Uterine POLE mutant endometrioid carcinoma combined with human papilloma virus-associated cervical adenocarcinoma: A case report and literature review / 北京大学学报(医学版)

Independent primary uterine and cervical adenocarcinoma are rare and difficult to identify their origins, which makes treatment decision difficult. A 46-year-old female with endometrioid carcinoma and adenocarcinoma, human papilloma virus (HPV)-associated of the uterine cervix was reported. The patient presented with increased menstrual flow, contact bleeding and watery leucorrhea for more than one year, and the imaging findings showed abnormal uterine morphology, irregular margins, and multiple abnormal signals in uterine cavity and myometrium, which suggested multiple leiomyomas of the uterus. The signal intensity in the right muscle layer was markedly enhanced, suggesting a smooth muscle tumor of uncertain malignant potential. A large number of cystic hypointensity was seen in the cervix, and multiple cysts were considered. The initial preoperative diagnosis was multiple leiomyoma of the uterus, and a hysterectomy operation was planned. During the operation, the uterus was sent for frozen sections. There was a mass in the endometrium of the fundus, with a soft grayish-red cut surface and a clear border with the myometrium, and there was a grayish-white nodule in the cervix with a hard grayish-white cut surface. The two masses were well demarcated from each other, and the distance between them was 30 mm. The result of the frozen sections indicated the malignant tumor of the endometrium, and the extended hysterectomy+pelvic lymphadenectomy+partial resection of the greater omentum was performed. After the operation, the paraffin sections were sent to the Department of Pathology of the Peking University Third Hospital for histochemistry, POLE gene sequencing and HPV RNAscope tests, and the final diagnosis was a synchronous endometrioid carcinoma (POLE-mutant according to the WHO classification) and an adenocarcinoma, HPV-associated of the uterine cervix. Now the patient had been treated with 2 cycles of chemotherapy and her condition was fine. Through the analysis of the histological, immunohistochemical and molecular detection results of this case, the importance of applying HPV RNAscope and TCGA molecular typing in the diagnosis of cervical adenocarcinomas and endometrial carcinomas was emphasized. At the same time, gynecologists should not blindly rely on intraoperative frozen sections, and should pay attention to preoperative pathological examination, and make appropriate operation methods according to the results in order to prevent passivity in the surgery.

Role of serum microRNAs as biomarkers for endometriosis, endometrioid carcinoma of ovary & endometrioid endometrial cancer

Background & objectives: Accurate and early diagnosis is imperial in the management of endometriosis, endometrioid carcinoma of ovary (ECO) and endometrioid endometrial cancer (EC), yet there are no definitive diagnostic methods available for these diseases. Therefore, the present study was aimed to evaluate the diagnostic potential of differentially expressed miRNAs in serum samples of women with endometriosis, ECO and EC to establish them as diagnostic biomarkers. Methods: Blood samples (5 ml) were obtained from 40 patients (n=10/study group) undergoing laparoscopy/laparotomy/hysterectomy. miRNA-rich RNA was extracted from the serum samples, and quantitative real-time (qRT)-PCR was performed to check the expression levels of miR-16, miR-99b, miR-20a, miR-145, miR-143 and miR-125a in all the samples. Receiver operating characteristic (ROC) curve analysis was done to check the diagnostic potential. Results: In endometriosis, miR-16 was downregulated (P<0.05) whereas miR-99b, miR-125a, miR-143 and miR-145 were upregulated (P<0.05). In ECO group, downregulated expression of miR-16 and miR-125a (P<0.05) was observed, whereas miR-99b, miR-143 and miR-145 were upregulated (P<0.05). In endometrioid EC, miR-16, miR-99b, miR-125 and miR-145 were downregulated (P<0.05), whereas miR-143 was upregulated (P<0.05). ROC curve analysis showed that, for endometriosis, miR-99b, miR-125a, miR-143 and miR-145 served as diagnostic markers. miR-145 showed diagnostic power for ECO, and for endometrioid EC, miR-16, miR-99b, miR-125a and miR-145 showed diagnostic potential. Interpretation & conclusions: The present findings suggested that certain circulating miRNAs (miB99b, miR-16, miR-125a, miR-145) might act as indicators and discriminators of endometriosis and endometrioid subtypes of EC and ovarian cancer and might serve as potential biomarkers for early diagnosis and management of these debilitating diseases.

