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A rare benign soft tissue tumor characterized by the development of nodules in the skin, striated muscles, bones, and in exceptional cases, visceral organs, leading to a broad spectrum of clinical symptoms. It contains myofibroblasts.
ORPHA:2591Classification level: Disorder
The estimated prevalence is 1/150,000 live births.
Infantile myofibromatosis (IM) presents at birth or develops shortly thereafter, with 90% of cases occurring before the age of 2 years. IM is characterized by solitary or multiple nodules that are firm, flesh-colored to purple (''myofibroma''), and usually painless (except in case of compression of adjacent nerves). Tumors are located in the skin, subcutaneous tissue, striated muscles and in exceptional cases, visceral organs or bones. There are 4 patterns of clinical presentation: solitary (single lesion affecting the skin and/or muscles in the head, neck, or trunk (75% cases)); congenital multiple (multicentric limited to skin and muscles); congenital multiple with single visceral involvement; and congenital multiple with multiple visceral involvement (multiple lesions of skin and/or muscles, bones, lungs, heart and gastrointestinal tract). Rarely, prenatal diagnosis could be evoked.
Most of these tumors are sporadic and isolated. Rare familial cases of IM have been described and 2 genes have been identified as disease causing: PDGFRB and NOTCH3 which encode PDGFRB and NOTCH3 respectively. PDGFRB is a tyrosine kinase receptor for platelet derived growth factors which are mitogens for cells of mesenchymal origin. PDGFRB expression is up regulated by NOTCH3. This suggests that genetic defects in the 2 genes are involved in the same mechanism.
Diagnosis is evoked partly on family history and physical examination at this age. Myofibromas are identified through ultrasound (mass with an anechoic center), MRI (low signal on T1-weighted imaging and high or low signal intensity areas on T2-weighted imaging) and less frequently CT (mass with peripheral enhancement and calcifications). Histopathology remains the gold standard for the diagnosis of IM. Biopsy reveals interlacing fascicles of spindle cells (myofibroblasts) in the periphery. Immunochemistry reveals vimentin and smooth muscle actin expression while vascular markers (S100 and CD34) are negative. In some cases, molecular tumor analysis could found a PDGFRB gene mutation.
Differential diagnosis in case of solitary lesion includes hemangioma, lymphangioma, neurofibroma, infantile fibrosarcoma, Langerhans cell histiocytosis, inflammatory myofibroblastic tumor, desmoid tumors and dermoid or epidermoid tumors.
Prenatal diagnosis is achieved by ultrasound examination and confirm by fetal MRI.
IM is mostly isolated and sporadic. In cases of familial and multifocal lesions, IM can be inherited as an autosomal recessive or dominant trait (incomplete penetrance and variable expressivity).
Management and treatment
Due to the benignity of the lesion, therapies without long term effects are preferred. For lesions affecting the skin and/or muscles, treatment is not recommended and a wait-and-see policy is proposed (tendency towards spontaneous regression). Radical surgical excision is required if: vital organs are involved, lesions are in threatening sites, or lesions are symptomatic. In cases of incomplete resection, re-excision can be proposed later. Standard therapy is low dose weekly methotrexate and vinblastine and is indicated for multifocal progressive life threatening lesions. Other treatments such as conventional chemotherapy (vincristine, D-actinomycin, and cyclophosphamide) should be kept for patients with rapid symptomatic progression because of the long-term risks of secondary malignancy development. PDGFRB inhibitors have not already been studied in such disease.
In the majority of cases, which lack visceral involvement, prognosis is excellent and spontaneous regression is often observed. On the other hand, the presence of visceral lesions is associated with a significantly poor outcome and a mortality rate of up to 70%, in the absence of therapy. Death is generally related to organ compression and cardiopulmonary and gastrointestinal involvement.