{"paper_id":"168e7fc8-daf1-43de-9135-b9d6dc4f1537","body_text":"CASE STUDY Open Access\n© The Author(s) 2026. Open Access  This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, \nsharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and \nthe source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this \narticle are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included \nin the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will \nneed to obtain permission directly from the copyright holder. To view a copy of this licence, visit  h t t p  : / /  c r e a  t i  v e c  o m m  o n s .  o r  g / l i c e n s e s / b y / 4 . 0 /.\nCagaptay et al. Surgical and Experimental Pathology             (2026) 9:7 \nhttps://doi.org/10.1186/s42047-026-00219-6\nBoard 2020). They can rarely differentiate between intes -\ntinal and gastric types. It is rare to observe intestinal dif -\nferentiation in endometrial cancer. The phenomenon \nwas initially explained in 1984 by (Berger et al. 1984). \nSubsequently, additional cases of intestinal and gastric \ndifferentiation were documented in the literature (Abiko \net al. 2010; Buell-Gutbrod et al. 2013; Hino et al. 2016; \nKarpathiou et al. 2022; McCarthy et al. 2017; Mogor \net al. 2018; Rubio et al. 2016; Stolnicu et al. 2021; Trip-\npel et al. 2017; Zheng et al. 1995). Due to its infrequency \nand the lack of agreement until recently, this tumor has \nbeen assigned various names by different writers and is \nfrequently regarded as a Müllerian-type mucinous carci -\nnoma. In 2020, (Wong et al. 2020) described four patients \nwith endometrial cancer that had histologically unusual \nBackground\nEndometrioid carcinoma is the most prevalent type of \nendometrial cancer. Since it shows a wide variety of mor-\nphologies and metaplastic changes, it might be challeng -\ning to diagnose. Mucinous differentiation is common in \nendometrioid carcinomas (Bartosch, Manuel Lopes and \nOliva 2011; WHO Classification of Tumours Editorial \nSurgical and Experimental \nPathology\n*Correspondence:\nSumru Cagaptay\nsumru.cagaptay@deu.edu.tr\n1Department of Pathology, Dokuz Eylul University School of Medicine, \nIzmir, Turkey\n2Institute of Oncology, Dokuz Eylul University, Izmir, Turkey\n3Department of Obstetrics and Gynecology, Dokuz Eylul University \nSchool of Medicine, Izmir, Turkey\nAbstract\nPrimary gastric (gastrointestinal) mucinous carcinoma of the endometrium is a newly defined entity in the \nlatest WHO classification. It is known to have an aggressive clinical course compared to conventional mucinous \nendometrial carcinomas. The case we present is a 65-year-old female patient. The patient underwent total \nabdominal hysterectomy, bilateral salpingooophorectomy, bilateral pelvic and para-aortic lymph node dissection, \nand omentectomy. Histologically, the tumor contains enterocyte-like cells with a brush border, as well as abundant \neosinophilic cytoplasm with mild or moderate atypia and occasional goblet cells. In immunohistochemical \nevaluation, CK7, CK20, CDX2, Villin, and CEA was positive in the tumor. The patient was diagnosed as primary \nintestinal type mucinous endometrial carcinoma based on morphological and immunohistochemical findings. \nThe patient’s molecular examination revealed mutations in the TP53, RB, and FBXW7 genes. The patient has been \nfollowed up for 6 months without disease after receiving 6 cycles of chemotherapy. The clinical, histopathological, \nimmunohistochemical, and molecular features of the case were described, and the literature was reviewed. The \nrecognition and differential diagnosis of this rare tumor will contribute to appropriate patient management and \naccurate prognostication.\nKeywords Endometrial cancer, Mucinous carcinoma, Intestinaltype mucinous carcinoma, Molecular features\nPrimary intestinal type endometrial mucinous \ncarcinoma: a case report and review of the \nliterature\nSumru Cagaptay1*, Tekincan Aktas2, Tunc Timur3, Zeynep Bayramoglu1, Sefa Kurt3 and Safiye Aktas1,2\n\nPage 2 of 8\nCagaptay et al. Surgical and Experimental Pathology              (2026) 9:7 \nmucinous differentiation into a gastric (gastrointestinal) \nphenotype. Following this paper, the World Health Orga-\nnization (WHO) classification of female genital tract can-\ncers in 2020 included a new type of carcinoma: Primary \ngastric (gastrointestinal)–type endometrial mucinous \ncarcinoma (WHO Classification of Tumours Editorial \nBoard 2020). WHO classification defines this rare tumor \nas a carcinoma with mucinous gastric/gastrointestinal \ncharacteristics. Morphologically, it consists of glands \nformed by mucin-secreting epithelium, which may con -\ntain goblet cells with low grade nuclei. The exclusion of \ncervical origin and/or metastases from the gastrointes -\ntinal tract, the lack of an endometrioid component, and \nmorphological characteristics are required (WHO Clas -\nsification of Tumours Editorial Board 2020). The estab -\nlishment of criteria has contributed to the recognition \nand description of new cases in recent years. However, \nthe number of cases in the literature is still around 20 and \nthe clinical, pathological and molecular features of the \ntumor have not been sufficiently elucidated. It is thought \nthat recognition of this tumor type is important because \nit has been stated that it has an aggressive clinical course \n(Travaglino et al. 2020; Wong et al. 2020). With the case \nwe present, we hope to add data to the literature that will \nincrease the recognition of the tumor.