Endometrial carcinomas: a review emphasizing overlapping and distinctive morphological and immunohistochemical features

This review focuses on the most common diagnostic pitfalls and helpful morphologic and immunohistochemical markers in the differential diagnosis between the different subtypes of endometrial carcinomas, including: (1) endometrioid versus serous glandular carcinoma, (2) papillary endometrioid (not otherwise specified, villoglandular and nonvillous variants) versus serous carcinoma, (3) endometrioid carcinoma with spindle cells, hyalinization, and heterologous components versus malignant mixed müllerian tumor, (4) high-grade endometrioid versus serous carcinoma, (5) high-grade endometrioid carcinoma versus dedifferentiated or undifferentiated carcinoma, (6) endometrioid carcinoma with clear cells versus clear cell carcinoma, (7) clear cell versus serous carcinoma, (8) undifferentiated versus neuroendocrine carcinoma, (9) carcinoma of mixed cell types versus carcinoma with ambiguous features or variant morphology, (10) Lynch syndrome-related endometrial carcinomas, (11) high-grade or undifferentiated carcinoma versus nonepithelial uterine tumors. As carcinomas in the endometrium are not always primary, this review also discusses the differential diagnosis between endometrial carcinomas and other gynecological malignancies such as endocervical (glandular) and ovarian/peritoneal serous carcinoma, as well as with extra-gynecologic metastases (mainly breast and colon).     

Undifferentiated carcinoma of the endometrium: a review

Undifferentiated carcinoma of the endometrium is a high grade carcinoma and under-recognised, frequently diagnosed as grade 3 endometrioid carcinoma. We have found that undifferentiated carcinoma represents 9% of all endometrial carcinomas; it is composed of solid sheets of epithelial cells and in most cases only 5-10% of the cells are positive for keratin. The recognition of undifferentiated carcinoma is extremely important when this neoplasm is associated with a grade 1 or grade 2 endometrioid adenocarcinoma. In this situation it is important to diagnose the solid areas of carcinoma as undifferentiated and avoid evaluating them as the solid component of endometrioid carcinoma because there is significant difference between the excellent prognosis of grade 2 endometrioid carcinoma, the intermediate prognosis of grade 3 carcinoma, and the poor prognosis of undifferentiated carcinoma, which in cases of association with differentiated areas should be diagnosed as dedifferentiated endometrioid carcinoma.     

Clinicopathologic study of endometrial dedifferentiated endometrioid adenocarcinoma: a case report

In 2006, dedifferentiated endometrioid adenocarcinoma (undifferentiated carcinoma associated with low-grade endometrioid carcinoma) of the uterus was first proposed. Dedifferentiated endometrioid carcinoma is part of the spectrum of undifferentiated carcinoma of the endometrium which is a highly aggressive tumor even when the undifferentiated component represents only 20% of the entire neoplasm. Therefore, accurate diagnosis and appropriate classification of this neoplasm are important in patient management. Lack of the recognition may lead to misclassification of dedifferentiated endometrioid adenocarcinoma as a pure endometrioid adenocarcinoma which is less aggressive. Only 4 papers have appeared in the literature so far on the topic of dedifferentiated endometrioid carcinoma. We report herein a first case of endometrial dedifferentiated endometrioid carcinoma in a 51-year old woman in Chinese population. We performed immunoperoxidase studies for 12 markers. Among them, cytokeratins, keratin 7, keratin 18, EMA, estrogen receptor (ER), progesterone receptor (PR), and vimentin show significantly differential expression between differentiated and undifferentiated area.     

Focal adhesion kinase overexpression in endometrial neoplasia.

