Successful treatment of hepatoblastoma in a child with hypoplastic left heart syndrome and mosaic trisomy 7

We report the successful treatment of hepatoblastoma in a child with hypoplastic left heart syndrome and mosaic trisomy 7. Severe cardiac comorbidities compromised venous access, and the risk of chemotherapy-related toxicity posed significant challenges. A multidisciplinary team opted for cisplatin monotherapy and tailored surgical timing. Despite anatomical and genetic complexity, the patient achieved complete remission and long-term survival. At age 13.5, he remains tumor-free with good Fontan circulation. This case illustrates the feasibility of curative cancer therapy in children with single-ventricle physiology when guided by individualized and collaborative decision-making.

Hepatoblastoma (HB) is a rare malignant pediatric liver tumor and the most common primary hepatic malignancy in early childhood.[1] Hypoplastic left heart syndrome (HLHS) is a severe congenital heart defect (CHD), characterized by underdevelopment of the left ventricle and associated structures, resulting in impaired systemic circulation.[2] Without surgical intervention, HLHS is uniformly fatal. Advances in staged surgical palliation (Norwood/Hybrid, Glenn, and Fontan procedures) have improved survival, though long-term outcomes remain guarded.[3,4] Recent reports suggest a higher prevalence of CHD (19.2%) among patients with HB, though HLHS remains exceptionally rare in this context.[5] Only one publication has described the coexistence of HB and HLHS in two infants.[6] Genetic syndromes such as trisomy 18 have been linked to both conditions.[5] Here, we report a unique case of a boy with HB, HLHS, and mosaic trisomy 7, complicated by venous occlusions, necessitating individualized and multidisciplinary treatment planning. Case report The patient was diagnosed prenatally with HLHS and mosaic trisomy 7 via chorionic villus sampling. Pregnancy was complicated by oligohydramnios and intrauterine growth restriction. He was delivered via cesarean section at 39 weeks, weighing 2190 g. He received prostaglandin E1 after birth and underwent a modified Norwood procedure with Sano shunt on day 9 of life. The postoperative period was prolonged due to pleural effusions, requiring re-drainage and delayed extubation. Cardiac decompensation necessitated high-flow oxygen, inotropes (including levosimendan), and intensive care until the bidirectional Glenn operation at 3.5 months. Neonatal screening also revealed pathologic otoacoustic emissions. At 6 weeks, routine abdominal ultrasound revealed a 1.8 cm hyperechoic lesion in liver segment 5 with normal AFP levels of 287 ng/ml ( Fig. 1A ). Serial imaging showed progressive enlargement with involvement of segments 5 and 6 ( Fig. 1B ), and AFP rose to 3246 ng/ml. At 5 months, biopsy confirmed fetal type hepatoblastoma. Preoperative MRI demonstrated involvement of segments 5 and 6, and a new 7 mm lesion in segment 2 ( Fig. 1C ), corresponding to involvement of the right anterior and right posterior sections.[7] Computed tomography of the lungs excluded lung metastases. Based on SIOPEL 3 criteria (radiological PRETEXT stage III and significantly elevated AFP), the tumor was classified as standard-risk.[7,8] Vascular access was severely limited by thromboses in both femoral veins and the inferior vena cava ( Fig. 2 ). Given the Glenn shunt, inserting a central line via the superior vena cava was high-risk. A multidisciplinary team decided on a peripherally inserted central catheter (PICC) via the left cubital vein. Neoadjuvant chemotherapy with cisplatin monotherapy was chosen, omitting doxorubicin to avoid cardiotoxicity.[8] Four cycles were well tolerated and led to marked tumor shrinkage. Given continued response and good tolerance, two additional cisplatin cycles were administered. Preoperative MRI showed near-complete regression; the lesion in segment 2 was no longer visible, and the main tumor measured only 2.1 × 1.5 × 1.3 cm. AFP declined to 95.7 ng/ml. The patient underwent extended right hemihepatectomy with cholecystectomy. Postoperatively, he received one additional cisplatin dose. MRI one month later confirmed complete remission, and the patient proceeded to regular oncology, cardiology, and audiology aftercare. Five years later, the patient successfully underwent the Fontan procedure. Hearing loss was managed with hearing aids. At 13.5 years, the boy shows good Fontan circulation on echocardiography and no tumor recurrence. Due to a global intellectual developmental delay, he attends an integrative school. However, he has good motor skills and participates in various sports, including swimming, cycling, and soccer.

