Search Results (215)

Immune remodeling within the tumor microenvironment (TME) influences the progression and clinical outcome of uterine corpus endometrial carcinoma (UCEC), but the contribution of chemokine-related regulatory genes remains incompletely characterized. This study aimed to evaluate the prognostic relevance of CXCL13 and its association with immune microenvironmental features in UCEC using publicly available transcriptomic and single-cell datasets. RNA-sequencing profiles and clinical annotations from 589 UCEC cases in The Cancer Genome Atlas (TCGA) were analyzed to assess TME composition using ESTIMATE (Estimation of Stromal and Immune cells in MAlignant Tumours using Expression data) and CIBERSORT (Cell-type Identification By Estimating Relative Subsets Of RNA Transcripts), followed by survival analysis, differential gene expression analysis, protein–protein interaction network construction, Cox regression, and gene set enrichment analysis. A public single-cell RNA-sequencing dataset from the Gene Expression Omnibus (GEO; GSE173682) was further used to infer the cellular sources of CXCL13. Elevated CXCL13 expression was associated with favorable overall survival and enrichment of immune-activation pathways. CIBERSORT-based analysis indicated that high CXCL13 expression correlated with increased estimated fractions of CD8⁺ T cells and plasma cells, together with transcriptional features related to tertiary lymphoid structure-associated immune activation, whereas several immunosuppressive cell populations showed lower estimated abundance. Single-cell analysis suggested that CXCL13 was mainly expressed by follicular helper T cells and exhausted CD8⁺ T cells. These findings indicate that CXCL13 may serve as a prognostic biomarker associated with an immune-active TME in UCEC. Further histological, spatial, and functional validation is warranted to confirm its mechanistic role and translational potential. Full article

Background and Objectives: Uterine metastasis from breast carcinoma is rare but poses substantial diagnostic and therapeutic challenges. Invasive lobular carcinoma (ILC) demonstrates a documented predilection for unusual metastatic patterns including the female genital tract, while tamoxifen-associated endometrial pathology may complicate diagnosis in breast cancer survivors. Materials and Methods: We performed a structured PubMed/MEDLINE and Google Scholar search (1980–2025) for cases with histologically confirmed breast primary and uterine involvement; a pooled analysis of demographic, histological, molecular, and clinical variables was performed. Results: 105 individual cases were identified. ILC accounted for 58.0% of histologically classified cases despite representing only 10–15% of breast cancers. Endometrial involvement was present in 68.6%, myometrial in 25.7%, and cervical in 26.7%. Tamoxifen exposure was strongly associated with polyp-substrate metastasis (29.3% vs. 4.7%; Fisher’s exact p = 0.0009; OR 8.41, 95% CI 2.20–32.14). Abnormal uterine bleeding was the dominant presentation (68.1%); 19.8% were asymptomatic. Median latency was 36 months (range from 24 months before to 360 months after the breast cancer diagnosis). Conclusions: Uterine metastasis from breast carcinoma is dominated by invasive lobular histology and frequently involves tamoxifen-associated polyps. A combined immunohistochemical panel (GATA3, TRPS1, E-cadherin, hormone receptors, PAX8) is essential for distinguishing metastatic disease from primary uterine pathology. Endometrial sampling should be considered with a low threshold in breast cancer survivors with abnormal uterine bleeding, and breast imaging is warranted when discohesive cells are encountered without a known breast primary. These proportions describe the published case literature rather than population-based prevalence; because the evidence is limited to case reports and small series, they should not be read as the true frequency of uterine involvement among women with breast cancer. Full article

Background: Metastases to the uterine cervix from extragenital malignancies represent uncommon clinical events, with breast invasive lobular carcinoma (ILC) documented as the predominant primary source in reported literature. Objectives/Aim: To characterize the clinicopathologic features of ILCs metastatic to the uterine cervix. Methods: We performed a PubMed search using several keywords. Results: A total of 29 studies were included in the final analysis. The mean age at presentation of cervical metastasis was 56.8 ± 2.0 years. The mean interval between the initial diagnosis of ILC and the detection of cervical metastasis was 55.6 ± 8.2 months. Clinical presentations included vaginal bleeding, pelvic pain, and unhealthy enlarged, indurated uterine cervix on local examination. The diagnosis was established via tissue biopsy and immunohistochemical stains (positive reactivity for CK7, ER, PR, E-Cadherin, GATA3, GCDP-15 and mammaglobin). There are no consensus treatment protocols, and therapy should be tailored individually based on the extent of disease. Combined surgical and systemic therapy was the most commonly used modality. Conclusions: Metastasis of breast ILCs to the uterine cervix poses a significant diagnostic challenge. A high index of clinical suspicion and detailed clinical history are essential for accurate diagnosis. Full article