Endometrial cancer with implantation metastasis to vagina: a case report

Authors present a case of vaginal implantation metastasis following a diagnosis of endometrial cancer. A 58-year-old lady presented with postmenopausal bleeding and was later diagnosed to have endometrial cancer. She underwent an extra-fascial hysterectomy and bilateral salpingo-oophrorectomy with pelvic lymphadenectomy for Stage 3A endometrioid adenocarcinoma of the endometrium. The lymph nodes and cervix were free from the disease and no lymphovascular invasion was seen on the pathological specimen. She defaulted adjuvant radiotherapy and was lost to follow up. Six months later she had a tumour recurrence at the vaginal introitus just below the urethral orifice and awal from the vaginal vault with similar histopathological findings as previous cancer. This case highlights the rare occurrence of implantation metastasis of endometrial cancer.

A report of two cases of dedifferentiated endometrioid carcinoma: A newly described underrecognized tumor of poor prognosis

Dedifferentiated endometrioid carcinoma or dedifferentiated endometrioid adenocarcinoma (DEAC) is defined by the presence of undifferentiated carcinoma with endometrioid carcinoma. Undifferentiated component can be misinterpreted as solid component of high-grade endometrioid carcinoma or sarcomatous component of malignant mixed mullerian tumor. We present two cases of DEAC. Two postmenopausal women underwent hysterectomy for vaginal bleeding. Microscopically, sections from the endometrial tumors showed a biphasic growth consisting of an undifferentiated component and a glandular component with sharp transition between the two components. The undifferentiated component showed focal positivity for cytokeratin and vimentin, while glandular component was diffusely positive for cytokeratin and negative for vimentin expression.

The prognostic significance of estrogen and progesterone receptors in grade I and II endometrioid endometrial adenocarcinoma: hormone receptors in risk stratification / 부인종양

OBJECTIVES: Although patients with grade I and II endometrioid endometrial adenocarcinoma (EEA) are considered with good prognosis, among them 15%–25% died in 5 years. It is still unknown whether integrating estrogen receptor (ER) and progesterone receptor (PR) into clinical risk stratification can help select high-risk patients with grade I–II EEA. This study was to investigate the prognostic value of ER and PR double negativity (ER/PR loss) in grade I–II EEA, and the association between ER/PR loss and The Cancer Genome Atlas (TCGA) classification. METHODS: ER and PR were assessed by immunohistochemistry on hysterectomy specimens of 903 patients with grade I–II EEA. ER and PR negativity were determined when < 1% tumor nuclei were stained. Gene expression data were obtained from the TCGA research network. RESULTS: Compared with ER or PR positive patients (n=868), patients with ER/PR loss (n=35) had deeper myometrial infiltration (p=0.012), severer FIGO stage (p=0.004), and higher rate of pelvic lymph node metastasis (p=0.020). In univariate analysis, ER/PR loss correlated with a shorter progression-free survival (PFS; hazard ratio [HR]=5.25; 95% confidence interval [CI]=2.21–12.52) and overall survival (OS; HR=7.59; 95% CI=2.55–22.60). In multivariate analysis, ER/PR loss independently predicted poor PFS (HR=3.77; 95% CI=1.60–10.14) and OS (HR=5.56; 95% CI=1.37–22.55) for all patients, and poor PFS for patients in stage IA (n=695; HR=5.54; 95% CI=1.28–23.89) and stage II–IV (n=129; HR=5.77; 95% CI=1.57–21.27). No association was found between ER/PR loss and TCGA classification. CONCLUSION: Integrating ER/PR evaluation into clinical risk stratification may improve prognosis for grade I–II EEA patients.

