Serous Intraepithelial Carcinoma Research Articles

Microdissection and Dissociation of the Murine Oviduct: Individual Segment Identification and Single Cell Isolation.

Mouse model systems are unmatched for the analysis of disease processes because of their genetic manipulability and the low cost of experimental treatments. However, because of their small body size, some structures, such as the oviduct with a diameter of 200-400 μm, have proven to be relatively difficult to study except by immunohistochemistry. Recently, immunohistochemical studies have uncovered more complex differences in oviduct segments than were previously recognized; thus, the oviduct is divided into four functional segments with different ratios of seven distinct epithelial cell types. The different embryological origins and ratios of the epithelial cell types likely make the four functional regions differentially susceptible to disease. For example, precursor lesions to serous intraepithelial carcinomas arise from the infundibulum in mouse models and from the corresponding fimbrial region in the human fallopian tube. The protocol described here details a method for microdissection to subdivide the oviduct in such a way to yield a sufficient amount and purity of RNA necessary for downstream analysis such as reverse transcription-quantitative PCR (RT-qPCR) and RNA sequencing (RNAseq). Also described is a mostly non-enzymatic tissue dissociation method appropriate for flow cytometry or single cell RNAseq analysis of fully differentiated oviductal cells. The methods described will facilitate further research utilizing the murine oviduct in the field of reproduction, fertility, cancer, and immunology.

Endometrial carcinoma: molecular subtypes, precursors and the role of pathology in early diagnosis.

Endometrial carcinoma (EC) is classified into a wide range of morphological variants; this list has expanded over the past decade with the inclusion of mesonephric-like and dedifferentiated carcinoma as EC variants in the fifth edition of the WHO Classification of Female Genital Tumours, and recognition that carcinosarcoma is a biphasic carcinoma rather than a sarcoma. Each EC variant has distinct molecular abnormalities, including TCGA-based molecular subtypes, allowing further subclassification and adding complexity. In contrast to this rapid progress in understanding EC, there are only two recognized EC precursor lesions: endometrial atypical hyperplasia/endometrioid intraepithelial neoplasia (EAH/EIN) and serous intraepithelial carcinoma, a situation that has not changed for many years. Diagnosis of EC precursors is a cornerstone of surgical pathology practice, with early diagnosis contributing to the relatively favorable prognosis of EC. In this review we relate the precursor lesions to each of the EC morphological variants and molecular subtypes, discuss how successful early diagnosis is for each variant/molecular subtype and how it might be improved, and identify knowledge gaps where there is insufficient understanding of EC histogenesis. © 2020 The Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The Association and Significance of p53 in Gynecologic Cancers: The Potential of Targeted Therapy.

Dysfunction of p53 is observed in the many malignant tumors. In cervical cancer, p53 is inactivated by degradation through the complex with human papilloma virus (HPV) oncoprotein E6 and E6-associated protein (E6AP), an E3 ubiquitin protein ligase. In endometrial cancer, overexpression of p53 in immunohistochemistry is a significant prognostic factor. A discrepancy between p53 overexpression and TP53 mutations is observed in endometrioid endometrial cancer, indicating that the accumulation of p53 protein can be explained by not only gene mutations but also dysregulation of the factors such as ERβ and MDM2. Furthermore, the double-positive expression of immunoreactive estrogen receptor (ER) β and p53 proteins is closely associated with the incidence of metastasis and/or recurrence. High-grade serous ovarian carcinoma (HGSC) arises from secretary cells in the fallopian tube. The secretary cell outgrowth (SCOUT) with TP53 mutations progresses to HGSC via the p53 signature, serous intraepithelial lesion (STIL), and serous intraepithelial carcinoma (STIC), indicating that TP53 mutation is associated with carcinogenesis of HGSC. Clinical application targeting p53 has been approved for some malignant tumors. Gene therapy by the adenovirus-mediated p53 gene transfer system is performed for head and neck cancer. A clinical phase III trial using MDM2/X inhibitors, idasanutlin (RG7388) combined with cytarabine, is being performed involving relapse/refractory acute myeloid leukemia patients. The use of adenoviruses as live vectors which encode wild-type p53 has given promising results in cervical cancer patients.

