Cases of Yolk sac tumor associated with gynecological malignant tumor.

BACKGROUND: Yolk sac tumour (YST) is the second most common ovarian germ cell tumour and usually presents in children and young women. However, tumours rarely occur as malignant gynaecological tumours with YST components. CASE PRESENTATION: We present one case of endometrioid carcinoma and clear cell carcinoma with YST components and two other cases of YSTs associated with high-grade serous carcinoma of the ovary in females. After surgery and adjuvant chemotherapy, the patient with endometrioid carcinoma had progressive disease and died 20 months later, and the other two were still alive at the last follow-up. CONCLUSIONS: To our knowledge, these mixed neoplasm associations are unusual, and these cases illustrate the diagnosis and prognosis of YST associated with malignant gynaecological tumours, emphasizing early recognition and aggressive treatment.

Mismatch repair protein deficiency in endometriosis: Precursor of endometriosis-associated ovarian cancer in women with lynch syndrome.

OBJECTIVE: We aimed to elucidate the pathogenesis of ovarian cancer through the loss of mismatch repair (MMR) proteins in women with Lynch syndrome (LS) in this report. CASE REPORT: Two women with LS underwent surgery for synchronous endometrial cancer and ovarian cancer. In both cases, immunohistochemical examination showed concomitant MMR protein deficiency in endometrial cancer, ovarian cancer, and contiguous ovarian endometriosis. In Case 1, the macroscopically normal ovary included multiple endometrioses with MSH2 and MSH6 expression, and FIGO grade 1 endometrioid carcinoma and contiguous endometriosis without MSH2 and MSH6 expression. In Case 2, all endometriotic cells contiguous with carcinoma in the lumen of the ovarian cyst showed loss of the expression of MSH2 and MSH6. CONCLUSION: Ovarian endometriosis with MMR protein deficiency may progress to endometriosis-associated ovarian cancer in women with LS. Diagnosing endometriosis in women with LS during surveillance is important.

Endometrioid adenocarcinoma arising in adenomyosis in a patient with pelvic organ prolapse-case report.

BACKGROUND: Adenomyosis is a frequent finding in endometrial carcinoma patients. Endometrioid adenocarcinoma is the most common type of endometrial carcinoma; however, endometrioid adenocarcinoma arising from adenomyosis is extremely rare. CASE PRESENTATION: In this case report, we describe a 69-year-old woman who required surgical treatment for pelvic organ prolapse (POP). The patient had been postmenopausal for 20 years and had no abnormal bleeding after menopause. The patient underwent transvaginal hysterectomy, repair of anterior and posterior vaginal walls, ischium fascial fixation and repair of an old perineal laceration. Histological examination of surgical specimens revealed endometrioid adenocarcinoma of the uterus. Bilateral adnexectomy, pelvic lymphadenectomy and para-aortic lymphadenectomy were then performed. The postoperative histopathological diagnosis was stage IB endometrial cancer (endometrioid carcinoma G2). CONCLUSIONS: In summary, endometrioid adenocarcinoma arising from adenomyosis (EC-AIA) is a rare entity and the early diagnosis is difficult. Adequate preoperative assessment and enhanced inquiry of occult clinical symptoms of postmenopausal women before hysterectomy may contribute to the diagnosis of EC-AIA preoperatively.

Association of smoking, alcohol, and coffee consumption with the risk of ovarian cancer and prognosis: a mendelian randomization study.

