Endometrioid endocervical adenocarcinoma in a postmenopausal woman: a case report and review of the literature

In terms of a clinical case, this is a 62-year-old woman with gravid 2, para 2. Her BMI was 26.67 kg/m 2 . Her medical, allergic, family, and social histories were insignificant. In terms of personal obstetric history, the patient underwent a left fallopian tube surgery in 2002 for ectopic pregnancy. She had two vaginal deliveries. There was no history of itching or offensive smell. She had no history of HPV vaccination, experienced menopause at the age of 52 years, and did not take any medications, smoke, drink alcohol, or use illicit drugs. Routine smear test and screening for high-risk HPV test were both negative 2 years ago. On 30 March 2025, the general practitioner referred the patient to the gynecology clinic after finding fluid in the endometrial cavity during a transvaginal ultrasound. The patient claimed no symptoms. On 4 April 2025, a routine gynecological ultrasound performed at a local hospital revealed an intrauterine fluid collection measuring 6 mm, suggesting endometrial fluid retention. Given the suspicion of endometritis, the patient was initially prescribed a 2-week course of broad-spectrum oral antibiotics, including Cefixim, Metronidazole, and Doxycycline. On 18 April 2025, the patient came to University Medical Center Ho Chi Minh City – Campus 2. During her gynecologic examination, after speculum insertion, there was no obvious contact bleeding when wiping the surface of the cervix with a cotton swab. In the bimanual gynecological examination, the cervix was palpable, normal in size, with well-defined borders, firm, and slightly elastic. The vaginal fornices were soft with no obvious mass. No masses were touched on both sides of the para-uterine spaces. During rectovaginal examination, the soft rectal mucosa was touched without abnormal masses. No other abnormality was found during the palpation of the uterus and the bilateral adnexal area. Transvaginal ultrasound was performed, revealing: homogeneous uterine echotexture, thin endometrial thickness and a persistent intrauterine fluid, measuring 8 mm (Fig. 1 ). Figure 1. Image of transvaginal ultrasound. Image of transvaginal ultrasound. A fractional curettage with histopathology was performed, and the results were as follows: high-grade squamous intraepithelial lesion of the cervix with co-existing adenocarcinoma, unable to rule out cervical origin (Fig. 2 ). Cervical cancer was suspected, warranting a contrast-enhanced magnetic resonance imaging (MRI). Figure 2. Histological examination of the fractional curettage specimen [hematoxylin and eosin (H&E) stain]. The image illustrates the coexistence of two distinct lesions: (A) high-grade squamous intraepithelial lesion (HSIL/CIN 3) of the cervix, characterized by pleomorphic and dysplastic nuclei occupying nearly the full thickness of the epithelium, and (B) co-existing adenocarcinoma, showing atypical glandular structures infiltrating the stroma, accompanied by numerous mitotic figures. Histological examination of the fractional curettage specimen [hematoxylin and eosin (H&E) stain]. The image illustrates the coexistence of two distinct lesions: (A) high-grade squamous intraepithelial lesion (HSIL/CIN 3) of the cervix, characterized by pleomorphic and dysplastic nuclei occupying nearly the full thickness of the epithelium, and (B) co-existing adenocarcinoma, showing atypical glandular structures infiltrating the stroma, accompanied by numerous mitotic figures. On 8 May 2025, MRI showed