Focal adhesion kinase (FAK) is a protein tyrosine kinase that is a critical mediator of signaling events between cells and their extracellular matrix. Elevations in FAK mRNA and protein overexpression have been linked to tumor cell capacity for invasion and metastasis. FAK expression has been shown to be elevated in a variety of solid tumors. The purpose of this study was to evaluate for FAK upregulation in endometrial neoplasia. Tissue microarray blocks were made from formalin-fixed, paraffin-embedded archival tissue, including 115 carcinoma (100 endometrioid, 10 serous, and 5 clear cell), 28 hyperplasia, and 38 normal specimens using 1-mm punches. The tissue was immunostained with monoclonal antibody for FAK and p53. Immunoreactivity was scored by intensity (0-4+ scale) and percent positive staining. FAK overexpression was categorized as 4+ cytoplasmic intensity in more than 90% of neoplastic cells. Positive p53 was categorized at least 2+ nuclear intensity in more than 10% of neoplastic cells. Higher rates of FAK upregulation were identified in endometrial hyperplasia (P = 0.025) and carcinoma (P < 0.001) versus normal endometrium. FAK overexpression in carcinoma correlated with higher FIGO grade (P = 0.025) and p53 overexpression (P < 0.001). FAK was consistently overexpressed in high-grade tumors regardless of subtype, including 8 of 10 serous tumors, 4 of 5 clear cell tumors, and 16 of 23 grade 3 endometrioid tumors. In conclusion, upregulation of FAK is seen in both endometrial hyperplasia and carcinoma, implying that FAK may play an important role in endometrial carcinogenesis. FAK overexpression in endometrial carcinoma correlates with higher FIGO grade and p53 overexpression.     

Common epithelial tumors of the ovary: proliferating and of low malignant potential

Ovarian tumors of low malignant potential (LMP) must be distinguished from benign, "proliferating" ovarian tumors and from frank ovarian carcinoma. Serous and mucinous tumors of LMP demonstrate epithelial stratification, the formation of epithelial tufts, cytologic atypia, and mitotic activity, but they do not demonstrate stromal invasion by epithelial cells, which is a feature of frank carcinoma. Mucinous carcinoma may also be recognized by epithelial stratification exceeding three cell layers and the formation of true cribriform glandular patterns. Although controversial, we do not at present recognize a LMP tumor of endometrioid type but prefer to classify those endometrioid neoplasms with a prominent fibrous stroma and glandular complexity similar to adenomatous endometrial hyperplasia as proliferating endometrioid adenofibromatous and cystadenofibromatous tumors. There is only mild cytologic atypia in such tumors. Because of the moderate to marked cytologic atypia that occurs in some clear cell neoplasms with a prominent fibrous stroma, we believe those tumors do merit a designation of LMP tumors. In both the proliferating endometrioid and LMP clear cell adenofibromatous and cystadenofibromatous tumors, carcinoma must be excluded by an absence of stromal invasion, which is frequently recognized by a confluent glandular pattern. The histologic features of proliferating Brenner tumors are similar to those of low grade, papillary, noninvasive, urothelial carcinoma, whereas we propose that Brenner tumors of LMP show high grade cytologic atypia but remain noninvasive in the ovary.     

Undifferentiated endometrial carcinoma arising in the background of high-grade endometrial carcinoma – Expanding the definition of dedifferentiated endometrial carcinoma

Dedifferentiated endometrial adenocarcinoma (DEC) is defined by the coexistence of undifferentiated carcinoma with low-grade (FIGO grade 1 or 2) endometrioid carcinoma. Few cases of DEC arising in the background of high-grade carcinoma (DEC-HG) have been reported, however, this phenomenon is poorly characterized. In this study we describe the morphologic, immunohistochemical and clinico-pathologic characteristics of DEC-HG. 18 DECs were diagnosed at our institution between 2008-2019, and in 11 (61%), the undifferentiated component was associated with high-grade carcinoma (8 endometrioid FIGO grade 3, 2 with ambiguous features, 1 serous). The remaining 7 (39%) represented DEC-LG (3 FIGO grade 1 and 4 FIGO grade 2). 7/11 (64%) patients with DEC-HG presented with advanced stage (FIGO stage III/IV), whereas most with DEC-LG (6/7, 86%) were stage I. On follow up, 2 patients in the DEC-HG group died of disease and 2 had progressive disease within 2 months of surgery. There was only one recurrence in the DEC-LG, 6 months post-surgery. The DEC component in both groups showed similar morphology and immunophenotype, with predominantly focal or complete loss of expression of pan-keratin, EMA, E-cadherin, CK8/18, PAX8 and ER. The DEC component in the DEC-HG group had wild-type p53 expression in 8/11 (73%) cases, loss of MLH1 and PMS2 in 6/11 (55%) and loss of SMARCA4 in 3/9 (33%). Although numbers are small, we show that DEC-HG is a previously under-recognized phenomenon, with morphologic and immunophenotypic similarities to DEC-LG, which supports expanding the definition of DEC to include DEC-HG. DEC-HG may be more aggressive than DEC-LG.     

Immunophenotypic diversity of endometrial adenocarcinomas: implications for differential diagnosis.