OBJECTIVE: Currently, the association between smoking, alcohol, and coffee intake and the risk of ovarian cancer (OC) remains conflicting. In this study, we used a two-sample mendelian randomization (MR) method to evaluate the association of smoking, drinking and coffee consumption with the risk of OC and prognosis. METHODS: Five risk factors related to lifestyles (cigarettes per day, smoking initiation, smoking cessation, alcohol consumption and coffee consumption) were chosen from the Genome-Wide Association Study, and 28, 105, 10, 36 and 36 single-nucleotide polymorphisms (SNPs) were obtained as instrumental variables (IVs). Outcome variables were achieved from the Ovarian Cancer Association Consortium. Inverse-variance-weighted method was mainly used to compute odds ratios (OR) and 95% confidence intervals (Cl). RESULTS: The two-sample MR analysis supported the causal association of genetically predicted smoking initiation (OR: 1.15 per SD, 95%CI: 1.02-1.29, P = 0.027) and coffee consumption (OR: 1.40 per 50% increase, 95%CI: 1.02-1.93, P = 0.040) with the risk of OC, but not cigarettes per day, smoking cessation, and alcohol consumption. Subgroup analysis based on histological subtypes revealed a positive genetical predictive association between coffee consumption and endometrioid OC (OR: 3.01, 95%CI: 1.50-6.04, P = 0.002). Several smoking initiation-related SNPs (rs7585579, rs7929518, rs2378662, rs10001365, rs11078713, rs7929518, and rs62098013), and coffee consumption-related SNPs (rs4410790, and rs1057868) were all associated with overall survival and cancer-specific survival in OC. CONCLUSION: Our findings provide the evidence for a favorable causal association of genetically predicted smoking initiation and coffee consumption with OC risk, and coffee consumption is linked to a greater risk of endometrioid OC.

Stratifying the risk of ovarian cancer incidence by histologic subtypes in the Korean Epithelial Ovarian Cancer Study (Ko-EVE).

INTRODUCTION: This study aimed to verify the association between ovarian cancer (OC) and reproductive- and lifestyle-related risk factors stratified by the subtype of OC. METHODS: In this matched case-control study derived from the Korean epithelial ovarian cancer study (Ko-EVE), we calculated the risk of OC subtypes using odds ratios (ORs) and 95% confidence intervals (95% CIs) in a logistic regression model. RESULTS: As a result of matching, 531 cases and 2,124 controls were selected. Smoking had positive association with high-grade serous (HGS) OC (OR = 2.69, 95% CI = 1.15-6.30), whereas alcohol consumption had positive association with mucinous type (MUC) (OR = 3.63, 95% CI = 1.39-9.49). Obesity (≥30 kg/m2 ) was associated with clear cell type (CLC) (OR = 4.57, 95% CI = 1.06-19.77). Spontaneous abortion was negatively associated with CLC (OR = 0.34, 95% CI = 0.13-0.90), in contrast to HGS (OR = 1.43, 95% CI = 0.96-2.15). Tubal ligation, hysterectomy, and oophorectomy were associated with decreased risk of HGS (OR = 0.14, 95% CI = 0.05-0.39; OR = 0.23, 95% CI = 0.07-0.73; OR = 0.28, 95% CI = 0.08-0.97, respectively). Early menarche was strongly associated with increased risk of CLC, but not MUC (OR = 6.11, 95% CI = 1.53-24.42; OR = 3.23, 95% CI = 0.98-10.86). Further, childbirth (≥2 times) was negatively associated with endometrioid type OC and CLC (OR = 0.11, 95% CI = 0.04-0.35; OR = 0.12, 95% CI = 0.02-0.37, respectively). Oral contraceptives and hormone replacement therapy were negatively associated with OC (OR = 0.61, 95% CI = 0.40-0.93; OR = 0.51, 95% CI = 0.32-0.80, respectively), and similar negative associations were also observed in HGS (OR = 0.69; OR = 0.60, respectively). Associations between family history of breast cancer and OC, regular exercise (≥5/week), and artificial abortion and OC were similar across all subtypes (OR = 3.92; OR = 0.41; OR = 0.72, respectively). CONCLUSION: A heterogeneous association between some risk factors and the incidence of each subtype of epithelial OC was observed, suggesting that the carcinogenic mechanisms of each subtype may be partly different.

Membranous and nuclear staining of CLDN18 in HPV-independent and HPV-associated endocervical adenocarcinomas.