Background/Objectives: Ultrasound elastography (UE) is a non-invasive imaging technique that evaluates tissue stiffness and may complement conventional ultrasound in the assessment of uterine diseases. This systematic review aimed to summarize the current evidence on the role of strain elastography (SE) and shear wave elastography (SWE) in the diagnosis and management of benign and malignant uterine pathologies. Methods: A systematic literature search of MEDLINE (PubMed) and Embase was performed to identify studies published between January 2018 and February 2026. Original studies evaluating UE in adenomyosis, uterine fibroids, cervical lesions, and endometrial pathologies were included. Data were qualitatively synthesized according to pathology type and elastographic technique. Results: Twenty studies met the inclusion criteria. In benign myometrial disorders, adenomyosis and uterine fibroids generally showed higher stiffness than normal myometrium, although differentiation between these entities was not always consistent across studies. In cervical disease, malignant and high-grade lesions typically demonstrated increased stiffness compared with benign or low-grade lesions. In endometrial pathology, endometrial carcinoma was generally associated with higher stiffness values than benign lesions and elastography also showed potential in assessing myometrial invasion. Across studies, UE demonstrated promising diagnostic performance, but substantial heterogeneity was observed in acquisition methods, parameters, and reported thresholds. Conclusions: UE appears to be a promising adjunct to conventional ultrasound for the evaluation of uterine pathologies. However, further standardized, large-scale studies are needed to define reproducible protocols and clinically applicable diagnostic thresholds. Full article

Background/Objectives: Ciliated epithelial change in endometrial lesions is a recognized morphologic finding, but its immunophenotypic correlates and biological significance remain insufficiently defined. We investigated whether endometrial lesions with ciliated epithelial change show reproducible immunohistochemical alterations across benign, premalignant, and malignant diagnostic categories. Methods: We performed a retrospective immunohistochemical study of 315 formalin-fixed paraffin-embedded eutopic uterine endometrial specimens (no endometriotic/ectopic lesions included) collected between 2019 and 2024 and distributed equally across seven diagnostic categories (n = 45 each): normal endometrium, endometrial polyp, hyperplasia with cystic/disordered glands, hyperplasia with crowded glands, atypical hyperplasia/EIN, endometrioid carcinoma, and serous carcinoma. Marker expression was quantified by digital image analysis and compared between lesions with and without ciliated epithelial change, including lesions with ciliated epithelial change showing cytological atypia. Results: Ciliated epithelial change (CEC) was identified in 86/315 cases (27.3%), including 41 cases (13.0%) with atypical CEC. In benign categories, lesions with CEC showed lower E-cadherin expression and higher β-catenin expression, including more frequent nuclear β-catenin localization. In carcinomas, these patterns were not recapitulated and instead showed an opposite or attenuated profile, supporting a context-dependent rather than linear model. Vimentin was consistently reduced in lesions with CEC across diagnostic categories. p53 and CD44 showed heterogeneous findings and were less informative than the adhesion- and phenotype-related markers. Conclusions: Endometrial lesions with CEC show reproducible, context-dependent immunohistochemical alterations, most consistently involving E-cadherin, β-catenin, and vimentin. In particular, nuclear β-catenin reactivity in this setting should not be interpreted as evidence of canonical Wnt-pathway activation in the absence of CTNNB1 sequencing or validated downstream readouts, and the carcinoma findings cannot be assigned to a specific TCGA/ProMisE molecular subgroup using immunohistochemistry alone. The observations should therefore be regarded as exploratory and warrant validation in studies incorporating molecular classification, direct ciliogenesis markers (FOXJ1, acetylated α-tubulin, basal body markers), and outcome data. Full article

