Gastric-type endocervical adenocarcinoma with Peutz-Jeghers syndrome: a case report and literature review

Abstract

Gastric-type endocervical adenocarcinoma (G-EAC) is a mucinous adenocarcinoma with gastric differentiation, and its preoperative diagnosis is challenging due to nonspecific symptoms. Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple gastrointestinal hamartomatous polyps, associated with an increased risk of G-EAC and other gynecological malignancies. We report a 44-year-old woman presenting with a 10-year cervical mass and 3-year vaginal discharge. She did not seek further medical attention because the cervical mass was asymptomatic and grew slowly. At age 35, she underwent partial jejunectomy for multiple small bowel polyps and intussusception, and postoperative pathology confirmed PJS. Her ultrasound revealed a 4.9 × 3.5 × 3.3 cm cervical mass, while cervical cytology examination was normal. G-EAC was unexpectedly diagnosed on postoperative pathology following total hysterectomy. Postoperative PET-CT imaging demonstrated pelvic lymph node metastasis. She subsequently underwent radical parametrectomy, bilateral oophorectomy, pelvic lymph node dissection, followed by chemotherapy. We also reviewed previously G-EAC cases with PJS, summarizing the pathogenesis and key points for diagnosis and treatment. We provide an in-depth analysis of the reasons for missed diagnosis of G-EAC and highlight the diagnostic challenges. The aim is to enhance gynecologists’ understanding of G-EAC in patients with PJS.

1. Introduction

Gastric-type endocervical adenocarcinoma (G-EAC) is the most common type of non-human papillomavirus (HPV)-associated cervical cancer, accounting for approximately 10% of all cervical adenocarcinomas (1). Minimal deviation adenocarcinoma (MDA), also historically termed adenoma malignum(AM), represents the extremely well-differentiated morphological subtype of G-EAC (2). Due to the lack of typical clinical manifestations, most early-stage G-EAC patients present solely with profuse watery vaginal discharge. Clinically, G-EAC is frequently mistaken for inflammatory conditions such as vaginitis or cervicitis, and the preoperative pathological diagnosis rate is low. However, G-EAC exhibits highly malignant biological behavior. Its 5-year disease-specific survival rate (DSS) was 42%, significantly lower than that of common-type cervical adenocarcinoma (91%) (3).

Peutz-Jeghers syndrome (PJS) is a rare genetic disorder associated with serine/threonine kinase 11 (STK11)/liver kinase B1 (LKB1) gene mutations. It is characterized by mucocutaneous pigmentation, gastrointestinal hamartomatous polyps, and a high susceptibility to malignancies. First described by Peutz (1921) and Jeghers (1949), it has a prevalence of 1/50,000–1/250,000 (4). As a tumor susceptibility syndrome, PJS increases the risk of developing multiple cancers. In patients with PJS, tumors commonly arise in the gastrointestinal tract, cervix, ovary, breast, lung, and pancreas. It has been reported that the risk of gynecological tumors in female PJS patients is approximately 15-fold higher than in the general female population (5).

Here, we report a rare case of G-EAC combined with PJS and summarize previously published similar cases to enhance clinicians’ diagnostic and therapeutic capabilities for this disease.

