Gestational Trophoblastic Neoplasia in Perimenopausal Women: Clinical Analysis, Case Series, and Literature Review

Summary

Gestational trophoblastic neoplasia (GTN) is a rare invasive placental malignancy in perimenopausal women that is easily confused with abnormal vaginal bleeding. This article analyzes five cases (three choriocarcinomas and two invasive hydatidiform moles) to clarify diagnosis and treatment for clinical reference.

Abstract

Most gestational trophoblastic neoplasia (GTN) occurs in women of reproductive age, and its occurrence in perimenopausal women is extremely rare. A key symptom of GTN is vaginal bleeding, which can be difficult to distinguish from abnormal uterine bleeding commonly seen during perimenopause, making diagnosis in this population particularly challenging. This study retrospectively analyzed five cases of perimenopausal women diagnosed with GTN at the Department of Obstetrics and Gynecology, Beijing Friendship Hospital, Capital Medical University, between June 2013 and June 2023, including three cases of choriocarcinoma and two cases of invasive mole. The clinical features (age, parity, pregnancy history, main symptoms), diagnostic indicators (serum β-hCG levels, transvaginal ultrasound findings, pathological results), treatment protocols (surgical procedures, chemotherapy regimens), and follow-up outcomes were analyzed. The goal of this report is to provide a standardized clinical reference for the diagnosis and treatment of GTN in perimenopausal women, improve the accuracy of differential diagnosis, optimize treatment strategies, and enhance patient outcomes. All five patients completed treatment and follow-up (up to 2 years), with no recurrence observed. The results suggest that for perimenopausal women presenting with abnormal vaginal bleeding, combining serum β-hCG testing with pelvic imaging is crucial for early diagnosis. For patients without fertility requirements, comprehensive treatment with surgery (total hysterectomy plus bilateral adnexectomy) and chemotherapy may reduce chemotherapy dosage and improve treatment efficacy. This case series provides practical guidance for managing the diagnostic and therapeutic challenges of GTN in perimenopausal women.

Introduction

Gravid trophocyte disease, also known as gestational trophoblastic disease (GTD), is a collective term for placental trophocyte abnormalities caused by abnormal fertilization. It includes benign hydatidiform mole and malignant gestational trophoblastic neoplasia (GTN)¹. Hydatidiform mole is divided into complete and partial forms, while GTN includes invasive mole (IM), choriocarcinoma (CC), placental site trophoblastic tumor (PSTT), epithelioid trophoblastic tumor (ETT), and atypical placental site nodules². Among these, invasive mole (IM) and choriocarcinoma (CC) are the most common types of GTN.

Multiple studies have shown that age ≥40 years is a high-risk factor for the development of hydatidiform mole¹ and its malignant transformation into GTN^3,4. Perimenopausal women may experience abnormal vaginal bleeding due to decreased ovarian function, which resembles the typical manifestation of GTN and complicates diagnosis. Therefore, abnormal bleeding in perimenopausal women requires careful differential diagnosis to exclude gestational trophoblastic tumors. This article reviews the diagnosis and treatment of three cases of perimenopausal choriocarcinoma and two cases of invasive mole, aiming to provide clinical reference for the management of perimenopausal trophoblastic tumors. All five cases were diagnosed at the Department of Obstetrics and Gynecology, Beijing Friendship Hospital, Capital Medical University, between June 2013 and June 2023.

Case Presentation
All five patients were perimenopausal women aged 47–55 years, with a mean age of 51 ± 4.3 years. The number of pregnancies ranged from two to six, with a median of three, and all were natural pregnancies. Serum β-hCG levels were abnormally elevated in all five patients. Detailed clinical information is provided below.

Case 1: A woman with a history of full-term pregnancy, presenting with abnormal vaginal bleeding as the main symptom.

Case 2: A woman without a previous pregnancy history who developed an invasive mole secondary to a complete hydatidiform mole (progression time: 46 days). She had irregular menstruation for one year and amenorrhea for two months, with irregular menstruation as the main symptom.

Case 3: A woman with a history of early abortion, presenting with abnormal vaginal bleeding as the main symptom.

Case 4: A woman without a previous pregnancy history who developed an invasive mole secondary to a complete hydatidiform mole (progression time: 40 days), presenting with abnormal vaginal bleeding as the main symptom.

Case 5: A woman without a previous pregnancy history who developed an invasive mole secondary to a complete hydatidiform mole (progression time: 42 days), presenting with abnormal vaginal bleeding as the main symptom.

Diagnosis, Assessment, and Plan

Diagnosis confirmation
The diagnosis of GTN in all cases was confirmed by surgical pathology examination, which is the gold standard for GTN diagnosis.

