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Biopsies of mixed endometrial carcinomas. Each contains a spatially distinct component of low-grade endometrioid carcinoma but the high grade component defines the behavior and management. Mixed serous carcinoma and endometrioid carcinoma (A-C). B is a highmagnification view of the serous component and C of the endometrioid component. Mixed clear cell carcinoma and endometrioid carcinoma (D, E). Mixed high grade neuroendocrine carcinoma and endometrioid carcinoma (F-H); G is a high-magnification view of the neuroendocrine component and H of the endometrioid component.
Source publication
This article provides practical recommendations developed from the International Society of Gynecological Pathologists Endometrial Carcinoma Project to address 4 issues that may arise in the diagnosis of uterine corpus low-grade endometrioid carcinoma: (1) The distinction between atypical hyperplasia and low-grade endometrioid carcinoma. (2) The di...
Context in source publication
Context 1
... endometrial carcinoma has evolved as the overall classification scheme for endo- metrial carcinomas has been refined. The 2014 World Health Organization (WHO) classification defines mixed endometrial carcinoma as a tumor composed of 2 or more spatially distinct tumor subtypes, at least one of which is serous carcinoma or clear cell carcinoma (Fig. 7) (28). The most common mixed endometrial carcinoma is a mixture of endometrioid carcinoma and serous carcinoma. Mixed carcinomas with a component of neuroendocrine carcinoma also occur but these are not discussed further. The rationale for recognizing mixed endometrial carcinoma is that even a minor component of serous or clear cell ...
Similar publications
The aim of this review was to update current knowledge on the conservative treatment of endometrial cancer (EC) based on a literature review. A web-based search in the MEDLINE database was carried out on EC management and treatment. All relevant information has been collected and analysed. Case series were mainly found in the literature search. Con...
Citations
... Patients with these tumors generally present with a favorable prognosis, largely due to the heightened immunogenicity conferred by the high mutational load, which may stimulate a more effective immune response against the tumor [6]. This feature also opens new avenues for therapeutic interventions, particularly with immunotherapeutic agents, which have shown promise in preliminary studies [7]. ...
... At the molecular level, the mutations in the POLE gene lead to a dysfunctional DNA polymerase that is unable to correctly proofread DNA, thus increasing the rate of mutagenesis. This biochemical pathway not only results in the cancer phenotype but also makes these cells targets for immunemediated destruction due to the presentation of novel antigens that are recognized as non-self by the immune system [7]. ...
POLE ultramutated endometrial carcinoma is characterized by a unique genetic profile with a high mutation burden due to alterations in the polymerase epsilon (POLE) gene. This review explores the distinctive clinicopathological features, prognosis, and therapeutic implications of this rare subset of endometrial cancer. POLE mutations confer a hypermutated state that may enhance immunogenicity and improve patient outcomes compared to other endometrial carcinoma variants. This type of carcinoma typically shows favorable prognostic factors, including reduced rates of myometrial invasion and lymphovascular space involvement, leading to better overall survival and disease-specific outcomes. The review also discusses the potential for targeted immunotherapeutic strategies, leveraging the high mutational load to improve response rates to treatment. Future challenges include the need for precise diagnostic tools to identify POLE mutation status accurately and the exploration of novel therapeutic avenues that could further enhance the management of patients with this promising yet challenging form of endometrial carcinoma.
... Low-grade endometrioid carcinoma with squamous differentiation is usually associated with CHEC, and the histological grade depends on the grade of conventional endometrioid carcinoma. Cytokeratin and EMA are often weakly to moderately positive in the corded and spindled components [17]. Beta-catenin nuclear expression in all components and the loss of E-cadherin expression in the spindle and corded epithelioid cells [18] suggest the epithelial-mesenchymal transition. ...
The previous endometrial cancer (EC) FIGO staging primarily relied on the extent of the disease spread into the anatomical sites at diagnosis. The most recent one (2023) incorporates clinicopathological features such as histological subtype, tumor grade, the extent of lymphovascular space invasion (LVI), and, when available, molecular subtypes of EC. The emphasis on accurate histological typing, tumor grading, and the molecular features of the cancer is stronger than ever. This review addresses challenging diagnostic patterns in the histologic subtyping and grading EC under five categories: 1. EC with spindle cells, 2. EC with clear cells, 3. EC with a papillary architecture, 4. EC with a biphasic morphology, and 5. EC with a microglandular architecture. The morphological features differentiating low- and high-grade cancers are discussed, along with relevant clinical work-ups. Recent molecular genetic findings regarding the diagnosis and prognosis of the disease and the results of related clinical trials are summarized. The potential challenges in the evaluation of LVI follow these sections. The final section of the review includes an overview of the literature on incorporating molecular subtypes of EC into clinical practice.
