CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms

AIMS: The CD10 antigen is expressed in acute lymphoblastic leukaemia and follicle centre cell lymphoma. A recent study investigating the expression of CD10 in a wide range of non-haematopoietic neoplasms found positive staining in a small number of endometrial stromal sarcomas as well as in normal endometrial stroma. The present study aimed to ascertain whether CD10 positivity is indeed found in normal endometrial stroma and endometrial stromal neoplasms. Staining of a range of tumours which can be confused morphologically with endometrial stromal neoplasms was also undertaken to ascertain whether antibodies against CD10 are of value in a diagnostic sense. METHODS AND RESULTS: Neoplasms included in the study were endometrial stromal nodule (n=1), low-grade endometrial stromal sarcoma (ESS) (n=13), high-grade ESS (n=6), mixed endometrial stromal-smooth muscle tumour (n=1), uterine cellular leiomyoma (n=10), uterine leiomyosarcoma (n=5), adult granulosa cell tumour (AGCT) (n=10), undifferentiated endometrial carcinoma (n=6), uterine carcinosarcoma with an endometrial stromal component (n=1) and type II uterine mesenchymal tumour with sex cord-like elements (n=1). Cases of proliferative (n=5), secretory (n=5) and atrophic (n=3) endometrium were also stained. There was positive staining of stroma but not of glands in all cases of non-tumorous endometrium. There was positive staining of the endometrial stromal nodule and of all low-grade ESS. Staining in these varied but was often diffuse and of moderate to strong intensity. There was positive staining of four of six high-grade ESS, but this was usually focal. There was also positive staining of the endometrial stromal component in the mixed endometrial stromal-smooth muscle tumour and in the uterine carcinosarcoma. Most cellular leiomyomas were completely negative although three exhibited weak positivity. There was some positivity, usually focal or weak, of three of five leiomyosarcomas. Most AGCT and undifferentiated carcinomas were completely negative although one case of each exhibited focal staining. There was focal staining of the type II uterine mesenchymal tumour with sex cord-like elements. CONCLUSION: CD10 is a reliable and sensitive immunohistochemical marker of normal endometrial stroma. Positivity, which is often strong and/or diffuse is found in endometrial stromal nodules and low-grade ESS. Positive staining with CD10, when strong and diffuse, may be useful in distinguishing these tumours from histological mimics, especially cellular leiomyoma and AGCT which are generally negative. In this situation, CD10 should be used as part of a panel which might include desmin and alpha-inhibin depending on the differential diagnosis considered. Positive staining with CD10 in a high-grade uterine sarcoma which is negative with muscle markers might indicate endometrial stromal differentiation and identify a group of neoplasms which it is correct to diagnose as high-grade ESS rather than undifferentiated uterine sarcoma.     

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.     

Nucleolar organizer regions in myogenic stromal tumours of the stomach

Summary Silver staining of nucleolar organizer regions (AgNOR) was studied in 26 primary benign and malignant gastric stromal tumours of myogenic origin. The absolute number of AgNOR per nucleus and the size of AgNOR were compared with histomorphologic features of the tumours.The total number of AgNOR per nucleus in epithelioid and spindle cell leiomyosarcomas significantly (p<0.001) exceeded that in leiomyomas, cellular leiomyomas and epithelioid leiomyoblastomas. The mean number or the size of AgNOR did not correlate with the number of mitoses or the tumour size. In addition, large and bizarre AgNOR were seen predominantly in histologically malignant tumours. Only one exceptional epithelioid leiomyoblastoma recurred despite a lack of conventional characteristics of malignancy and a low AgNOR count.Therefore, quantitative determination of the number of AgNOR is a new independent variable in myogenic gastric tumours. It provides additional information for the histopathological evaluation of this heterogenous group of mesenchymal tumours.     