Serous endometrial intraepithelial carcinoma diagnosed by hysteroscopic transcervical resection

Serous endometrial intraepithelial carcinoma diagnosed by hysteroscopic transcervical resection

Precursor lesions of endometrial carcinoma

The 2014 WHO classification distinguishes between endometrial hyperplasia without atypia (EH) and atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN). AEH/EIN is characterized by crowded glands with cytologically atypical epithelium separated by little intervening stroma. Cellular atypia is characterized by nuclear enlargement and rounding, pleomorphism, loss of polarity, and presence of nucleoli. The diagnosis of atypia is facilitated by comparison with areas of adjacent normal and non-atypical glands, respectively. AEH/EIN is often associated with squamous but also secretory and mucinous metaplasia. Loss of PTEN and/or PAX2 immunoreactivity occurs in up to two thirds of AEH/EIN. In contrast, invasive low-grade endometrioid carcinoma shows confluent growth with loss of stroma and formation of labyrinth-like or cribriform structures. Differential diagnosis includes different forms of metaplasias, papillary proliferations, and hyperplastic polyps. Epithelial metaplasia may be present in various benign endometrial lesions as well as in endometrioid adenocarcinoma. AEH/EIN may also occur in endometrial polyps. Progestin therapy of AEH/EIN has low level of evidence but frequently leads to complete regression. Serous intraepithelial carcinoma (SEIC) is characterized by high-grade cellular atypia and polymorphism, detachment of cells, amutant immunoreactive pattern for the P53 and anincreased Ki67 labeling index. Although designated as precursor of serous carcinoma of the endometrium, biologically it is considered a non-invasive serous carcinoma since it may already be associated with massive extrauterine spread.

Characterization of MicroRNA-200 pathway in ovarian cancer and serous intraepithelial carcinoma of fallopian tube

BackgroundOvarian cancer is the leading cause of death among gynecologic diseases in Western countries. We have previously identified a miR-200-E-cadherin axis that plays an important role in ovarian inclusion cyst formation and tumor invasion. The purpose of this study was to determine if the miR-200 pathway is involved in the early stages of ovarian cancer pathogenesis by studying the expression levels of the pathway components in a panel of clinical ovarian tissues, and fallopian tube tissues harboring serous tubal intraepithelial carcinomas (STICs), a suggested precursor lesion for high-grade serous tumors.MethodsRNA prepared from ovarian and fallopian tube epithelial and stromal fibroblasts was subjected to quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) to determine the expression of miR-200 families, target and effector genes and analyzed for clinical association. The effects of exogenous miR-200 on marker expression in normal cells were determined by qRT-PCR and fluorescence imaging after transfection of miR-200 precursors.ResultsOvarian epithelial tumor cells showed concurrent up-regulation of miR-200, down-regulation of the four target genes (ZEB1, ZEB2, TGFβ1 and TGFβ2), and up-regulation of effector genes that were negatively regulated by the target genes. STIC tumor cells showed a similar trend of expression patterns, although the effects did not reach significance because of small sample sizes. Transfection of synthetic miR-200 precursors into normal ovarian surface epithelial (OSE) and fallopian tube epithelial (FTE) cells confirmed reduced expression of the target genes and elevated levels of the effector genes CDH1, CRB3 and EpCAM in both normal OSE and FTE cells. However, only FTE cells had a specific induction of CA125 after miR-200 precursor transfection.ConclusionsThe activation of the miR-200 pathway may be an early event that renders the OSE and FTE cells more susceptible to oncogenic mutations and histologic differentiation. As high-grade serous ovarian carcinomas (HGSOC) usually express high levels of CA125, the induction of CA125 expression in FTE cells by miR-200 precursor transfection is consistent with the notion that HGSOC has an origin in the distal fallopian tube.

Ovarian cancer stem cells more questions than answers.

