Choriocarcinoma at an Abdominal Wall Cesarean Scar: Recurrence After Multi-Line Chemotherapy and Exploration of Salvage Therapy.

The patient was a 40-year-old woman (gravida 4, para 2) who delivered a second full-term infant via cesarean section with concurrent bilateral tubal ligation in 2013. She had regular menstruation, with her last menstrual period on 28 January 2024. On 18 February, the patient experienced light vaginal bleeding. Laboratory tests performed on 3 March revealed a serum β-hCG level of 316.7 mIU/mL ( Figure 1 ) and a progesterone level of 0.62 ng/mL. A pelvic ultrasound performed the same day at an outside hospital demonstrated an endometrial thickness of 12.4 mm. She then underwent two dilation and curettage (D&C) procedures on 4 and 21 March, both of which revealed a secretory-phase endometrium with polypoid alterations, raising a high suspicion of ectopic pregnancy. Despite three doses of methotrexate (MTX) therapy, totaling 175 mg for suspected ectopic pregnancy, her serum β-hCG progressively increased, reaching 964.1 mIU/mL on 10 April. Figure 1 Pre-and post-diagnosis serum β-hCG monitoring in the present case. A line graph tracks Serum beta hCG levels over dates in 2024, with shaded bands for medical procedures: Dilation and curettage (D and C), Methotrexate (MTX) and Lesion resection. The x-axis shows dates from 3-Mar-2024 to 30-Apr-2024 and the y-axis displays Serum beta hCG (mIU/mL) ranging from 200 to 1800. Key data points: 3-Mar is 316.7; 5-Mar is 337.4; 8-Mar is 490.9; 12-Mar is 514.7; 18-Mar is 460.2; 21-Mar is 532.7; 22-Mar is 536; 27-Mar is 713.9; 3-Apr is 922.6; 10-Apr is 964.1; 12-Apr is 1482; 15-Apr is 1010.1; 22-Apr is 1729; 23-Apr is 586.8; 30-Apr is 567.8. Shaded bands are around 4-Mar and 21-Mar for D and C, 5-Mar, 12-Mar and 3-Apr for MTX and 22-Apr for Lesion resection. A line graph showing serum beta hCG monitoring with marked procedures and treatments over time. Pre-and post-diagnosis serum β-hCG monitoring in the present case. The patient was transferred to our hospital on 12 April 2024. Physical examination demonstrated a 14 cm old longitudinal cesarean scar at the midline hypogastrium. A palpable mass measuring approximately 4 cm in diameter was detected subjacent to the cesarean scar above the pubic symphysis, which was firm, well-circumscribed, and nontender. Gynecological examination revealed no abnormalities. On the same day, her serum β-hCG was 1482 mIU/mL, which decreased to 1010 mIU/mL on 15 April, with a progesterone level of 1.01 ng/mL. Gynecological ultrasonography performed on 12 April revealed a medium-echoic area (1.8 cm in diameter) within the uterine cavity, as well as a hypoechoic mass (3.92 cm × 3.80 cm × 3.96 cm) located anterior to the uterus, which had ill-defined margins and punctate vascularity. Pelvic magnetic resonance imaging (MRI) with plain and contrast-enhanced scanning on 15 April revealed a patchy abnormal signal (3.4 cm × 1.7 cm) within the uterine cavity, with mild enhancement and no diffusion restriction, and a solid mass (4.4 cm × 4.2 cm × 3.6 cm) in the anterior inferior abdominal wall musculature, which showed a heterogeneously high T2-weighted imaging (T2WI) signal, high diffusion-weighted imaging (DWI) signal, reduced apparent diffusion coefficient (ADC) values, and marked heterogeneous enhancement on post-contrast images without peritoneal breach ( Figure 2 ). Overall, imaging diagnoses included an abnormal uterine cavity signal (suspected endometrial hyperplasia with polyps) and an anterior inferior abdominal wall mass (considering the history of cesarean section and suspected cesarean scar endometriosis). Figure 2 Preoperative MRI findings of the abdominal wall cesarean scar lesion. ( A ) Axial T1-weighted, ( B ) axial T2-weighted, ( C ) sagittal T2-weighted, and ( D ) sagittal contrast-enhanced T1-weighted turbo spin-echo images, with the lesion indicated by orange arrows. Four pelvic MRI scans (A to D) with orange arrows highlighting soft tissue focus on axial and sagittal views. Preoperative MRI findings of the abdominal wall cesarean scar lesion. ( A ) Axial T1-weighted, ( B ) axial T2-weighted, ( C ) sagittal T2-weighted, and ( D ) sagittal contrast-enhanced T1-weighted turbo spin-echo images, with the lesion indicated by orange arrows. After multidisciplinary discussion, given that the patient had undergone bilateral tubal ligation, two D&C showed no villi or trophoblasts, MTX treatment was ineffective, progesterone was consistently <1 ng/mL, and both gynecological ultrasonography and MRI revealed no signs of abdominopelvic pregnancy, pregnancy could be essentially ruled out. Although other rare etiologies of positive serum β-hCG in a non-pregnant state need consideration, her reproductive age, prior pregnancy history, and concurrent lesions in the uterine cavity and abdominal wall cesarean scar collectively made GTN the most likely diagnosis. For classic GTN (invasive mole or choriocarcinoma), a clinical diagnosis can be made based solely on dynamic serum β-hCG monitoring when preceded by molar pregnancy. In this case, however, the patient’s last pregnancy was a full-term cesarean section, and two D&C procedures yielded no pathological evidence of a molar pregnancy. Considering the suspicion of non-molar GTN (including choriocarcinoma, placental site trophoblastic tumor (PSTT), and epithelioid trophoblastic tumor (ETT)), histopathological confirmation remains the gold standard for definitive diagnosis. Furthermore, the nature of the uterine and abdominal wall lesions remains unclear, and we recommend hysteroscopic lesion resection combined with excision of the abdominal wall mass to obtain adequate tissue samples for histopathological confirmation. If necessary, laparoscopic or transabdominal exploration can be performed intraoperatively to identify suspicious lesions in the pelvic and abdominal cavities. On 22 April 2024, serum β-hCG was 1729 mIU/mL, and progesterone was 1.13 ng/mL. Electroresection of the hysteroscopic lesion combined with abdominal wall mass excision was performed on the same day. Intraoperatively, polypoid tissue was observed in the uterine cavity and electroresected. The abdominal wall mass (5.5 cm in diameter) was located in the extraperitoneal vesical space beneath the rectus abdominis muscle, surrounded by an indurated and thickened rectus abdominis muscle and anterior sheath. Intraoperative frozen section examination of the abdominal wall mass suggested a malignant tumor, favoring a GTN ( Figure 3 ). To exclude occult metastases, accurately stage the disease, and guide subsequent chemotherapy, further abdominopelvic exploration was performed and revealed no tumors, enlarged lymph nodes, or gross abnormalities of the uterus or bilateral adnexa. Pathological examination of the postoperative specimen confirmed that the resected uterine tissue showed a proliferative endometrium with polypoid changes. Immunohistochemical (IHC) staining of the abdominal wall mass revealed positive staining for β-hCG, hPL (scattered cells), p63 (partial), SALL4 (focal), CK7, CKpan, and inhibin-α (focal), with weak focal positivity for glypican-3, and Ki-67 positivity of approximately 65%. Negative staining was observed for ER, PR, PAX-8, and Napsin A, whereas p53 exhibited a wild-type pattern ( Figure 3 ). Hematoxylin and eosin (H&E) staining, together with the immunohistochemical results, confirmed the pathological diagnosis of choriocarcinoma. Moreover, both the chest CT and brain MRI performed for staging evaluation revealed no evidence of metastases. Collectively, these findings established the final diagnosis of choriocarcinoma at the abdominal wall cesarean scar, with a prognostic score of 10 according to the FIGO 2000 scoring system, and reevaluation based on the FIGO 2026 criteria confirmed the same score of 10 ( Table 1 ). 7 Figure 3 H&E staining shows the biphasic mixture of cytotrophoblasts and syncytiotrophoblasts, with immunohistochemical markers further confirming the diagnosis of choriocarcinoma at the abdominal wall cesarean scar (scale bar: 100 µm, ×120). 