Low-grade endometrioid carcinoma of the ovary associated with undifferentiated carcinoma: case report and review of the literature

The association of low-grade endometrioid carcinoma with undifferentiated carcinoma (UC) was first reported in endometrium carcinoma, termed with dedifferentiated carcinoma (DC). However, the coexistence of low-grade endometrioid carcinoma (LGEC) or serous carcinoma (LGSC) with UC has received minimal attention in ovary, and the behavior of this kind of neoplasm remains at further discussion. In this study, we reported a case of low-grade ovarian endometrioid carcinoma associated with UC and reviewed another four cases previously reported. We found a histological continuity between the LGEC and UC components in H&E section, which suggested a dedifferentiation from LGEC to UC components. In summary, this kind of pathological type has aggressive behavior and these patients have very poor prognosis regardless of the amount of undifferentiated carcinoma.     

Atypical squamous cells in the urine revealing endometrioid adenocarcinoma of the endometrium with squamous cell differentiation: A case report

Urine cytology is mainly used to detect urothelial carcinoma (UC), especially for high‐grade lesions including urothelial carcinoma in situ. Benign squamous cells are often seen in the urine specimens of women, they are either exfoliated from the trigone area of the bladder, the urethra, or the cervicovaginal region. However, abnormal squamous cells in the urine raise concerns of abnormalities of the urinary tract and cervicovaginal area which range from squamous metaplasia of the urothelium, a cervicovaginal squamous intraepithelial lesion, condyloma acuminatum of the bladder, UC with squamous differentiation, and squamous cell carcinoma. We present here a unique case of atypical squamous cells (ASCs) in the urine subsequently leading to the diagnosis of endometrioid adenocarcinoma of the endometrium with squamous differentiation. The presence of ASCs in voided urine is a rare finding that may indicate an underlying malignancy. Careful evaluation of squamous cells in the urine is an important part of our daily cytopathology practice. Diagn. Cytopathol. 2015;43:49–52. © 2014 Wiley Periodicals, Inc.     

子宫内膜样腺癌中ARID1A蛋白的表达及意义

目的探讨ARID1A蛋白表达与子宫内膜样腺癌发生、发展的关系。方法采用免疫组化SP法检测子宫内膜的增生期、分泌期、孕期、简单性增生、复杂性增生、不典型增生和子宫内膜样腺癌中ARID1A蛋白的表达,分析其表达与临床病理特征及生存期的相关性。结果子宫内膜的增生期、分泌期、孕期、简单性增生及复杂性增生组织中ARID1A蛋白均呈阳性;子宫内膜不典型增生和子宫内膜样腺癌组织中ARID1A蛋白缺失率分别为8.33%(3/36)和41.51%(44/106),较不伴不典型增生的子宫内膜显著升高,子宫内膜样腺癌的ARID1A蛋白缺失率较不典型增生显著升高(χ2=13.358,P0.01);子宫内膜样腺癌的ARID1A蛋白缺失率与病理组织学分级呈负相关(P0.05)。ARID1A蛋白缺失率与患者年龄、是否绝经、子宫体肌层浸润深度、FIGO分期、淋巴结转移及生存期无关。结论 ARID1A蛋白缺失是子宫内膜样腺癌发生的早期事件,在子宫内膜样腺癌发生过程中具有重要作用,而对子宫内膜样腺癌进展的作用不明显。     

A novel case of endometrial dedifferentiated adenocarcinoma associated with MLH1 promotor hypermethylation and microsatellite instability

Endometrial dedifferentiated carcinoma is a rare, malignant tumor whose molecular alterations have not been clarified yet. We report a novel case of a 61-year old woman who presented with irregular vaginal bleeding after menopause and a 3?cm uterus mass. Histology revealed endometrial dedifferentiated adenocarcinoma, a rare subtype comprised of undifferentiated adenocarcinoma. The patient still survived 1?year after surgery without chemotherapy and radiotherapy. Immunohistochemistry revealed loss of MLH1/PMS2 expression and retained MSH2/MSH6 expression. Consistently, microsatellite instability was detected indicative of high microsatellite instability (MSI-H). No BRAF V600E, KRAS and POLE mutations were identified. Remarkably, the promoter regions of mutL homolog 1(MLH1) were methylated. Furthermore, several tumor cells were PD-L1 positive in this case with a concentration at the infiltrating tumor edge indicating MSI-H in endometrial dedifferentiated adenocarcinoma is a potential predictive factor for response to immunotherapy targeting the PD-1 or its ligand PD-L1.     

