Knowledge of the clinicopathological and molecular spectrum of pediatric renal cell carcinomas (RCCs) remains limited, and approximately 16-24% of these neoplasms cannot be classified into specific subtypes.
In our review of 168 pediatric RCC prospectively registered on Children's Oncology Group AREN03B2 protocol, we identified six RCC (3. 5%) that demonstrated a unique epithelioid morphology and a peculiar immunophenotypic profile that includes expression of ALK, TFE3 and retention of INI1. Further investigation revealed ALK rearrangements in all cases, manifested molecularly by fusion transcripts of either VCL-ALK (3 patients all with sickle cell trait which had been previously reported) or TPM3-ALK (3 patients, none with sickle cell trait). Based on the shared unique morphologic, immunophenotypic and genetic features, we propose that these neoplasms belong to a distinct subgroup of RCC frequently occurring in pediatric patients, which we have termed ALK-rearranged RCC. Importantly, additional therapeutic options may be available for these patients. This article is protected by copyright. All rights reserved.
Genes, chromosomes & cancer. 2016 Jan 16 [Epub ahead of print]
Mariana M Cajaiba, Lawrence J Jennings, Stephen M Rohan, Antonio R Perez-Atayde, Adrian Marino-Enriquez, Jonathan A Fletcher, James I Geller, Katrin M C Leuer, Julia A Bridge, Elizabeth J Perlman
Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL. , Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL. , Department of Pathology, Colorado Pathology Consultants and Saint Joseph Hospital, Denver, CO. , Department of Pathology, Boston Children's Hospital and Harvard Medical School, Boston, MA. , Department of Pathology, Brigham Women's Hospital and Harvard Medical School, Boston, MA. , Department of Pathology, Brigham Women's Hospital and Harvard Medical School, Boston, MA. , Division of Pediatric Oncology, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, Ohio. , Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL. , Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE. , Department of Pathology and Laboratory Medicine, Ann & Robert H. Lurie Children's Hospital of Chicago and Northwestern University Feinberg School of Medicine, Chicago, IL.