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Molecular and Cellular Pediatrics

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Open Access 01-12-2021 | Tyrosine Kinase Inhibitors | Case Study

Aggressive infantile myofibromatosis with intestinal involvement

Authors: Tristan Römer, Norbert Wagner, Till Braunschweig, Robert Meyer, Miriam Elbracht, Udo Kontny, Olga Moser

Published in: Molecular and Cellular Pediatrics | Issue 1/2021

Abstract

Background

Infantile myofibromatosis (IM) is the most common cause of multiple fibrous tumors in infancy. Multicentric disease can be associated with life-threatening visceral lesions. Germline gain-of-function mutations in PDGFRB have been identified as the most common molecular defect in familial IM.

Case presentation

We here describe an infant with PDGFRB-driven IM with multiple tumors at different sites, including intestinal polyposis with hematochezia, necessitating temporary chemotherapy.

Conclusions

PDGFRB-driven IM is clinically challenging due to its fluctuating course and multiple organ involvement in the first years of life. Early molecular genetic analysis is necessary to consider tyrosine kinase inhibitor treatment in case of aggressive visceral lesions.

Mashiah J, Hadj-Rabia S, Dompmartin A, Harroche A, Laloum-Grynberg E, Wolter M, Amoric JC, Hamel-Teillac D, Guero S, Fraitag S, Bodemer C (2014) Infantile myofibromatosis: a series of 28 cases. J Am Acad Dermatol 71(2):264–270. https://doi.org/10.1016/j.jaad.2014.03.035CrossRefPubMed

Parham DM (2018) Fibroblastic and myofibroblastic tumors of children: new genetic entities and new ancillary testing. F1000Res 7. F1000 Faculty Rev-1963. https://doi.org/10.12688/f1000research.16236.1

Sargar KM, Sheybani EF, Shenoy A, Aranake-Chrisinger J, Khanna G (2016) Pediatric fibroblastic and myofibroblastic tumors: a pictorial review. Radiographics 36(4):1195–1214. https://doi.org/10.1148/rg.2016150191CrossRefPubMed

Zhao G, Zhu M, Qin C, Liu X, Zhao X (2019) Infantile myofibromatosis: 32 patients and review of the literature. J Pediatr Hematol Oncol 42(8):495–498. https://doi.org/10.1097/MPH.0000000000001603CrossRef

Levine E, Fréneaux P, Schleiermacher G, Brisse H, Pannier S, Teissier N, Mesples B, Orbach D (2012) Risk-adapted therapy for infantile myofibromatosis in children. Pediatr Blood Cancer 59(1):115–120. https://doi.org/10.1002/pbc.23387CrossRefPubMed

Weaver MS, Navid F, Huppmann A, Meany H, Angiolillo A (2015) Vincristine and dactinomycin in infantile myofibromatosis with a review of treatment options. J Pediatr Hematol Oncol 37(3):237–241. https://doi.org/10.1097/MPH.0000000000000286CrossRefPubMed

Wu SY, McCavit TL, Cederberg K, Galindo RL, Leavey PJ (2015) Chemotherapy for generalized infantile myofibromatosis with visceral involvement. J Pediatr Hematol Oncol 37(5):402–405. https://doi.org/10.1097/MPH.0000000000000132CrossRefPubMed

Arts FA, Sciot R, Brichard B, Renard M, de Rocca SA, Dachy G, Noël LA, Velghe AI, Galant C, Debiec-Rychter M, Van Damme A, Vikkula M, Helaers R, Limaye N, Poirel HA, Demoulin JB (2017) PDGFRB gain-of-function mutations in sporadic infantile myofibromatosis. Hum Mol Genet 26(10):1801–1810. https://doi.org/10.1093/hmg/ddx081CrossRefPubMed

Cheung YH, Gayden T, Campeau PM, LeDuc CA, Russo D, Nguyen VH, Guo J, Qi M, Guan Y, Albrecht S, Moroz B, Eldin KW, Lu JT, Schwartzentruber J, Malkin D, Berghuis AM, Emil S, Gibbs RA, Burk DL, Vanstone M, Lee BH, Orchard D, Boycott KM, Chung WK, Jabado N (2013) A recurrent PDGFRB mutation causes familial infantile myofibromatosis. Am J Hum Genet 92(6):996–1000. https://doi.org/10.1016/j.ajhg.2013.04.026CrossRefPubMedPubMedCentral

10.

Martignetti JA, Tian L, Li D, Ramirez MC, Camacho-Vanegas O, Camacho SC, Guo Y, Zand DJ, Bernstein AM, Masur SK, Kim CE, Otieno FG, Hou C, Abdel-Magid N, Tweddale B, Metry D, Fournet JC, Papp E, McPherson EW, Zabel C, Vaksmann G, Morisot C, Keating B, Sleiman PM, Cleveland JA, Everman DB, Zackai E, Hakonarson H (2013) Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. Am J Hum Genet 92(6):1001–1007. https://doi.org/10.1016/j.ajhg.2013.04.024CrossRefPubMedPubMedCentral

11.

