Pleomorphic hyalinizing angiectatic
tumor (PHAT) is a rare, locally aggressive
tumor of the distal extremities with a proclivity for local recurrence. PHATs contain characteristic ectatic, thin-walled vessels, lined by
fibrin, and are surrounded by groups of variably pleomorphic spindled to epithelioid neoplastic cells. The putative precursor lesion of PHAT, originally termed "early PHAT" shares many clinicopathologic features with hemosiderotic fibrolipomatous
tumor (HFLT). HFLT, myxoinflammatory fibroblastic
sarcoma (MIFS), and
tumors showing hybrid features of HFLT and MIFS often show
TGFBR3 and MGEA5 gene rearrangements. To date, only a small number of PHATs has been tested for either rearrangement; all have been negative. We hypothesized that PHATs contain
TGFBR3 and/or MGEA5 rearrangements. Cases of PHAT (all containing areas of HFLT) (N=10), HFLT (N=7), MIFS (N=6), hybrid HFLT/MIFS (N=3), and PHAT-like undifferentiated pleomorphic
sarcomas (N=7) were retrieved from our institutional and consultation archives and analyzed for
TGFBR3 and MGEA5 rearrangements using a break-apart probe strategy for FISH. Six of 10 PHATs harbored
TGFBR3 and/or MGEA5 gene rearrangements: 4 cases had both
TGFBR3 and MGEA5 rearrangements, and 2 cases contained MGEA5 rearrangements. Two of 7 HFLTs were positive: 1 case had a
TGFBR3 rearrangement, and 1 case had an MGEA5 rearrangement. One of 6 MIFSs had an MGEA5 rearrangement. All 3 hybrid HFLT/MIFS cases were positive: 2 cases had both
TGFBR3 and MGEA5 rearrangements, and 1 case had a
TGFBR3 rearrangement. All PHAT-like undifferentiated pleomorphic
sarcomas were negative. We report, for the first time, the presence of
TGFBR3 and/or MGEA5 rearrangements in
tumors showing mixed features of HFLT and PHAT. The presence of such rearrangements strongly suggests that HFLT is related to both PHAT and MIFS and that the latter 2
tumors may represent morphologic variants of a single, genetically defined entity in which only MIFS has acquired the capacity to metastasize.