Infantile myofibromatosis (IMF) is a rare tumor found in 1 in 150,000 to 1 in 400,000 live births. It is nonetheless the most common tumor derived from fibrous connective tissue that occurs primarily in infants and young children. IMF tumors are benign in the sense that they do not metastasize to distant tissues although when occurring in the viscera, i.e. internal organs, carry guarded to poor prognoses and can be life-threatening, particularly in newborns and young infants.IMF tumors occur in three clinical patterns: 1) solitary IMF tumors (also called myofibromas) which often regress spontaneously and rarely cause serious issues; 2) multiple tumors (no viscera involvement) which consists of numerous (i.e. dozens to >100) IMF lesions most of which are located in the skin, subcutaneous tissues, and non-visceral but not visceral organs, may regress spontaneously, and rarely cause serious issues; and 3) multiple tumors (with viscera involvement) (also called generalized myofibromatosis) which rarely regress spontaneously and consist of numerous IMF lesions in non-visceral tissues plus one or more visceral tumors that may be life-threatening.A minority of infantile myofibromatosis tumors present in individuals with a strong family history of the disease. These familial cases are associated with mutations in either the PDGFRB or NOTCH3 gene. However, most IMF cases have no family history of the disease but nonetheless have PDGFRB gene mutations in their tumor cells; these mutations are similar to those occurring in the familial PDGFRB gene mutations. Regardless of these genetic variations, all IMF tumors consist of bland-appearing, benign (i.e. non-malignant) myofibroblasts, i.e.
PDGFβ receptor) proteins that contribute to the development and/or progression of IMF.A mutation in one of the two NOTCH3 genes has been reported to occur in a single family with autosomal dominant inheritance of IMF: 9 of this familys members had IMF plus the mutation while 7 of its members did not have IMF or the mutation. Since the mutated NOTCH3 gene in this family produces an overactive neurogenic locus notch homolog protein 3 product that in cell culture studies increases the expression of the PDGFRB genes product, the PDGFβ receptor, this NOTCH3 mutation may promote the development and/or progression of IMF in a manner similar to PDGFRB mutant genes, i.e. by increasing the number and therefore overall activity of the PDGFβ receptor. Further studies are needed to define NOTCH3 gene mutations frequency of occurrence in, and contribution to the development of, IMF. Solitary IMF tumors
Solitary IMF tumors represent 50 to 74% of all IMF cases. These tumors commonly present with a mass that infiltrates the surrounding tissue in the head and neck areas (e.g. in the ethmoid sinus/maxillary sinus, infratemporal fossa, tongue, hard palate, behind an ear, or temporal bone); less commonly in other sites such as the scapula/axilla area, lower back, or soft tissue/bone in the lower leg; and also less commonly in visceral organs such as the pancreas, spleen, lung, or heart. Solitary IMF tumors often (i.e. 25 to 61% of cases in different studies) regress spontaneously.