Endometrial cancer (EC) development is driven by the interaction between the tumor and the microenvironment. However, the immune microenvironment dynamics during this process are not clear. Here, we applied single-cell RNA sequencing (scRNA-seq) to uterine blood samples collected at hysterectomy from 15 individuals encompassing four groups-benign controls, endometrial intraepithelial neoplasia (EIN), the transition from EIN to carcinoma, and EC. Uterine blood, obtained without prior enrichment, provides a liquid biopsy of the local tumor milieu, enabling high-resolution profiling of both immune and stromal cells in a minimally invasive manner. Our analysis revealed simultaneous immune and stromal remodeling in early premalignant lesions. Notably, even in EIN, we observed significant immune cell reprogramming alongside the emergence of protumorigenic stromal-epithelial interactions. Importantly, we discovered predictive single-cell transcriptomic signatures derived from neutrophils that stratify patients according to disease state, highlighting the potential of tumor-educated innate immune cells as biomarkers. These findings yield candidate cellular and molecular signatures, particularly from neutrophils, that could enhance early EC detection and guide therapeutic strategies. Our work provides a proof-of-concept for leveraging local liquid biopsies in single-cell oncology, offering new insights into EC initiation and development, paving the way for noninvasive diagnostics on the basis of single-cell transcriptomic profiles.

Lymphovascular invasion (LVI) is a prognostic and treatment-driving parameter for low-stage, low-grade endometrial endometrioid adenocarcinoma (EEAC). There is lack of organizational recommendations/guideline consensus regarding the clinically significant cutoff and pathologist agreement on cutoff thresholds has not been extensively studied. Digitized unannotated tumor-containing slides from 52 low-grade/uterine corpus-confined EEAC of no specific molecular profile (NSMP) and mismatch repair-deficient (MMRd) molecular subgroups were reviewed by 6 gynecologic pathologists. The reviewers, blinded to the originally reported LVI status, independently evaluated for the presence of LVI and the maximum number of involved vessels in a single slide or slides, per case. To quantify inter-rater reliability, intraclass correlation coefficient (ICC) estimates and their 95% confidence intervals were calculated (ICC<0.5=poor, 0.5 to 0.75=moderate, and 0.75 to 0.9=good and >0.9=excellent). A total of 280 slides were evaluated. The overall inter-rater reliability for the presence of LVI was moderate (ICC=0.53) and was slightly higher in the MMRd (ICC=0.56) compared with NSMP (ICC=0.52) group. For specific quantification of LVI, the overall inter-rater reliability was also moderate (ICC=0.71) and higher in the MMRd (ICC=0.76) compared with NSMP (ICC=0.69) group. Perfect agreement (6/6 reviewers with same assessment) only occurred for designations of no LVI or ≥5 involved vessels. There was a moderate level of inter-rater reliability that was not significantly affected by shifting the cutoff of involved vessels (from 3 to 4 to 5). Since a specific cutoff has no apparent bearing on the most reproducible cutoff for pathologists, future efforts should be directed towards obtaining clinical consensus for reporting purposes.