2. Case report

A 44-year-old female was admitted to the Department of Gynecology at Guangxi Medical University First Affiliated Hospital on September 27, 2024, presenting with a 10-year history of a cervical mass and a 3-year history of vaginal discharge. She first discovered the cervical mass during a physical examination 10 years prior, when it measured approximately 2×2×2 cm. In 2016, she underwent hysteroscopic surgery due to an ultrasound indicating a cervical canal mass (4.1×3.6×3 cm). Hysteroscopy revealed multiple masses within the cervical canal (the largest approximately 2 cm in diameter). The operating surgeon misinterpreted the cervical canal masses as Nabothian cysts and therefore did not perform a biopsy. Subsequently, regular gynecological ultrasound follow-ups showed gradual enlargement of the cervical masses. Since the patient’s cervical mass was asymptomatic and growing slowly, she did not seek further medical attention after the hysteroscopy, aside from annual ultrasound examinations. She began experiencing vaginal discharge three years ago and was treated for vaginitis without improvement. Over the past three years, her vaginal secretions have gradually increased, appearing as clear, mucus-like discharge. She has no symptoms of irregular vaginal bleeding or contact bleeding. On July 21, 2023, she underwent a transvaginal ultrasound re-examination. The ultrasound image demonstrated a well-defined, mixed-echoic mass measuring 4.9 × 3.5 × 3.3 cm in the cervix. On August 12, 2024, the patient underwent pelvic magnetic resonance imaging (MRI), which revealed a cervical cystic-solid mass measuring 4.7 × 5.8 × 5.2 cm. The cervical thinprep cytologic test (TCT) showed no abnormalities, and the HPV test result was negative. The levels of tumor markers: SCCA: 0.80 ng/mL; Carbohydrate antigen 125 (CA125): 29.80 U/mL; Carbohydrate Antigen 199 (CA199): 50.21 U/mL. In 2015, she underwent partial jejunectomy with intestinal anastomosis due to multiple small bowel polyps and intussusception. The patient had a history of two pregnancies, with one full-term delivery and one abortion. She had no further fertility requirements. Her menstrual cycles were regular, with normal flow and absence of dysmenorrhea. Her last menstrual period was September 21, 2024. She had no history of smoking and no significant family history. Gynecological examination demonstrated abundant clear fluid in the vaginal cavity. The cervix was smooth but enlarged, with multiple well-defined cystic masses at the external os. The uterus was slightly enlarged, and bilateral adnexal regions were non-palpable for masses. Preoperative diagnosis: Cervix neoplasm.

After completing the preoperative preparations, the patient underwent robot-assisted laparoscopic total hysterectomy and bilateral salpingectomy. Gross pathological examination (Figure 1A): The uterus measured 10 × 6.6 × 3.9 cm. A 6.2 × 4.2 × 2.4 cm cystic-solid mass was identified in the cervix, with a gray-white solid component and clear mucus within the cystic component. The lesion involved >1/2 of the cervical wall. Postoperative histopathology (Figures 1B–D) revealed the cervical mass to be G-EAC, with an infiltration depth exceeding 2/3 of the cervical canal wall (1.2 cm/1.5 cm). Immunohistochemistry results: p16 (–), Ki-67 (approximately 10% positive), p53 (wild-type), ER (–), PR (–), Muc-6 (+), Claudin 18.2 (+), HER2 (1+).

Figure 1.

(A) A raised mass (6.2×4.2×2.4 cm) was observed on the cervix. (B) Postoperative pathological examination. The tumor cells demonstrate well-formed glandular structures with orderly cellular arrangement. They exhibit abundant mucinous cytoplasm, which appears clear or pale eosinophilic. The tumor cell borders are distinct. (C, D) Tumor tissue: tumor cells MUC6(+) and ER (–). Magnifications ×400.

After the operation, she further underwent positron emission tomography-computer tomography (PET-CT) (Figures 2A, B), and the results indicated that the tumor had metastasized to the lymph nodes adjacent to the right internal iliac artery and the right common iliac artery. The abdominal and pelvic enhanced computed tomography (CT) indicated that the lymph nodes on the side of the right iliac artery were involved. Under gastrointestinal endoscopy, multiple polyps were observed in the stomach, duodenum, and colon/rectum. The pathological types included hyperplastic polyps, tubulovillous adenomas, and serrated adenomas/hamartomas. Genetic testing variant sites: STK11 p.P179Rfs*108, ERBB3 p.G284R, KRAS p.G12D. Review of the patient’s medical history revealed that she had been pathologically diagnosed with PJS at the time of partial jejunectomy in 2015.

Figure 2.

(A) PET-CT indicated that the tumor had metastasized to the lymph nodes adjacent to the right internal iliac artery. (B) PET-CT indicated that the tumor had metastasized to the lymph nodes adjacent to the right common iliac vessels.

