Uterine endometrial stromal sarcoma with rhabdoid and smooth muscle differentiation.

Uterine and extrauterine tumors composed of cells featuring endometrial stromal cells often show ovarian sex cord-like structures and smooth muscle differentiation. A few cases of endometrial stromal tumors showing rhabdoid differentiation have been reported. The present case is a 20-year-old woman with endometrial stromal sarcoma that had sex cord-like structures, smooth muscle components and rhabdoid differentiation.     

Low-grade endometrial stromal sarcoma with an extensive epithelial-like element

A case of low-grade endometrial stromal sarcoma with extensive epithelial-like element (ELE) is reported. This tumor was composed of classical endometrial stromal sarcoma (CESS) showing diffuse proliferation, and ELE occupying approximately 72% of the tumor mass. On immunohistochemistry, ELE was negative for sex-cord differentiation markers, and was positive for myogenic markers used in our investigation, and had a particularly prominent positivity for alpha-smooth muscle actin within the ELE. Therefore, it was considered that ELE showed no true sex cord feature, but smooth muscle differentiation. Moreover, ELE was also positive for CD10, suggesting that it was derived from CESS. It has been reported that there is a distinct clinical behavior between endometrial stromal tumors with abundant ELE and those with limited ELE. In the present case, the Ki-67 labeling index was markedly higher in CESS than in ELE. Therefore, a difference in cell proliferative activity between ELE and CESS might underlie a different clinical prognosis.     

Myxoid endometrial stromal sarcoma of the uterus

A rare case of a myxoid type of endometrial stromal sarcoma of the uterus in a 41-year-old woman is reported. A tumor was found in the myometrium and was well circumscribed, measuring 9 x 7 x 7 cm in size. The tumor was mainly composed of a hypocellular area with tumor cells separated by prominent myxoid stroma. The tumor cells were spindle-shaped and resembled endometrial stromal cells. Numerous small thin-walled vessels were seen throughout the tumor. Immunohistochemically, the tumor cells were diffusely stained for estrogen and progesterone receptors and CD10, and focally and weakly for HHF35, alpha-smooth muscle actin and desmin, but not stained for h-caldesmon. These results indicated that the tumor originated from endometrial stromal cells. The tumor had an increased mitotic activity (MIB-1 labeling index: 1-10%), and focally showed nuclear pleomorphism. Thus, this tumor had a malignant potential and was diagnosed as a myxoid type of low-grade endometrial stromal sarcoma. The patient is currently well with no evidence of local recurrence or metastasis 21 months after the operation. This case indicates a wide morphological spectrum of endometrial stromal tumor. A myxoid endometrial stromal sarcoma should be considered in the different diagnosis of the intramural myxoid tumors in the uterus.     

Endometrial stromal sarcoma with sex cord-like areas and focal rhabdoid differentiation

An unusual uterine lesion is described in a patient with postmenopausal bleeding. Grossly, a yellow, polypoid mass projected into the uterine cavity. Histological examination showed a distinct biphasic pattern, with areas of typical low-grade endometrial stromal sarcoma and areas where tumour cells were arranged in cords and trabeculae, resulting in a sex cord-like pattern. In these areas the cells assumed a rhabdoid morphology with eccentric vesicular nuclei, prominent nucleoli and eosinophilic hyaline cytoplasmic inclusions. Immunohistochemistry showed positive cytoplasmic staining of both components for vimentin, desmin and the cytokeratin marker CAM 5.2. but no staining for CEA and EMA. Electronmicroscopy revealed prominent paranuclear arrays of intermediate filaments. This is the second reported case of endometrial stromal sarcoma with rhabdoid differentiation and the first documented example of rhabdoid cells in sex cord-like areas. The report adds to the list of diverse neoplasms which may display a characteristic rhabdoid morphology and supports the hypothesis that extrarenal rhabdoid tumours are not a distinct clinicopathological entity. A diagnosis of malignant rhabdoid tumour of the uterus should be considered only when extensive sampling fails to disclose areas with an appearance typical of an endometrial stromal lesion.     

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.     

