Primary intestinal type endometrial mucinous carcinoma: a case report and review of the literature

Endometrioid carcinoma is the most prevalent type of endometrial cancer. Since it shows a wide variety of mor- phologies and metaplastic changes, it might be challeng - ing to diagnose. Mucinous differentiation is common in endometrioid carcinomas (Bartosch, Manuel Lopes and Oliva 2011; WHO Classification of Tumours Editorial Surgical and Experimental Pathology *Correspondence: Sumru Cagaptay [email protected] 1Department of Pathology, Dokuz Eylul University School of Medicine, Izmir, Turkey 2Institute of Oncology, Dokuz Eylul University, Izmir, Turkey 3Department of Obstetrics and Gynecology, Dokuz Eylul University School of Medicine, Izmir, Turkey

Primary gastric (gastrointestinal) mucinous carcinoma of the endometrium is a newly defined entity in the latest WHO classification. It is known to have an aggressive clinical course compared to conventional mucinous endometrial carcinomas. The case we present is a 65-year-old female patient. The patient underwent total abdominal hysterectomy, bilateral salpingooophorectomy, bilateral pelvic and para-aortic lymph node dissection, and omentectomy. Histologically, the tumor contains enterocyte-like cells with a brush border, as well as abundant eosinophilic cytoplasm with mild or moderate atypia and occasional goblet cells. In immunohistochemical evaluation, CK7, CK20, CDX2, Villin, and CEA was positive in the tumor. The patient was diagnosed as primary intestinal type mucinous endometrial carcinoma based on morphological and immunohistochemical findings. The patient’s molecular examination revealed mutations in the TP53, RB, and FBXW7 genes. The patient has been followed up for 6 months without disease after receiving 6 cycles of chemotherapy. The clinical, histopathological, immunohistochemical, and molecular features of the case were described, and the literature was reviewed. The recognition and differential diagnosis of this rare tumor will contribute to appropriate patient management and accurate prognostication.

Endometrial cancer, Mucinous carcinoma, Intestinaltype mucinous carcinoma, Molecular features Primary intestinal type endometrial mucinous carcinoma: a case report and review of the literature Sumru Cagaptay1*, Tekincan Aktas2, Tunc Timur3, Zeynep Bayramoglu1, Sefa Kurt3 and Safiye Aktas1,2 Page 2 of 8 Cagaptay et al. Surgical and Experimental Pathology (2026) 9:7 mucinous differentiation into a gastric (gastrointestinal) phenotype. Following this paper, the World Health Orga- nization (WHO) classification of female genital tract can- cers in 2020 included a new type of carcinoma: Primary gastric (gastrointestinal)–type endometrial mucinous carcinoma (WHO Classification of Tumours Editorial Board 2020). WHO classification defines this rare tumor as a carcinoma with mucinous gastric/gastrointestinal characteristics. Morphologically, it consists of glands formed by mucin-secreting epithelium, which may con - tain goblet cells with low grade nuclei. The exclusion of cervical origin and/or metastases from the gastrointes - tinal tract, the lack of an endometrioid component, and morphological characteristics are required (WHO Clas - sification of Tumours Editorial Board 2020). The estab - lishment of criteria has contributed to the recognition and description of new cases in recent years. However, the number of cases in the literature is still around 20 and the clinical, pathological and molecular features of the tumor have not been sufficiently elucidated. It is thought that recognition of this tumor type is important because it has been stated that it has an aggressive clinical course (Travaglino et al. 2020; Wong et al. 2020). With the case we present, we hope to add data to the literature that will increase the recognition of the tumor. Case presentation A 65-year-old female patient has a history of two spon - taneous vaginal births. She has a history of appendec - tomy and thyroidectomy. She received radioactive iodine treatment with a diagnosis of thyroid papillary carci - noma. There is no feature in her family history. Endo - metrial curettage was performed on her application to another center with a complaint of postmenopausal bleeding. Endometrioid adenocarcinoma was reported as FIGO grade I. She was referred to our hospital for further examination. No abnormal findings were found in the physical examination performed in our hospital. In the radiological evaluation, a 5 mm irregular thick - ness increase was detected in the uterine fundus on transvaginal ultrasonography. Contrast-enhanced pelvic magnetic resonance imaging revealed an 8 mm segment of increased continuous wall thickness and endome - trial irregularity within the myometrium of the uterine fundus. Consultation blocks of curettage material were re-evaluated preoperatively in our department. In micro - scopic evaluation, there is well-differentiated carcinoma morphology. The tumor consists of complex glandular structures composed of tall columnar cells with mild to moderate atypia (Fig. 1). In immunohistochemical exami- nation, estrogen receptor (ER) and progesterone receptor (PR) are negative P53 displays a mutant type, while p16 exhibits patchy positive staining. The proliferation index for Ki-67 is high. Due to the unexpected immunophenotype of the tumor with low-grade morphology, human papilloma virus (HPV) Chromogenic In situ hybridization (ISH) was per - formed to investigate the possible cervical origin, and the