On December 17, 2024, she underwent radical parametrectomy with removal of a vaginal cuff, bilateral oophorectomy, pelvic lymph node dissection, pelvic tumor resection, abdominal adhesion release surgery, sigmoid colon and rectal partial resection, and colo-rectal anastomosis. Postoperative pathology demonstrated tumor metastasis to the bilateral ovaries, peritoneum, and mesorectum. Immunohistochemical results: HER2 (–), WT1 (–), p53 (positive, mutant type), Ki-67 (10% positive), ER (–), PR (–). Final diagnosis: (1) G-EAC (FIGO IIB) (2) PJS. She received 6 cycles of combination chemotherapy with gemcitabine and cisplatin from January 2 to April 22, 2025. However, on June 16, 2025, CT revealed tumor metastasis to the vaginal stump, with suspected metastases involving multiple sites in the pelvic and abdominal cavities.

3. Discussion

Cases of G-EAC co-occurring with PJS are relatively rare. We searched the Web of Science database using the terms “gastric-type endocervical adenocarcinoma,” “minimal deviation adenocarcinoma,” “adenoma malignum,” “gastric-type adenocarcinoma,” and “Peutz-Jeghers syndrome”. As of September 2025, a total of 25 English-language published cases of G-EAC combined with PJS were identified (6–29) (Table 1). Across all cases, the median age at onset for PJS was 19 years (range: 2 months–41 years), while the median age for G-EAC onset was 33 years (range: 24–50 years). Previous studies report a prevalence of G-EAC among women with PJS ranging from 15% to 30%. Compared to women without PJS, those with PJS are diagnosed with G-EAC at a significantly younger age (55 years vs. 33 years) (30). Putative precursors of G-EAC include benign lesions (lobular endocervical glandular hyperplasia (LEGH) and pyloric gland metaplasia), as well as atypical LEGH and gastric-type adenocarcinoma in situ arising from them (31). The precursor lesions of G-EAC have a long course, with a median interval of approximately 18 years (range: 2 months–31 years) from the diagnosis of PJS to the development of LEGH or G-EAC (32). In addition, PJS also increases the risk of various other tumors. Sixteen patients (16/25) had one or more concomitant tumors in addition to G-EAC. The most common was ovarian sex cord tumor with annular tubules (SCTAT) (12/25), followed by ovarian mucinous tumors (6/25).

Table 1.

Cases report of G-EAC with PJS.

