What is new in pericytomatous, myoid, and myofibroblastic tumors?

  • Ivy John
  • Karen J. FritchieEmail author


Recent advances in molecular techniques in soft tissue pathology, including the widespread application of next-generation sequencing, have led to significant progress in our understanding of mesenchymal tumors. Recognition of the genetic signatures of these neoplasms not only clarifies the relationship of these entities but also provides a mechanism for more accurate diagnosis. More importantly, insight into the genetic underpinnings of these lesions may offer therapeutic targets for cases not amenable to surgical treatment. This review highlights the clinicopathologic features and novel molecular findings in pericytic, myoid, and myofibroblastic tumors.


Pericytic neoplasms PDGFRB SRF-RELA GLI1 Fibrous hamartoma of infancy Calcifying aponeurotic fibroma Lipofibromatosis 


Author contributions

Both authors contributed equally to writing the manuscript. Both authors read and approved the final manuscript.

Compliance with ethical standards

No research involving human participants and/or animals was performed for this study.

Conflict of interest

The authors declare that they have no conflict of interest.


  1. 1.
    Diaz-Flores L, Gutiérrez R, Varela H et al (2009) Pericytes. Morphofunction, interactions and pathology in a quiescent and activated mesenchymal cell niche. Histol Histopathol 24(7):909–969PubMedGoogle Scholar
  2. 2.
    Armulik A, Genove G, Betsholtz C (2011) Pericytes: developmental, physiological, and pathological perspectives, problems, and promises. Dev Cell 21(2):193–215PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Granter SR, Badizadegan K, Fletcher CD (1998) Myofibromatosis in adults, glomangiopericytoma, and myopericytoma: a spectrum of tumors showing perivascular myoid differentiation. Am J Surg Pathol 22(5):513–525PubMedCrossRefGoogle Scholar
  4. 4.
    Mentzel T, Dei Tos AP, Sapi Z et al (2006) Myopericytoma of skin and soft tissues: clinicopathologic and immunohistochemical study of 54 cases. Am J Surg Pathol 30(1):104–113PubMedCrossRefGoogle Scholar
  5. 5.
    Dictor M, Elner A, Andersson T, Fernö M (1992) Myofibromatosis-like hemangiopericytoma metastasizing as differentiated vascular smooth-muscle and myosarcoma. Myopericytes as a subset of “myofibroblasts”. Am J Surg Pathol 16(12):1239–1247PubMedCrossRefGoogle Scholar
  6. 6.
    Martignetti JA, Tian L, Li D, Ramirez MC et al (2013) Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. Am J Hum Genet 92(6):1001–1007PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Cheung YH, Gayden T, Campeau PM et al (2013) A recurrent PDGFRB mutation causes familial infantile myofibromatosis. Am J Hum Genet 92(6):996–1000PubMedPubMedCentralCrossRefGoogle Scholar
  8. 8.
    Arts FA, Sciot R, Brichard B et al (2017) PDGFRB gain-of-function mutations in sporadic infantile myofibromatosis. Hum Mol Genet 26(10):1801–1810PubMedCrossRefGoogle Scholar
  9. 9.
    Agaimy A, Bieg M, Michal M et al (2017) Recurrent somatic PDGFRB mutations in sporadic infantile/solitary adult myofibromas but not in angioleiomyomas and myopericytomas. Am J Surg Pathol 41(2):195–203PubMedCrossRefGoogle Scholar
  10. 10.
    Hung YP, Fletcher CDM (2017) Myopericytomatosis: clinicopathologic analysis of 11 cases with molecular identification of recurrent PDGFRB alterations in myopericytomatosis and myopericytoma. Am J Surg Pathol 41(8):1034–1044PubMedCrossRefGoogle Scholar
  11. 11.