Demoulin JB, Essaghir A (2014) PDGF receptor signaling networks in normal and cancer cells. Cytokine Growth Factor Rev 25(3):273–283. https://doi.org/10.1016/j.cytogfr.2014.03.003CrossRefPubMed

12.

Arts FA, Chand D, Pecquet C, Velghe AI, Constantinescu S, Hallberg B, Demoulin JB (2016) PDGFRB mutants found in patients with familial infantile myofibromatosis or overgrowth syndrome are oncogenic and sensitive to imatinib. Oncogene 35(25):3239–3248. https://doi.org/10.1038/onc.2015.383CrossRefPubMed

13.

Sidney LE, Branch MJ, Dunphy SE, Dua HS, Hopkinson A (2014) Concise review: evidence for CD34 as a common marker for diverse progenitors. Stem Cells 32(6):1380–1389. https://doi.org/10.1002/stem.1661CrossRefPubMedPubMedCentral

14.

Koscielniak E, Klingebiel T; Cooperative Weichteilsarkom Studiengruppe (CWS) of the Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) (2014) CWS-Guidance for risk adapted treatment of soft tissue sarcoma and soft tissue tumours in children, adolescents, and young adults. Version 1.6.1. from 24.05.2014, Stuttgart

15.

Dessanti A, Massarelli G, Bosincu L, Canu L, Noya G, Dettori G (1999) Aggressive congenital fibromatosis of the small intestine in the newborn. Report of a case and review of the literature. Eur J Pediatr Surg 9(6):422–425. https://doi.org/10.1055/s-2008-1072298CrossRefPubMed

16.

Jones VS, Philip C, Harilal KR (2007) Infantile visceral myofibromatosis--a rare cause of neonatal intestinal obstruction. J Pediatr Surg 42(4):732–734. https://doi.org/10.1016/j.jpedsurg.2006.12.006CrossRefPubMed

17.

Dhall D, Frykman PK, Wang HL (2008) Colorectal infantile myofibromatosis: an unusual cause of rectal prolapse and sigmoid colo-colonic intussusception: a case report. Cases J 1(1):397. https://doi.org/10.1186/1757-1626-1-397CrossRefPubMedPubMedCentral

18.

Ortiz E, Kochhar A, Chandrasekar I (2020) Invasive myofibromatosis with visceral involvement in a term newborn: a case report. Am J Pediatr 6(2):173–177. https://doi.org/10.11648/j.ajp.20200602.30CrossRef

19.

Tamburrini G, Gessi M, Colosimo C Jr, Lauriola L, Giangaspero F, Di Rocco C (2003) Infantile myofibromatosis of the central nervous system. Childs Nerv Syst 19(9):650–654. https://doi.org/10.1007/s00381-003-0744-yCrossRefPubMed

20.

Inoue M, Tanaka S, Nakatomi H, Takayanagi S, Takahashi M, Tanaka M, Momose T, Mukasa A, Saito N (2016) Intracranial infantile myofibromatosis mimicking malignant brain tumor: a case report and literature review. World Neurosurg 93:487.e15–487.e20CrossRef

21.

Al Qawahmed R, Sawyer SL, Vassilyadi M, Qin W, Boycott KM, Michaud J (2019) Infantile myofibromatosis with intracranial extradural involvement and PDGFRB mutation: a case report and review of the literature. Pediatr Dev Pathol 22(3):258–264. https://doi.org/10.1177/1093526618787736CrossRefPubMed

22.

Murray N, Hanna B, Graf N, Fu H, Mylène V, Campeau PM, Ronan A (2017) The spectrum of infantile myofibromatosis includes both non-penetrance and adult recurrence. Eur J Med Genet 60(7):353–358. https://doi.org/10.1016/j.ejmg.2017.02.005CrossRefPubMed

23.

Weller JM, Keil VC, Gielen GH, Herrlinger U, Schäfer N (2019) PDGFRB mutation-associated myofibromatosis: response to targeted therapy with imatinib. Am J Med Genet A 179(9):1895–1897. https://doi.org/10.1002/ajmg.a.61283CrossRefPubMed

24.

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 (2020) Genetic testing and surveillance in infantile myofibromatosis: a report from the SIOPE Host Genome Working Group. Fam Cancer. https://doi.org/10.1007/s10689-020-00204-2

25.

