ReviewMechanismMixed resultsModerate evidenceTier 4 · clinical
Oncology research · Nov 2025 · narrative review
ovarian endometrioid carcinomaepithelial ovarian cancer
This narrative review summarizes contemporary evidence about ovarian endometrioid carcinoma (OEC), applying the endometrial cancer molecular taxonomy (POLE‑ultramutated, MMRd, p53‑abnormal, NSMP) to OEC. The authors report that OEC is enriched for Lynch syndrome and recommend routine MMR testing; POLEmut/MMRd tumors generally have favorable outcomes and may be candidates for de‑escalation or immunotherapy, while p53‑abnormal/high‑grade tumors have poorer prognosis and may need intensified management or HRD‑directed strategies.
Reported effect: proportion_of_epithelial_ovarian_cancers 10%
Studied with: immune checkpoint inhibitors, HRD-directed strategies.
Key findings
- Ovarian endometrioid carcinoma (OEC) accounts for ~10% of epithelial ovarian cancers and displays broad morphologic diversity that complicates diagnosis and grading.
- The endometrial cancer molecular taxonomy (POLE‑ultramutated, MMRd, p53‑abnormal, NSMP) also applies to OEC.
- OEC is enriched for Lynch syndrome‑associated tumors, supporting routine MMR testing.
- Integrating morphology with molecular classification refines diagnosis and prognostication.
- POLEmut/MMRd subsets generally have excellent outcomes and are candidates for de‑escalation or immunotherapy.
- p53abn/high‑grade tumors carry a poorer prognosis and may warrant intensified management and trials of HRD‑directed strategies.
- Routine MMR immunohistochemistry with reflex germline testing improves Lynch detection.
- Future priorities include prospective validation and multi‑omics to refine NSMP and identify new targets.
Limitations: Narrative review rather than primary research; no new patient‑level data reported.; Recommendations (e.g., de‑escalation, therapeutic strategies) lack prospective validation in OEC as noted by the authors.; Broad morphologic diversity and diagnostic/grading challenges in OEC may limit generalizability of some recommendations.; NSMP group remains heterogeneous and requires further molecular refinement per the authors..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Case reportMechanismInconclusiveLimited evidenceTier 3 · early humann = 3
Human pathology · Oct 2025 · case series
endometrial carcinomaendometrioid carcinomapilomatrix-like high-grade endometrioid carcinoma (PiMHEC)
The authors report three human cases of high-grade endometrioid carcinoma with pilomatrix-like features (PiMHEC) that lacked CTNNB1 exon 3 mutations and nuclear β-catenin by IHC. All tumors had characteristic pilomatrix-like morphology, presented at advanced stage, showed aggressive clinical behavior (two recurrences within 12 months), and targeted NGS identified alternative likely oncogenic alterations including FGFR4 p.T259A, TSC2 mutations, KRAS p.G12D, and MYC amplification.
Reported effects: number_of_cases 3, n=3 · patients_presenting_with_advanced_stage_disease 3, n=3 · +6 more
Key findings
- Three cases of high-grade endometrioid carcinoma with pilomatrix-like features were analyzed.
- All tumors demonstrated two components: a high-grade basaloid component with solid sheets of atypical basaloid cells, geographic necrosis, and focal "ghost" cells, and an associated low-grade FIGO grade 1 endometrioid carcinoma component.
- None of the three cases showed nuclear β-catenin expression by IHC, and all lacked CTNNB1 exon 3 mutations.
- All the patients presented with advanced-stage disease (stages IIC-IVB).
- Two patients had a recurrence within 12 months.
- NGS revealed no CTNNB1 mutations, but identified alternative likely oncogenic alterations: one tumor harbored an FGFR4 p. T259A mutation, two tumors had pathogenic TSC2 mutations, one had a KRAS p.G12D mutation, and two showed MYC amplification.
Limitations: Very small sample size (n=3) and single case-series design.; Case reports are descriptive and cannot establish causal relationships between identified mutations and the PiMHEC phenotype.; No functional validation provided to show that the alternative oncogenic alterations drive the pilomatrix-like phenotype.; Limited follow-up data reported (recurrence noted within 12 months for two patients), limiting assessment of long-term outcomes and prognostic significance..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Case reportMechanismInconclusiveLimited evidenceTier 3 · early humann = 1
International journal of surgical pathology · Sep 2025 · Case report
Endometrial endometrioid carcinomaPilomatrix-like high-grade endometrioid carcinoma
This is a single-patient case report of a 56-year-old woman whose high-grade endometrial endometrioid carcinoma showed complete transdifferentiation to a pilomatrix-like carcinoma pattern, with metastases to ovaries and lymph nodes. Pathology showed basaloid cells with ghost cell keratinization, aberrant cytoplasmic and nuclear β-catenin expression, focal CDX2, absent PAX8 and ER/PR, and NGS identified a CTNNB1 (p.Ser37Phe) mutation with a variant allele frequency of 18.6%. The authors note this tumor is rare, diagnostically challenging, presented at high stage, and it is unknown whether standard adjuvant therapies are effective for this subtype.