    Antonescu CR, Sung YS, Zhang L et al (2017) Recurrent SRF-RELA fusions define a novel subset of cellular myofibroma/myopericytoma: a potential diagnostic pitfall with sarcomas with myogenic differentiation. Am J Surg Pathol 41(5):677–684PubMedPubMedCentralCrossRefGoogle Scholar
  12. 12.
    Mosquera JM, Sboner A, Zhang L et al (2013) Novel MIR143-NOTCH fusions in benign and malignant glomus tumors. Gene Chromosome Canc 52(11):1075–1087CrossRefGoogle Scholar
  13. 13.
    Ikediobi NI, Iyengar V, Hwang L et al (2003) Infantile myofibromatosis: support for autosomal dominant inheritance. J Am Acad Dermatol 49(2 Suppl Case Reports):S148–S150PubMedCrossRefGoogle Scholar
  14. 14.
    Levéen P, Pekny M, Gebre-Medhin S et al (1994) Mice deficient for PDGF B show renal, cardiovascular, and hematological abnormalities. Genes Dev 8(16):1875–1887PubMedCrossRefGoogle Scholar
  15. 15.
    Soriano P (1994) Abnormal kidney development and hematological disorders in PDGF beta-receptor mutant mice. Genes Dev 8(16):1888–1896PubMedCrossRefGoogle Scholar
  16. 16.
    Lindahl P, Johansson BR, Levéen P et al (1997) Pericyte loss and microaneurysm formation in PDGF-B-deficient mice. Science 277(5323):242–245PubMedCrossRefGoogle Scholar
  17. 17.
    Arts FA, Chand D, Pecquet C et al (2016) PDGFRB mutants found in patients with familial infantile myofibromatosis or overgrowth syndrome are oncogenic and sensitive to imatinib. Oncogene 35(25):3239–3248PubMedCrossRefGoogle Scholar
  18. 18.
    Dachy G, de Krijger RR 2019, Fraitag S, et al Association of PDGFRB Mutations With Pediatric Myofibroma and Myofibromatosis. JAMA Dermatol,Google Scholar
  19. 19.
    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):142–150PubMedCrossRefGoogle Scholar
  20. 20.
    Mudry P, Slaby O, Neradil J et al (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):119PubMedPubMedCentralCrossRefGoogle Scholar
  21. 21.
    Linos K, Carter JM, Gardner JM et al (2014) Myofibromas with atypical features: expanding the morphologic spectrum of a benign entity. Am J Surg Pathol 38(12):1649–1654PubMedCrossRefGoogle Scholar
  22. 22.
    Coletti D, Daou N, Hassani M et al (2016) Serum response factor in muscle tissues: from development to ageing. Eur J Transl Myol 26(2):6008PubMedPubMedCentralCrossRefGoogle Scholar
  23. 23.
    Folpe AL, Fanburg-Smith JC, Miettinen M et al (2001) Atypical and malignant glomus tumors: analysis of 52 cases, with a proposal for the reclassification of glomus tumors. Am J Surg Pathol 25(1):1–12PubMedCrossRefGoogle Scholar
  24. 24.
    Folpe AL, Brems H, Legius E (2013) Glomus tumours. In: Fletcher CDM, Bridge JA, Hogendoorn PCW (eds) WHO classification of tumours of soft tissue and bone, 4th edn. IARC Press, Lyons, pp 116–117Google Scholar
  25. 25.
    Boon LM, Brouillard P, Irrthum A et al (1999) A gene for inherited cutaneous venous anomalies (“glomangiomas”) localizes to chromosome 1p21-22. Am J Hum Genet 65(1):125–133PubMedPubMedCentralCrossRefGoogle Scholar
  26. 26.
    Brouillard P, Boon LM, Mulliken JB et al (2002) Mutations in a novel factor, glomulin, are responsible for glomuvenous malformations (“glomangiomas”). Am J Hum Genet 70(4):866–874PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Brouillard P, Olsen BR, Vikkula M (2000) High-resolution physical and transcript map of the locus for venous malformations with glomus cells (VMGLOM) on chromosome 1p21-p22. Genomics 67(1):96–101PubMedCrossRefGoogle Scholar
  28. 28.
    Klaber R (1938) Morbus Recklinghausen with Glomoid Tumours. Proc R Soc Med 31(4):347PubMedPubMedCentralGoogle Scholar
  29. 29.