was negative. Material limitations prevented addi - tional immunohistochemical examination for histological typing of the tumor at this stage. The patient underwent total abdominal hysterectomy and bilateral salpingooo - phorectomy, bilateral pelvic and para-aortic lymph node dissection, and omentectomy. In macroscopic evaluation, a tumor measuring 1.5x1 cm was found in the poste - rior wall of the uterus and showed an expansile growth pattern. The tumor invaded the upper half of the myo - metrium. No cervical extension was observed. Bilateral ovaries and fallopian tubes showed no tumor involve - ment. Histologically, the tumor contains enterocyte-like cells with a brush border, as well as abundant eosinophilic cytoplasm with mild or moderate atypia and occasional goblet cells (Fig. 2). Not accompanied by a typical endo - metrioid component. Adjacent to the tumor, we observe areas resembling high-grade intestinal type dysplasia and the non-tumoral endometrium was atrophic. The cervi - cal gland and stroma showed no tumor involvement. The lymph nodes and omentum were histologically examined, and there was no tumor. In immunohistochemical evalu - ation (Fig. 3), ER, PR, PAX-8, WT-1, GATA-3, p40, and Napsin A were negative in the tumor. CK7, CK20, CDX2, Villin, and CEA was positive. There was focal positivity with AMACR. The tumor was negative with MUC-2 and MUC6 and stained weak positive with MUC5AC. P16 demonstrated block type positivity and p53 mutant type staining. The Ki-67 proliferation index was high. Addi - tionally, MLH-1, MSH2, MSH6, and PMS2 mismatch Fig. 1 Well-differentiated carcinoma morphology in curetage material. The tumor consists of complex glandular structures composed of tall co - lumnar cells with mild to moderate atypia (H&E staining, x200) Page 3 of 8 Cagaptay et al. Surgical and Experimental Pathology (2026) 9:7 repair (MMR) immunohistochemistry did not detect any loss of nuclear expression in the tumor. The patient was also evaluated with endoscopy and colonoscopy for possible metastasis of a gastrointestinal system tumor, and no tumor focus was found. Morpho - logical and immunohistochemical findings were evalu - ated together, and a diagnosis of primary intestinal type mucinous endometrial carcinoma was given. The tumor stage was determined as p T1bN0 (FIGO 2023 stage 1B). Molecular analysis was also performed to understand the tumor pathogenesis and to provide a possible targeted therapy option. In molecular analysis, DNA and RNA were isolated from formalin-fixed paraffin-embedded tis- sue by microdissection of the lesion area for next-genera- tion sequencing (NGS) and fusion detection. OncoReveal Multi-Cancer with CNV v4 Panel developed by Pillar Biosciences was used for NGS (for panel details; h t t p s : / / 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 M - 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 n e l - 6 3 0 7 - 1 . p d f). OncoReveal Multi-Cancer RNA Fusion v2 Panel developed by the same company was used for fusion detection (for panel details; h t t p s : / / 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 M - 0 0 2 8 - O N C O R 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). Following the isolation of genetic material, we processed the sample in accordance with Pillar Bioscience’s instruc- tions. The data threshold in the ClinVar database was used to interpret the detected variants to exclude known polymorphisms and identify pathogenicity. There was no fusion detected in RNA fusion detec - tion. NGS analysis performed on the sample detected 39 variants. 31 of these variants belong to intronic, 3’UTR or synonymous mutations. NM_000546.6:c0.817C > T (R273C missense) mutation in the TP53 gene was inter - preted as pathogenic based on the data in ClinVar. NM_000455.5:c0.1062C > G (F354L missense) muta - tion in the STK11 gene and NM_000222.3:c0.1621A > C (M541L missense) mutation in the KIT gene were evaluated as benign. NM_004448.4:c0.1963A > G (I655V missense) mutation in the ERBB2 gene was interpreted as a variation due to its frequency in the population. NM_000222.3:c0.1454A > C (H485P missense) mutation in the KIT gene, NM_001349798.2:c0.1387A > G (T463A missense) and NM_033632.3:c0.1452 G > T(A484S missense) mutation in the FBXW7 gene, NM_000321.3:c0.2377C > T(P793S missense) mutation were detected in the RB1 gene. Since there was no data or sufficient data in ClinVar for these mutations, they were evaluated in the unknown significance category. Considering the possibility of tumor recurrence in the postoperative treatment planning, it was decided to administer chemotherapy and radiotherapy to the patient. The patient received 6 cycles of carboplatin and pacitaxel combination treatment and has been followed up for 6 months without recurrence or metastasis.

