E-cadherin nuclear staining is useful for the diagnosis of ovarian adult granulosa cell tumor

We recently have demonstrated nuclear localization of E-cadherin in ovarian adult granulosa cell tumors (Histopathology 2011;58:423). The purpose of the present study is to investigate the diagnostic utility of E-cadherin nuclear staining for the differential diagnosis between ovarian adult granulosa cell tumor and its morphological mimics. Tissue samples taken from 81 ovarian tumors and 20 extraovarian tumors were immunohistochemically stained using monoclonal anti-E-cadherin antibody recognizing cytoplasmic domain (clone 36 supplied by BD Biosciences, San Jose, CA). The ovarian tumors consisted of 30 adult granulosa cell tumors, 3 Sertoli-stromal cell tumors, 14 fibrothecomas, 5 carcinoid tumors, 1 large cell neuroendocrine carcinoma, 18 endometrioid adenocarcinomas, and 10 poorly differentiated serous adenocarcinomas. Extraovarian tumors consisted of 16 uterine endometrial stromal neoplasms and 4 pulmonary small cell carcinomas. Only tumor cells with nuclear staining were considered positive in this study. Ninety percent of adult granulosa cell tumors, 67% of Sertoli-stromal cell tumors, 64% of fibrothecomas, 75% of endometrial stromal neoplasms, 75% of small cell carcinomas, and the one large cell neuroendocrine carcinoma showed E-cadherin nuclear expression, whereas all the ovarian carcinoid tumors, endometrioid adenocarcinomas, and poorly differentiated serous adenocarcinomas were negative. E-cadherin nuclear staining is useful in distinguishing between adult granulosa cell tumors and ovarian adenocarcinomas or carcinoid tumors. However, it is of limited use for distinguishing between adult granulosa cell tumors and endometrial stromal neoplasms or small cell carcinomas. E-cadherin should be included in the immunohistochemical panel for an accurate diagnosis of ovarian adult granulosa cell tumors.     

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

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

Computerized image analysis of p53 and proliferating cell nuclear antigen expression in benign, hyperplastic, and malignant endometrium.

CONTEXT: The endometrium is an intrinsically dynamic tissue with great capability for regeneration and proliferation; consequently, there is some overlap between features seen in benign, premalignant, and malignant lesions. This leads to marked intrabiopsy, interbiopsy, and interobserver variability. OBJECTIVE: We studied the specificity and sensitivity of computerized image analysis of molecular markers to evaluate its potential use as a diagnostic tool. DESIGN: Specimens from 100 patients were examined and the following histologic diagnoses were assigned: proliferative endometrium (n = 10), secretory endometrium (n = 10), endometrial hyperplasia (n = 40; 30 with no atypia, 10 with atypia), and carcinoma (n = 40; 20 endometrioid, 10 serous, and 10 clear cell). All cases were evaluated immunohistochemically for p53 and proliferating cell nuclear antigen (PCNA) expression. Computerized image analysis was performed with a CAS 200 digital analyzer. RESULTS: Expression of p53 was found only in carcinomas (65%) and endometrial hyperplasia with atypia (30%). Expression of p53 was higher in the poor prognostic categories (serous carcinoma and clear cell carcinoma) than in endometrioid carcinoma. In endometrioid carcinoma, p53 expression correlated with grade. Proliferating cell nuclear antigen showed a similar pattern of results to p53 in the various carcinoma subtypes and endometrioid carcinoma grades. Endometrial hyperplasia PCNA values were the lowest among all the groups. Both carcinomas and proliferative endometrium showed higher glandular and stromal PCNA values, significantly different from endometrial hyperplasia with atypia. In proliferative endometrium, stromal PCNA was the highest among all of the groups. The p53 and PCNA results correlated with each other for carcinoma. CONCLUSIONS: Computerized image analysis correlates well with the established morphologic groups of endometrial pathology and yields results consistent with previous studies. Owing to its higher degree of sensitivity, computerized image analysis is of potential use in cases of diagnostic dilemmas and can help objectively allocate the case in the correct category (e.g., proliferative endometrium vs. endometrial hyperplasia, endometrial hyperplasia with atypia vs. endometrioid carcinoma). It is particularly useful in the evaluation of stromal changes.     

