Invasive mole after heterotopic pregnancy in a postmenopausal woman: A rare case report from a tertiary hospital in northern Tanzania.

A 48-year-old woman, P3 A1 L2, from Northern Tanzania, presented to our tertiary facility with a 3-month history of cramping lower abdominal pain associated with intermittent per vaginal bleeding, brownish discharge, abdominal bloating, recurrent vomiting of recently ingested food, and chest pain. She denied fever, cough, shortness of breath, urinary symptoms, or bowel habit changes. She was three years postmenopausal, with her last normal menstrual period at age 45. Her gynecological history was unremarkable: she had regular menstrual cycles prior to menopause, no history of abnormal uterine bleeding, fibroids, endometriosis, or sexually transmitted infections, and had never used hormonal contraception or assisted reproductive technology (ART). Her obstetric history included four pregnancies: three term deliveries, all live births, and one spontaneous abortion. She was a nonsmoker, did not consume alcohol, and lived with her relatives. Three months before this admission, she experienced intermittent metrorrhagia, prompting her to attend a local hospital. She was diagnosed with heterotopic pregnancy and underwent a left salpingectomy. Her postoperative recovery was uneventful, and she was discharged home. Two weeks later, she re-presented to a nearby hospital with recurrent vaginal bleeding. She was diagnosed with incomplete abortion and underwent uterine evacuation. However, she was not placed on the recommended weekly serum β-hCG monitoring post-procedure. One month later, she developed further vaginal bleeding, and a serum β-hCG level taken at that time was markedly elevated at 388,000 mIU/mL. She was subsequently referred to our tertiary center for evaluation and management of suspected choriocarcinoma. On examination, she appeared unwell with a pale complexion. The patient was afebrile, with a BP of 142/85 mmHg, a PR of 95 bpm, a respiratory rate of 18 bpm, and SP02: 99 % in room air. Per abdominal examination was slightly distended. On a speculum examination, the cervix looked healthy with blood clots on the posterior fornix of the vaginal. Laboratory workup results highlighted a hemoglobin level of 11 g/dL. Other basic laboratory parameters, including blood glucose, liver enzymes, and renal function tests, were within normal limits. Serum β-hCG level was 254,579 mUI/mL elevated. Similarly, electrolytes, ECG, ECHO, and chest X-ray revealed no evidence of distant metastases ( Fig. 1 A). Fig. 1 (A) AP View shows normal chest X-ray. (B) An abdominal ultrasound showed a bulky uterus with heterogenous enhancing mass with involvement of the myometrium and increased internal vascularity measures 9 × 6 × 7 cm. An impression of uterine choriocarcinoma was considered. Fig. 1 (A) AP View shows normal chest X-ray. (B) An abdominal ultrasound showed a bulky uterus with heterogenous enhancing mass with involvement of the myometrium and increased internal vascularity measures 9 × 6 × 7 cm. An impression of uterine choriocarcinoma was considered. An abdominal ultrasound showed a bulky uterus with heterogenous enhancing mass with involvement of the myometrium and increased internal vascularity measures 9 × 6 × 7 cm ( Fig. 1 B). An impression of uterine choriocarcinoma was considered. Due to her condition, it was decided to perform a total abdominal hysterectomy and intraoperative visualization of the abdomen revealed a large uterus corresponding with a gestational age of 14 weeks. Other abdominal organs appeared healthy. The uterine specimen ( Fig. 2 ) was submitted for histopathology evaluation. Her postoperative course was uneventful, and on postoperative day 4, β-hCG was repeated, which was 2043 mUI/mL and she was discharged 7 days after surgery. Histopathological examination showed a chorionic villi invading myometrium with less hydropic changes with increased trophoblast hyperplasia ( Fig. 3 A-B). This morphology was consistent with invasive mole, stage I, FIGO score 7 according to the FIGO staging system. A multidisciplinary tumor board team of gynecologists, oncologists, and pathologists convened and decided to start her on chemotherapy with EMA-CO (Etoposide + Methotrexate + Actinomycin in-Oncovin + Cyclophosphamide. Unfortunately, the patient opted not to undergo any form of chemotherapy treatment due to cultural beliefs and financial constraints. She was discharged with close follow-up and monitoring of β-hCG, after 4 months β-hCG levels fell to 741mUI/mL. She will be followed until β-hCG is undetectable. Fig. 2 The specimen which was taken for histology shows uterine cavity filled with grape-like vesicles with myometrial invasion. Fig. 2 Fig. 3 (A) Photo-microscopy of invasive mole demonstrating chorionic villi with less hydropic changes with increased trophoblast hyperplasia, H&E staining at 100 x original magnification. (B) histopathology of invasive mole highlighting chorionic villi invading myometrium, H&E staining at 200 x original magnification. Fig. 3 The specimen which was taken for histology shows uterine cavity filled with grape-like vesicles with myometrial invasion. (A) Photo-microscopy of invasive mole demonstrating chorionic villi with less hydropic changes with increased trophoblast hyperplasia, H&E staining at 100 x original magnification. (B) histopathology of invasive mole highlighting chorionic villi invading myometrium, H&E staining at 200 x original magnification.