15 tissue images: 1 H&E stain, 14 immunohistochemistry stains on white background. Table 1 FIGO-Modified WHO Risk Score for GTN (2026) Applied to the Present Case Prognostic Factor Risk Score The present case 0 1 2 4 Age (years) <40 ≥40 – – 1 Antecedent pregnancy Hydatidiform mole Abortion/miscarriage/ectopic Term pregnancy – 2 Interval months from index pregnancy 12 4 Pretreatment hCG (mIU/mL) <10 3 10 3 to <10 4 10 4 to <10 5 ≥10 5 1 Largest size of tumor (in uterus/metastatic site) (cm) 5 – 2 Site of metastases Lung, vagina Spleen, kidney Gastrointestinal tract Brain, liver 0 Number of metastases identified – 1–4 5–8 >8 0 Total score 10 H&E staining shows the biphasic mixture of cytotrophoblasts and syncytiotrophoblasts, with immunohistochemical markers further confirming the diagnosis of choriocarcinoma at the abdominal wall cesarean scar (scale bar: 100 µm, ×120). FIGO-Modified WHO Risk Score for GTN (2026) Applied to the Present Case On postoperative day 8, serum β-hCG decreased to 567.8 mIU/mL. Eight cycles of EMA/CO (etoposide, methotrexate, dactinomycin/cyclophosphamide, vincristine) chemotherapy were administered from May to September 2024, and the serum β-hCG progressively declined and normalized after the 5 th cycle, followed by three cycles of consolidation chemotherapy ( Figure 4 ). However, in December 2024, her serum β-hCG was 51.74 mIU/mL, rising to 92.31 mIU/mL on 7 January 2025, and same-day pelvic MRI with plain and contrast-enhanced scanning revealed an early dynamic enhancing strip-like lesion located anterior and superior to the pubic symphysis in the right lower abdominal wall, findings that together suggested local recurrence. Figure 4 Serial serum β-hCG levels during primary EMA/CO chemotherapy in the present case. A line graph with shaded vertical bands labeled C1 through C8 and a legend listing, Serum beta hCG and, 8 cycles of EMA slash CO regimen. The x axis shows dates from 6 May 2024 to 7 Jan 2025. The y axis label is, Serum beta hCG, with unit, milli international unit per milliliter, on a logarithmic scale with labeled ticks at 1, 5, 10 and 100. A dotted horizontal reference line is at 5 milli international unit per milliliter. The plotted serum beta hCG values, in order, are 304.57, 172.57, 62.62, 33.94, 13.78, 9.16, 10.34, 8.48, 6.64, 4.51, 5.37, 3.86, 4.05, 3.52, 2.56, 2.58, 4.97, 6.64, 4.94, 51.74 and 92.31. A line graph showing serial serum beta hCG levels during 8 cycles of EMA slash CO regimen. Serial serum β-hCG levels during primary EMA/CO chemotherapy in the present case. Salvage therapy was initiated with four cycles of the EMA/EP (etoposide, methotrexate, dactinomycin/etoposide, cisplatin) regimen between January and March 2025 ( Figure 5 ). However, given the suboptimal serum β-hCG level decline, the patient underwent excision of the abdominal wall mass on 2 April 2025. Histopathological examination revealed nests of markedly atypical tumor cells infiltrating the sclerotic fibrous tissue, favoring a malignant tumor. Furthermore, IHC staining showed β-hCG (focal+), inhibin-α (partial+), Ki-67 (approximately 30%+), CD10 (+++), CK7 (+++), and MC (++) with AFP, SALL4, and PRL (−), confirming choriocarcinoma. Serum β-hCG measured in the immediate postoperative period decreased to 4.05 mIU/mL, yet subsequently rose to 10.30 mIU/mL within 2 weeks. The salvage chemotherapy regimen was then switched to FAV (floxuridine, dactinomycin, and vincristine) for 5 cycles from April to July 2025; during this period, serum β-hCG normalized after the first cycle, followed by 4 cycles of consolidation chemotherapy. In March 2026, her serum β-hCG level rebounded to >1,000 mIU/mL, indicating a second recurrence. Figure 5 Serial serum β-hCG levels during salvage therapy with EMA/EP regimen, surgical excision, and FAV regimen in the present case. A line graph tracks serum beta human chorionic gonadotropin levels over time, with treatment periods marked by shaded blocks. The x-axis spans from January 7, 2025, to March 2026, with key dates labeled. The y-axis, on a logarithmic scale, measures serum levels in milli international units per milliliter, with ticks at 1, 5, 10, 100 and 1000. A dashed line indicates 5 milli international units per milliliter. Data points show levels: 92.31 on January 7, 2025; 27.8 on January 27, 2025; 26.8 on February 16, 2025; 8.54 