Endometrial stromal sarcoma of vaginal and para-vaginal localization. Morphology, diagnosis and differential diagnosis

Endometrial stromal sarcomas constitute a subgroup of malignant mesenchymal uterine neoplasms and comprise biologically somewhat different variants. Their occurrence in extrauterine tissues is possible but extremely rare and therefore they are quite often mistaken for other tumours. Reported in this paper is a stromal sarcoma in vaginal and paravaginal localization (64-years old woman). It was the purpose of our study to present the histological structure in comparison to uterine neoplasms and to discuss differential diagnosis. It could be demonstrated that histological features of the actual case corresponded precisely to the respective uterine tumours originating within the myometrium. In extrauterine position, haemangiopericytomas, leiomyosarcoma, malignant schwannomas, fibrosarcomas and synovial sarcomas as well as Müllerian adenosarcomas and carcinosarcomas should be taken into account. Important histological features facilitating distinction of endometrial stromal sarcomas from the aforementioned malignant tumours are discussed, and some comments are added with regard to histogenetical interpretation.     

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.     

AgNOR counts and determination of malignancy in stromal tumours of the stomach and small intestine.

Twenty four primary stromal tumours of the stomach and small intestine were investigated by silver staining of interphase nucleolar organiser regions (AgNORs) in an attempt to obtain an objective criterion for prediction of malignant tumour behaviour. Malignant tumours tended to have higher AgNOR counts than their benign counterparts, but this increase was small and there was some overlap between the two groups. There was a correlation between the mean AgNOR count and the mitotic count. There was no correlation between tumour size and these two measurements. This study suggests that in these stromal tumours the AgNOR count is not a useful independent predictor of malignant behaviour.     

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.     

Different methylation levels in the KLF4, ATF3 and DLEC1 genes in the myometrium and in corpus uteri mesenchymal tumours as assessed by MS-HRM

Mesenchymal tumours of the corpus uteri comprise common benign lesions – leiomyomas and very rare malignant variants – sarcomas. It can be difficult to distinguish between the particular types of mesenchymal tumours pre-surgically. Primarily, leiomyomas and the very aggressive leiomyosarcomas can be easily misdiagnosed when using only imaging devices. Therefore, a reliable non-invasive marker for these tumour types would provide greater certitude for patients that the lesion remains benign. Our collection comprises 76 native leiomyomas, an equal number of healthy myometrium samples and 49 FFPE samples of various types of sarcomas. The methylation level was assessed by MS-HRM method and we observed differences in the methylation level between healthy, benign and (semi)malignant tissues in the KLF4 and DLEC1 genes. The mean methylation levels of leiomyomas compared to myometrium and leiomyosarcomas were 70.7% vs. 6.5% vs. 39.6 % (KLF4) and 66.1% vs. 14.08% vs. 37.5% (DLEC1). The ATF3 gene was differentially methylated in leiomyomatous and myometrial tissues with 98.1% compared to 76.6%. The AUC values of the predictive logistic regression model for discrimination between leiomyomas and leiomyosarcomas based on methylation levels were 0.7829 (KLF4) and 0.7719 (DLEC1). Finally, our results suggest that there should be distinct models for the methylation events in benign leiomyomas and sarcomas, and that the KLF4 and DLEC1 genes can be considered potential methylation biomarkers for uterine leiomyomas.     

Expression of CD10 in malignant müllerian mixed tumors and adenosarcomas: an immunohistochemical study.