OBJECTIVES: A classification system for endocervical adenocarcinoma (ECA) based on high-risk human papillomavirus (HPV) status has been established; however, the immunohistochemical markers distinguishing HPV-independent and HPV-associated ECAs have not been fully described. Here, we aimed to characterize ECA immunopathological features. METHODS: We evaluated the immunohistochemical profile of CLDN18, CDX2, PAX8, p16, p53, and CEA in 60 ECAs comprising 10 HPV-independent ECAs and 50 HPV-associated ECAs. Both the membranous and nuclear expression levels of CLDN18 were analyzed. RESULTS: Membranous CLDN18 (CLDN18 [M]) was found to be expressed in the mucinous epithelium of all HPV-independent ECAs, including eight gastric-type ECAs (G-ECAs), one endometrioid ECA, and one clear cell ECA, but no nuclear CLDN18 (CLDN18 [N]) expression was detected in HPV-independent ECAs. Among HPV-associated ECAs, CLDN18 (M) expression levels in intestinal-type (I-ECAs) and usual-type ECAs (U-ECAs) were significantly different from those in invasive stratified mucin-producing (iSMILE) carcinomas (p = 0.036). Positive CLDN18 (M) staining was present in 55.6% (5/9) of intestinal-type and 39.4% (13/33) of usual-type ECAs and was not present in iSMILE ECAs. Silva pattern C cancers expressed higher levels of CLDN18 (M) than Silva pattern A and B cancers (p = 0.004), whereas the CLDN18 (N) expression levels in cancers showing Silva pattern A were significantly higher than those in cancers exhibiting Silva patterns B and C (p < 0.001). CONCLUSION: Membranous CLDN18 is expressed in ECAs and is particularly frequently expressed in HPV-independent ECAs, and membranous CLDN18 expression has potential as a therapeutic target. Nuclear staining of CLDN18 is a new immunohistochemical marker for diagnosing Silva pattern A HPV-associated ECAs and is associated with a good prognosis. Further studies should investigate the therapeutic and prognostic significance of membranous and nuclear CLDN18 expression and develop a related test that can be implemented in the clinical evaluation of ECAs.

Microscopic Sertoliform Sex Cord Proliferations: A Rare Incidental Finding Associated With Endometriosis and Ovarian Epithelial Neoplasia.

Microscopic sex cord proliferations are a rare incidental finding seen in association with ovarian and uterine stromal or epithelial neoplasms and more uncommonly non-neoplastic conditions such as endometriosis and adenomyosis. They may also occur in the absence of other pathology, as an incidental finding in the ovaries of pregnant women and in heterotopic locations such as the fallopian tube. Most reports of this phenomenon describe adult granulosa cell tumor-like morphology. Herein, we describe 4 cases of microscopic sex cord proliferations with Sertoliform features, occurring in the stromal component of endometriosis or in the wall of an epithelial ovarian neoplasm; 2 of the patients with endometriosis had concurrent endometrioid adenocarcinoma (1 uterine corpus, 1 ovary). The proliferations were positive with sex cord markers inhibin and calretinin. As far as we are aware, such Sertoliform proliferations have not been reported previously in endometriosis and have only rarely been described in association with ovarian epithelial neoplasia. It is likely that such proliferations represent a benign non-neoplastic phenomenon. Awareness of this phenomenon is important in order to avoid misdiagnosis as a sex cord or other neoplasm. In reporting this unusual phenomenon, we review incidental sex cord and sex cord-like proliferations in the female genital tract.

Endometrial cancer with concomitant endometriosis is highly associated with ovarian endometrioid carcinoma: a retrospective cohort study.