Seromucinous component in endometrioid endometrial carcinoma as a histological predictor of prognosis / 부인종양

OBJECTIVE: In 2014 World Health Organization criteria, seromucinous carcinoma was defined as a new histological subtype in ovarian carcinomas, but “seromucinous carcinoma” was not defined in endometrial carcinomas. The aim of this study was to identify seromucinous carcinoma resembling ovarian seromucinous carcinoma in endometrial carcinomas, and to evaluate the clinical significance for prognoses of the patients. METHODS: Central pathological review was conducted for patients with endometrioid carcinoma of the endometrium treated by primary surgery at our hospital between 1990 and 2013. RESULTS: Among 340 cases included in the study, no case had all tumor cells resembling ovarian seromucinous carcinoma in all specimens, and 31 cases (9.1%) had seromucinous component in combination with endometrioid carcinomas. Immunohistochemical analysis revealed seromucinous component had positive reactivity for cytokeratin (CK) 7, and negative reactivity for CK20 and caudal type homeobox 2 (CDX2) in all cases. Seromucinous component showed lower immunoreactivity of estrogen receptor and progesterone receptor, compared with endometrioid carcinoma component. Progression-free survival of the cases with seromucinous component was better than those without seromucinous component (p=0.049). CONCLUSION: Seromucinous component was identified in approximately 10% of endometrioid carcinoma, and could be a histological predictor for prognosis.

Clinical outcomes of patients with clear cell and endometrioid ovarian cancer arising from endometriosis / 부인종양

OBJECTIVE: The aim of this investigation is to compare outcomes of patients according to the presence of cancer arising from endometriosis in ovarian clear cell carcinoma (CCC) and endometrioid carcinoma (EC). METHODS: This study retrospectively investigated 224 CCC and EC patients treated in Samsung Medical Center from 2001 to 2015 to identify cancer arising from endometriosis according to Sampson and Scott criteria. Propensity score matching was performed to compare patients arising from endometriosis to patients without endometriosis (ratio 1:1) according to stage, age, lymph node metastasis (LNM), cancer antigen (CA)-125 level, and residual status after debulking surgery. RESULTS: Forty-five cases arising from endometriosis were compared with 179 cases without endometriosis. CCC and EC arising from endometriosis tended to present with early age (mean, 45.2 vs. 49.2 years; p=0.003), early-stage (stages I and II, 92.7% vs. 62.3%; p < 0.001), lower CA-125 level (mean, 307.1 vs. 556.7; p=0.041), higher percentages of no gross residual disease after surgery (87.8% vs.56.8%; p=0.001), and higher percentages of negative LNM (82.9% vs. 59.0%; p=0.008) compared to cases without endometriosis. Kaplan-Meier curves for progression-free survival (PFS) and overall survival (OS) showed better outcomes for groups with cancer arising from endometriosis (p=0.014 for PFS; and p=0.010 for OS). However, the association with endometriosis was not significant in multivariate analysis. Also, after propensity score matching, survival differences between the 2 groups were not significant. CONCLUSION: CCC and EC arising from endometriosis are diagnosed at an earlier age and stage. However, cancer arising from endometriosis was not a significant prognostic factor.

Impact of lymph node ratio on survival in stage IIIC endometrioid endometrial cancer: a Turkish Gynecologic Oncology Group study / 부인종양

