Hemostatic Radiotherapy for Life-Threatening Vaginal Hemorrhage in High-Risk Gestational Trophoblastic Neoplasia Following Partial Hydatidiform Mole: A Rare Case Report

Abstract

Introduction

Gestational trophoblastic neoplasia (GTN) developing after molar pregnancy is highly responsive to treatment when diagnosed early. However, delayed recognition, particularly following a partial hydatidiform mole, may lead to advanced disease with life-threatening hemorrhagic complications.

Case Description

A 47-year-old multiparous woman underwent uterine evacuation at an outside hospital on December 2, 2025, where histopathological examination was reported as a partial hydatidiform mole. No serial quantitative serum β-hCG monitoring was performed after evacuation. She subsequently presented on January 23, 2026, with massive vaginal bleeding, hemorrhagic shock, and severe anemia (hemoglobin 5.7 g/dL). Emergency exploratory laparotomy with total abdominal hysterectomy was performed. Histopathological evaluation of the surgical specimen confirmed an invasive hydatidiform mole characterized by myometrial invasion of hydropic chorionic villi with extensive hemorrhage and necrosis. The postoperative course was complicated by recurrent vaginal bleeding due to clinically suspected vaginal metastasis, while chest imaging demonstrated pulmonary metastases consistent with FIGO stage III GTN. Hemostatic radiotherapy (20 Gy in five fractions) successfully controlled the bleeding and improved the hemoglobin level to 9.6 g/dL. Following hemodynamic stabilization, the patient was classified as having high-risk GTN (FIGO/WHO prognostic score 8) and was treated with multi-agent EMA-CO chemotherapy, achieving an excellent biochemical response with normalization of serum β-hCG during follow-up.

Conclusion

Recurrent or massive vaginal bleeding after molar pregnancy should prompt immediate evaluation for GTN. Early diagnosis, multidisciplinary management, and timely risk-adapted chemotherapy are essential to optimize outcomes in patients with high-risk disease.

Introduction

Gestational trophoblastic disease (GTD) comprises a spectrum of disorders ranging from premalignant lesions, including complete and partial hydatidiform moles, to malignant gestational trophoblastic neoplasia (GTN), such as invasive mole, choriocarcinoma, and other rare trophoblastic tumors.^1–4 Approximately 13%–20% of complete hydatidiform moles (CHM) and 0.5%–5% of partial hydatidiform moles (PHM) subsequently progress to gestational trophoblastic neoplasia (GTN).¹ Advances in standardized diagnostic approaches, centralized management, and risk-adapted chemotherapy have resulted in excellent cure rates for most patients.^1–5 Nevertheless, considerable morbidity and early mortality may still occur, particularly among patients with delayed diagnosis, advanced disease, extensive metastatic burden, or life-threatening hemorrhage at presentation.^1,2,4

The current international classification is based on the 2000 International Federation of Gynecology and Obstetrics (FIGO) staging system in combination with the modified World Health Organization (WHO) prognostic scoring system. This combined classification stratifies patients into low-risk (score <7) and high-risk (score ≥7) groups, providing the basis for selecting either single-agent or multi-agent chemotherapy.^1,2,6,7 In patients with molar pregnancy, serial quantitative serum β-hCG monitoring is essential for the early detection of postmolar GTN. According to FIGO criteria, GTN is diagnosed by characteristic β-hCG plateau or rising patterns, persistent elevation beyond six months after molar evacuation, or histopathologic confirmation of choriocarcinoma, allowing timely treatment before severe complications develop.^1,6–8

The lungs are the most common site of metastasis in GTN, followed by the vagina. Vaginal metastasis is relatively rare, with a reported incidence ranging from 4.5% to 27% among patients with GTN.⁹ In high-risk GTN, pulmonary metastasis is the most frequent metastatic manifestation, occurring in approximately 80% of cases, while hepatic metastasis occurs in approximately 10% of cases.¹⁰

Although vaginal metastases occur infrequently, they represent an important clinical challenge because of their marked vascularity and high propensity for severe hemorrhage.^9,11–13 Biopsy or surgical manipulation of these lesions is generally discouraged, as it may precipitate uncontrollable bleeding unless required for life-saving hemostasis.^11–13 We report the case of a woman initially diagnosed with a partial hydatidiform mole who subsequently presented with hemorrhagic shock. Histopathological examination following emergency hysterectomy confirmed an invasive hydatidiform mole, and the patient ultimately required multidisciplinary management, including hemostatic radiotherapy, for clinically suspected metastatic gestational trophoblastic neoplasia.