BACKGROUND: Endometriosis is assumed to be involved in ovarian cancer development, which is called endometriosis-associated ovarian cancer (EAOC). Uterine endometrial cells may be the cell of origin of EAOC. Accumulated carcinogenic changes in the uterine endometrial cells may increase the risk of developing EAOC. To further understand the pathogenesis of EAOCs, we focused on the clinicopathological characteristics of EAOCs in endometrial cancer patients with concomitant endometriosis. METHODS: We retrospectively reviewed 376 patients who were surgically treated for stage I-III endometrial cancer. Clinicopathological characteristics were compared between patients with and without endometriosis. Furthermore, the incidence of simultaneous endometrial and ovarian cancer (SEOC) and the histological characteristics of SEOC were compared between the two groups. RESULTS: Among 376 patients with endometrial cancer, 51 had concomitant endometriosis. Patients with endometriosis were significantly younger and more frequently had endometrioid G1/G2 tumors than those without endometriosis. The incidence of SEOCs was significantly higher in endometrial cancer patients with endometriosis than those without it (p < 0.0001); notably, 12 of 51 endometrial cancer patients with endometriosis (24%) had SEOCs. All of the ovarian cancers in endometrial cancer patients with endometriosis were endometrioid carcinomas. Moreover, even in those without endometriosis, endometrioid carcinoma was the most common histological type of SEOC. CONCLUSION: We revealed that endometrial cancer patients with endometriosis had a high probability of SEOC and that endometrioid carcinoma was the most common histological subtype of SEOC regardless of the presence of endometriosis. For patients with endometrial cancer and endometriosis, careful examination of ovarian endometriotic lesions may be important to detect EAOCs.

Effect of coexisting adenomyosis on patients with endometrioid adenocarcinoma: Determination of intraoperative risk factors for tumor metastasis and estimation of prognosis.

Context: We sought to clarify the impact of adenomyosis on the clinical and pathological prognosis of endometrial cancer to aid the selection of appropriate surgical intervention based on the diagnosis of adenomyosis. Aims: Our study aimed to report the frequency of adenomyosis in patients with endometrioid cancer and correlate its incidence rate with the survival and prognostic factors. Materials and Methods: This retrospective study included 357 patients. Patients with endometrioid adenocarcinoma were divided into two groups based on the presence of adenomyosis. The groups were compared in terms of tumor diameter, lymphovascular space invasion (LVSI), low-high risk pathologic status, stage of the disease, and survival outcome. Statistical Analysis Used: Continuous variables were analyzed using the Student's t or Mann-Whitney U-test. Survival data were analyzed using the Kaplan-Meier test. Results: The average age was similar between the two groups. In total, 47 (13.2%) of 357 patients had adenomyosis. A total of 43 (91.4%) cases with adenomyosis and 258 (83.2%) cases without adenomyosis had Stage I endometrioid adenocarcinoma (n = 301, 84.3%). Moreover, 32 (68.1%) cases with adenomyosis and 187 (60.3%) cases without adenomyosis were in the low-risk group. There was no statistically significant correlation between the risk groups (P = 0.309) and overall survival between the two groups (P = 0.416). Conclusion: No correlation was seen between the characteristics of endometrioid type endometrial cancer and survival rates in patients with or without adenomyosis. The impact of adenomyosis as a factor in evaluating the perioperative prognosis and planning postoperative adjuvant therapy for endometrial cancer should be assessed by further studies.

Laparoscopic resection surgery for malignant transformation of extragonadal endometriosis by the "pincer" approach.

