Infantile myofibromatosis

Infantile myofibromatosis
Other namesMyofibromas, Multicentric fibromatosis,[1] Congenital generalized fibromatosis,[2] and Congenital multicentric fibromatosis[2]
SpecialtyNeonatology, Pediatrics
Usual onsetInfancy, early childhood
TypesSolitary tumor, Multiple tumors (no viscera involvement), and Multiple tumors (with viscera involvement)
CausesFamilial and non-familial somatic mutations in the PDGFRB gene
PrognosisGuarded in multiple tumors (with visceral involvement); otherwise, good to excellent
Frequencyrare

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.[1] The condition was first described by Arthur Purdy Stout as congenital generalized fibromatosis – in which he coined the word fibromatosis – in 1954.[3]

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 and subcutaneous tissues 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[1] and consist of numerous IMF lesions in non-visceral tissues plus one or more visceral tumors that may be life-threatening.[4][5]

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.[6] 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.[6] Regardless of these genetic variations, all IMF tumors consist of bland-appearing, benign (i.e. non-malignant) myofibroblasts, i.e. cells that blend a variable set of features seen in fibroblasts, the most common cell type in connective tissue, with a variable set of features seen in smooth muscle cells.[4]

Treatment of IMF tumors depends upon the tumor numbers, locations, and genetic abnormalities found in each individual and often include more than one therapeutic regimen. Individuals with solitary tumors are usually treated by observation with the expectation that many of these tumors will regress spontaneiously.[7] Single tumors located in vital areas (e.g. intracranial tumors) and tumors that do not regress over suitable observation periods are often treated by surgical removal. Multiple tumors (with viscera involvement) and surgically inaccessible life-threatening IMF tumors have been treated with one or a combination of chemotherapy drugs, radiation therapy or, in tumors with certain PDGFRB gene mutations, drugs directed specifically against this mutated gene's protein product.[1]

  1. ^ a b c d Manisterski M, Benish M, Levin D, Shiran SI, Sher O, Gortzak Y, Elhasid R (February 2021). "Diverse presentation and tailored treatment of infantile myofibromatosis: A single-center experience". Pediatric Blood & Cancer. 68 (2): e28769. doi:10.1002/pbc.28769. PMID 33063933. S2CID 222826034.
  2. ^ a b Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1.
  3. ^ Beck, Jill C.; Devaney, Kenneth O.; Weatherly, Robert A.; Koopmann, Charles F.; Lesperance, Marci M. (1999-01-01). "Pediatric Myofibromatosis of the Head and Neck". Archives of Otolaryngology–Head & Neck Surgery. 125 (1): 39–44. doi:10.1001/archotol.125.1.39. ISSN 0886-4470. PMID 9932585.
  4. ^ a b Fraitag S, Boccara O (August 2021). "What to Look Out for in a Newborn with Multiple Papulonodular Skin Lesions at Birth". Dermatopathology. 8 (3): 390–417. doi:10.3390/dermatopathology8030043. PMC 8395860. PMID 34449594.
  5. ^ Sparber-Sauer M, Vokuhl C, Seitz G, Sorg B, Tobias M, von Kalle T, Münter M, Bielack SS, Ladenstein R, Ljungman G, Niggli F, Frühwald M, Loff S, Klingebiel T, Koscielniak E (October 2021). "Infantile myofibromatosis: Excellent prognosis but also rare fatal progressive disease. Treatment results of five Cooperative Weichteilsarkom Studiengruppe (CWS) trials and one registry". Pediatric Blood & Cancer. 69 (3): e29403. doi:10.1002/pbc.29403. PMID 34636137. S2CID 238636902.
  6. ^ a b Hettmer S, Dachy G, Seitz G, Agaimy A, Duncan C, Jongmans M, Hirsch S, Kventsel I, Kordes U, de Krijger RR, Metzler M, Michaeli O, Nemes K, Poluha A, Ripperger T, Russo A, Smetsers S, Sparber-Sauer M, Stutz E, Bourdeaut F, Kratz CP, Demoulin JB (October 2021). "Genetic testing and surveillance in infantile myofibromatosis: a report from the SIOPE Host Genome Working Group". Familial Cancer. 20 (4): 327–336. doi:10.1007/s10689-020-00204-2. PMC 8484085. PMID 32888134.
  7. ^ Pekar-Zlotin M, Levinsohn-Tavor O, Livneh A, Sher O, Melcer Y, Maymon R (October 2019). "Gynecology and Oncology Fetal Myofibromatosis: A Challenge for Prenatal Diagnosis Mini Review of the English Literature". Obstetrical & Gynecological Survey. 74 (10): 607–610. doi:10.1097/OGX.0000000000000717. PMID 31670833. S2CID 204966175.