Case Illustration

A 47-year-old multiparous woman was referred to tertiary Hospital after undergoing uterine evacuation at an outside hospital on December 2, 2025. Histopathological examination of the curettage specimen was reported as a partial hydatidiform mole. Following evacuation, the patient was advised to undergo routine serial serum β-hCG surveillance; however, due to financial limitations and the lack of health insurance coverage for β-hCG examinations, she did not undergo the recommended follow-up. Approximately seven weeks later, she presented with one week of vaginal bleeding that worsened during the 24 hours before admission. The bleeding was accompanied by nausea, vomiting, and significant unintentional weight loss of approximately 11 kg over the preceding two months. Her medical history was otherwise unremarkable, with no documented chronic illnesses such as hypertension or diabetes mellitus.

On January 23, 2026, the patient presented in hemorrhagic shock. Following initial resuscitation, her blood pressure was 79/49 mmHg, accompanied by tachycardia and tachypnea. Laboratory evaluation revealed severe anemia with a hemoglobin level of 5.7 g/dL. Pelvic examination was limited because of profuse vaginal bleeding, although one examination documented cervical dilatation of approximately 2 cm. Emergency pelvic ultrasonography demonstrated an enlarged uterus with a vesicular appearance without evidence of an adnexal mass (Figure 1).

Figure 1.

Emergency transabdominal on admission. Ultrasonography demonstrates an enlarged uterus with a heterogeneous vesicular intrauterine lesion, consistent with gestational trophoblastic disease. No adnexal mass or significant free intraperitoneal fluid was identified.

In view of ongoing life-threatening hemorrhage and the clinical suspicion of gestational trophoblastic neoplasia arising from a previously diagnosed partial hydatidiform mole, the patient underwent emergency exploratory laparotomy with total abdominal hysterectomy on the day of admission. Intraoperatively, the uterus was enlarged to approximately the size of a 10–12-week gestation, appeared diffusely reddish, and was associated with grossly normal adnexa without pelvic adhesions. Estimated blood loss was approximately 500 mL, while urine output during the procedure was approximately 200 mL. The surgical specimen was submitted for histopathological evaluation (Figure 2).

Figure 2.

Gross appearance of the hysterectomy specimen. (A) External view of the uterus following emergency total abdominal hysterectomy. (B) Cut section of the uterus demonstrating an intrauterine friable hemorrhagic mass.

Histopathological examination, reported on February 2, 2026, revealed an intrauterine friable mass with gelatinous material occupying the cervical canal. Microscopic evaluation demonstrated hydropic chorionic villi of variable size and irregular configuration lined by cytotrophoblasts and syncytiotrophoblasts with no significant nuclear atypia (Figure 3). Clusters of intermediate trophoblasts infiltrating the myometrium were identified, accompanied by extensive hemorrhage and necrosis (Figure 3). These findings established the diagnosis of an invasive hydatidiform mole.

Figure 3.

Histopathological features of invasive hydatidiform mole (hematoxylin and eosin staining). (A and B) Hydropic chorionic villi of variable size and irregular contour lined by cytotrophoblasts and syncytiotrophoblasts (yellow arrows). (C and D) Clusters of intermediate trophoblasts infiltrating the myometrium (Orange arrows), accompanied by extensive hemorrhage and necrosis, consistent with the diagnosis of invasive hydatidiform mole.