Reported effect: CTNNB1 variant allele frequency 18.6%, n=1
Key findings
- Hysterectomy specimen confirmed high-grade endometrioid carcinoma with secondary involvement of both ovaries, left tubo-ovarian ligament and obturator lymph nodes.
- Microscopically the tumor had a solid, nested/insular pattern with peripheral basaloid cells, central ghost cell keratinization, and extensive geographic necrosis.
- No low-grade endometrioid carcinoma component was identified in the primary tumor or metastases after extensive sampling.
- Immunohistochemistry showed aberrant cytoplasmic and nuclear expression of β-catenin, focal CDX2 expression, and negativity for PAX8 and estrogen and progesterone receptors (ER/PR).
- Next-generation sequencing found a CTNNB1 pathogenic mutation (p.Ser37Phe, c.110C > T) with a variant allele frequency of 18.6%.
- Based on morphology, immunohistochemistry and NGS analysis, the diagnosis of pilomatrix-like high-grade endometrioid carcinoma was established.
Limitations: Single-patient case report — findings may not be generalizable.; No data presented on treatment given or therapeutic outcomes for this patient.; Follow-up and clinical outcome details are not reported in the abstract.; Unable to assess effectiveness of standard adjuvant therapies for this subtype from this report..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Human · observationalMechanismMixed resultsLimited evidenceTier 3 · early humann = 18
International journal of molecular sciences · Apr 2025
dedifferentiated endometrioid carcinomaendometrial cancer
This observational study analyzed 18 Japanese cases of dedifferentiated endometrioid carcinoma, with immunostaining on tumor components and whole-exome sequencing in three cases. The authors report that DDEC comprised 2.0% of endometrial cancers, had poor 5-year outcomes (PFS ≈40%, OS ≈30%), and that 66.7% of patients were mismatch repair deficient; they found differing mutation patterns between well-differentiated and undifferentiated components and suggest several targeted therapies could be relevant based on genetics.
Reported effects: incidence of DDEC among endometrial cancers 2% · 5-year progression-free survival 40% · +2 more
Key findings
- Incidence of DDEC was 2.0% among endometrial cancers.
- The 5-year progression-free survival for DDEC was approximately 40%.
- The 5-year overall survival for DDEC was approximately 30%.
- Immunohistochemistry indicated 66.7% of patients were mismatch repair deficient.
- The rate of p53 mutations in this series was higher than reported previously, and p53 mutations in undifferentiated components were associated with poor prognosis.
- Whole-exome sequencing (n = 3) showed different gene mutations and mutation signatures between well-differentiated and undifferentiated components.
- New genetic mutations in undifferentiated regions were uncommon in the three sequenced cases.
- Among the three sequenced cases: one showed homologous recombination deficiency, and the other two had MSI-high and hypermutator phenotypes.
- Authors suggest that immune checkpoint inhibitors, PARP inhibitors, and drugs targeting the p53 pathway may be therapeutically relevant to DDEC based on the genetic findings.
Limitations: Small overall sample size (18 cases); Whole-exome sequencing performed in only 3 cases; Observational, descriptive design with no interventional testing of suggested therapies; Single-country (Japanese) cohort which may limit generalizability; No functional validation of suggested therapeutic targets reported in the abstract.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Case reportMechanismInconclusiveLimited evidenceTier 3 · early humann = 2
Pathologica · Feb 2025 · case report (two cases)
corded and hyalinized endometrioid carcinomaendometrioid carcinomaendometrial carcinoma
This paper reports two human cases of high-grade corded and hyalinized endometrioid carcinoma (CHEC) that showed a "no specific molecular profile" (NSMP). Both tumors had a markedly atypical, mitotically active corded component merging with FIGO G3 endometrioid carcinoma and squamous/morular differentiation, and both showed nuclear β-catenin accumulation, retained mismatch repair protein expression, wild-type p53 pattern, and no POLE mutations. The authors note heterogeneity in age and presentation (patients aged 25 and 81) and suggest these tumors be considered a variant of FIGO G3 endometrioid carcinoma.