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.     

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).     

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.     

Neuroendokrine Tumoren des Gastrointestinaltrakts

The diffuse neuroendocrine cell system of the gastrointestinal tract gives rise to the neuroendocrine neoplasms. The WHO classification distinguishes between well differentiated neuroendocrine tumors of benign or uncertain behavior, well differentiated neuroendocrine carcinomas of low grade malignancy and poorly differentiated neuroendocrine carcinomas of high grade malignancy. The well differentiated neuroendocrine tumors and carcinomas correspond to the carcinoids of earlier classifications. Further biological and prognostic classification of these neoplasms must consider the localization of the tumors within the gastrointestinal tract. This system allows a clinically relevant diagnosis and includes all so far known tumor entities.     

Prognostic parameters of endometrial carcinoma

Endometrial carcinoma is the most common malignant tumor of the female genital tract in the Western world. Approximately 80% of cases are well- to moderately differentiated (endometrioid) adenocarcinomas, which are confined to the uterine corpus at diagnosis, and thus most can be cured. Conversely, high-grade (ie, clear cell and serous) carcinomas account for only 15% to 20% of cases and show marked nuclear atypia. These tumors usually invade the myometrium and may extend beyond the uterus at the time of hysterectomy. In addition to clinical and morphological differences, these 2 groups of endometrial carcinomas differ in their pathogenesis. Whereas prognosis in the latter group is generally poor, the pathologist's role in establishing the outcome in the former group is crucial. Furthermore, it has become progressively apparent that both groups overlap to some extent, making the dualistic model a guideline at best. Over the last 2 decades, several studies have demonstrated the prognostic importance of various key surgical and pathological parameters, including histological type, histological grade, surgical-pathological stage, depth of myometrial invasion, vascular invasion, and cervical involvement. This review presents the most important prognostic factors of endometrial carcinomas from the pathologist's viewpoint, and attempts to clarify existing conflicts in the classification and diagnosis of these tumors.     

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.     

Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas

Mutation of the ARID1A gene and loss of the corresponding protein BAF250a has recently been described as a frequent event in clear cell and endometrioid carcinomas of the ovary. To determine whether BAF250a loss is common in other malignancies, immunohistochemistry (IHC) for BAF250a was performed on tissue microarrays (TMAs) in more than 3000 cancers, including carcinomas of breast, lung, thyroid, endometrium, kidney, stomach, oral cavity, cervix, pancreas, colon and rectum, as well as endometrial stromal sarcomas, gastrointestinal stromal tumours, sex cord-stromal tumours and four major types of lymphoma (diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, mantle cell lymphoma and follicular lymphoma). We found that BAF250a loss is frequent in endometrial carcinomas but infrequent in other types of malignancies, with loss observed in 29% (29/101) of grade 1 or 2 and 39% (44/113) of grade 3 endometrioid carcinomas of the endometrium, 18% (17/95) of uterine serous carcinomas and 26% (6/23) of uterine clear cell carcinomas. Since endometrial cancers showed BAF250a loss, we stained whole tissue sections for BAF250a expression in nine cases of atypical hyperplasia and 10 cases of atypical endometriosis. Of the nine cases of complex atypical endometrial hyperplasia, all showed BAF250a expression; however, of 10 cases of atypical endometriosis (the putative precursor lesion for ovarian clear cell and endometrioid carcinoma), one case showed loss of staining for BAF250a in the atypical areas, with retention of staining in areas of non-atypical endometriosis. This was the sole case that recurred as an endometrioid carcinoma, indicating that BAF250a loss may be an early event in carcinogenesis. Since BAF250a loss is seen in endometrial carcinomas at a rate similar to that seen in ovarian carcinomas of clear cell and endometrioid type, and is uncommon in other malignancies, we conclude that loss of BAF250a is a particular feature of carcinomas arising from endometrial glandular epithelium.     