\nCase presentation\nA 65-year-old female patient has a history of two spon -\ntaneous vaginal births. She has a history of appendec -\ntomy and thyroidectomy. She received radioactive iodine \ntreatment with a diagnosis of thyroid papillary carci -\nnoma. There is no feature in her family history. Endo -\nmetrial curettage was performed on her application \nto another center with a complaint of postmenopausal \nbleeding. Endometrioid adenocarcinoma was reported \nas FIGO grade I. She was referred to our hospital for \nfurther examination. No abnormal findings were found \nin the physical examination performed in our hospital. \nIn the radiological evaluation, a 5 mm irregular thick -\nness increase was detected in the uterine fundus on \ntransvaginal ultrasonography. Contrast-enhanced pelvic \nmagnetic resonance imaging revealed an 8 mm segment \nof increased continuous wall thickness and endome -\ntrial irregularity within the myometrium of the uterine \nfundus. Consultation blocks of curettage material were \nre-evaluated preoperatively in our department. In micro -\nscopic evaluation, there is well-differentiated carcinoma \nmorphology. The tumor consists of complex glandular \nstructures composed of tall columnar cells with mild to \nmoderate atypia (Fig. 1). In immunohistochemical exami-\nnation, estrogen receptor (ER) and progesterone receptor \n(PR) are negative P53 displays a mutant type, while p16 \nexhibits patchy positive staining. The proliferation index \nfor Ki-67 is high.\nDue to the unexpected immunophenotype of the tumor \nwith low-grade morphology, human papilloma virus \n(HPV) Chromogenic In situ hybridization (ISH) was per -\nformed to investigate the possible cervical origin, and the \nresult was negative. Material limitations prevented addi -\ntional immunohistochemical examination for histological \ntyping of the tumor at this stage. The patient underwent \ntotal abdominal hysterectomy and bilateral salpingooo -\nphorectomy, bilateral pelvic and para-aortic lymph node \ndissection, and omentectomy. In macroscopic evaluation, \na tumor measuring 1.5x1 cm was found in the poste -\nrior wall of the uterus and showed an expansile growth \npattern. The tumor invaded the upper half of the myo -\nmetrium. No cervical extension was observed. Bilateral \novaries and fallopian tubes showed no tumor involve -\nment. Histologically, the tumor contains enterocyte-like \ncells with a brush border, as well as abundant eosinophilic \ncytoplasm with mild or moderate atypia and occasional \ngoblet cells (Fig. 2). Not accompanied by a typical endo -\nmetrioid component. Adjacent to the tumor, we observe \nareas resembling high-grade intestinal type dysplasia and \nthe non-tumoral endometrium was atrophic. The cervi -\ncal gland and stroma showed no tumor involvement. The \nlymph nodes and omentum were histologically examined, \nand there was no tumor. In immunohistochemical evalu -\nation (Fig. 3), ER, PR, PAX-8, WT-1, GATA-3, p40, and \nNapsin A were negative in the tumor. CK7, CK20, CDX2, \nVillin, and CEA was positive. There was focal positivity \nwith AMACR. The tumor was negative with MUC-2 and \nMUC6 and stained weak positive with MUC5AC. P16 \ndemonstrated block type positivity and p53 mutant type \nstaining. The Ki-67 proliferation index was high. Addi -\ntionally, MLH-1, MSH2, MSH6, and PMS2 mismatch \nFig. 1  Well-differentiated carcinoma morphology in curetage material. \nThe tumor consists of complex glandular structures composed of tall co -\nlumnar cells with mild to moderate atypia (H&E staining, x200)\n \n\nPage 3 of 8\nCagaptay et al. Surgical and Experimental Pathology              (2026) 9:7 \nrepair (MMR) immunohistochemistry did not detect any \nloss of nuclear expression in the tumor.\nThe patient was also evaluated with endoscopy and \ncolonoscopy for possible metastasis of a gastrointestinal \nsystem tumor, and no tumor focus was found. Morpho -\nlogical and immunohistochemical findings were evalu -\nated together, and a diagnosis of primary intestinal type \nmucinous endometrial carcinoma was given. The tumor \nstage was determined as p T1bN0 (FIGO 2023 stage 1B).\nMolecular analysis was also performed to understand \nthe tumor pathogenesis and to provide a possible targeted \ntherapy option. In molecular analysis, DNA and RNA \nwere isolated from formalin-fixed paraffin-embedded tis-\nsue by microdissection of the lesion area for next-genera-\ntion sequencing (NGS) and fusion detection. OncoReveal \nMulti-Cancer with CNV v4 Panel developed by Pillar \nBiosciences was used for NGS (for panel details;  h t t p  s : /  \n/ w w w  . p  i l l  a r b  i o s c  i .  