Reference	No	Reporter (Year)	Age at PJS onset	Age at G-EAC onset	Symptom	HPV test	Cervical cytology	Biopsy pathology	Imaging examination methods	Initial surgical plan	Second surgery	Postoperative adjuvant therapy	Concurrent tumors	Genetic mutation testing
(6)	1	Mcgowan et al. (1980)	11	29	irregular uterine bleeding	–	–	adenocarcinoma	–	RH + PLND	–	radiotherapy	SCTAT	–
(6)	2	Mcgowan et al. (1980)	11	27	irregular uterine bleeding	–	–	well-differentiated adenocarcinoma	–	RH+RSO+PLND+upper vaginectomy	–	–	ovarian mucinous cystadenoma of borderline malignancy	–
(7)	3	Kaku et al.(1985)	2	29	Abnormal vaginal bleeding, postcoital bleeding and a moderate increase of mucoid vaginal discharge	–	suspicious for carcinoma	adenomatous proliferation of endocervical glands	–	TH	–	chemotherapy	–	–
(8)	4	Chen et al.(1986)	7	33	menometrorrhagia and an adnexal mass	–	–	–	–	TH + RSO	–	–	ovarian mucinous tumors,SCTAT	–
(9)	5	Soeters et al.(1989)	16	40	menorrhagia	–	–	–	–	TH + BSO	–	–	–	–
(10)	6	Podczaski et al.(1991)	17	40	pelvic mass	–	–	–	–	TH + RSO+left ovarian cystectomy	–	–	ovarian mucinous cystadenoma,SCTAT	–
(11)	7	Choi et al.(1993)	17	35	progressive abdominal distension	–	–	–	US,CT	TH + BSO + partial omentectomy	–	–	ovarian mucinous cystadenoma of borderline malignancy,SCTAT	–
(12)	8	Hizawa et al.(1993)	25	25	genital discharge	–	negative	–	US,CT	RH +BSO+PLND	–	–	SCTAT	–
(13)	9	Tsuruchi et al.(1994)	25	25	loss of appetite and hematemesis,occasional abdominal pain and tarry stools,increased vaginal discharge	–	atypical columnar cells	negative	US,CT,MRI	cornization	RH+ BSO + PLND + para-aortic lymph node biopsy	–	SCTAT	–
(14)	10	Srivatsa et al.(1994)	29	29	abdominal fulliness, constipation, increasing abdominal girth, and watery mucosa discharge	–	–	negative	US,CT	TH + BSO + complete omentectomy + appendectomy + retroperitoneal cystotomy + carcinomatous debulking	–	chemotherapy	SCTAT	–
(15)	11	Fujiwaki et al. (1996)	27	29	increased vaginal discharge	–	–	well-differentiated adenocarcinoma	–	RH + PLND	–	radiotherapy	–	–
(16)	12	Mangili et al. (2004)	41	41	left adnexal mass, abdominal pain, postprandial dyspepsia, vomiting and episodic proctorrhagia	–	–	–	US,CT	TH+ omentectomy + bilateral sampling of external iliac lymph nodes + ileal resection.	–	–	ovarian serous-papillary cystoadenoma,ovarian mixed serous and mucinousl borderline tumor,SCTAT	–
(17)	13	Song et al. (2006)	31	41	right adnexal palpable mass,lower abdominal pain.	–	atypical metaplastic cells	adenoma malignum	US	RH + BSO	–	chemotherapy	breast cancer, ovarian mucinous borderline tumors, SCTAT	–
(18)	14	Clements et al. (2009)	13	43	pelvic mass	-	-	-	US,CT	RH + BSO	-	chemoradiation	breast cancer,SCTAT	STK11 gene mutation
(19)	15	Mccluggage et al. (2010)	–	50	a thickened endometrium,a fluid filled endometrial cavity	negative	-	mucinous metaplasia	US	TH +BSO	radical parametrectomy with removal of a vaginal cuff + PLND	chemoradiation	breast cancer	–
(20)	16	Kobayashi et al. (2014)	30	30	excessive watery vaginal discharge	negative	atypical glandular cells	focal lymphovascular space invasion was suspected	CT,MRI	RH + BSO	-	chemotherapy	–	STK11 gene mutation
(21)	17	Peng et al. (2015)	10	33	watery vaginal discharge	-	tumor cells	mucinous adenocarcinoma	MRI	TH	-	–	–	–
(22)	18	Neyaz et al. (2017)	24	24	white mucoid discharge and bleeding per vaginum	-	-	mucinous adenocarcinoma	US,MRI	RH+BSO+PLND+vaginal reconstruction	-	radiotherapy	–	–
(23)	19	Kotaka et al. (2021)	11	45	watery discharge	-	atypical glandular cells	-	US,MRI,CT	TH	radical parametrectomy+BSO+PLND	–	peritoneal carcinoma	STK11 gene mutation
(24)	20	Dinh et al. (2021)	32	39	vaginal discharge and chronic pelvic pain	-	-	atypical glandular cells	US,MRI	RH+BSO+PLND	-	chemoradiation	–	–
(25)	21	Tong et al. (2023)	2 months	32	recurrent watery vaginal discharge and prolonged menstrual periods	negative	-	moderately differentiated G-EAC	MRI	RH+BSO+PLND+PALND	-	chemoradiation	breast fibroma	STK11 gene mutation
(26)	22	Wu et al. (2023)	30	32	lower abdominal mass with abdominal distension	-	-	G-EAC	CT	RH+abdominal and pelvic mass resection	-	chemotherapy	–	CDKN2A gene mutation
(27)	23	Li et al. (2023)	24	31	increased vaginal discharge	negative	negative	G-EAC	US,MRI	conization	RH+BSO+PLND	chemoradiation	SCTAT	–
(28)	24	Zhou et al. (2024)	8	38	abdominal distension and gradual enlargement of the lower abdomen	-	negative	-	US	TH++LSO+right salpingectomy+right ovary biopsy+greater omental resection+appendectomy	-	chemotherapy	–	STK11 gene mutation
(29)	25	Sun et al. (2025)	21	39	thin and mucoid vaginal discharge and vaginal odor	negative	-	HPV-unrelated G-EAC	US,CT,MRI,PET-CT	TH+BSO+PLNDy+pelvic adhesionlysis	-	chemoradiation	cervicovaginal myofibroblastoma,SCTAT	–

