Serous Endometrial Intraepithelial Carcinoma Research Articles

Morphological and immunohistochemical evaluation in distinguishing post-radiotherapy serous-like endometrial change (PoRSEC) and serous endometrial intraepithelial carcinoma (SEIC).

Uteri from women undergoing chemoradiotherapy (CRT) may show reactive atypia which may mimic serous endometrial intraepithelial carcinoma (SEIC). We aimed to assess the prevalence and morphological/immunohistochemical features of post-radiotherapy serous-like endometrial changes (PoRSEC) in women undergone CRT for locally advanced cervical cancer, with a focus on the differential diagnosis with SEIC. Consecutive patients with locally advanced cervical cancer undergone CRT between 2011 and 2018 were reviewed. Endometrial histological specimens were assessed for the presence of PoRSEC. Twenty-two cases of SEIC were included for comparison. Immunohistochemistry for p53, p16, and Ki67 was performed. Out of 244 reviewed patients, 36 (14.7%) showed PoRSEC. The degree of nuclear atypia was similar between PoRSECs and SEIC. However, a papillary architecture with areas of confluent papillae was only observed in SEIC. SEIC cases showed a high mitotic activity as opposed to PoRSEC cases. The expression of p53 was aberrant in all SEICs but in none of the PoRSECs; however, 13/36 PoRSECs showed p53 positivity in most tumor cells, potentially mimicking a mutation pattern. A block-type p16 expression was observed in all SEICs and in 16/36 PoRSECs. Mean Ki67 expression was 26.9% in SEIC (range 5-70%) and 8.16% in PoRSEC (range 5-35%). While SEIC showed sharp morphological and immunohistochemical demarcation, PoRSEC were more heterogenous and merged imperceptibly with normal endometrium. In conclusion, PoRSEC may mimic SEIC both morphologically and immunohistochemically. However, a papillary architecture with cytological demarcation is typically observed in SEIC but not in PoRSEC.

Prognostic value of the presence of serous endometrial intraepithelial carcinoma in uterine serous carcinoma

Prognostic value of the presence of serous endometrial intraepithelial carcinoma in uterine serous carcinoma

Serous Endometrial Intraepithelial Carcinoma with High-Grade Serous Ovarian Carcinoma: A Synchronous Presentation

Serous Endometrial Intraepithelial Carcinoma with High-Grade Serous Ovarian Carcinoma: A Synchronous Presentation

Serous endometrial intraepithelial carcinoma (SEIC) with metachronous umbilical cutaneous, pleural, and peritoneal metastases: Case report and literature review

Serous endometrial intraepithelial carcinoma (SEIC) with metachronous umbilical cutaneous, pleural, and peritoneal metastases: Case report and literature review

Serous endometrial intra-epithelial carcinoma: an observational study

BackgroundSerous endometrial intra-epithelial carcinoma is described as a malignant, superficial spreading lesion with risk of extra-uterine spread at time of diagnosis, and poor outcome.ObjectiveTo evaluate the surgical management of patients...

Serous endometrial intraepithelial carcinoma coexistence with atypical polypoid adenomyoma in a young woman: a rare case

Serous endometrial intraepithelial carcinoma coexistence with atypical polypoid adenomyoma in a young woman: a rare case

Serous endometrial intraepithelial carcinoma (SEIC): Current clinical practice in The Netherlands