CD10 has been demonstrated to be positive in endometrial stromal sarcoma (ESS) and thus is useful in establishing the diagnosis, but its expression in malignant müllerian mixed tumor (MMMT) and müllerian adenosarcoma remains to be clarified. In this study, 12 cases of MMMT (9 uterine, 2 tubal, and 1 metastatic), 6 cases of müllerian adenosarcoma (three corporeal, two cervical, and one tubal), and 7 cases of primary uterine sarcomas had their tissues examined immunohistochemically for expression of CD10, desmin, myoglobin, alpha-smooth muscle actin (SMA), and cytokeratin. Of the primary uterine sarcomas, two were primary rhabdomyosarcomas (one cervical and one corporeal), two were ESSs, two were high-grade leiomyosarcomas, and one was a high-grade endometrial sarcoma. Sarcomatous components in all cases of MMMT and müllerian adenosarcoma, as well as all uterine sarcomas, were positive for CD10, showing moderate to marked staining intensity with varying distribution except in one MMMT, which showed weak and very focal staining. In four MMMTs, three adenosarcomas, and one rhabdomyosarcoma, myoglobin- and/or desmin-positive rhabdomyoblastic cells were positive for CD10. The immunoreactivity for CD10 showed the same distribution for alpha-SMA and myoglobin in three and two MMMTs, respectively. In five cases of MMMT, carcinomatous components were focally positive for CD10, and in two cases small populations of round or short spindle cells in sarcomatous components were positive for CD10, alpha-SMA, and cytokeratin (CAM5.2). These results indicate that CD10 expression is not restricted to ESS but can be positive in MMMT and müllerian adenosarcoma as well as in a variety of uterine tumors including high-grade leiomyosarcoma and rhabdomyosarcoma. CD10 expression might be one of the characteristics of müllerian system-derived neoplastic mesenchymal cells.     

Transforming growth factor-alpha, epidermal growth factor receptor, and PCNA immunoexpression in uterine leiomyosarcomas and leiomyomas in B6C3F1 mice.

The role of growth factors in the development of murine uterine mesenchymal tumors is unknown. In this study, immunohistochemical expression of transforming growth factor alpha (TGF-alpha) and its receptor epidermal growth factor (EGF-R) was assessed in spontaneous uterine leiomyomas and leiomyosarcomas in B6C3F1 mice. Cell proliferation, which has been induced by some growth factors, was evaluated by immunohistochemical detection of an endogenous marker of cell proliferation, proliferating cell nuclear antigen (PCNA). PCNA labeling indices were determined and compared to the intensity and distribution of TGF-alpha staining in sequential sections of control myometrium or tumor tissue. Results showed uterine leiomyosarcomas had positive cytoplasmic staining for TGF-alpha; however, all uterine leiomyomas evaluated were negative. Positive EGF-R staining was also observed in the uterine leiomyosarcomas, but not in the leiomyomas. EGF-R immunoexpression was detected primarily within the cytoplasm of the leiomyosarcoma cells, with occasional nuclear immunoreactivity. Immunohistochemical staining for PCNA was more intense and there were increased numbers of positively staining nuclei in the leiomyosarcomas compared to samples of control myometrium or leiomyomas. The mean labeling index for the uterine leiomyosarcomas (7.40%) was significantly (p < 0.01) higher than that of leiomyomas (0.29%) and control uterine myometrium (0.13%). We conclude, that TGF-alpha and its receptor, EGF-R, are expressed more intensely in uterine leiomyosarcomas, compared to leiomyomas in B6C3F1 mice. Immunoexpression of TGF-alpha may be an important biomarker of malignancy in uterine smooth muscle tumors in mice. Futhermore, TGF-alpha may play a critical role in increased proliferation of uterine smooth muscle tumor cells as suggested by increased immunolocalization of PCNA in rodent leiomyosarcomas expressing TGF-alpha, although other factors regulating cell replication can not be ruled out.     

Comparative clinicopathologic and immunohistochemical analysis of uterine sarcomas diagnosed using the World Health Organization classification system