on March 25, 2025; 4.05 at Post-op exam; 10.3 on April 14, 2025; 4.2 on May 5, 2025; 1.5 on July 8, 2025; and over 1000 in March 2026. The legend includes: Serum beta human chorionic gonadotropin; 4 EMA/EP regimen cycles; Abdominal wall mass excision; 5 FAV regimen cycles. EMA/EP cycles (C1 to C4) span January to March 2025. Abdominal wall mass excision is around April 2, 2025. FAV cycles (C1 to C5) run mid-April to mid-July 2025, with C5 near July 10, 2025. A line graph of serum beta human chorionic gonadotropin showing decline, brief rise, then rebound above 1000. Serial serum β-hCG levels during salvage therapy with EMA/EP regimen, surgical excision, and FAV regimen in the present case. To further explore the potential therapeutic options for this refractory case, IHC analysis was performed on the abdominal wall lesion. The tumor was positive for CD8+T cell infiltration and PD-1 expression. PD-L1 expression, assessed using 22C3 antibody (SK006, Dako), demonstrated a 40% tumor proportion score with moderate intensity. MLH1, MSH2, MSH6, and PMS2 retained intact nuclear expression, indicating a proficient mismatch repair (pMMR) phenotype. Moreover, VEGF and EGFR were positively expressed in tumor cells ( Figure 6 ). Collectively, these immunohistochemical features support using immune checkpoint inhibitors (ICIs), potentially in combination with chemotherapy and/or anti-angiogenic agents, as a rational salvage strategy for this patient. However, the patient was transferred to another institution before the proposed regimen was administered, leaving this promising strategy unexplored in the present case. Figure 6 IHC analysis of CD8+T cell infiltration, immune checkpoint protein expression, microsatellite status, and angiogenic factors identified potential therapeutic targets for the present case (scale bar: 100 µm, ×120). A grid of 9 micrographs showing immunohistochemistry stains (CD8, PD-1, PD-L1, MLH-1, MSH2, MSH6, PMS2, VEGF, and EGFR). The staining appears brown against a blue counterstain. Scale bar: 100 µm. IHC analysis of CD8+T cell infiltration, immune checkpoint protein expression, microsatellite status, and angiogenic factors identified potential therapeutic targets for the present case (scale bar: 100 µm, ×120). In a telephone follow-up in September 2026, the patient provided a general account of treatment courses after transfer. However, detailed timelines and β-hCG monitoring data could not be precisely verified. She initially received two cycles of TP/TE (paclitaxel, cisplatin, paclitaxel, etoposide) chemotherapy, during which serum β-hCG levels continued to rise, and was subsequently switched to the FAEV (floxuridine, dactinomycin, etoposide, and vincristine) regimen starting in June 2026. Although β-hCG initially declined logarithmically under FAEV treatment, it subsequently plateaued without returning to normal. The overall treatment course after transfer indicated limited efficacy of conventional high-dose chemotherapy and underscored the potential benefit of incorporating immunotherapy.

Choriocarcinoma is a highly aggressive malignant gestational trophoblastic neoplasia (GTN), which primarily originates in the uterine cavity or deep myometrium and is markedly sensitive to chemotherapy, with a relatively high cure rate even in advanced cases. 1 Extrauterine choriocarcinoma is rare and sporadically reported in the ovary, fallopian tube, cervix, greater omentum, peritoneum, and other sites. 2–4 Among these, cases of abdominal wall cesarean scars are even rarer, 5 , 6 with isolated reports worldwide. Given the atypical clinical presentation and radiological features, such cases are frequently misdiagnosed as ectopic pregnancy or abdominal wall endometriosis (AWE), leading to diagnostic challenges and subsequent treatment delays. This article reports a case of choriocarcinoma arising from an abdominal wall cesarean scar, which was high-risk and recurrent after multi-line chemotherapy. We focused on the diagnostic challenges, treatment course, and salvage strategies, along with a systematic literature review, aiming to guide the clinical management of similar rare cases.