Epithelial ovarian cancer is a highly lethal disease, which is usually diagnosed at a late stage with extensive metastases in the abdominal cavity. Ovarian cancer either develops from the ovarian surface epithelium (OSE) or from serous intra-epithelial carcinoma (STIC). Primary therapy consists of debulking surgery and platinum based chemotherapy. The success of debulking surgery depends on surgical skills but also on the gene signature of the tumour. Debulking surgery combined with first line platinum based chemotherapy, frequently leads to complete remission. However, most ovarian cancers relapse. Once the disease has relapsed, the interval between subsequent therapies decreases steadily due to rapid progression and therapy resistance. Research on therapy resistance of ovarian cancer is frequently devoted to genetic alterations in cancer cells, leading to drug inactivation, enhanced DNA repair mechanisms and intracellular pathway derangements. However the knowledge of ovarian cancer stem cells (OCSC) and the role they play in the development of cancer and therapy resistance is sparse. In this review current knowledge on the characteristics of OCSCs and the micro environmental mechanisms leading to the development or activation of OCSCs resulting in ovarian cancer is reviewed. Moreover the role of OCSC in both surgical and systemic therapy resistance and the relation with epithelial mesenchymal transformation (EMT) is discussed, as are micro-environmental signals leading to OCSC or EMT activation.

Serous Endometrial Intraepithelial Carcinoma Involving Endometrial Polyp Diagnosed by Transcervical Resection: A Case Report

Uterine serous carcinoma is a representative histological subtype of endometrial type II cancer. Uterine serous intraepithelial carcinoma is thought to be a precursor lesion of uterine serous carcinoma. Uterine serous intraepithelial carcinoma is frequently found to involve an endometrial polyp. Preoperative diagnosis of uterine serous intraepithelial carcinoma is difficult due to its localized occurrence in the endometrial cavity. We experienced a case of postmenopausal women with abnormal endometrial cytology. Endometrial biopsy suggested the possibility that she has a malignant uterine tumor, but it did not reached to the confirmative pathological diagnosis. Hysteroscopy revealed that she has an endometrial polyp. Pathological analysis of the resected endometrial polyp confirmed that her disease is uterine serous intraepithelial carcinoma involving endometrial polyp. She underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy and retroperitoneal lymphadenectomy. No extrauterine lesion was detected. Our case suggested the possibility that transcervical resection under the hysteroscope might be useful to detect serous endometrial intraepithelial carcinoma.

Pathologic features of fallopian tubal fimbriae in patients with endometrial serous carcinoma

To discuss the potential relationship between endometrial serous carcinoma (ESC) and tubal epithelial lesions by pathologic examination of fallopian tubes with ESC. A total of 30 cases of typical ESC were reexamined and chosen by the pathologist. In each case, bilateral fallopian tubes were submitted to examination of pathologic morphology and immunostaining for p53, annexin IV (ANX-IV), human epidermal growth factor receptor 2 (HER2)/neu, and high-mobility group protein A2 (HMGA2). Fallopian tubal epithelial lesions were found in 15 cases, including 9 cases tubal serous carcinoma, 2 cases serous tubal intraepithelial carcinoma (STIC) and 2 cases epithelial hyperplasia. Both sides of tubal serous carcinoma and STIC were found in 1 case. The results showed the positive expression for p53 in 26 (87%) out of 30 endometrial malignant specimens tissues and 9 (30%) tubal tissues samples (P > 0.05). Twenty-five (83%) endometrial malignant specimens tissues and 6 (20%) tubal tissues samples showed the positive expression of ANX-IV. Twenty-one (70%) endometrial malignant tissues and 7 (23%) tubal tissues showed the positive expression of HER2/neu. Twenty-five (83%) endometrial malignant tissues and 6 (20%) tubal tissues showed the positive expression of HMGA2. While, there were significant differences among the expression of three proteins between endometrium and the fallopian tube site (all P < 0.05). STIC may be associated with the occurrence of ESC. The expression of p53 was positively correlated between the fallopian tube and the endometrium. ANX-IV, HER2/neu and HMGA2 were extensively expressed in ESC.

Vanishing endometrial cancer in hysterectomy specimens: a myth or a fact.

