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

Abstract

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare, low-grade soft tissue neoplasm preferentially arising in the extremities of young to middle-aged adults that is characterized histologically by a variegated appearance and absence of a distinctive immunophenotype. Herein a series of 80 cases of MIFS has been evaluated 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 (95%), FXIIIa (90%), CD10 (83%), 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 4 of 56 cases (7.1%). 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.Albeit not entirely specific, demonstration of amplification of VGLL3 on chromosome 3 in combination with expression of bcl-1 and FXIIIa may help support the diagnosis. Until a more robust genetic signature is identified, the diagnosis of MIFS rests on its characteristic clinicopathological features.

Hybrid schwannoma–perineurioma frequently harbors VGLL3 rearrangement

“…While its physiologic role is uncertain, it appears to promote cell proliferation through activation of the Hippo pathway ( 23 ); interestingly, it has been suggested to have a role in nerve formation and neural crest migration ( 24 ). Amplification has been reported in myxoinflammatory fibroblastic sarcoma ( 14 , 25 , 26 ), along with several other sarcomas ( 27 ); however, to our knowledge, fusion genes involving VGLL3 have not previously been reported. The precise role of members of the chromodomain helicase DNA-binding (CHD) protein family, including CHD7/9, are also unclear ( 28 ).…”

Myxoinflammatory Fibroblastic Sarcoma of the Parotid Gland: First Case Report and Literature Review

“…Immunohistochemistry has been widely used in MIFS, but no specific immunophenotype has been found. However, differential responsiveness to the various markers has been observed in the previous studies, including Vimentin, D2-40, CD68, bcl-1, CD10, and CD163 ( 3 , 12 ). In the present study, we found consistent and strong immunoreactivity for Vimentin and CD10 in the tumor cells in this case.…”

“…In the mucus background, the tumor spindle cells and epithelioid cells are usually connected to each other to form a complex network structure, and a large number of the neutrophils, macrophages, and plasma cells can be seen, but the mitotic figures and necrosis are not commonly observed in this tumor. Immunohistochemistry has been found to play a very limited role in the diagnosis of MIFS because it has no specific tumor markers ( 12 ).…”

Clinicopathologic and Molecular Study of Hybrid Nerve Sheath Tumors Reveals Their Common Association With Fusions Involving VGLL3

“…In vitro studies have shown that VGLL3 can activate the Hippo pathway and cellular proliferation through the inhibition of the YAP/TAZ axis in lung and breast carcinomas 25. Moreover, genomic amplification spanning the locus of VGLL3 has been reported in a subset of soft tissue sarcomas, including myxofibrosarcomas, myxoinflammatory fibroblastic sarcomas, and hemosiderotic fibrolipomatous tumors 26–29. More rarely, VGLL3 can also act as a tumor suppressor gene in cancers such as ovarian carcinomas which harbor recurrent genomic deletions of VGLL3 30.…”