Pediatric dermatofibrosarcoma protuberans: A clinicopathologic and genetic analysis of 66 cases in the largest institution in Southwest China

Abstract

BackgroundDermatofibrosarcoma protuberans (DFSP) is an uncommon cutaneous tumor in children. Most published articles are sporadic or small series and lack systematically molecular analyses. The aim of our study is to better understand the clinicopathologic and genetic features of these rare lesions.MethodsAll patients diagnosed with DFSP aged ≤ 18 years were retrospectively reviewed from January 2006 to May 2022.ResultsA total of 66 cases (32 male and 34 female patients) were identified, with ages ranging from 0.3 to 18 years (median, 13 years). Tumor locations predominantly occurred on the trunk (38/66, 57.6%), followed by the extremities (20/66, 30.3%) and head/neck (8/66, 12.1%). Histological findings revealed classic (41/66, 62.1%), myxoid (4/66, 6.1%), pigmented (6/66, 9.1%), plaque-like (3/66, 4.5%), giant cell fibroblastoma (GCF; 6/66, 9.1%), and fibrosarcomatous (6/66, 9.1%) variants of DFSP. Immunochemistry revealed minority tumors (9/66, 13.6%) showing patchy or negative staining for CD34. Fluorescence in situ hybridization (FISH) indicated that 49 of 53 tested cases including all detected biopsy specimens (11/11) contained COL1A1-PDGFB fusion, in which the average copy number gain of COL1A1-PDGFB was 0.68. There were four cases negative for COL1A1-PDGFB rearrangement, one of which was found to harbor a novel COL3A1-PDGFB fusion by next-generation sequencing (NGS). Treatment for 63 patients comprised 40 marginal excisions and 23 wide local excisions (WLEs), including 1 with imatinib therapy. Follow-up information was available on 49 patients with a duration of 12–161 months (median, 60 months). Fourteen patients developed tumor recurrence, all with initial marginal excisions. The others survived with no evidence of disease.ConclusionsThis study of pediatric DFSP indicates certain discrepancies in clinicopathologic characteristics between children and adults. The majority of pediatric DFSPs contain COL1A1-PDGFB fusion, the same as their adult counterparts. The COL3A1-PDGFB chimerism might be associated with the special morphology of GCF, which needs further investigation. FISH is valuable in biopsy tissues and cases with atypical CD34 immunostaining, while supplementary NGS could be helpful to identify the cytogenetically cryptic DFSP. Overall, an urgent accurate diagnosis is needed to formulate an optimal therapeutic strategy in the pediatric population.

A cutaneous spindle cell neoplasm characterized by a COL3A1::PDGFRA fusion

“…2 Most commonly, the breakpoint is located (as in the case described here) within the exon 12 juxtamembrane kinase regulatory domain (JMD) of PDGFRA, and it has been shown that rearrangements disrupting this domain lead to activation of the kinase irrespective of the 5 0 partner. 3 COL3A1 has been described (albeit with different breakpoints) as a 5 0 partner in oncogenic fusions with PLAG1 in lipoblastoma 4 and also, interestingly, with PDGFB in a case of pediatric dermatofibrosarcoma protuberans (DFSP), 5 a cutaneous spindle cell neoplasm characterized by fusion of PDGFB 6 (or rarely the closely related PDGFD gene 7 ) to another collagen gene, COL1A1 (or rarely the related gene COL6A3 8 ). PDGFB is a ligand for PDGFRA, and upregulation of both genes by placing them under the control of a collagen gene promoter (and/or, in the current case, by disrupting the JMD of PDGFRA) might be posited to have biologically comparable consequences.…”