Following surgery, the patient required intensive care because of persistent hypovolemic shock. Her condition gradually stabilized, allowing transfer to the general ward on approximately postoperative day 3. However, recurrent vaginal bleeding developed around postoperative day 6 while discharge was being considered. Re-evaluation revealed a vaginal mass that was clinically consistent with vaginal metastasis (Figure 4). Surgical intervention was deferred because of the substantial risk of catastrophic hemorrhage. Quantitative serum β-hCG measured on January 30, 2026, was 11,970.2 mIU/mL, while chest radiography performed on January 28, 2026, demonstrated multiple intrapulmonary metastatic lesions. Based on these findings, the patient was diagnosed with Stage III gestational trophoblastic neoplasia involving the lungs and vaginal wall, complicated by recurrent hemorrhage, severe anemia, and hypoalbuminemia. Hemostatic radiotherapy (20 Gy in five fractions) was administered to control vaginal bleeding. Clinical improvement was observed after two fractions, with a reduction in bleeding and recovery of hemoglobin to 9.6 g/dL. No significant treatment-related liver enzyme alterations or neutropenia were observed. Owing to a FIGO/WHO prognostic score of 8, consistent with high-risk disease, multi-agent chemotherapy with the EMA-CO regimen was initiated once hemostasis had been achieved and chemotherapy eligibility criteria were satisfied. The patient subsequently received EMA-CO Cycle II on February 20, 2026 with good clinical tolerance and a continued decline in serial serum β-hCG levels.

Figure 4.

Speculum examination demonstrating a clinically suspected vaginal metastatic lesion. A friable, highly vascular nodular lesion (green arrow) involving the vaginal cuff with active hemorrhage, clinically consistent with vaginal metastasis from gestational trophoblastic neoplasia. Biopsy was avoided because of the high risk of catastrophic bleeding.

On March 6, 2026, the patient was re-admitted to Hospital after being referred from District Hospital. She had experienced intermittent vaginal bleeding for one week, which markedly increased during the day before admission despite previous treatment, resulting in hemodynamic instability requiring intensive care, vasopressor support, blood transfusions, and vaginal packing at the referring hospital. On arrival, she remained hypotensive (89/37 mmHg) despite norepinephrine infusion, with tachycardia (122 beats/min) and severe anemia (lowest documented hemoglobin 4.5 g/dL after transfusion at the district hospital). After successful hemodynamic stabilization and control of vaginal bleeding, the patient proceeded with Cycle III of EMA-CO chemotherapy on March 21–22, 2026.

The patient demonstrated an excellent response to EMA-CO chemotherapy. Serial quantitative serum β-hCG levels showed a progressive decline from 11,970.2 mIU/mL on January 30, 2026, to 961.6 mIU/mL on February 21, 704.9 mIU/mL on March 9, 64.2 mIU/mL on April 6, 27.9 mIU/mL on April 15, and 6.3 mIU/mL on May 11, ultimately reaching an undetectable level (<2.30 mIU/mL) on June 29, 2026. The patient subsequently completed EMA-CO Cycles and is currently undergoing consolidation chemotherapy. At the most recent follow-up, serum β-hCG remained undetectable (<2.30 mIU/mL), indicating a sustained biochemical remission and favorable treatment response. The patient’s clinical course and treatment timeline are illustrated in Figure 5.

Figure 5.

The patient’s clinical course and treatment timeline.

Discussion

This case highlights two important and uncommon clinical features: the development of invasive gestational trophoblastic neoplasia (GTN) following an initial diagnosis of partial hydatidiform mole and the occurrence of life-threatening hemorrhage requiring emergency hysterectomy followed by hemostatic radiotherapy for clinically suspected vaginal metastasis. Although GTN most commonly develops after complete hydatidiform mole, it may also occur following partial mole, albeit less frequently. Regardless of the initial pathology, serial quantitative serum β-hCG surveillance after molar evacuation remains the cornerstone for early detection of postmolar GTN and prevention of advanced disease. In the present case, the absence of routine post-evacuation β-hCG monitoring likely contributed to delayed diagnosis and disease progression.^1,3,5,

An important diagnostic challenge in this case was the discrepancy between the initial histopathological diagnosis of a partial hydatidiform mole and the subsequent diagnosis of invasive hydatidiform mole following hysterectomy. Invasive mole is a malignant form of gestational trophoblastic disease characterized by hydropic chorionic villi invading the myometrium and is classified as gestational trophoblastic neoplasia.^1,3,5 Distinguishing complete from partial hydatidiform mole based solely on morphology may be difficult because of overlapping histopathological features. Ancillary techniques, including p57 immunohistochemistry and molecular genotyping, have been recommended to improve diagnostic accuracy, particularly in atypical or equivocal cases.⁵ In the absence of these ancillary investigations, the present findings may represent either progression of a partial mole to invasive disease, which has been reported although infrequently, or an initial histopathological misclassification.^1,5,

