Nodular Necrotizing Fibroblastic Sarcoma and Myxoinflammatory Fibroblastic Sarcoma: A Comparative Clinicopathological, Molecular, and Epigenetic Study

Abstract

Background

There is morphological overlap between nodular necrotizing fibroblastic sarcoma (NNFS) and myxoinflammatory fibroblastic sarcoma (MIFS). Whether they represent neoplasms within the same tumor spectrum remains unclear. We performed a comparative clinicopathological, molecular, and epigenetic study of these two tumors.

Methods

We analyzed the clinicopathological features, immunophenotypes, and molecular profiles of three cases each of NNFS and MIFS. DNA methylation profiling was also performed.

Results

All three NNFS cases were located in the trunk, presenting as well-circumscribed subcutaneous nodules with central necrosis, whereas the three MIFS cases all arose in acral sites with an infiltrative or ill-defined growth pattern. Morphologically, both NNFS and MIFS were characterized by large polygonal to epithelioid cells with virocyte-like, ganglion cell-like, or Reed–Sternberg-like appearance. Unlike MIFS, NNFS did not exhibit prominent myxoid stroma or vacuolated pseudolipoblasts. On immunohistochemistry, NNFS cases uniformly showed focal positivity for pancytokeratin (AE1/AE3), whereas MIFS cases exhibited variable CD34 expression. Molecular analysis identified YAP1::MAML2 fusions in all three NNFS cases, while a BRAF rearrangement was detected in one of the three MIFS cases. DNA methylation profiling demonstrated that NNFS and MIFS cases clustered together forming a distinct group.

Conclusions

Although NNFS and MIFS each harbor unique genetic alterations, our DNA methylation profiling demonstrates a potential relationship between these two morphologically similar entities.