Introduction: Endometrial carcinoma is the most common invasive cancer of the female genital tract. Serous carcinoma of endometrium is highly aggressive and has a predilection for deep myometrial and lymphovascular invasion, peritoneal and distant metastatic spread. HER2/neu is an important prognostic protein in high-grade and higher-stage endometrial serous carcinomas Aim: To study the expression of HER2/neu in relation to tumour grade in endometrial carcinoma. Materials and Methods: The present cross-sectional study was conducted in the Department of Pathology, Government medical college, Thrissur, Kerala, India, over a period of 18 months from 1st January 2018 to 30th June 2019. A total of 63 cases of both hysterectomy specimens and endometrial biopsies whose histopathologic diagnosis was endometrial adenocarcinoma were included. Four micrometer thick sections were obtained for Haematoxylin and Eosin (H&amp;E) and immunohistochemical staining with rabbit monoclonal HER2 antibody following antigen retrieval was done. H&amp;E staining was done to assess the tumour grade. HER2/neu staining was evaluated using regular light microscope at the magnification of 40x. The Immunohistochemistry (IHC) score was determined by evaluating subcellular localisation, circumferential versus incomplete staining, intensity and the percentage of cells positive. Intensity of HER2 expression was graded according to the 2014 American Society of Clinical Oncology/College of American Pathologist (ASCO/CAP) guidelines for HER2 reporting. Data thus obtained was analysed using software Statistical Package for Social Sciences (SPSS) version 20.0. The statistical test used is the Fisher’s-exact test and p-value&lt;0.05 was considered statistically significant. Results: Most of the patients were in the age group of 51-60 years (23 out of 63 patients, 36.50%). Among the 63 patients seven were nulliparous and 56 were post menopausal women. Most of the patients presented with complaints of post menopausal bleeding which was noted in 85.71% of patients (54 out of 63). More than half of myometrial invasion was noted in 33 cases of hysterectomy specimens. HER2 positivity (score 2 and score 3) was observed in 7 (11.11%) cases. None of the grade 1 endometrial carcinoma showed HER2 positivity. Grade 2 endometrial carcinoma showed HER2 positivity in 1 (6.67%) case. Grade 3 tumours showed HER2 positivity in 6 (28.57%) cases. Compared to grade 1 and grade 2 endometrial carcinoma, grade 3 endometrial carcinoma showed increased HER2 expresssion. A statisticaly significant association between HER2 expression and tumour grade was obtained (p-value=0.004). Conclusion: As tumour grade in endometrial adenocarcinoma increases expression of HER2/neu also increases. A statistically significant association between HER2 expression and tumour grade was obtained (p-value=0.004). The study suggests that endometrial carcinoma shows HER2/neu expression in significant proportion of cases and its expression is more in highgrade endometrial carcinoma. Patients with HER2/neu positive endometrial carcinoma may benefit from adjuvant HER2/neu targeted therapies like trastuzumab. Further clinical studies are necessary to establish the prognostic and therapeutic significance of HER2/neu in endometrial adenocarcinoma.

Correspondence on “Long-term oncological and reproductive outcomes following treatment with the levonorgestrel intrauterine device for endometrial hyperplasia and adenocarcinoma – Results from the feMMe phase 2 randomized clinical trial” by Baxter et al.

Pre-operative endometrial assessment may be discordant with final pathology. We sought to determine the outcome of discordant cases. We identified patients who had primary surgical treatment of stage I endometrioid endometrial carcinoma found on final hysterectomy specimen from January 1, 2000, to December 31, 2020. We collected relevant patient, clinical, and pathologic characteristics and defined low grade as cases with pre-operative grade 1 or 2 tumors and concordant final pathology, and high grade as cases with pre-operative grade 3 tumors and concordant final pathology. We defined discordant as cases with a high-grade histology on pre-operative biopsy, inclusive of non-endometrioid histology, and grade 1 or 2 on final pathology. We compared clinicopathologic characteristics and used Kaplan-Meier survival estimates to compare outcomes between groups. Overall, 2936 patients were included: 2606 (89%) low grade, 247 (8%) high grade, and 83 (3%) discordant. Five-year progression-free survival was 95.1% for low-grade, 86.9% for discordant, and 86.0% for high-grade tumors (p <.001). Five-year overall survival was 95.0% for low-grade, 93.4% for discordant, and 85.7% for high-grade tumors (p <.001). After adjusting for age, myometrial invasion, lymphovascular space invasion, washings (progression-free survival), performance of nodal dissection (overall survival), and adjuvant therapy, discordant cases were not independently associated with progression-free survival (hazard ratio 1.82, 95% confidence interval 0.71 to 4.65), and only high-grade tumors were independently associated with worse overall survival. The clinical behavior of stage I endometrioid endometrial carcinoma diagnosed as high grade on pre-operative biopsy and low grade on subsequent hysterectomy seems to differ from cases diagnosed as low grade on both pre-operative and final pathology. Further analyses and larger series will be needed to better clarify this question. Both pre-operative and final hysterectomy results should be considered along with age, myometrial invasion, and lymphovascular space invasion when counseling patients regarding prognosis and need for adjuvant therapy.