Endometriale Karzinome und Vorstufen – Neue Aspekte

Endometrial carcinomas can be separated into two groups which are designated as type I and type II carcinomas today. Both groups of tumors are clearly different with regard to conventional light microscopy, immunohistochemistry, molecular pathology and clinical features. Only type I carcinomas are associated with hyperestrogenism. The group of type I carcinomas consists of endometrioid carcinoma and its variants, and mucinous carcinoma. The prototypes of type II carcinomas are serous and clear cell carcinoma. Not all carcinomas, however, can be assigned to one of the two groups, because there are hybrid tumors and mixed carcinomas, e.g. endometrioid carcinoma with a serous component. The precursor lesions of the endometrioid carcinoma and the serous carcinoma are well characterized morphologically and by molecular pathology. Atypical hyperplasia is the precursor lesion of endometrioid carcinoma, whereas endometrial intraepithelial carcinoma (EIC) is the precursor lesion of serous carcinoma. No precursor lesion has as yet been identified for clear cell carcinoma. Immunohistochemical markers for endometrial carcinoma are CK7 and vimentin, for serous carcinoma markers are p53 and p16. Correct typing is of essential prognostic necessity in endometrial carcinoma. Of utmost importance is the detection of a serous component, because serous carcinoma leads to early tumor spread with the necessity of radical surgery, chemotherapy and radiotherapy.     

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.     

Precursor lesions of endometrial carcinoma: diagnostic approach and molecular pathology

For endometrial adenocarcinoma two precursor lesions are known: endometrioid adenocarcinoma which is the most frequent type 1 carcinoma develops from atypical endometrial hyperplasia whereas endometrial intraepithelial carcinoma (EIC) is the precursor of serous carcinoma and a subset of clear cell carcinoma both representing type 2 carcinomas. Atypical hyperplasia which shows progression rates into carcinoma of up to 40% is challenged by its poor interobserver reproducibility. A better reproducibility is obtained by the endometrial intraepithelial neoplasia (EIN) concept with fewer categories but it is not compatible with the World Health Organization (WHO) classification of endometrial hyperplasia. The EIN concept includes not only the vast majority of the WHO atypical hyperplasia but also approximately half of the complex hyperplasia without atypia. Rarely, atypical hyperplasia is associated with a secretory or mucinous cell type and two thirds of atypical hyperplasia resolve under long-term high dosage progestin therapy. Immunohistochemistry aids in the differential diagnosis of atypical hyperplasia and EIC. Atypical hyperplasia/EIN frequently show PTEN and/or Pax-2 negativity and low Ki-67 and differ from EIC which shows strong diffuse p53 staining and high Ki-67 staining index.     

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.     

Schnellschnittdiagnostik bei Erkrankungen des weiblichen Genitaltrakts

Intraoperative frozen sections are particularly important for ovarian tumors because definitive preoperative histology is not possible. The diagnostic accuracy of frozen sections is highest for primary invasive ovarian carcinomas and benign ovarian lesions, followed by borderline tumors and poorest for ovarian metastases and rare neoplasms, such as germ cell tumors. Endometrial carcinoma should be diagnosed preoperatively by curettage or biopsy. For endometrioid endometrial carcinomas the indications for lymphadenectomy are often based on intraoperative assessment of the uterus. The differential diagnosis of low grade stromal neoplasms is based on myometrial invasion and can be supported by assessment of frozen sections as well as the diagnosis of other mesenchymal uterine tumors suspected of being malignant. Frozen sections of pelvic lymph nodes provide the possibility of immediate subsequent para-aortic lymphadenectomy in endometrial and cervical carcinomas but have recently lost importance. Sentinel node biopsy with intraoperative frozen section analysis is routinely performed only for vulval carcinoma. The German Association of Gynecological Oncology (AGO) recommends deferred diagnosis and a two stage surgical procedure for any doubtful intraoperative ovarian histology. Intraoperative frozen sections for endometrial carcinoma and lymphadenectomy specimens as well as for sentinel node biopsies are currently not recommended but are also not completely rejected.     

Image cytometry DNA ploidy correlates with histological subtypes in endometrial carcinomas.