HB typically presents before age 3 and is associated with low birth weight and prematurity.[9,10] Several congenital syndromes have been associated with hepatoblastoma, including Edwards syndrome, familial adenomatous polyposis, and Beckwith-Wiedemann syndrome.[11] The largest series of patients with HB and CHD reports a strong association with trisomy 18, with a prevalence of 17.2% in those with both conditions compared to 0.8% in patients with HB only.[5] Genetic findings were not provided for the two patients with HB and HLHS published by Windom & Campbell.[6] Our patient has mosaic trisomy 7, which is a rare chromosomal disorder. The effects of this condition vary widely depending on the proportion of affected cells and the specific organs involved.[12] Life expectancy is highly variable and depends on the severity of associated medical issues. The major challenge in the decision to treat HB and the treatment management posed the severe CHD and its complications, particularly the previous protracted cardiac decompensation and the multiple thrombotic venous occlusions. Those comorbidities were of particular concern, as standard combination systemic chemotherapy for high-risk HB requires a central venous line, high-volume hydration during platinum application, and contains the cardiotoxic anthracycline doxorubicin.[13] Use of cisplatin alone, supported by SIOPEL 3 data, minimized risks while maintaining efficacy.[8] Avoiding anthracyclines reduced hematologic and cardiac side effects. PICC placement avoided Glenn-related thrombosis. The neoadjuvant treatment was delivered without any complications and achieved an excellent tumor response, enabling radical resection. This case underlines the importance of individualized, multidisciplinary planning. With tailored chemotherapy and careful surgical timing, curative treatment was feasible even in this highly complex setting. Long-term follow-up confirms both oncological and cardiological success.

We report the successful treatment of hepatoblastoma in a child with HLHS and mosaic trisomy 7. Despite significant comorbidities and vascular complications, a personalized and multidisciplinary approach enabled full remission and excellent cardiac outcome. This case adds to the limited literature on the coexistence of HB and HLHS and emphasizes the feasibility of curative therapy with careful planning. Acknowledgments We sincerely thank all colleagues and nurses involved in the patient’s clinical care.

1. Spyridakis I, Kepertis C, Lampropoulos V, et al. Embryonal/Fetal subtype hepatoblastoma: a case report. J Clin Diagn Res 2014:8(9):ND01-02.2. Barron DJ, Kilby MD, Davies B, et al. Hypoplastic left heart syndrome. Lancet 2009:374(9689):551-564.3. Pundi KN, Johnson JN, Dearani JA, et al. 40-Year Follow-Up After the Fontan Operation: Long-Term Outcomes of 1,052 Patients. J Am Coll Cardiol 2015:66(15):1700-1710.4. Yabrodi M, Mastropietro CW. Hypoplastic left heart syndrome: from comfort care to long-term survival. Pediatr Res 2017:81(1-2):142-149.5. Espinoza AF, Montgomery AE, Maamari NC, et al. The impact of congenital heart disease on treatment and survival of patients with hepatoblastoma: A single-center experience. Pediatr Blood Cancer 2024:71(11):e31214.6. Windom MO, Campbell MJ. Hepatoblastoma diagnosed in infancy occurring in single-ventricle patients: a case series. Cardiol Young 2020:30(12):1967-1969.7. Roebuck DJ, Aronson D, Clapuyt P, et al. 2005 PRETEXT: a revised staging system for primary malignant liver tumours of childhood developed by the SIOPEL group. Pediatr Radiol 2007:37(2):123-132; quiz 249-150.8. Perilongo G, Maibach R, Shafford E, et al. Cisplatin versus cisplatin plus doxorubicin for standard-risk hepatoblastoma. N Engl J Med 2009:361(17):1662-1670.9. Feusner J, Plaschkes J. Hepatoblastoma and low birth weight: a trend or chance observation? Med Pediatr Oncol 2002:39(5):508-509.10. Maruyama K, Ikeda H, Koizumi T, et al. Case-control study of perinatal factors and hepatoblastoma in children with an extremely low birthweight. Pediatr Int 2000:42(5):492-498.11. von Schweinitz D. Hepatoblastoma: recent developments in research and treatment. Semin Pediatr Surg 2012:21(1):21-30.12. Hou F, Li Y, Jin H. Clinical manifestations and the prenatal diagnosis of trisomy 7 mosaicism: Two case reports. World J Clin Cases 2024:12(8):1544-1548.13. Pritchard J, Brown J, Shafford E, et al. Cisplatin, doxorubicin, and delayed surgery for childhood hepatoblastoma: a successful approach–results of the first prospective study of the International Society of Pediatric Oncology. J Clin Oncol 2000:18(22):3819-3828. Legends to the Figures Figure 1. Pretreatment course of the tumor. 1A. Incidental hyperechoic liver mass in segment 5 on routine sonography at 6 weeks; 1B. MRI, T1-Flash coronal plane after contrast, at 3.5 months, demonstrating a significant increase of the lesion affecting segments 5 and 6; 1C. MRI, T1-Flash coronal plane after contrast, at 5.5 months, showing the lesion in segments 5 and 6, and a second lesion in segment 2. Figure 2. Post-interventional thrombotic occlusions of the femoral veins . (MRT, TOF-angio coronal plane). Information & Authors Information Version history Peer review timeline Published Pediatric Blood & Cancer Version of Record26 Jun 2025Published Copyright This work is licensed under a Non Exclusive No Reuse License.

Authors Metrics & Citations Metrics Article Usage 255views 125downloads Citations Download citation Silvia Pironkova, Barbara Winkler, Rudolf Mair, et al. Successful treatment of hepatoblastoma in a child with hypoplastic left heart syndrome and mosaic trisomy 7. Authorea. 02 June 2025. DOI: https://doi.org/10.22541/au.174884601.10158156/v1 DOI: https://doi.org/10.22541/au.174884601.10158156/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu.