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

• Published in: Human pathology 2016-07, Vol.53, p.14-24
• Main Authors: Zreik, Riyam T., MD, Carter, Jodi M., MD, PhD, Sukov, William R., MD, Ahrens, William A., MD, Fritchie, Karen J., MD, Montgomery, Elizabeth A., MD, Weiss, Sharon W., MD, Folpe, Andrew L., MD
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Ankle; Antigens, Neoplasm - genetics; Artificial chromosomes; Biomarkers, Tumor - genetics; Cell Differentiation; Disease Progression; Female; Fibroblasts - enzymology; Fibroblasts - pathology; Fibroma - enzymology; Fibroma - genetics; Fibroma - pathology; Fingers & toes; Gene Rearrangement; Genetic Predisposition to Disease; Hemosiderosis - enzymology; Hemosiderosis - genetics; Hemosiderosis - pathology; Hemosiderotic fibrolipomatous tumor; Histone Acetyltransferases - genetics; Humans; Hyaluronoglucosaminidase - genetics; Hybrid hemosiderotic fibrolipomatous tumor/myxoinflammatory fibroblastic sarcoma; Hybridization; In Situ Hybridization, Fluorescence; Lipoma - enzymology; Lipoma - genetics; Lipoma - pathology; Male; MGEA5; Middle Aged; Morphology; Myxoinflammatory fibroblastic sarcoma; Pathology; Phenotype; Pleomorphic hyalinizing angiectatic tumor; Predictive Value of Tests; Proteoglycans - genetics; Receptors, Transforming Growth Factor beta - genetics; Sarcoma - enzymology; Sarcoma - genetics; Sarcoma - pathology; Soft Tissue Neoplasms - enzymology; Soft Tissue Neoplasms - genetics; Soft Tissue Neoplasms - pathology; TGFBR3; Tumors; Young Adult
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/j.humpath.2016.02.005

Summary Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare low-grade sarcoma that most often involves the distal extremities of adults. Some MIFS have been reported to show TGFBR3 and MGEA5 rearrangements. TGFBR3 and MGEA5 rearrangements have also been reported in hemosiderotic fibrolipomatous tumor (HFLT), 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 HFLT are only very rarely encountered in previous series of MIFS. 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 verified by 5 soft tissue pathologists. Using previously validated break-apart FISH probes, we analyzed for TGFBR3 and MGEA5 rearrangements. Only two of 31 MIFS harbored MGEA5 rearrangements; all lacked TGFBR3 rearrangements. Six of 8 hybrid HFLT-MIFS harbored rearrangements of TGFBR3 and/or MGEA5 . Both PHAT were positive for rearrangements of TGFBR3 and/or MGEA5 . The HFLT was positive for rearrangements of both TGFBR3 and MGEA5 . All UDPS were negative. We conclude that: 1) TGFBR3 and/or MGEA5 rearrangements are much more common in hybrid HFLT-MIFS than in classic MIFS, 2) HFLT and MIFS may be unrelated lesions, and 3) hybrid HFLT-MIFS most likely represent HFLT with sarcomatous progression, rather than tumors strictly related to classic MIFS.