IntroductionSerous endometrial intraepithelial carcinoma (SEIC) is a rare diagnosis, defined as an intraepithelial lesion with cells identical to serous type endometrial carcinoma. SEIC is considered to be potentially metastatic, however clear and robust data on prognosis are lacking, potentially leading to variability in clinical management. Objective: The aim is to establish the opinion of gynecologists on the optimal management of patients with SEIC. Methods: An online questionnaire with 15 multiple choice questions was sent to all gynecologists with expertise in gynecological oncology in 19 expert centers in The Netherlands. Results: A total of 24 gynecologists participated. The majority of respondents (n = 18/24, 75%) do not consult a guideline regarding the treatment of SEIC. In current practice, 14 of the 24 respondents perform surgical staging in women with SEIC (58.3%) while seven choose hysterectomy with bilateral salpingo-oophorectomy (29.2%), and three (12.5%) have no firm preference. Eleven of the 14 respondents who perform a surgical staging procedure believe that this is certainly the optimal treatment. The majority of respondents have no firm opinion on whether lymph node sampling or lymph node dissection is preferable during surgical staging (n = 15/23, 65.2%). Most respondents do not give adjuvant therapy (n = 15/24, 62.5%), 25.0% recommend brachytherapy (n = 6/24). Follow-up is for 5 years in almost all cases (n = 23/24). Conclusion: There is no consensus on the optimal surgical treatment and the use of adjuvant therapy for patients with SEIC. Our research team is therefore conducting a nationwide cohort study in which treatment modality, morbidity and survival will be evaluated.

Serous endometrial intraepithelial carcinoma: A clinico-pathological study of 48 cases and its association with endometrial polyps – A tertiary care oncology centre experience

BackgroundEndometrial serous carcinoma (ESC) is an aggressive neoplasm wherein the recent studies have shown that it arises from its putative precursor namely the serous endometrial intraepithelial carcinoma (SEIC). SEIC usually arises in inactive/ atrophic endometrium but surprisingly is frequently associated endometrial polyps (EPs). The aim of this study was to assess the incidence of SEIC with or without invasion, its clinical behaviour and association with endometrial polyp. Materials and MethodsAfter Institutional review board approval, a total of 205 samples (belonging to 120 patients); diagnosed as ESC from January 2009 to December 2015 were retrieved and reviewed for presence of in situ carcinoma and also for associated endometrial polyp. ResultsThe mean age at diagnosis was 62.40 years with postmenopausal bleeding being the most common presenting symptom. The incidence of SEIC with or without invasive tumor was 40% (48/120). Of these 48 cases; 25 cases were associated with in-situ carcinoma arising in the EPs which amounted to 52% of the total cases. The overall three year survival and disease free survival in SEIC with or without invasion were 1.9% and 0.25%, indicating the aggressive nature of the disease. ConclusionSEIC is a difficult histopathological diagnosis and one should carefully look for these lesion, especially in the EPs which are frequently associated with them. Extensive sampling of the EP will be helpful to pick up in-situ carcinoma arising in EP. SEIC is an aggressive disease on its own with a propensity to develop distant metastasis even in the absence of myometrial invasion and hence should be treated with optimum surgical staging and if indicated aggressive adjuvant treatment protocols.

A case of synchronous serous ovarian cancer and uterine serous endometrial intraepithelial carcinoma

BackgroundSerous endometrial intraepithelial carcinoma (SEIC) is now considered to represent an early stage of uterine serous carcinoma (USC). It is an intraepithelial lesion but has been reported to cause extrauterine metastases. We report a case of SEIC with serous ovarian carcinoma and lymph node metastasis.Case presentationA 57-year-old post-menopausal woman (gravida 3, para 2, SA1) was referred to our hospital with lower abdominal pain. An ultrasound and MRI showed that the ovary had swollen to 8 cm in size and had a solid lesion. The uterus was normal. The patient underwent exploratory laparoscopy on the suspicion of torsion of the ovarian tumor. Intraoperative findings showed a right ovarian tumor, but no ovarian tumor torsion was observed. A small amount of bloody ascites was found in the Douglas fossa, and bleeding was observed from the tumor itself. A right salpingo-oophorectomy was then performed. Histopathological results revealed a high-grade serous carcinoma. Forty days after the first surgery, we performed a staging laparotomy: a total abdominal hysterectomy, left salpingo-oophorectomy, systematic pelvic and paraaortic lymphadenectomy, and a partial omentectomy. A complete cytoreduction was achieved. In the pathological examination, the invasion of the serous carcinoma was observed in the left ovarian ligament, and lymph node metastasis was found in the paraaortic lymph nodes. Atypical columnar cells formed irregular papillary lesions which had proliferated in the endometrium, and this was diagnosed as SEIC. The final diagnosis was serous ovarian cancer, FIGO stage IIIA1(ii), pT2bN1M0, with SEIC.ConclusionWe report a case of SEIC with synchronous serous carcinoma of the adnexa uteri. Both were serous carcinomas and, thus, it was difficult to identify the primary lesion. The distinction between metastatic cancer and two independent primary tumors is important for an accurate diagnosis and tumor staging. Histological diagnostic criteria remain controversial, and further development of a method for differentiating between both diseases is required.