OBJECTIVE: The purpose of this study was to investigate the prognostic value of lymph node ratio (LNR) in women with stage IIIC endometrioid endometrial cancer (EC). METHODS: A multicenter, retrospective department database review was performed to identify patients with stage IIIC pure endometrioid EC at 6 gynecologic oncology centers in Turkey. A total of 207 women were included. LNR, defined as the percentage of positive lymph nodes (LNs) to total nodes recovered, was stratified into 2 groups: LNR1 (≤0.15), and LNR2 (>0.15). Kaplan-Meier method was used to generate survival data. Factors predictive of outcome were analyzed using Cox proportional hazards models. RESULTS: One hundred and one (48.8%) were classified as stage IIIC1 and 106 (51.2%) as stage IIIC2. The median age at diagnosis was 58 (range, 30–82) and the median duration of follow-up was 40 months (range, 1–228 months). There were 167 (80.7%) women with LNR ≤0.15, and 40 (19.3%) women with LNR >0.15. The 5-year progression-free survival (PFS) rates for LNR ≤0.15 and LNR >0.15 were 76.1%, and 58.5%, respectively (p=0.045). An increased LNR was associated with a decrease in 5-year overall survival (OS) from 87.0% for LNR ≤0.15 to 62.3% for LNR >0.15 (p=0.005). LNR >0.15 was found to be an independent prognostic factor for both PFS (hazard ratio [HR]=2.05; 95% confidence interval [CI]=1.07–3.93; p=0.03) and OS (HR=3.35; 95% CI=1.57–7.19; p=0.002). CONCLUSION: LNR seems to be an independent prognostic factor for decreased PFS and OS in stage IIIC pure endometrioid EC.

Características clínico-epidemiológicas y manejo del cáncer endometrial (2010-2013) / Clinical-epidemiological characteristics and management of endometrial cancer (2010-2013)

Introducción: el cáncer de endometrio ha incrementado su incidencia y se asocia a factores de riesgo presentes en muchas mujeres en la perimenopausia. El síntoma más común es el sangramiento y la modalidad de tratamiento más empleada es la cirugía. Objetivo: caracterizar el cáncer endometrial en el Hospital América Arias desde enero de 2010 hasta junio de 2013. Métodos: se realizó un estudio descriptivo en el Hospital América Arias, desde 1ro de enero de 2010 hasta el 30 de junio de 2013. Se incluyó el total las pacientes con sangramiento uterino anormal en la etapa peri y posmenopáusico a partir de 40 años de edad. Las pacientes con diagnóstico histopatológico de cáncer endometrial constituyeron la muestra (n= 49). Resultados: la edad promedio de las pacientes fue de 60,8 ± 9,9 años. Presentaban sobrepeso 30,6 por ciento, y 44,9 por ciento eran obesas. El examen histopatológico posquirúrgico muestra que la lesión estuvo limitada al endometrio en 14,3 por ciento de las pacientes; pero hubo invasión de los dos tercios externos del miometrio en 61,2 por ciento de ellas. La extensión al cuello y a los anejos uterinos fue de 38,8 por ciento y 22,4 por ciento respectivamente. Conclusiones: existe una tendencia a la aparición del adenocarcinoma endometrial en edades cada vez más avanzadas. Se asocia a factores de riesgo como obesidad, infertilidad y el uso de terapia hormonal de remplazo. Además de la cirugía, algunas pacientes requirieron tratamiento oncológico específico(AU)

Introduction: The incidence of endometrial cancer has increased and it is associated with risk factors present in many perimenopausewomen. The most common symptom is bleeding and the most widely used treatment modality is surgery. Objective: Characterize endometrial cancer at America Arias Hospital from January 2010 to June 2013. Methods: A descriptive study was conductedat America Arias Hospital, from 1 January 2010 to 30 June 2013. The total included over 40 year patients with abnormal uterine bleeding in perimenopausal and postmenopausal. Patients with histopathologic diagnosis of endometrial cancer constituted the sample (n= 49). Results: The mean age of patients was 60.8 ± 9.9 years. 30.6 percent were overweight and 44.9 percent were obese. Postoperative histopathologic examination shows that the lesion was limited to the endometrium in 14.3 percent of patients, but there was invasion of the two outer thirds of the myometrium in 61.2 percent. The extension cervix and adnexa was 38.8 percent and 22.4 percent, respectively. Conclusions: There is a tendency to the appearance of endometrial adenocarcinoma at increasingly advanced ages. It is associated with risk factors such as obesity, infertility, and the use of hormone replacement therapy. In addition to surgery, some patients required specific cancer treatment(AU)

Significance of mutant p53, Ki-67, ER and PR in differential diagnosis of uterine endometrial carcinoma and uterine serous carcinoma / 肿瘤研究与临床