John Lugata: Conceptualization, study design, prepared initial manuscript version and approved the final manuscript draft. Glory Maringo: Conceptualization, study design, prepared initial manuscript version and approved the final manuscript draft. Tecla Lyamuya: Involved in the patient management, provided supervision and reviewed, and approved the final manuscript draft. Eusebious Maro: Conceptualization, study design, prepared initial manuscript version and approved the final manuscript draft. Joseph Mlay: A lead Obstetrician and Gynaecologist, provided expertise throughout the entire process and revised and approved the final draft. Alex Mremi: Conceptualization, and also performed histopathological analysis and prepared the final manuscript draft.

Written informed consent was obtained from the patient to publish this case report and accompanying images. On request, a copy of the written consent is available for review by the Editor in-Chief of this journal.

This case series report is exempt from ethical approval in our institute.

This work did not receive any fund from any source.

N/A.

Dr. John Lugata.

This case highlights the rarity of invasive mole in a postmenopausal woman following heterotopic pregnancy, emphasizing the diagnostic challenges in resource-limited settings where atypical presentations may be misinterpreted as ectopic pregnancy or other gynecologic conditions. It underscores the critical importance of serial β-hCG surveillance after uterine evacuation, regardless of age or presumed diagnosis, to enable early detection of gestational trophoblastic neoplasia. While multi-agent chemotherapy remains the standard of care for high-risk disease, hysterectomy can serve as a valuable adjunct for selected patients, particularly those with completed fertility or at risk of hemorrhage. However, surgery alone should not be considered definitive treatment in high-risk disease, given the risk of occult metastases.