漿液性子宮内膜上皮内癌（serous endometrial intraepithelial carcinoma）3症例の報告と内膜細胞診の役割について

漿液性子宮内膜上皮内癌（serous endometrial intraepithelial carcinoma）3症例の報告と内膜細胞診の役割について

Distinct Histologic, Immunohistochemical and Clinical Features Associated With Serous Endometrial Intraepithelial Carcinoma Involving Polyps.

The origin of serous endometrial intraepithelial carcinoma (SEIC) is debated, due to its premalignant and independently malignant nature. It often arises next to endometrial serous carcinoma (ESC), with a propensity for polypoid growth. We aimed to better characterize this discrepancy by analyzing the clinical, histologic, and immunohistochemical features of polypoid carcinoma associated with SEIC (P-SEIC), and compared them with usual endometrial serous carcinoma without SEIC (UESC). Consecutive patients with P-SEIC were recruited and compared with UESC controls from our institutional research center. Clinical, histologic, and immunohistochemical (IHC, ER, PR, P53, Napsin-A, WT1, P16) were analyzed. BRCA testing results and familial history were also extracted from clinical databases. Welch T test, Pearson χ, and Fisher exact test were performed in SPSS version 23. A total of 37 P-SEIC and 25 UESC were the basis of a case-control study. P-SEIC was associated with more bilateral ovarian involvement (P=0.026), yet showed lower rates of myometrial invasion (P=0.002). P-SEIC showed a statistically different IHC profile: p53+, p16+, ER+, PR+, and WT-1+, and high rates of Napsin-A, while UESC was p53+, p16+, WT-1-, Napsin-A-, with lower rates of ER and PR. We also identified 2 patients who received prophylactic salpingo-oophorectomy for BRCA mutations and who subsequently developed P-SEIC with its unique IHC pattern. Our results suggest different underlying expression profiles and possibly diverging molecular signatures between both P-SEIC and UESC. If confirmed in further molecular studies, it could lead to a distinct molecular subclass.

Serous endometrial intraepithelial carcinoma diagnosed by hysteroscopic transcervical resection

Serous endometrial intraepithelial carcinoma diagnosed by hysteroscopic transcervical resection

Uterine serous carcinoma accompany with serous endometrial intraepithelial carcinoma and papillary proliferation of the endometrium: report of a case

目的： 探讨Ⅱ型子宫内膜癌的临床病理特点。 方法： 回顾性分析2018年5月就诊于浙江大学医学院附属妇产科医院的1例子宫浆液性癌伴浆液性子宫内膜上皮内癌及子宫内膜乳头状增生的临床病理资料。 结果： HE染色以及免疫组织化学提示该肿瘤同时具有子宫浆液性癌、浆液性子宫内膜上皮内癌及子宫内膜乳头状增生的病理形态特点。子宫内膜乳头状增生伴发于子宫浆液性癌及浆液性子宫内膜上皮内癌。 结论： 子宫内膜性癌伴浆液性子宫内膜上皮内癌及子宫内膜乳头状增生兼具3种病理形态特点。.