... Sarcomas of mesenchymal origin account for less than 9% of diagnoses. Among EC, around 80% are classified as type I and histologically belong to the endometrioid type, with the majority diagnosed as low grade (International Federation of Gynecology and Obstetrics (FIGO) grade 1 or 2) [2]. This type of EC usually manifests with early symptoms such as postmenopausal bleeding or abnormal uterine bleeding in premenopausal women, thus generally resulting in early diagnosis with a good prognosis and high survival rates. ...
Background: Sentinel lymph node (SLN) biopsy in early-stage endometrial cancer is recommended over systematic lymphadenectomy due to reduced morbidity and comparable detection rates. The main objective of this study was to compare the overall and bilateral detection rates of SLN in early-stage endometrial cancer using three techniques. Methods: a prospective cohort study was designed to detect the difference in SLN detection rate in three cohorts: Indocyanine green (ICG), methylene blue (MB), and tracer combination (ICG + MB). Mapping characteristics, detection rate, number of SLNs, and positive SLNs of the three cohorts were compared. Results: A total of 99 patients were enrolled. A total of 109 SLN sites with 164 lymph nodes were detected. No differences were found between the three cohorts in terms of age, BMI, tumor diameter, or other histologic characteristics. The overall SLN detection rate (DR) was 54.3% in the MB group, 72.7% in ICG, and 80.6% in the ICG-MB group. Bilateral DR was 22.9%, 39.4%, and 54.8% in groups, respectively, with the MB method yielding significantly inferior results. Conclusions: The ICG-MB group demonstrated superior overall and bilateral detection rates, but a significant difference was found only in the MB cohort. Combining tracer agents can enhance the accuracy of SLN identification in initial-stage endometrial cancer without additional risk to the patient.
... P53 IHC is widely used as a surrogate for TP53 mutation testing in diagnostic gynecologic pathology [77]. P53 IHC is a reliable diagnostic adjunct for histotyping and molecular subtyping of endometrial carcinomas [48, 66,78]. Another use of p53 IHC is triaging gynecological sarcomas for molecular testing based on the assumption that TP53-mutated gynecological sarcomas do not harbor cancer driving translocations [77]. ...
Introduction: The role of p16 and p53 immunohistochemistry in the diagnosis of rare and aggressive uterine carcinosarcoma (UCS) has been well established. However, enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a member of the polycomb group family is a relatively new biomarker, with limited published data on its significance in this tumor type. The goal of this study was to examine EZH2 expression in UCS and its components, in correlation with morphological features, and p16 and p53 staining patterns.
Methods: Twenty-eight UCSs were included in the study. EZH2, p16 and p53 immunoreactivity were assessed independently by two pathologists in both tumor components (epithelial and mesenchymal). EZH2 and p16 immunostains were scored semiquantitatively: based on the percentage and intensity of tumor cell staining a binary staining index (“high- or low-expressing”) was calculated. The p53 staining pattern was evaluated as wild-type or aberrant (diffuse nuclear, null, or cytoplasmic expression). Statistical tests were used to evaluate the correlation between staining patterns for all three markers and the different tumor components and histotypes.
Results: High EZH2 and p16 expression and aberrant p53 patterns were present in 89.3% 78.6% and 85.7% of the epithelial component and in 78.6%, 62.5% and 82.1% of the mesenchymal component, respectively. Differences among these expression rates were not found to be significant (p > 0.05). Regarding the epithelial component, aberrant p53 pattern was found to be significantly (p = 0.0474) more frequent in the serous (100%) than in endometrioid (66.6%) histotypes. Within the mesenchymal component, p53 null expression pattern occurred significantly (p = 0.0257) more frequently in heterologous sarcoma components (71.4%) compared to the homologous histotype (18.8%).
Conclusion: In conclusion, EZH2, p16 and p53 seem to play a universal role in the pathogenesis of UCS; however, a distinctive pattern of p53 expression appears to exist between the serous and endometrioid carcinoma components and also between the homologous and heterologous sarcoma components.
... Myxoid, osteoid, and chondroid stroma may be present. 73,76 The CHEC pattern is often a minor component of the tumor, with the remainder composed of gland-forming endometrioid carcinoma, usually FIGO grade 1 or 2 (45 of 47 cases; 96%). In rare cases, a higher-grade endometrioid carcinoma may be present (Figure 4, D). ...
... 70,73 The current recommendation is to grade CHEC based on the architecture of the conventional glandular component. 76 Immunohistochemically, the corded and hyalinized areas often show less extensive cytokeratin expression and more vimentin expression than the typical endometrioid component. The corded and hyalinized areas typically show nuclear positivity for b-catenin (Figure 4, E), and the glandular areas can also show at least focal nuclear staining. ...
Context.—
A variety of uncommon malignant endometrial tumors can be challenging to diagnose because of overlapping morphology with more common entities. In some cases, immunohistochemical stains and/or molecular testing allow for more definitive diagnosis or prognostication.