The incidence of endometrial cancers diagnosed on biopsy that have no residual cancer identified at hysterectomy is not well studied. The aim of our study was to determine the incidence and long-term follow-up of this "vanishing cancer" phenomenon. All slides from the initial biopsy/curettage and hysterectomy specimens were reviewed and the diagnosis confirmed by a gynecologic pathologist. The entire endometrium was serially sectioned and submitted for histologic examination. Clinical and pathologic variables were analyzed, including patient demographics, tumor histologic type and grade, stage, biopsy method, adjuvant therapy, surgical procedure, recurrence, and disease-specific survival. We identified 23 biopsy-proven cases of endometrial cancer with no residual disease on hysterectomy specimen. Of the 23 patients, 15 (65.2%) were diagnosed as endometrioid, 6 (26%) serous, 1 clear cell (4.3%), and 1 (4.3%) serous intraepithelial carcinoma. Seventeen underwent dilatation and curettage, and 6 had endometrial biopsy as the primary procedure. The median follow-up was 8.8 years (range, 1.2 to 17 y). Only 2 cases with serous carcinoma underwent adjuvant chemotherapy, and none received radiation therapy. Only 1 patient died of disease after 27 months and was diagnosed as FIGO grade II endometrioid carcinoma on dilatation and curettage. The inability to identify cancer in a hysterectomy specimen for biopsy-confirmed carcinoma does not indicate technical failure. Although there is no specific standard treatment for patients with "vanishing endometrial cancer," the prognosis is excellent; however, close follow-up is suggested.

Differential Expression of p-ERM, a Marker of Cell Polarity, in Benign and Neoplastic Oviductal Epithelium

Serous tubal intraepithelial carcinoma (STIC) is a noninvasive phase of pelvic serous cancer at risk for metastasizing. Because of its biologic significance, its accurate distinction from nonmalignant mimics is important. Loss of cell orientation is an important feature of STIC. We sought to determine whether the immunohistochemical localization of cytoskeletal-organizing proteins phospho-ezrin-radaxin-moesin (p-ERM) would be useful in making this distinction. The benign oviductal entities (normal and p53 signatures), premalignant atypias (tubal intraepithelial lesions in transition), serous intraepithelial carcinomas (STICs), and carcinomas were analyzed for 5 staining patterns and compared. Linear or uniform luminal p-ERM staining was strongly associated with benign mucosa in contrast to STICs, in which it was lost and often replaced by nonlinear or nonuniform patterns highlighting individually cell groups or single cells. Premalignant atypias were similar to benign mucosa by p-ERM staining and retained the linear luminal pattern. This study shows, for the first time, that patterns of staining for an immunohistochemical correlate of cell polarity (p-ERM) differ between STICs, their benign counterparts and premalignant atypias that do not fulfill the criteria for STICs. If confirmed, these findings warrant further analysis of indices of cell polarity as objective markers for the diagnosis and mapping of the evolution of pelvic serous precursors.

Support of the ‘fallopian tube hypothesis’ in a prospective series of risk-reducing salpingo-oophorectomy specimens

ObjectiveTo determine the prevalence, localisation and type of occult (non)invasive cancer in risk-reducing salpingo-oophorectomy (RRSO) specimens in BRCA-mutation carriers and high-risk women from BRCA-negative families. MethodsA consecutive series of RRSO specimens of asymptomatic, screen-negative high-risk women were prospectively collected in our tertiary multidisciplinary cancer clinic from January 2000 until March 2012. All high-risk women in this study underwent genetic testing on BRCA-mutations. The surgico-pathological protocol comprised complete resection of ovaries and fallopian tubes, transverse sectioning at 2–3mm (sectioning and extensively examining the fimbrial end [SEE-FIM] protocol from 2006) and double independent pathology review of morphologically deviant sections. ResultsThree hundred and sixty RRSOs were performed in 188 BRCA1-carriers, 115 BRCA2-carriers and 57 BRCA-negative women at a median age of 44.0years. Four occult invasive cancers were detected in BRCA-carriers (1.3%, 95%-confidence interval (CI) 0.03–2.61), all in BRCA1-carriers >40years of age. All cancers, of which two tubal and two ovarian cancers, were FIGO-stage I/II. Three non-invasive serous intraepithelial carcinomas (STICs) were detected in BRCA-carriers (1.0%, 95%-CI 0.00–2.10). In BRCA-negative women one STIC was found (1.8%, 95%-CI 0.00–5.16), however she carried an unclassified variant in BRCA2. Total follow-up after RRSO was 1691 woman-years, in which one BRCA1-carrier developed peritoneal cancer (0.3%, 95%-CI 0.00–0.82). ConclusionsA low prevalence of occult invasive cancer (1.1%) was found in young asymptomatic, screen-negative women at increased ovarian cancer risk undergoing RRSO. This study adds to the advice to perform RRSO in BRCA1-carriers before the age of 40. Our findings support the hypothesis of the fallopian tube as the primary site of origin of pelvic high-grade serous cancer.

Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Endometrial cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up

Precursor Lesions of High-Grade Serous Ovarian Carcinoma: Morphological and Molecular Characteristics

The lack of proven screening tools for early detection and the high mortality of ovarian serous carcinoma (OSC), particularly high grade, have focused attention on identifying putative precursor lesions with distinct morphological and molecular characteristics. The finding of occult invasive and intraepithelial fallopian tube carcinomas in prophylactically removed specimens from asymptomatic high-risk BRCA 1/2-mutation carriers supports the notion of an origin for OSC in the fallopian tube. The intraepithelial carcinomas have been referred to as serous intraepithelial carcinomas (STICs) but our own findings (unpublished data) and recent reports have drawn attention to a spectrum of changes that fall short of STICs that we have designated serous tubal intraepithelial lesions (STILs).

Minimal Uterine Serous Carcinoma With Extrauterine Tumor of Identical Morphology: An Immunohistochemical Study of 13 Cases

Minimal uterine serous carcinoma includes endometrial intraepithelial serous carcinoma and superficial invasive serous carcinoma. Although they represent in situ and early invasive serous carcinomas, more than 50% of them present with extrauterine tumors of identical morphology. It has not been completely clear whether the extrauterine involvement represents a synchronous tumor arising independently or a metastatic lesion from the endometrial primary. To investigate the relationship between the extrauterine tumor and minimal uterine serous carcinoma, 13 cases of such condition were studied by histologic examination and immunohistochemical staining of 5 related protein markers: estrogen receptor, progestin receptor, p53, WT1, and Ki-67. Morphologic assessment of all extrauterine tumors showed similar histologic features to their corresponding endometrial minimal serous carcinomas. Immunostaining revealed almost identical patterns of 5 protein markers with similar intensities between the endometrial tumors and their corresponding extrauterine lesions. WT1 nuclear staining was observed in most of our cases indicating WT1 expression is not a specific marker in distinguishing ovarian serous carcinoma from uterine serous carcinoma. In conclusion, our findings support the hypothesis that a transtubal metastatic process is responsible for the extrauterine involvement by minimal endometrial serous carcinoma.

Evidence for a latent precursor (p53 signature) that may precede serous endometrial intraepithelial carcinoma

Both serous intraepithelial carcinoma and endometrial glandular dysplasia are associated with uterine serous carcinoma. Recently a candidate serous cancer precursor containing p53 mutations (p53 signature) was described in the fallopian tube. We analyzed normal and neoplastic endometrium for a similar entity. In total 10 endometrial polyps involved by intraepithelial and/or invasive carcinoma and 137 benign polyps were studied. All were stained for p53 and MIB-1. A subset of p53 signatures and carcinomas were analyzed for γ-H2AX and p53 mutations. p53 signatures were identified in 7 of 10 cases intraepithelial carcinoma and were multicentric in 2. In one case, the signature was in continuity with intraepithelial carcinoma. Of 137 benign polyps (4%), 6 contained p53 signatures. The MIB-1 fraction in most signatures was less than 5%, and ranged from 50 to 90% in carcinomas. DNA damage (γ-H2AX) was demonstrated in both p53 signatures and adjacent carcinomas but not in benign polyps. Shared identical p53 mutations were found in paired signatures and carcinomas in two of three cases analyzed, including one case with multiple signatures. In one, a coexistent invasive serous cancer was not found to contain a p53 mutation. In a third, a p53 signature and an invasive cancer harbored two different p53 mutations. This is the first description of p53 signatures adjacent to carcinoma, suggesting a role for this entity in the genesis of serous malignancy. The significance of p53 signatures in benign conditions (polyps) remains to be determined. The role of the p53 signature in early serous neoplasia is discussed.

Human papilloma virus (HPV) status, p16 INK4a, and p53 overexpression in epithelial malignant and borderline ovarian neoplasms

This investigation is the first to evaluate simultaneously human papilloma virus (HPV) status, p16 INK4a, and p53 immunoreactivity in epithelial ovarian neoplasms. The results were analyzed and correlated with histological type, histological grade, and survival of patients. Subtypes considered are papillary serous and mucinous. Polymerase chain reaction (PCR) analysis, performed in our previous study, had already demonstrated a small number of HPV-positive epithelial ovarian neoplasms. No significant correlation was found between the presence of HPV DNA and subtypes of ovarian neoplasms; thus, HPV cannot be considered responsible for epithelial ovarian neoplasm. Since p16 immunoreactivity was present in many other HPV-negative cases of epithelial ovarian neoplasms, this study suggests that p16 overexpression in some neoplasms of the female genital tract is not related to HPV carcinogenesis. A higher p53 expression rate observed between borderline and malignant serous tumors and between serous and mucinous neoplasms can confirm a recent dualistic model of ovarian carcinogenesis. According to this theory, low-grade serous carcinomas (serous intraepithelial carcinomas, serous borderline neoplasm, and ovarian mucinous neoplasms) (type I tumors) develop from mutations of KAS and BRAF, while high-grade serous carcinomas (type II tumors) develop from mutation of p53. In malignant neoplasms, for univariate analysis, patient survival seems to be related to p53, strong and diffuse p16 overexpression, and the stage of development of neoplasms at the diagnosis. In multinomial logistic regression, used to evaluate the role of staging, grading, p16 and p53 immunopositivity as predictor variables of unfavorable outcome of the disease, only p16 positivity was significantly related to the poor prognosis of the cancer.

Serous Intraepithelial Carcinoma Arising in an Endometrial Polyp: A Proposal for Modification of Terminology

Endometrial adenocarcinoma is the most common gynecologic malignancy in the United States, most frequently presenting in postmenopausal women. Two major subtypes of endometrial adenocarcinoma are now well recognized. The more common (type 1) has an endometrioid morphology with several variants. The far more aggressive subtype (type II) that accounts for only 10% of cases more frequently displays a serous morphology, but may have pure clear cell differentiation. We present here an interesting aspect of the type II carcinoma manifested in a case we recently received for consultation at the Department of Pathology, Yale New Haven Hospital. Seven slides were available for review from a 67-year-old woman, who had undergone a total hysterectomy and bilateral salpingo-oophorectomy. An endometrial polyp (Figure 1) was the major finding. Within the polyp, a high-grade malignant serous epithelium focally replaced the surface epithelium and superficial glands of the endometrial polyp (Figure 2). Despite the absence of any myometrial invasion, endocervical mucosal involvement without stromal invasion was identified (Figure 3). The non-neoplastic endometrium was atrophic. The neoplastic cells were immunoreactive for p53 (Figure 4) and showed a high mitotic index on Ki-67 immunostain, supporting the morphologic impression. The clinical, morphologic examination, and immunohistochemical profile were classic for the so-called endometrial intraepithelial carcinoma (EIC).

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.

Stage IA uterine serous carcinoma: a study of 13 cases.

Although in endometrioid type endometrial carcinoma depth of invasion is a powerful predictor of extrauterine disease and survival, in serous carcinoma its importance is unclear. Recurrences and death in patients with serous tumors confined to the endometrium or an endometrial polyp have been reported. In other studies, however, the absence of myometrial invasion was correlated with a more favorable course. In an attempt to clarify this issue, we reviewed 13 completely staged, stage IA serous carcinomas with follow-up from 10 to 93 months (median 38), in which extensive histologic examination had been performed. Serous carcinoma was identified in an endometrial polyp in six cases, in an endometrial polyp and associated endometrium in four, and solely in the endometrium in three cases. No other histologic types of endometrial carcinoma were present, and there was no myometrial invasion. Multifocal serous intraepithelial carcinoma was also seen in 12 cases. Two of the patients died of disease with intraabdominal carcinomatosis at 10 and 14 months after presentation. The overall estimated survival was 83%, showing a relatively favorable prognosis. In conclusion, although the absence of histologically detected myometrial invasion may be associated with recurrences and death in serous carcinoma, an accurately assessed stage based on a careful histologic examination appears to be, at present, the most reliable predictor of survival.