a suspicious hyperintense 1 × 1.5 × 1.4 cm solid mass arising from the cervical canal. There was no invasion of uterine corpus or vagina. No parametrial involvement or significant retroperitoneal lymph node enlargement was detected. MRI diagnosis of stage IB1 [International Federation of Gynecology and Obstetrics (FIGO) 2018] was made based on the findings (Fig. 3 ). Figure 3. MRI – T2-weighted views. (A) The sagittal plane shows a T2w intermediate tumor (arrow) limited to the cervix. (B) The axial plane (T2w) confirms the tumor’s boundary and the absence of parametrial infiltration, confirming cervical carcinoma FIGO IB1 staging. MRI – T2-weighted views. (A) The sagittal plane shows a T2w intermediate tumor (arrow) limited to the cervix. (B) The axial plane (T2w) confirms the tumor’s boundary and the absence of parametrial infiltration, confirming cervical carcinoma FIGO IB1 staging. A diagnosis of the cervical carcinoma (T1b1N0M0) led to a radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. The final pathology result showed moderately differentiated ECA. The tumor size was 1.5 cm. The tumor invaded the endocervical canal and uterine isthmus. No parametrial invasion or no vaginal invasion was detected. It revealed no evidence of vaginal metastasis. Crucially, all 34 examined lymph nodes were negative for metastatic disease. Immunohistochemical (IHC) analysis revealed tumor cells positive for carcinoembryonic antigen (CEA) and patchy-positive for p16, while being negative for estrogen receptor (ER), progesterone receptor (PR), and Vimentin. This specific IHC pattern (CEA+, ER−/PR−/Vimentin−) strongly supports a primary cervical origin over endometrial carcinoma (Fig. 4 ). Figure 4. Histological and IHC examination of the final surgical specimen. (A, B) H&E staining showing the morphology of moderately differentiated ECA. The tumor is characterized by atypical glandular structures (black arrow) and thick cellular clumps infiltrating the stroma, composed of cells with large, pleomorphic nuclei and numerous mitotic figures. (C, D) IHC staining differentiating ECA from endometrial carcinoma. (C) Tumor cells showing strong, diffuse cytoplasmic positivity for CEA (brown staining). (D) Tumor cells are negative for Vimentin (blue nuclear counterstain only). Histological and IHC examination of the final surgical specimen. (A, B) H&E staining showing the morphology of moderately differentiated ECA. The tumor is characterized by atypical glandular structures (black arrow) and thick cellular clumps infiltrating the stroma, composed of cells with large, pleomorphic nuclei and numerous mitotic figures. (C, D) IHC staining differentiating ECA from endometrial carcinoma. (C) Tumor cells showing strong, diffuse cytoplasmic positivity for CEA (brown staining). (D) Tumor cells are negative for Vimentin (blue nuclear counterstain only). After surgery, the patient’s condition was stable. Because of the patient’s normal post-operative recovery, she was discharged after 7-day treatment. The patient was scheduled 2 weeks for follow-up routinely and her health conditions were still stable. One month later, we tried to contact the patient about follow-up treatment. Following consultation with the radiation oncology department, adjuvant concurrent radiotherapy was deemed necessary. After surgery, the patient underwent radiotherapy for 6 weeks. Currently, at 6 months of follow-up post-treatment, the patient remains in stable condition with no evidence of disease recurrence. Method: This case report adheres to the SCARE criteria [ 8 ] .