Objective.—
To review classic morphologic features of uncommon endometrial tumors, pathologic features of these tumors and their mimics, and the evidence for use of immunohistochemistry and molecular testing in the diagnosis of these tumors.
Data Sources.—
University of Michigan (Ann Arbor) cases and review of pertinent literature about each entity.
Conclusions.—
Although each of these uncommon endometrial tumors has morphologic mimics, key histologic features, immunohistochemical stains, and molecular testing allow for accurate classification.
... The rationale for accurately diagnosing mixed endometrial carcinoma is that even a minor component of serous or clear-cell carcinoma within an otherwise typical endometrioid carcinoma may confer an adverse outcome similar to a pure serous or clear-cell carcinoma [13][14][15]. ...
Mixed endometrial carcinoma (MEEC) refers to rare endometrial tumours that are composed of two or more distinct histotypes, at least one of which is serous or clear cell. The aim of this study was to evaluate the epidemiology, treatment outcomes and survival rates of patients with mixed endometrial carcinoma. The medical records of 34 patients diagnosed with MEEC between March 2010 and January 2020 were reviewed retrospectively. Clinicopathological variables and treatment strategies were assessed, and overall survival and disease-free survival rates were evaluated. The histology of endometrioid and serous component was found in 26 (76.5%) patients, followed by serous and clear-cell components (5/34, 14.5%) and mixed endometrioid serous and clear-cell components (3/34, 8.8%). The median age at diagnosis was 70 years (range 52-84), and the median follow-up time was 55 months. The 5-year disease-free survival and the 5-year overall survival were 50.4% and 52.4%, respectively. Advanced disease stage was identified as an independent predictor of inferior disease-free (<0.003) and overall survival (p < 0.001). Except for stage, none of the traditional prognostic factors was associated with disease recurrence or death from disease. MEECs represent rare high-risk endometrial carcinomas with significant diagnostic and treatment challenges. Undoubtedly, the implementation of a molecular analysis can offer further diagnostic and management insights.
... The rationale for accurately diagnosing mixed endometrial carcinoma is that even a minor component of serous or clear-cell carcinoma within an otherwise typical endometrioid carcinoma may confer an adverse outcome similar to a pure serous or clear-cell carcinoma [13][14][15]. ...
Introduction/Background
Mixed endometrial carcinoma refers to rare endometrial tumours that are comprised of two or more distinct histotypes, at least one of which is serous or clear cell. Limited data is available on the recurrence rates for mixed epithelial endometrial carcinoma, as it comrises a relatively understudied subtype of endometrial cancer. The aim of this study is to evaluate the epidemiology, treatment outcomes and survival rates of patients with mixed endometrial carcinoma.
Methodology
Medical records of the patients diagnosed with mixed endometrial carcinoma between March 2010 and January 2020 reviewed retrospectively. Clinicopathological variables and treatment strategies were assessed, and overall survival (OS) and disease-free survival (DFS) rates were evaluated.
Results
A total of 34 patients were included in the study. Histology of endometrioid and serous component was found in 26 (76.5%) patients, followed by serous and clear cell components (5/354 14.5%) and a mixture of endometrioid, serous and clear cell components (3/34, 8.8%). The median age was 70 years (range 52–84), and median follow-up time was 55 months. Most patients (70%) were treated with laparoscopy. Overall, the 5-year disease-free survival rate (DFS) and the 5-year overall survival (OS) rate was 50.4% and 52.4%, respectively. Advanced disease stage was found to be independently correlated with worse 5-year disease-free survival (DFS) and overall survival (OS) rates (p<0.001).
Conclusion
The management of mixed epithelial endometrial carcinoma presents several challenges for clinicians and researchers that need to be addressed to improve oncologic outcomes. Accurate and early diagnosis plays a fundamental role to determine the appropriate treatment plan. Improved diagnostic techniques, such as molecular profiling and imaging technologies, as well as identification of specific biomarkers associated with the distinct features of the tumour, can help clinicians effectively stratify the patients and tailor treatment accordingly. Undoubtedly, the implementation of molecular analysis will offer further diagnostic and management insights.
Disclosures
no
... Leiomyomas are the most common benign mesenchymal neoplasms, whereas endometrioid endometrial carcinoma is the most common type of corpus uteri carcinoma, accounting for approximately 80% of all endometrial carcinomas (10,11). ...