Uterine sarcomas are rare tumors that account for 3% to 7% of uterine cancers. Their histopathologic classification was revised by the World Health Organization (WHO) in 2003. The objectives of this study were to determine the frequency of different subtypes of uterine sarcoma applying the WHO criteria to a series of cases, compare the outcome of patients with different subtypes, and compare their immunoprofiles using a panel of immunomarkers. Thirty-four uterine sarcomas were identified for a 20-year period (1988-2008). Eighteen benign tumors of smooth muscle or endometrial stromal origin served as a comparison group. A tissue microarray was prepared and immunostaining performed for 10 selected oncoproteins involved in cell proliferation (Ki-67, P53, p16, and phosphatase and tensin homolog [PTEN]), cell differentiation (CD10, h-caldesmon, estrogen receptor, and progesterone receptor), and apoptosis (bcl-2 and Twist). Hierarchical clustering analysis of the immunohistochemical results was performed. The uterine sarcomas were classified as follows: 20 leiomyosarcomas, 9 endometrial stromal sarcomas, and 5 undifferentiated endometrial sarcomas. The outcome for patients with uterine sarcoma was poor, irrespective of histologic type, even for those with stage I tumors. Of the patients with follow-up available, 12 (67%) of 18 with leiomyosarcoma, 4 of 5 with undifferentiated sarcoma, and 4 of 7 with endometrial stromal sarcoma experienced recurrence and 8 patients with high-grade sarcomas died of tumor. In our series, most uterine sarcomas were leiomyosarcomas. Comparison was made between leiomyosarcomas that recurred and those with a favorable outcome and 3 patients with leiomyosarcoma without evidence of recurrence on long-term follow-up had tumors that were negative/low expressors of Ki-67, p53, p16, and Twist, with strong expression of bcl-2. A subset of undifferentiated endometrial sarcomas composed of cells with uniform nuclei may be a separate entity from those with nuclear anaplasia and may be related to low-grade endometrial stromal sarcomas. It may be possible to identify a subset of leiomyosarcomas with a favorable prognosis based on staining with a panel of immunomarkers for cell proliferation and apoptosis.     

Carbonic anhydrase isozymes II, IX, and XII in uterine tumors

Histopathological diagnostics of gynecological malignancies continues to be challenging despite the well established criteria. For example, the morphological distinction of uterine leiomyosarcoma from certain variants of benign leiomyoma can be difficult. Herein, we investigated the expression of Carbonic anhydrase (CA) II, IX, and XII in the normal endometrium, leiomyomas, uterine sarcomas, and endometrial adenocarcinomas using immunohistochemistry. These isozymes are considered promising diagnostic markers and therapeutic targets. The normal endometrium showed high CA XII expression, whereas the signals were lower in endometrial adenocarcinoma (p < 0.004). Only sporadic CA IX staining was found in the normal endometrium, whereas the enzyme was overexpressed in most cases of endometrial adenocarcinoma (p < 0.005). CA II expression was slightly weaker in the normal endometrium than that in the adenocarcinomas (p < 0.008). Positive immunostaining reactions for CAs were observed in the uterine sarcomas, whereas all leiomyomas were negative for CA II and XII. A comparison between leiomyomas and sarcomas showed statistically significant differences for all studied isozymes (p < 0.001). Our study shows that CA isozymes could together serve as histopathological biomarkers for differential diagnosis between uterine leiomyosarcoma and leiomyoma. In addition to being found in leiomyosarcomas, CA II and IX were overexpressed in endometrial adenocarcinoma, where they might regulate the pH of the tumor microenvironment.     

Recent developments in uterine mesenchymal neoplasms

Smooth muscle and endometrial stromal tumours represent the two most common uterine mesenchymal neoplasms that may present diagnostic dilemmas for the practising surgical pathologist. Recent changes in morphological and staging criteria, as well as the discovery of new immunohistochemical markers, have improved the diagnosis and classification of these tumours. We highlight the difficulty in distinguishing tumour cell necrosis from infarct‐type necrosis and the limited utility of p16 immunohistochemical expression in the diagnosis of leiomyosarcoma. We also discuss the controversial use of mitotic activity and necrosis as prognostic factors in endometrial stromal sarcomas. Emerging genetic information has also greatly expanded our understanding of ‘sarcomagenesis’ in both tumour types and may provide insight into potential therapeutic targets for the treatment of leiomyosarcoma and endometrial stromal sarcomas, harboring MED12 (mediator complex subunit 12) mutations and recurrent gene rearrangements, respectively. In this review, we discuss the core updates in the diagnosis and classification of uterine leiomyosarcomas and endometrial stromal sarcomas, highlighting new and important molecular genetic findings that may drive pathogenesis.     

Expression of metalloproteinases endometrial stromal sarcoma: immunohistochemical study using image analysis.