-indicates that the result was not reported in the original publication. US, Ultrasound; RH, Radical hysterectomy; TH, Total hysterectomy; PLND, Pelvic lymph node dissection; BSO, Bilateral salpingo-oophorectomy; RSO, Right salpingo-oophorectomy; LSO, Left salpingo-oophorectomy; PALND, Para-aortic lymph node dissection.

Although the etiology of G-EAC remains unclear, multiple studies have explored its molecular genetic characteristics through gene sequencing, revealing that TP53, STK11, CDKN2A, and ARID1A are the most frequently mutated genes, primarily involved in cell cycle regulation and the PI3K/AKT signaling pathway (33–36). Among the 25 previously reported cases, genetic testing was performed in 6 patients. The results revealed STK11 mutations in five cases, including insertion and deletion mutations, and a CDKN2A frameshift mutation in 1 case. STK11 is a tumor suppressor gene located on chromosome 19p13.3 and is involved in the regulation of cellular DNA damage responses, proliferation, senescence, apoptosis, differentiation, and aerobic glycolysis (37). In G-EAC, STK11 mutations correlate with poorer prognosis and are more prevalent in cases exhibiting high differentiation and extensive lymphovascular invasion (33). The patient in our case harbored a frameshift mutation in STK11, leading to protein truncation and loss of function, which may contribute to rapid tumor progression and therapy resistance.

Early-stage G-EAC lacks typical symptoms and presents no specific physical signs. Common manifestations include increased vaginal mucus-like or watery discharge, abdominal pain or distension, and pelvic or abdominal masses. Among the 25 cases, abnormal vaginal discharge was the most common symptom in patients with G-EAC and PJS (13/25), followed by abdominal pain or distension (7/25), abdominal or pelvic mass (6/25), and abnormal uterine bleeding (5/25). These symptoms may present singly or in combination. The cervix of G-EAC patients is enlarged, with a smooth or eroded external os. Lesions are predominantly located in the middle to upper portion of the cervical canal, forming a “barrel-shaped” cervix. Clinically, this condition is prone to misdiagnosis or missed diagnosis. In the present case, the patient had a cervical mass for 10 years that grew slowly. Before her first hospitalization, she had experienced recurrent vaginal discharge for 3 years. Insufficient understanding of the clinical characteristics of G-EAC precursor lesions among clinicians contributed to missed and delayed diagnosis.

G-EAC commonly involves the upper cervix and is predominantly an endogenous invasive lesion. These manifestations affect the positive rate of cervical biopsy. During the sampling process of cervical cytology, it is difficult to reach the deep part of the cervical canal, thus, the referral rate for colposcopy and the rate of cervical biopsy are relatively low. Even if the patient undergoes colposcopy, the probability of detecting and accurately obtaining deep lesions in the cervical canal is limited (38). Among the 25 cases identified in the literature, 5 underwent HPV screening, all with negative results. 9 underwent cervical cytology screening: 3 were negative, and 6 showed abnormal results; 4 with atypical cells, 1 with suspected malignancy, and 1 with tumor cells. 15 patients underwent cervical biopsy: 4 were negative, and 11 showed cancerous pathology. In this case, since both HPV and TCT were negative, no further colposcopy or cervical biopsy was performed. This was one of the reasons for the preoperative missed diagnosis.