Serum β-hCG level assessment
Cases 1, 2, and 3: At initial diagnosis, the serum β-hCG levels were all >200,000 mIU/mL.

Case 4: At initial diagnosis, the serum β-hCG level was not specifically recorded but was abnormally elevated.

Case 5: At initial diagnosis, the serum β-hCG level was 1,286 mIU/mL; however, on the first day after surgery, it rebounded to >269,800 mIU/mL.

Uterine size and imaging assessment
All cases showed uterine enlargement, with the following findings:

Case 1: Transvaginal ultrasound showed a uterine body measuring approximately 8.9 × 7.0 × 5.7 cm; no fetal sac was present in the uterine cavity. A honeycomb-shaped, uneven low-echo mass (5.0 × 4.8 × 3.5 cm) was identified in the anterior lip of the cervix. Abundant annular blood flow was detected in the uterus, with a resistance index (RI) of 0.68.

Case 2: Transvaginal ultrasound showed a uterine body measuring approximately 7.5 × 8.2 × 6.9 cm. The uterine cavity was filled with uneven high-echo tissue (6.0 × 6.3 × 4.7 cm) (Figure 1). Lung CT revealed nodules that were not considered metastatic; plain head CT showed no abnormalities.

Case 3: Transvaginal ultrasound showed a uterine body of 9.8 × 9.3 × 10.1 cm. The endometrium measured 3.1 cm in thickness, with uneven echogenicity and high vascularity in the endometrial cavity (Figure 2).

Case 4: Transvaginal ultrasound showed a uterine body of 10.4 × 6.7 × 5.3 cm. An uneven echo measuring 5.2 × 5.4 cm was visible in the uterine cavity, with a honeycomb appearance.

Case 5: The uterine body measured 19.4 × 16.9 × 10.3 cm—the largest among all cases. Transvaginal ultrasound showed a bubble-like mass in the uterine cavity with minimal blood flow, suggestive of trophoblastic disease. The surgically removed uterus measured 28 × 25 × 18 cm and weighed approximately 2,650 g. The uterine cavity was filled with transparent, grape-like tissue (Figure 3). The patient also experienced intermittent nausea, dizziness, edema, increased abdominal girth, poor appetite and sleep, and a weight gain of 5 kg. Her blood pressure was 164/84 mmHg, heart rate was 100 beats/min, and thyroid-stimulating hormone (TSH) level was 0.01 uIU/mL (with normal FT3 and FT4 levels). The 24 h urine protein was 3.58 g. Two months after surgery, chest CT revealed multiple pulmonary nodules.

Protocol

The operation followed standard procedures and received ethics approval (2024-P2-537) from the Ethics Committee of Beijing Friendship Hospital, Capital Medical University. Informed written consent was obtained from the patient. The study was conducted in accordance with institutional ethical standards. The reagents and equipment used in the study are listed in the Table of Materials.

1. Preoperative preparation

1. Bowel and fasting preparation
   1. One day before surgery, the patient was instructed to take oral sodium phosphate salt (concentration: 45 mL/bottle, dosage: two bottles, taken at 12 h intervals) for bowel preparation to ensure the intestinal tract was empty. The patient fasted for 8 h before surgery and was allowed to drink water until 4 h prior to minimize aspiration risk during anesthesia and maintain hemodynamic stability.
2. Urinary catheter insertion
   1. Before entering the operating room, a 14 Fr latex urinary catheter was inserted under sterile conditions to maintain bladder decompression and reduce intraoperative injury risk.
3. Anesthesia and positioning
   1. The patient was placed in a supine position on the operating table, with arms on the side armrests and legs slightly separated. Endotracheal intubation was performed using a 7.0–7.5 mm endotracheal tube by an anesthesiologist: after sedation and muscle relaxation, the laryngoscope was inserted to expose the glottis, and the tube was placed under direct vision. The cuff was inflated (5–8 mL) to ensure tightness. General anesthesia was induced with propofol (1.5–2 mg/kg), maintained with sevoflurane (1–2%), and analgesia was provided with fentanyl (2–4 µg/kg).
4. Surgical area disinfection and draping
   1. The surgical area—from the xiphoid process to the upper third of the thigh—was disinfected with 2% iodine tincture, followed by 70–75% medical ethanol for deiodination. Disinfection began at the perineum, extended to the lower abdomen, and then to the upper abdomen, covering 15 cm beyond the incision field. Sterile drapes were applied sequentially to isolate the surgical field.

2. Surgical procedure

NOTE: Throughout the surgical process, strict aseptic techniques were maintained (including replacement of contaminated sterile gloves and avoidance of contact between sterile instruments and non-sterile areas), and the surgical team continuously monitored the patient's vital signs (heart rate, blood pressure, and oxygen saturation) to ensure procedural safety.

1. Abdominal incision
   1. A midline abdominal incision was made from 1 cm above the symphysis pubis to 2 cm above the umbilicus (total length: 8–12 cm, adjusted for uterine size). A scalpel was used to incise the skin and subcutaneous tissue; electric cautery (45 W for cutting and hemostasis) was used to incise the fascia and peritoneum, with simultaneous hemostasis. After entering the cavity, a sterile gauze pad protected the incision edge. Abdominal organs were explored to assess uterine and adnexal position, size, and abnormalities, and check for unexpected pathology.
2. Exposure of uterus and adnexal structures
   1. Moistened laparotomy pads (in warm sterile saline) were used to retract and pack intestines. The bilateral round ligaments were identified, clamped 2 cm from the uterine fundus, and cut between clamps. Absorbable sutures (4-0 Vicryl) were used to ligate both proximal and distal ends.
3. Handling of utero-ovarian ligaments and fallopian tubes
   1. The mesosalpinx was separated to expose the utero-ovarian ligaments and fallopian tubes. These were clamped together 1 cm from the uterine cornua and cut between hemostats. Absorbable sutures (7 silk) ligated the proximal end twice and the distal end once.
4. Separation of uterus from surrounding tissues
   1. A bladder retractor was used to gently push the bladder downward to separate it from the lower part of the uterus (the vesicouterine pouch was opened) until the cervix was fully exposed.
   2. The peritoneum covering the anterior and posterior surfaces of the uterus was incised with scissors along the uterine midline.
   3. The bilateral uterine vessels (located on both sides of the uterus, in the broad ligament) were carefully identified using a hemostat and dissected free (avoiding injury to the ureters). Two curved hemostats were used to clamp the uterine artery and vein on each side (the clamping range included the entire vessel and a small amount of surrounding connective tissue to prevent vessel slipping), and the vessels were cut between the two hemostats.
   4. Strong non-absorbable sutures (2-0 Ethibond) were used to ligate the proximal end of the vessel twice (the first ligation was close to the hemostat, and the second ligation was 0.5 cm away from the first ligation) to ensure firm ligation and prevent bleeding.
   5. After handling the uterine vessels, the remaining connective tissues (such as the cardinal ligament, uterosacral ligament) connecting the uterus to the pelvic floor and lateral pelvic walls were dissected using scissors and hemostats (for tough tissues, electric cautery could be used for dissection and hemostasis), further mobilizing the uterus.
5. Removal of uterus and adnexal structures
   1. Once mobilized, the uterus, ovaries, and fallopian tubes were lifted from the cavity using tissue forceps, avoiding contamination. Specimens were fixed in 10% neutral buffered formalin and sent for histopathological confirmation.
6. Hemostasis and inspection
   1. The pelvic cavity was inspected visually or by laparoscope for bleeding points (e.g., uterine vessel ligation sites). Bleeding was controlled using electric cautery (20–30 W), absorbable sutures (3-0 Vicryl), hemostatic agents (e.g., fibrin glue, 2–5 mL). The site was reinspected to ensure ligatures were secure and no residual adnexal tissue remained.
7. Closure of incision
   1. Warm sterile saline (temperature: 37–38 °C, volume: 500–1000 mL) was used to irrigate the abdominal cavity to remove blood clots, tissue debris, and potential contaminants. After irrigation, as much saline as possible was aspirated.
   2. The peritoneum was sutured continuously with absorbable sutures (4-0 Vicryl), with a suture spacing of 0.5–1 cm. The fascia was sutured intermittently with non-absorbable sutures (2-0 Prolene), with a suture spacing of 1–1.5 cm and a depth of 0.5 cm to ensure sufficient tension. The subcutaneous tissue was sutured continuously with absorbable sutures (4-0 Vicryl), and the skin was closed with skin staples (absorbable sutures [4-0 Vicryl] for intradermal suture).
   3. A sterile dressing (gauze pad + transparent adhesive film) was applied to the surgical wound to protect it and prevent infection.
      NOTE: This protocol was performed on all five patients. For patients with special conditions (e.g., Case 5 with severe preeclampsia and hyperthyroidism), intraoperative blood pressure and thyroid function monitoring were enhanced, and the surgical time was shortened when possible to reduce trauma.

3. Postoperative management

1. Vital sign monitoring
   1. In the recovery room and during the first 24 h postoperatively, the patient’s heart rate, blood pressure, respiratory rate, and oxygen saturation were closely monitored. Vital signs were initially assessed every 15 min for the first 2 h, then every 30 min for 2–6 h, and hourly thereafter. If abnormal changes occurred (e.g., heart rate >120 beats/min, blood pressure <90/60 mmHg, oxygen saturation <95%), appropriate interventions were administered to stabilize blood pressure or control heart rate.
2. Pain management, fluid and nutritional support, and early ambulation
   1. Pain management: Patient-controlled intravenous analgesia (PCA) was used for the first 48 h, with fentanyl (0.5 µg∙kg^-1∙h^-1 background; 20 µg bolus; 10 min lockout). Oral acetaminophen (500 mg every 6 h as needed) was used thereafter.
   2. Fluid and nutrition: Lactated Ringer’s solution (1,000–1,500 mL) was administered in the first 24 h. Once bowel sounds returned, patients resumed oral intake: liquid (e.g., rice soup), then semi-liquid (e.g., porridge), and finally regular food. Nutritional supplements were added if needed.
   3. Early ambulation: On the first postoperative day, the patient ambulated for 5–10 min (with assistance), increasing to 15–30 min twice daily on the second day to promote gut motility and reduce venous thromboembolism (VTE) risk.
3. VTE prophylaxis and urinary catheter removal
   1. VTE prophylaxis: Enoxaparin sodium (40 mg subcutaneously once daily) was initiated 12 h after surgery and continued for 7 days or until normal ambulation resumed. Elastic stockings were also worn.
   2. Urinary catheter was removed within 48 h postoperatively to reduce urinary tract infection (UTI) risk.
4. Antibiotic prophylaxis and laboratory monitoring
   1. Antibiotics: Cefazolin sodium (1 g IV every 8 h) was administered for up to 48 h. If the patient developed fever > 38.5 °C or lab abnormalities (WBC > 12 × 10⁹/L, neutrophils >80%), the duration was extended and the antibiotic adjusted per culture and sensitivity.

4. Lab monitoring

1. Serum β-hCG was measured every 3 days for 2 weeks, then weekly until two consecutive normal results, then monthly for 6 months. Routine blood tests, liver/kidney function, and electrolytes were assessed every 3–5 days to monitor for complications or chemotherapy-related side effects.

Results

The surgical characteristics and perioperative outcomes of all five patients are summarized in Table 1.

Case 1 (Choriocarcinoma)
Treatment process:
The patient received two courses of chemotherapy before surgery using 5-fluorouracil (5-FU, 28 mg∙kg^-1∙day^-1, IV infusion for 8 days) and actinomycin D (ACT-D, 6 µg∙kg^-1∙day^-1, IV infusion for 8 days). After each course, serum β-hCG levels decline...

Discussion

Gestational trophoblastic neoplasia (GTN) results from abnormal fertilization. In 1984, Davis et al. identified Y chromosome material in 9% of hydatidiform mole cases, 50% of invasive mole cases, and 74% of choriocarcinoma cases, suggesting that overexpression of paternal genes may contribute to malignant transformation⁵. Additional genetic alterations have also been implicated in GTN development⁶. GTN is rare, accounting for less than 1% of all female reproductive tract tu...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
5-fluorouracil	Tianjin Jinhui Pharmaceutical Co., Ltd.	H12020959
Ablation electrode	Tangshan Tianen Technology Co., Ltd.	(01) 06959137400020	sterile,single-use
Calcium Folinate Injection	Jiangsu Hengrui Medicine	H20000584
CT Scanner	GE/Canon	TSX-301C/0103300063	stable
Dactinomycin for Injection	Hanhui Pharmacerutical Co.,Ltd	H20023504
Fentanyl Citrate Injection	Yichang Renfu	H2003688
Medical gauze pad	Zhen De Medical Supplies Co., Ltd.		sterile,single-use
Methotrexate	Pfizer (Perth) Pty Limited	HJ20140207
One-time use precision filtration infusion set	Bayer Medical (Shan Dong)Co., Ltd.	25G30R8SF1	sterile,single-use
Propofol Injectable Emulsion	Guangdong Jiabo	H20051842
Sevoflurane for Inhalation	Baxter Healthcare Corporation	H20140431
SILK BRAIDED NON-ABSORBABLE SUTURE	ETHICON	V502413	sterile,single-use
Single-use sterile urinary catheter kit	Beijing Huatongtong Technology Co., Ltd.	C14-05-03	sterile,single-use
Sterile surgical blade	Shanghai Lianhui Medical Supplies Co., Ltd.	####################	sterile,single-use
Synthetic absorbable surgical sutures	Covidien IIC	A4L1357Y	sterile,single-use
Ultrsonic equipment	medical ultrasound instrument	E40482	stable,probe sterile