Undifferentiated Endometrial Sarcoma Research Articles

Undifferentiated Uterine Sarcoma Presenting as a Pathologic Humerus Fracture

Undifferentiated uterine sarcomas are rare malignancies often presenting at advanced stage. A female in her ninth decade presented to our MEDCEN emergency department complaining of onset of severe right arm pain while performing activities of daily living. A pathologic humeral fracture was diagnosed and subsequent orthopedic evaluation resulted in a biopsy and placement of her arm in a cooptation splint and sling. An abdominal exam revealed a 10-cm mass in the right lower quadrant that was thought to originate from the uterus. Computed tomography imaging was concerning for a primary endometrial process and she was referred to gynecologic oncology. Her humeral biopsy was consistent with a poorly differentiated metastatic sarcoma. An endometrial biopsy was consistent with undifferentiated uterine sarcoma, the origin of her humeral lesion. Humeral metastasis is an uncommon presentation for undifferentiated endometrial sarcomas.

Immunohistochemical study and fluorescent in situ hybridization analysis of JAZF1 in 67 cases of endometrial stromal tumors collected in a tissue microarray.

10069 Background: Endometrial stromal tumours are rare uterine lesions comprising undifferentiated endometrial sarcoma (UES), endometrial stromal sarcoma low grade (ESS) and stromal nodule (SN). Complex caryotypes and frequent 7p deletion are found in the malignant types, and a translocation t(7;17) involving two finger zinc gene JAZF1 and JJAZ1/SUZ12 has also been recently described. Methods: We performed an immunohistochemical study to evaluate the expression of oestrogen and progesterone receptors, Ki67, P16 and P53 and a in situ fluorescent hybridization (FISH) studying JAZF1(7p15) locus using formalin fixed paraffin embedded tissues of 12 SN, 41 ESS and 14 UES collected in a tissue microarray. Results: Immunohistochemical analysis of SN and ESS showed a high nuclear expression of both oestrogen receptor (OR) and progesterone receptor (PR), associated with a low nuclear expression of Ki67, P16 and P53. In opposite, UES exhibit a low expression of OR and PR and a high nuclear expression of Ki67, P16 and P53. The difference for each of the immunostainings was highly statistically significant between ESS and UES (p<0,0005), but not between SN and ESS. Among the 44 cases with available FISH status, the dissociation of JAZF1 (7p15) meaning the specific translocation was found in 25% of SN (n=2/8), 35% of ESS (n=8/23), and was absent in UES (n=0/13). Interestingly, we observed also a deletion of the second allele of the JAZF1 gene in 80% of the 10 cases with dissociation of JAZF1. Conclusions: Immunohistochemical analysis of OR, PR, P16, P53 and Ki67 could be very useful for the differential diagnosis of endometrial stromal tumours especially between ESS and UES. The absence of JAFZ1 dissociation in UES suggest different oncogenic pathways between UES and NS/ESS, that support the current World Health Organization classification of tumours. Moreover, the translocation was associated in 80% with deletion of second JAZF1 allele suggesting a loss of function of the gene. However, further study are necessary to find out the regulatory consequences of JAZF1 function's loss and translocation. No significant financial relationships to disclose.

Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Soft tissue sarcomas: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Endometrial Stromal Sarcomas

Endometrial stromal tumors are uncommon mesenchymal tumors of the uterus. The classification of these tumors has evolved and the most current World Health Organization classification (2003) divides these neoplasms into: endometrial stromal nodule, low-grade endometrial stromal sarcoma, and undifferentiated endometrial sarcoma. The salient clinicopathologic features of these tumors are described, and a comprehensive review of literature pertaining to potential prognostic factors in endometrial stromal sarcomas is provided. Clinical factors, including age, race, parity and menopausal status, and pathologic factors, including tumor size, tumor stage, nuclear atypia, mitotic activity, tumor necrosis, lymphovascular space invasion, DNA ploidy and proliferative activity, and expression of hormone receptors, have been explored with varying outcomes. Surgicopathologic stage seems to be the most important prognostic factor in low-grade endometrial stromal sarcomas. The impact of other prognostic factors on survival is unclear or controversial, especially in patients with stage I tumors.