Perivascular epithelioid cell tumors are very rare mesenchymal neoplasms arising in various locations, such as the female genital tract, kidney, lung, prostate, bladder, pancreas, soft tissues, and bone. They possess a unique immunophenotype, co-expressing myogenic and melanocytic markers; molecular findings include mutations of tuberous sclerosis complex and translocations of transcription factor E3, a member of the microphthalmia transcription factor gene family. We herewith report a uterine collision tumor consisting of a perivascular epithelioid cell tumor and a moderately differentiated endometrial endometrioid carcinoma in a patient with genetically proven tuberous sclerosis; two leiomyomas were also found in contact with the tumor. Although two such cases one with a benign and another with a malignant perivascular epithelioid cell tumor have previously been reported, ours is, to our knowledge, the first reported in a tuberous sclerosis patient.
... During pre and postmenopausal period of time, the incidence of abnormal uterine bleeding among all gynecological problems is beyond 70%. 1 Mainly, abnormalities in the uterine bleeding are investigated with an intention to rule out intrauterine pathology, more specifically, the cancer of the endometrium. 2,3 Literature shows that a high percentage (90%) of endometrial cancer patients exhibit irregular or post-menopausal bleeding. 4 In advanced countries, endometrial carcinoma is the commonest gynecologic malignancy with 142,200 newly diagnosed patients annually showing the rate of incidence as 12.9 per 100,000 females. ...
Objective: To compare the effectiveness of endometrial biopsy and diagnostic dilatation and curettage (D&C) in terms of adequate specimen collection for histopathology for diagnosing endometrial carcinoma in patients with abnormal vaginal bleeding. Study Design: Randomized Controlled Trial. Setting: Department of Obstetrics & Gynecology, Bahawalpur Medical & Dental College, Bahawalpur. Period: October 2022 to March 2023. Material & Methods: A total of 172 peri and post-menopausal women with abnormal uterine bleeding of more than 6 months were analyzed. Randomization was 1:1 for biopsy group (n=86) and D&C group (n=86). Patients in biopsy group underwent biopsy endometrial sampling while those in D&C group underwent diagnostic D&C for endometrial sampling. In biopsy group pipelle suction curette was used to collect the specimen. In D&C group, procedures were done employing general anesthesia. Obtained samples were sent for histopathology examination. Results: In a total of 172 women, the mean duration of abnormal vaginal bleeding were 9.267±2.37 months and 9.174±2.33 months in in biopsy and D&C groups respectively. Adequate specimen collection was noted in 93% women in biopsy group as compare to 97.7% in D&C group (p=0.147). Conclusion: Diagnostic dilatation and curettage as well as endometrial biopsy were effective in terms of adequate specimen collection for histopathology. Endometrial sampling using Pipelle was safe and accurate procedure conducted in outpatient department that avoided general anesthesia.
... However, usual-type endocervical adenocarcinomas often show apical mitoses and cribriforming, whereas serous carcinomas should be recognized based on discordance between the ''low-grade'' architecture and marked cytologic atypia. 41 Ancillary testing can be helpful, with wild-type p53 expression and patchy p16 expression in most endometrioid adenocarcinomas, diffuse blocklike p16 staining and/or positive high-risk HPV RNA in situ hybridization in most usual-type endocervical adenocarcinomas, and abnormal p53 expression and diffuse block-like p16 staining in most serous carcinomas. [42][43][44][45] For the differential diagnosis of usual-type endocervical adenocarcinoma and endometrioid adenocarcinoma in small biopsies, the most commonly used panel consists of high-risk HPV RNA in situ hybridization and IHC for vimentin, estrogen receptor (ER), p16, and monoclonal carcinoembryonic antigen (mCEA), with positive high-risk HPV RNA in situ hybridization, diffuse p16 and mCEA staining, and negative ER and vimentin in the former, and negative high-risk HPV RNA in situ hybridization, negative to focal p16 and mCEA staining, and diffuse ER and vimentin expression in the latter. ...
Context.—:
Clinical management of endometrial carcinoma largely depends on the morphologic parameters ascertained based on the pathologic evaluation of surgical resection specimens. However, there are numerous controversial and nonstandardized aspects of both the macroscopic and microscopic assessment of surgical specimens, including grossing, adequate sampling, diagnosis, staging, reporting, and ancillary testing.
Objective.—:
To provide a comprehensive practical review of standardized grossing, key morphologic findings for reporting and staging, and diagnostic and prognostic use of ancillary testing in endometrial carcinomas.
Data sources.—:
The existing literature, recommendations of the International Society of Gynecological Pathologists, and specialty consensus guidelines.
Conclusions.—:
This review article summarizes important aspects of the grossing and sampling of surgical resection specimens for microscopic examination, key morphologic parameters that are required for reporting and staging, and morphologic features and immunoprofiles helpful in the differential diagnosis of low-grade and high-grade endometrial carcinomas, as well as the current status of the molecular classification of endometrial carcinoma and HER2 testing in serous carcinoma. The information presented herein can be helpful in overcoming diagnostic challenges and issues related to the pathology reporting of endometrial carcinoma to practicing anatomic pathologists.