This study describes a rare case of an invasive mole in a postmenopausal woman following heterotopic pregnancy. Given the global rarity of this condition, particularly in our setting, to the best of our knowledge, this is the first case report to be reported in Sub-Saharan Africa, the initial clinical diagnosis was suspected to be uterine choriocarcinoma. However, histopathological evaluation following surgical intervention confirmed the diagnosis of invasive mole, allowing for the initiation of adjuvant chemotherapy, unfortunately the patient denied treatment. This case underscores how GTN specifically an invasive mole can present in a postmenopausal woman and masquerade as other gynecologic entities, especially when the antecedent course includes heterotopic or ectopic pregnancy and uterine evacuation. An invasive mole is marked by the presence of swollen chorionic villi with excessive trophoblastic growth that can infiltrate the myometrium of the uterus and extend to nearby structures such as the vagina, vulva, broad ligament, and even the uterine blood vessels [ 14 ]. An invasive mole develops in about 10–15 % of cases following a complete hydatidiform mole. The outlook for most GTN cases is often defined by the extensive spread of metastasis. Usually, invasive mole disseminates locally, however distant metastasis can occur in some cases, most frequently involving the lung, vagina, pelvis, liver as well as the brain [ 15 ]. In this case, the development of the invasive mole occurred within 3 months following the evacuation of the incomplete pregnancy. Close follow-up of these patients is crucial to detect malignant trophoblastic tumors early and to reduce the mortality rate. Although all women within the reproductive age have the potential of getting GTD, women in younger age around and perimenopausal women are more likely to be at risk therefore high clinical suspicion and histopathological analysis are necessary to detect GTD [ 15 ]. Invasive mole usually occurs in women of reproductive age and is extremely rare in postmenopausal women. Only 5 cases of hydatidiform mole in postmenopausal women have been reported in literature since 2004 [ 16 ]. The pathogenesis of invasive mole in perimenopausal women is unclear, but it is believed that it may be due to immature spontaneous ovulation of oocytes leading to decreased fertility in perimenopausal patients and eventually to postmenopausal patients [ 17 ]. Several reports describe postmenopausal GTD including invasive mole and choriocarcinoma presenting with bleeding and very high β-hCG, sometimes with metastases, emphasizing the diagnostic pitfall in this age group [ 18 ]. Our case represents an unusual presentation of invasive mole in a 48-year-old postmenopausal woman, further complicated by an initial misdiagnosis of heterotopic pregnancy and incomplete abortion. Our patient's trajectory (heterotopic pregnancy → evacuation for presumed incomplete abortion → delayed β-hCG surveillance) highlights two recurrent themes in the literature. First, invasive mole can mimic or follow ectopic pathology, including cornual/interstitial and tubal disease. Case reports and reviews describe patients initially managed as ectopic pregnancy, with the diagnosis clarified only by histopathology and serial β-hCG [ 19 , 20 ]. Second, omission of serial β-hCG monitoring after evacuation is a critical gap. Both FIGO and the NCI PDQ recommend weekly β-hCG until normalization and then less frequent surveillance to detect post-molar GTN early [ 21 , 22 ]. In a retrospective review, Braga et al. [ 12 ] emphasized that the absence of routine β-hCG monitoring after molar evacuation is a major risk factor for delayed recognition of malignant transformation. Similarly, Sebire and Seckl [ 8 ] reported that up to 15 % of complete moles can progress to invasive mole, and careful β-hCG surveillance is critical in early detection. In our case, lack of β-hCG follow-up after uterine evacuation led to disease progression until referral. Generally, it is difficult to differentiate an invasive mole from other forms of GTDs on imaging. Imaging studies like ultrasound can be informative with features such as thickened cystic appearance of villous with no obvious gestational sac and an enlarged placenta, however, findings can sometimes be more subtle leading to a low predictive value [ 23 ]. To detect partial mole through ultrasound is more challenging due to viable fetus displaying signs of triploidy such as developmental abnormalities and early growth restriction [ 23 ]. CT scan of the chest, abdomen and pelvis can be done to rule out distant metastasis. FIGO staging and score should be used once the criteria is met. The two components of staging are a FIGO risk score to assess the likelihood of disease progression and resistance to single-agent treatment and a FIGO anatomic staging. The sum of the points allotted to different clinical and tumor risk facts is used to determine the score [ 24 ]. For the patients who prefer to preserve their fertility, suction and curettage can be the method of for evacuation. Oxytocic drugs and medical evacuation is advised against to prevent the risk further dissemination of the disease and for being linked with increased maternal mortality. For older age women such as those >40 years or those who do not wish to preserve their fertility, Total abdominal hysterectomy (TAH) can be done. While TAH does not prevent metastasis, it can however minimize the risk of locally invasive disease and shows 50 % reduce risk of persistent trophoblastic disease [ 25 ]. In our patient, total abdominal hysterectomy produced a rapid β-hCG fall (to 2043 mIU/mL by postoperative day 4), followed by continued decline to 741 mIU/mL at 4 months, despite refusal of chemotherapy.While isolated reports describe remission after surgery alone most often in low-risk, non-metastatic GTN current guidance cautions that high-risk disease should not be managed expectantly, due to risk of occult micrometastases and relapse even when β-hCG initially falls [ 21 ]. Seckl et al. [ 7 ] emphasize that hysterectomy, although not curative by itself, may be appropriate in older women who no longer desire fertility, especially in resource-limited settings where chemotherapy access is restricted. In a series from India, Ngan et al. [ 3 ] noted that postmenopausal women undergoing hysterectomy had favorable outcomes when combined with chemotherapy, but poor outcomes if chemotherapy was declined. Our case diverges, as the patient showed marked β-hCG decline without adjuvant chemotherapy, although longer-term follow-up is needed to rule out late relapse. The best treatment option for invasive mole is chemotherapy and the cure rate is nearly 100 % in low risk patients and 90 % in high-risk patient [ 14 ]. Surprisingly, our patient for reasons unknown to us, she refused to undergo oncological treatment and opted to go for traditional medicines. Patients who refuse recommended treatment are at higher risk of recurrence and mortality. The refusal of treatment poses significant challenges for health care providers in terms of patient outcomes and highlights the need for culturally sensitive approaches in patient education and counseling, which in turn forms a barrier to understanding disease management and progression [ 25 ]. Therapy with nearly a 100 % complete remission rate is available for treating this condition. For high-risk patients (FIGO score ≥ 7), the preferred treatment option is the polychemotherapy regimen EMA-CO (Etoposide, Methotrexate, Actinomycin D, alternating with Cyclophosphamide and Vincristine). The EMA-CO regimen achieves a 98 % rate of β-hCG remission and normalization. If the response to this treatment is inadequate, alternative regimens such as EMA-EP or BEP (Bleomycin, Etoposide, and Cisplatin) should be considered [ 7 ]. Research with randomized controlled trials showed the incidence of GTN has decreased from about 40 % to 10 % to 15 % when prophylactic chemotherapy is administered at the evacuation of high-risk complete Hydatiform mole [ 26 ]. Patients are recommended not to become pregnant for at least six months following the normalization of their BhCG levels in the event of complete mole and for a full year in the case of GTD during the B-hCG follow-up period [ 27 ]. For future fertility in patients with the disease, some studies demonstrate that subsequent pregnancies following GTN had obstetrical outcomes comparable to those for women without a history of GTN, with the exception of an increased likelihood of second molar pregnancy [ 28 ]. More research is, however, required on the subject. Moreover, the antecedent heterotopic pregnancy diagnosis in our case is particularly unusual. Literature search reveals no previous documented case of invasive mole following heterotopic pregnancy in a postmenopausal woman, underscoring the rarity and novelty of this report.

