Document Type : Original Research
Authors
- Geetha V PATIL Oklay 1
- Akina Prakash 1
- Akshatha C 1
- Ashwini Nargund 1
- Libin Babu Cherian 1
- Balu S 1
- Arun Kumar A R 2
1 Department of Pathology, Kidwai Memorial Institute of Oncology, Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, India
2 Department of Pediatric Oncology, Kidwai Memorial Institute of Oncology, Rajiv Gandhi University of Health Sciences, Bangalore, Karnataka, India
Abstract
Background & Objective: Hepatoblastoma encompasses 1% of pediatric malignancies and is the most common liver malignancy in children. Ninety percent of cases are under 5 years of age. Clinical and pathological risk stratification forms a crucial role in determining the treatment strategy. This study aimed to assess the clinicopathological profile of hepatoblastoma with risk stratification and follow-up in children.
Methods: A retrospective evaluation was performed on all pediatric patients recognized with hepatoblastoma between 2016 and 2020 in our institution. Clinical, radiological, biochemical, pathological, and treatment data were analyzed. Cases were stratified based on the SIOPEL protocol and compared with the outcome.
Results: The median age of all children was 1 year, the male-to-female ratio was 2.3:1, and elevated α-fetoprotein (AFP) was observed in all cases. SIOPEL risk stratification showed that 50% of children are at high risk. The histopathological types were fetal (30%), embryonal (20%), and macrotrabecular (5%) patterns under epithelial type and mixed epithelial and mesenchymal type (45%) with 1 case showing teratoid features. During the follow-up period, of the 7 children who died, 6 belonged to the high-risk SIOPEL category, and 5 had a mixed epithelial and mesenchymal pattern.
Conclusion: Our study found a significant correlation between clinicopathological data, histopathological patterns, and outcomes. Accordingly, histopathological patterns could be considered one of the criteria for risk stratification. Histopathological risk stratification indicators (such as SIOPEL and PRETEXT) have strong prognostic and predictive outcomes; hence, our study emphasizes such parameters to aid oncologists.
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Main Subjects
- Herzog CE, Andrassy RJ, Eftekhari F. Childhood cancers: hepatoblastoma. Oncol. 2000 Dec;5(6):445-53. [DOI:10.1634/the oncologist.5-6-445] [PMID]
- Hung GY, Lin LY, Yu TY, Lee CY, Yen HJ, Horng JL. Hepatoblastoma incidence in Taiwan: a population-based study. J Chin Med Assoc. 2018 Jun 1;81(6):541-7. [DOI:10.1016/j.jcma.2017.11.012] [PMID]
- Reynolds P, Urayama KY, Von Behren J, Feusner J. Birth characteristics and hepatoblastoma risk in young children. Cancer. 2004;100(5):1070-6. [DOI:10.1002/cncr.20061] [PMID]
- Spector LG, Birch J. The epidemiology of hepatoblastoma. Pediatr Blood Cancer. 2012;59(5):776-9. [DOI:10.1002/pbc.24215] [PMID]
- Otten J, Smets R, De Jager R, Gerard A, Maurus R. Hepatoblastoma in an infant after contraceptive intake during pregnancy. N Engl J Med. 1977; 297: 222. [DOI:10.1056/NEJM197707282970417] [PMID]
- Perilongo G, Shafford E, Maibach R, Aronson D, Brugie'res L, Brock P, et al. Risk-adapted treatment for childhood hepatoblastoma: final report of the second study of the International Society of Paediatric Oncology SIOPEL 2. Eur J Cancer. 2004; 40:411e21.