This case comprehensively illustrates the diagnostic and therapeutic process of a patient with high-risk, multi-line chemotherapy-recurrent choriocarcinoma arising from an abdominal wall cesarean scar. Against the backdrop of rising cesarean section rates, GTN should be strongly suspected in patients presenting with unexplained positive serum β-hCG levels after cesarean section and an abdominal wall scar mass without typical cyclic pain. MRI, particularly with contrast enhancement, helps differentiate these lesions from AWE. For high-risk GTN (FIGO score 7–12), EMA/CO remains the most commonly used initial regimen and requires close monitoring of serum β-hCG dynamics for early detection of resistance and recurrence. Platinum-based EMA/EP and fluorouracil-based FAEV regimens are common salvage chemotherapy options for EMA/CO failure. For isolated resistant or recurrent lesions, surgical resection provides a definitive histopathological diagnosis and reduces the tumor burden, thereby playing an irreplaceable role in comprehensive salvage treatment strategies. For GTN that has failed multi-line chemotherapy (including EMA/EP and TP/TE), ICIs such as pembrolizumab, whether alone or in combination, achieve CR rates markedly superior to those with standard or high-dose chemotherapy regimens. Both the 2025 ESGO/EOTTD/GCIG/ISSTD and FIGO guidelines recommend immunotherapy after chemoresistance. In summary, early recognition, pathological diagnosis, standardized chemotherapy, timely surgery, and the appropriate introduction of immunotherapy are key to improving the prognosis of this rare condition.

A reproductive-age woman with amenorrhea and positive serum β-hCG was initially treated for suspected ectopic pregnancy with D&C procedures and three doses of MTX therapy, but her serum β-hCG level continued to rise. Imaging examinations further revealed coexisting uterine and abdominal wall cesarean scar lesions, which posed a diagnostic dilemma. In clinical practice, for reproductive-age women with amenorrhea and a positive serum β-hCG result, pregnancy, whether intrauterine or ectopic, must be the primary diagnostic consideration. 8 But in this case, given the combination of tubal ligation, negative D&C findings, persistent serum β-hCG elevation after MTX therapy, no imaging evidence of pregnancy, and a consistently low progesterone level (fluctuating around 1 ng/mL), a value consistent with both the <2.5 ng/mL threshold for GTN vs pregnancy 9 and the mean levels reported in non-molar GTN (1.20 ng/mL vs 5.57 ng/mL in ectopic pregnancy), 10 pregnancy was essentially ruled out. In this context, considering the patient’s reproductive age, prior pregnancy, and concurrent uterine and cesarean scar lesions, GTN remained the most likely diagnosis in the non-pregnant state, although other rare causes of β-hCG elevation (eg, pituitary, phantom, or exogenous hCG, and non-trophoblastic malignancies) cannot be completely excluded. 11 It is important to note that a clinical diagnosis of invasive mole or choriocarcinoma arising after molar pregnancy can be established based on dynamic changes in serum β-hCG levels. 1 For GTN secondary to non-molar pregnancy, the diagnostic process must first exclude retained products of conception and re-pregnancy, with histopathology serving as the gold standard. 1 Among these, intermediate trophoblastic tumors, including PSTT and ETT, often present with atypical serum β-hCG levels, and their diagnosis ultimately relies on histopathology and immunohistochemistry. 12 Furthermore, owing to extensive myometrial and vascular invasion, D&C often fails to obtain representative tissue specimens in PSTT, leading to a missed diagnosis. 13 The patient in the present case delivered a second full-term infant via cesarean section, and two D&C procedures indicated no evidence of hydatidiform mole, suggesting non-molar GTN, which cannot be clinically diagnosed solely based on serum β-hCG. Given the undetermined nature of both the uterine and abdominal wall lesions, hysteroscopic electroresection combined with abdominal wall mass excision was performed to obtain adequate tissue for a definitive diagnosis. This conservative approach was chosen over extensive surgical resection (eg, abdominal hysterectomy), primarily due to diagnostic priority, the established role of systemic chemotherapy for GTN, and the desire for uterine preservation in this relatively young patient. In the present case, differentiation from AWE was essential for lesions at the abdominal wall cesarean scar. AWE is typically characterized by cyclic pain related to menstruation and characteristic MRI features, including heterogeneous T2WI signals, slight DWI hyperintensity, a mean ADC of approximately 1.47 × 10 −3 mm 2 /s, and mild-to-moderate post-contrast enhancement. 