Many endometrial adenocarcinomas, particularly those of endometrioid type, express estrogen receptors (ERs), progesterone receptors (PRs), and vimentin. This typical immunophenotype is frequently considered a standard against which others are compared when immunohistochemistry is used for differential diagnosis. We tested large numbers of endometrial cancers, enriched for high-grade tumors, to determine whether this reported immunophenotype was valid and whether expression differences between types of endometrial carcinoma could be exploited for diagnostic purposes. Immunohistochemical stains were performed on the following types of endometrial cancers using established methodology: International Federation of Gynecology and Obstetrics (FIGO) grades 1 and 2 endometrioid-42; FIGO grade 3 endometrioid-40; serous-24; clear cell-11; carcinosarcoma-9. In total, 92% of serous carcinomas expressed p16 strongly compared to weak-to-moderate expression of p16 in 7-67% of other tumors (FIGO grades 1 and 2 carcinoma and carcinosarcoma, respectively). A total of 84% of FIGO grades 1 and 2 carcinomas expressed ER compared to 9-54% of other tumors (clear cell and serous carcinomas respectively); 83% of FIGO grades 1 and 2 expressed PR compared to 11-54% of other carcinomas (carcinosarcoma and serous carcinoma, respectively). Most carcinomas were negative for monoclonal carcinoembryonic antigen (mCEA), and those that were positive showed mostly only focal membrane expression. Vimentin was expressed in nearly every tumor. Most tumors were diffusely vimentin positive, but a large range of expression patterns, from focal to diffuse and from weak to strong, was noted. Only 70% of FIGO grades 1 and 2 endometrioid carcinomas and 26% of grade 3 endometrioid carcinomas possessed the reportedly characteristic endometrial cancer immunophenotype p16 (-), ER (+), PR (+), mCEA (-), and vimentin (+). Endometrial cancers demonstrate substantial immunophenotypic diversity that remained apparent even within groups of similar histologic subtype and grade. ER, PR, and p16 expression was more illustrative of tumor type and degree of differentiation than they were of endometrial origin. In contrast, the vimentin-positive/CEA-negative phenotype remained the most constant among all endometrial cancers.     

Grading gynäkologischer Tumoren

Histopathological assessment of the tumor grade and cell type is central to the management and prognosis of various gynecological malignancies. Conventional grading systems for squamous carcinomas and adenocarcinomas of the vulva, vagina and cervix are poorly defined. For endometrioid tumors of the female genital tract as well as for mucinous endometrial, ovarian and seromucinous ovarian carcinomas, the 3?tiered FIGO grading system is recommended. For uterine neuroendocrine tumors the grading system of the gastrointestinal counterparts has been adopted. Uterine leiomyosarcomas are not graded. Endometrial stromal sarcomas are divided into low and high grades, based on cellular morphology, immunohistochemical and molecular findings. A chemotherapy response score was established for chemotherapeutically treated high-grade serous pelvic cancer. For non-epithelial ovarian malignancies, only Sertoli-Leydig cell tumors and immature teratomas are graded. At this time molecular profiling has no impact on the grading of tumors of the female genital tract.     

Endometrial carcinoma recurring as carcinosarcoma: report of two cases

Endometrial carcinosarcoma is a rare, aggressive disease, accounting for approximately 3% of all uterine neoplasms. The emergence of sarcomatous elements is considered the evolution of subclones arising from high grade endometrial carcinomas. Here, we report two cases of primary endometrial carcinomas recurring as carcinosarcoma. Case 1. a 58-year-old postmenopausal woman diagnosed to have a poorly differentiated endometrial endometrioid adenocarcinoma (FIGO stage IB) developed an intra-abdominal recurrence of disease after 17 months from diagnosis. Histopathological analysis documented a biphasic neoplasia consisting of an epithelial (grade 3 endometrial endometrioid adenocarcinoma) and a sarcomatous component. Salvage chemotherapy with cisplatin, ifosfamide, epirubicin, and then with taxotere was attempted. The patient died after 2 months. Case 2. A 56-year-old woman with a diagnosis of grade 3 endometrial adenosquamous carcinoma of the endometrium (FIGO stage IIIA) experienced pelvic recurrence after five months from completion of chemotherapy. Definitive histology was malignant mixed mesodermal tumor with focal areas of chondrosarcomatous elements. The patient was triaged to exclusive concomitant chemoradiotherapy and salvage chemotherapy. The patient died after 3 months. We describe two cases of high grade endometrial carcinomas recurring as carcinosarcoma, thus providing evidence that the metaplastic sarcomatous evolution is a very rare event which can occur in patients with anaplastic endometrial cancer.     