- Aronson DC, Schnater JM, Staalman CR, Weverling GJ, Plaschkes J, Perilongo G, et al. Predictive value of the pretreatment extent of disease system in hepatoblastoma: Results from the international society of Pediatric Oncology Liver Tumor Study Group SIOPEL-1 study. J Clin Oncol. 2005;23:1245-52. [DOI:10.1200/JCO.2005.07.145] [PMID]
- Roebuck DJ, Aronson D, Clapuyt P, Czauderna P, de Ville de Goyet J, Gauthier F, et al. International Childhood Liver Tumor Strategy Group 2005 PRETEXT: A revised staging system for primary malignant liver tumors of childhood developed by the SIOPEL group. Pediatr Radiol. 2007;37:123-32. [DOI:10.1007/s00247-006-0361-5] [PMID] [PMCID]
- Shanmugam N, Scott JX, Kumar V, Vij M, Ramachandran P, Narasimhan G, et al. Multidisciplinary management of hepatoblastoma in children: Experience from a developing country. Pediatr Blood Cancer. 2017;64:e26249. [DOI:10.1002/pbc.26249] [PMID]
- Czauderna, B. Haeberle, E. Hiyama, A. Rangaswami, M. Krailo, R. Maibach, et al. The Children's Hepatic tumors International Collaboration (CHIC): novel global rare tumor database yields new prognostic factors in hepatoblastoma and becomes a research model. Eur J Cancer. 52 (2016), 92-101 [DOI:10.1016/j.jped.2015.12.001]
- Ninane J, Perilongo G, Stalens JP, Guglielmi M, Otte JB, Mancini A. Effectiveness and toxicity of cisplatin and doxorubicin (PLADO) in childhood hepatoblastoma and hepatocellular carcinoma: A SIOP pilot study. Med Pediatr Oncol. 1991;19:199-203. [DOI:10.1002/mpo.2950190310] [PMID]
- Ortega JA, Kralio MD, Haas JE, King DR, Ablin AR, Quinn JJ, et al. Effective treatment of unresectable or metastatic hepatoblastoma with cisplatin and continuous infusion doxorubicin: A report from the Children's Cancer Study Group. J Clin Oncol. 1991;9:2167-76 [DOI:10.1200/JCO.1991.9.12.2167] [PMID]
- Douglass EC, Reynolds M, Finegold M, Cantor AB, Glicksman A. Cisplatin, vincristine, and fluorouracil therapy for hepatoblastoma: A pediatric oncology group study. J Clin Oncol. 1993;11:96-9. [DOI:10.1200/JCO.1993.11.1.96] [PMID]
- Weinblatt ME, Siegel SE, Siegel MM, Stanley P, Weitzman JJ. Preoperative chemotherapy for unresectable primary hepatic malignancies in children. Cancer. 1982;50:1061-4. [DOI:10.1002/1097-0142(19820915)50:63.0.CO;2-Q] [PMID]
- Filler RM, Ehrlich PF, Greenberg ML, Babyn PS. Preoperative chemotherapy in hepatoblastoma. Surgery. 1991;110:591-7.
- Von Schweinitz D, Byrd DJ, Hecker H, Weinel P, Bode U, Bürger D, et al. Efficiency and toxicity of ifosfamide, cisplatin, and doxorubicin in the treatment of childhood hepatoblastoma. Study committee of the Cooperative Paediatric Liver Tumor Study HB89 of the German Society of Paediatric Oncology and Haematology. Eur J Cancer.1997;33:1243-9. [DOI:10.1016/S0959-8049(97)00095-6] [PMID]
- Kalifa C, Lemerle J, Caillaud JM. Resectability of childhood hepatoblastoma is improved by primary chemotherapy. Proc Am Soc Clin Oncol. 1984:c308.
