Uterine tumors resembling ovarian sex cord tumors (UTROSCT) with metastasis: clinicopathological study of two cases

Uterine tumors with sex cord-like elements are divided in two groups; uterine tumors resembling ovarian sex cord tumors (UTROSCT), and endometrial stromal tumors with sex cord-like elements (ESTSCLE). UTROSCT is currently defined as the neoplasm predominantly or exclusively composed of sex cord-like elements, and generally behaves in a benign fashion. We studied two unusual cases of UTROSCT with metastasis. One case was a 38-year-old multiparous woman presented with hypermenorrhea. The tumor grew as an intramural mass, and metastasized to a pelvic lymph node. Another case was a 57-year-old woman presented with genital bleeding. The tumor grew as a submucosal exophytic mass, and metastasized to the epiploic appendix. Microscopic examination of the 2 cases revealed that they were composed of sex cord-like cells, epithelioid cells and spindle cells. They exhibited solid pattern in predominance. Both solid and sex cord-like elements showed similar immunoreactivities for more than 3 sex cord markers, but simultaneously showed different staining patterns for some other markers. Characteristic features of endometrial stroma such as tongue-like infiltration and spiral arteries-like arterioles were not observed. RT-PCR analysis confirmed the absence of JAZF1-SUZ12 gene fusion, supporting the histopathological diagnosis of UTROSCT rather than ESTSCLE. The current cases warned the potential risk of UTROSCT whose biological behavior is still uncertain. We discuss histopathological, immunohistochemical and molecular findings of UTROSCT with metastasis.     

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

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

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

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

Uterine tumor resembling ovarian sex cord tumor (UTROSCT). Report of case suggesting neoplastic origin of intratumoral myoid cells

We report a case of double uterine tumor resembling ovarian sex cord tumor (UTROSCT). The tumor was composed of sex cord-like cords, nests and tubules, and bundles of myoid cells. The lesion was interesting especially in regard to histogenesis of intratumoral myoid cells. It is not known whether these cells are neoplastic or whether they represent preexisting myometrial smooth muscle cells entrapped into the tumor. In the present case, the sex cord-like epithelioid cells showed immunohistochemically myoid features in addition to features of epithelial, sex cord and endometrial stromal differentiation. The spindle cells expressed myoid, epithelial and endometrial stromal markers, but some of them were positive for sex cord marker calretinin. This immunophenotypic overlap between sex cord-like and myoid spindle elements indicates that the spindle cells of UTROSCT represent divergent line of differentiation of neoplastic cell rather than entrapped myometrial cells. It further expands the spectrum of possible differentiations in this polyphenotypic neoplasm.     

An update in pathologic diagnosis of uterine mesenchymal tumours

Recent discovery of new disease-defining molecular alterations and development of novel targeted therapies has dramatically changed the classification and management of uterine mesenchymal neoplasms. This review discusses diagnostic updates in endometrial stromal sarcoma, PEComa, uterine tumor resembling ovarian sex cord tumor (UTROSCT), inflammatory myofibroblastic tumor, NTRK fusion uterine sarcoma, COL1A1-PDGFB fusion sarcoma, and SMARC-deficient uterine sarcoma. Key clinical, morphologic, immunophenotypic, and molecular features are reviewed, with emphasis on common differential diagnoses and pitfalls, and their impact on prognosis or management. Where applicable, the role of novel targeted therapies is discussed. A stepwise approach to uterine mesenchymal neoplasms can achieve a proper diagnosis and guide appropriate clinical management in most cases. Nonetheless, given the rarity of these tumors, their overlapping pathologic features, and rapid evolution in their classification and management, we advocate a low threshold for diagnostic consultation.     

Tamoxifen related Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT): A case report and literature review of this possible association

It is well known that a large number of patients treated with Tamoxifen develops endometrial pathologies ranging from benign endometrial polyps and hyperplasia to adenocarcinomas, carcinosarcomas and adenosarcomas. UTROSCT (Uterine Tumor Resembling Ovarian Sex Cord Tumor) is defined as a mesenchymal tumors of the uterine corpus that morphologically resembles ovarian sex cord tumors, without recognizable endometrial stroma. To date only 4 cases have been reported in patients treated with tamoxifen. In this article, we describe an additional case occurring in a 62-years-old patient undergoing 3 years of Tamoxifen therapy for bilateral breast carcinoma. The present work represents a further evidence of the possible association between Tamoxifen therapy and UTROSCT. A comprehensive literature review on this topic is also provided.     

Endometrial stromal tumors: an update on a group of tumors with a protean phenotype

Endometrial stromal tumors are reviewed with emphasis on their wide morphologic spectrum and problems in differential diagnosis, highlighting issues that have received particular attention in the recent literature. These neoplasms are divided into two major categories--endometrial stromal nodules and endometrial stromal sarcomas--a distinction made on the basis of the lack of significant infiltration at the periphery of the former. The division of endometrial stromal sarcomas into low-grade and high-grade categories has fallen out of favor and the designation endometrial stromal sarcoma is now considered best restricted to neoplasms that were formally referred to as "low-grade" stromal sarcoma. Endometrial sarcomas without recognizable evidence of a definite endometrial stromal phenotype, designated poorly differentiated "endometrial sarcomas," are almost invariably high grade and often resemble the mesenchymal component of a malignant mullerian mixed tumor. Two features of endometrial stromal tumors that may cause confusion are smooth muscle differentiation and epithelial patterns. Cases in the former category often have a characteristic "starburst" pattern of collagen formation. The most common epithelial patterns resemble those seen in ovarian sex-cord stromal tumors. Much less common is endometrioid gland differentiation. Some endometrial stromal tumors have a prominent fibrous or myxoid appearance and the myxoid tumors should be distinguished from myxoid leiomyosarcoma. Other unusual features of endometrial stromal tumors are also discussed. Lesions in the differential diagnosis of uterine endometrial stromal neoplasms include highly cellular leiomyoma, cellular intravenous leiomyomatosis, adenomyosis with sparse glands, metastatic carcinoma, and lymphoma. Endometrial stromal sarcomas at extrauterine sites may be primary or metastatic from a uterine tumor, the latter sometimes being occult and difficult to definitively establish, particularly if there is a history of a remote hysterectomy for "leiomyomas." Endometrial stromal sarcomas of the ovary, whether primary or metastatic, may be difficult to distinguish from ovarian sex-cord stromal tumors. Extragenital endometrial stromal sarcomas may be confused with diverse lesions such as gastrointestinal stromal tumors, hemangiopericytoma, lymphangiomyomatosis, or mesenchymal cystic hamartoma of the lung. Immunohistochemistry may play a role in evaluating these tumors and in some instances establishing the diagnosis although conventional light microscopic analysis suffices in the majority of cases. The unusual tumor, the "uterine tumor resembling an ovarian sex-cord tumor," is also considered in this review as it is almost certainly of endometrial stromal derivation in many cases. These neoplasms may have a striking resemblance to granulosa cell tumors or Sertoli cell tumors, including those with a retiform pattern, and have recently been shown to be frequently inhibin positive.     

Mesenchymale Uterustumoren

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

Uterine tumors resembling ovarian sex cord-stromal tumors: synchronous uterine tumors resembling ovarian sex cord-stromal tumors and ovarian sex cord tumor

Uterine tumors resembling ovarian sex cord-stromal tumors (UTROSCTs) are very rare. In this article, we present 3 cases that manifest classical histomorphological features alongside diverse immunohistochemical findings. As a distinctive finding, one of the patients had UTROSCT in the uterus and an ovarian sex cord tumor, called granulosa cell tumor, in the left ovary, simultaneously. Problems in diagnosing such pathologic condition generally arise because of the variable histologic picture of UTROSCT and may cause problems for general and other nongynecologic surgical pathologists. Immunohistochemically, these tumors express different markers that indicate their polyphenotypic origins.     

Uterine tumor resembling ovarian sex cord tumor: report of a case with t(X;6)(p22.3;q23.1) and t(4;18)(q21.1;q21.3).

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare tumor of reproductive-age and postmenopausal women. We present the first case of UTROSCT with cytogenetic analysis. The tumor occurred in a 34-year-old woman who presented with menorrhagia and a uterine mass. Histologic examination showed tumor with features of sex cord-like epithelium and abundant fibromuscular stroma without an endometrial stromal sarcoma component. The tumor cells expressed cytokeratin, CD99, vimentin, desmin, smooth muscle actin, and estrogen and progesterone receptors. The majority of the cells analyzed by cytogenetic studies showed two balanced chromosomal translocations: t(X;6)(p22.3;q23.1) and t(4;18)(q21.1;q21.3). Several known tumor-related genes (bcl-2, MALT-1, FVT1, SCCA1, SCCA2, and DCC at 18q21; RAP1 at 4q21; and STL at 6q23) and a gonadal-development related gene (H-Y regulator gene at Xp22.3) are located at or near the translocation breakpoints. The tumor cells of sex cord-like elements were strongly and diffusely immunoreactive for bcl-2 antibody. These cytogenetic and immunohistochemical data may suggest potential molecular mechanisms of tumorigenesis of UTROSCT.     

Mesenchymal tumors of the ovary and uterine corpus. Selected review

In the large group of uterine and ovarian tumors, the knowledge was updated in recent years substantially. New entities were defined and changes in classification of the lesions were performed. This review is limited to updates, such as evaluation of uterine smooth muscle tumors, new variants of uterine stromal tumors, uterine tumors resembling ovarian sex-cord tumor (UTROSCT), perivascular epithelioid cell tumors (PEC-omas), ovarian fibroma and fibrosarcoma, sclerosing stromal tumor and myxoma. Group of tumors of specialized gonadal stroma is not discussed as it represents particular area and thus requires a separated review article.     

The diagnosis of uterine leiomyosarcoma and endometrial stromal sarcoma]

The diagnostic problems in uterine smooth muscle tumors and endometrial stromal tumors are reviewed and discussed with analysis of 14 selective cases collected from the affiliated hospital. Data suggested that, in the differential diagnosis of benign and malignant uterine smooth muscle tumors, it is not comprehensive to use mitotic activity as the only criterion. Nuclear atypia and some other clinico-pathological features should be considered together, and, it is important to recognize the "mitotic active" leiomyoma which runs a benign course despite a high mitotic rate. In endometrial stromal sarcoma, the growth pattern and the extent of tumor spreading seem not closely correlated with the mitotic activity, nor the atypia, and, the clinical stage was considered as a significant reference in the prognosis. Thus, it is suggested that the differentiation of endometrial stromal sarcoma into low and high malignancy according to the mitotic rate alone is not the best reliable guide in evaluating the tumor behavior. It is emphasized that the extent of spreading of the tumor should be stated in the diagnosis. Immunohistochemical study revealed that the sex cord element in endometrial stromal sarcoma and other uterine tumors expressed a myogenous rather than an epithelial phenotype.     

低度恶性子宫内膜间质肉瘤临床病理分析

目的 探讨低度恶性子宫内膜问质肉瘤(LESS)的临床病理学特征、诊断和鉴别诊断。方法 分析17例LESS的临床病理特点,通过网织纤维染色、免疫组化染色和电镜观察来研究其病理学特征。结果 LESS临床上主要表现为阴道不规则流血。HE染色见肿瘤组织成巢团样浸润,肿瘤细胞圆形、卵圆形或梭形。肿瘤内有大量的小血管。网织纤维染色见网状纤维丰富,围绕瘤细胞生长。肿瘤细胞14例CD10阳性,12例ER阳性,13例PR阳性,3例actin阳性,C1934、CDll7、Melan—A肿瘤细胞均阴性。电镜观察见肿瘤细胞胞质内的中间丝呈杂乱无序的排列。结论 LESS易误诊,确诊主要依靠组织病理学和免疫组织化学;病理形态上看似良好的低度恶性子宫内膜间质肉瘤,预后不一定好。     

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.     