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.     

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.     

Aspiration biopsy cytology of metastatic endometrial stromal sarcoma and extragenital mixed mesodermal tumor

Aspiration biopsy from metastatic tumors in two cases of endometrial stromal sarcoma and one case of endometrial adenosarcoma revealed malignant endometrial stromal cells with ill-defined cytoplasm and round or oval hyperchromatic nuclei showing irregular chromatin clumping and conspicuous nucleoli. They were seen mainly in clusters. Aspirate from a metastatic tumor of a mixed mesodermal tumor arising from the omentum showed similar malignant endometrial stroma cells, irregular tight clusters of malignant glandular cells having scanty but well-defined cytoplasm and vesicular nuclei with conspicuous nucleoli, and fragments of atypical smooth muscle tissue. The diagnostic malignant endometrial stromal cells in those reported cases did not display any distinctive cellular features permitting their cytologic identification. They were difficult to differentiate from those of other types of sarcoma. In a clinical setting, with a known primary endometrial stromal sarcoma or mixed mesodermal tumor, however, a cytodiagnosis of its metastases may be suggested when malignant endometrial stromal-cell-like cells are seen in aspirated material, oviating an open-tissue biopsy.     

Rhabdoid epithelioid leiomyosarcoma of the uterine corpus: a case report and literature review

A case of epithelioid leiomyosarcoma of the uterus with rhabdoid phenotype and early rhabdomyoblastic differentiation is described. A 72-year-old woman with a 5-week history of increased abdominal girth was found to have a large pelvic mass. The uterus revealed a large intramyometrial and left adnexal necrotic tumor that had spread to the small bowel mesentery and to the anterior abdominal peritoneum. The tumor was an epithelioid leiomyosarcoma with rhabdoid phenotype and focal early rhabdomyoblastic differentiation, as confirmed by immunohistochemical and ultrastructural techniques. Also called composite extrarenal rhabdoid tumor (CERT), this lesion should be differentiated from malignant mixed müllerian tumor, rhabdomyosarcoma, endometrial stromal sarcoma, and pure rhabdoid tumors of the uterus. The recognition of a rhabdoid phenotype is of clinical importance since these tumors are prone to be aggressive.     

High‐grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation: Report of a case with cytomorphologic and immunocytologic analysis

We report a case of high‐grade endometrial stromal sarcoma with cytological and immunocytochemical findings. Cytologically, major tumor cells showed round‐to‐short spindle shapes with round‐ to oval‐shaped nuclei and moderately abundant delicate cytoplasm. Tumor cells with tapered shapes and eccentric nuclei were also observed. A few spindle cells having enlarged cigar‐shaped nuclei with conspicuous nucleoli and delicate wispy cytoplasm, which resembled leiomyosarcoma, were intermingled. One rhabdomyoblast cell with both α‐sarcomeric muscle actin and myoglobin was also observed. Most of the tumor cells, including the leiomyosarcomatous spindle cells, were positive for CD10, and negative for desmin and h‐caldesmon. Accordingly, when relatively monotonous round‐to‐short spindle tumor cells and taper‐shaped tumor cells are observed in the female genital tract, high‐grade endometrial stromal sarcoma should be considered in the differential diagnosis. Immunocytochemistry contributed to the correct diagnosis. This case was high‐grade endometrial stromal sarcoma with smooth muscle and skeletal muscle differentiation. Diagn. Cytopathol. 2010. © 2010 Wiley‐Liss, Inc.     

Low-grade endometrial stromal sarcoma with intracardiac extension. Evolution of extensive smooth muscle differentiation and usefulness of immunohistochemistry for its recognition and distinction from intravenous leiomyomatosis.