c o m  / w p  - c o n  t e  n t /  u p l  o a d s  / 2  0 2 3  / 0 8  / U \nM -  0 0  2 6 -  O N C  O R e v  e a  l - M  u l t  i - C a  n c  e r -  R N A  - F u s  i o  n - v 2 - P a \nn e l - 6 3 0 7 - 1 . p d f). OncoReveal Multi-Cancer RNA Fusion \nv2 Panel developed by the same company was used for \nfusion detection (for panel details;  h t t p  s : /  / w w w  . p  i l l  a r b  i o \ns c  i .  c o m  / w p  - c o n  t e  n t /  u p l  o a d s  / 2  0 2 3  / 0 8  / U M -  0 0  2 8 -  O N C  O \nR e v  e a  l - M  u l t  i - C a  n c  e r -  v 4 -  w i t h  - C  N V - P a n e l - 6 3 0 9 - 2 . p d f). \nFollowing the isolation of genetic material, we processed \nthe sample in accordance with Pillar Bioscience’s instruc-\ntions. The data threshold in the ClinVar database was \nused to interpret the detected variants to exclude known \npolymorphisms and identify pathogenicity.\nThere was no fusion detected in RNA fusion detec -\ntion. NGS analysis performed on the sample detected 39 \nvariants. 31 of these variants belong to intronic, 3’UTR \nor synonymous mutations. NM_000546.6:c0.817C > T \n(R273C missense) mutation in the TP53 gene was inter -\npreted as pathogenic based on the data in ClinVar. \nNM_000455.5:c0.1062C > G (F354L missense) muta -\ntion in the STK11 gene and NM_000222.3:c0.1621A > C \n(M541L missense) mutation in the KIT gene were \nevaluated as benign. NM_004448.4:c0.1963A > G (I655V \nmissense) mutation in the ERBB2 gene was interpreted \nas a variation due to its frequency in the population. \nNM_000222.3:c0.1454A > C (H485P missense) mutation \nin the KIT gene, NM_001349798.2:c0.1387A > G (T463A \nmissense) and NM_033632.3:c0.1452 G > T(A484S \nmissense) mutation in the FBXW7 gene, \nNM_000321.3:c0.2377C > T(P793S missense) mutation \nwere detected in the RB1 gene. Since there was no data or \nsufficient data in ClinVar for these mutations, they were \nevaluated in the unknown significance category.\nConsidering the possibility of tumor recurrence in \nthe postoperative treatment planning, it was decided \nto administer chemotherapy and radiotherapy to the \npatient. The patient received 6 cycles of carboplatin and \npacitaxel combination treatment and has been followed \nup for 6 months without recurrence or metastasis.\nDiscussion\nThe diagnosis of gastrointestinal type endometrial carci -\nnoma requires a comprehensive evaluation of all findings, \nas morphological and immunohistochemical features \nalone are not sufficient. When there is no expression \nof hormone receptors and no squamous morule in a \nlow-grade endometrial carcinoma, and if the morphol -\nogy supports it, the possibility of gastric (gastrointesti -\nnal) type endometrial carcinoma should be considered. \nAccording to the criteria defined by Wong et al. (Wong \net al. 2020), the tumor is ‘’(i) endometrial adenocarci -\nnoma with no evidence of any other primary site and the \npresence of gastric-type morphology (voluminous, pale \neosinophilic or clear cytoplasm with distinct cell borders) \nand/or goblet cells.\n(ii) absence of typical endometrioid component (iii) \nabsence of cervical glandular or stromal involvement \n(with complete sampling of the cervix) (iv) at least focal \nimmunohistochemical expression of one or more gas -\ntrointestinal markers (eg, MUC6, CK20, and CDX2) \nFig. 2 a, b: enterocyte-like cells with a brush border, as well as abundant eosinophilic cytoplasm with mild or moderate atypia and occasional goblet cells \n(H&E staining, x200, H&E staining, x400, respectively)\n \n\nPage 4 of 8\nCagaptay et al. Surgical and Experimental Pathology              (2026) 9:7 \n(v) absent or minimal ( < 5%) expression of ER’’ it can \nbe diagnosed as gastrointestinal type endometrioid \ncarcinoma.\nDifferential diagnoses include conventional (Müllerian) \ntype endometrial mucinous carcinoma, gastric/intestinal \ntype endocervical adenocarcinoma, endometrial metas -\ntases of a gastrointestinal malignancy, and benign lesions \nwith gastrointestinal type mucinous metaplasia.\nThe latest WHO classification (WHO Classification of \nTumours Editorial Board 2020) does not include the cri -\nterion of the 4th edition (CMHCYR, 2014) regarding the \ndefinition of conventional mucinous tumors, which states \nthat “the tumor should be classified as mucinous carci -\nnoma if it contains more than 50% mucinous component” . \nThis histological type is now included under the heading \nof other endometrial carcinomas as “Mucinous carci -\nnoma, gastric (gastrointestinal) type” . The terminology \nFig. 3 a: mutant type staning at p53 immunohistochemistry, b: ER negativitiy in the tumor, c: positivity with villin immunohistochemistry, d: positivity \nwith CDX2 immunohistochemistry, 3e: weak positivity with MUC5AC immunohistochemistry\n \n\nPage 5 of 8\nCagaptay et al. Surgical and Experimental Pathology              (2026) 9:7 \nof mucinous differentiation in endometrioid endometrial \ncarcinomas has been retained, but no cut-off value has \nbeen specified (Parkash et al. 2023; WHO Classification \nof Tumours Editorial Board 2020). Therefore, the need \nfor these distinctions arises not from the specification \nof conventional mucinous endometrial carcinomas as a \ndistinct entity but rather from their superior prognosis \ncompared to gastric (gastrointestinal) type mucinous car-\ncinomas (CMHCYR, 2014; Wong et al. 2020; Wong, Talia \nand Mccluggage 2020). Morphologically, conventional - \ntype mucinous carcinomas consist of endocervical type \nepithelium and do not have the cytomorphological and \nimmunohistochemical features of gastric/gastrointestinal \ndifferentiation. They contain typical endometrioid com -\nponents. It is generally diffusely positive with ER and PR \n(Shabani et al., 2007,Lax et al.,. 