AIM: To investigate the expression of matrix metalloproteinases (MMP), a group of proteolytic enzymes with a central role in extracellular matrix invasion and degradation, in stromal sarcomas. METHODS: 11 endometrial stromal sarcomas (four low grade tumours, seven high grade) were stained for MMP-2, MMP-3, and MMP-9 using immunohistochemical stains. The surgical material consisted of nine hysterectomy specimens and two pelvic recurrences. Three hysterectomy specimens, removed for leiomyomas, were studied as controls. Staining area was evaluated using image analysis. RESULTS: Age at the time of diagnosis ranged from 21 to 67 years. Four of the 11 patients (three with high grade tumours and one with a low grade tumour) died of the disease, six remained free of disease, and one was lost to follow up. Staining for MMP-2, MMP-3, and MMP-9 was more diffuse in high grade tumours than in low grade tumours and controls. Staining for MMP-3 and MMP-9 was more pronounced in high grade than in low grade tumours (p = 0.04; p = 0.05). Staining for MMP-9 was significantly greater in all stromal sarcomas than in controls (p < 0.001 for high grade tumours v controls; p < 0.01 for low grade tumours v controls). Diffuse staining for MMP-2, exceeding 90% of the tumour area, was observed in three of seven high grade tumours but in no low grade tumours. There was no apparent correlation between staining for any of the three enzymes and survival. CONCLUSIONS: Both low and high grade endometrial stromal tumours express matrix metalloproteinases. MMP-3 and MMP-9 are expressed more diffusely in high grade than in low grade tumours. In the individual case, diffuse staining for MMP-2 appears to best characterise the high grade tumours. Thus staining for MMP-2 may aid in differentiating high grade from low grade tumours, and MMP-9 in differentiating normal endometrial stroma from low and high grade endometrial stromal sarcomas. MMP expression does not appear to predict disease outcome in endometrial stromal sarcoma.     

Significance of AgNOR score in benign and malignant soft tissue tumours

AgNOR staining was employed on FNAC and histopathological sections obtained from patients with soft tissue tumours. The study comprised of 20 normal appearing soft tissues, 74 benign and 36 malignant soft tissue tumours. The slides were stained with AgNOR in order to differentiate between benign and malignant soft tissue tumours. The mean AgNOR count in normal appearing soft tissues, benign lesions and malignant lesions was 1.04+/-0.10 (0.94-1.14), 1.51+/-0.21 (1.1-2.1) and 4.96+/-1.33 (2.57-7.21) respectively. The mean AgNOR count was found to be higher in benign soft tissue tumours as compared to normal appearing soft tissues and the difference was found to be statistically significant. The mean AgNOR count in soft tissue sarcomas was found to be higher as compared to both normal appearing soft tissues and benign soft tissue tumours and the results were found to be statistically significant. The increased AgNOR score in both benign and malignant soft tissue tumours as compared to normal appearing soft tissues indicates high proliferative activity. Thus AgNOR staining is a simple and useful method for estimating tumour cell proliferation thereby differentiating normal appearing soft tissues from benign and malignant soft tissue tumours.     

Proliferative Activity in Normal Salivary Gland and Pleomorphic Adenoma A Study by Argyrophilic Nucleolar Organizer Region (AgNOR) Staining

Proliferative activity of the structural components of normal salivary glands (27 cases) and characteristic histological areas in salivary pleomorphic adenoma (51 cases) was examined by visualization of argyrophilic nucleolar organizer regions (AgNORs). In the normal salivary gland, there were clusters of cells, each with two or three AgNOR dots, within the intercalated ducts. The mean number of AgNORs in this portion was 1.80, which was significantly higher than in the other epithelial parts. This indicates vigorous proliferative activity of the intercalated ducts, and thus the ducts may play an important role as reserve cells in neoplastic transformation. In pleomorphic adenoma, solid nests had a high AgNOR count (1.61), showing a significant difference from the tumor cells scattered in the "stroma". Thus the decrease in proliferative ability might occur concurrently with formation of the extracellular matrix. Acta Pathol Jpn 42: 573 578, 1992.     