Endometrioid adenocarcinoma of the ovary arising in atypical endometriosis

Ovarian endometriosis can transform into malignant tumors, and ovarian carcinomas relatively frequently contain foci of endometriosis. In this study, the author reviewed 15 cases of endometrioid adenocarcinoma of the ovary in the last 15 years of our pathology laboratory in search for the presence of endometriosis within the tumor. Six (40%) of the 15 endometrioid adenocarcinoma were found to have endometriosis in the tumor. All of the endometriosis were atypical. The age of the 6 patients ranged from 44 year to 78 year with a median of 59 years. Grossly, the endometrial adenocarcinomas with endometriosis were characterized by unilocular cystic tumors in 5 cases and multilocular cystic tumor in one case. Histologically, the grade of endometrioid carcinoma was grade I in 3 cases, grade II in 2 cases and grade III in 1 case. Endometriosis was mixed with the tumors or was present adjacent to the tumor. The endometriosis was composed of a layer of atypical epithelium (atypical endometriosis), and gradual merges between endometriosis and carcinoma were present in 3 cases. These findings suggest that atypical endometriosis can transform into endometrioid carcinoma.     

Metastatic and independent cancers of the endometrium and ovary: a clinicopathologic study of 34 cases

Twenty-one of 34 simultaneous cancers involving the endometrium and ovary were classified as endometrial primary tumors with ovarian metastases. The criteria for this classification were either a multinodular ovarian pattern (major criterion) or two or more of the following minor criteria: small (less than 5 cm) ovary(ies), bilateral ovarian involvement, deep myometrial invasion, vascular invasion, and tubal lumen involvement. Twelve cancers were classified as independent neoplasms, primarily by the absence of the above criteria. Although they were classified as independent, the histologic features of the endometrial and ovarian tumors were the same in 11 of these 12 cases. Only one case represented an ovarian primary tumor with an endometrial metastasis. Both the group believed to have endometrial primaries with ovarian metastases and that with independent primaries showed high incidences of associated endometrial hyperplasia, supporting the belief that the endometrium is a primary site in both groups. The cancers classified as metastatic, with no known spread outside the endometrium-myometrium and ovary, were found to involve other sites significantly (P less than 0.01) more frequently than those classified as independent. Grade 3 endometrioid carcinoma, adenosquamous carcinoma, and malignant mixed müllerian tumors occurred only in the metastatic group, whereas the independent group had a variety of endometrioid and nonendometrioid tumors.     

Non-endometrioid carcinomas of the uterine corpus: a review of their pathology with emphasis on recent advances and problematic aspects

This review considers the clinical and pathologic features of the various histologic subtypes of endometrial carcinoma excluding those of pure endometrioid type, as the latter tumors were the subject of a previous contribution in the Journal (Vol. 9, No. 2). Non-endometrioid carcinomas, which account for about 10% of endometrial carcinomas, may pose a great array of problems in differential diagnosis, including their distinction not only from benign lesions but also endometrioid carcinoma and various tumors that may secondarily involve the uterine corpus. The most common subtypes are serous, mucinous, and undifferentiated. Rarer tumors are clear cell, squamous, transitional cell carcinomas, and a variety of poorly differentiated carcinomas with unusual forms of differentiation, such as hepatoid carcinoma, carcinomas with trophoblastic elements, and giant cell carcinoma. Mixed carcinomas, which are common, are also discussed, including those with a component of endometrioid carcinoma. The final section deals with endometrial involvement by metastatic tumors, lesions that, albeit rare, are sometimes neglected in the differential diagnosis of endometrial carcinomas. Important aspects emphasized are: (1) The potential for serous carcinoma to be mimicked by various forms of papillary endometrioid carcinoma. (2) The rarity of clear cell carcinoma and the greater frequency of clear cells in endometrioid carcinoma. (3) The frequency of mucinous epithelium in tumors of mixed cell type. (4) The frequency with which neoplastic mucinous epithelium originates from the endometrium. (5) The striking degree of differentiation of some squamous cell carcinomas. (6) The occasional predominance of non-endometrioid carcinomas (especially serous or undifferentiated carcinoma) within malignant mullerian mixed tumors. (7) The spectrum of reactive epithelial changes and other non-neoplastic abnormalities that may mimic serous or clear cell carcinoma.     