The diagnosis of gastrointestinal type endometrial carci - noma requires a comprehensive evaluation of all findings, as morphological and immunohistochemical features alone are not sufficient. When there is no expression of hormone receptors and no squamous morule in a low-grade endometrial carcinoma, and if the morphol - ogy supports it, the possibility of gastric (gastrointesti - nal) type endometrial carcinoma should be considered. According to the criteria defined by Wong et al. (Wong et al. 2020), the tumor is ‘’(i) endometrial adenocarci - noma with no evidence of any other primary site and the presence of gastric-type morphology (voluminous, pale eosinophilic or clear cytoplasm with distinct cell borders) and/or goblet cells. (ii) absence of typical endometrioid component (iii) absence of cervical glandular or stromal involvement (with complete sampling of the cervix) (iv) at least focal immunohistochemical expression of one or more gas - trointestinal markers (eg, MUC6, CK20, and CDX2) Fig. 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 (H&E staining, x200, H&E staining, x400, respectively) Page 4 of 8 Cagaptay et al. Surgical and Experimental Pathology (2026) 9:7 (v) absent or minimal ( < 5%) expression of ER’’ it can be diagnosed as gastrointestinal type endometrioid carcinoma. Differential diagnoses include conventional (Müllerian) type endometrial mucinous carcinoma, gastric/intestinal type endocervical adenocarcinoma, endometrial metas - tases of a gastrointestinal malignancy, and benign lesions with gastrointestinal type mucinous metaplasia. The latest WHO classification (WHO Classification of Tumours Editorial Board 2020) does not include the cri - terion of the 4th edition (CMHCYR, 2014) regarding the definition of conventional mucinous tumors, which states that “the tumor should be classified as mucinous carci - noma if it contains more than 50% mucinous component” . This histological type is now included under the heading of other endometrial carcinomas as “Mucinous carci - noma, gastric (gastrointestinal) type” . The terminology Fig. 3 a: mutant type staning at p53 immunohistochemistry, b: ER negativitiy in the tumor, c: positivity with villin immunohistochemistry, d: positivity with CDX2 immunohistochemistry, 3e: weak positivity with MUC5AC immunohistochemistry Page 5 of 8 Cagaptay et al. Surgical and Experimental Pathology (2026) 9:7 of mucinous differentiation in endometrioid endometrial carcinomas has been retained, but no cut-off value has been specified (Parkash et al. 2023; WHO Classification of Tumours Editorial Board 2020). Therefore, the need for these distinctions arises not from the specification of conventional mucinous endometrial carcinomas as a distinct entity but rather from their superior prognosis compared to gastric (gastrointestinal) type mucinous car- cinomas (CMHCYR, 2014; Wong et al. 2020; Wong, Talia and Mccluggage 2020). Morphologically, conventional - type mucinous carcinomas consist of endocervical type epithelium and do not have the cytomorphological and immunohistochemical features of gastric/gastrointestinal differentiation. They contain typical endometrioid com - ponents. It is generally diffusely positive with ER and PR (Shabani et al., 2007,Lax et al.,. 1998). In curettage specimens, both HPV-related and HPV- unrelated endocervical adenocarcinomas can complicate differential diagnosis. Intestinal type endocervical adeno - carcinomas are associated with HPV, and a significant proportion exhibit ISH positivity. In gastric type endo - cervical adenocarcinomas that are not associated with HPV, HPV ISH will yield negative results. While p16 block positivity may occasionally occur, this is less com - mon compared to gastrointestinal type endometrial car - cinoma. It is recommended to sample the entire cervix to rule out endometrial extension of primary endocervi - cal adenocarcinoma (Dridi, Peoc’h and Karpathiou 2023; Stolnicu et al. 2018; Stolnicu, Hoang and Soslow 2019; Wong et al. 2020). Since the morphological and immunohistochemical findings of endometrial metastasis from a tumor of gas - trointestinal and pancreaticobiliary system origin may be very similar to gastrointestinal type endometrial car - cinoma, evaluation of the patient together with clinical history, endoscopic and imaging findings may help deter- mine the primary focus. Despite conflicting immunohis - tochemical findings, positivity with Müllerian markers may support gynecological origin (Choi et al. 2020; Dridi, Peoc’h and Karpathiou 2023; Ronquillo and Pinto 2022). Benign lesions containing gastrointestinal type meta - plasia can be distinguished from gastrointestinal type endometrial adenocarcinoma by the presence of ER expression, being