The relative proportions of the two zones can vary within different areas of a tumor and between tumors. Immunohistochemical analyses indicate that the spindle-shaped cells strongly express smooth muscle actin, calponin, and, less commonly, desmin proteins. Gene abnormalities
Familial IMF
Twenty families with inherited IMF have been shown to have mutations in one of their two PDGFRB genes. The PDGFRB gene is located in band 32 on the long (or "q") arm of chromosome 5. Of the 20 families with PDGFRB gene mutations, 15 carried a p.Arg561Cys mutation. This mutation substitutes the amino acid Arg, i.e. arginine, for the amino acid cystine at the 561st amino acid position as numbered starting at the N-terminus of the genes product protein, the PDGFβ receptor. Four of the remaining families carried either a p.Pro560Leu (Pro=proline, Leu=leucine); p.Arg561Ser (Ser=serine); p. Lys567Glu (Lys=lysine, Glu=glutamate); or p.Pro660Thr (Thr=threonine) mutation in this protein. The NOTCH3 gene (located in band 13.12 on the short (or "p") arm of chromosome 19) mutation in the carrier family was p. Leu1519Pro. The p.Arg561Cys, p.Pro560Leu, p.Arg561Ser, and p. Lys567Glu mutations are regarded as contributing to the development and/or progression of IMF while the p.Pro660Thr PDGFRB gene mutation and the p. Leu1519Pro NOTCH3 p. Leu1519Pro gene mutation require further study to determine more clearly their clinical significances. Non-familial IMF
Somatic PDGFRB gene mutations have been found in 29% of individuals with solitary IMF tumors and 68% of individuals with multiple tumors (with viscera involvement) plus multiple tumors (no visceral involvement) IMF.
Cases where surgical resection of a single symptomatic tumor is not a good option and cases with multiple visceral tumors are treated by non-surgical methods. These tumors typically respond to conventional systemic chemotherapy with reductions in their sizes; these responses are usually observed only after several weeks of therapy. Chemotherapy regimes that have successfully treated these cases include low dosage: vincristine plus dactinomycin; vinblastine plus methotrexate; vinblastine plus the glucocorticoid, prednisolone; vincristine plus actinomycin D plus the glucocorticoid, prednisone; and vincristine plus dactinomycin plus cyclophosphamide. A cytokine, interferon alpha, has also been used as a single-drug treatment in at least one of these cases. Multiple tumors (with viscera involvement) have also been treated with surgical resection in combination with these drugs and/or with radiation therapy alone or combined with these drugs.Recently, tyrosine kinase inhibitors have been used to treat PDGFRB-associated IMF cases. Imatinib or imatinib plus a second tyrosine kinase inhibitor, sorafenib, have successful treated several cases and chemotherapy plus imatinib have successfully treated a few cases of life-threatening IMF. Studies suggest that: 1) the tyrosine kinase inhibitor should be selected based on the PDGFRB oncoproteins sensitivity to it (e.g. dasatinib or ponatinib should be used to treat patients with the imatinib-resistant p.Asp850Val PDGFRB gene mutation.