Beta-catenin and E-cadherin expression patterns in high-grade endometrial carcinoma are associated with histological subtype.

Both beta-catenin and E-cadherin are epithelial cell adhesion molecules. In addition, beta-catenin is an important element of the Wnt signal transduction pathway, which has been implicated in embryogenesis and carcinogenesis, including the development of endometrial and ovarian endometrioid carcinomas. We hypothesized that the expression pattern of these two adhesion molecules may depend upon the histological subtype of endometrial carcinomas. Therefore, we compared the immunohistochemical expression of beta-catenin and E-cadherin in a set of uterine adenocarcinomas matched for high histologic grade, that is, poorly differentiated (International Federation of Gynecology and Obstetrics [FIGO] Grade III) uterine endometrioid carcinomas and uterine serous carcinomas. Seventeen FIGO Grade III endometrioid adenocarcinomas and 17 serous carcinomas were evaluated histologically and immunohistochemically with commercially available monoclonal antibodies against beta-catenin and E-cadherin. Nuclear expression of beta-catenin was observed in 8 of 17 (47%) endometrioid adenocarcinomas but in none of the serous carcinomas (P = .003). Moderate or strong E-cadherin expression was identified in 7 of 17 (41%) serous carcinomas as opposed to in only 1 of 17 (6%) endometrioid adenocarcinomas (P = .02). The majority of endometrioid adenocarcinomas showed strong beta-catenin expression coupled with weak E-cadherin expression; serous carcinomas did not exhibit a comparable trend. Our results indicate that the expression of beta-catenin and E-cadherin in high-grade endometrial cancers is strongly associated with histological subtype. These data provide further support for the distinct molecular profiles of endometrioid adenocarcinoma and serous carcinoma. Notably, differences in cell adhesion molecule expression could account for variations in patterns of tumor dissemination. The immunohistochemical staining pattern may also be useful for diagnostic purposes.     

Hypomethylation-induced expression of S100A4 in endometrial carcinoma.

Expression of various S100 genes has been associated with clinically aggressive subtypes in a variety of different cancers. We hypothesized that S100A4 would be overexpressed in endometrial carcinoma compared to benign endometrium. Quantitative real-time RT-PCR (qRT-PCR) was used to quantify the mRNA level of S100A4 in benign endometrium (n=19), endometrioid adenocarcinoma (n=87), and non-endometrioid tumors (n=21). Immunohistochemistry was used to verify the results of qRT-PCR and to assess protein localization. Possible mechanisms of S100A4 gene regulation were also examined. S100A4 was overexpressed in the grade 3 endometrioid tumors, uterine papillary serous carcinoma, and uterine malignant mixed müllerian tumor. Expression in grade 1 and grade 2 endometrioid tumors was comparable to that of normal endometrium, which was quite low. Expression was significantly higher in stage III and IV tumors compared with stage I. By immunohistochemistry, S100A4 was expressed in the tumor cell cytoplasm of poorly differentiated tumors, but was not detected in normal endometrial glandular epithelium. In benign endometrium, S100A4 expression was confined to stromal cells. S100A4 was not regulated by estrogen or progesterone, and its expression in tumors was not significantly correlated to estrogen receptor or progesterone receptor content. However, methylation of the S100A4 gene was detected in benign endometrium and grade 1 tumors with low S100A4 expression. In contrast, grade 3 endometrioid tumors with high S100A4 mRNA and protein expression showed no methylation of the gene. These methylation results were verified in endometrial cancer cell lines with differential baseline levels of S100A4 protein. These results suggest that hypomethylation is an important mechanism of regulating the expression of the S100A4 gene. These results support the emerging concept that hypomethylation may play a role in the upregulation of genes during later stages of tumorigenesis.     

Ezrin expression is related to poor prognosis in FIGO stage I endometrioid carcinomas.