1998).\nIn curettage specimens, both HPV-related and HPV-\nunrelated endocervical adenocarcinomas can complicate \ndifferential diagnosis. Intestinal type endocervical adeno -\ncarcinomas are associated with HPV, and a significant \nproportion exhibit ISH positivity. In gastric type endo -\ncervical adenocarcinomas that are not associated with \nHPV, HPV ISH will yield negative results. While p16 \nblock positivity may occasionally occur, this is less com -\nmon compared to gastrointestinal type endometrial car -\ncinoma. It is recommended to sample the entire cervix \nto rule out endometrial extension of primary endocervi -\ncal adenocarcinoma (Dridi, Peoc’h and Karpathiou 2023; \nStolnicu et al. 2018; Stolnicu, Hoang and Soslow 2019; \nWong et al. 2020).\nSince the morphological and immunohistochemical \nfindings of endometrial metastasis from a tumor of gas -\ntrointestinal and pancreaticobiliary system origin may \nbe very similar to gastrointestinal type endometrial car -\ncinoma, evaluation of the patient together with clinical \nhistory, endoscopic and imaging findings may help deter-\nmine the primary focus. Despite conflicting immunohis -\ntochemical findings, positivity with Müllerian markers \nmay support gynecological origin (Choi et al. 2020; Dridi, \nPeoc’h and Karpathiou 2023; Ronquillo and Pinto 2022).\nBenign lesions containing gastrointestinal type meta -\nplasia can be distinguished from gastrointestinal type \nendometrial adenocarcinoma by the presence of ER \nexpression, being generally associated with endometrial \npolyps, and not containing atypia (Wong et al. 2020).\nWe conducted a comprehensive review of the literature \nand compiled the cases presented to date (Additional file \n1, summarizes the findings in cases of endometrial ade -\nnocarcinoma with gastric (gastrointestinal) type differen-\ntiation described in the literature).\nMorphologically, the cases presented in the literature \nreview to date consist of cases that generally show a glan-\ndular pattern, and less frequently a papillary, cribriform \nand solid pattern. Two cases describe tumor cells that \nform small aggregates or small fused glands within muci -\nnous pools (Rubio et al. 2016; Trippel et al. 2017). In our \ncase, the tumor consists predominantly of glandular and \ncribriform patterns.\nIn the cases presented, gastric (Abiko et al. 2010; \nMcCarthy et al. 2017; Travaglino et al. 2020; Wong et al. \n2020; Wong, Talia and Mccluggage 2020) and intestinal \n(Ardighieri et al. 2020; Berger et al. 1984; Buell-Gutbrod \net al. 2013; Nakano et al. 2023; Trippel et al. 2017; Zheng \net al. 1995) type differentiation, as well as gastrointesti -\nnal type differentiation (Karpathiou et al. 2022; Rubio et \nal. 2016; Stolnicu et al. 2021), were observed. According \nto Wong et al. (Wong et al. 2020), the term ‘’gastrointes-\ntinal type differentiation’’ refers to cases where the dif -\nferentiation is not pure and of a single type but includes \nboth gastric and intestinal features. When morphologi -\ncally gastric/intestinal/gastrointestinal differentiation is \nsuspected, intestinal (CDX2, CK20) and gastric differen -\ntiation markers (MUC6, HIK1083) may be useful (Dridi, \nPeoc’h and Karpathiou 2023; Wong et al. 2020). However, \nsince these markers can also be positive in conventional \nendometrioid adenocarcinomas (Alameda et al. 2007; \nHodgson, Parra-Herran and Mirkovic 2019), it is recom -\nmended to evaluate cytomorphological features together \nwith immunohistochemical features (Wong et al. 2020). \nIn our case, CDX2 and CK20 positivity and MUC6 nega -\ntivity were interpreted as intestinal differentiation con -\nsidering the cytomorphological features.\nThe level of atypia is defined as mild and moderate in \nmost cases and severe in some cases (Karpathiou et al. \n2022; Travaglino et al. 2020; Wong et al. 2020). In most \ncases, the tumor appears to contain goblet cells and \nenterocyte-like tall columnar cells. In some cases, the \ntumor has been reported to contain varying amounts \nof neuroendocrine cells (Berger et al. 1984; Zheng et al. \n1995), Paneth cells (Berger et al. 1984), and signet ring \ncells (Berger et al. 1984; Travaglino et al. 2020). Tumor \nmay exhibit morphological heterogeneity. Contrary \nto the established criteria, cases with an accompany -\ning endometrioid (Ardighieri et al. 2020; Berger et al. \n1984; Buell-Gutbrod et al. 2013; McCarthy et al. 2017) \nor serous (Travaglino et al. 2020) component have been \nreported. In the case we present, similar to most cases in \nthe literature, the tumor consists of enterocyte-like cells \nwith a brush border, abundant eosinophilic cytoplasm \nwith mild to moderate atypia, and occasional goblet cells, \nand does not contain a typical endometrioid component.