Objective To investigate the expression of mutant p53,Ki-67,ER and PR in uterine endometrial carcinoma and uterine serous carcinoma,and explore their significance in differential diagnosis.Methods The samples including 37 cases of uterine endometrial carcinoma and 37 cases of uterine serous carcinoma were analyzed.The expression of mutant p53,Ki-67,estrogen receptor and progesterone receptor were performed by using the immunocytochemical (IHC) EnVision system.Data were analyzed with SPSS 11.5 statistic software.Results The positive rate of mutant p53 in uterine endometrial carcinoma was statistically lower than that in uterine serous carcinoma [21.62 ％ (8/37) vs 64.86 ％ (24/37) (P ＜ 0.01)].The positive rate of Ki-67 in uterine endometrial carcinoma was statistically lower than that in uterine serous carcinoma [37.84 ％ (14/37) vs 70.27 ％ (24/37) (P ＜ 0.01)].The positive rate of estrogen receptor in uterine endometrial carcinoma was statistically higher than that in uterine serous carcinoma [78.38 ％ (29/37) vs 32.43 ％ (12/37) (P ＜ 0.01)].The positive rate of progesterone receptor in uterine endometrial carcinoma was statistically higher than that in uterine serous carcinoma [75.67 ％ (28/37) vs 29.73 ％ (11/37) (P ＜ 0.01)].Conclusions The expression of mutant p53 and Ki-67 are higher in uterine serous carcinoma.The expression of estrogen receptor and progesterone receptor are higher in uterine endometrial carcinoma.Combined detection of mutant p53,Ki-67,ER and PR has important significance in screening and preventing uterine endometrial carcinoma and uterine serous carcinoma.

Microscopic lesions of fallopian tubes in endometrioid carcinoma of the endometrium: How effective are the macroscopic tubal sampling techniques? / 부인종양

OBJECTIVE: Extrauterine involvement of endometrial carcinoma has a significant effect on the patients' prognosis and treatment decision. In classical method, macroscopic section is taken from the fallopian tube sparing the fimbrial ends. Fimbrial end of fallopian tube may be involved by tumors and precursor lesions. This study aims to determine the importance of sampling of fimbrial ends of fallopian tube in endometrioid endometrial carcinoma specimens. METHODS: We reevaluated the fallopian tubes of 200 cases of endometrioid endometrial carcinoma cases that have no macroscopic tubal lesion. A hundred cases were sampled with classical method, and the other 100 were sampled with a new method that includes the fimbrial ends. Statistical difference was examined by Fisher's exact test. RESULTS: No microscopic tubal lesion lesion was detected in cases that were sampled with the classical method. In contrast, there were 4 cases with tubal lesions in patients sampled with the new technique; 3 of them were located in the fimbrial end. Of the 3, there was one microscopic invasive carcinoma and two proliferative endometrial glandular lesions. Endometriosis was detected in two of the 4 cases with tubal lesions. CONCLUSION: Including the fimbrial end of fallopian tube to macroscopic sampling could detect more tubal lesions, which might provide additional prognostic and pathogenetic information of endometrioid endometrial carcinoma.

A comparison of uterine papillary serous, clear cell carcinomas, and grade 3 endometrioid corpus cancers using 2009 FIGO staging system / 부인종양

OBJECTIVE: This study was designed to compare survival outcomes of patients with uterine papillary serous carcinoma (UPSC) or clear cell carcinoma (CC) to those of patients with grade 3 endometrioid carcinoma (G3EC) according to 1988 and 2009 International Federation of Gynecology and Obstetrics (FIGO) staging systems. METHODS: We retrospectively reviewed all patients with endometrial cancer treated at a single institution between 1995 and 2009. Among the 647 patients with endometrial cancer, 51 with G3EC and 46 with UPSC and CC histology were confirmed. RESULTS: 1988 FIGO stage, 2009 FIGO stage, and extrauterine metastasis were significantly different between the UPSC and CC group and G3EC group (p=0.002, p=0.041, and p=0.020, respectively). Restaging from the 1988 FIGO to the 2009 FIGO criteria increased the number of stage I cases by 10 (11.0%). Overall, 8 in the UPSC and CC and 2 in the G3EC group were down-staged to stage I. In the UPSC and CC group, the 3-year overall survival for 1988 FIGO stage I was 92.9%. When UPSC and CC patients were restaged using the 2009 staging system, the 3-year overall survival of 2009 FIGO stage I dropped to 81.6%. UPSC and CC was associated with poor OS outcome compared with G3EC, after adjustment for 2009 FIGO stage and other clinicopathologic factors. CONCLUSION: We observed that UPSC and CC patients had different prognosis according to the old and new FIGO staging system. Our results suggest that UPSC and CC compared with the G3EC may retain the 1988 FIGO to be a slightly better discriminator than 2009 FIGO.