As a cortical cytoskeletal protein, ezrin adapts the cytoplasmic tail of CD44 to the actin-based cytoskeleton and is functionally involved in migration and adhesion that are prerequisites for metastasis. To assess the importance of ezrin and its associated protein osteopontin for the progression of endometrioid carcinoma in FIGO stage I, we analyzed paraffin-embedded tissue from 164 patients by immunohistochemistry and correlated these data with clinicopathological parameters. Ezrin was expressed in normal proliferating endometrial glands, as was confirmed by quantitative PCR and immunohistochemistry. In endometrioid carcinoma, enhanced ezrin expression correlated with a reduced overall survival in univariate analysis (P = 0.041). In contrast, no significant correlation was found for osteopontin. In multivariate survival analysis, among FIGO grade 3 and age, ezrin was still found to be an independent risk factor (relative risk 2.2, confidence interval 1.0-5.4, P = 0.047). Hence, elevated ezrin expression is a new independent prognostic marker in FIGO stage I endometrioid carcinoma, and thus provides further evidence for an important role of ezrin in tumor progression.     

Dedifferentiated endometrial cancer: an atypical case diagnosed from cerebellar and adrenal metastasis: case presentation and review of literature

Dedifferentiated endometrial cancer (DEC) is microscopically characterized by the presence of high-grade areas emerging from low-grade tumour. DEC is an aggressive tumour even when the dedifferentiated component represents only 20% of the entire neoplasm. A proper histological diagnosis is essential to define the most appropriate therapeutic approach for these tumors, since they are characterized by a particularly aggressive trend and by an extremely poor prognosis. We report a single case of DEC associated with dedifferentiated and adrenal metastasis, for which the patient underwent both abdominal-pelvic and cerebellar surgery. Dedifferentiated carcinoma of the endometrium is a poorly recognized neoplasm since they have not been clearly defined the histological features discriminating this neoplasm from high-grade endometrioid adenocarcinoma. Revising existing literature we found 79 described cases of central nervous system secondary involvement and 13 cases where the onset of the disease was characterized by neurological signs and symptoms. We could only find two reported cases of adrenal metastases originating from endometrial neoplasia but in no case of dedifferentiated endometrial carcinoma previously described has been reported the concomitant adrenal-cerebellar involvement.     

Loss of DNA mismatch repair protein hMSH6 in ovarian cancer is histotype-specific

Microsatellite instability (MSI) due to defects in DNA mismatch repair genes may be involved in the development of a subset of human ovarian carcinomas. The role of one such gene, hMSH6, in ovarian cancer is not well documented. We investigated the expression of hMSH6 protein in different histotypes of ovarian carcinoma and the associations between loss of hMSH6 protein and tumor grade, disease stage, familial history of cancer and patient survival. We stained an ovarian carcinoma tissue microarray consisting of formalin-fixed, paraffin-embedded tissue samples from 322 patients with an anti-hMSH6 antibody and scored the results semiquantitatively as negative or positive. Twelve cases were excluded owing to loss of cores during staining. Absence of hMSH6 protein was noted in 20 of 230 serous carcinomas (8.7%), in 7 of 16 clear cell carcinomas (43.7%), in 4 of 34 endometrioid carcinomas (11.7%), in 1 of 14 malignant mixed Müllerian tumors, 2 of 6 mucinous carcinomas, 0 of 2 transitional cell carcinomas and in 0 of 8 undifferentiated carcinomas. Loss of hMSH6 protein was not associated with survival, patient age, tumor grade, or disease stage but was associated with clear cell, mucinous and endometrioid carcinoma histology (P<0.007). These findings indicate that loss of hMSH6 expression in ovarian carcinoma is more common in certain histologic subtypes, particularly in clear cell, endometrioid, and mucinous carcinoma, suggesting that loss of hMSH6 function may participate in the pathogenesis of these subtypes of cancer. Loss of hMSH6 expression did not predict survival and was not associated with disease stage, tumor grade, patient age or family history of cancer.     

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.     

Low-grade endometrioid carcinoma of the ovary associated with undifferentiated carcinoma: case report and review of the literature

The association of low-grade endometrioid carcinoma with undifferentiated carcinoma (UC) was first reported in endometrium carcinoma, termed with dedifferentiated carcinoma (DC). However, the coexistence of low-grade endometrioid carcinoma (LGEC) or serous carcinoma (LGSC) with UC has received minimal attention in ovary, and the behavior of this kind of neoplasm remains at further discussion. In this study, we reported a case of low-grade ovarian endometrioid carcinoma associated with UC and reviewed another four cases previously reported. We found a histological continuity between the LGEC and UC components in H&E section, which suggested a dedifferentiation from LGEC to UC components. In summary, this kind of pathological type has aggressive behavior and these patients have very poor prognosis regardless of the amount of undifferentiated carcinoma.