Endometrial stromal tumors of the uterus: Epidemiology, pathological and biological features, treatment options and clinical outcomes.

Endometrial stromal tumors (EST) are uterine mesenchymal tumors, which histologically resemble endometrial stroma of the functioning endometrium. The majority of EST are malignant tumors classified as low-grade endometrial stromal sarcoma (LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS), and undifferentiated uterine sarcoma (UUS). Overall, ESTs are rare malignancies, with an annual incidence of approximately 0.30 per 100'000 women, mainly affecting peri- or postmenopausal women. The most common genetic alteration identified in LG-ESS is the JAZF1-SUZ12 rearrangement, while t(10;17)(q23,p13) translocation and BCOR gene abnormalities characterize two major subtypes of HG-ESS. The absence of specific genetic abnormalities is the actual hallmark of UUS. Unlike HG-ESSs, LG-ESSs usually express estrogen and progesterone receptors. Total hysterectomy without morcellation and bilateral salpingo-oophorectomy (BSO) is the first-line treatment of early-stage LG-ESS. Ovarian preservation, fertility-sparing treatment, and adjuvant hormonal therapy ± radiotherapy may be an option in selected cases. In advanced or recurrent LG-ESS, surgical cytoreduction followed by hormonal treatment, or vice versa, are acceptable treatments. The standard treatment for apparently early-stage HG-ESS and UUS is total hysterectomy without morcellation with BSO. Ovarian preservation and adjuvant chemotherapy ± radiotherapy may be an option. In advanced or recurrent HG-ESS, surgical cytoreduction and neoadjuvant or adjuvant chemotherapy can be considered. Alternative treatments, including biological agents and immunotherapy, are under investigation. LG-ESSs are indolent tumor with a 5-year overall survival (OS) of 80-100% and present as stage I-II at diagnosis in two third of patients. HG-ESSs carry a poor prognosis, with a median OS ranging from 11 to 24 months, and 70% of patients are in stage III-IV at presentation. UUS median OS ranges from 12 to 23 months and, at diagnosis, 70% of patients are in stage III-IV. The aim of this review is to assess the clinical, pathological, and biological features and the therapeutic options for malignant ESTs.

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.

IFITM1, CD10, SMA, and h-caldesmon as a helpful combination in differential diagnosis between endometrial stromal tumor and cellular leiomyoma.

BACKGROUND: The differential diagnosis of endometrial stromal tumor (EST) and uterine cellular leiomyoma (CL) remains a challenge in clinical practice, especially low grade endometrial stromal sarcoma (ESS) and CL, suggesting the need for novel immunomarkers panels for differential diagnosis. Interferon-induced transmembrane protein 1 (IFITM1) is a novel immunomarker for endometrial stromal cells, h-caldesmon is an immunomarker for smooth muscle cells and has a higher specificity than smooth muscle actin (SMA). So this study aimed to evaluate whether IFITM1, cluster of differentiation 10(CD10), SMA, and h-caldesmon are useful biomarker combinations for the differential diagnosis of EST and CL. METHODS: Tissue microarrays were used to detect IFITM1, CD10, SMA, and h-caldesmon immunohistochemical staining in 30 EST and 33 CL cases. RESULTS: The expressions of IFITM1 and CD10 were high in EST (86.7 and 63.3%, respectively) but low in CL (18.2 and 21.2%), whereas those of h-caldesmon and SMA were high in CL (87.9 and 100%) and low in EST (6.9 and 40%). In diagnosing EST, IFITM1 shows better sensitivity and specificity (86.7 and 81.8%, respectively) than CD10 (63.3 and 78.8%). The specificity of h-caldesmon in diagnosing CL was significantly higher (93.1%) than that of SMA (60%). When all four antibodies were combined for the differential diagnosis, the area-under-the-curve (AUC) predictive value was 0.995. The best combination for diagnosing EST was IFITM1 (+) or CD10 (+) and h-caldesmon (-) (sensitivity 86.7%, specificity 93.9%). CONCLUSION: The best combination for diagnosing CL were h-caldesmon (+) and SMA (+) (sensitivity 87.9%, specificity 100%). IFITM1, CD10, SMA, and h-caldesmon are a good combination for the differential diagnosis of EST and CL.