This case, a rare example of low-grade endometrial stroma sarcoma with extensive smooth muscle differentiation which extended to the inferior vena cava and cardiac chambers closely resembling intravenous leiomyomatosis grossly and microscopically, illustrates the importance of extensive sectioning and the usefulness of immunohistochemistry. Although spindle cell components arranged in interlacing bundles consistent with smooth muscle differentiation were recognizable in the primary tumor (on retrospective review), extensive smooth muscle differentiation in the recurrent tumors masked prototypical morphologic features of stromal sarcoma and only small neoplastic stromal components were preserved in limited areas, leading to initial failure to distinguish the lesion from intravenous leiomyomatosis. The immunophenotyping disclosed two distinct cell populations in the tumor: i.e. vimentin-positive and smooth muscle marker negative stromal cells, and vimentin-negative spindle-shaped desmin-positive smooth muscle cells. Our observation suggests that the predominance of a smooth muscle component in such a tumor can be misleading and does not always warrant a diagnosis of intravenous leiomyomatosis, nor does it predict a benign clinical course. This case also provides an insight into the relationship of the endometrial stroma and myometrium, and their cell of origin and the histogenesis of endometrial stromal sarcoma.     

Mixed endometrial stromal and smooth muscle tumor: Report of a case with focal anaplasia and early postoperative lung metastasis

A rare case of a mixed endometrial stromal and smooth muscle tumor arising in the uterus of a 74‐year‐old woman is reported. The patient underwent hysterectomy for an enlarging uterine mass, and a large intramural tumor, showing marked central hyaline necrosis with calcification, was found. The tumor consisted of an admixture of a low‐grade endometrial stromal sarcoma (ESS) and a fascicular proliferation of spindle cells suggesting smooth muscle differentiation, and a characteristic ‘star‐burst’ appearance was found. In the ESS region, there were a few small foci of anaplasia where large polygonal cells with atypical nuclei and abundant eosinophilic cytoplasm proliferated, and the proliferative activity was locally increased in these foci. A small metastatic nodule appeared in the lung nine months after the hysterectomy, and the resected metastatic lesion showed features of anaplastic spindle cell sarcoma which was immunoreactive for CD10 but not for smooth muscle markers. Mixed endometrial stromal and smooth muscle tumors should be regarded as malignant neoplasms with the potential for hematogenous metastasis, particularly when they contain foci of cellular anaplasia.     

子宫内膜间质肉瘤9例临床病理分析

目的 探讨子宫内膜间质肉瘤(endometrial stromal sarcoma,ESS)的临床病理特征、诊断、鉴别诊断及预后.方法 对9例ESS患者进行临床、病理资料分析、免疫组化检测及随访.结果 患者年龄39～64岁,中位46.3岁.临床主要表现为阴道流血及子宫增大/占位.肿瘤直径2.3～11 cm,平均4.6 cm.光镜下8例呈低度恶性子宫内膜间质肉瘤(low grade endometrial stromal sarcoma,LGESS),均由类似增殖期子宫内膜间质肿瘤细胞构成,细胞密集,异型性不明显,呈不规则舌状或岛状浸润肌层,并伴较多薄壁螺旋小血管;1例为高度恶性子宫内膜间质肉瘤/未分化子宫内膜肉瘤(high grade endometrial stromal sarcoma/undifferentiated endometrial sarcoma,HGESS/UES),肿瘤细胞直接替代子宫肌层,具有明显的细胞异型性,无LGESS常见的螺旋小血管.免疫组化检测显示肿瘤细胞CD10、vimentin均阳性,PR、ER大部分阳性,SMA和desmin及h-Caldesmon为极少数局灶阳性,S-100、CD34均阴性.术后随访7例(平均53个月),只有1例HGESS/UES死亡.结论 ESS是女性生殖道很少见的一种恶性肿瘤,恶性度相差很大.确诊主要依靠其临床病理特点,并辅以免疫组化标记综合分析.诊断时要与子宫内膜间质结节、平滑肌肿瘤、低分化癌等鉴别.     