generally associated with endometrial polyps, and not containing atypia (Wong et al. 2020). We conducted a comprehensive review of the literature and compiled the cases presented to date (Additional file 1, summarizes the findings in cases of endometrial ade - nocarcinoma with gastric (gastrointestinal) type differen- tiation described in the literature). Morphologically, the cases presented in the literature review to date consist of cases that generally show a glan- dular pattern, and less frequently a papillary, cribriform and solid pattern. Two cases describe tumor cells that form small aggregates or small fused glands within muci - nous pools (Rubio et al. 2016; Trippel et al. 2017). In our case, the tumor consists predominantly of glandular and cribriform patterns. In the cases presented, gastric (Abiko et al. 2010; McCarthy et al. 2017; Travaglino et al. 2020; Wong et al. 2020; Wong, Talia and Mccluggage 2020) and intestinal (Ardighieri et al. 2020; Berger et al. 1984; Buell-Gutbrod et al. 2013; Nakano et al. 2023; Trippel et al. 2017; Zheng et al. 1995) type differentiation, as well as gastrointesti - nal type differentiation (Karpathiou et al. 2022; Rubio et al. 2016; Stolnicu et al. 2021), were observed. According to Wong et al. (Wong et al. 2020), the term ‘’gastrointes- tinal type differentiation’’ refers to cases where the dif - ferentiation is not pure and of a single type but includes both gastric and intestinal features. When morphologi - cally gastric/intestinal/gastrointestinal differentiation is suspected, intestinal (CDX2, CK20) and gastric differen - tiation markers (MUC6, HIK1083) may be useful (Dridi, Peoc’h and Karpathiou 2023; Wong et al. 2020). However, since these markers can also be positive in conventional endometrioid adenocarcinomas (Alameda et al. 2007; Hodgson, Parra-Herran and Mirkovic 2019), it is recom - mended to evaluate cytomorphological features together with immunohistochemical features (Wong et al. 2020). In our case, CDX2 and CK20 positivity and MUC6 nega - tivity were interpreted as intestinal differentiation con - sidering the cytomorphological features. The level of atypia is defined as mild and moderate in most cases and severe in some cases (Karpathiou et al. 2022; Travaglino et al. 2020; Wong et al. 2020). In most cases, the tumor appears to contain goblet cells and enterocyte-like tall columnar cells. In some cases, the tumor has been reported to contain varying amounts of neuroendocrine cells (Berger et al. 1984; Zheng et al. 1995), Paneth cells (Berger et al. 1984), and signet ring cells (Berger et al. 1984; Travaglino et al. 2020). Tumor may exhibit morphological heterogeneity. Contrary to the established criteria, cases with an accompany - ing endometrioid (Ardighieri et al. 2020; Berger et al. 1984; Buell-Gutbrod et al. 2013; McCarthy et al. 2017) or serous (Travaglino et al. 2020) component have been reported. In the case we present, similar to most cases in the literature, the tumor consists of enterocyte-like cells with a brush border, abundant eosinophilic cytoplasm with mild to moderate atypia, and occasional goblet cells, and does not contain a typical endometrioid component. Some lesions that may have originated from or been associated with the tumor have been described in the literature. The lesions identified are atypical endome - trial hyperplasia (Buell-Gutbrod et al. 2013; Mogor et al. 2018), mucinous adenocarcinoma in situ and mucinous metaplasia (Abiko et al. 2010), intestinal metaplasia in endometrial polyp (Rubio et al. 2016), gastric metaplasia Page 6 of 8 Cagaptay et al. Surgical and Experimental Pathology (2026) 9:7 and low-grade dysplasia accompanying lobular glandu - lar hyperplasia (Travaglino et al. 2020), mucinous gastric type metaplasia in adenomyomatous polyp and adeno - carcinoma in situ on the basis of müllerian malforma - tion (Wong et al. 2020). Metaplastic lesions that are associated with the tumor have been observed in certain cases. Additionally, there is a study in the literature that indicates that endometrial adenocarcinomas are associ - ated with multifocal and synchronous gastric metaplastic lesions in the female genital tract (Mikami et al. 2009). In the case we present, the non-neoplastic endome - trium is atrophic, does not contain metaplastic benign lesions, and areas resembling high-grade intestinal dys - plasia are observed adjacent to the tumor. It seems appro- priate to use the terminology of “atypical gastrointestinal type mucinous proliferation” (Fig. 4) for this lesion, as it meets the criteria defined by Wong et al. (Wong et al. 2020). However, due to the wide range of potential tumor-related or precursor lesions identified and the small number of cases, it is