Multiple tumors (no viscera involvement)
Multiple tumors (no viscera involvement) typically occur as dozens to hundreds of mostly small tumors located in various areas such as the skin, muscles, and frontal eye socket, These tumors do not involve visceral organs, often take a benign course, and may regress spontaneously. Multiple tumors (with viscera involvement)
Multiple tumors (with viscera involvement) typically occur as dozens to hundreds of tumors located in the same sites as multiple tumors (no viscera involvement) but also occur in one or more visceral organs such as those in the gastrointestinal tract and upper respiratory tract and/or the heart, liver, cerebellum, rectum, parietal cortex of brain, and lung. This form of IMF, particularly in cases with tumors involving the gastrointestinal tract, heart, and/or lung, has a far higher morbidity and mortality than the other forms with death occurring in infants during the first weeks to 4 months of life in 30–70% of cases Death is typically due to a tumors compression of vital organs or tissues (e.g. blood vessels). However, there are uncommon cases of multiple tumors (with viscera involvement) that were not associated with serious symptoms, were observed without treatment, and over time showed spontaneous regressions of all or almost all of their tumors. Pathology
Microscopic histopathologic analyses of IMF tumor tissues commonly show repeated patterns of a central zone consisting of spindle-shaped cells lining capillaries and round-to-oval cells arranged around prominent "antler-shaped" vascular spaces all of which are surrounded by a peripheral zone of clustered smooth muscle-like cells.
In about 50% of these cases, these somatic mutations were the same as those found in familial IMF with the remaining cases having mutations in other sites of the gene. These other somatic mutation sites included 2 cases of p.Asp850Val (Asp=aspartate, Val=valine), 2 case of p.Asn666Lys (Asn=asparagine, Lys=lysine), and concurrent double mutations p.Arg561Cyt plus Asp666Lys in one case and p.Trp566Arg (Trp=tryptophan) plus AspN666Lys in another case. Three cases had more complex mutations involving multiple gene sites with two of them having the p.Asn666Lys mutation gene in combination with other mutations. PDGFRB gene
The PDGFRB gene product, the PDGFβ receptor, is normally highly expressed in fibroblasts and other cells of mesenchymal origin including vascular smooth muscle cells. When activated, the PDGFβ receptors tyrosine kinase stimulates cell signaling proteins such as phosphatidylinositol-3 kinase, STAT proteins, phospholipase Cγ, and GRB2 which in turn promote their parent cells to grow, proliferate, and survive for abnormally prolonged times. The PDGFβ receptor gene is a proto-oncogene, i.e. a normal gene that when mutated could form a cancer-causing oncoprotein. Studies show that the PDGFRB mutant proteins in IMF are constitutively overactive and that the tyrosine kinase inhibitor imatinib blocks the activity of the p.Arg561Cys and p.Asn666Lys mutants as well as the p.Arg561Cyt plus Asp666Lys and p.Trp566Arg plus AspN666Lys double mutants but not the p.Asp850Val mutant. Two other tyrosine kinase inhibitors, dasatinib and ponatinib, do inhibit the p.Asp850Val mutants tyrosine kinase activity. Limited initial studies suggest that these inhibitors are useful in treating severe cases of IMF.