Endometrial stromal sarcoma of the sigmoid colon arising in endometriosis: a case report with a review of literatures

Most of malignant tumors arising in ovarian and extraovarian endometriosis are carcinomas. Mixed mullerian tumor and endometrial stromal sarcoma arising in intestinal endometriosis are rarely described, but its clinicopathologic features have not been well characterized. Here we report a case of endometrial stromal sarcoma of the sigmoid colon arising in endometriosis with a review of six additional cases of endometrial stromal sarcoma arising in intestinal endometriosis found in English literatures. The patients ranged in age from 36 to 64 yr. Presenting symptoms were pain, bloody diarrhea, and tenesmus. Some patients had a previous history of endometriosis. Most of the tumors arose in the rectosigmoid colon. The histologic features were the same as their uterine counterpart. No death of disease had been reported. This rare tumor should not be confused with gastrointestinal stromal tumor clinically and histologically.     

Endometrial low-grade stromal sarcoma with ovarian sex cord-like differentiation: Report of two cases with an immunohistochemical and flow cytometric study

Two cases of endometrial low-grade stmmal sarcoma with ovarian sex cord-like differentiation occurring in a 39-year-old woman and a 42-yearold woman are presented. Both tumors, which were intramyometrial and measured 7.5 cm and 7.0 cm in greateat diameter, respectively, showed a multinodular, ill-demarcated, and yellowish white cut-surface. Histologically, most parts of the tumors were composed of trabecular, cord-like, or plexiform arrangements that were reminiscent of the growth pattern seen In ovarian sex cord tumors. Features of conventional endometrial low-grade sttomat sarcoma were only focally observed. The tumors showed inflitrative margins and lymphatic invasion. The tumor cells were positive for vimentin, desmin, α-smooth muscle actin, and muscle actin (HHF35).The tumors were also positive for both estrogen and progesterone receptors. Both tumors were DNA diploid as determined by flow cytometry. One patient had recurrences, Including oste olytic lesions in the pelvic bones, but had no evidence of recurrence or metastasis 11 months after the last surgery. The other patient had no evidence of tumor in a limited follow-up. Famillarity with the neoplasm and other uterine mesenchymal tumors with ovarian sex cord-like differentiation by gynecologists and pathologists is essential in avoiding misdiagnosis because adjuvant hormonal therapy may be effective in treating lowgrade stromal gammas.     

Gastrointestinal Stromal Tumor of the Stomach with Rhabdoid Phenotype: Immunohistochemical,Ultrastructural, and Immunoelectron Microscopic Evaluation

A variety of neoplasms with rhabdoid differentiation have been reported in many sites. The authors describe a case of gastrointestinal stromal tumor (GIST) of the stomach that exhibited prominent rhabdoid features. Immunohistochemically, the tumor cells displayed positive staining for vimentin, c-kit, CD34, and alpha smooth muscle actin. Ultrastructural examination of the rhabdoid tumor cells revealed paranuclear whorls of intermediate filaments, which were immunoreactive for vimentin by both light microscopic immunohistochemical and protein A gold immunoelectron microscopic techniques. On H&E light microscopic examination alone, such a tumor could be mistaken for a variety of epithelial, mesenchymal, or other neoplasms that may show rhabdoid features. One report of GIST with a rhabdoid histologic phenotype has been described. This is the second known report of such a case with immunophenotypic and ultrastructural evaluation, and the first case with immunoelectron microscopic examination.     

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.     

Gastrointestinal stromal tumor of the stomach with rhabdoid phenotype: immunohistochemical, ultrastructural, and immunoelectron microscopic evaluation

A variety of neoplasms with rhabdoid differentiation have been reported in many sites. The authors describe a case of gastrointestinal stromal tumor (GIST) of the stomach that exhibited prominent rhabdoid features. Immunohistochemically, the tumor cells displayed positive staining for vimentin, c-kit, CD34, and alpha smooth muscle actin. Ultrastructural examination of the rhabdoid tumor cells revealed paranuclear whorls of intermediate filaments, which were immunoreactive for vimentin by both light microscopic immunohistochemical and protein A gold immunoelectron microscopic techniques. On H&E light microscopic examination alone, such a tumor could be mistaken for a variety of epithelial, mesenchymal, or other neoplasms that may show rhabdoid features. One report of GIST with a rhabdoid histologic phenotype has been described. This is the second known report of such a case with immunophenotypic and ultrastructural evaluation, and the first case with immunoelectron microscopic examination.     

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.