Gestational trophoblastic disease (GTD) encompasses tumors arising from abnormal pregnancies, with benign forms including complete and partial hydatidiform moles and malignant forms known as gestational trophoblastic neoplasia (GTN), such as choriocarcinomas and invasive moles [ 1 ]. Molar pregnancies, which are premalignant, can progress to invasive moles if not properly managed [ 1 ]. An invasive mole is characterized histologically by hydropic chorionic villi with trophoblastic hyperplasia invading the myometrium and, occasionally, extra-uterine tissues [ 2 ]. It most often occurs following molar evacuation, but can also develop after other gestational events such as miscarriage, term pregnancy, or ectopic pregnancy [ 3 ]. Incidence rates for molar pregnancies are 3:1000 for partial moles and 1:1000 for complete moles, with increased risk at reproductive age extremes. Clinically, invasive mole often presents with abnormal uterine bleeding, pelvic pain, and uterine enlargement. Without treatment, it can cause uterine rupture or metastasis, most commonly to the lungs [ 1 ]. While GTD commonly affects women of reproductive age, the condition is exceptionally rare in perimenopausal and postmenopausal women, leading to delayed or missed diagnoses due to low clinical suspicion [ 4 ]. Its occurrence in postmenopausal women is extremely rare, with only a handful of cases reported globally [ 5 , 6 ]. Moreover, advanced maternal age (≥40 years) has been identified as a significant risk factor for GTN development, and older patients are more likely to present with high-risk disease and poorer outcomes [ 7 ]. Postmenopausal GTD often presents with nonspecific symptoms such as abnormal uterine bleeding, leading to frequent misdiagnosis as more common conditions such as endometrial carcinoma or dysfunctional uterine bleeding [ 8 ]. Another extremely unusual occurrence is heterotopic pregnancy, the simultaneous presence of intrauterine and extra-uterine gestations. While rare in spontaneous conceptions (estimated at 1 in 30,000), heterotopic pregnancies are significantly more common in women undergoing assisted reproductive technologies [ 9 , 10 ]. Reports of spontaneous heterotopic pregnancy in women without ART or known risk factors are limited, and presentation in postmenopausal women is virtually unheard of [ 10 , 11 ]. To our knowledge, no published case has documented invasive mole developing after a heterotopic pregnancy in a postmenopausal woman. In low-resource settings, this is further complicated by limited access to reliable β-hCG monitoring, imaging, and histopathological evaluation, which can delay diagnosis and compromise management [ 12 ]. This work has been reported in line with the SCARE criteria 2025 [ 13 ]. Herein, we present a rare case report of invasive mole in a 48-year-old woman, three years postmenopausal, initially diagnosed as heterotopic pregnancy and later managed as incomplete abortion before proper identification at a tertiary hospital in Northern Tanzania.

All authors have declared that no competing interests exist.