Low-grade endometrial stromal sarcoma combined with leiomyoma (stromomyoma): A bizarre tumor of the uterus in a premenopausal woman.

OBJECTIVE: Uterine sarcomas are very rare malignancies, and when a hysterectomy is performed for benign causes, a risk of about 1/500 is mentioned for possible uterine sarcomas. Endometrial stromal neoplasms are a rare subgroup of uterine sarcomas that account for less than 10% of all uterine sarcomas. Mixed endometrial stromal and smooth muscle tumors, also known as stromomyomas, are defined as having at least 30% each of endometrial stromal and smooth muscle components. As a result, stromomyoma is an extremely rare malignant mixed mesenchymal tumor of the uterus. Both clinically and histologically, the differential diagnosis is challenging. Stromomyoma should be kept in mind in the differential diagnosis of large uterine masses, even if these masses are seen in an asymptomatic woman of reproductive age. In this study, we aimed to present this bizarre tumor of the uterus detected in a premenopausal woman.

Proliferative Lesions of the Endometrium of 50 Four-Toed Hedgehogs ( Atelerix albiventris).

Uteri from 50 four-toed hedgehogs ( Atelerix albiventris) with clinical signs of uterine disease were histopathologically examined. Sixteen animals (32%) were diagnosed with endometrial hyperplasia, 7 animals (14%) were diagnosed with endometrial polyp, and 27 animals (54%) were diagnosed with endometrial neoplasia. The mean ages of the animals with endometrial hyperplasia, polyp, and neoplasia were 28.7 months, 29.4 months, and 25.2 months, respectively. The neoplasms were classified into 7 endometrial mixed tumors, 12 endometrial stromal nodules, and 8 endometrial stromal sarcomas. However, the endometrial stromal nodules and endometrial stromal sarcomas often developed within or were contiguous with an endometrial polyp or mixed tumor. Interestingly, the stromal tumors and the stromal components of the endometrial polyp and mixed tumor displayed extraendometrial differentiation (eg, into adipocytes, granular cells, smooth muscle cells, and osteoid tissue). The endometrial stromal sarcomas exhibited severe cellular atypia and invaded subendometrial tissue. Immunohistochemical examinations demonstrated that the stromal cells of the hyperplastic lesions as well as the neoplastic lesions were positive for CD10, the progesterone receptor, and Wilms tumor 1. The four-toed hedgehog develops unique uterine neoplasms that are mainly composed of endometrial stromal cells and probably arise from endometrial polyps and/or mixed tumors.

Uterine tumors resembling ovarian sex cord tumors, a clinicopathologic study of six cases.

Uterine tumors resembling ovarian sex cord tumors (UTROSCTs) cause difficulties, both with respect to diagnosis as well as to the nomenclature. They belong to the group of low-grade malignant neoplasms, and their clinical course likely depends on the percentage of the sex cord-like component. Morphologically, they can be divided into type I and type II with less or more than 50% of sex cord-like areas, respectively. Six patients with an age range of 24 to 63 years underwent the treatment for primary UTROSCT at the Cancer Center and Institute of Oncology in Warsaw, Poland, between 2000 and 2011. In addition to the surgery, 4 patients were treated with gestagens. Biopsies or excisions from the tumors were examined microscopically and immunohistochemically. Two cases were classified as type I, and 4 cases, as type II tumors. The tumor size ranged from 3 to 24 cm. The sex cord component varied from 25% to 70%. By immunohistochemical examination, the sex cord-like component was calretinin positive, whereas the stromal component was positive for CD10 and negative for h-caldesmon in all the cases studied. In addition, progesterone receptor positivity was found in all the cases, and 4 tumors were positive for smooth muscle actin, cytokeratin AE1/3, and inhibin. No recurrences were noted in any of the 6 patients over 3 to 14.5 years of follow-up period. A correct subclassification of sarcomas of UTROSCT type is of crucial importance because most patients with this rare neoplasm respond well to gestagen therapy and have a good prognosis, compared with other uterine stromal sarcomas.

Cellular Leiomyoma versus Endometrial Stromal Sarcoma: A Report of a Rare Case Presenting a Diagnostic Challenge on Intraoperative Frozen Section.

Endometrial stromal sarcomas (ESSs) account for approximately 0.2% of all uterine malignancies. Cellular leiomyoma (CL) often simulates low-grade ESS due to similar cytology. We report the case of a 34-year-old female with a mass per abdomen. Frozen sections showed a tumor with many thin- and thick-walled vessels along with hyaline material. A differential diagnosis of CL and endometrial stromal tumor was suggested. The index case was diagnostically challenging to pathologists. Paraffin sections supplemented by immunohistochemistry (smooth muscle actin, CD10, and beta-catenin) favored CL. Frozen section sometimes leads to over/underestimation of tumor in view of small sampling area of tumor.

Pulmonary Metastasizing Low-Grade Endometrial Stromal Sarcoma: Case Report and Review of Diagnostic Pitfalls.

Pulmonary manifestations of benign metastasizing leiomyoma (BML) usually include multiple well-defined, round, bilateral nodules. Low-grade endometrial stromal sarcoma (LG-ESS) is a rare uterine tumor. A 70-year-old woman visited the clinic complaining of acute cough and dyspnea in April 2017. Chest computed tomography (CT) revealed pneumothorax and multiple pulmonary nodules. She had a history of hysterectomy for uterine leiomyoma 23 years ago. Biopsy revealed that the pulmonary masses were consistent with BML. However, the patient had two subsequent episodes of acute, recurrent respiratory distress, accompanied by massive pleural effusions and hydropneumothorax over the next two years. A chest CT performed for acute dyspnea revealed large and multiple hydropneumothoraces. The size and distribution of pulmonary masses were aggravated along with cystic changes and bilateral pleural effusions. Given this aggressive feature, additional immunohistochemical findings and gynecologic pathologist review confirmed the correct diagnosis to be LG-ESS. After initiating anti-estrogen therapy, the patient achieved a partial response, without recurrence of symptoms, for 28 months. Metastatic LG-ESS responds well to anti-hormonal therapy. If the clinical pattern of a disease is different than expected, the possibility of a correction in the diagnosis should be considered.

Uterine tumor resembling an ovarian sex cord tumor: A case report and review of literature.

BACKGROUND: Endometrial stromal tumors originate from the endometrial stroma and account for < 2% of all uterine tumors. Uterine tumor resembling an ovarian sex cord tumor (UTROSCT) is a rare histological class of endometrial stromal and related tumors according to the latest World Health Organization classification of female genital tumors. Here, we report a case of UTROSCT in a 51-year-old woman. CASE SUMMARY: A 51-year-old woman had irregular menses for 6 mo. The patient visited a local hospital for vaginal bleeding. Pelvic computed tomography (CT) showed a mass in the pelvic cavity. Five days later, she came to our hospital for further diagnosis. The results of contrast-enhanced CT and pelvic ultrasound at our hospital suggested a malignant pelvic tumor. She then underwent total removal of the uterus with bilateral salpingectomy. Postoperative histological examination showed that the tumor cells had abundant cytoplasm, ovoid and spindle-shaped nuclei, fine chromatin, a high nucleoplasm ratio, and a lamellar distribution. The findings were consistent with UTROSCT, and the results of immunohistochemical analysis supported that diagnosis. The tumor was International Federation of Gynecology and Obstetrics stage IB. No adjuvant therapy was administered after radical surgery. The patient was followed up for 58 mo, and no recurrence was found. CONCLUSION: We report a case of UTROSCT with abnormal menstruation as a symptom, which is one of the most common symptoms. In patients with vaginal bleeding, ultrasonography can be used as a screening test because of its convenience, speed, and lack of radiation exposure. For patients with long-term tamoxifen use, routine monitoring of the endometrium is recommended. As UTROSCT may have low malignant potential, surgery remains the primary management strategy. Additionally, fertility preservation in patients of childbearing age is a vital consideration.

Uterine sarcomas.

Uterine sarcomas comprise a small percentage of uterine malignancies. The most common uterine sarcoma is leiomyosarcoma (LMS). Early stage uterine LMS is curable with complete hysterectomy with removal of an intact uterus. Patients with metastatic disease may achieve tumor responses with improvements in quality of life, but long-term remissions are rare. In this review article, I outline adjuvant therapies for early stage resected uterine LMS, as well as treatment of metastatic disease.

Uterine lesions with sex cord-like architectures: a systematic review.

BACKGROUND: Sex cord-like elements are rarely observed in uterine lesions, but these morphological patterns could appear in a variety of uterine tumors and non-tumorous lesions. In this review, we collected the literatures regarding the uterine tumorous and non-tumorous lesions containing sex cord-like elements and summarized these lesions in terms of clinicopathological, immunohistochemical, and molecular features in order to further understand these lesions and provide some new ideas for differential diagnosis. MAIN BODY: This section provides a comprehensive overview of the clinicopathological, immunohistochemical, and molecular features of uterine lesions with sex cord-like architectures including uterine tumors resembling ovarian sex cord tumors, endometrial stromal tumors, adenomyosis, endometrial polyps, leiomyoma, epithelioid leiomyosarcoma, adenosarcoma, sertoliform endometrioid carcinoma, corded and hyalinized endometrioid carcinoma, mesonephric adenocarcinoma, and mesonephric-like adenocarcinoma. The differential diagnosis based on morphology, immunohistochemistry, and molecular alterations has also been discussed. CONCLUSION: The sex cord-like areas in these lesions show heterogeneous but similar morphological features. Additionally, immunohistochemical staining plays a limited role in differential diagnosis. Furthermore, it is of significance for pathologists to better understand these lesions in order to avoid confusion and mistakes during pathological diagnosis, especially in a biopsy/curettage specimen.

Angioleiomyoma of Uterus: A Clinicopathologic Study of 6 Cases.

BACKGROUND AND OBJECTIVES: Angioleiomyoma is a benign perivascular neoplasm commonly involving subcutaneous tissue of extremities, head, and trunk region. They rarely involve the female genital tract. This study analyses clinicopathological features of 6 cases of uterine angioleiomyoma. METHODS: Routine sections of 6 cases were reviewed and immunohistochemical markers namely muscle-specific actin, h-caldesmon, desmin, CD10, WT-1, HMB-45, and melan-A were done. RESULTS: Of the 6 cases, 4 cases had tumor involving the corpus and 2 cases had tumor in the cervix. Grossly, all tumors had a whorled and congested cut surface. Microscopic examination of all the cases revealed circumscribed neoplasms composed of interlacing fascicles of benign perivascular smooth muscle cells with evenly distributed slit-like blood vessels (solid variant) along with vessels exhibiting thick muscular walls with swirling pattern (venous variant). In only 2 cases many dilated vessels were seen (cavernous variant). Immunohistochemically, all cases were positive for muscle-specific actin, h-caldesmon, and desmin. All cases were negative for CD10 and WT-1 ruling out endometrial stromal tumor and were negative for HMB-45 and melan-A ruling out perivascular epithelioid cell tumor (both endometrial stromal tumor and perivascular epithelioid cell tumor have prominent vessels but have different histomorphology). In all cases, surgical excision was curative and there were no intraoperative or postoperative complications. Follow-up of all the cases has been unremarkable. CONCLUSION: As the World Health Organization has not included angioleiomyoma in the classification of mesenchymal tumors of uterine corpus and cervix, we recommend that it should be included in the classification.

Low-grade endometrial stromal sarcoma with extensive sex cord differentiation, heterologous elements, and complex atypical hyperplasia: Case report and review of literature.

•Endometrial stromal sarcoma (ESS) may have sex cord differentiation, usually focal.•Diagnosis of ESS is difficult when variant morphology predominates.•Prognosis differs between ESS and UTROSCT; therefore, distinction is critical.•Extensive tumor sampling is mandatory to identify neoplastic endometrial stroma.•Sex cord differentiation may be associated with endometrial hyperplasia.

Hyperhaploid uterine mesenchymal tumors-a novel genetic subgroup?

Hyperhaploid karyotypes have been described to occur in subsets of various solid tumors and leukemias. In these cases, monosomy is noted for most of the chromosomes while a few chromosomes still remain disomic. Evidence has emerged that at least in some tumor entities these remaining chromosomes are non-randomly selected. In addition, structural alterations can accompany the reduced chromosome number and secondary duplication of the chromosome complement is also a frequent finding. In this report, we describe hyperhaploidy in a case of an endometrial stromal nodule of a 50 year old woman who underwent hysterectomy because of symptomatic uterine fibroids. In addition, we review two other recently described cases of uterine mesenchymal tumors with that type of genetic alteration. Despite some histologic differences, striking similarities between these three cases exist with respect to the chromosomes were retained as disomic. Thus, the question arises if hyperhaploidy defines a novel genetic subgroup of uterine mesenchymal tumors.

Cellular leiomyoma versus endometrial stromal tumor: A pathologists' dilemma.

Uterine smooth muscle tumors and endometrial stromal tumors (ESTs) are the two major types of mesenchymal tumors of the uterus, the latter being fairly uncommon. Among these, endometrial stromal sarcoma (ESS) accounts for 0.2-1.5% of all uterine malignancies. Although routine histopathological examination is sufficient to distinguish between ESS and smooth muscle tumors in most of the cases, the distinction between ESTs and highly cellular leiomyomas (CMs), on several occasions becomes a great diagnostic challenge for the pathologist. The differentiation between EST and CM is necessary on account of the variable clinical course and slight variation in the therapy. However, this is difficult due to the tendency of endometrial stromal cells to differentiate into well-developed smooth muscle cells as well as overlapping immunohistochemical profile in some cases. We hereby report a series of cases which posed a diagnostic challenge to us as to whether they are CMs or ESTs. We therefore discuss the histological features which helped us resolve this dilemma as well as the utility of immunohistochemistry (IHC) as a diagnostic aid in arriving at a final diagnosis in such problematic cases.

Malignant potential of endometrial stromal tumor with limited infiltration: a case report.

Endometrial stromal tumors (ESTs) with limited infiltration were first proposed by Dionigi et al.(1) However, the prognostic significance of these tumors is unclear. We report a case of a 60-year-old woman who presented with a prolapsed uterine corpus and then underwent laparoscopic-assisted vaginal hysterectomy. A very small EST was incidentally found. The tumor manifested focal irregularity and finger-like permeation into the adjacent myometrium not exceeding 3 mm but exceeding 3 in number, features intermediate between a low-grade endometrial stromal sarcoma and an endometrial stromal nodule. By definition, we rendered a descriptive diagnosis of "endometrial stromal tumor with limited infiltration." A subsequent staging operation confirmed metastasis and, hence, a malignant potential.

Uterine tumor resembling ovarian sex cord tumor (UTROSCT), case report with literature review.

INTRODUCTION: Uterine tumors resembling ovarian sex cord tumors (UTROSCT) are uterine neoplasms of unknown histiogenesis which show near complete differentiation towards ovarian sex cord elements and are postulated to arise from pluripotential uterine mesenchymal cells or endometrial stromal cells with secondary sex cord differentiation. CASE PRESENTATION: A 48 year old post-menopausal women presented with abnormal uterine bleeding for which she underwent total abdominal hysterectomy with bilateral salpingo-ophorectomy. Gross examination revealed a gelatinous grayish white tumor confined to the myometrium, 7 cm in maximum dimention. Microscopic examination revealed monomorphic round to oval tumor cells in anastomosing cords and trabeculae with myxoid background. Immunohistochemically, tumor cells showed diffuse positivity for vimentin, CD99 and S100, while focal positivity was seen with pancytokeratin immunostain. The case was diagnosed as UTROSCT. No evidence of metastasis was found on systemic clinical and radiologic workup. CONCLUSION: UTROSCT are rare uterine tumors which can be diagnosed with certainty on morphologic and immunohistochemical grounds. It is important to recognize these tumors as they behave differently from endometrial stromal tumors with sex cord like elements (ESTSCLE).

Adenocarcinoma endometrial concomitante con tumor estromal benigno del endometrio / Endometrial carcinoma concomitant with endometrial stromal tumor benign

La asociación de tumor epitelial y estromal maligno es muy infrecuente, habiendo pocos casos reportados, más infrecuente aún es la asociación de tumor epitelial maligno y tumor estromal benigno. Se presenta el caso de mujer de 65 años con diagnóstico preoperatorio de carcinoma endometrial, que durante el procesamiento de la pieza quirúrgica se encontró además una lesión intramural nodular estromal benigna, sin continuidad entre ambas lesiones.

The association of epithelial and stromal malignant neoplasm is very rare, with few reported cases, rarer still is the prescence of malignant epithelial tumor and stromal benign tumor. We present the case of women aged 65 with preoperative diagnosis of endometrial carcinoma, which in the pathological examination was found an intramural benign endometrial stromal lesión, without continuity between both tumors.