unclear whether these lesions are true precursor lesions, and there is no consensus on this issue in the literature. It is believed that additional data are needed to understand this issue. The immunohistochemistry panels utilized in the cases presented in the literature exhibited variations. Upon reviewing the findings based on the common mark - ers utilized, positivity was observed in most cases for CK7, CK20, and CDX2. In two cases, CDX2 was nega - tive (Wong et al. 2020). Villin positivity was observed in all cases where villin was administered (Rubio et al. 2016; Wong et al. 2020). PAX8 was positive in some cases and negative in others (Karpathiou et al. 2022; Mogor et al. 2018). In the majority of cases, ER and PR were reported as negative, while focally positive in a few cases and weakly positive in one case (Zheng et al. 1995). Only two of the cases where CEA was used yielded negative results (McCarthy et al. 2017). MUC6 was the most used mucin immunohistochemical marker, with positive results. In one case, all three mucin immunohistochemistry tests were performed, and the result was found to be positive for all three markers (Rubio et al. 2016). In p16 immuno- histochemistry, there have been cases of both block (Kar- pathiou et al. 2022; Stolnicu et al. 2021; Wong et al. 2020; Wong, Talia and Mccluggage 2020) and patchy type posi- tivity (Ardighieri et al. 2020; McCarthy et al. 2017; Rubio et al. 2016). There have been cases where p53 immuno - histochemistry has revealed both mutant (Karpathiou et al. 2022; Wong et al. 2020) and wild type (Stolnicu et al. 2021; Travaglino et al. 2020; Wong et al. 2020) stain- ing. HER2 immunohistochemistry was performed on only one of the cases, and the result was negative (Wong et al. 2020). Similar to the cases in the literature, CDX2, CK20, CK7, villin were positive and ER, PR were negative in our case. MUC2 and MUC6 were negative. Like only one case presented in the literature, MUC5AC was posi - tive (Rubio et al. 2016). MLH1, PMS2, MSH6, and MSH2 nuclear expression were preserved (Karpathiou et al. 2022; McCarthy et al. 2017; Stolnicu et al. 2021) in three of the six cases in which MMR immunohistochemistry was utilized. In two cases, nuclear expression of MLH1 and PMS2 was lost, and molecular analysis revealed MLH1 hypermethylation (McCarthy et al. 2017; Trip - pel et al. 2017). In a single case, MSH6 and MSH2 were reported to have lost nuclear expression. In this case, molecular analysis confirmed the MMR defect/MSI-H status (Ardighieri et al. 2020). Loss of nuclear expression of MMR markers was not observed in our case. The molecular pathogenesis of gastric (gastrointesti - nal) type endometrial carcinoma is not well understood. Molecular features have been described in only a small fraction of cases presented in the literature. In the case series by Wong et al., a SMARCB1 missense mutation and a RB1 nonsense mutation were described in one case. In the case with RB1 mutation, it was stated that the RB gene from the HPV-unrelated pathway may be effective in pathogenesis due to the presence of block type p16 positivity. In two cases with mutant type stain - ing with p53, it was reported that the TP53 gene may be Fig. 4 Transition between areas of high-grade intestinal dysplasia and non-dysplastic epithelium a: H&E staining, x400, b: mutant-type staining of dys - plastic areas in p53 immunohistochemistry Page 7 of 8 Cagaptay et al. Surgical and Experimental Pathology (2026) 9:7 responsible for pathogenesis (Wong et al. 2020). In three cases, pathogenesis was associated with MMR defect (Ardighieri et al. 2020; McCarthy et al. 2017; Trippel et al. 2017). It has been stated that mutations in the STK11 tumor suppressor gene may be effective in pathogenesis in cases accompanied by synchronous mucinous meta - plastic lesions of the female genital tract, with or without Peutz-Jeghers syndrome (Mikami et al. 2009). Our molecular analysis results show that the TP53 and RB genes play an important role in pathogenesis. Although there is insufficient data for mutations in the FBXW7 gene in ClinVar, the literature reports that the T463A mutation is moderately effective in serous endo - metrial carcinomas and the A484S mutation is highly effective in endometrial carcinomas (Le et al. 2012). The role of the FBXW7 gene in the pathogenesis of gastric (gastrointestinal) type endometrial carcinomas is not yet known, but it is thought that both mutations may be effective in pathogenesis since they affect the WD repeat domain. The combination of TP53, RB1, and FBXW7 mutations detected in our case has not been previously reported in the literature. However, this combination of mutations seems to clarify the aggressive nature of the tumor.