Differential Diagnosis of Ovarian Mucinous, Serous, and Endometrioid Adenocarcinoma in Peritoneal Washing Cytology / 대한세포병리학회지

This study presents the cytologic features of peritoneal washings, with particular emphasis on the cytologic discrimination among serous, mucinous, and endometrioid adenocarcinoma of the ovary. We selected histologically confirmed 27 cases of peritoneal washing : 8 cases of serous cystadenocarcinomas, 5 cases of mucinous cystadenocarcinomas, and 14 cases of endometrioid adenocarcinomas. The most frequent cytologic pattern of three tumors was clusters. Ball pattern was found in serous cystadenocarcinoma(36%) and acinar pattern in endometrioid adenocarcinoma (36%). Mucinous adenocarcinoma showed mucoid background(100%) and endometrioid adenocarcinoma revealed inflammatory background(43%). The cytoplasmic vacuoles were noted in 80%, 13%, and 43% of mucinous, serous, and endometrioid adenocarcinoma, respectively. The endometrioid adenocarcinoma showed prominent nucleoli(64%). In conclusion, the cytologic findings of mucinous cystadenocarcinoma were different from that of serous and endometrioid carcinomas, such as mucoid background, abundant cytoplasm with vacuolated cytoplasm, and peripherally located cytoplasm. Although endometrioid carcinoma showed acinar pattern and prominent nucleoli, the differential diagnosis between serous cystadenocarcinoma and endometrioid adenocarcinoma in peritoneal washing cytology was not always possible.

Ovarian Sertoliform Endometrioid Carcinoma

Sertolifonn endometrioid carcinoma (SEC) is a very rare malignant neoplasm arising from the surface epithelium of the ovary. We report one case of SEC occuring in the left ovary of a 73-year-old woman. The left ovary was totally replaced by a yellowish tan lobulated solid mass with focal cystic areas. Small tubules and elongated solid cord-like structures resembling a Sertoli-Leydig cell tumor or a Sertoli cell tumor were found microscopically. In some areas, confluent typical endometrioid carcinoma, adenofibromatous stroma, squamoid foci, and lutenizing stromal cell nests were noted. The tumor also demonstrated strong immunoreactivity with EMA (epithelial membrane antigen). Certain points of differentiation between SEC and SertoliLeydig or Sertoli cell tumors are discussed.

A case of endometrioid carcinoma of prostate / 대한비뇨기과학회지

In the rare group of atypical adenocarcinomas of the prostate, endometrioid carcinoma is thought to be in unique but controversial position among them. In 1967, Melicow and pachter first reported a prostatic malienancy whose pattern was similar to endometrial adenocarcinoma of the female uterus. Because of the distinctive morphologic appearance and location near the prostatic verumontanum, it was suggested that it might originate from the mtllerian (female) remnant, the prostatic utricle, and consequently display estrogen dependence. But recent immunohistochemical and ultrastructural studies suggests that endometriold carcinoma of prostate is a unusual histologic variant of prostatic duct adenocarcinoma. We experienced a case of endometriold carcinoma of prostate, who was treated by radital surgery and pelvic lymph node dissection with radiation. And this may be the first reported case of its kind in Korea. Till now he is under the follow up for 2 years and 2 months after surgery with no evidence of disease.