Background: Endometrial carcinoma (EC) is now classified primarily by molecular subtype—POLE-ultramutated, mismatch repair–deficient (dMMR), TP53-mutant/copy-number-high (CNH), and “no specific molecular profile” (NSMP)—a framework that has reshaped prognostic counseling and adjuvant therapy decisions. Yet several practically important questions remain insufficiently addressed in real-world cohorts: whether all four mismatch repair genes confer an equivalent favorable prognosis, whether all POLE alterations carry the same survival benefit or only specific pathogenic variants, and whether molecular subtypes retain prognostic value after adjustment for histology and tumor burden. Methods: We addressed these questions in 2901 patients pooled from the MSK-IMPACT 50K Clinical Sequencing Cohort (n = 2372; discovery) and the TCGA UCEC PanCancer Atlas (n = 529; validation)—the largest dual-cohort genomic analysis of EC reported to date. We performed individual MMR gene and combined dMMR survival stratification, multivariable Cox regression adjusted for age, histology, and sample type, and a pathogenicity-aware sensitivity analysis for POLE variants, with tumor mutational burden (TMB) compared across subgroups. Results: Across both cohorts, all four MMR gene–mutant subgroups (MLH1, MSH2, MSH6, PMS2) conferred equivalently favorable overall survival (OS) (six-group log-rank p = 7.66 × 10⁻¹² in discovery; p = 6.78 × 10⁻³ in validation), confirming dMMR as a class-level prognostic designation independent of which MMR gene is altered. Multivariable Cox regression demonstrated that POLE-ultramutated status retained an independent favorable effect (HR = 0.62, p = 0.038 in MSK; HR = 0.35, p = 0.028 in TCGA) after adjustment for age, histology, and sample type, while the favorable dMMR effect was largely accounted for by histologic context. Critically, a pathogenicity-aware sensitivity analysis revealed that the exceptional survival of the POLE subgroup is confined to canonical exonuclease-domain hotspot mutations (event rate 0.9% in MSK), whereas POLE variants of uncertain significance behave indistinguishably from NSMP-like tumors. Consistent with this finding, TMB was markedly elevated in canonical pathogenic POLE cases (median 138.7 mut/Mb in MSK; 247.4 in TCGA) but not in POLE-VUS-only cases (median 29.0 and 15.0, respectively; p < 0.001 between groups in both cohorts), confirming that the ultramutator phenotype is confined to canonical pathogenic POLE variants. We additionally characterize Uterine Clear Cell Carcinoma as a distinct histologic entity (n = 73; 3.0%) and report the POLE + TP53 co-mutant group (n = 90; 3.8%). Conclusions: These findings refine the molecular classification of EC in clinically meaningful ways: they support class-level immunotherapy eligibility based on dMMR status regardless of the specific MMR gene altered, demonstrate that POLE-ultramutated classification requires variant-level pathogenicity assessment, and identify TP53-mutant/CNH patients as the population with the most urgent unmet therapeutic need. Full article

This study aimed to develop and validate a transcriptomic risk signature for uterine corpus endometrial carcinoma (UCEC) and to investigate whether the identified prognostic program reflects immune–tumor uncoupling within the tumor microenvironment. Using transcriptomic data from The Cancer Genome Atlas (TCGA) UCEC cohort, we identified a 28-gene transcriptomic signature defining a high-risk state. The derived risk score robustly stratified patients into distinct survival groups and remained an independent predictor of overall survival after adjustment for clinical covariates. Functional analyses revealed that high-risk tumors are characterized by a distinct immune–tumor uncoupling phenotype, in which interferon-gamma (IFNG)-associated inflammatory signaling is preserved but fails to translate into effective antitumor immune activity. Specifically, effector immune programs, including CD8 T cell-related signatures and cytotoxic activity, were consistently reduced despite elevated IFNG-associated signaling, indicating a functional discordance between immune activation and immune execution rather than classical T cell exhaustion. In parallel, high-risk tumors exhibited consistently elevated cell cycle and DNA repair-associated transcriptional programs, suggesting that proliferative and stress-adaptive mechanisms represent dominant drivers of poor prognosis. External assessment in an independent GEO cohort (GSE17025) demonstrated consistent associations between signature activity, tumor status, and histological grade, supporting the reproducibility of the underlying transcriptional program at the biological and clinicopathological level. Collectively, this study provides transcriptomic evidence for a previously underappreciated immune–tumor uncoupling state in UCEC and highlights the importance of integrating immune signaling and tumor-intrinsic programs to understand disease progression. Full article