Prognostic value of Musashi-1 in endometrioid adenocarcinoma

Aims: Musashi-1, a RNA-binding protein, is suggested to be a cancer stem cell-related marker; its high level of protein expression is reported to be associated with high histological grade in some tumors. The aim of this study was to investigate the prognostic value of Musashi-1 in patients with endometrioid adenocarcinoma (EAC). Methods: We examined the Musashi-1 mRNA expression level in 35 fresh EAC tissue samples and 15 normal endometrium samples by real-time RT-PCR, and its protein expression level in 148 paraffin EAC tissue samples and 20 paraffin normal endometrium samples by immunohistochemistry. The correlation between Musashi-1 and overall survival (OS) used Cox proportional hazards regression. The prognostic accuracy of Musashi-1 compared with other clinicopathological risk factors by logistic regression. Furthermore, we examined whether Musashi-1 expression is correlated with another cancer stem cell marker CD133 by real-time RT-PCR. Results: Musashi-1 mRNA expression of EAC is 2.8-fold higher than that of normal endometrium (P = 0.0009). Musashi-1 protein expression level is correlated with tumor stage, grade and vascular invasion. Patients with higher protein expression level of Musashi-1 are associated with poor survival rate than those with negative or low level of expression (HR = 2.073, P = 0.001). The area under the curve (AUC) for Musashi-1 is 0.8, which is higher than other clinicopathological factors (P = 0.000). In addition, Musashi-1 mRNA expression seems to be closely correlated with CD133 expression (r = 0.7167, P < 0.0001). Conclusions: Our results suggest high level of Musashi-1 protein expression is associated with poor survival in EAC patients, which may be an independent prognostic factor for EAC.     

A case of ovarian endometrioid adenocarcinoma with yolk sac tumor component in a postmenopausal woman

The co-existence of an endometrioid adenocarcinoma with an ovarian yolk sac tumor is very rare. Only eight cases have been reported in the English language literature. A 54-year-old postmenopausal woman with a 6-month history of progressive abdominal distension was seen at our hospital. MR imaging revealed a large cyst with a solid intramural node. Serum alpha-fetoprotein and CA125 levels were 13143 ng/ml and 170 U/ml, respectively. At laparotomy, a large tumor approximately 20 cm in diameter was found to occupy the abdominal cavity, adhering to the swollen appendix and part of the omentum. Microscopically, foci of endometrioid adenocarcinoma together with a yolk sac tumor component were observed within a large endometriotic cyst. Since the tumor was clinically staged 1c, the patient was given 500 mg of intraperitoneal carboplatin postoperatively, followed by five courses of combination chemotherapy consisting of cisplatin, etoposide and peplomycin at 4-week intervals. The levels of both serum alpha-fetoprotein and CA 125 decreased gradually to normal ranges and remained normal at the most recent follow-up on 29 December, 2001. In contrast to a very poor prognosis of this tumor in previously reported cases, our patient showed no sign of recurrence during a 21-month follow-up period.     

宫颈与宫体子宫内膜样腺癌的临床病理及免疫表型分析

目的探讨宫颈子宫内膜样腺癌和宫体子宫内膜样腺癌的临床病理和免疫表型差异。方法采用HE及免疫组化En-Vision两步法对8例宫颈内膜样腺癌和76例宫体内膜样腺癌的组织学形态和免疫表型进行比较观察。结果宫颈子宫内膜样腺癌和宫体子宫内膜样腺癌在组织学形态上相似。两组标本的免疫标记物阳性率分别为vimentin(0,95.45%)、CEA(100%,45.45%)、p53(12.50%,31.82%)、ER(0,54.54%)、PR(0,60.61%)、Ki-67(75.0%,12.12%)、HPV16/18(100%,3.03%)、p16(100%,46.97%)、Cam5.2(12.50%,62.12%)。两者相比,vimentin、CEA、ER、PR、p16、Ki-67、HPV16/18、PAS、Cam5.2的表达差异有显著性(P<0.05),而p53的表达差异无统计学意义(P>0.05)。结论应用免疫标记物vimentin、CEA、ER、PR、p16、Ki-67、HPV16/18、PAS、Cam5.2检测是鉴别宫颈和宫体子宫内膜样腺癌的一种重要的有效方法,p53可作为辅助鉴别的免疫标记物。     

