Small cell undifferentiated (SCUD) hepatoblastomas: All malignant rhabdoid tumors?

Small cell undifferentiated (SCUD) hepatoblastoma is a rare variant of hepatoblastoma with poor outcome and loss of INI1 expression, sharing this with malignant rhabdoid tumors (MRT). We studied all tumors from the files of the Kiel Pediatric Tumor Registry (KTR) with the initial diagnosis of SCUD and MRT. After re‐review, we performed immunistochemistry, fluorescence in situ hybridization, and multiplex ligation dependent probe amplification for loss of expression and deletion of INI1/SMARCB1 in 23 tumors. Morphologically, 12 of the tumors had a small cell morphology, 9 showed the typical picture of MRT, and 2 were composed of both small cells and rhabdoid cells. All but 1 of the 23 tumors showed loss of INI1 protein expression by immunohistochemistry. Nineteen of the INI1 negative tumors were analyzed by FISH technique and all showed a deletion of the INI1/SMARCB1 gene (17 homozygous deletions, 2 heterozygous deletions). We investigated 14 of these cases by multiplex ligation dependent probe amplification and verified the deletions in all cases. In conclusion, we postulate that SCUD hepatoblastoma is not a hepatoblastoma but represents a malignant rhabdoid tumor of the liver. © 2016 Wiley Periodicals, Inc.

[1]  E. Gomulia,et al.  Is INI1-retained small cell undifferentiated histology in hepatoblastoma unfavorable? , 2015, Human pathology.

[2]  R. Siebert,et al.  SMARCA4-mutated atypical teratoid/rhabdoid tumors are associated with inherited germline alterations and poor prognosis , 2014, Acta Neuropathologica.

[3]  Yukichi Tanaka,et al.  Towards an international pediatric liver tumor consensus classification: proceedings of the Los Angeles COG liver tumors symposium , 2014, Modern Pathology.

[4]  R. Siebert,et al.  High‐resolution genomic analysis suggests the absence of recurrent genomic alterations other than SMARCB1 aberrations in atypical teratoid/rhabdoid tumors , 2013, Genes, chromosomes & cancer.

[5]  J. Feusner,et al.  Rhabdoid tumors of the liver: Rare, aggressive, and poorly responsive to standard cytotoxic chemotherapy , 2011, Pediatric Blood & Cancer.

[6]  A. Zimmermann,et al.  INI1 (BAF 47) Immunohistochemistry is an Essential Diagnostic Tool for Children With Hepatic Tumors and Low Alpha Fetoprotein , 2010, Journal of pediatric hematology/oncology.

[7]  R. Siebert,et al.  Germline nonsense mutation and somatic inactivation of SMARCA4/BRG1 in a family with rhabdoid tumor predisposition syndrome. , 2010, American journal of human genetics.

[8]  R. Siebert,et al.  Clinical and molecular features in patients with atypical teratoid rhabdoid tumor or malignant rhabdoid tumor , 2010, Genes, chromosomes & cancer.

[9]  C. Rodríguez-Galindo,et al.  Age, stage, and radiotherapy, but not primary tumor site, affects the outcome of patients with malignant rhabdoid tumors , 2010, Pediatric blood & cancer.

[10]  N. Sebire,et al.  Clinical and pathological features of paediatric malignant rhabdoid tumours , 2010, Pediatric blood & cancer.

[11]  A. Pappo,et al.  Amifostine does not prevent platinum‐induced hearing loss associated with the treatment of children with hepatoblastoma , 2009, Cancer.

[12]  G. Tomlinson,et al.  Small cell undifferentiated variant of hepatoblastoma: Adverse clinical and molecular features similar to rhabdoid tumors , 2009, Pediatric blood & cancer.

[13]  J. Biegel,et al.  Malignant Rhabdoid Tumor Mimicking Hepatoblastoma: A Case Report and Literature Review , 2007, Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society.

[14]  R. Siebert,et al.  Non‐linkage of familial rhabdoid tumors to SMARCB1 implies a second locus for the rhabdoid tumor predisposition syndrome , 2006, Pediatric blood & cancer.

[15]  W. London,et al.  Intensified platinum therapy is an ineffective strategy for improving outcome in pediatric patients with advanced hepatoblastoma. , 2006, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[16]  G. Tiao,et al.  The current management of hepatoblastoma: a combination of chemotherapy, conventional resection, and liver transplantation. , 2005, The Journal of pediatrics.

[17]  J. Biegel,et al.  Immunohistochemical Analysis of hSNF5/INI1 Distinguishes Renal and Extra-renal Malignant Rhabdoid Tumors From Other Pediatric Soft Tissue Tumors , 2004, The American journal of surgical pathology.

[18]  J. Biegel,et al.  Immunohistochemical Analysis of hSNF5/INI1 in Pediatric CNS Neoplasms , 2004, The American journal of surgical pathology.

[19]  G. Perilongo,et al.  Risk-adapted treatment for childhood hepatoblastoma. final report of the second study of the International Society of Paediatric Oncology--SIOPEL 2. , 2004, European journal of cancer.

[20]  D. V. von Schweinitz,et al.  [Differentiated treatment protocols for high- and standard-risk hepatoblastoma--an interim report of the German Liver Tumor Study HB99]. , 2003, Klinische Padiatrie.

[21]  F. Gilles,et al.  Aberrations of the hSNF5/INI1 gene are restricted to malignant rhabdoid tumors or atypical teratoid/rhabdoid tumors in pediatric solid tumors , 2002, Genes, chromosomes & cancer.

[22]  J. Feusner,et al.  Small cell undifferentiated histology in hepatoblastoma may be unfavorable , 2001 .

[23]  M. Yaniv,et al.  The murine SNF5/INI1 chromatin remodeling factor is essential for embryonic development and tumor suppression , 2000, EMBO reports.

[24]  J. Quinn,et al.  Randomized comparison of cisplatin/vincristine/fluorouracil and cisplatin/continuous infusion doxorubicin for treatment of pediatric hepatoblastoma: A report from the Children's Cancer Group and the Pediatric Oncology Group. , 2000, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[25]  Olivier Delattre,et al.  Truncating mutations of hSNF5/INI1 in aggressive paediatric cancer , 1998, Nature.

[26]  J. Biegel,et al.  Narrowing the critical region for a rhabdoid tumor locus in 22q11 , 1996, Genes, chromosomes & cancer.

[27]  D. V. von Schweinitz,et al.  Complete resection before development of drug resistance is essential for survival from advanced hepatoblastoma--a report from the German Cooperative Pediatric Liver Tumor Study HB-89. , 1995, Journal of pediatric surgery.

[28]  G. Crabtree,et al.  Binding and stimulation of HIV-1 integrase by a human homolog of yeast transcription factor SNF5. , 1994, Science.

[29]  C. Anthony Tumors of the liver. , 1983, Seminars in roentgenology.

[30]  T. Hishiki,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. , 2016, European journal of cancer.

[31]  S. Kondo,et al.  Outcome of hepatoblastomas treated using the Japanese Study Group for Pediatric Liver Tumor (JPLT) protocol-2: report from the JPLT , 2010, Pediatric Surgery International.

[32]  G. Perilongoa,et al.  Risk-adapted treatment for childhood hepatoblastoma: final report of the second study of the International Society of Paediatric Oncology—SIOPEL 2§ , 2004 .

[33]  J. Feusner,et al.  Small cell undifferentiated histology in hepatoblastoma may be unfavorable. , 2001, Cancer.