Up to 1% of women with endometriosis develop endometriosis-associated neoplasms [1]. Most endometriosis-associated malignant tumors develop from the ovarian endometriomas, whereas those developing from extragonadal lesions are extremely rare, estimated at 0.2% [2]. Because they are uncommon, a treatment protocol for the malignant transformation of extragonadal endometriosis lesions has not been clearly defined. When the lesion is confined to the site of origin and R0 resection is achieved, the 5-year survival rate is between 82% and 100%; therefore, complete resection should be performed [3]. The patient in this video had previously undergone hysterectomy, bilateral salpingo-oophorectomy, left nephrectomy, and low-anterior resection of the rectum due to severe endometriosis. Ten years after the surgery, the patient had a 6 cm endometrioid adenocarcinoma developing from the residual endometriosis lesion at the left uterosacral ligament that involved the bladder, left ureter, and rectum. In this case, the tumor was attached to the pelvis due to infiltration of the left sacrospinous ligament. To completely remove the tumor, we used laterally extended endopelvic resection with abdominoperineal resection of the rectum. We used the laparoscopic-perineal-laparoscopic approach (pincer approach) because improved visualization of the left sacrospinous ligament increases the probability of achieving complete resection [4]. Pathological R0 resection was achieved without intraoperative or postoperative complications. Thus, for tumors that are firmly attached to the pelvic floor, the pincer approach can be useful for achieving R0 resection. The informed consent for use of this video was taken from the patient.

Keratin Granulomas in the Peritoneum on Frozen Section: A Case Report with Multiple Suspects and the Search for the Culprit.

Keratin granulomas in the peritoneum are a rare finding with multiple etiologies and can be especially challenging for both the pathologist and the surgeon when these lesions are grossly visible. We report a case of a unique frozen section diagnostic scenario of evaluation of keratin granulomas in the peritoneum of a 47-year-old woman in the setting of multiple potential culprits: endometrial endometrioid adenocarcinoma following fertility sparing treatment, and a concurrent dermoid cyst. We discuss the various etiologies of keratin granulomas in the peritoneum, mechanism of their formation, diagnostic significance, as well as implications of fertility sparing treatments. To the best of our knowledge, this is the only case of keratin granulomas in the peritoneum with multiple distinct potential pathologic culprits as well the only case following fertility sparing treatment.

Dusp6 immunohistochemistry is associated with the response of atypical endometrial hyperplasia and early endometrial cancer to conservative treatment.

OBJECTIVE: Dual-specificity phosphatase 6 (Dusp6) was proposed as a predictive marker of response of atypical endometrial hyperplasia (AEH) and early endometrial cancer (EEC) to conservative treatment. However, its predictive accuracy has never been calculated. We aimed to define it in conservatively treated AEH and EEC. METHODS: All patients <45 years with AEH or EEC and conservatively treated with hysteroscopic resection + LNG-IUD insertion from 2007 to 2018 were retrospectively assessed. Dusp6 immunohistochemical expression was assessed and dichotomized as "strong" vs "weak". Relative risk (RR) for "no regression" and "recurrence" or AEH/EEC was calculated. Predictive accuracy was calculated as sensitivity, specificity, positive and negative predictive values (PPV, NPV) and area under the curve (AUC) on receiver operating characteristic curve. RESULTS: Thirty-six women were included. Weak Dusp6 immunohistochemical expression was significantly associated with increased risk of resistance to treatment, with a RR = 16 (P = 0.0074); predictive accuracy analysis showed sensitivity = 80%, specificity = 90%, PPV = 57.1%, NPV = 96.4%, AUC = 0.85. A weak Dusp6 expression was not significantly associated with the risk of recurrence after an initial regression (RR = 0.4; P = 0.53). CONCLUSION: Weak Dusp6 expression appears as a significant predictor of resistance of AEH/EEC to fertility-sparing treatment, with moderate predictive accuracy. Weak Dusp6 expression is significantly associated with resistance of atypical endometrial hyperplasia or early endometrial cancer to fertility-sparing treatment, with moderate predictive accuracy.

Medical Significance of Uterine Corpus Endometrial Carcinoma Patients Infected With SARS-CoV-2 and Pharmacological Characteristics of Plumbagin.