Coincident expression of β-catenin and cyclin D1 in endometrial stromal tumors and related high-grade sarcomas

Aberrant activation of the Wnt signaling pathway has been implicated in tumorigenesis of a wide range of tumors, including colorectal cancer. Regarding endometrial stromal tumors and related high-grade sarcomas, there have been some reports regarding nuclear accumulation of β-catenin. To clarify the function of the aberrant Wnt signaling pathway in these tumors, we searched for mutations of the CTNNB1 (β-catenin) gene and APC gene by PCR direct sequencing and analyzed the methylation status of SFRP genes. We also examined overexpression of cyclin D1 and MMP-7, which are direct target genes of β-catenin. Eight endometrial stromal nodules, 16 low-grade endometrial stromal sarcomas, and 13 undifferentiated endometrial sarcomas were examined. PCR and direct sequencing revealed no mutation of the β-catenin gene or the APC gene. Concerning the promoter methylation status of SFRP genes, methylation-specific PCR revealed no significant difference between the group with nuclear β-catenin expression and that without nuclear β-catenin expression. Immunohistochemistry revealed overexpression of cyclin D1 in 2 out of 8 endometrial stromal nodules, 1 out of 17 low-grade endometrial stromal sarcomas, and 6 out of 13 undifferentiated endometrial sarcomas, and these 6 undifferentiated endometrial sarcomas simultaneously expressed nuclear β-catenin. Interestingly, all six undifferentiated endometrial sarcoma cases with cyclin D1 overexpression histologically featured rather uniform nuclei. In contrast, the six cases of undifferentiated endometrial sarcoma with highly pleomorphic nuclei were all negative for cyclin D1. In conclusion, among endometrial stromal tumors and related sarcomas, undifferentiated endometrial sarcomas featuring uniform nuclei were characterized by frequent coincident expression of β-catenin and cyclin D1. This finding raises the possibility that cyclin D1 is upregulated by β-catenin in these high-grade sarcomas previously called high-grade endometrial stromal sarcoma.

Molecular Profiling of Endometrial Malignancies

Molecular profiling of endometrial neoplasms reveals genetic changes in endometrial carcinomas that support the dualistic model, in which type I carcinomas are estrogen-dependent, low grade lesions and type II carcinomas are nonestrogen dependent and high grade. The molecular changes in type I endometrial carcinomas include mutations in PTEN, PIK3CA, KRAS, and β-catenin, along with microsatellite instability, whereas type II endometrial carcinomas are characterized by genetic alterations in p53, HER2/neu, p16, and E-cadherin. For endometrial neoplasms with a malignant mesenchymal component, C-MYC mutations and loss of heterozygosity are frequently seen in carcinosarcomas, and a fusion gene, JAZF1/JJAZ1, is distinctive for endometrial stromal sarcoma. In addition, p53 mutations may play an important role in tumorigenesis of undifferentiated endometrial sarcoma. These molecular changes can help in the diagnosis of endometrial neoplasms, as well as form the basis of molecular targeted therapy.

Undifferentiated Endometrial Sarcoma of the Ovary: A Case Report with Review of Recent Literature and Discussion of Lacking Specificity of CD10 Immunoreactivity

Undifferentiated endometrial sarcomas (UESs) of the ovary are very rare tumors. This paper presents a case of a 56-year-old patient with a history of hysterectomy and bilateral salpingectomy seven years ago for uterine leiomyomata. Intraoperatively, a tumor originating from the left ovary, adherent to the sigmoid colon, with infiltration of the small intestine and the vaginal apex was found. Histologically, the tumor was composed of pleomorphic round and oval to spindled cells with polymorphous vesicular nuclei with coarse chromatin and large nucleoli. Mitotic activity was brisk. There were large necrotic areas. Adjacent to the tumor tissue endometrium-like glands surrounded by fibrous stroma with macrophages corresponding to ovarian endometriosis were noted. Tumor cells showed diffuse strong immunoreactivity for vimentin and patchy strong staining for CD10; no reactivities were found for AE1/AE3, desmin, S-100, LCA, CD20, c-kit, and CD31. The patient died of her neoplastic disease four months postoperatively. CD10 is frequently expressed in different gynecopathological as well as other lesions, and, thus, nonspecific without relevance to the classification of this case. Morphological features, extensive sampling, and appropriate immunohistochemistry including markers for cytokeratins and myogenic differentiation are mandatory to arrive at the correct diagnosis.