Recognizing and making a differential diagnosis of this tumor, known for its aggressive clinical course despite its low-grade morphological features, is crucial for appro - priate clinical management and treatment preference (Travaglino et al. 2020; Wong et al. 2020; Wong, Talia and Mccluggage 2020). Although the histomorphologi - cal and immunohistochemical features of this tumor are relatively well understood, there is insufficient data in the literature regarding its molecular characteristics and biological behavior. In the case we present, we identified a combination of TP53, RB1, and FBXW7 mutations, which are rare but which we believe are associated with the aggressive course of the tumor. The incorporation of additional cases in the literature will enhance our com - prehension of the tumor’s characteristics. Abbreviations WHO World Health Organization ER Estrogen receptor PR Progesterone receptor HPV Human papilloma virus ISH In situ hybridization MMR Mismatch repair NGS Next-generation sequencing Supplementary Information The online version contains supplementary material available at h t t p s : / / d o i . o r g / 1 0 . 1 1 8 6 / s 4 2 0 4 7 - 0 2 6 - 0 0 2 1 9 - 6. Supplementary Material 1

Not applicable. Author contributions Authors SC and ZB were responsible for patient data collection and preparation of the manuscript. Authors TA and SA performed the molecular analyses and analyzed the results. Authors TT and SK provided their clinical expertise. Authors ZB and SA critically revised the manuscript for important intellectual content. All authors approved the final manuscript and agreed to be responsible for all aspects of the work and to ensure that any questions about the work’s accuracy or integrity are properly investigated and resolved. Funding Not applicable. Data availability The data generated and analyzed during the current study are not publicly available due to their personal data content but are available from the corresponding author upon reasonable request. Declarations Ethics approval and consent to participate Our institution does not require ethical approval for reporting individual cases or case series. The research was conducted in accordance with the International Committee of Medical Journal Editors guidelines and the Helsinki Declaration as revised in 2013. All nonessential identifying details have been omitted. Consent for publication Informed consent was obtained from the patient. The participant has Competing interests The authors declare no competing interests. Received: 29 November 2025 / Accepted: 12 January 2026

Abiko K, Baba T, Ogawa M, Mikami Y, Koyama T, Mandai M, et al. Minimal deviation mucinous adenocarcinoma (‘adenoma malignum’) of the uterine corpus. Pathol Int . 2010 Jan 1;60(1):42–47 . [cited 2024 Aug 25]. Available from: h t t p s : / / 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 Alameda F, Mejías-Luque R, Garrido M, Bolós C D. Mucin genes (MUC2, MUC4, MUC5AC, and MUC6) detection in normal and pathological endometrial tis- sues. Int J Gynecological Pathol [Internet]. 2007, Jan;26(1):61–65. [cited 2024 Sep 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 0 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. Ardighieri L, Palicelli A, Ferrari F, Bugatti M, Drera E, Sartori E, et al. Endometrial carcinomas with intestinal-type metaplasia/differentiation: does mismatch repair System defects matter? Case report and systematic review of the literature. J Clin Med [Internet]. 2020;9(8):1–13. [cited 2024 Sep 28]. 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 2 7 8 1 6 6 6 /. Bartosch C, Manuel Lopes J, Oliva E. Endometrial carcinomas: a review emphasiz- ing overlapping and distinctive morphological and immunohistochemical features. Adv Anat Pathol [Internet]. 2011 Nov;18(6):415–37. [cited 2024 Aug 25]. 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 /. Berger G, Fétissof F, Vitrey D, Chayvialle J, Feroldi J. Endometrial carcinoma of the intestinal type. A first case report. Appl Pathol. 