Background: Clinically, evidence shows that uterine corpus endometrial carcinoma (UCEC) patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have a higher death-rate. However, current anti-UCEC/coronavirus disease 2019 (COVID-19) treatment is lacking. Plumbagin (PLB), a pharmacologically active alkaloid, is an emerging anti-cancer inhibitor. Accordingly, the current report was designed to identify and characterize the anti-UCEC function and mechanism of PLB in the treatment of patients infected with SARS-CoV-2 via integrated in silico analysis. Methods: The clinical analyses of UCEC and COVID-19 in patients were conducted using online-accessible tools. Meanwhile, in silico methods including network pharmacology and biological molecular docking aimed to screen and characterize the anti-UCEC/COVID-19 functions, bio targets, and mechanisms of the action of PLB. Results: The bioinformatics data uncovered the clinical characteristics of UCEC patients infected with SARS-CoV-2, including specific genes, health risk, survival rate, and prognostic index. Network pharmacology findings disclosed that PLB-exerted anti-UCEC/COVID-19 effects were achieved through anti-proliferation, inducing cytotoxicity and apoptosis, anti-inflammation, immunomodulation, and modulation of some of the key molecular pathways associated with anti-inflammatory and immunomodulating actions. Following molecular docking analysis, in silico investigation helped identify the anti-UCEC/COVID-19 pharmacological bio targets of PLB, including mitogen-activated protein kinase 3 (MAPK3), tumor necrosis factor (TNF), and urokinase-type plasminogen activator (PLAU). Conclusions: Based on the present bioinformatic and in silico findings, the clinical characterization of UCEC/COVID-19 patients was revealed. The candidate, core bio targets, and molecular pathways of PLB action in the potential treatment of UCEC/COVID-19 were identified accordingly.

Tissue factor expression and tumor-infiltrating T lymphocytes in ovarian carcinomas and their association with venous thromboembolism.

Ovarian cancer is a known risk factor of venous thromboembolism (VTE). Thrombogenic factor expression and lymphocytic infiltrate have been reported in endometriosis and ovarian cancers. We reviewed 30 cases of ovarian carcinomas (high grade serous carcinoma, 10; endometrioid carcinoma, 10; clear cell carcinoma (CCC), 10) and 16 endometriotic lesions. We immunohistochemically investigated the expressions of tissue factor (TF), podoplanin, P-selectin, and number of CD4 and CD8 positive lymphocytes in cancer tissue and endometriotic lesions, along with their relationship with VTE. The expression of TF was higher in CCC. The TF expression and the number of CD8 positive cells were higher in cancer tissues with VTE than in those without VTE. The podoplanin or P-selectin expression did not differ among histological types or between cases with and without VTE. Our results demonstrated a high TF expression and intraepithelial CD8 cells in CCC, which were associated with VTE. The results suggest that infiltrating lymphocytes may affect TF expression that, in turn, influences VTE.

Pulmonary metastasis with coexisting pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma 20 years after endometrioid adenocarcinoma surgery: A case report.

Late pulmonary metastasis from endometrioid adenocarcinoma (EA) is rare, and occurrence after >20 years is extremely rare. Here, we report a case of pulmonary metastasis with coexisting pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma that occurred 20 years after surgery for EA. A 60-year-old Japanese woman had previously undergone surgery for primary EA, and 20 years later presented with an abnormality that was detected on chest radiography. Chest computed tomography (CT) revealed two nodules in the right lower lung lobe, which were suspected to be primary lung cancer. Wedge resection was performed, and the intraoperative pathological diagnosis was that of adenocarcinoma with MALT lymphoma; this prompted additional right lower lobectomy. The final pathological diagnosis was pulmonary metastasis from EA with coexisting MALT lymphoma. This is probably the first report on late pulmonary metastasis coexisting with MALT lymphoma 20 years after surgery for EA. Surgeons should be aware of the possibility of late pulmonary recurrence of EA after more than 20 years and should consider aggressive resection. KEY POINTS: SIGNIFICANT FINDINGS OF THE STUDY: Although extremely rare, pulmonary metastasis can occur more than 20 years after surgery for endometrioid adenocarcinoma. Furthermore, pulmonary metastasis from endometrioid adenocarcinoma may coexist with mucosa-associated lymphoid tissue lymphoma. WHAT THIS STUDY ADDS: Endometrioid adenocarcinoma requires long-term postoperative follow-up to detect recurrence, even in early-stage cases. Video-assisted thoracoscopic surgery (VATS) is useful for resecting pulmonary metastasis from endometrioid adenocarcinoma.