    De Smet L, Sciot R, Legius E (2002) Multifocal glomus tumours of the fingers in two patients with neurofibromatosis type 1. J Med Genet 39(8):e45PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Sawada S, Honda M, Kamide R et al (1995) Three cases of subungual glomus tumors with von Recklinghausen neurofibromatosis. J Am Acad Dermatol 32(2 Pt 1):277–278PubMedCrossRefGoogle Scholar
  31. 31.
    Brems H, Park C, Maertens O et al (2009) Glomus tumors in neurofibromatosis type 1: genetic, functional, and clinical evidence of a novel association. Cancer Res 69(18):7393–7401PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Chakrapani A, Warrick A, Nelson D et al (2012) BRAF and KRAS mutations in sporadic glomus tumors. Am J Dermatopathol 34(5):533–535PubMedCrossRefGoogle Scholar
  33. 33.
    Karamzadeh Dashti N, Bahrami A, Lee SJ et al (2017) BRAF V600E Mutations Occur in a Subset of Glomus Tumors, and Are Associated With Malignant Histologic Characteristics. Am J Surg Pathol 41(11):1532–1541PubMedCrossRefGoogle Scholar
  34. 34.
    Dahlin LB, Scherman P, Besjakov J et al (2017) Intraneural glomus tumor of “uncertain malignant potential” and with BRAF mutation in the median nerve - an unusual case. Clin Neuropathol 36(4):164–170PubMedCrossRefGoogle Scholar
  35. 35.
    Cuviello A, Goyal A, Zick A et al 2018 Sporadic Malignant Glomus Tumor of the Brachial Plexus With Response to Targeted Therapy Directed Against Oncogenic BRAF. JCO Precis Oncol.Google Scholar
  36. 36.
    Cordes KR, Sheehy NT, White MP et al (2009) miR-145 and miR-143 regulate smooth muscle cell fate and plasticity. Nature 460(7256):705–710PubMedPubMedCentralCrossRefGoogle Scholar
  37. 37.
    Wang Q, Zhao N, Kennard S et al (2012) Notch2 and Notch3 function together to regulate vascular smooth muscle development. PLoS One 7(5):e37365PubMedPubMedCentralCrossRefGoogle Scholar
  38. 38.
    High FA, Zhang M, Proweller A et al (2007) An essential role for Notch in neural crest during cardiovascular development and smooth muscle differentiation. J Clin Invest 117(2):353–363PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Bridge JA, Sanders K, Huang D et al (2012) Pericytoma with t(7;12) and ACTB-GLI1 fusion arising in bone. Hum Pathol 43(9):1524–1529PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Dahlén A, Fletcher CD, Mertens F et al (2004) Activation of the GLI oncogene through fusion with the beta-actin gene (ACTB) in a group of distinctive pericytic neoplasms: pericytoma with t(7;12). Am J Pathol 164(5):1645–1653PubMedPubMedCentralCrossRefGoogle Scholar
  41. 41.
    Castro E, Cortes-Santiago N, Ferguson LM, Rao PH, Venkatramani R, López-Terrada D (2016) Translocation t(7;12) as the sole chromosomal abnormality resulting in ACTB-GLI1 fusion in pediatric gastric pericytoma. Hum Pathol 53:137–141PubMedCrossRefGoogle Scholar
  42. 42.
    Koh NWC, Seow WY, Lee YT et al (2018) Pericytoma With t(7;12): The First Ovarian Case Reported and a Review of the Literature. Int J Gynecol PatholGoogle Scholar
  43. 43.
    Antonescu CR, Agaram NP, Sung YS et al (2018) A Distinct Malignant Epithelioid Neoplasm With GLI1 Gene Rearrangements, Frequent S100 Protein Expression, and Metastatic Potential: Expanding the Spectrum of Pathologic Entities With ACTB/MALAT1/PTCH1-GLI1 Fusions. Am J Surg Pathol 42(4):553–560PubMedPubMedCentralCrossRefGoogle Scholar
  44. 44.
    Agaram NP, Zhang L, Sung YS et al (2019) GLI1-amplifications expand the spectrum of soft tissue neoplasms defined by GLI1 gene fusions. Mod PatholGoogle Scholar