Primary extrauterine undifferentiated endometrial sarcoma with osseous and cartilaginous differentiation

Primary extrauterine undifferentiated endometrial sarcoma with osseous and cartilaginous differentiation

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.

Klinik der uterinen Sarkome

There are many common features between uterine sarcomas - leiomyosarcoma, endometrial stromal sarcoma, undifferentiated endometrial sarcoma and adenosarcoma -with regards to course, therapy and follow-up, such as post-menopausal bleeding or additional premenopausal bleeding, as well as rapid growth. There is a new staging system according to FIGO and new therapy recommendations according to NCCN. Prior to therapy, imaging staging of the pelvis, abdomen and chest should be carried out due to the frequency with which metastases are found at the time of diagnosis. In the case of disease spread in uterine sarcomas and malignant mixed tumors, good supportive therapy is a possible therapy option instead of chemo- or radiotherapy. The approach - observation, surgery, lymphonodectomy, mono- or polychemotherapy, radiotherapy, hormone therapy - is chosen according to the extent of spread and the resection status. Neoadjuvant therapies are not as yet established.

Low-Grade Endometrial Stromal Sarcoma and Undifferentiated Endometrial Sarcoma: A Comparative Analysis Emphasizing the Importance of Distinguishing Between These Two Groups

Endometrial stromal sarcomas (ESSs) are rare tumors whose classification is still controversial. In this study, the authors studied 19 patients diagnosed with ESS at the Hospital S João, Porto, Portugal; reviewed their files and material; and performed immunohistochemical study for CD10, desmin, and smooth muscle actin markers, aiming to compare low-grade endometrial stromal sarcomas (LG-ESSs) and undifferentiated endometrial sarcomas (UESs) using the World Health Organization (WHO) classification. Twelve cases (63%) were classified as LG-ESS and 7 (37%) as UES. The median age at diagnosis was 49 years, and women with LG-ESS tended to be younger than those with UES. Most cases (7/11) had a previous echographic diagnosis of leiomyoma. A biopsy or curettage was performed in 6 cases, providing a definitive diagnosis of malignancy in 4. Frozen section was performed in 4 patients. The majority (63%) of patients were FIGO stage I. Twelve (63%) cases showed diffuse or focal expression of CD10. Desmin and smooth muscle actin expression was focal in 4 (21%) tumors. Patients with LG-ESS had a significant better overall survival than those with UES (P = .026). Mitotic count had no prognostic significance. Our data emphasize the clinical importance of the WHO classification in ESS. It is of utmost importance to establish a proper classification to increase the consistency of data that may be useful for improving clinical and therapeutic management of patients with ESS.

Endometrial Stromal Sarcomas and Related High-grade Sarcomas: Immunohistochemical and Molecular Genetic Study of 31 Cases