Objective: To determine the frequency and clinicopathological features of incidental premalignant and malignant gynecological lesions detected after hysterectomies performed for benign indications, and to identify associated risk factors. Methodology: This retrospective study reviewed 1,047 hysterectomies performed for benign conditions at a tertiary center in Ankara, Turkiye, over a ten years period (January 2006-December 2015). Demographic characteristics, preoperative assessments, surgical indications, and histopathological outcomes were analyzed. Incidental lesions were defined as pre-malignant or malignant pathologies identified postoperatively without prior clinical suspicion. Statistical analyses were performed using chi-square and t-tests. Results: Incidental pre-malignant or malignant lesions were identified in 6% (n=63) of cases, including cervical dysplasia/HSIL (0.9%), borderline ovarian tumors (1.1%), endometrial adenocarcinoma (0.5%), leiomyosarcoma (0.5%), and high-grade serous ovarian carcinoma (0.6%). Postmenopausal women had a significantly higher incidence than premenopausal women (9.2% vs. 3.8%, p&lt;0.001). Patients with incidental findings were older than those with benign pathology (55.4 ± 11.2 vs. 52.7 ± 9.6 years, p=0.034). Larger myomas were associated with uterine sarcoma (172 ± 92 mm vs. 71 ± 39 mm, p&lt;0.001). Ovarian malignancies were detected in 2.4% of cases without suspicious ultrasound features and in 14.8% of cases with ≥2 malignancy criteria (p=0.013). Serous tubal intraepithelial carcinoma (STIC) was identified in 0.28% (n=3). Conclusion: Incidental pre-malignant or malignant lesions were present in 6% of hysterectomies performed for benign indications. Age, menopausal status, myoma size, and suspicious imaging features were significant predictors. Preoperative evaluation may not completely exclude the possibility of occult pathology; therefore, this risk should be discussed during preoperative counseling.

Painless jaundice in elderly patients typically suggests primary pancreaticobiliary malignancy, but metastatic disease to the periampullary region represents an uncommon yet important differential diagnosis that can present with identical clinical features. We present a case of a 65‐year‐old woman with a history of Stage IIIB endometrial adenocarcinoma with known pelvic and mesenteric metastases, previously treated with salvage chemotherapy, who presented with 3 days of progressive painless jaundice, dark urine, and a year‐long history of worsening diarrhea with significant weight loss. Laboratory evaluation revealed a cholestatic pattern of liver injury (total bilirubin 8.1 mg/dL and alkaline phosphatase 862 U/L), and imaging demonstrated new intra‐ and extrahepatic biliary ductal dilation with a spiculated duodenal mass infiltrating the ampulla and pancreatic head, along with bilateral hydroureteronephrosis from pelvic disease. Endoscopic retrograde cholangiopancreatography confirmed an infiltrative ampullary mass with successful biliary stent placement for decompression, resulting in improvement of hyperbilirubinemia. This case demonstrates that metastatic endometrial carcinoma can present as painless obstructive jaundice through duodenal and ampullary involvement, closely mimicking primary pancreatic adenocarcinoma both clinically and radiographically. Recognition of atypical metastatic patterns is essential for appropriate oncologic management, as treatment strategies and prognosis differ significantly between primary pancreaticobiliary malignancy and metastatic disease.

Preferentially expressed antigen of melanoma (PRAME) is a cancer antigen with limited expression in normal tissues and has emerged as a diagnostic and immunotherapeutic target for certain types of cancer. While originally utilized in the evaluation of melanocytic neoplasms, PRAME immunohistochemistry (IHC) has since shown diagnostic utility in a wide range of epithelial and mesenchymal tumors. In gynecologic pathology, PRAME expression has been reported in endometrial and tubo-ovarian carcinomas, with more limited expression in cervical tumors. Data from The Cancer Genome Atlas (TCGA) has shown increased PRAME mRNA expression in gynecologic malignancies, with the highest frequency observed in uterine corpus endometrial carcinoma (UCEC), uterine carcinosarcoma (UCS), and ovarian serous cystadenocarcinoma (OV), and lower levels in cervical tumors. Based on these preliminary data, we evaluated PRAME nuclear expression by IHC in endocervical, endometrial, and tubo-ovarian precursor lesions and carcinomas. We assessed PRAME mRNA expression across 33 TCGA tumor types using the Broad GDAC and TIMER2.0 databases. Expression levels in UCEC, UCS, OV, and cervical and endocervical cancers (CESC) were evaluated using predefined specificity filters. PRAME IHC was performed on 158 gynecologic lesions, including 90 endometrial lesions [84 carcinomas and 6 endometrial intraepithelial neoplasia (EIN)], 34 endocervical adenocarcinomas, and 34 tubo-ovarian carcinomas. PRAME positivity was defined as moderate to strong nuclear staining in >25% of tumor cells. In-depth mRNA analysis from TCGA revealed significantly higher PRAME expression in UCEC, UCS, and OV compared with cervical and other solid tumors (P<0.001). By IHC, PRAME was positive in all endometrial lesions (90/90; 100%) and most tubo-ovarian carcinomas (28/34; 82%), while negative in 94% (32/34) of endocervical adenocarcinomas (P<0.001). PRAME was mostly negative in squamous lesions and benign cervical tissue, but strongly and diffusely positive in benign endometrium. Sensitivity and specificity for distinguishing endometrial versus endocervical adenocarcinoma were 100% and 94%, respectively. In conclusion, PRAME demonstrates strong concordance between protein and mRNA expression in endometrial and tubo-ovarian carcinomas, showing minimal expression in endocervical adenocarcinomas. PRAME nuclear expression is highly sensitive and specific for carcinomas of endometrial and tubo-ovarian origin, with minimal expression in endocervical adenocarcinomas and ovarian mucinous carcinomas. PRAME IHC may be an adjunct tool to determine the site of origin in gynecologic carcinomas of uncertain primary.

A 13-y-old Vietnamese Pot-bellied sow (Sus scrofa) was presented because of blood-tinged mucoid vulvar discharge of 5-d duration and a 4-mo history of intermittent coughing and weight loss. Computed tomography revealed diffuse, multilobulated cystic and mineralized uterine masses, numerous lung nodules, and abdominal lymphadenopathy. Malignant neoplasia was suspected. Gross and histologic findings were diffuse cystic endometrial hyperplasia and endometrial adenocarcinoma of the mid-body of the left uterine horn. Metastatic foci were evident in the lungs, liver, and spleen. Neoplastic cells were immunoreactive for pan-cytokeratin. Metastatic endometrial adenocarcinoma and diffuse cystic endometrial hyperplasia have not been previously reported antemortem using computed tomography in a sow, to our knowledge.

Background: Currently, there are no accurate clinical biomarkers for the management of patients diagnosed with endometrial cancer. The biomarker HE4 is often overexpressed and found to be elevated in the serum of patients with endometrial cancers. Objective: The objective of this trial was to assess the utility of HE4 as a biomarker for monitoring patients with endometrial cancer.Methods: This was an IRB-approved trial utilizing residual serial serum samples from patients diagnosed with endometrial cancer. Clinical status was determined by a combination of physician assessment, physical exam, serum CA125 levels, and imaging. Two separate analyses were performed to assess changes in HE4 serum levels. The first method used a change of 25% over that of the previous serum HE4 value, and the second analysis employed a velocity of change calculation of serum HE4 levels over time.Results: A total of 92 patients providing 799 serum samples were identified for analysis. Using a ≥25.0% increase of serum HE4 levels as an indicator of disease recurrence or progression, HE4 had an accuracy of 81.9% and a negative predictive value of 91.4%. The velocity of change analysis an accuracy of 85.4% with a negative predictive value of 86.7%.Conclusion: HE4 is highly accurate for detecting disease recurrence or progression and is a valuable clinical tool for monitoring patients with endometrial cancer.