[The influence of endometrioid heterotopias on the red blood parameters.] / Влияние эндометриоидной гетеротопии на показатели красной крови.

Endometrioid heterotopia can have an adverse systemic effect on the organism through erythropoietin synthesis, which can affect erythropoiesis and reflect in blood analysis. The aim of the study was to investigate the effect of endometrioid heterotopia on parameters of red blood. The investigated group included patients with endometrioid heterotopias of various localisations (115 cases), functional ovarian cysts made up the control group (28 cases). Retrospectively, the number of red blood cells, the amount of hemoglobin, and the level of (CA-125) were recorded in the medical histories. The parameters were taken into account both before and after radical surgery. The highest values of the number of red blood cells and hemoglobin are observed in endometrioid ovarian cysts, followed by adenomyosis, endometriosis of the pelvic peritoneum and skin scar, respectively. After surgery, these differences have disappeared. Comparison of the number of red blood cells and hemoglobin before and after surgery revealed significant changes for both parameters in the group of patients with endometriosis, while in the control group the number of red blood cells and the level of hemoglobin did not change significantly. The number of cases with endometrioid ovarian cysts, where the red blood cell count was higher than normal, significantly differed from the control group; on the contrary, with non-endometrioid ovarian cysts, a significantly more frequent decreased number of red blood cells was observed. In addition, red blood counts in patients with endometriosis before surgery had a moderate negative correlation with the level of CA-125 protein.The possible systemic influence of endometrioid heterotopias on erythropoiesis in the form of its stimulation is demonstrated. In non-endometrioid ovarian cysts a significantly more frequent decrease in the number of red blood cells is observed. The reveales pecularities can be used for complex differential diagnostics of ovarian cysts at the preoperative stage due to their easy accessibility and minimally invasive nature.

The clinicopathological characteristics and survival outcomes of endometrial carcinoma coexisting with or arising in adenomyosis: A pilot study.

Little is known about the epidemiological and clinicopathological characteristics of endometrial endometrioid carcinoma (EEC) coexisting with or arising in adenomyosis (EEC-A or EEC-AIA) due to their rarity. This study compared EEC-A and EEC-AIA with endometrial carcinoma without adenomyosis. Cases of endometrial cancer treated at the study center from June 1, 2010, to June 1, 2017, were reviewed. The epidemiological, clinicopathological characteristics and survival outcomes were compared among three groups of endometrioid subtypes: group A, stage IA endometrial carcinoma patients without coexisting adenomyosis; group B, patients with EEC-A; and group C, patients with EEC-AIA. Among the 2080 patients reviewed, groups A, B, and C included 1043, 230 and 28 patients, respectively. Patients in group A and group B had similar clinicopathological and survival outcomes. Patients in group C were significantly younger and had less gravidity and parity than patients in groups A and B. More tumors from group C were grade 1, and they had a smaller maximum diameter and less mismatch repair deficiency than those from groups A and B. After a median follow-up of 57.0 months, the 5-year disease-free survival (DFS) rates of groups A, B and C were 96%, 91% and 100% (p = 0.045), respectively; the 5-year overall survival (OS) rates were 98%, 93% and 100%, respectively (p = 0.001), in the Kaplan-Meier analysis. However, these difference disappeared in a subgroup of stage IA patients in univariate and multivariate analysis. Cox regression analysis in stage IA patients also revealed no significant differences in survival outcome across the three groups. In conclusion, EEC-AIA exhibited specific clinicopathological characteristics that were probably associated with favorable survival outcomes. The characteristics and survival outcomes of EEC-A were similar to those of EEC without adenomyosis in stage IA patients.

