low mitotic rate but a high proliferative index and ran an aggressive course. All high-stage sarcomas were clinically aggressive, irrespective of their histologic classification or DNA characteristics. The proliferative index by flow cytometry may offer an objective adjunct in predicting the aggressive potential of a subset in low-stage neoplasms.