Atypical endometrial cells (AEMc) detected in cervical cytology are uncommon yet significantly associated with an elevated risk of precancerous and malignant lesions. Nevertheless, limited data are available on the histopathological correlation of AEMc cases. This study aims to evaluate the immediate histological outcomes in women diagnosed with AEMc and to assess how HPV status and patient age influence oncogenic potential. A retrospective analysis was conducted on 163 women diagnosed with AEMc at the International Peace Maternity and Child Health Hospital between January 2019 and December 2023. Each patient underwent liquid-based cytology (LBC) and high-risk HPV (hrHPV) testing for 14 genotypes, followed by histological evaluation within six months after the cytological assessment. Among the 163 AEMc patients, 86.5% (141/163) were classified as AEMc-not otherwise specified (NOS) and 13.5% (22/163) as AEMc-favor neoplasia (FN). Histological analysis indicated that 2.5% (4/163) had precancerous lesions and 12.9% (21/163) had cancer. Immediate pathological severity was significantly higher in AEMc-FN than in AEMc-NOS (p = 0.015), with endometrial carcinoma more prevalent in AEMc-FN (27.3% vs. 9.9%, p = 0.037; odds ratio 3.30, 95% CI: 1.11–9.79). The diagnostic accuracy of AEMc-FN for endometrial carcinoma was 81.6% (95% CI: 74.8%–87.3%). hrHPV status did not reliably predict cancer risk stratification in AEMc, however, age was significantly associated with disease severity. Compared with younger patients, those aged > 65 years showed a markedly higher prevalence of high-grade endometrial glandular abnormalities (AEH +) and adenocarcinoma (AC) (p = 0.001 and p = 0.000401, respectively). With an age cutoff of 45 years, older AEMc patients had an increased prevalence of AEH + and AC, a trend also evident in the AEMc-NOS subgroup. Women aged ≥ 45 years, especially those classified as AEMc-NOS, exhibit a substantially higher risk of high-grade endometrial glandular lesions, underscoring the need for more vigilant follow-up. Given the significantly higher prevalence of endometrial carcinoma in AEMc-FN patients compared to AEMc-NOS patients, it may be advisable for cytopathologists to annotate the presence or absence of “favor neoplasia” when diagnosing AEMc. Refining the diagnostic criteria for AEMc-FN may facilitate earlier detection of endometrial cancer.

1045 SOX17 Stays Strong: Near-Universal Expression in Endometrial Endometrioid Adenocarcinoma Challenges Its Suggested Prognostic Significance

1062 Histologic Review of Nuclear Grade in Endometrioid Endometrial Adenocarcinomas Stratified by Molecular Subtype

Estrogen receptor-negative (ER-negative) endometrial carcinomas represent an emerging and historically underrecognized diagnostic concept encompassing a biologically aggressive and heterogeneous subset of endometrial cancers. Although loss of ER expression is increasingly recognized as an adverse prognostic indicator, ER negativity alone is insufficient for precise classification and must be interpreted within a histotype-specific and molecularly informed context. In this commentary, we review the evolving role of ER negativity in endometrial carcinoma through an integrated morphologic, immunophenotypic, and molecular framework, emphasizing both pathogenetic insights and practical diagnostic considerations. We highlight specific high-grade ER-negative tumor entities that merit particular diagnostic attention, including endometrial gastrointestinal-type adenocarcinoma, pilomatrix-like high-grade endometrial carcinoma, mesonephric-like adenocarcinoma, endometrial clear cell carcinoma, and ER-negative high-grade carcinomas not otherwise specified. These tumors exhibit distinct morphologic features and marked molecular heterogeneity that cannot be captured by hormone receptor status alone. Key diagnostic clues and common pitfalls are discussed, underscoring a practical workflow in which ER negativity serves as a diagnostic signal rather than a terminal category. Improved recognition and subclassification of ER-negative endometrial carcinomas are essential for accurate diagnosis, prognostic stratification, and optimized clinical management.

Endometrial cancer significantly impacts women’s reproductive health and quality of life, with lymph node metastasis serving as a crucial prognostic factor. Given the low metastasis rate, not all early-stage patients require lymph node dissection. The NCCN upgraded Sentinel Lymph Node Biopsy (SLNB) technology to Class 2A evidence. However, the applicability of SLNB for Chinese patients remains uncertain. This study evaluates the efficacy and safety of SLNB in a Chinese population. A retrospective cohort study was conducted at Guangdong Provincial Hospital of Chinese Medicine from August 2019 to December 2022, involving 166 early-stage endometrial adenocarcinoma patients. Of these, 137 patients were assessed as moderate to high-differentiated endometrioid adenocarcinoma. Patients were divided into Sentinel Lymph Node Biopsy (SLNB, N = 43) and systematic lymph node dissection (SLND, N = 94) groups, with a median follow-up time of 39 (24, 55) months. Primary outcomes were postoperative disease progression-free survival and one-month complication rates, with secondary endpoints including surgical parameters and quality of life indicators. During the follow-up(median follow-up time 39 months), 1 recurrence occurred in the SLNB group, with no recurrences in the SLND group. Sentinel Lymph Node Biopsy (SLNB) showed no statistically significant differences compared with traditional Sentinel Lymph Node Dissection (SLND) in oncological assessment, with no significant variations in postoperative pathological staging (β = 0.80, 95%CI: -1.29 to 2.90, p = 0.455), pathological grading (β = -0.115, 95%CI: -0.99 to 0.76, p = 0.800), and additional treatment evaluation (β = -0.214, 95%CI: -1.52 to 1.09, p = 0.749), with one recurrence in the SLNB group during follow-up. SLNB significantly improved surgical indicators: operation time reduced by 85.13 min (p < 0.001), blood loss decreased by 44.82 ml (p < 0.001), hospital stay shortened by 1.19 days (p = 0.030), with significantly lower postoperative day 1 pain scores. At 6 h post-surgery, both groups showed significant BADL decline (β = -21.53, 95%CI: -25.7 to -17.4, p < 0.001), with less functional impairment in the SLNB group and significantly shorter urinary catheter placement time (β = + 1.24, 95%CI: 0.90 to 1.59, p < 0.001). Complication analysis revealed significantly higher rates of lymphatic reflux obstruction (β = 18.22, 95%CI: 17.38 to 19.05, p < 0.001) and intestinal obstruction (β = 18.17, 95%CI: 16.16 to 20.17, p < 0.001) in the SLND group, suggesting a marked advantage of SLNB in complication management. For early-stage endometrial cancer patients with moderate to high differentiation and lesions confined to the inner half of the myometrium, SLNB demonstrates safety and efficacy as a minimally invasive alternative, significantly improving surgical outcomes and patient prognosis.

Grade 3 Endometrial Adenocarcinoma: a Comparative Assessment of Clinicopathological and Immunohistochemical Features of Endometrioid and Serous Carcinoma

Metastatic Müllerian carcinomas, including endometrial and ovarian adenocarcinomas, are challenging to diagnose due to factors like similar malignancies, insufficient clinical history, multiorgan dissemination, and small tumor specimens. Immunohistochemistry (IHC) stains are commonly used to identify these cancers. PAX8 is a widely used IHC marker with varying sensitivity levels for different types of gynecologic carcinomas. SOX17, a transcription factor involved in embryonic differentiation and development, has high specificity for ovarian and endometrial carcinomas but is weakly expressed in other epithelial neoplasms. . 56 endometrial carcinomas cases,56 ovarian cancer case and 56 cases of non-gynecological cancer, were subjected to immunohistochemical (IHC) analysis of SOX17 and PAX8. In endometrial carcinomas, PAX8-high/SOX17-high co-expression strongly favored endometrioid histology (90% vs. 68.8%, p = 0.04), while ovarian high-grade serous carcinomas commonly expressed PAX8 (78.9% high) with heterogeneous SOX17 expression (47.4% high). Notably, double-negative PAX8/SOX17 status completely excluded Müllerian origin in metastases from colorectal, breast, and pulmonary primary tumors (100% specificity), though renal (all PAX8+) and thyroid neoplasms (63.6% PAX8+) required additional markers for distinction. Statistical analyses confirmed subtype-specific trends (p < 0.05 for all applicable comparisons) with loss of SOX17 associated with aggressive histotypes (25% negative in serous versus 10% in endometrioid). Müllerian carcinomas can be distinguished from non-gynecological metastases using PAX8 and SOX17 immunohistochemistry, with PAX8-high/SOX17-high patterns strongly indicating endometrioid differentiation and double-negative results excluding gynecologic origin with consistency in colorectal, breast, and pulmonary carcinomas. Renal and thyroid carcinomas are the diagnostic traps on the basis of PAX8 expression and require additional markers for final classification in metastatic workups.

Metachronous endometrial endometrioid adenocarcinoma following treated cervical squamous cell carcinoma: A rare second primary malignancy detected through routine post-radiation surveillance

Ovarian high-grade serous carcinoma and synchronous mesonephric-like endometrial adenocarcinoma: a case report and literature review

Background:Endometrial carcinoma arising from adenomyosis (EC-AIA) is remarkably uncommon, and its underlying molecular mechanisms are not yet fully elucidated. This knowledge gap is particularly significant given that most reported EC-AIA cases are well-differentiated and hormone receptor-positive, creating a critical need to characterize the rare, aggressive variants and their clinical implications.Objective:This study aims to address this gap by presenting a unique case of poorly differentiated endometrioid adenocarcinoma with adenomyosis, exploring their potential association, and to synthesize current understanding through literature review to inform clinical decision-making.Case presentation:A 45-year-old woman with a history of adenomyotic lesion resection presented with abnormal uterine bleeding. Postoperative pathology confirmed poorly differentiated endometrioid adenocarcinoma (International Federation of Gynecology and Obstetrics IIIC2 stage), with immunohistochemistry showing estrogen receptor/progesterone receptor (PR) negativity, p53 mutation pattern, and nonspecific molecular profile. Concurrent adenomyosis (0.6 cm) was identified, though direct histological transition between adenomyosis and carcinoma was not established. The patient underwent cytoreductive surgery and platinum-based chemotherapy.Discussion:Our analysis reveals that the relationship between adenomyosis and endometrial carcinoma remains debated. This case (characterized by high-grade histology, hormone receptor negativity, and widespread metastases) provides crucial evidence diverging from the classic EC-AIA profile (typically well-differentiated and hormone-sensitive), implying a distinct malignant transformation mechanism. These findings challenge the conventional understanding of EC-AIA and highlight the spectrum of its clinical presentations.Conclusion:This study underscores that the management of suspected malignant transformation of adenomyosis requires multidisciplinary evaluation. More importantly, our findings demonstrate that aggressive treatment should be initiated even without definitive pathological confirmation when clinical suspicion is high. The significance of this work lies in its contribution to recognizing the heterogeneous nature of EC-AIA, urging future research to focus on elucidating molecular mechanisms and developing personalized therapeutic strategies for these aggressive variants.