\nSome lesions that may have originated from or been \nassociated with the tumor have been described in the \nliterature. The lesions identified are atypical endome -\ntrial hyperplasia (Buell-Gutbrod et al. 2013; Mogor et al. \n2018), mucinous adenocarcinoma in situ and mucinous \nmetaplasia (Abiko et al. 2010), intestinal metaplasia in \nendometrial polyp (Rubio et al. 2016), gastric metaplasia \n\nPage 6 of 8\nCagaptay et al. Surgical and Experimental Pathology              (2026) 9:7 \nand low-grade dysplasia accompanying lobular glandu -\nlar hyperplasia (Travaglino et al. 2020), mucinous gastric \ntype metaplasia in adenomyomatous polyp and adeno -\ncarcinoma in situ on the basis of müllerian malforma -\ntion (Wong et al. 2020). Metaplastic lesions that are \nassociated with the tumor have been observed in certain \ncases. Additionally, there is a study in the literature that \nindicates that endometrial adenocarcinomas are associ -\nated with multifocal and synchronous gastric metaplastic \nlesions in the female genital tract (Mikami et al. 2009).\nIn the case we present, the non-neoplastic endome -\ntrium is atrophic, does not contain metaplastic benign \nlesions, and areas resembling high-grade intestinal dys -\nplasia are observed adjacent to the tumor. It seems appro-\npriate to use the terminology of “atypical gastrointestinal \ntype mucinous proliferation” (Fig. 4) for this lesion, as \nit meets the criteria defined by Wong et al. (Wong et \nal. 2020). However, due to the wide range of potential \ntumor-related or precursor lesions identified and the \nsmall number of cases, it is unclear whether these lesions \nare true precursor lesions, and there is no consensus on \nthis issue in the literature. It is believed that additional \ndata are needed to understand this issue.\nThe immunohistochemistry panels utilized in the cases \npresented in the literature exhibited variations. Upon \nreviewing the findings based on the common mark -\ners utilized, positivity was observed in most cases for \nCK7, CK20, and CDX2. In two cases, CDX2 was nega -\ntive (Wong et al. 2020). Villin positivity was observed in \nall cases where villin was administered (Rubio et al. 2016; \nWong et al. 2020). PAX8 was positive in some cases and \nnegative in others (Karpathiou et al. 2022; Mogor et al. \n2018). In the majority of cases, ER and PR were reported \nas negative, while focally positive in a few cases and \nweakly positive in one case (Zheng et al. 1995). Only two \nof the cases where CEA was used yielded negative results \n(McCarthy et al. 2017). MUC6 was the most used mucin \nimmunohistochemical marker, with positive results. In \none case, all three mucin immunohistochemistry tests \nwere performed, and the result was found to be positive \nfor all three markers (Rubio et al. 2016). In p16 immuno-\nhistochemistry, there have been cases of both block (Kar-\npathiou et al. 2022; Stolnicu et al. 2021; Wong et al. 2020; \nWong, Talia and Mccluggage 2020) and patchy type posi-\ntivity (Ardighieri et al. 2020; McCarthy et al. 2017; Rubio \net al. 2016). There have been cases where p53 immuno -\nhistochemistry has revealed both mutant (Karpathiou \net al. 2022; Wong et al. 2020) and wild type (Stolnicu et \nal. 2021; Travaglino et al. 2020; Wong et al. 2020) stain-\ning. HER2 immunohistochemistry was performed on \nonly one of the cases, and the result was negative (Wong \net al. 2020). Similar to the cases in the literature, CDX2, \nCK20, CK7, villin were positive and ER, PR were negative \nin our case. MUC2 and MUC6 were negative. Like only \none case presented in the literature, MUC5AC was posi -\ntive (Rubio et al. 2016). MLH1, PMS2, MSH6, and MSH2 \nnuclear expression were preserved (Karpathiou et al. \n2022; McCarthy et al. 2017; Stolnicu et al. 2021) in three \nof the six cases in which MMR immunohistochemistry \nwas utilized. In two cases, nuclear expression of MLH1 \nand PMS2 was lost, and molecular analysis revealed \nMLH1 hypermethylation (McCarthy et al. 2017; Trip -\npel et al. 2017). In a single case, MSH6 and MSH2 were \nreported to have lost nuclear expression. In this case, \nmolecular analysis confirmed the MMR defect/MSI-H \nstatus (Ardighieri et al. 2020). Loss of nuclear expression \nof MMR markers was not observed in our case.