Classification and terminology of non-low-grade endometrial sarcomas, which show significant nuclear atypia, have been controversial. Currently, these tumors seem to be classified all together into "undifferentiated endometrial sarcoma (UES)." However, it remains unclear whether these non-low-grade sarcomas are universally "undifferentiated." We divided these sarcomas morphologically into undifferentiated endometrial sarcoma with nuclear uniformity (UES-U) and undifferentiated endometrial sarcoma with nuclear pleomorphism (UES-P), and compared their molecular genetic and immunohistochemical profiles. Eighteen low-grade endometrial stromal sarcomas (ESS-LG), 7 UES-U, and 6 UES-P were examined. All the patients with ESS-LG were still alive, either with or without disease, whereas 4 of the 5 patients with advanced stage UES-U and all 3 of the patients with advanced stage UES-P had died of the disease. JAZF1-JJAZ1 fusion transcript was detected in 6 (50%) out of 12 ESS-LG and in 1 (33%) of 3 UES-U, whereas it was not detected in any of the cases of UES-P. ESS-LG and UES-U frequently showed positive immunoreaction for estrogen receptor (ESS-LG: 94%, UES-U: 57%) and progesterone receptor (ESS-LG: 94%, UES-U: 57%), whereas all the UES-P were negative for these receptors. Nuclear beta-catenin expression was more frequently recognized in ESS-LG (47%) and UES-U (85%), compared with UES-P (33%). Moreover, nuclear accumulation of p53 and TP53 gene missense mutations were limited to 3 UES-P cases. Our data suggest that UES-U shares some molecular genetic and immunohistochemical characteristics with ESS-LG, but UES-P considerably differs from ESS-LG.

Diagnostic use of nuclear Β-catenin expression for the assessment of endometrial stromal tumors

Alterations in Β-catenin degradation cause it to accumulate to immunohistochemically detectable levels in the nuclei of tumor cells. Although it has been shown that nuclear Β-catenin immunostaining is useful for the diagnosis of some mesenchymal tumors, there is little known about Β-catenin expression in endometrial stromal tumors. In this study, nuclear Β-catenin immunoreactivity was evaluated in normal endometrium and endometrial mesenchymal tumors and then compared with that of CD10. The endometrial mesenchymal tumors evaluated included endometrial stromal nodules (n=2), low-grade endometrial stromal sarcomas (n=12), undifferentiated endometrial sarcomas (n=8) and uterine cellular leiomyomata (n=9). In addition, direct DNA sequencing of Β-catenin exon 3 was conducted in 15 endometrial stromal tumors. Normal endometrial stromal cells showed strong cytoplasmic reactivity for CD10 but no detectable reactivity for Β-catenin. Nuclear Β-catenin immunoreactivity was detected in 11 low-grade endometrial stromal sarcomas (92%) and 6 undifferentiated endometrial sarcomas (75%). Ten low-grade endometrial stromal sarcomas (83%) and six undifferentiated endometrial sarcomas (75%) were positive for CD10. Eight low-grade endometrial stromal sarcomas (67%) exhibited diffuse, strong nuclear immunoreactivity with Β-catenin, whereas only four cases (33%) expressed diffuse, strong immunoreactivity with CD10. All nine cases of uterine cellular leiomyomata were completely negative for both CD10 and Β-catenin. Β-catenin mutations were rare in endometrial stromal tumors. Taken together, these results indicate that nuclear Β-catenin immunostaining can serve as a sensitive immunohistochemical marker for the diagnosis of endometrial stromal tumors and is useful for differentiating low-grade endometrial stromal sarcomas from uterine cellular leiomyomata.

A case of primary retroperitoneal undifferentiated endometrial stromal sarcoma after concurrent chemoradiation therapy for cervical cancer

Endometrial stromal sarcoma (ESS) is a relatively rare uterine sarcoma, especially extrauterine ESS. Furthermore, retroperitoneal ESS are extremely rare. Up to now, there are only four cases of primary retroperitoneal ESS reported in the literature. We report one case of primary retroperitoneal undifferentiated endometrial stromal sarcoma after concurrent chemoradiation therapy for cervical cancer with a brief review of the literature.