Transvaginal ultrasound and MRI are commonly used imaging modalities for G-EAC. G-EAC ultrasound images typically show small cysts arranged in a honeycomb pattern at the cervix, surrounded by larger cystic masses (“cosmos sign”). Concurrently, the cervix exhibits polycystic or cystic-solid lesions accompanied by vesicular structures in the lower uterine segment and/or myometrium (“vesicular implantation sign”). These characteristics may be helpful for the early diagnosis of G-EAC (39). MRI findings of G-EAC are specific. The typical MRI manifestation of G-EAC is the “cosmos sign”. The lesion has a small cyst or solid component in the center, surrounded by larger cysts. If the T1WI shows low signal and T2WI shows high signal, the possibility of G-EAC should be highly suspected. This sign is useful for differential diagnosis between G-EAC and cervical nabothian cysts (40). Some G-EAC lesions may also present as purely solid or purely cystic (41). MRI offers multiparametric, multi-directional imaging with high soft tissue resolution, making it particularly effective at revealing the characteristics of G-EAC. It can serve as a routine screening method for patients with PJS and those highly suspected of having G-EAC. CT examination has a greater advantage in determining the involvement of lymph nodes and distant metastasis. However, compared with usual-type endocervical adenocarcinoma (UEA), the preoperative imaging staging has lower diagnostic performance and sensitivity for G-EAC. The endogenous and highly invasive growth pattern of G-EAC may lead to an underestimation of the extent of tumor involvement in imaging examinations (42).

Pathological examination remains the cornerstone of G-EAC diagnosis. Kojima et al. proposed three morphological criteria for diagnosing G-EAC: abundant mucinous cytoplasm, clear or pale eosinophilic cytoplasm, and well-defined tumor cell borders (43). However, G-EAC exhibits significant morphological heterogeneity. Combined methods such as immunohistochemistry are helpful for diagnosis and differential diagnosis. HIK1083 and MUC6 are important immunohistochemical markers for diagnosing G-EAC. Statistics indicate that HIK1083 has a sensitivity/specificity of 0.64/0.94, while MUC6 has 0.51/0.74 (44). p16 negative expression or focal positivity holds significant value in differentiating G-EAC from conventional cervical adenocarcinoma. Diffuse strong p16 positivity may occur in rare cases. Relying solely on p16 immunohistochemical staining to assess HPV infection status is inaccurate (45). Approximately 50% of G-EAC patients exhibit TP53 mutations (46). This may correlate with the tumor’s high malignancy and poor prognosis. PAX8 typically shows focal positivity in G-EAC. It is negative in the vast majority of gastrointestinal tumors, including pancreaticobiliary cancers. PAX8 positivity helps in distinguishing metastatic adenocarcinomas of digestive tract origin. However, PAX8 negativity does not rule out the possibility of a primary cervical tumor (46, 47). ER, PR, PAX2, and HER2 are typically negative in G-EAC patients, aiding in differentiation from normal or benign non-gastric cervical glandular lesions (46). Over 70% of G-EAC patients express PD-L1 (Combined Positive Score ≥ 1) (48). Accurate pathological diagnosis depends on obtaining adequate preoperative cervical biopsy specimens. Intraoperative frozen section provides only localized histological information and has limitations in detecting molecular markers. Therefore, for G-EAC patients with inconclusive preoperative diagnoses, postoperative pathology serves as definitive confirmation, increasing the risk of secondary surgery.