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.     

Role of Electron Microscopy in Metastatic Endometrial Stromal Tumors

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

A critical appraisal of the value of immunohistochemistry in diagnosis of uterine neoplasms

In recent years there have been a plethora of publications regarding the value of immunohistochemical studies in diagnosis in gynecological pathology. In many instances, papers are published initially that suggest that a certain antibody or panel of antibodies is of value in the diagnosis of a particular neoplasm and in the distinction of this from mimics. However, this is usually quickly followed by other studies that somewhat contradict these findings. The aim of this review is to present a critical appraisal of the value of immunohistochemical studies in the diagnosis of uterine neoplasms with emphasis on the recent literature. It is stressed that immunohistochemistry is necessary in relatively few cases and a knowledge of the potential immunoreactivity of utilized antibodies is required. With regard to endometrial carcinoma, topics discussed in this review include antibodies of value in the distinction between type 1 and type 2 carcinoma, in the characterization of focal serous proliferations in endometrial polyps and non-polypoid endometrium, in the sometimes problematic distinction between an endometrial and an endocervical adenocarcinoma, and in the distinction between a uterine and ovarian serous carcinoma. The value of CD10 as a proposed marker of mesonephric adenocarcinoma is also discussed. With regard to uterine mesenchymal neoplasms, a critical appraisal of the value of relatively new antibodies, including CD10 and h-caldesmon, in distinguishing between a smooth muscle and an endometrial stromal neoplasm is discussed as is the immunophenotype of two rare uterine mesenchymal neoplasms, uterine tumor resembling ovarian sex cord tumor (UTROSCT) and perivascular epithelioid cell tumor (PEComa).     

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.     

Lung metastases of a uterine tumor resembling ovarian sex‐cord tumor: Report of a rare case

Uterine tumor resembling an ovarian sex‐cord tumor (UTROSCT) is a rare type of uterine neoplasm. We present an extremely rare case of lung metastases from a UTROSCT focusing on the cytologic features. A 69‐year‐old Japanese woman was admitted to our hospital for further examination and treatment for abnormal shadows in the right lung field. She had a history of total hysterectomy for UTROSCT. Moreover, she underwent wedge resection of the right middle lobe for lung metastasis of UTROSCT in 2011. Enhanced chest computed tomography scan revealed a solid nodule 8 mm in diameter in the right upper lobe and a well‐demarcated 33‐mm mass or nodule in the lower lobe. Under the diagnosis of metastatic tumors from UTROSCT, she underwent wedge resection of the right upper lobe and segmentectomy of the right S8. Cytologically, the stump smear from the resected tumors revealed round to short spindle‐shaped neoplastic small cells arranged in sheets with poor cohesion and no cluster formation. The nuclei were irregular in shape, and the chromatin was finely granular, uniform, and increased. Mitotic figures were not observed. Necrosis was absent in the background. Histologically, the final diagnosis was UTROSCT group II. This is an unusual case of metastatic UTROSCT to the lung in which the cytologic features are described.     

Endometrial stromal sarcoma of the uterus with rhabdoid features

A case of endometrial stromal sarcoma of the uterus with rhabdoid features, occurring in a 57 year old woman is reported. Electron microscopy and immunohistochemistry revealed that the rhabdoid cells contained intermediate filaments which were positive for vimentin, cytokeratin, alpha-smooth muscle actin, and muscle specific actin, but not for myoglobin and desmin. This indicated that the tumor in this case differed somewhat from the three rhabdoid tumors and an endometrial stromal sarcoma with rhabdoid differentiation previously reported and that, therefore, these tumors were heterogeneous.