Nuclear features in endometrial cytology: Comparison of endometrial glandular and stromal breakdown and endometrioid adenocarcinoma grade 1

This study was to clarify the nuclear features of “condensed clusters of stromal cells (EGBD‐stromal cells)” and “metaplastic clumps with irregular protrusions (EGBD‐metaplastic cells)” which may be recognized in endometrial glandular and stromal breakdown (EGBD) cases in liquid‐based cytologic (LBC) preparations of endometrial brushings. The material consists of cytologic smears of 20 cases of proliferative endometrium (PE), 20 cases of EGBD, and 20 cases of endometrioid adenocarcinoma grade 1 (G1) for which histopathological diagnosis was obtained by endometrial curettage. Nuclear findings were examined in PE cells, EGBD‐stromal cells, EGBD‐metaplastic cells, and G1 cells, respectively. It was examined about the following items: (1) Nuclear shape; (2) A long/minor axis ratio in cell nuclei; (3) An area of cell nuclei; (4) Overlapping nuclei; (5) The distribution pattern of nuclei within cell clusters. The following observations were made: (1) In PE cells, round‐oval nuclei appeared to predominate, overlapping nuclei were not observed, and a slightly abnormal distribution pattern of nuclei was recorded; (2) In EGBD‐stromal cells, reniform nuclei were characteristically observed, nuclei had small size and a generally elongated appearance, overlapping nuclei were recognized, and a remarkable abnormal distribution pattern of nuclei was found; (3) In EGBD‐metaplastic cells, spindle nuclei were a characteristic feature, nuclei were larger in size and had a bipolar appearance, overlapping nuclei with moderately abnormal distribution pattern of nuclei were identified; (4) In G1 cells round‐oval nuclei predominated, overlapping nuclei with moderately abnormal distribution pattern of nuclei were found. The study demonstrates that the analysis of selected nuclear findings appears to be very useful in the cytopathological assessment of endometrial lesions in LBC samples, especially for the discrimination of EGBD and G1. Diagn. Cytopathol. 2012. © 2012 Wiley Periodicals, Inc.     

Primary endometrioid adenocarcinoma of the large intestine arising in colorectal endometriosis

AIMS: Three cases of endometrioid adenocarcinoma arising in colorectal endometriosis are described with discussion of their macroscopic and microscopic pathology and diagnosis, using immunohistochemistry. METHODS AND RESULTS: Three middle-aged women presented with symptoms and signs of colorectal mass effect. Two had a preceding history of gynaecological endometriosis and all three had either been on hormone replacement therapy or had functioning ovaries prior to presentation with colorectal disease. Each underwent resection of tumours of the distal large intestine. The definitive diagnosis was dependent on histological examination and immunohistochemistry, which was used to demonstrate an origin in endometriotic tissue. CONCLUSIONS: Endometrioid adenocarcinoma is a rare complication of colorectal endometriosis, this report contributing to a total of 25 cases in the literature. Definitive diagnosis, aided by immunohistochemical studies, is important to enable the identification of the optimal management for this uncommon condition.     

Expression of immunoreactivity of nuclear findings by p53 and cyclin a in endometrial cytology: Comparison with endometrial glandular and stromal breakdown and endometrioid adenocarcinoma grade 1