Serous Endometrial Intraepithelial Carcinoma: Case Report and Literature Review

Serous endometrial intraepithelial carcinoma (SEIC) is a rare but highly aggressive form of uterine endometrial cancer. We present a case of a premenopausal 42-year-old patient who presented with copious vaginal bleeding without a specific medical history. A total abdominal hysterectomy was performed. Pathologic results showed SEIC. We report this case and include a brief literature review. J Clin Gynecol Obstet. 2017;6(2):49-52 doi: https://doi.org/10.14740/jcgo446w

Serous Endometrial Intraepithelial Carcinoma: Case Report and Literature Review

Serous Endometrial Intraepithelial Carcinoma: Case Report and Literature Review

Pathology of Endometrial Carcinoma.

On a clinicopathological and molecular level, two distinctive types of endometrial carcinoma, type I and type II, can be distinguished. Endometrioid carcinoma, the typical type I carcinoma, seems to develop through an estrogen-driven "adenoma carcinoma" pathway from atypical endometrial hyperplasia/endometrioid intraepithelial neoplasia (AEH/EIN). It is associated with elevated serum estrogen and high body mass index and expresses estrogen and progesterone receptors. They are mostly low grade and show a favorable prognosis. A subset progresses into high-grade carcinoma which is accompanied by loss of receptor expression and accumulation of TP53 mutations and behaves poorly. Other frequently altered genes in type I carcinomas are K-Ras, PTEN, and ß-catenin. Another frequent feature of type I carcinomas is microsatellite instability mainly caused by methylation of the MLH1 promoter. In contrast, the typical type II carcinoma, serous carcinoma, is not estrogen related since it usually occurs in a small uterus with atrophic endometrium. It is often associated with a flat putative precursor lesion called serous endometrial intraepithelial carcinoma (SEIC). The molecular pathogenesis of serous carcinoma seems to be driven by TP53 mutations, which are present in SEIC. Other molecular changes in serous carcinoma detectable by immunohistochemistry involve cyclin E and p16. Since many of the aforementioned molecular changes can be demonstrated by immunohistochemistry, they are useful ancillary diagnostic tools and may further contribute to a future molecular classification of endometrial carcinoma as recently suggested based on The Cancer Genome Atlas (TCGA) data.

Stromal p16 expression is significantly increased in endometrial carcinoma.

p16 is a negative regulator of cell proliferation and is considered a tumor suppressor protein. Alterations in p16 protein expression are associated with tumor development and progression. However, the p16 expression status in the peritumoral stroma has not been investigated in the endometrium. Therefore, we evaluated stromal p16 expression in different types of endometrial lesions using immunohistochemistry. Differences in the p16 expression status according to the degree of malignancy and histological type were analyzed. This study included 62, 26, and 36 cases of benign, precancerous, and malignant endometrial lesions, respectively. Most benign lesions showed negative or weak expression, whereas precancerous lesions showed a variable degree of staining proportion and intensity. Atypical hyperplasia/endometrial intraepithelial neoplasia (AH/EIN) and serous endometrial intraepithelial carcinoma (SEIC) had significantly higher stromal p16 expression levels than benign lesions. Endometrioid carcinoma (EC), serous carcinoma (SC), and carcinosarcoma showed significantly elevated stromal p16 expression levels compared with benign and precancerous lesions. In addition, there were significant differences in stromal p16 expression between AH/EIN and SEIC and between EC and SC. In contrast, differences in stromal p16 expression among nonpathological endometrium, atrophic endometrium, endometrial polyp, and hyperplasia without atypia were not statistically significant. Our observations suggest that stromal p16 expression is involved in the development and progression of endometrial carcinoma, and raise the possibility that p16 overexpression in the peritumoral stroma is associated with aggressive oncogenic behavior of endometrial SC.