Cervical cancer remains a significant global health concern, ranking as the fourth most common cancer in women, with an estimated 604 000 new cases and 342 000 deaths worldwide in 2020 [ 1 ] . Endocervical squamous cell carcinoma (SCC) and endocervical adenocarcinoma (ECA) are the two major histological subtypes of cervical cancer. Human papillomavirus (HPV) infection is responsible for nearly all cases of SCC [ 2 ] and approximately 85% of ECA cases [ 3 ] . Thanks to widespread HPV vaccination and effective screening programs, the rate of SCC is declining. Conversely, the incidence of ECA has been rising in recent years, partly because current screening methods are less effective at detecting this specific type of cancer [ 4 ] . HIGHLIGHTS Endometrioid ECA is an exceptionally rare cervical tumor. Diagnosis is challenging due to overlap with endometrial adenocarcinoma morphology. Rapid progression despite a negative Pap smear highlights limitations in current screening. Radical hysterectomy with adjuvant radiotherapy remains effective for early-stage disease. HIGHLIGHTS Endometrioid ECA is an exceptionally rare cervical tumor. Diagnosis is challenging due to overlap with endometrial adenocarcinoma morphology. Rapid progression despite a negative Pap smear highlights limitations in current screening. Radical hysterectomy with adjuvant radiotherapy remains effective for early-stage disease. In response to these diagnostic challenges, the International Endocervical Adenocarcinoma Criteria and Classification (IECC) introduced a new framework in 2018. This system classified tumors as either HPV-associated (HPVA) or non-HPV-associated (NHPVA) based on their morphological features [ 5 ] . The 2020 World Health Organization (WHO) Classification adopted this approach and further defined the NHPVA category into four distinct subtypes: gastric, clear cell, mesonephric, and endometrioid adenocarcinomas [ 6 ] . The diagnosis and clinical management of the endometrioid subtype are particularly difficult. This is due to its rarity and its strong histological resemblance to endometrioid endometrial carcinoma [ 6 ] . Additionally, adenocarcinoma generally carries a poorer prognosis than SCC of the same stage and size because of its higher tendency to metastasize. It is also important to note the rare phenomenon of “rapid-onset” carcinoma, which is an invasive cancer diagnosis within 2–3 years of a normal Pap smear [ 7 ] . This report provides a comprehensive account of a patient with ECA, tracing the disease from initial surveillance and diagnosis through therapeutic management. While previous reports have documented endometrioid ECA, this case is distinct due to the combination of “rapid-onset” progression in a postmenopausal patient who had a documented negative Pap smear and HPV test just 2 years prior. Our goal is to highlight the unusually rapid progression observed in this case, drawing attention to a critical aspect of this type of cancer. Furthermore, this clinical course highlights a critical diagnostic blind spot in current screening protocols for NHPVA glandular lesions.

Globally, while SCC remains the most common type, ECA (a subtype of cervical cancer) accounts for approximately 10–15% of all cervical cancer cases, though this proportion can vary by region. Cervical epithelial tumors have been largely reported due to HPV infection, and over 90% squamous cancer and 40% adenocarcinoma were related to HPV infection [ 9 ] . Persistent infection with high-risk HPV types, particularly HPV16, 18, and 45, is the primary cause of ECA, responsible for about 75% of cases. However, HPV infection is undetected in about 15% of ECA cases [ 10 ] . In cervical cancer, although the incidence of ECA is relatively lower compared to endocervical SCC, ECA may exhibit a higher degree of malignancy, lower survival rates, and a greater risk of distant metastasis [ 11 ] . An endometrioid-type ECA is a very rare primary tumor of the cervix that is said to arise in the setting of endometriosis. Barbu et al reviewed clinicomorphological data of 16 cases of adenocarcinoma during 2006–2011. The majority of cervical adenocarcinoma developed in the fifth and sixth decades of life (both with an equal number of cases – six cases), with an average of 56.125 years. The median onset age was 60.5 (range: 58–63) endometrioid subtype. According to the WHO classification criteria (2003), the most encountered histopathological variant of ECA was the endometrioid subtype tumors counting four cases (25%) [ 12 ] . The 2020 WHO/2018 IECC guidelines define endometrioid ECA as having endometrioid morphology with “confirmatory endometrioid features.” These features include at least focal identification of low-grade endometrioid glands lined by columnar cells with pseudostratified nuclei showing no more than moderate atypia, with or without squamous differentiation and/or associated endometriosis, and lacking HPVA features [ 5 , 19 ] . When strict diagnostic criteria are used, this is an extremely rare tumor, accounting for <1% of cervical carcinomas [ 5 , 13 ] . Little is known about its derivation, clinical correlates, and biological properties (Table 1 ) [ 19 , 20 ] . Table 1 Reported cases of endometrioid endocervical adenocarcinoma (2020–2025). References Year Age (years) Tumor diameter (cm) FIGO stage p16 expression HPV status Coexistent precursor/cancer First-line treatment Outcome Seay et al [ 14 ] 2020 76 2.4 IB1 Focal Neg None RoH a + PLNB + OMB, followed by CCRT NED (15 M) Akizawa et al [ 15 ] 2020 68 3.0 IB1 Neg n/a Endometrial squamous cell carcinoma TAH + BSO, followed by PTX + CBDCA NED (12 M) Uehara et al [ 16 ] 2020 49 4.0 IIB Focal Neg Atypical endometriosis RaH + BSO + PLND, followed by DOX + CDDP NED (12 M) Li et al [ 17 ] 2023 75 3.4 IB1 Patchy n/a Endometrial endometrioid adenocarcinoma TAH + BSO + PLND n/a Monist et al [ 18 ] 2023 60 9.0 IB1 Patchy n/a Endometrial endometrioid adenocarcinoma TAH + BSO + OM + PALND n/a Tomoko Oishi et al [ 6 ] 2024 58 11 IIIA Focal Neg n/a CCRT, followed by PTX + CBDCA Liver metastasis (18 M) Present case 2025 62 1.5 IB1 Patchy Neg None RaH + BSO + PLND, followed by radiotherapy NED (6 M) FIGO, International Federation of Gynecology and Obstetrics; HPV, human papillomavirus; RoH, robotic-assisted simple hysterectomy; PLNB, pelvic lymph node biopsy; OMB, omental biopsy; CCRT, concurrent chemoradiotherapy; n/a, not available; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; PTX, paclitaxel; CBDCA, carboplatin; RaH, radical hysterectomy; PLND, pelvic lymph node dissection; DOX, docetaxel; CDDP, cisplatin; PALND, para-aortic lymph node dissection; NED, no evidence of disease. a Status after BSO. Reported cases of endometrioid endocervical adenocarcinoma (2020–2025). FIGO, International Federation of Gynecology and Obstetrics; HPV, human papillomavirus; RoH, robotic-assisted simple hysterectomy; PLNB, pelvic lymph node biopsy; OMB, omental biopsy; CCRT, concurrent chemoradiotherapy; n/a, not available; TAH, total abdominal hysterectomy; BSO, bilateral salpingo-oophorectomy; PTX, paclitaxel; CBDCA, carboplatin; RaH, radical hysterectomy; PLND, pelvic lymph node dissection; DOX, docetaxel; CDDP, cisplatin; PALND, para-aortic lymph node dissection; NED, no evidence of disease. Status after BSO. The etiology and pathogenesis of endometrioid ECA are not fully understood. The oncogenic virus infection of squamocolumnar junction cells within the transformation zone (TZ) is hypothesized to drive the progression to atypical glandular cells and adenocarcinoma in situ , a process estimated to span 5–13 years [ 21 ] . Endometrioid cancer reportedly develops from cervical endometriosis. Some authors suspected endometrioid ECA could arise from a malignant transformation of endometriotic areas [ 16 , 22 ] . Unlike typical ECAs, which are strongly associated with high-risk HPV infection, endometrioid-type adenocarcinoma of the cervix appears to have a weaker or absent association with HPV. This suggests distinct molecular pathways driving its development. In the current report, HPV infection remained undetected. “Rapid-onset” cervical carcinoma is an unusual and rarely seen phenomenon, defined as the diagnosis of invasive cervical carcinoma within 2–3 years of a “normal” Pap smear [ 21 ] . A study by Wain et al investigated this issue and found that a significant portion of patients (21.5%) with invasive cervical cancer had a normal cervical smear within 2 years of diagnosis. However, upon reviewing the original slides, they discovered that most of these “normal” smears were either misdiagnosed (29%), lacked sufficient cellular material for a proper analysis, or were missing altogether. The researchers concluded that very few (2.5%), if any, cases of truly rapid-onset carcinoma actually occurred after a definitively normal and adequately reviewed smear. This led them to suggest that this phenomenon is far less common than previously thought [ 7 ] . As in our case, routine smear test and screening for