Original ArticleA rare case of pediatric lipoma with t(9;12)(p22;q14) and evidence of HMGA2-NFIB gene fusion
Introduction
Lipoma, a benign tumor composed of mature white adipocytes, is the most common mesenchymal neoplasm in adults, occurring most frequently in individuals between 40-60 years of age (1). The typical presentation is a painless, soft tissue mass, although larger tumors that compress peripheral nerves can be painful. Patients with lipoma generally have good outcomes, and tumor recurrence is quite rare (1).
Genetic analyses of lipomas often reveal simple structural chromosome rearrangements that are more commonly balanced than unbalanced; numerical changes are not commonly observed. Four cytogenetic subgroups have been distinguished: (1) aberrations involving 12q13-15 (in 65% of cases); (2) loss of a portion of 13q (in 10%); (3) abnormalities involving 6p21-23 (in 5%); and (4) aberrations at other loci or normal karyotype (in 15-20%). However, combinations of these primary cytogenetic findings are also frequently observed 1, 2.
In a subset of lipomas, the high-mobility group AT-hook 2 (HMGA2) gene, which is localized on 12q14.3, has an important role in tumor pathogenesis. In cases with rearrangements of 12q14.3, HMGA2 is typically truncated, altering its regulation and often resulting in chimeric transcripts with neomorphic activity. In these fusion products, the DNA-binding AT-hook domains of HMGA2 are retained and fused with the transcriptional regulatory domains of their fusion partners (3). Some of these partner genes include LPP, CXCR7, EBF1, LHFP, PPAP2B and, in approximately 1% of all lipoma cases with 12q13-15 rearrangements, nuclear factor 1B (NFIB) 4, 5, 6, 7, 8, 9, 10.
Pediatric lipoma is uncommon, and among those cases that have been characterized with molecular and cytogenetic analyses, rearrangement of 12q14 involving HMGA2 is the predominant finding, while rearrangement of HMGA1 at 6p21, and of the 8q11-q13 region, presumably affecting PLAG1, were each observed in one previous case; other rearrangements have been reported in individual patients, although the specific genes involved in these rearrangements were not determined (reviewed in Dadone, et al. 2015 (11)).
While t(9;12)(p22;q14) with evidence of HMGA2-NFIB gene fusion has been reported in several previous adult lipoma cases 8, 11, 12, 13, 14, 15, to our knowledge it has been reported only twice in pediatric cases 11, 15. Herein, we describe a rare case of lipoma with t(9;12)(p22;q14) in the biceps femoris of a 9 year-old boy.
Section snippets
Methods and results
The patient was a 9 year-old boy who presented with a large mass on his posterior right thigh. Upon examination of the patient, asymmetry of the thighs was observed; magnetic resonance imaging (MRI) revealed a 5.5 × 9.8 × 21.6 cm (AP × TR × CC) mass within the right biceps femoris with T1 hyperintensity that was suspicious of an atypical lipomatous tumor or well-differentiated liposarcoma (Figure 1A-B). Following an initial needle core biopsy, the mass was surgically removed and grossly it
Discussion
Several previous cases of lipoma have been described with t(9;12); most of these have been observed in men who were 35-50 years of age and who had lipomas that were deep-seated in the thigh or arm 8, 11, 12, 14. In general, lipoma is more commonly observed in adults, and a previous study of a series of 272 lipomas revealed a trend towards male predominance 12, 17. In the current study, we suggest that cases of lipoma with t(9;12) and evidence of HMGA2-NFIB fusion are more likely to occur in
Conflict of interest
None.
Funding sources
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
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