  45. 45.
    Gonnissen A, Isebaert S, Haustermans K (2015) Targeting the Hedgehog signaling pathway in cancer: beyond Smoothened. Oncotarget 6(16):13899–13913PubMedPubMedCentralCrossRefGoogle Scholar
  46. 46.
    Gonnissen A, Isebaert S, Haustermans K (2013) Hedgehog signaling in prostate cancer and its therapeutic implication. Int J Mol Sci 14(7):13979–14007PubMedPubMedCentralCrossRefGoogle Scholar
  47. 47.
    Li J, Cai J, Zhao S et al (2016) GANT61, a GLI inhibitor, sensitizes glioma cells to the temozolomide treatment. J Exp Clin Cancer Res 35(1):184PubMedPubMedCentralCrossRefGoogle Scholar
  48. 48.
    Geng L, Lu K, Li P et al (2017) GLI1 inhibitor GANT61 exhibits antitumor efficacy in T-cell lymphoma cells through down-regulation of p-STAT3 and SOCS3. Oncotarget 8(30):48701–48710PubMedCrossRefGoogle Scholar
  49. 49.
    Vlčková K, Réda J, Ondrušová L et al (2016) GLI inhibitor GANT61 kills melanoma cells and acts in synergy with obatoclax. Int J Oncol 49(3):953–960PubMedCrossRefGoogle Scholar
  50. 50.
    Reye RD (1956) A consideration of certain subdermal fibromatous tumours of infancy. J Pathol Bacteriol 72(1):149–154PubMedCrossRefGoogle Scholar
  51. 51.
    Enzinger FM (1965) Fibrous hamartoma of infancy. Cancer 18:241–248PubMedCrossRefGoogle Scholar
  52. 52.
    Lakshminarayanan R, Konia T, Welborn J (2005) Fibrous hamartoma of infancy: a case report with associated cytogenetic findings. Arch Pathol Lab Med 129(4):520–522PubMedGoogle Scholar
  53. 53.
    Rougemont AL, Fetni R, Murthy S et al (2006) A complex translocation (6;12;8)(q25;q24.3;q13) in a fibrous hamartoma of infancy. Cancer Genet Cytogenet 171(2):115–118PubMedCrossRefGoogle Scholar
  54. 54.
    Tassano E, Nozza P, Tavella E et al (2010) Cytogenetic characterization of a fibrous hamartoma of infancy with complex translocations. Cancer Genet Cytogenet 201(1):66–69PubMedCrossRefGoogle Scholar
  55. 55.
    Park JY, Cohen C, Lopez D et al (2016) EGFR Exon 20 Insertion/Duplication Mutations Characterize Fibrous Hamartoma of Infancy. Am J Surg Pathol 40(12):1713–1718PubMedCrossRefGoogle Scholar
  56. 56.
    Ellington N, Park JY, King K et al (2017) EGFR Exon 20 Insertion/Duplication Mutation in Fibrous Hamartoma of Infancy With Predominantly Pseudoangiomatous Pattern Mimicking Giant Cell Fibroblastoma. Int J Surg Pathol 25(5):421–424PubMedCrossRefGoogle Scholar
  57. 57.
    Al-Ibraheemi A, Martinez A, Weiss SW et al (2017) Fibrous hamartoma of infancy: a clinicopathologic study of 145 cases, including 2 with sarcomatous features. Mod Pathol 30(4):474–485PubMedCrossRefGoogle Scholar
  58. 58.
    Puls F, Hofvander J, Magnusson L et al (2016) FN1-EGF gene fusions are recurrent in calcifying aponeurotic fibroma. J Pathol 238(4):502–507PubMedCrossRefGoogle Scholar
  59. 59.
    Singh P, Carraher C, Schwarzbauer JE et al (2010) Assembly of fibronectin extracellular matrix. Annu Rev Cell Dev Biol 26:397–419PubMedPubMedCentralCrossRefGoogle Scholar
  60. 60.
    Zeng F, Harris RC (2014) Epidermal growth factor, from gene organization to bedside. Semin Cell Dev Biol 28:2–11PubMedCrossRefGoogle Scholar
  61. 61.
    Al-Ibraheemi A, Folpe AL, Perez-Atayde AR et al (2019) Aberrant receptor tyrosine kinase signaling in lipofibromatosis: a clinicopathological and molecular genetic study of 20 cases. Mod Pathol 32(3):423–434PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Anatomic PathologyUniversity of PittsburghPittsburghUSA
  2. 2.Department of Laboratory Medicine and PathologyMayo ClinicRochesterUSA

Personalised recommendations