Proliferative activity in normal salivary gland and pleomorphic adenoma. A study by argyrophilic nucleolar organizer region (AgNOR) staining.

Proliferative activity of the structural components of normal salivary glands (27 cases) and characteristic histological areas in salivary pleomorphic adenoma (51 cases) was examined by visualization of argyrophilic nucleolar organizer regions (AgNORs). In the normal salivary gland, there were clusters of cells, each with two or three AgNOR dots, within the intercalated ducts. The mean number of AgNORs in this portion was 1.80, which was significantly higher than in the other epithelial parts. This indicates vigorous proliferative activity of the intercalated ducts, and thus the ducts may play an important role as reserve cells in neoplastic transformation. In pleomorphic adenoma, solid nests had a high AgNOR count (1.61), showing a significant difference from the tumor cells scattered in the "stroma". Thus the decrease in proliferative ability might occur concurrently with formation of the extracellular matrix.     

Expression of CD44 standard and isoforms V3 and V6 in uterine smooth muscle tumors: a possible diagnostic tool for the diagnosis of leiomyosarcoma.

Alterations of CD44 proteins, a family of cell adhesion molecule, have been linked with tumorigenesis, carcinogenesis, and prognosis in various neoplasms. Our aims were to evaluate and compare CD44 isoforms expression patterns in normal myometrium, uterine leiomyomas, and leiomyosarcomas and to correlate CD44 expression with clinicopathologic parameters. Fresh (n = 15) and formalin-fixed, paraffin-embedded (n = 76) tissues samples of myometrium, leiomyomas, and leiomyosarcomas were used for immunoblotting and immunohistochemistry, respectively. Semiquantitative evaluation was made after immunostaining. Monoclonal antibodies were used. By immunoblotting in myometrium and leiomyomas samples, we observed a band at 85 kd, corresponding to the apparent molecular weight of CD44s, and bands at 140 kd with the monoclonal antibodies against CD44v3 and CD44v6. In leiomyosarcomas, CD44s and CD44v6 were detected, but not CD44v3. By immunohistochemistry, decreased CD44s expression was found in leiomyomas and leiomyosarcomas (73.9% +/- 16.6% and 82.1% +/- 20.7%, respectively) compared with myometrium (97.3% +/- 6.2%; P < .0001). No CD44v6 staining was detected in myometrium, leiomyomas, and leiomyosarcomas. No CD44v3 expression was detected in leiomyosarcomas, whereas myometrium and leiomyomas expressed CD44v3. For the diagnosis of leiomyosarcoma, the absence of CD44v3 staining had a sensitivity, specificity, and positive and negative predictive values of 100%. In patients with recurrence of leiomyosarcomas, CD44s expression was decreased (P = .03). We conclude that CD44s immunostaining in leiomyosarcomas may have prognostic significance. The loss of CD44v3 expression could be used as a putative diagnostic tool for uterine leiomyosarcomas.     

The Stromal and Myogenic Sarcomas of the UterusDie stromatogenen und myogenen Sarkome des Uterus

Stromal sarcomas of the uterus generally originate as homologous tumors from endometrial stromal cells with fixed potentialities. They may be composed of one type of cell or of several types, or rarely they may consist only of endometrial granulocytes. From the same source but with a more favorable prognosis is endolymphatic stromatosis, which arises primarily in the myometrium but does not diffusely invade it, as the stromal sarcoma does. By contrast, heterologous malignant mesenchymal mixed tumors of the endometrium originate from Müllerian epithelium derived from the mesoderm, and are therefore pluripotential. In this group we find rhabdomyosarcomas and chondroblastomas which have a very poor prognosis.The myogenic sarcomas are three times more common, and arise from smooth muscle cells of the myometrium or its blood vessels. The degree of nuclear pleomorphism may vary considerably, from normal to giant cell types, and may differentiate also as clear-cell myoblasts. They portend a somewhat more favorable prognosis than the stromal sarcomas.