It is well known that “condensed cluster of stromal cells (CCSC)” and “metaplastic clumps with irregular protrusion (MCIP)” in endometrial glandular and stromal breakdown (EGBD) cases may simulate “clumps of cancer cells (CCC)” in endometrioid adenocarcinoma grade 1 (G1), leading to difficulty in cytological interpretation. The aim of this study was undertaken to clarify the cytological immunoreactivity of nuclear findings about CCSC and MCIP which may be recognized in EGBD cases by using p53 protein and cyclin A in liquid‐based cytologic (LBC) preparations. The material consists of cytologic smears of 20 cases of EGBD and 20 cases of G1 for which histopathological diagnosis was obtained by endometrial curettage at the JA Suzuka General Hospital. The evaluation of immunoreactivity was performed by using the intensity of nuclear staining and the nuclear labeling index (N‐LI). The intensity of nuclear staining was scored as negative (0), weak (1), moderate (2), or strong (3). The N‐LI was scored as less than 10% (0), from 10 to 25% (1), from 26 to 50% (2), or greater than 50% (3). The final score was calculated of the addition of both partial scores. Results are as follows: As for the p53 protein immunoreactivity, CCC (2.4 ± 1.4) was a significantly higher value in comparison with CCSC (0) and MCIP (0.8 ± 0.4), respectively. As for the cyclin A immunoreactivity, CCC (2.8 ± 1.1) was a significantly higher value in comparison with CCSC (0) and MCIP (0.6 ± 0.5), respectively. CCSC and MCIP in EGBD are misunderstood as cellular atypia and structural atypia on occasion; but, as for results of the immunoreactivity scores of p53 protein and cyclin A in our study, it seemed that those biochemical characters proved that the biological activity level was low (or degenerative). The results of the current study demonstrated that the cytological immunoreactivity of nuclear findings by p53 and cyclin A appear to be more useful for the LBC assessment of endometrial lesions, especially for the discrimination of EGBD and G1.Diagn. Cytopathol. 2013;41:303–307. © 2011 Wiley Periodicals, Inc.     

子宫内膜样腺癌中Stathmin和Ki-67的表达及意义

目的:研究Stathmin和Ki-67在子宫内膜样腺癌和正常子宫内膜中的表达差异,探讨Stathmin和Ki-67在子宫内膜样腺癌发生发展过程中的意义.方法:采用免疫组织化学法检测99例子宫内膜样腺癌及67例正常子宫内膜中Stathmin和Ki-67的表达情况.结果:子宫内膜样腺癌中Stathmin和Ki-67表达率分别为75.8%,70.7%,显著高于正常子宫内膜中的9.0%,4.5%,差异有统计学意义(P<0.05);Stathmin和Ki-67表达与子宫内膜样腺癌组织学分级相关(P<0.05),与患者年龄、临床分期、浸润深度、淋巴结转移及脉管侵犯无关(P>0.05);Stathmin表达和Ki-67表达呈正相关(r=0.672,P<0.05).结论:子宫内膜样腺癌中Stathmin和Ki-67高表达可能共同参与子宫内膜样腺癌发生和分化;Stathmin和Ki-67表达呈正相关,提示Stathmin高表达可能与子宫内膜样腺癌高增殖性相关.     

Minimal deviation endometrioid adenocarcinoma of the cervix: report of three cases with exfoliative cytology

Three histologically confirmed minimal deviation endometrioid adenocarcinomas (MDEA) of the uterine cervix with cytologic evaluation by cervical scraping were reviewed. The smears were cellular and showed tall columnar tumor cells arranged in monolayered sheets with nuclei in palisade at free borders, rosettes, and irregular clusters. Cellular strips with palisading nuclei was noted in one case. The individual tumor cells showed monomorphic, round or oval, hyperchromatic nuclei with chromatin clumping, small nucleoli, and granular, nonvacuolated cytoplasm with cytoplasmic extensions or tails. The smear background showed a variable amount of necrotic debris admixed with polymorphonuclear leukocytes in two cases. The cytologic manifestations of those three cervical MDEAs overlapped, to some extents, with those of a cervical adenocarcinoma in situ and with those of a well-differentiated endometrial adenocarcinoma invading the cervix.     

Distinction of low-grade endometrioid carcinoma in endometrial samplings from high-grade mimics: a practical pattern-based approach

Low grade endometrioid carcinoma may exhibit a diverse spectrum of morphological variations that mimic high grade cancers. In an endometrial sampling, the distinction between low grade endometrioid carcinoma versus higher grades or other tumor types of carcinoma directly affects clinical decisions regarding the type and extent of surgery and lymph node dissection. This review takes a practical pattern-based approach to this differential diagnosis, highlighting glandular, papillary, solid, spindle-cell, clear-cell rich, mucin-rich, and necrotic patterns of low grade endometrioid carcinoma. Morphological distinctions and immunohistochemical strategies for navigating common diagnostic pitfalls are discussed in alignment with the consensus recommendations on tumor typing from the 2019 International Society of Gynecological Pathologists' Endometrial Cancer Project.     