\nThe molecular pathogenesis of gastric (gastrointesti -\nnal) type endometrial carcinoma is not well understood. \nMolecular features have been described in only a small \nfraction of cases presented in the literature. In the case \nseries by Wong et al., a SMARCB1 missense mutation \nand a RB1 nonsense mutation were described in one \ncase. In the case with RB1 mutation, it was stated that \nthe RB gene from the HPV-unrelated pathway may be \neffective in pathogenesis due to the presence of block \ntype p16 positivity. In two cases with mutant type stain -\ning with p53, it was reported that the TP53 gene may be \nFig. 4 Transition between areas of high-grade intestinal dysplasia and non-dysplastic epithelium a: H&E staining, x400, b: mutant-type staining of dys -\nplastic areas in p53 immunohistochemistry\n \n\nPage 7 of 8\nCagaptay et al. Surgical and Experimental Pathology              (2026) 9:7 \nresponsible for pathogenesis (Wong et al. 2020). In three \ncases, pathogenesis was associated with MMR defect \n(Ardighieri et al. 2020; McCarthy et al. 2017; Trippel et \nal. 2017). It has been stated that mutations in the STK11 \ntumor suppressor gene may be effective in pathogenesis \nin cases accompanied by synchronous mucinous meta -\nplastic lesions of the female genital tract, with or without \nPeutz-Jeghers syndrome (Mikami et al. 2009).\nOur molecular analysis results show that the TP53 \nand RB genes play an important role in pathogenesis. \nAlthough there is insufficient data for mutations in the \nFBXW7 gene in ClinVar, the literature reports that the \nT463A mutation is moderately effective in serous endo -\nmetrial carcinomas and the A484S mutation is highly \neffective in endometrial carcinomas (Le et al. 2012). The \nrole of the FBXW7 gene in the pathogenesis of gastric \n(gastrointestinal) type endometrial carcinomas is not \nyet known, but it is thought that both mutations may be \neffective in pathogenesis since they affect the WD repeat \ndomain. The combination of TP53, RB1, and FBXW7 \nmutations detected in our case has not been previously \nreported in the literature. However, this combination of \nmutations seems to clarify the aggressive nature of the \ntumor.\nConclusion\nRecognizing and making a differential diagnosis of this \ntumor, known for its aggressive clinical course despite its \nlow-grade morphological features, is crucial for appro -\npriate clinical management and treatment preference \n(Travaglino et al. 2020; Wong et al. 2020; Wong, Talia \nand Mccluggage 2020). Although the histomorphologi -\ncal and immunohistochemical features of this tumor are \nrelatively well understood, there is insufficient data in \nthe literature regarding its molecular characteristics and \nbiological behavior. In the case we present, we identified \na combination of TP53, RB1, and FBXW7 mutations, \nwhich are rare but which we believe are associated with \nthe aggressive course of the tumor. The incorporation of \nadditional cases in the literature will enhance our com -\nprehension of the tumor’s characteristics.\nAbbreviations\nWHO  World Health Organization\nER  Estrogen receptor\nPR  Progesterone receptor\nHPV  Human papilloma virus\nISH  In situ hybridization\nMMR  Mismatch repair\nNGS  Next-generation sequencing\nSupplementary Information\nThe online version contains supplementary material available at  h t t p  s : /  / d o i  . o  r \ng /  1 0 .  1 1 8 6  / s  4 2 0 4 7 - 0 2 6 - 0 0 2 1 9 - 6.\nSupplementary Material 1\nAcknowledgements\nNot applicable.\nAuthor contributions\nAuthors SC and ZB were responsible for patient data collection and \npreparation of the manuscript. Authors TA and SA performed the molecular \nanalyses and analyzed the results. Authors TT and SK provided their clinical \nexpertise. Authors ZB and SA critically revised the manuscript for important \nintellectual content. All authors approved the final manuscript and agreed to \nbe responsible for all aspects of the work and to ensure that any questions \nabout the work’s accuracy or integrity are properly investigated and resolved.\nFunding\nNot applicable.\nData availability\nThe data generated and analyzed during the current study are not publicly \navailable due to their personal data content but are available from the \ncorresponding author upon reasonable request.\nDeclarations\nEthics approval and consent to participate\nOur institution does not require ethical approval for reporting individual \ncases or case series. The research was conducted in accordance with the \nInternational Committee of Medical Journal Editors guidelines and the \nHelsinki Declaration as revised in 2013. All nonessential identifying details \nhave been omitted.\nConsent for publication\nInformed consent was obtained from the patient. The participant has\nCompeting interests\nThe authors declare no competing interests.\nReceived: 29 November 2025 / Accepted: 12 January 2026\nReferences\nAbiko K, Baba T, Ogawa M, Mikami Y, Koyama T, Mandai M, et al. Minimal deviation \nmucinous adenocarcinoma (‘adenoma malignum’) of the uterine corpus. \nPathol Int . 2010 Jan 1;60(1):42–47 . [cited 2024 Aug 25]. Available from:  h t t p  s : \n/  / o n l  i n  e l i  b r a  r y . w  i l  e y .  c o m  / d o i  / f  u l l  / 1 0  . 1 1 1  1 /  j . 1  4 4 0  - 1 8 2  7 .  2 0 0 9 . 0 2 4 7 3 . x \nAlameda F, Mejías-Luque R, Garrido M, Bolós C D. Mucin genes (MUC2, MUC4, \nMUC5AC, and MUC6) detection in normal and pathological endometrial tis-\nsues. Int J Gynecological Pathol [Internet]. 2007, Jan;26(1):61–65. [cited 2024 \nSep 29]. Available from:  h t t p  s : /  / j o u  r n  a l s  . l w  w . c o  m /  i n t  j g y  n p a t  h o  l o g  y / f  u l l t  e x  t / 2  \n0 0 7  / 0 1 0  0 0  / m u  c i n  _ g e n  e s  _ _ m  u c 2  , _ m u  c 4  , _ m u c 5 a c , _ a n d _ m u c 6 _ . 