TGFBR3 and MGEA5 rearrangements are much more common in “hybrid” hemosiderotic fibrolipomatous tumor-myxoinflammatory fibroblastic sarcomas than in classical myxoinflammatory fibroblastic sarcomas: a morphological and fluorescence in situ hybridization study

Recurrent BRAF Gene Rearrangements in Myxoinflammatory Fibroblastic Sarcomas, but Not Hemosiderotic Fibrolipomatous Tumors

“…6 However, further studies showed a significantly lower incidence of this fusion in pure MIFS, being present in 17% (1/6) or 6% (2/31) of the cases. 9,10 As MIFS display a wide spectrum of morphologic variations, which may overlap with other entities, such discrepancy might be related to different diagnostic criteria used. In the present study, among the total cohort of 27 pure MIFS using very strict morphologic criteria, 7 (26%) cases had TGFBR3 and/or MGEA5 rearrangements (6, both genes; 1, TGFBR3 only), 7 (26%) cases had BRAF alterations (6, rearrangements; 1, amplification), and 13 (48%) cases were negative for TGFBR3, MGEA5 and BRAF gene rearrangements.…”

“…6,9,10 No studies to date have attempted to investigate the genetic alterations in MIFS lacking t(1;10). Triggered by an index case with a novel BRAF -related fusion we sought to investigate the recurrent potential of this alteration in a large cohort of TGFBR3-MGEA5 fusion negative MIFS and HFLT.…”

Aggressive myxoinflammatory fibroblastic sarcoma with multiple site metastases

“…Molecular genetic studies have not been used for the diagnosis of MIFS and show inconsistent results. Zreik et al reported that most pure MIFS lack specific genetic findings and that TGFBR3 and MGEA5 rearrangements are more common in hybrid HFTL–MIFS tumours than in classic MIFS 17. The variability in clinicoradiological, histopathological and molecular findings, the diagnosis of MIFS is still a diagnostic challenge for clinicians and pathologists.…”

Deep sequencing of myxoinflammatory fibroblastic sarcoma

“…Additional FISH studies by others with probes flanking TGFBR3 and OGA confirmed a high frequency of juxtapositioning of the TGFBR3 and OGA regions in MIFS and HFLT, but no rearrangement of either gene was seen in PHAT . In contrast, other FISH studies found a high frequency of TGFBR3 and/or OGA rearrangements in PHAT, HFLT, hybrid PHAT/HFLT, and hybrid HFLT/MIFS tumors, but not in MIFS . Recently, RNA‐sequencing of a PHAT identified an out‐of‐frame fusion between TGFBR3 and FBXW4 , mapping 11 kb centromeric of OGA .…”

“…Myxoinflammatory fibroblastic sarcoma (MIFS), hemosiderotic fibrolipomatous tumor (HFLT), and pleomorphic hyalinizing angiectatic tumor (PHAT) are three borderline malignant soft tissue lesions with partly overlapping clinical and morphological features; in addition, a recurrent balanced or, more often, unbalanced translocation t(1;10)(p22‐31;q24‐25), hereafter referred to as t(1;10), has been detected in varying proportions of these tumors . The criteria for separating MIFS, HFLT, and PHAT from each other and other tumors, and their potential developmental relationship(s) have been discussed in several publications, but a consensus remains to be reached …”