Objectives: CD93, an angiogenesis-related transmembrane glycoprotein, is transcriptomically downregulated in uterine corpus endometrial carcinoma, yet circulating protein levels have not been clinically evaluated. This study aimed to evaluate serum CD93 as a diagnostic biomarker for EC and to examine its association with clinicopathological parameters. Methods: In this single-center case–control study, serum CD93 concentrations were measured by enzyme-linked immunosorbent assay in 46 patients with histologically confirmed primary EC and 35 controls with histologically verified benign gynecological pathology. Logistic regression and receiver operating characteristic (ROC) curve analyses were performed. Results: Serum CD93 was significantly lower in EC patients than controls (median 4.55 [IQR 3.51–6.97] vs. 10.24 [7.18–12.14] ng/mL; p < 0.001). In multivariable analysis adjusted for age and body mass index, lower CD93 remained independently associated with EC (OR = 0.521; 95% CI 0.061–0.720; p < 0.001). ROC analysis yielded an area under the curve of 0.845 (95% CI 0.759–0.921), with 82.6% sensitivity and 74.3% specificity at a cut-off of 7.338 ng/mL. CD93 levels showed no significant association with histological subtype, grade, lymphovascular space invasion, nodal metastasis, or recurrence. Conclusions: Serum CD93 is significantly reduced in EC and demonstrates independent diagnostic performance, supporting its prospective validation as a non-invasive biomarker in larger multicenter cohorts. Full article

Background/Objectives: Uterine serous carcinoma (USC) is an aggressive subtype of endometrial cancer characterized by high recurrence rates and poor response to conventional therapies, resulting in unfavorable clinical outcomes. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, has demonstrated anti-cancer activity in multiple malignancies. Methods: This study used two USC cell lines, ARK1 and SPEC2, to evaluate the effects of EPA on cell proliferation, invasion, cell cycle profile, stress response, and apoptosis. The potential synergistic effects of EPA combined with carboplatin were also examined. Western blotting was used to examine EPA’s effects on downstream pathways related to cellular stress, inflammation, and epithelial–mesenchymal transition (EMT). Results: EPA treatment markedly reduced cell proliferation and colony formation, with IC₅₀ values of 28.96 µM for ARK-1 cells and 14.96 µM for SPEC-2 cells compared with control groups. It also induced G1 phase cell cycle arrest, increased cellular stress, triggered caspase-dependent apoptotic cell death, and suppressed invasive capacity. Moreover, EPA effectively counteracted TNF-α-stimulated upregulation of COX-2 and phosphorylated NF-κB. The combined treatment with EPA and carboplatin resulted in synergistic inhibition of cell viability and migration. Western blotting analysis showed that EPA attenuates the NF-κB and AKT/mTOR signaling pathways, promotes the expression of cellular stress-related proteins, and inhibits the expression of EMT-related proteins in both cell lines. Conclusions: EPA exhibits potent anti-tumor activity against USC cells and enhances the efficacy of carboplatin. These data indicate that EPA has potential as a low-toxicity, multi-target adjuvant treatment for USC, necessitating additional pre-clinical and clinical investigation. Full article

Background: Primary endometrial lymphomas (PELs) are exceedingly rare and diagnostically challenging lesions. Objective: To assess the clinicopathologic features of PELs. Methods: We adhered to the PRISMA-2020 guidelines for reporting systematic reviews. A PubMed literature search (1956–2025) was conducted using keyword combinations including “endometrium” and “lymphoma,” “lymphoid proliferation,” or “lymphoproliferative lesions.” Only original articles published in the English peer-reviewed journals were considered. The inclusion criteria were: (i) studies involving human subjects, and (ii) studies published in the English language. Reviews, editorials, meeting abstracts, and non-English publications were excluded. Results: We identified 42 studies for our analysis, collectively reporting 58 cases of PELs. Abnormal uterine bleeding was the main complaint. Non-Hodgkin lymphoma (57 cases) and Hodgkin lymphoma (one case) were identified. In most cases, lymphoma was the sole lesion. In five cases, lymphoma coexisted with, preceded, or followed endometrial carcinoma. Histologically, PELs either diffusely involved the endometrium (50 cases) or were localized to endometrial polyps (eight cases). Marginal zone lymphoma (MZL) was the most frequently reported type, followed by diffuse large B-cell lymphoma (DLBCL). Other rare types included intravascular large B-cell lymphoma, NK/T-cell lymphoma, T-cell lymphoma, and low-grade B-cell lymphoma. Conclusions: Our study indicates that MZL and DLBCL were the most common types of PELs. Other extremely rare subtypes were also identified. Moreover, some PELs developed in the background of endometrial polyps and, in exceptional cases, in association with endometrial carcinoma. Radiological findings were critical for provisional diagnosis, staging, and follow-up. Key modalities included ultrasonography (US), computed tomography (CT), magnetic resonance imaging (MRI), and 18F-fluoro-2-deoxyglucose positron emission tomography/CT (18F-FDG PET/CT). Full article