Image cytometric DNA ploidy analysis of endometrial carcinomas was performed to determine whether ploidy status and ploidy-related parameters like DNA index, percentage of cells exceeding 5c and 9c, correlate with histologic subtype. This is a prospective study of 391 patients with stage I endometrial carcinoma which included 331 (85%) endometrioid adenocarcinoma, 22 (6%) serous adenocarcinoma, 7 (2%) clear cell adenocarcinoma, 2 (0.5%) small cell carcinoma, 1 (0.3%) undifferentiated carcinoma, and 28 (7%) unclassifiable adenocarcinoma. Twenty-five percent of endometrioid adenocarcinomas were non-diploid. In contrast, all clear cell adenocarcinomas and 21/22 (95%) of serous adenocarcinomas were non-diploid. Hyperdiploidy (25 cases) was found only in endometrioid adenocarcinomas. Mean DNA index of the stemline in serous adenocarcinoma (1.72) and clear cell adenocarcinoma (1.81) was higher than in endometrioid adenocarcinoma (1.1). The difference in ploidy-related parameters between endometrioid adenocarcinoma and serous adenocarcinoma was highly significant (P<0.001). In addition, Grade 3 endometrioid adenocarcinoma showed significant difference in all ploidy-related parameters compared with grade 1 and grade 2 tumors (P<0.001). Our results show that DNA ploidy-related parameters may be valuable in subtyping histologically difficult cases of endometrial carcinomas.     

Minimal uterine serous carcinoma: a clinicopathological study of 40 cases.

The term 'minimal uterine serous carcinoma' has been proposed to include serous carcinomas with invasion limited to the endometrium (superficial serous carcinoma), and those without stromal invasion (intraepithelial serous carcinoma or endometrial intraepithelial carcinoma). Both lesions display similar cytological and immunohistochemical profiles of a typical invasive serous carcinoma with a high nuclear grade and an overexpression of mutant p53 protein. We studied the clinicopathologic features of 40 cases of minimal uterine serous carcinoma. All patients were postmenopausal and underwent hysterectomy and surgical staging procedures. There were nine cases of intraepithelial serous carcinoma and 31 cases of superficial serous carcinoma. Five intraepithelial serous carcinomas and 16 superficial serous carcinomas exclusively involved an endometrial polyp. A total of 18 minimal uterine serous carcinomas also involved, in addition to a polyp, the endometrium proper in the form of intraepithelial serous carcinoma (13 cases) and superficial serous carcinoma (five cases). Overall, minimal uterine serous carcinomas were found to involve an endometrial polyp in 88% of the cases (35/40) and were confined to the polyp in 53% (21/40). Extrauterine tumors were present in 45% of the cases (18/40). In all, 22 patients with tumor limited to their uteri demonstrated an overall survival of 94% (2-73 months of follow-up). Eight of 18 patients with extrauterine tumors died of their malignancy (1.5-62 months of follow-up). In conclusion, a significant majority of minimal uterine serous carcinomas involve an endometrial polyp. Complete surgical staging is important to predict the prognosis. When the lesion is confined to an endometrial polyp and/or the endometrium proper, the clinical outcome is excellent.     

Tumoren des endokrinen Pankreas

The neuroendocrine tumors of the pancreas are rare, but belong to the most common endocrine neoplasms of the abdomen. In most cases, they show a characteristic macroscopic and microscopic pathology. On the basis of morphological, immunohistological and biological criteria, the WHO classification distinguishes between well differentiated tumors with benign or uncertain behavior, well differentiated (low grade malignant) carcinomas and poorly differentiated (high grade malignant) carcinomas. The functional tumor entities on which the classification is based are briefly described and discussed.     

Cytogenetic and molecular aberrations in endometrial stromal tumors

Endometrial stromal tumors (ESTs) are rare uterine mesenchymal tumors, comprising <10% of all uterine mesenchymal neoplasms. The latest World Health Organization classification divides endometrial stromal tumors into 3 categories based on morphologic features: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma, and undifferentiated endometrial sarcoma. Specific cytogenetic aberrations and molecular genetic alterations have recently been identified in endometrial stromal tumors, providing insights into their molecular biology, potential diagnostic markers, and possible therapeutic targets. Currently, recurrent chromosomal rearrangements resulting in gene fusion play a substantive role in the pathogenesis of endometrial stromal nodules, endometrial stromal sarcomas, and a small subset of undifferentiated endometrial sarcomas. Loss of heterozygosity of tumor suppressor genes and deregulation of the Wnt signaling pathway have also been implicated in EST tumorigenesis. In this review, we summarize the recent advances in the molecular pathology of endometrial stromal tumors.