Treatment options in stage I endometrial stromal sarcoma: A retrospective analysis of 53 cases

Objective. To discuss the optimal treatment options for stage I patients with endometrial stromal sarcoma (ESS). Methods. We reviewed hospital records and pathology of 53 patients with ESS at stage I. Statistical analysis was performed using SPSS 12.0 software, and Chi-square test, t-test and log rank test were adopted. Results. Among 53 patients, 37 had low-grade tumors, 11 had undifferentiated endometrial sarcoma (UES) and 5 had unclassified ESS. The median follow-up time was 66 months, and 48 cases were still alive. The overall 2-year and 5-year survival rates were 91.5% and 85.9%, respectively. The recurrence rate of the patients with preserved ovarian function was remarkably higher than that of patients without (100% vs. 22.7%, P < 0.001). The patients who received adjuvant whole pelvic radiation (Dt 40∼45 Gy) had obviously higher local control rate than the patients who did not (93.8% vs. 57.1%, P = 0.007), but they had similar survival ( P = 0.963). Among 7 of the 11 UES patients without distant recurrence, 5 received the adjuvant chemotherapy with IAP (ifosfamide 1.0 g, d1–4; epirubicin 25 mg/m 2, d1–2; cisplatin 20 mg, d1–5; mensa 0.2 g, 0, 4, 8 h from the application of ifosfamide, d1–4, q 28 days) or VAD (vincristine 1.2 mg/m 2, d1; adriamycin 20 mg/m 2, d1–3; dacarbazine 250 mg/m 2, d1–5, q 28 days), and none of the other 4 cases recurring distantly received the chemotherapy with IAP or VAD. Conclusions. Surgeries not preserving ovarian function were helpful to decrease the risk of recurrence compared with those surgeries sparing ovarian function. Adjuvant radiotherapy could improve local control but not survival. Adjuvant chemotherapy with IAP or VAD seemed to be beneficial to UES patients.

Grading of malignancy has no clinical relevance in patients with endometrial stromal sarcoma

We read with great interest the publication by Amant et al. [1], who report two cases of low-grade endometrial stromal sarcoma (ESS) that recurred as high-grade sarcoma. This report postulates that ESS may undergo transformation or dedifferentiation into a high-grade tumour upon recurrence, but that these lesions should not be confused with undifferentiated endometrial sarcoma (UES), formerly called high-grade endometrial stromal sarcoma. The current WHO classification [2] distinguishes ESS from UES which lacks specific differentiation and resembles the sarcomatous component of carcinosarcoma.

Molecular genetic changes in epithelial, stromal and mixed neoplasms of the endometrium

Endometrial carcinoma, endometrial stromal tumours and mixed malignant mesodermal tumours (MMMT) develop along distinctive molecular genetic pathways. Two distinctive types of endometrial carcinoma are distinguished, type I and type II, which develop along distinctive pathways and show different clinical behaviour and histological features. Type I carcinomas show endometrioid histology, are oestrogen-related and develop from atypical endometrial hyperplasia. The molecular tumorigenesis is comparable to colorectal carcinoma with a step-like progression and an accumulation of genetic alterations. Alterations of PTEN, K-Ras mutations and microsatellite instability are frequent and early events in type I carcinoma, whereas p53 mutations occur during progression to grade 3 carcinoma. Serous and clear cell carcinomas are considered type II carcinomas which are mostly unrelated to oestrogen. p53 mutations occur in almost all serous carcinomas and seem to occur early, leading to massive chromosomal instability and rapid tumour progression. Gene expression profiling has supported this dualistic model of endometrial carcinoma. There is evidence of molecular differences between serous and clear cell carcinomas as well as between endometrioid carcinomas with and without microsatellite instability. A dualistic model of tumorigenesis may be also suggested for endometrial stromal tumours. Endometrial stromal sarcomas (ESS; type I endometrial sarcoma) are oestrogen-related and seem to develop from endometrial stromal nodules (ESN). They are histologically and genetically distinct from undifferentiated endometrial sarcoma (UES) which seem to be mostly unrelated to oestrogen (type II endometrial sarcoma). ESS and ESN share the fusion gene JAZF1/JJAZ1 caused by a t(7;17)(p15;q21) translocation, whereas UES lacks a distinctive molecular alteration so far. In MMMT, which is considered a metaplastic carcinoma, p53 alteration occurs early, before clonal expansion and acquisition of genetic diversity during progression.