Development of prediction models for lymph node metastasis in endometrioid endometrial carcinoma.

BACKGROUND: In endometrioid endometrial cancer (EEC), current clinical algorithms do not accurately predict patients with lymph node metastasis (LNM), leading to both under- and over-treatment. We aimed to develop models that integrate protein data with clinical information to identify patients requiring more aggressive surgery, including lymphadenectomy. METHODS: Protein expression profiles were generated for 399 patients using reverse-phase protein array. Three generalised linear models were built on proteins and clinical information (model 1), also with magnetic resonance imaging included (model 2), and on proteins only (model 3), using a training set, and tested in independent sets. Gene expression data from the tumours were used for confirmatory testing. RESULTS: LNM was predicted with area under the curve 0.72-0.89 and cyclin D1; fibronectin and grade were identified as important markers. High levels of fibronectin and cyclin D1 were associated with poor survival (p = 0.018), and with markers of tumour aggressiveness. Upregulation of both FN1 and CCND1 messenger RNA was related to cancer invasion and mesenchymal phenotype. CONCLUSIONS: We demonstrate that data-driven prediction models, adding protein markers to clinical information, have potential to significantly improve preoperative identification of patients with LNM in EEC.

Incidence of endometrioid and clear-cell ovarian cancer in histological proven endometriosis: the ENOCA population-based cohort study.

BACKGROUND: Several studies have suggested that endometriosis is associated with an increased risk of ovarian cancer, especially for the clear-cell and endometrioid subtypes. However, previous studies lack sufficient power or diagnostic certainty. OBJECTIVE: The objective of the study was to assess the association between histologically proven endometriosis and ovarian cancer in a large population-based cohort study. STUDY DESIGN: We identified 131,450 women with a histological diagnosis of endometriosis between 1990 and 2015 from the Dutch nationwide registry of histopathology and cytopathology (PALGA). For the control cohort 132,654 women with a benign dermal nevus were matched on age and inclusion year with the endometriosis cases. Histological diagnoses of ovarian, fallopian tubes, and peritoneal cancers between January 1990 and July 2017 were retrieved. Incidence rate ratios were estimated for ovarian cancer and its subtypes for the whole follow-up period as well as for women with more than 1 person-year at risk. RESULTS: We found a crude incidence rate ratio of 4.79 (95% confidence interval, 4.33-5.31) and an age-adjusted incidence rate ratio of 7.18 (95% confidence interval, 6.17-8.36) for ovarian cancer overall. Endometrioid and clear-cell ovarian cancer had the highest age-adjusted incidence rate ratio of 29.06 (95% confidence interval, 20.66-40.87) and 21.34 (95% confidence interval, 14.01-32.51), respectively. Median age at ovarian cancer diagnosis was 56 years (interquartile range, 49-63) for the endometriosis cohort and 60 years (interquartile range, 53-67) for the nevus cohort, (P < .05). After excluding women with less than 1 person-year at risk following an endometriosis diagnosis, we found a crude incidence rate ratio of 1.04 (95% confidence interval, 0.91-1.19) and an age-adjusted incidence rate ratio of 1.08 (95% confidence interval, 0.87-1.35) for ovarian cancer overall. However, statistically significant age-adjusted incidence rate ratios of 2.29 (95% confidence interval, 1.24-4.20) for clear-cell ovarian cancer and 2.56 (95% confidence interval, 1.47-4.47) for endometrioid ovarian cancer were found. CONCLUSION: A significantly higher incidence of clear-cell and endometrioid ovarian cancer was found in women with histologically proven endometriosis. Additionally, we found an increased incidence of all ovarian cancer subtypes in histologically proven endometriosis; however, in many of these women, endometriosis and ovarian cancer were diagnosed synchronously after the average menopausal age, which may suggest that the risk of ovarian cancer in endometriosis patients remains, even when clinical endometriosis symptoms are no longer present.