high-risk HPV test were both negative 2 years prior. Interestingly, research by Hildesheim et al found that patients with rapid-onset cervical cancer tended to be younger and were more likely to be diagnosed with an early-stage adenocarcinoma. While HPV was a factor in most cases (75.2%), with HPV18 specifically linked to a higher risk, the study did not find a strong connection to other common risk factors like oral contraceptive use, smoking, or parity [ 23 ] . While Pap smears are highly effective for detecting SCC, they have significant limitations in identifying adenocarcinoma, which can lead to “rapid-onset” cases. A key reason for this is that adenocarcinomas often do not originate in the easily accessible TZ of the cervix, making them more difficult to sample during a routine Pap smear. The low sensitivity of Pap smears for this type of cancer is a major concern and may explain why some “rapid-onset” cases appear to bypass regular screening. Unlike SCCs, which typically develop slowly, some adenocarcinomas may grow more quickly and in areas that are harder to sample, leading to a false-negative result on a routine smear. This highlights the need for more effective screening methods that can reliably detect both types of cervical cancer. A review by Schwartz et al at Yale New Haven Hospital highlighted this issue, finding that a substantial number of patients (7.2%) with rapid-onset cancer were diagnosed due to persistent symptoms even after a negative Pap smear. They suggested that this phenomenon might be a sign of inadequate screening for adenocarcinoma [ 24 ] . There are difficulties in the early detection of ECA. Kalir et al searched whether Pap smears were less effective for the detection of in situ glandular lesions than for the detection of squamous counterparts [ 25 ] . Furthermore, research at New York University Medical Center found that Pap smears were notably less effective at detecting adenocarcinoma when the lesion did not involve the TZ. Specifically, they found that a quarter of invasive cancers that spared the TZ had a history of negative Pap smears within 3 years, compared to a much smaller percentage of cancers (5%) that did involve the TZ [ 26 , 27 ] . Diagnosing ECA is a significant challenge due to its rarity and its remarkable histological similarity to other tumor types. Therefore, correlation with clinical, radiological, and macroscopic features is essential, as management strategies are heavily dependent on the tumor’s primary site of origin. When considering endometrioid adenocarcinoma involving the cervix, three primary differential diagnoses should be entertained: (a) Primary ECA, (b) Uterine Fundus Cancer, and (c) Uterine Isthmus Cancer [ 21 ] . We must correlate histopathological findings with a patient’s clinical history and use advanced imaging studies like MRI. As demonstrated in our case, MRI is particularly useful for differentiating between uterine fundus cancer and ECA by showing whether the endometrial cavity is spared or distended with fluid, regardless of the tumor’s specific histological type [ 28 ] . The 2020 WHO classification represents a major improvement over the poorly reproducible and biologically limited morphological categories used previously. The new system divides ECA into HPVA and HPV-independent types. This distinction is crucial for diagnosis and treatment [ 29 ] . HPVA tumors typically show diffuse p16 positivity, often with characteristic signs of HPV infection. Conversely, non-HPV-related adenocarcinomas are usually p16-negative or show only focal positivity. Diffuse p16 positivity in such cases is rare and usually attributable to non-HPV-related mechanisms [ 30 ] . Distinguishing endometrioid-type from an ECA with mucinous differentiation or a primary endometrial carcinoma that has extended to the cervix can be challenging. IHC markers play a vital role in this differentiation. In general, ER-/PR-/diffuse p16+ supports the diagnosis of cervical primary. On the contrary, ER+/PR+/patchy p16+ is more inclined to uterine endometrioid adenocarcinoma. Typically, the IHC profile of endometrioid ECA often mirrors that of endometrial adenocarcinoma, which can further complicate diagnosis. Both are typically positive for ER, PR, vimentin and negative or only weakly positive for p16 and CEA. This is in contrast to typical ECA, which are generally positive for p16 and CEA. According to the 2018 IECC system and the 2020 WHO classification, the diagnosis of Endometrioid ECA relies on a specific