title: 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.
abstract: Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade sarcoma that most often involves the distal extremities of adults. Some MIFSs have been reported to show TGFBR3 and MGEA5 rearrangements. TGFBR3 and MGEA5 rearrangements have also been reported in hemosiderotic fibrolipomatous tumor (HFLT), in pleomorphic hyalinizing angiectatic tumor (PHAT), and in rare tumors allegedly showing features of both HFLT and MIFS (hybrid HFLT-MIFS). These findings have led to speculation that HFLT, MIFS, PHAT, and hybrid HFLT-MIFS are closely related; however, areas resembling HFLTs are only very rarely encountered in previous series of MIFSs. We studied classic examples of these tumors with the goal of clarifying the relationship between MIFS and HFLT-MIFS. Cases of MIFS (n=31), hybrid HFLT-MIFS (n=8), PHAT (n=2), HFLT (n=1), and undifferentiated pleomorphic sarcoma (n=4) were retrieved from our archives, and the diagnoses were verified by 5 soft tissue pathologists. Using previously validated break-apart fluorescence in situ hybridization probes, we analyzed for TGFBR3 and MGEA5 rearrangements. Only 2 of 31 MIFSs harbored MGEA5 rearrangements; all lacked TGFBR3 rearrangements. Six of 8 hybrid HFLT-MIFSs harbored rearrangements of TGFBR3 and/or MGEA5. Both PHATs were positive for rearrangements of TGFBR3 and/or MGEA5. The HFLT was positive for rearrangements of both TGFBR3 and MGEA5. All undifferentiated pleomorphic sarcomas with focal myxoid change were negative. We conclude that (1) TGFBR3 and/or MGEA5 rearrangements are much more common in hybrid HFLT-MIFSs than in classic MIFSs, (2) HFLTs and MIFSs may be unrelated lesions, and (3) hybrid HFLT-MIFSs most likely represent HFLTs with sarcomatous progression, rather than tumors strictly related to classic MIFSs.
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.
authors.forename: Riyam T
authors.initials: RT
authors.lastname: Zreik
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.
authors.forename: Jodi M
authors.initials: JM
authors.lastname: Carter
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.
authors.forename: William R
authors.initials: WR
authors.lastname: Sukov
authors.affiliation: Department of Pathology, Carolinas Medical Center, Charlotte, NC 28203.
authors.forename: William A
authors.initials: WA
authors.lastname: Ahrens
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Fritchie
authors.affiliation: Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21287.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Montgomery
authors.affiliation: Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA 30322.
authors.forename: Sharon W
authors.initials: SW
authors.lastname: Weiss
authors.affiliation: Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN 55905. Electronic address: folpe.andrew@mayo.edu.
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Folpe
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000951:Antigens, Neoplasm / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics*; D002454:Cell Differentiation; D018450:Disease Progression; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D005350:Fibroma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D015321:Gene Rearrangement; D020022:Genetic Predisposition to Disease; D006486:Hemosiderosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D051548:Histone Acetyltransferases / Q000235:genetics*; D006801:Humans; D006821:Hyaluronoglucosaminidase / Q000235:genetics*; D017404:In Situ Hybridization, Fluorescence; D008067:Lipoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011237:Predictive Value of Tests; D011509:Proteoglycans / Q000235:genetics*; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*; D012509:Sarcoma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D012983:Soft Tissue Neoplasms / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D055815:Young Adult
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D011509:Proteoglycans; D018125:Receptors, Transforming Growth Factor beta; C071736:betaglycan; D051548:Histone Acetyltransferases; C115866:OGA protein, human; D006821:Hyaluronoglucosaminidase
keywords: Hemosiderotic fibrolipomatous tumor; Hybrid hemosiderotic fibrolipomatous tumor/myxoinflammatory fibroblastic sarcoma; MGEA5; Myxoinflammatory fibroblastic sarcoma; Pleomorphic hyalinizing angiectatic tumor; TGFBR3