1 0 . a s p x.\nArdighieri L, Palicelli A, Ferrari F, Bugatti M, Drera E, Sartori E, et al. Endometrial \ncarcinomas with intestinal-type metaplasia/differentiation: does mismatch \nrepair System defects matter? Case report and systematic review of the \nliterature. J Clin Med [Internet]. 2020;9(8):1–13. [cited 2024 Sep 28]. Available \nfrom:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l m  . n  i h . g o v / 3 2 7 8 1 6 6 6 /.\nBartosch C, Manuel Lopes J, Oliva E. Endometrial carcinomas: a review emphasiz-\ning overlapping and distinctive morphological and immunohistochemical \nfeatures. Adv Anat Pathol [Internet]. 2011 Nov;18(6):415–37. [cited 2024 Aug \n25]. Available from:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l m  . n  i h . g o v / 2 1 9 9 3 2 6 8 /. \nBerger G, Fétissof F, Vitrey D, Chayvialle J, Feroldi J. Endometrial carcinoma of the \nintestinal type. A first case report. Appl Pathol. 1984\nBuell-Gutbrod R, Sung CJ, Lawrence WD, Quddus MR. Endometrioid adenocarci-\nnoma with simultaneous endocervical and intestinal-type mucinous differen-\ntiation: report of a rare phenomenon and the immunohistochemical profile. \nDiagn Pathol [Internet]. 2013 Aug 2;8(1):128. [cited 2024 Aug 25]. Available \nfrom:/pmc/articles/PMC3849525/\nChoi S, Joo JW, Do SI, Kim HS. Endometrium-limited metastasis of extragenital \nmalignancies: a challenge in the diagnosis of endometrial curettage speci-\nmens. Diagn (Basel) [Internet]. 2020;10(3). [cited 2024 Sep 23]. Available from:  \nh t t p  s : /  / p u b  m e  d . n  c b i  . n l m  . n  i h . g o v / 3 2 1 6 4 2 1 0 /. \n\nPage 8 of 8\nCagaptay et al. Surgical and Experimental Pathology              (2026) 9:7 \nDridi M, Peoc’h M, Karpathiou G. Primary endometrial gastric (gastro-intestinal)-\ntype carcinoma: a practical approach. Pathol Res Pract [Internet]. 2023 Jan \n1;241. [cited 2024 Sep 23] Available from:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l m  . n  i h . g o v / \n3 6 5 0 2 7 3 6 /. \nHino M, Yamaguchi K, Abiko K, Yoshioka Y, Hamanishi J, Kondoh E, et al. Magnetic \nresonance imaging findings and prognosis of gastric-type mucinous adeno-\ncarcinoma (minimal deviation adenocarcinoma or adenoma malignum) \nof the uterine corpus: two case reports. Mol Clin Oncol [Internet]. 2016 \nMay;4(5):699. [cited 2024 Aug 25]. Available from:/pmc/articles/PMC4840738/\nHodgson A, Parra-Herran C, Mirkovic J. Immunohistochemical expression of \nHIK1083 and MUC6 in endometrial carcinomas. Histopathology [Internet]. \n2019 Oct 1;75(4):552–58. [cited 2024 Sep 29]. Available from:  h t t p  s : /  / o n l  i n  e l i  b \nr a  r y . w  i l  e y .  c o m  / d o i  / f  u l l  / 1 0  . 1 1 1  1 /  h i s . 1 3 8 8 7. \nKarpathiou G, Chauleur C, Mathonat L, Dridi M, Picot T, Devouassoux-Shisheboran \nM, et al. Morphologic diversity of the endometrial gastrointestinal-type \nadenocarcinoma. Pathol Res Pract [Internet]. 2022 Feb 1;230. [cited 2024 Sep \n23]. Available from:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l m  . n  i h . g o v / 3 5 0 2 6 6 4 4 /. \nLax SF, Pizer ES, Ronnett BM, Kurman RJ. Comparison of estrogen and progester-\none receptor, Ki-67, and p53 immunoreactivity in uterine endometrioid car-\ncinoma and endometrioid carcinoma with squamous, mucinous, secretory, \nand ciliated cell differentiation. Hum Pathol. 1998 Sep 1;29(9):924–31\nLe Gallo M, O’Hara AJ, Rudd ML, Urick ME, Hansen NF, O’Neil NJ, et al. Exome \nsequencing of serous endometrial tumors identifies recurrent somatic \nmutations in chromatin-remodeling and ubiquitin ligase complex genes. Nat \nGenet [Internet]. 2012 Dec [cited 2024 Oct 19];44(12):1310. Available from:  h t \nt p  s : /  / p m c  . n  c b i  . n l  m . n i  h .  g o v  / a r  t i c l  e s  / P M C 3 5 1 5 2 0 4 /\nMcCarthy WA, Makhijani R, Miller K, Rojas K, Beffa L, Mathews C, et al. Gastric-type \nendometrial adenocarcinoma: report of two cases in patients from the \nUnited States.  h t t p  s : /  / d o i  . o  r g /  1 0 .  1 1 7 7  / 1  0 6 6 8 9 6 9 1 7 7 4 3 0 1 0 [Internet]. 2017 \nDec 27;26(4):377–81. [cited 2024 Aug 25]. Available from  h t t p  s : /  / j o u  r n  a l s  . s a  g e \np u  b .  c o m  / d o  i / 1 0  . 1  1 7 7  / 1 0  6 6 8 9  6 9  1 7 7 4 3 0 1 0.\nMikami Y, Kiyokawa T, Sasajima Y, Teramoto N, Wakasa T, Wakasa K, et al. Reappraisal \nof synchronous and multifocal mucinous lesions of the female genital tract: \na close association with gastric metaplasia. Histopathology [Internet]. 2009 \nJan;54(2):184–91. [cited 2024 Sep 30] Available from:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l \nm  . n  i h . g o v / 1 9 2 0 7 9 4 3 /. \nMogor O, Hargrave E, Rush D, Hatch K. Mucinous adenocarcinoma of the endo-\nmetrium with metastasis to the clitoral glans after pelvic exenteration for \nradiation resistant vaginal cuff recurrence. Gynecol Oncol Rep [Internet]. 2018 \nFeb 1;27:46–49. [cited 2024 Sep 23]. Available from:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l m  \n. n  i h . g o v / 3 0 6 2 7 6 1 4 /. \nNakano C, Fukuda T, Tanaka S, Noda T, Uchikura E, Awazu Y, et al. Intestinaltype \nmucinous carcinoma of the endometrium showing a polypoidal exophytic \nform: a case report. Oncol Lett [Internet]. 