Isolated pelvic nodal metastasis from carcinoma of unknown primary origin (CUP) is rare. Evaluation should prioritize gynecological and anorectal sites based on pelvic lymphatic drainage. Although spontaneous regression of these primary lesions is exceptional, regressed lesions can present as CUP, necessitating diagnostic caution. Here, we report the case of a 40-year-old woman with a solitary, intensely fluorodeoxyglucose F-18 avid left obturator lymph node and a subtle endocervical abnormality on pelvic magnetic resonance imaging. Loop electrosurgical excision revealed a Nabothian cyst only. Excisional nodal biopsy by polymerase chain reaction revealed metastatic squamous cell carcinoma with diffuse block-type p16 and human papillomavirus (HPV) 16. Considering the potential for a primary cervical tumor along the obturator drainage pathway, the patient underwent hysterectomy with pelvic lymph node dissection. No residual invasive carcinoma was found; however, HPV16 was detected in the cervix with a low-grade squamous intraepithelial lesion, supporting a regressed cervical focus. She received adjuvant cisplatin-based chemoradiotherapy and has remained disease-free for 56 months. This case highlights the diagnostic value of integrating lymphatic anatomy with the molecular profile of HPV. Cervical squamous cell carcinoma rarely regresses and presents solely as an isolated nodal disease. Full article

Background: CDKN2A (p16^INK4a^) is integral to the regulation of the RB–E2F cell-cycle checkpoint and is widely acknowledged as a surrogate marker for high-risk human papillomavirus (HPV)-related cervical neoplasia. Nevertheless, its diagnostic and prognostic significance in uterine corpus endometrial carcinoma (UCEC), a predominantly HPV-independent malignancy, remains inadequately characterized. This study utilized an integrated multi-omics approach to examine CDKN2A dysregulation in cervical squamous cell carcinoma (CESC) and UCEC. Methods: Pan-cancer and tumor–normal differential expression analyses were performed using TIMER2.0 and GEPIA2 (TCGA/GTEx). Clinicopathological correlations were assessed with UALCAN. Protein expression patterns were analyzed using immunohistochemistry data from the Human Protein Atlas (HPA). Prognostic significance and immune-infiltration associations were evaluated using TCGA survival data and TIMER modules. Independent transcriptomic validation and diagnostic classification performance were assessed using GEO datasets GSE9750 (CESC) and GSE63678 (UCEC), including ROC-AUC analysis with cross-validation. Results: Integrated analyses revealed elevated CDKN2A expression in both CESC and UCEC across multiple transcriptomic cohorts, with pronounced tumor-specific protein expression on immunohistochemistry. TCGA-only tumor–normal RNA comparisons were non-significant, likely due to limited normal sample representation. In independent GEO cohorts, CDKN2A exhibited excellent tumor–normal discrimination in CESC (AUC = 0.982) and moderate discrimination in UCEC (AUC = 0.761). Survival analysis indicated tumor-specific patterns, with limited prognostic stratification in CESC and context-dependent associations in UCEC. Immune-infiltration analysis suggested tumor-type-specific interactions between CDKN2A expression and immune cell subsets. Conclusions: CDKN2A exhibits strong diagnostic performance in HPV-associated cervical cancer and moderate, cohort-dependent discriminatory ability in endometrial carcinoma. These findings reinforce its established diagnostic role in CESC and propose adjunctive utility in UCEC, underscoring the importance of tumor-contextual interpretation of CDKN2A expression in gynecologic malignancies. Full article