14 In contrast, the present mass showed no cyclic pain, and MRI revealed features indicative of a malignant neoplasm, 15 namely heterogeneously high T2WI signal, marked DWI hyperintensity, a low ADC of 0.99 × 10 −3 mm 2 /s, and early-phase marked heterogeneous enhancement, which closely mirrors the imaging findings reported in uterine or uterine cesarean-scar choriocarcinoma. 16–18 Although a malignant abdominal wall tumor was not initially considered given its rarity, retrospective analysis revealed that the atypical clinical presentation and MRI features, particularly the absence of cyclic pain, marked restricted diffusion, and prominent enhancement pattern, served as key differentiators between AWE and an abdominal wall malignancy. Intraoperative frozen sections of the abdominal wall mass were suggestive of choriocarcinoma. To exclude occult metastases, stage the disease, and guide chemotherapy, an abdominopelvic exploration and imaging examinations of the chest and brain were performed, revealing no metastatic disease. In conjunction with postoperative histopathology, the final diagnosis was choriocarcinoma arising from an abdominal wall cesarean section scar. This rare entity has an unclear pathogenesis, with three main hypotheses proposed: 5 , 6 , 19 (1) hematogenous dissemination from a regressed primary uterine choriocarcinoma, (2) iatrogenic implantation of trophoblasts during cesarean section with subsequent malignant transformation, and (3) non-gestational origin from primitive germ cells or somatic carcinoma differentiation. In this case, the patient had a clear history of cesarean delivery; the lesion was located at the cesarean scar; and intraoperative exploration identified no uterine, ovarian, or other primary tumors, all of which favored iatrogenic implantation as the most likely mechanism. Risk stratification based on the WHO/FIGO prognostic score and subsequent systemic therapy for GTN is the cornerstone of successful treatment. In this case, the patient’s prognostic score was 10 per the FIGO 2000 criteria, 20 with 0 for “previous failed chemotherapy”, as the MTX used for ectopic pregnancy treatment was far lower-dose than standard GTN chemotherapy. 21 This scoring approach also aligns with the principle of the updated 2026 guidelines, 7 which have removed this factor from scoring. According to the FIGO guidelines, a score of 7–12 defines high-risk GTN, for which multi-agent chemotherapy is the preferred regimen, and EMA/CO remains the classic first-line chemotherapy. 20 In this case, the patient received eight cycles of EMA/CO postoperatively, and her serum β-hCG normalized for the first time after the 5 th cycle, validating the efficacy of the regimen. However, subsequent follow-up revealed recurrence based on the serum β-hCG levels and imaging findings. For patients who fail to achieve a complete response to EMA/CO, EMA/EP or TP/TE regimens are the most commonly used salvage chemotherapy options. 22 , 23 After recurrence, this patient received four cycles of EMA/EP, but the suboptimal serum β-hCG decline suggested a poor response to platinum-based regimens. In China, the fluoropyrimidine-based FAEV regimen is an effective alternative to EMA/CO as first-line treatment and also serves as an effective salvage regimen. 24 , 25 After a poor response to platinum-based chemotherapy, the patient was switched to the FAV regimen (similar to FAEV), with the serum β-hCG normalized after the first administration, and she subsequently completed four additional cycles as consolidation therapy. In managing GTN, particularly in cases of chemoresistance or recurrence, adjuvant surgery is recognized as an indispensable therapeutic strategy, as supported by clinical guidelines and evidence. 