clinicopathologic profile: endometrioid morphology combined with a lack of HPVA features. In our case, the tumor demonstrated classic endometrioid morphology, characterized by moderately differentiated glandular structures resembling endometrial tissue. Crucially, the IHC analysis showed patchy p16 expression and CEA positivity, while the high-risk HPV test was negative. This constellation of findings (p16 patchy/HPV-negative) fulfills the IECC criteria for NHPVA adenocarcinoma, endometrioid type, confirming the diagnosis. The molecular characteristics of endometrioid carcinoma are still unknown. In 2020, Jenkins et al analyzed the genomes of eight cases of HPV-negative endometrioid adenocarcinoma and detected several somatic genetic mutations: PIK3CA (50%), PTEN (50%), CTNNB1, FBXW7, KRAS, AKT1, and MSI-H. In the future, it will be helpful to identify genetic similarities with endometriosis-related carcinomas or molecular peculiarities that may help in the differential diagnosis of endometrial cancer that extends to the cervix [ 7 ] . Regarding clinical behavior and prognosis, data on ECA are limited due to its rarity. So, the impact of the recent paradigm shift in diagnosing endometrioid ECA, coupled with its historically low morbidity, has limited the availability of comprehensive prognostic data for affected patients [ 6 ] . Treatment approaches generally follow established guidelines for ECA, including surgery, radiation therapy, and chemotherapy, either alone or in combination, depending on the stage and other patient-specific factors. The most common treatment currently is surgery. Surgical management, such as hysterectomy with bilateral salpingo-oophorectomy, is often recommended for early-stage disease. Depending on the situation, pelvic lymph node resection and partial vaginectomy may be performed simultaneously. In the presented case, the patient underwent abdominal hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection, aiming to achieve complete resection of the tumor and prevent disease progression. Because of its rarity, data about endometrioid ECA prognosis are still limited. A recent study compared usual-type adenocarcinoma with endometrioid adenocarcinoma in terms of overall and disease-specific survival and found no statistically significant difference between them. The 5-year overall survival for ECA was 75.6% [ 22 ] . So, further research is critical to better understand the molecular landscape, risk factors, and optimal management strategies for endometrioid adenocarcinoma of the cervix. Improved diagnostic criteria and a deeper understanding of its biological behavior will be instrumental in improving patient outcomes.

We report the case of a woman with an endometrioid ECA that was diagnosed based on the 2020 WHO/2018 IECC guidelines and treated with a radical hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph node dissection. The patient responded well to the combination of radical surgery and adjuvant radiotherapy, remaining disease-free at 6 months of follow-up. Even with an ECA classification based on HPV status, diagnosing the origin of an endometrioid carcinoma presents a challenge. Although pathological assessment should be considered, the final diagnostic decision should be made clinically. MRI plays a crucial role in accurately assessing prognostic indicators of cervical and corpus cancers at initial diagnosis. During post-therapeutic surveillance, it is crucial to differentiate between entities that can mimic both malignancies. Further prospective investigations characterizing the clinicopathological, radiologic, and molecular profiles of ECA according to the 2020 WHO/2018 IECC guidelines are warranted. What is more, the issue related to the “rapid-onset” cervical carcinoma needs attention and most of them are adenocarcinomas. Compared to squamous lesions, the sensitivity of Papanicolaou tests is lower for the detection of glandular lesions. Multidisciplinary collaboration, bringing together gynecologists, oncologists, and pathologists, is absolutely essential for optimizing outcomes and improving survival rates in patients diagnosed with endometrioid ECA. This integrated approach allows for comprehensive patient evaluation, precise staging, tailored treatment planning, and ongoing management, ultimately leading to more effective and individualized care. Concurrently, routine gynecological screening is imperative for all women to facilitate the early identification of any potential underlying abnormalities.