Abstract
Undifferentiated soft tissue sarcomas are a group of diagnostically challenging tumors in the pediatric population. Molecular techniques are instrumental for the categorization and differential diagnosis of these tumors. A subgroup of recently identified soft tissue sarcomas with undifferentiated round cell morphology was characterized by Capicua transcriptional receptor (CIC) rearrangements. Recently, an array-based DNA methylation analysis of undifferentiated tumors with small blue round cell histology was shown to provide a highly robust and reproducible approach for precisely classifying this diagnostically challenging group of tumors. We describe the case of an undifferentiated sarcoma of the abdominal wall in a 12-year-old girl. The patient presented with a voluminous mass of the abdominal wall, and multiple micro-nodules in the right lung. The tumor was unclassifiable with current immunohistochemical and molecular approaches. However, DNA methylation profiling allowed us to classify this neoplasia as small blue round cell tumor with CIC alterations. The patient was treated with neoadjuvant chemotherapy followed by complete surgical resection and adjuvant chemotherapy. After 22 months, the patient is disease-free and in good clinical condition. To put our experience in context, we conducted a literature review, analyzing current knowledge and state-of-the-art diagnosis, prognosis, and clinical management of CIC rearranged sarcomas. Our findings further support the use of DNA methylation profiling as an important tool to improve diagnosis of non-Ewing small round cell tumors.
Highlights
Primitive small blue round cell tumors (SBRCTs) in children and young adults pose a diagnostic challenge
An advance in the diagnosis of Ewing’s sarcoma was the discovery of recurrent, highly-specific balanced translocations leading to a chimeric gene fusion involving the RNA-binding TET gene family members, mainly EWSR1, and members of the E26 transformation-specific (ETS) gene family
Wilms’ tumor (WT1): positive (Figure 2F), nuclear; INI: positive; Bcl6: weak positivity; Transducin-like enhancer of split 1 (TLE1): positive Epithelial membrane antigen(EMA), Synaptophysin, Actins, CK7, Desmin, Myogenin, MyoD, Leukocyte common antigen (LCA), CD30, Activin receptor-like kinase (ALK1), Myeloperoxidase (MPO), Terminal deoxynucleotidyl transferase (TdT), Melanoma-associated antigen recognized by T cells (MART1), CD34, p63, NUT, CD56, Placental alkaline phosphatase (PLAP) Int
Summary
Primitive small blue round cell tumors (SBRCTs) in children and young adults pose a diagnostic challenge. Molecular techniques, including extended Fluorescent in situ hybridization (FISH) analysis and generation sequencing, have allowed the separation of ES with canonical translocations from a subset of lesions that remains unclassified These are termed “Ewing-like sarcomas”, or SBRCTs not otherwise specified in the last World Health Organization classification [11,12]. A number of SBRCTs remains unclassified, emerging molecular evidence, most notably transcriptome analysis, has helped to distinguish previously unrecognized tumor entities that many investigators consider as distinct from ES [2,13] These are Ewing-like sarcomas most commonly harboring CIC and BCL6 Corepressor (BCOR) rearrangements [1,2,14,15,16,17]. We conclude that DNA-methylation-based tumor classification can be an important tool in advancing the diagnosis, pathological analysis, and management of these tumors
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