Abstract 1703: Expression of Hedgehog signals and growth inhibition by itraconazole in endometrial cancer

Abstract Background: There are limited therapeutic opportunities for the treatment of endometrial cancer (EC). Itraconazole, a common antifungal agent and a potent inhibitor of the Hedgehog pathway, has been shown to be clinically effective for various types of cancer, but its clinical efficacy for EC is unknown. Herein, we evaluated the efficacy of itraconazole in treating EC. Patients and Methods: We reviewed cases of patients with serous endometrial intraepithelial carcinoma (SEIC) and patients who were diagnosed with EC with endometrioid adenocarcinoma grade 1 or 2 at FIGO stage IA with myometrial invasion and negative cytology of ascites and who recurred at our institution from January 2005 to December 2013. We also reviewed cases with endometrioid adenocarcinoma grade 1 or 2 at FIGO stage IA with myometrial invasion and negative cytology of ascites without recurrence over 5 years after surgery during 2006 and 2007. Immunohistochemistry was performed on EC tumour samples including SEIC for sonic Hedgehog (sHh), glioma-associated oncogene homolog 1 (GLI1), Progesterone receptor (PR), and chemokine ligand 18 (CCL18). Furthermore, we examined the effects of itraconazole on human EC cell lines (Ishikawa and HEC-1A cells) using a modified methylthiazol tetrazolium (MTT) assay and a migration assay. Results: SHh and GLI1 were expressed in SEIC and endometrioid adenocarcinoma. Immunohistochemical evaluation of sHh and GLI1 did not distinguish between recurrent and non-recurrent low-grade FIGO stage IA EC. The MTT assay revealed that itraconazole significantly inhibited the growth of Ishikawa and HEC-1A cells in a dose-dependent and time-dependent manner. However, migration was not significantly effected for either Ishikawa or HEC-1A cells. HEC-1A cells exhibited dose-dependent migration retardation. Conclusion: Hedgehog signalling plays a role in carcinogenesis and malignant progression in EC. Itraconazole at a physiological dose may suppress progression of EC. Citation Format: Kayo Inoue, Hiroshi Tsubamoto, Hiroaki Shibahara, Kazuo Tamura. Expression of Hedgehog signals and growth inhibition by itraconazole in endometrial cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1703.

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.

Primary sources of pelvic serous cancer in patients with endometrial intraepithelial carcinoma

Serous endometrial intraepithelial carcinoma is often associated with extrauterine disease. It is currently unclear where does the extrauterine disease come from. This study addressed this issue. A total of 135 samples from 21 serous endometrial intraepithelial carcinoma patients were studied. Cellular lineage relationships between intrauterine and extrauterine serous carcinomas were determined by TP53-mutation analysis and correlated to the clinicopathologic features. There were three conditions contributing the extrauterine disease: metastasis from serous endometrial intraepithelial carcinoma (n=10) showed identical TP53 mutation between intrauterine lesions and extrauterine disease, cases of adnexal origin (n=5) had discordant TP53 mutations, and the mixed cellular origin cases (n=6) with both identical and discordant mutation status. Patients with extrauterine disease from serous endometrial intraepithelial carcinoma metastasis typically had small tumor masses (<2 cm) in extrauterine sites and without finding of serous tubal intraepithelial carcinoma, while extrauterine disease with adnexal or tubal origin commonly had larger tumor masses in extrauterine sites including ovary and omentum and serous tubal intraepithelial carcinoma. The majority of extrauterine diseases associated with serous endometrial intraepithelial carcinoma are metastasized from the endometrium. Serous endometrial intraepithelial carcinoma is frequently associated with serous cancers of adnexal or tubal origin, indicating that endometrial and adnexal or tubal serous cancers may share similar etiologies. TP53-mutation analysis provides a strong linkage for cellular lineage analysis. Tumor size in extrauterine disease and presence of serous tubal intraepithelial carcinoma or not are useful clinicopathologic features to determine primary cancer site, which helps in clinical management.