Due to the lack of prospective clinical research evidence, there are currently no specific treatment guidelines for G-EAC. Treatment for G-EAC primarily follows the principles for cervical squamous cell carcinoma and UEA. However, G-EAC exhibits higher malignancy, increased susceptibility to drug resistance and distant metastasis, and poorer prognosis, emphasizing the importance of individualized treatment plans. The 2023 Chinese expert consensus recommends surgery as the mainstay for early-stage patients. The recommended surgical procedure is radical hysterectomy with pelvic lymph node dissection ± para-aortic lymph node dissection. Concurrent resection of bilateral adnexa, omentum, appendix, and any metastatic lesions within the pelvic and abdominal cavities is recommended. Ovarian preservation and fertility-sparing approaches are not recommended for early-stage G-EAC patients (49). Postoperative adjuvant therapy, including chemoradiation ± targeted therapy, depends on intraoperative findings and pathological diagnosis. Given the high malignancy of G-EAC, postoperative chemoradiation indications may be appropriately expanded (49). In the reported cases of G-EAC with concomitant PJS, all patients underwent surgical treatment, and 60% received postoperative adjuvant therapy. Immunotherapy may be an effective treatment for PD-L1-positive G-EAC (50). However, STK11 mutations are associated with the development of resistance to PD-1/PD-L1 inhibitors (51). A considerable proportion of patients with G-EAC carry STK11 mutations, and whether such patients can benefit from immunotherapy warrants further investigation. The application of targeted therapy in G-EAC patients is still under exploration.

In summary, several valuable lessons can be learned from this case. First, clinicians should prioritize the early identification of PJS through careful physical examination and thorough family history assessment. Second, for the management of PJS patients, annual physical examinations and routine screening using imaging modalities such as MRI are essential. Clinicians must remain vigilant for characteristic symptoms such as abdominal or pelvic pain, vaginal bleeding, and mucus-like or watery vaginal discharge. Third, PJS patients with abnormal TCT results should undergo colposcopy and cervical biopsy promptly. For patients with normal TCT results but a history of vaginal discharge and other symptoms highly suggestive of G-EAC, colposcopy and multipoint cervical biopsy, targeted needle biopsy, endocervical curettage, or even cervical conization may be performed as necessary to obtain pathological specimens. Finally, an accurate pathological diagnosis is crucial for G-EAC patients. Pathologists must fully recognize the histological diversity of G-EAC and utilize immunohistochemistry for differential diagnosis to reduce or avoid pathological misdiagnosis and oversight.

4. Conclusion

G-EAC associated with PJS is a rare yet highly aggressive malignancy that poses significant diagnostic and therapeutic challenges. Greater awareness of the link between PJS and gynecologic tumors among gynecologists is warranted. Pathology plays a crucial role in diagnosing G-EAC. Future research should focus on identifying immunohistochemical markers with higher specificity and sensitivity. Treatment strategies for G-EAC remain non-standardized and warrant further investigation through large-scale, prospective, multicenter clinical studies.

Funding Statement

The author(s) declared that financial support was received for this work and/or its publication. This study was supported by Clinical Research “Climbing” Program of the First Affiliated Hospital of Guangxi Medical University(No. YYZS2024006), Guangxi Natural Science Foundation(No. 2025GXNSFDA069002), Guangxi Natural Science Foundation (No. 2025GXNSFAA069050) and Young Medical Reserve Talent Training Program of Guangxi province.

Data availability statement

The original contributions presented in the study are included in the article/supplementary material. Further inquiries can be directed to the corresponding author/s.

Ethics statement

The studies involving humans were approved by Ethics Committee of First Affiliated Hospital of Guangxi Medical University (2025-E0810). The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants' legal guardians/next of kin in accordance with the national legislation and institutional requirements. Written informed consent was obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article.

Author contributions

JL: Investigation, Data curation, Writing – original draft, Writing – review & editing. RL: Investigation, Data curation, Writing – original draft, Writing – review & editing. HL: Resources, Writing – review & editing. DS: Funding acquisition, Supervision, Writing – review & editing. JF: Funding acquisition, Supervision, Writing – review & editing.

Conflict of interest

The author(s) declared that this work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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