Case study Congenital fibrosarcoma with a novel complex 3-way translocation t(12;15;19) and unusual histologic features Adrián Mariño-Enríquez MD a,b , Peining Li PhD c , Joan Samuelson BSc c , Michael R. Rossi PhD c , Miguel Reyes-Múgica MD b,d, ⁎ a Departamento de Anatomía Patológica, Hospital Universitario La Paz, 28046 Madrid, Spain b Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA c Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA d Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06520, USA Received 29 August 2007; revised 3 April 2008; accepted 4 April 2008 Keywords: Congenital fibrosarcoma; Cytogenetics; Pediatric solid tumor; t(12;15;19) Summary Congenital mesenchymal tumors are diagnostically challenging as they are rare and may feature overlapping patterns between several benign, low-grade, and tumors of intermediate malignancy, including myofibromatosis, myofibroma/hemangiopericytoma, congenital fibrosarcoma, and inflammatory myofibroblastic tumor. Their immunophenotype is either silent or minimally expressive, and their ultrastructural features are generically consistent with “fibroblastic/myofibro- blastic” differentiation. Cytogenetic analysis allows refined diagnoses, improved classifications, and bettering of our therapeutic armamentarium. However, genotype/phenotype correlations continue rendering novel findings that must be examined for their potential value in diagnosis and treatment. We describe a retroperitoneal congenital fibrosarcoma with an unusually bland histopathology and novel 3-way t(12;15;19) translocation involving chromosome bands 12p13.2, 15q25.3, and 19p13.1, associated with trisomies 8, 11, and 20. Fluorescence in situ hybridization showed one fusion signal in the normal chromosome 12p13.2 and break-apart 3′ETV6 and 5′ETV6 signals in the rearranged 12p13.2 and 15q25.3, respectively. The importance of molecular diagnosis and genotype-phenotype correlations is emphasized. © 2008 Elsevier Inc. All rights reserved. 1. Introduction Congenital fibrosarcoma (CFS) is a rare, rapidly growing, low-grade soft tissue sarcoma. The terms congenital, infan- tile, congenital-infantile, and juvenile fibrosarcoma have been used synonymously to designate this tumor that occurs preferentially during the first months of life, almost always before 5 years of age [1-4]. It typically affects the distal portion of the extremities, but it can be located in the head and neck region, and an abdominal or retroperitoneal location has been reported in up to 7% of cases [5]. Despite its morphological similarity to adult fibrosarcoma, CFS is a distinct clinicopathologic entity given its relatively benign clinical behavior and low rate of distant metastases (b8%) [1,2]. The significant controversy that persisted for many ⁎ Corresponding author. Current address: Department of Pathology, Children's Hospital of Pittsburgh, 3705 5th Ave, Pittsburgh, PA 15213, USA. E-mail address: miguel.reyes@chp.edu (M. Reyes-Múgica). www.elsevier.com/locate/humpath 0046-8177/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.humpath.2008.04.013 Human Pathology (2008) 39, 1844–1848