1 , 26–28 Primary indications for surgery in GTN include the presence of an isolated resistant lesion, persistent low-level β-hCG with residual imaging findings after chemotherapy, or life-threatening hemorrhage. In this case, the solitary abdominal wall lesion was resectable and was excised twice. This surgical approach provided a dual benefit: first, complete resection yielded a definitive histopathological diagnosis to guide further therapy; second, cytoreduction of the resistant lesion reduced the tumor burden and thus shortened the chemotherapy course. However, despite comprehensive salvage therapy comprising EMA/EP and FAV regimens, along with lesion resection, the patient failed to achieve long-term remission. In March 2026, the serum β-hCG level exceeded 1000 mIU/mL, which confronted her with the dilemma of selecting a new salvage regimen, underscoring the urgent need for novel therapeutic strategies for GTN refractory to multi-line chemotherapy and surgery. The ubiquitous and high PD-L1 expression in GTN 29–31 has provided a strong biological rationale for ICIs as a promising option in chemoresistant or recurrent disease. Notably, despite the universal microsatellite stable (MSS) and low tumor mutational burden (TMB) profiles in GTN, 31 clinical trials have consistently demonstrated ICI efficacy, 32–35 suggesting that PD-L1 expression, rather than microsatellite or TMB status, may be the primary determinant of ICI response in this disease. Specifically, pembrolizumab monotherapy achieved a complete response (CR) rate of 71.4% (5/7) and an overall response rate (ORR) of 85.7% (6/7) in single agent chemotherapy-resistant GTN; 32 the DART trial reported an ORR of 75% with ipilimumab plus nivolumab in chemorefractory cases; 33 the TROPHIMMUN trial showed a CR rate of 53.3% (8/15) with avelumab in low-risk drug-resistant GTN; 34 and camrelizumab plus apatinib achieved an ORR of 55% (10/20 CR) in high-risk chemorefractory or recurrent GTN. 35 In GTN resistant to EMA/EP or TE/TP, ICI-based regimens (alone or combined with chemotherapy) achieved CR rates exceeding 70%, substantially higher than those of standard or high-dose chemotherapy. Consequently, the ESGO/GCIG/EOTTD/ISSTD guidelines recommend prioritizing immunotherapy over high-dose chemotherapy in suitable patients, 26 and the 2025 FIGO guidelines also recommend considering immunotherapy for recurrent GTN. 1 To guide the selection of subsequent salvage therapy for this patient, IHC profiling of the lesion was performed. The tumor showed positive PD-L1 expression, CD8+T cell infiltration, and PD-1 positivity, corroborating the immunological features that underpin ICI responsiveness in GTN. However, ICIs are often insufficient as monotherapy; as shown in the TROPHIMMUN trial, 57.1% (4/7) of avelumab-resistant patients required additional chemotherapy or surgery to achieve remission. 34 Given the second recurrence despite comprehensive salvage therapy and the suboptimal response to subsequent high-dose chemotherapy, a combination strategy incorporating ICIs is strongly supported. Taken together, a personalized salvage regimen incorporating ICIs in combination with well-established chemotherapy and/or antiangiogenic agents (supported by VEGF/EGFR positivity and the preliminary efficacy of camrelizumab plus apatinib in chemorefractory GTN), 35 with surgery reserved for residual or refractory lesions, may be considered for this patient to pursue durable remission. This report is limited by its retrospective nature, which precluded detailed documentation of perioperative counseling and psychosocial support, an aspect particularly important for such diagnostically challenging cases with prolonged treatment courses. In addition, detailed timelines and serum β-hCG values after the patient’s transfer could not be precisely verified, limiting accurate assessment of post-transfer treatment response. Beyond this report, managing this rare entity is challenging due to diagnostic ambiguity, the need for multidisciplinary expertise, and the lack of standard salvage regimens after multi-line chemotherapy failure. In resource-limited settings, these challenges are further compounded by the cost and availability of novel agents (such as ICIs) and their companion diagnostics. Nevertheless, core measures such as β-hCG monitoring, standard chemotherapy, and timely surgery remain feasible and can still be implemented to improve patient outcomes.