Uterine sarcomas

A wide variety of sarcomas occur in the uterus but two subtypes - leiomyosarcoma and endometrial stromal sarcoma - account for a majority of those more routinely encountered. Using the 2003 World Health Organization classification, this review focuses on six uterine sarcomas: endometrial stromal sarcoma, undifferentiated endometrial sarcoma, leiomyosarcoma, rhabomyosarcoma, angiosarcoma and liposarcoma. The epidemiological, clinical, pathological and molecular features are presented along with therapeutic approaches. Familiarity with molecular aspects of these tumors and application of novel technologies in their assessment should be encouraged as they may provide alternate therapies resulting in improved survival for the patient. Clinical information necessary for accurate diagnosis of these lesions is emphasised. A multidisciplinary approach to management of patients with uterine sarcomas is essential for optimal management.

KIT-negative undifferentiated endometrial sarcoma with the amplified epidermal growth factor receptor gene showing a temporary response to imatinib mesylate

Undifferentiated endometrial sarcoma (UES) is a high-grade sarcoma that lacks specific differentiation. Here, we present a unique case of UES that temporarily responded to imatinib mesylate. A 61-year-old woman presented with a pelvic mass, which rapidly increased in size over the course of 3 months. The mass in the hysterectomy specimen consisted of pleomorphic cells that did not show any endometrial stromal or smooth muscle differentiations; thus, the diagnosis of UES was made. Multiple regional recurrences around the urinary bladder were noted after 5 months, and treatment with imatinib mesylate was started, based on the provisional interpretation of KIT immunoreactivity on a biopsy specimen of the recurrent tumor. Two weeks later, the tumor shrunk significantly, as evaluated by computed tomography. However, they became enlarged under the therapy after 3 months since imatinib was first started. KIT immunohistochemical staining on the previously mentioned biopsy was reviewed thereafter, but it was not convincing. We also investigated for aberrations of c-kit and platelet-derived growth factor receptor alpha by polymerase chain reaction with direct sequencing, but no aberration was observed. Instead, focal but definite immunoreactivity to epidermal growth factor receptor (EGFR) was observed. In addition, EGFR gene amplification was confirmed by fluorescence in situ hybridization. We speculated that imatinib was temporarily effective on the clone with amplified EGFR, and that it became ineffective after this clone was eradicated. The amplified EGFR in UES has not been reported previously, and further studies are necessary to consider the possibility of EGFR-targeted therapy in such sarcomas.

JAZF1/JJAZ1 Gene Fusion in Endometrial Stromal Sarcomas : Molecular Analysis by Reverse Transcriptase-Polymerase Chain Reaction Optimized for Paraffin-Embedded Tissue

Endometrial stromal tumors are rare uterine neoplasms including benign stromal nodules, low-grade endometrial stromal sarcomas (ESS), and undifferentiated endometrial sarcomas (UES), the latter representing the most aggressive form. Morphological characteristics and cytogenetic abnormalities are heterogeneous, making diagnosis difficult. Recently, a gene fusion on chromosome 7 that includes two zinc-finger genes (JAZF1 and JJAZ1) has been discovered in these tumors. Hitherto only 31 cases, described by three different research groups, have shown JAZF1/JJAZ1 fusion in approximately 50% of all analyzed low-grade ESSs whereas it is less frequent in UESs. In this study we analyzed 20 ESS and 2 UES cases using two-step reverse transcriptase-polymerase chain reaction optimized for formalin-fixed, paraffin-embedded tissue. In our subset of samples, the JAZF1/JJAZ1 fusion transcript occurred in 80% of analyzed ESS cases and in none of two UES cases. In comparison to published data, our results identified the JAZF1/JJAZ1 gene fusion more frequently in endometrial stromal tumors than hitherto presumed. This cytogenetic abnormality was not present in normal endometria, leiomyomas, or leiomyosarcomas or in lung, gastric, or hepatic carcinomas, indicating its specificity for endometrial stromal tumors. In combination with other established methods, accurate reverse transcriptase-polymerase chain reaction analysis of JAZF1/JJAZ1 gene fusion may be useful in diagnosing difficult or unusual ESS/UES cases.