Dachy G, de Krijger RR, Fraitag S, Théate I, Brichard B, Hoffman SB, Libbrecht L, Arts FA, Brouillard P, Vikkula M, Limaye N, Demoulin JB (2019) Association of PDGFRB mutations with pediatric myofibroma and myofibromatosis. JAMA Dermatol 155(8):946–950. https://doi.org/10.1001/jamadermatol.2019.0114CrossRefPubMedPubMedCentral

26.

Linhares ND, Freire MC, Cardenas RG, Bahia M, Puzenat E, Aubin F, Pena SD (2014) Modulation of expressivity in PDGFRB-related infantile myofibromatosis: a role for PTPRG? Genet Mol Res 13(3):6287–6292. https://doi.org/10.4238/2014.August.15.11CrossRefPubMed

27.

Ito N, Watanabe S, Mishima H, Kinoshita A, Okada M, Moriuchi H, Yoshiura K (2019) A mutation in PDGFRB in a family with infantile myofibromatosis. Acta Med Nagasakiensia 63:49–53

28.

Mudry P, Slaby O, Neradil J, Soukalova J, Melicharkova K, Rohleder O, Jezova M, Seehofnerova A, Michu E, Veselska R, Sterba J (2017) Case report: rapid and durable response to PDGFR targeted therapy in a child with refractory multiple infantile myofibromatosis and a heterozygous germline mutation of the PDGFRB gene. BMC Cancer 17(1):119. https://doi.org/10.1186/s12885-017-3115-xCrossRefPubMedPubMedCentral

29.

Hassan M, Butler E, Wilson R, Roy A, Zheng Y, Liem P, Rakheja D, Pavlick D, Young LL, Rosenzweig M, Erlich R, Ali SM, Leavey PJ, Parsons DW, Skapek SX, Laetsch TW (2019) Novel PDGFRB rearrangement in multifocal infantile myofibromatosis is tumorigenic and sensitive to imatinib. Cold Spring Harb Mol Case Stud 5(5):a004440. https://doi.org/10.1101/mcs.a004440CrossRefPubMedPubMedCentral

30.

Sramek M, Neradil J, Macigova P, Mudry P, Polaskova K, Slaby O, Noskova H, Sterba J, Veselska R (2018) Effects of sunitinib and other kinase inhibitors on cells harboring a PDGFRB mutation associated with infantile myofibromatosis. Int J Mol Sci 19(9):E2599. https://doi.org/10.3390/ijms19092599CrossRefPubMed

31.

Pond D, Arts FA, Mendelsohn NJ, Demoulin JB, Scharer G, Messinger Y (2018) A patient with germ-line gain-of-function PDGFRB p.N666H mutation and marked clinical response to imatinib. Genet Med 20(1):142–150. https://doi.org/10.1038/gim.2017.104CrossRefPubMed

32.

Pilz T, Pilgrim TB, Bisogno G, Knietig R, Koscielniak E, Carli M, Treuner J (1999) Chemotherapy in fibromatoses of childhood and adolescence: results from the Cooperative soft tissue sarcoma study (CWS) and the Italian Cooperative study group (ICG-AIEOP). Klin Padiatr 211(4):291–295. https://doi.org/10.1055/s-2008-1043802CrossRefPubMed

33.

Azzam R, Abboud M, Muwakkit S, Khoury N, Saab R (2009) First-line therapy of generalized infantile myofibromatosis with low-dose vinblastine and methotrexate. Pediatr Blood Cancer 52(2):308. https://doi.org/10.1002/pbc.21797CrossRefPubMed

34.

Millot F, Guilhot J, Baruchel A, Petit A, Leblanc T, Bertrand Y, Mazingue F, Lutz P, Verite C, Berthou C, Galambrin C, Sirvent N, Yacouben K, Chastagner P, Gandemer V, Reguerre Y, Couillault G, Khalifeh T, Rialland F (2014) Growth deceleration in children treated with imatinib for chronic myeloid leukaemia. Eur J Cancer 50(18):3206–3211. https://doi.org/10.1016/j.ejca.2014.10.007CrossRefPubMed

Title: Aggressive infantile myofibromatosis with intestinal involvement
Authors: Tristan Römer
Norbert Wagner
Till Braunschweig
Robert Meyer
Miriam Elbracht
Udo Kontny
Olga Moser
Publication date: 01-12-2021
Publisher: Springer Berlin Heidelberg
Keywords: Tyrosine Kinase Inhibitors
Targeted Therapy
Tyrosine Kinase Inhibitors
Cytostatic Therapy
Published in: Molecular and Cellular Pediatrics / Issue 1/2021
Electronic ISSN: 2194-7791
DOI: https://doi.org/10.1186/s40348-021-00117-9

At a glance: The STEP trials

Springer Medicine

Aggressive infantile myofibromatosis with intestinal involvement

Abstract

Background

Case presentation

Conclusions

At a glance: The STEP trials

Springer Medicine

Abstract

Background

Case presentation

Conclusions

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