1984 Buell-Gutbrod R, Sung CJ, Lawrence WD, Quddus MR. Endometrioid adenocarci- noma with simultaneous endocervical and intestinal-type mucinous differen- tiation: report of a rare phenomenon and the immunohistochemical profile. Diagn Pathol [Internet]. 2013 Aug 2;8(1):128. [cited 2024 Aug 25]. Available from:/pmc/articles/PMC3849525/ Choi S, Joo JW, Do SI, Kim HS. Endometrium-limited metastasis of extragenital malignancies: a challenge in the diagnosis of endometrial curettage speci- mens. Diagn (Basel) [Internet]. 2020;10(3). [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 2 1 6 4 2 1 0 /. Page 8 of 8 Cagaptay et al. Surgical and Experimental Pathology (2026) 9:7 Dridi M, Peoc’h M, Karpathiou G. Primary endometrial gastric (gastro-intestinal)- type carcinoma: a practical approach. Pathol Res Pract [Internet]. 2023 Jan 1;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 / 3 6 5 0 2 7 3 6 /. Hino M, Yamaguchi K, Abiko K, Yoshioka Y, Hamanishi J, Kondoh E, et al. Magnetic resonance imaging findings and prognosis of gastric-type mucinous adeno- carcinoma (minimal deviation adenocarcinoma or adenoma malignum) of the uterine corpus: two case reports. Mol Clin Oncol [Internet]. 2016 May;4(5):699. [cited 2024 Aug 25]. Available from:/pmc/articles/PMC4840738/ Hodgson A, Parra-Herran C, Mirkovic J. Immunohistochemical expression of HIK1083 and MUC6 in endometrial carcinomas. Histopathology [Internet]. 2019 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 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 / h i s . 1 3 8 8 7. Karpathiou G, Chauleur C, Mathonat L, Dridi M, Picot T, Devouassoux-Shisheboran M, et al. Morphologic diversity of the endometrial gastrointestinal-type adenocarcinoma. Pathol Res Pract [Internet]. 2022 Feb 1;230. [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 5 0 2 6 6 4 4 /. Lax SF, Pizer ES, Ronnett BM, Kurman RJ. Comparison of estrogen and progester- one receptor, Ki-67, and p53 immunoreactivity in uterine endometrioid car- cinoma and endometrioid carcinoma with squamous, mucinous, secretory, and ciliated cell differentiation. Hum Pathol. 1998 Sep 1;29(9):924–31 Le Gallo M, O’Hara AJ, Rudd ML, Urick ME, Hansen NF, O’Neil NJ, et al. Exome sequencing of serous endometrial tumors identifies recurrent somatic mutations in chromatin-remodeling and ubiquitin ligase complex genes. Nat Genet [Internet]. 2012 Dec [cited 2024 Oct 19];44(12):1310. Available from: h t t 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 / McCarthy WA, Makhijani R, Miller K, Rojas K, Beffa L, Mathews C, et al. Gastric-type endometrial adenocarcinoma: report of two cases in patients from the United 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 Dec 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 p 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. Mikami Y, Kiyokawa T, Sasajima Y, Teramoto N, Wakasa T, Wakasa K, et al. Reappraisal of synchronous and multifocal mucinous lesions of the female genital tract: a close association with gastric metaplasia. Histopathology [Internet]. 2009 Jan;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 m . n i h . g o v / 1 9 2 0 7 9 4 3 /. Mogor O, Hargrave E, Rush D, Hatch K. Mucinous adenocarcinoma of the endo- metrium with metastasis to the clitoral glans after pelvic exenteration for radiation resistant vaginal cuff recurrence. Gynecol Oncol Rep [Internet]. 2018 Feb 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 i h . g o v / 3 0 6 2 7 6 1 4 /. Nakano C, Fukuda T, Tanaka S, Noda T, Uchikura E, Awazu Y, et al. Intestinaltype mucinous carcinoma of the endometrium showing a polypoidal exophytic form: a case report. Oncol Lett [Internet]. 2023 Oct 1;26(4). [cited 2024 Aug 25]. 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 /. Nieuwenhuizen L, Khalil MK, Naik VR, Othman NH. Prevalence of Goblet Cell Metaplasia in Endocervical and Endometrial Adenocarcinoma: A Histochemi- cal Study. Malays J Med Sci [Internet]. 