These cells may show high rates of replicating as judged by their mitotic index but these mitoses are normal in appearance. The tumor tissues often contain red blood cells, lymphocytes and giant osteoclast-like giant cells and may contain sites of bone-like tissue. NF is sometimes classified into three subtypes based on its predominant histopathological pattern: myxoid or reactive (type I), cellular (type II), and fibrous (type III). These patterns appear related to the duration of the lesion with the myxoid variant tending to have the shortest duration and the cellular and fibrous variants tending to have progressively longer durations.Immunohistochemical analyses indicate that the cells in NF usually express smooth muscle actin, muscle specific actin, and vimentin proteins but generally do not express CD34, S-100 protein, desmin, trypsin, factor VIII, F4/80 (also termed macrophage-specific antigen), or HLA-DR1 proteins. Uncommonly, the cells in NF tumors also express the CD68 (a histiocyte-specific marker) protein. The histopathology and expressions of marker proteins in cranial fasciitis tumors are similar to NF although its tumors tend to be more organized and have higher levels of inflammatory cell infiltrates, vascularity, and involvements of underlying bone than NF.The histopathology and expressions of marker proteins in intravascular fasciitis tumors are also similar to NF. In comparison to NF, however, its spindle-shaped tumor cells are more often arranged in a storiformed (i.e. whirled) or haphazard pattern and have vesicle-containing nuclei with prominent nucleoli.
ribosome binding protein 1) gene, CALU (calumenin) gene, CTNNB1 (catenin beta 1) gene, MIR22HG (produces the MIR22HG long non-coding RNA) gene, SPARC (secreted protein acidic and cysteine rich [also termed osteonectin]) gene, THBS2 (thrombospondin-2) gene, COL6A2 (collagen type VI alpha 2 chain) gene, SEC31A {SEC31 homolog A, COPII coat complex component) gene, EIF5A (eukaryotic translation initiation factor 5A) gene, COL1A1 (collagen type I alpha 1 chain) gene, COL1A2 (collagen type I alpha 2 chain) gene, COL3A1 (collagen type III alpha 1 chain) gene, PAFAH1B1 (platelet activating factor acetylhydrolase 1b regulatory subunit 1) gene, SERPINH1 (serpin family H member 1) gene which produces heat shock protein 47, PDLIM7 (PDZ and LIM domain protein 7) gene, and MYL12A (myosin regulatory light chain 12A) gene. While very few cases have been analyzed to date, USP6-containing fusion genes have been found in the tumor cells of 7 of 15 tested cases of cranial fasciitis and six of  six tested cases of intravascular fasciitis.All of the USP6-containing fusion genes in NF and variants overproduce a chimeric protein containing a part of the USP6 genes product, ubiquitin carboxyl-terminal hydrolase 6a, that has uncontrolled deubiquitinating enzyme activity. This may result in the inappropriate stimulation of  multiple cell signaling pathways including the Wnt signaling pathway, one of the JAK-STAT signaling pathways (i.e. the Jak1-STAT3 pathway), the c-Jun signaling pathway, and the NF-κB signaling pathway. Each of these pathways, when inappropriately activated, has been implicated in promoting the development of various tumors and cancers.