Stereological estimate of nuclear volume in endometrial adenocarcinoma of endometrioid type: reproducibility and intra-tumour variation

Stereological volume weighted mean nuclear volume estimate (Vv) is reported to be highly reproducible and to provide excellent prognostic information for some tumours. The aim of the present study was to investigate the reproducibility and the intra-tumour variation of nuclear Vv and compare it with a morphometric nuclear estimate, i.e. the mean shortest nuclear axis, and with conventional histopathological parameters used in the grading of endometrial adenocarcinomas. Sixty-three endometrioid adenocarcinomas were included in the study. Both Vv and mean shortest nuclear axis showed an acceptable reproducibility and the correlation between them was moderate (Sperman test; rs = 0.8). One-third of the tumours showed a marked intra-tumour variation. A considerable discrepancy between Vv and/or mean shortest nuclear axis and nuclear and architectural grade was found.     

Tumor-associated macrophages,epidermal growth factor receptor correlated with the triple negative phenotype in endometrial endometrioid adenocarcinoma

It has been well established that tumor-associated macrophages (TAMs) play a tumor-promoting role in endometrial endometrioid adenocarcinoma (EEC). However, the association with TAMs and the triple-negative phenotype (TNP) in EEC has not yet been reported. We used immunohistochemistry to examine the expression of CD68, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and epidermal growth factor receptor (EGFR) in 186 cases of EEC. Fluorescent in situ hybridization (FISH) was also used for HER2 amplification, and the association with TAMs count, EGFR expression, and triple-negative phenotype was analyzed. Twenty-eight of 186 patients (15.05%) had the TNP. It was associated with advanced stage disease (P < 0.0001), high grade disease (P < 0.0001), depth of myometrial invasion (P = 0.003), pelvic lymph node metastasis (P < 0.001), lymphovascular space invasion (P = 0.001), and EGFR expression (P = 0.032). Margin TAMs count was also significantly increased in the TNP-positive group, the EGFR-positive group, and the PR-negative group (P < 0.001, respectively). The TNP was associated with a significantly worse overall survival (OS) (log rank test, P = 0.018). The estimated 5-year OS of patients with TNP was 59.1%, while that without TNP was 78.5%. Multivariate analysis showed high margin TAMs, and the histopathological grades were significantly associated with OS. The TNP in EEC is associated with poor prognostic surgical–pathological factors, worse prognosis, as well as with high margin TAMs and overexpression of EGFR, which may serve as potential targeted therapies for the special phenotype in EEC.     

Molecular analysis of isolated tumor glands from endometrial endometrioid adenocarcinomas

We studied the extensive molecular alterations of endometrial endometrioid adenocarcinoma (EEA) using a crypt isolation method. We analyzed copy number variation (CNV) using a single nucleotide polymorphism (SNP) array, genetic mutations (KRAS, BRAF, p53, PIK3CA), DNA methylation and microsatellite instability (MSI) status. In addition, loss of PTEN protein expression was examined. Increased chromosome copy numbers of 1q21.2–44 (22%) and 10q11.21–23.31 (28%) were seen relatively frequently in EEA, and copy‐neutral loss of heterozygosity (LOH) was also observed in 10q22.1–26.3 (22%). The CNV patterns of EEA were classified into four groups through hierarchical cluster analysis. Cluster 1 had many CNVs of 10q, and cluster 2 was characterized by MSI status. In cluster 3, increased CNVs of 1q were often seen. In cluster 4, p53 mutations were detected. KRAS and PIK3CA mutations and reduced PTEN protein expression were common to all groups. On the other hand, CpG island methylator phenotype (CIMP) was rare in all groups. The data indicated an association with chromosomal gain of 1q and 10q or 10q copy‐neutral LOH in some cases. We suggest that EEA consists of four groups that are characterized with molecular alterations.