2007 Jan;14(1):56. [cited 2024 Sep 29]. Available from:/pmc/articles/PMC3351219/. Parkash V, Aisagbonhi O, Riddle N, Siddon A, Panse G, Fadare O. Recent advances in the Classification of gynecological tract tumors: updates from the 5th edition of the World Health Organization “blue book. Arch Pathol Lab Med [Internet]. 2023 Oct 1;147(10):1204–16. [cited 2024 Sep 30]. 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 6 5 9 6 2 7 0 /. Ronquillo N, Pinto A. Gynaecological or gastrointestinal origin? Recognising Müllerian neoplasms with gastrointestinal phenotype and determining the primary site in selected entities. Pathology [Internet]. 2022 Mar 1;54(2):207– 16. [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 8 4 4 7 4 6 /. Rubio A, Schuldt M, Guarch R, Laplaza Y, Giordano G, Nogales FF. Pseudomyxoma- type invasion in gastrointestinal adenocarcinomas of endometrium and cervix: a report of 2 cases. Int J Gynecol Pathol [Internet]. 2016;35(2):118–22. [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 5 9 7 9 /. Shabani N, Mylonas I, Jeschke U, Thaqi A, Kuhn C, Puchner T, et al. Expression of estrogen receptors α and β, and progesterone receptors A and B in human mucinous carcinoma of the endometrium. 2007 Jul;27(4A):2027–33. Stolnicu S, Barsan I, Hoang L, Patel P , Chiriboga L, Terinte C, et al. Diagnostic algo- rithmic proposal based on comprehensive immunohistochemical evaluation of 297 invasive endocervical adenocarcinomas. Am J Surg Pathol [Internet]. 2018 Aug 1;42(8):989. [cited 2024 Sep 23]. Available from:/pmc/articles/ PMC6041133/ Stolnicu S, Hoang L, Soslow RA. Recent advances in invasive adenocarcinoma of the cervix. Virchows Arch [Internet]. 2019 Nov 1;475(5):537–49. [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 i h . g o v / 3 1 2 0 9 6 3 5 /. Stolnicu S, Podoleanu C, Orban I, Francisc R. Endometrial adenocarcinoma with gastrointestinal differentiation – a newly described entity, with morphologic diversity. Pol J Pathol. Termedia Publishing House Ltd. 2021;72:84–86 Travaglino A, Raffone A, Gencarelli A, Mollo A, Zullo F, Insabato L. Endometrial gastric-type carcinoma: an aggressive and morphologically heterogenous New histotype arising from gastric metaplasia of the endometrium. Am J Surg Pathol [Internet]. 2020 Jul 1;44(7):1002–04. [cited 2024 Aug 25]. Avail- able 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 /. Trippel M, Imboden S, Papadia A, Mueller MD, Mertineit N, Härmä K, et al. Intestinal differentiated mucinous adenocarcinoma of the endometrium with sporadic MSI high status: a case report. Diagn Pathol. 2017 May 12;12(1) WHO Classification of Tumours Editorial Board. Female genital tumours [Internet]. (WHO classification of tumours series. 5th. Vol. 4). Lyon (France: International Agency for Research on Cancer; 2020 [cited 2024 08 25]. Available from: h t t p s : / / 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 WHO Classification of Tumours of female reproductive organs. In: Cmhcyr KRJ, editor. WHO classification of tumors. 4th. Vol. 3. Lyon, France: International Agency for Research on Cancer; 2014 Wong RWC, Ralte A, Grondin K, Talia KL, McCluggage WG. Endometrial gastric (gastrointestinal)-type mucinous lesions: report of a series illustrating the spectrum of benign and malignant lesions. Am J Surg Pathol [Internet]. 2020 Mar 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 l m . n i h . g o v / 3 1 5 6 7 2 8 0 /. Wong RWC, Talia KL, Mccluggage WG. Endometrial gastric-type carcinoma: an aggressive and morphologically heterogenous New histotype arising from gastric metaplasia of the endometrium. Am J Surg Pathol [Internet]. 2020 Dec 1;44(12):1736–37. [cited 2024 Sep 28]. 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 3 1 7 0 8 1 1 /. Zheng W, Yang GCH, Godwin TA, Caputo TA, Zuna RE. Mucinous adenocarcinoma of the endometrium with intestinal differentiation: a case report. Hum Pathol [Internet]. 1995;26(12):1385–88. [cited 2024 Aug 25]. 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 / 8 5 2 2 3 1 5 /. Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.