Reported effects: number_of_cases 2 · tumor_size_case1 6 · +2 more
Key findings
- Both cases demonstrated a markedly atypical and mitotically active corded component merging with a FIGO G3 endometrioid component and accompanied by squamous/morular differentiation.
- Both tumors showed nuclear β-catenin accumulation, retained MMR protein expression, wild-type p53 pattern, and no POLE mutations.
- Case #1 was a 6-cm endometrial mass in a 25-year-old woman, infiltrating the deep myometrium and cervical stroma, with diffuse lymphovascular space invasion.
- Case #2 was an advanced, unresectable endometrial carcinoma involving the lower third of the vagina in an 81-year-old woman.
- The corded component was absent in the hysterectomy specimen of case #1 and in the vaginal biopsy specimen of case #2.
- Authors conclude these cases expand the clinical and molecular heterogeneity of high-grade CHEC and suggest considering them as a variant of FIGO G3 endometrioid carcinoma.
Limitations: Very small sample size (two cases) — case report-level evidence.; Descriptive pathology series without systematic follow-up or outcome data reported in the abstract.; No control or comparison group.; Methods for molecular testing (e.g., POLE testing) and detailed molecular data are not provided in the abstract.; Findings may not be generalizable..
Pathology case report that expands the morphological and molecular spectrum of high-grade corded and hyalinized endometrioid carcinoma (CHEC) by describing two human cases with NSMP.
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Case reportMechanismInconclusiveLimited evidenceTier 3 · early humann = 2
International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists · Jan 2025 · Case report (2 cases)
Endometrial carcinomaCarcinosarcomaEndometrioid carcinoma
The authors report two cases that were morphologically suspicious for endometrial carcinosarcoma but did not meet essential diagnostic criteria. Molecular testing identified pathogenic POLE mutations in both cases, and the tumors were described as low-grade endometrioid carcinomas with a homologous sarcoma component. The report questions the existence of a true POLE-mutated carcinosarcoma entity.
Key findings
- Two cases had morphologic suspicion for endometrial carcinosarcoma but lacked essential criteria for that diagnosis.
- Pathogenic POLE mutations were detected on molecular testing in both cases.
- A descriptive diagnosis rendered was endometrial endometrioid carcinomas, low-grade, with a homologous sarcoma component.
- These observations challenge the existence of POLE-mutated 'carcinosarcoma.'
Limitations: Very small sample size (2 cases).; Case report design without a systematic series or controls.; No clinical follow-up, treatment, or outcome data reported in the abstract.; Abstract provides limited pathological and methodological detail..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed
Human · observationalMechanismReported positiveModerate evidenceTier 3 · early humann = 122
Histopathology · Nov 2024 · immunohistochemical analysis of a cohort of human tumours (122 cases) including STK11 adnexal tumours and morphological mimics
STK11 adnexal tumourovarian neoplasmsovarian endometrioid carcinomatubo-ovarian high-grade serous carcinomaovarian mesonephric-like adenocarcinomaovarian carcinosarcomaperitoneal malignant mesotheliomapelvic plexiform leiomyomaovarian solid pseudopapillary tumourgranulosa cell tumourSertoli-Leydig cell tumourLeydig cell tumourSertoli cell tumoursteroid cell tumourfemale adnexal tumour of Wolffian originextra-ovarian sex cord-stromal tumour
Researchers performed STK11 (LKB1) immunohistochemistry on 122 human tumour samples, including 17 STK11 adnexal tumours and 105 morphological mimics. All 17 STK11 adnexal tumours showed complete loss of cytoplasmic STK11 staining. Nearly all other tumour types retained cytoplasmic STK11 staining, with the exception of one endometrioid carcinoma with mucinous differentiation showing complete loss and one high-grade serous carcinoma showing subclonal loss. The authors conclude STK11 IHC is a highly sensitive and specific marker for distinguishing STK11 adnexal tumour in the appropriate morphological context and could obviate confirmatory molecular testing.
Reported effects: total tumours tested 122, n=122 · STK11 adnexal tumours included 17, n=17 · +3 more
Key findings
- IHC for STK11 was performed on 122 tumours, including 17 STK11 adnexal tumours and 105 morphological mimics (full list of mimics given in abstract).
- All STK11 adnexal tumours showed complete loss of cytoplasmic staining for STK11.
- All other tumour types showed retained cytoplasmic staining, except for one endometrioid carcinoma with mucinous differentiation which showed complete loss of STK11 expression and a high-grade serous carcinoma with subclonal loss.
- Authors conclude STK11 IHC is a highly sensitive and specific immunohistochemical marker for distinguishing STK11 adnexal tumour from histological mimics and may obviate the need for confirmatory molecular studies in the appropriate morphological context.
Limitations: Small number of STK11 adnexal tumours (n=17), reflecting rarity of the entity.; Study reports a single cohort with no external validation cohort mentioned in the abstract.; Potential selection bias because tumour types were a selected set of morphological mimics.; Abstract does not report blinding, interobserver reproducibility, or diagnostic performance statistics (sensitivity/specificity values) beyond descriptive counts.; Two non-STK11 tumours showed loss/subclonal loss of STK11, indicating imperfect specificity in this cohort..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismMixed resultsLimited evidenceTier 3 · early humann = 289
British journal of cancer · Nov 2024 · multi-omics molecular profiling of tumor cohort (targeted DNA sequencing, RNA sequencing, DNA methylation array, SNP array) with unsupervised clustering
ovarian high-grade endometrioid carcinoma (HGEC)ovarian high-grade serous carcinoma (HGSC)endometrial high-grade carcinoma
The authors performed multi-omics profiling (DNA/RNA sequencing, methylation, SNP arrays) of ovarian high-grade endometrioid and serous carcinomas from the JGOG-TR2 cohort and analyzed public TCGA data. They identified four copy-number-based tumor groups (C1–C4); one group (C4, denoted 'HGEC-type') showed endometrium-like methylation, lack of BRCA1/2 alterations and CCNE1 amplification, low HRD scores, and more favorable prognosis.
Reported effects: JGOG-TR2 HGEC sample count 15 · JGOG-TR2 HGSC sample count 274 · +6 more
Key findings
- Unsupervised clustering using copy number signatures identified four distinct tumor groups (C1, C2, C3 and C4).
- C1 (n = 41) showed CCNE1 amplification and poor survival.
- C2 (n = 160) and C3 (n = 59) showed high BRCA1/2 alteration frequency with low and moderate ploidy, respectively.
- C4 (n = 22) was characterized by favorable outcome, higher HGEC proportion, no BRCA1/2 alteration or CCNE1 amplification, and low levels of HRD score, ploidy, intra-tumoral heterogeneity, cell proliferation rate, and WT1 gene expression.
- C4 exhibited a normal endometrium-like DNA methylation profile and was defined as 'HGEC-type' tumors, which were also identified in TCGA-OV and TCGA-UCEC.
Limitations: Observational, cross-sectional molecular profiling without interventional or functional validation.; Relatively small number of HGEC samples in the primary cohort (15 HGEC samples) and small size of the C4 subgroup (n = 22).; Prognostic associations are reported but the abstract does not detail adjustment for potential clinical confounders or independent validation beyond TCGA re-analysis.; No therapeutic implications or prospective clinical validation provided in the abstract..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed · Full text
Human · observationalMechanismReported positiveLimited evidenceTier 3 · early human
Pathology, research and practice · Oct 2024 · Laser microdissection and RNA sequencing comparing EC with the MELF pattern; generation of MSLN-knockout and -knockdown endometrioid carcinoma cell lines for functional assays; immunohistochemical analysis of clinical tumor samples and comparison of blood CA125 levels.
endometrioid carcinomaendometrial neoplasms
The authors found mesothelin (MSLN) expression was predominant in endometrioid carcinoma cases with the MELF pattern. In cell-line experiments, MSLN promoted cell migration and epithelial–mesenchymal transition and regulated cadherin-6 (CDH6); CA125 was shown to regulate CDH6 via MSLN. Immunohistochemistry and blood measurements showed higher MSLN, CA125, and CDH6 in tumors with the MELF pattern.
Key findings
- MSLN was predominantly expressed in endometrioid carcinoma cases with the MELF pattern identified by laser microdissection and RNA sequencing.
- MSLN promoted migration and epithelial-mesenchymal transition (EMT) in MSLN-knockout and -knockdown endometrioid carcinoma cell lines.
- Cadherin-6 (CDH6) expression was regulated by MSLN.
- CA125 can regulate CDH6 expression via MSLN.
- Immunohistochemical analyses showed MSLN, CA125, and CDH6 expression levels were considerably elevated in endometrioid carcinoma with the MELF pattern.
- CA125 expression in tumors paralleled MSLN in staining intensity and also matched blood CA125 level patterns reported.
Limitations: Abstract does not report sample sizes for the clinical/immunohistochemical analyses.; Mechanistic functional data derive from cell-line (in vitro) knockout/knockdown models, not from in vivo models.; Correlative immunohistochemical findings do not prove causation in human tumors.; No clinical outcomes or intervention trial data are reported to link MSLN expression to patient prognosis or therapy response..
AI summary of the abstract, human-reviewed · Jun 2026. Describes what this study reported, not medical advice. View on PubMed