Author:

Keywords:

Science & Technology, Life Sciences & Biomedicine, Pathology, HEMOSIDEROTIC FIBROLIPOMATOUS TUMOR, CYCLIN D1 EXPRESSION, DIFFERENTIAL-DIAGNOSIS, MGEA5 REARRANGEMENTS, AMPLIFICATION, TGFBR3, RARE, Adult, Aged, Aged, 80 and over, Biomarkers, Tumor, Comparative Genomic Hybridization, Europe, Female, Fibroblasts, Fibrosarcoma, Gene Amplification, Gene Fusion, Gene Rearrangement, Genetic Predisposition to Disease, High-Throughput Nucleotide Sequencing, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Male, Middle Aged, Molecular Diagnostic Techniques, Phenotype, Soft Tissue Neoplasms, Translocation, Genetic, United States, Young Adult, 11 Medical and Health Sciences, 3202 Clinical sciences

Abstract:

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade soft tissue neoplasm preferentially arising in the extremities of young to middle-aged adults characterized histologically by a variegated appearance and absence of a distinctive immunophenotype. Herein we have evaluated a series of 73 cases of MIFS to define potential features and markers that may facilitate diagnosis. An immunohistochemical study with a large panel of antibodies showed strong positivity of the tumor cells for bcl-1 (94.5%), FXIIIa (89%), CD10 (80%), and D2-40 (56%). FISH and array comparative genomic hybridization (aCGH) were performed in a large subset of cases to investigate the utility for detecting the TGFBR3 and OGA t(1;10) rearrangement and BRAF abnormalities. Using a combination of FISH and/or aCGH, t(1;10) was detected in only 3 of 54 cases (5.5%). The aCGH study also demonstrated amplification of VGLL3 on chromosome 3 that was detected in 8 of 20 cases (40%). BRAF alterations were observed by FISH in 4 of 70 cases (5.7%) and correlated with gain of chromosome 3p12 (VGLL3). A novel fusion transcript involving exon 6 of ZNF335 and exon 10 of BRAF was identified in one case. Demonstration of amplification of VGLL3 on chromosome 3 in combination with expression of bcl-1 and FXIIIa may help support the diagnosis, however, due to their low specificity these markers are not sufficient for a definitive diagnosis in the absence of the appropriate clinical-pathological context. Until a more robust genetic or immunohistochemical signature is identified, the diagnosis of MIFS rests on its characteristic clinicopathological features.