2023 Oct 1;26(4). [cited 2024 Aug \n25]. Available from:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l m  . n  i h . g o v / 3 7 7 2 0 6 6 4 /.\nNieuwenhuizen L, Khalil MK, Naik VR, Othman NH. Prevalence of Goblet Cell \nMetaplasia in Endocervical and Endometrial Adenocarcinoma: A Histochemi-\ncal Study. Malays J Med Sci [Internet]. 2007 Jan;14(1):56. [cited 2024 Sep 29]. \nAvailable from:/pmc/articles/PMC3351219/.\nParkash V, Aisagbonhi O, Riddle N, Siddon A, Panse G, Fadare O. Recent advances in \nthe Classification of gynecological tract tumors: updates from the 5th edition \nof the World Health Organization “blue book. Arch Pathol Lab Med [Internet]. \n2023 Oct 1;147(10):1204–16. [cited 2024 Sep 30]. Available from:  h t t p  s : /  / p u b  \nm e  d . n  c b i  . n l m  . n  i h . g o v / 3 6 5 9 6 2 7 0 /.\nRonquillo N, Pinto A. Gynaecological or gastrointestinal origin? Recognising \nMüllerian neoplasms with gastrointestinal phenotype and determining the \nprimary site in selected entities. Pathology [Internet]. 2022 Mar 1;54(2):207–\n16. [cited 2024 Sep 23]. Available from:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l m  . n  i h . g o v / 3 4 \n8 4 4 7 4 6 /. \nRubio A, Schuldt M, Guarch R, Laplaza Y, Giordano G, Nogales FF. Pseudomyxoma-\ntype invasion in gastrointestinal adenocarcinomas of endometrium and \ncervix: a report of 2 cases. Int J Gynecol Pathol [Internet]. 2016;35(2):118–22. \n[cited 2024 Sep 23]. Available from:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l m  . n  i h . g o v / 2 6 5 3 \n5 9 7 9 /. \nShabani N, Mylonas I, Jeschke U, Thaqi A, Kuhn C, Puchner T, et al. Expression of \nestrogen receptors α and β, and progesterone receptors A and B in human \nmucinous carcinoma of the endometrium. 2007 Jul;27(4A):2027–33.\nStolnicu S, Barsan I, Hoang L, Patel P , Chiriboga L, Terinte C, et al. Diagnostic algo-\nrithmic proposal based on comprehensive immunohistochemical evaluation \nof 297 invasive endocervical adenocarcinomas. Am J Surg Pathol [Internet]. \n2018 Aug 1;42(8):989. [cited 2024 Sep 23]. Available from:/pmc/articles/\nPMC6041133/\nStolnicu S, Hoang L, Soslow RA. Recent advances in invasive adenocarcinoma of \nthe cervix. Virchows Arch [Internet]. 2019 Nov 1;475(5):537–49. [cited 2024 \nSep 23]. Available from:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l m  . n  i h . g o v / 3 1 2 0 9 6 3 5 /. \nStolnicu S, Podoleanu C, Orban I, Francisc R. Endometrial adenocarcinoma with \ngastrointestinal differentiation – a newly described entity, with morphologic \ndiversity. Pol J Pathol. Termedia Publishing House Ltd. 2021;72:84–86\nTravaglino A, Raffone A, Gencarelli A, Mollo A, Zullo F, Insabato L. Endometrial \ngastric-type carcinoma: an aggressive and morphologically heterogenous \nNew histotype arising from gastric metaplasia of the endometrium. Am J \nSurg Pathol [Internet]. 2020 Jul 1;44(7):1002–04. [cited 2024 Aug 25]. Avail-\nable from:  h t t p  s : /  / p u b  m e  d . n  c b i  . n l m  . n  i h . g o v / 3 2 2 5 1 0 0 8 /. \nTrippel M, Imboden S, Papadia A, Mueller MD, Mertineit N, Härmä K, et al. Intestinal \ndifferentiated mucinous adenocarcinoma of the endometrium with sporadic \nMSI high status: a case report. Diagn Pathol. 2017 May 12;12(1)\nWHO Classification of Tumours Editorial Board. Female genital tumours [Internet]. \n(WHO classification of tumours series. 5th. Vol. 4). Lyon (France: International \nAgency for Research on Cancer; 2020 [cited 2024 08 25]. Available from:  h t t p  s \n: /  / t u m  o u  r c l  a s s  i fi   c  a t  i o n  . i a  r c . w  h o  . i n t / c h a p t e r s / 3 4\nWHO Classification of Tumours of female reproductive organs. In: Cmhcyr KRJ, \neditor. WHO classification of tumors. 4th. Vol. 3. Lyon, France: International \nAgency for Research on Cancer; 2014\nWong RWC, Ralte A, Grondin K, Talia KL, McCluggage WG. Endometrial gastric \n(gastrointestinal)-type mucinous lesions: report of a series illustrating the \nspectrum of benign and malignant lesions. Am J Surg Pathol [Internet]. 2020 \nMar 1;44(3):406–19. [cited 2024 Aug 25]. Available from:  h t t p  s : /  / p u b  m e  d . n  c b i  \n. n l m  . n  i h . g o v / 3 1 5 6 7 2 8 0 /. \nWong RWC, Talia KL, Mccluggage WG. Endometrial gastric-type carcinoma: an \naggressive and morphologically heterogenous New histotype arising from \ngastric metaplasia of the endometrium. Am J Surg Pathol [Internet]. 2020 \nDec 1;44(12):1736–37. [cited 2024 Sep 28]. Available from:  h t t p  s : /  / p u b  m e  d . n  c \nb i  . n l m  . n  i h . g o v / 3 3 1 7 0 8 1 1 /. \nZheng W, Yang GCH, Godwin TA, Caputo TA, Zuna RE. Mucinous adenocarcinoma \nof the endometrium with intestinal differentiation: a case report. Hum Pathol \n[Internet]. 1995;26(12):1385–88. [cited 2024 Aug 25]. Available from:  h t t p s :   /  / p \nu b m e   d .  n c b   i . n   l m  . n  i h .  g o v / 8 5 2 2 3 1 5 /. \nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in \npublished maps and institutional affiliations.","source_license":"CC0","license_restricted":false}