Myxoinflammatory fibroblastic sarcoma: an immunohistochemical and molecular genetic study of 73 cases

• Published in: Modern pathology Vol. 33; no. 12; pp. 2520 - 2533
• Main Authors: Suster, David, Michal, Michael, Huang, Huiya, Ronen, Shira, Springborn, Stephanie, Debiec-Rychter, Maria, Billings, Steven D., Goldblum, John R., Rubin, Brian P., Michal, Michal, Suster, Saul, Mackinnon, A. Craig
• Format: Journal Article
• Language: English
• Published: New York Elsevier Inc 01.12.2020; Nature Publishing Group US; Elsevier Limited
• Subjects: 38/32; 38/91; 45/61; 631/67/1798; 631/67/68; 82/51; Adult; Aged; Aged, 80 and over; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Chromosome 3; Chromosomes; Comparative Genomic Hybridization; Diagnosis; Europe; Female; Fibroblasts - chemistry; Fibroblasts - pathology; Fibrosarcoma - chemistry; Fibrosarcoma - genetics; Fibrosarcoma - pathology; Gene Amplification; Gene Fusion; Gene Rearrangement; Genetic Predisposition to Disease; Genomics; High-Throughput Nucleotide Sequencing; Humans; Hybridization; Immunohistochemistry; In Situ Hybridization, Fluorescence; Laboratory Medicine; Male; Medicine; Medicine & Public Health; Middle Aged; Molecular Diagnostic Techniques; Neoplasia; Pathology; Phenotype; Sarcoma; Soft Tissue Neoplasms - chemistry; Soft Tissue Neoplasms - genetics; Soft Tissue Neoplasms - pathology; Transcription; Translocation, Genetic; Tumor cells; United States; Young Adult; United States; Europe
• ISSN: 0893-3952; 1530-0285
• DOI: 10.1038/s41379-020-0580-6

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.