- Perilongo, E. Shafford, R. Maibach, D. Aronson, L. Brugières, P. Brock, M. Risk-adapted treatment for childhood hepatoblastoma: final report of the second study of the International Society of Paediatric Oncology-SIOPEL 2. Eur J Cancer. 2004:40 (3),411-21. [DOI:10.1016/j.ejca.2003.06.003] [PMID]
- Dietrich von Schweinitz, Hepatoblastoma: recent developments in research and treatment, Seminars in Paediatric Surgery, Volume 21, Issue 1,2012,21-30. [DOI:10.1053/j.sempedsurg.2011.10.011] [PMID]
- Zsiros J, Brugieres L, Brock P, Roebuck D, Maibach R, Zimmermann A, et al. Dose-dense cisplatin-based chemotherapy and surgery for children with high-risk hepatoblastoma (SIOPEL-4): a prospective, single-arm, feasibility study. Lancet Oncol. 2013;14(9):834-42.
- Finegold MJ, López-Terrada DH. Hepatic tumors in childhood. Pathol Pediatr Gastrointest Liver Dis. 2014:547-614. [DOI:10.1007/978-1-4419-9066-2_13]
- International Agency for Research on Cancer, editor. WHO classification of tumours of the digestive system. International Agency for Research on Cancer; 2019.
- Cairo, C. Armengol, A. De Reyniès, Y. Wei, E. Thomas, C.A. Renard, et al. Hepatic stem-like phenotype and interplay of Wnt/β-catenin and Myc signaling in aggressive childhood liver cancer Cancer Cell, 14 (2008), 471-84 [DOI:10.1016/j.ccr.2008.11.002] [PMID]
- Wu JF, Lee CH, Chen HL, Ni YH, Hsu HY, Sheu JC, Tsuei DJ, Chang MH. Copy-number variations in hepatoblastoma associate with unique clinical features. Hepatol Int. 2013;7:208-14. [DOI:10.1007/s12072-012-9350-y] [PMID]
- Aronson DC, Schnater JM, Staalman CR, et al. Predictive value of the pre-treatment extent of disease system in hepatoblastoma: results from the International Society of Pediatric Oncology Liver Tumor Study Group SIOPEL-1 study. J Clin Oncol. 2005;23(6):1245-52. [DOI:10.1200/JCO.2005.07.145] [PMID]
- Meyers RL, Maibach R, Hiyama E, Häberle B, Krailo M, Rangaswami A, Aronson DC, Malogolowkin MH, Perilongo G, von Schweinitz D, Ansari M. Risk-stratified staging in paediatric hepatoblastoma: a unified analysis from the Children's Hepatic tumors International Collaboration. Lancet Oncol. 2017;18(1):122-31. [DOI:10.1016/S1470-2045(16)30598-8] [PMID]
- Rowland JM. Hepatoblastoma: assessment of criteria for histologic classification. Med Pediatr Oncol. 2002 Nov;39(5):478-83. [DOI:10.1002/mpo.10171] [PMID]
- Meyers RL, Rowland JR, Krailo M, Chen Z, Katzenstein HM, Malogolowkin MH. Predictive power of pretreatment prognostic factors in children with hepatoblastoma: a report from the Children's Oncology Group. Pediatr Blood Cancer. 2009;53(6):1016-22. [DOI:10.1002/pbc.22088] [PMID] [PMCID]
- Fuchs, J. Rydzynski, D. Von Schweinitz, U. Bode, H. Hecker, P. Weinel, et al. Pre-treatment prognostic factors and treatment results in children with hepatoblastoma: a report from the German Cooperative Paediatric Liver Tumor Study HB 94. Cancer, 95 (2002), 172-182.
- Wei-Yun Hsu, Hsiu-Hao Chang , Meng-Yao Lu , Yung-Li Yang. Clinical risk stratification of children with SIOPEL high-risk hepatoblastoma in Taiwan. Paediatr Neonatol. 2020;61: 393-8. [DOI:10.1016/j.pedneo.2020.03.012] [PMID]
31. Archana B, Thanka J,Sneha LM, Scott JJX, Arunan M, Agarwal P. Clinicopathological profile of hepatoblastoma: An experience from a tertiary care centre in India. Indian J Pathol Microbiol. 2019;62: 556-560. [DOI:10.4103/IJPM.IJPM_200_19] [PMID]
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