Background: Uterine serous carcinoma (USC) represents a rare but aggressive subtype of endometrial cancer, accounting for a disproportionate number of disease-related deaths. Although molecular classification has improved risk stratification, prognostic heterogeneity highlights the need for new prognostic markers. Methods: We retrospectively analyzed 83 patients with USC treated at our institution between 1 January 2015 and 31 December 2023. Clinicopathological characteristics, treatment strategies, molecular biomarkers accessed by immunohistology (TP53, ER, PR, HER2, and MMR status), and survival outcomes were collected. Patients were first staged by FIGO 2009 and retrospectively reclassified by FIGO 2023. Disease-free survival (DFS), progression-free survival (PFS), and overall survival (OS) were assessed using Kaplan–Meier and Cox regression analyses. Results: The majority of patients were presented with advanced disease (FIGO stage IIIC-IV). TP53 mutations were found in 88% of cases, HER2 amplification in 18%, and ER expression in 57.8%. ER-positive patients showed significantly improved DFS in the adjuvant setting compared with ER-negative patients, whereas no significant associations were observed for first-line PFS or OS in multivariable analyses. HER2 amplification was not associated with inferior survival in our cohort. The advanced stage remained an independent predictor of worse OS. Conclusions: USC is a biologically heterogeneous disease, and its treatment should be guided by its molecular profile. ER expression identifies a subset of patients with improved DFS, suggesting potential prognostic relevance in this high-risk histology. Full article

Background and Objectives: Uterine FIGO grade 3 endometrioid carcinoma (EC) is an uncommon but aggressive subtype of endometrial cancer with limited biomarker data to guide prognosis and management. This study aimed to evaluate the prognostic significance of programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) expression in tumor tissue (TT) and tumor microenvironment (TME). Materials and Methods: We retrospectively analyzed tumor samples from 53 patients with FIGO grade 3 EC. Immunohistochemistry was performed to assess PD-1 and PD-L1 expression in TT and TME. Clinicopathological data including age, stage, lymph node invasion (LNI), lymphovascular space invasion (LVSI), depth of myometrial invasion (MI), adjuvant therapy, and survival outcomes were collected. Survival analyses were conducted using Kaplan–Meier and Cox proportional hazards models. Results: PD-1 expression was identified in 34% of TT and 41.5% of TME, while PD-L1 was expressed in 22.6% of TT and 34% of TME. Except for PD-1 in TME, positive expression of these immune checkpoint molecules correlated with significantly shorter survival (log-rank p < 0.05) outcomes. In univariate analysis, PD-1 and PD-L1 expression in TT, deep MI, LNI and LVSI were associated with adverse outcomes. Multivariate analysis confirmed PD-1 and PD-L1 positivity in TT as independent prognostic factors (PD-1: HR 3.2, 95% CI 1.4–7.0; PD-L1: HR 3.3, 95% CI 1.4–7.8). Patients with concurrent PD-1 and PD-L1 expression in TT showed the poorest overall survival, suggesting a cumulative negative effect. Conclusions: PD-1 and PD-L1 expression in tumor tissue are independent predictors of poor prognosis in FIGO grade 3 EC. These findings support their role as clinically relevant biomarkers and potential therapeutic targets. Incorporating checkpoint evaluation into routine pathological assessment could improve prognostic accuracy and guide treatment strategies, particularly in high-risk patients who might benefit from immunotherapy approaches. Full article

Background: Nuclear protein in testis (NUT) carcinoma is a rare, aggressive, and poorly differentiated epithelial malignancy characterized by the rearrangement of NUTM1 (NUT midline carcinoma family member 1) on 15q14. It primarily originates along the midline structures, including the head, neck, thorax, and mediastinum. Although NUT carcinoma of the pelvic gynecological organs is exceedingly rare, reported cases have been limited to primary or metastatic ovarian tumors. Here, we present the first documented case of primary uterine NUT carcinoma. Case presentation: A 53-year-old postmenopausal woman presented with abnormal uterine bleeding and a uterine mass. She underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The initial postoperative histopathological evaluation suggested undifferentiated endometrial sarcoma; however, subsequent immunohistochemical (IHC) analysis and fluorescence in situ hybridization revealed NUTM1 rearrangement, confirming the diagnosis of NUT carcinoma. The patient experienced tumor recurrence six months postoperatively and succumbed to the disease nine months later. Discussion: The pathological diagnosis was challenging; the presence of abrupt squamous differentiation prompted further IHC analysis, leading to the definitive diagnosis. Primary uterine NUT carcinoma may be misdiagnosed as other undifferentiated uterine tumors due to its rarity and histological overlap. Conclusions: Given the diagnostic challenges, NUT IHC staining and molecular testing for NUTM1 rearrangement should be considered in undifferentiated uterine tumors with ambiguous histopathological features. Full article