The patient was diagnosed with FIGO stage III GTN because of pulmonary metastases and was classified as high risk with a FIGO/WHO prognostic score of 8. Current international guidelines recommend integrating anatomic staging with the WHO prognostic scoring system to guide treatment selection, as patients with stage III disease may belong to either low- or high-risk categories depending on their prognostic score.^1–3,6,7 In patients presenting with advanced disease and hemodynamic instability, prompt resuscitation should be accompanied by comprehensive staging investigations, including serial serum β-hCG measurements, complete blood count, renal and liver function tests, coagulation studies, and appropriate imaging to evaluate metastatic disease.^1–3,5,

Management of hemorrhage in this patient was consistent with current evidence and guideline recommendations. Although suction evacuation followed by serial β-hCG surveillance remains the standard treatment for molar pregnancy, hysterectomy is an accepted therapeutic option for women who have completed childbearing or present with uncontrollable uterine bleeding, extensive myometrial invasion, or life-threatening hemorrhage.^1,3,5,14 In this case, emergency hysterectomy successfully controlled the uterine source of bleeding and established the definitive histopathological diagnosis of invasive mole.

Recurrent vaginal bleeding after hysterectomy was attributed to clinically suspected vaginal metastasis, a well-recognized complication of GTN. Vaginal metastatic lesions are highly vascular and prone to catastrophic hemorrhage; therefore, biopsy or surgical manipulation is generally discouraged unless required for life-saving hemostasis.^9,11,12 Most vaginal metastases respond to systemic chemotherapy, although some patients require additional local hemostatic measures, including vaginal packing, selective arterial embolization, or radiotherapy.^9,11–13

Hemostatic radiotherapy represented an appropriate bridging strategy in this patient. While multi-agent chemotherapy remains the definitive treatment for metastatic GTN, radiotherapy can provide rapid local control of bleeding from highly vascular metastatic lesions when surgery or embolization is considered high risk or technically infeasible.^13,15 Similar approaches have been reported in trophoblastic disease referral centers, where radiotherapy has been successfully incorporated into multimodal management of hemorrhagic vaginal metastases.^9,13 The prompt reduction in vaginal bleeding after two fractions of radiotherapy in this patient enabled subsequent systemic treatment.

Selective arterial embolization is another established option for managing severe hemorrhage associated with GTN. Previous studies have demonstrated high rates of immediate bleeding control with embolization, allowing stabilization of patients before chemotherapy while preserving favorable oncologic outcomes.¹³ Although embolization was not performed in this case, it remained an important therapeutic consideration should bleeding have persisted despite conservative measures.

Following successful hemodynamic stabilization, the patient received multi-agent EMA-CO chemotherapy, the recommended first-line regimen for high-risk GTN. Patients with a FIGO/WHO prognostic score of ≥7 have an increased likelihood of resistance to single-agent chemotherapy and therefore require combination regimens, which achieve cure rates exceeding 80–90% even in metastatic disease.^{1–3,16–18} In the present case, treatment was associated with a rapid decline in serum β-hCG concentrations to an undetectable level, indicating an excellent biochemical response. The patient subsequently entered consolidation chemotherapy, consistent with international recommendations aimed at minimizing the risk of relapse.^1,2,17,18

Long-term follow-up remains an essential component of GTN management. International guidelines recommend serial quantitative serum β-hCG monitoring until normalization, followed by continued surveillance for the recommended duration together with effective contraception to prevent pregnancy-related interference with β-hCG interpretation and facilitate early detection of recurrence.

Conclusion

This case illustrates that gestational trophoblastic neoplasia may develop following an initial diagnosis of partial hydatidiform mole, emphasizing the importance of meticulous postmolar β-hCG surveillance regardless of the initial histopathological subtype. In patients presenting with life-threatening hemorrhage from metastatic disease, prompt multidisciplinary management—including emergency surgery, hemostatic radiotherapy, and timely initiation of risk-adapted multi-agent chemotherapy—may achieve rapid stabilization and effective disease control. Early recognition, appropriate risk stratification, and coordinated multidisciplinary care remain essential to optimize survival and reduce treatment-related morbidity in high-risk GTN.

Informed Consent Patient Statement

Institutional approval was not required for the publication of this single case report. Written informed consent was obtained from the patient for the publication of the case details, in accordance with the ethical principles outlined in the Declaration of Helsinki.

Disclosure

The author(s) report no conflicts of interest in this work.