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Pathogenesis, Classification, Histopathology, and Symptomatology of Fibroids

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Uterine Fibroids

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Abstract

Uterine fibroids (leiomyomas or benign tumors of the smooth muscle) represent the most common form of benign mesenchymal disease of the female genital tract. Clinical studies report an incidence of 25–30% of the female population of childbearing age, with higher prevalence after 40 years and in black women [1].

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References

  1. Sparic R, Mirkovic L, Malvasi A, Tinelli A. Epidemiology of uterine Myomas: a review. Int J Fertil Steril. 2016;9(4):424–35.

    PubMed  Google Scholar 

  2. Di Tommaso S, Massari S, Malvasi A, Vergara D, Maffia M, Greco M, et al. Selective genetic analysis of myoma pseudocapsule and potential biological impact on uterine fibroid medical therapy. Expert Opin Ther Targets. 2015;19(1):7–12.

    Article  PubMed  Google Scholar 

  3. Reis FM, Bloise E, Ortiga-Carvalho TM. Hormones and pathogenesis of uterine fibroids. Best Pract Res Clin Obstet Gynaecol. 2016;34:13–24. pii: S1521-6934(15)00229-1.

    Article  PubMed  Google Scholar 

  4. Puchar A, Luton D, Koskas M. Ulipristal acetate for uterine fibroid-related symptoms. Drugs Today (Barc). 2015;51(11):661–7.

    Article  CAS  Google Scholar 

  5. Sparic R, Hudelist G, Berisava M, Gudovic A, Buzadzic S. Hysterectomy throughout history. Acta Chir Iugosl. 2011;58(4):9–14.

    Article  PubMed  Google Scholar 

  6. Styer AK, Rueda BR. The epidemiology and genetics of uterine leiomyoma. Best Pract Res Clin Obstet Gynaecol. 2016;34:3–12. pii: S1521-6934(15)00232-1.

    Article  PubMed  Google Scholar 

  7. Wise LA, Laughlin-Tommaso SK. Epidemology of uterine fibroids: from menarche to menopause. Clin Obstet Gynecol. 2015;59(1):2–24.

    Article  Google Scholar 

  8. Laughlin S, Baird DD, Savitz DA, Herring AH, Hartmann KE. Prevalence of uterine leiomyomas in the first trimester of pregnancy: an ultrasound screening study. Obstet Gynecol. 2009;113(3):630–5.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Wise LA, Lauglin-Tommaso SK. Uterine leiomyomata. In: Goldman MB, Troisi R, Rexrode KM, editors. Women and health. San Diego: Academic; 2013. p. 285–306.

    Chapter  Google Scholar 

  10. Parazzini F, Di Martino M, Candiani M, Vigano P. Dietary components and uterine leiomyomas: a review of the publishe data. Nutr Cancer. 2015;67(4):569–79.

    Article  CAS  PubMed  Google Scholar 

  11. Brakta S, Diamond AS, Al-Hendy A, Diamond MP, Halder SK. Role of vitamin D in uterine fibroid biology. Fertil Steril. 2015;104(3):698–706.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Haan YC, Oudman I, de Lange ME, Timmermans A, Ankum WM, van Montfrans GA, et al. Hypertension risk in Dutch women with symptomatic uterine fibroids. Am J Hypertens. 2015;28(4):487–92.

    Article  PubMed  Google Scholar 

  13. Hashimoto K, Azuma C, Kamiura S, Kimura T, Nobunaga T, Kanai T, et al. Clonal determination of uterine leiomyomas by analyzing differential inactivation of the X-chromosome-linked phosphoglycerokinase gene. Gynecol Obstet Invest. 1995;40(3):204–8.

    Article  CAS  PubMed  Google Scholar 

  14. Ono M, Qiang W, Serna VA, Yin P, Coon JS 5th, Navaro A, et al. Role of stem cells in human uterine leiomyoma growth. PLoS One. 2012;7(5):e36935.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Sozen I, Arici A. Interactions of cytokines, growth factors, and the extracellular matrix in the cellular biology of uterine leiomyomata. Fertil Steril. 2002;78(1):1–12.

    Article  PubMed  Google Scholar 

  16. Bogusiewicz M, Stryjecka-Zimmer M, Postawski K, Jakimiuk AJ, Rechberger T. Activity of matrix metalloproteinase-2 and -9 and contents of their tissue inhibitors in uterine leiomyoma and corresponding myometrium. Gynecol Endocrinol. 2007;23(9):541–6.

    Article  CAS  PubMed  Google Scholar 

  17. Tinelli A, Malvasi A. Uterine fibroid pseudocapsule. In: Tinelli A, Malvasi A, editors. Uterine myoma, myomectomy and minimally invasive treatments. Cham: Springer Publisher; 2015. p. 73–93.

    Google Scholar 

  18. Grings AO, Lora V, Dias Ferreira G, Brum IS, Corleta HV, Capp E. Protein expression of estrogen receptors α and β and aromatase in myometrium and uterine leiomyoma. Gynecol Obstet Invest. 2012;73(2):113–7.

    Article  PubMed  Google Scholar 

  19. Maruo T, Matsuo H, Shimomura Y, Kurachi O, Nikago S, Yamada T, et al. Effects of progesterone on growth factor expression in human uterine leiomyoma. Steroids. 2003;68(10–13):817–24.

    Article  CAS  PubMed  Google Scholar 

  20. Sparic R, Terzic M, Malvasi A, Tinelli A. Uterine fibroids-clinical presentation and complications. Acta Chir Iugosl. 2014;61(3):41–8.

    Article  Google Scholar 

  21. Lora V, Grings AO, Capp E, von Eye CH, Brum IS. Gene and protein expression of progesterone receptor isoforms a and B, p53 and p21 in myometrium and uterine leiomyoma. Arch Gynecol Obstet. 2012;286(1):119–24.

    Article  CAS  PubMed  Google Scholar 

  22. Matsuo H, Kurachi O, Shimomura Y, Samoto T, Maruo T. Molecular bases for the actions of ovarian sex steroids in the regulation of proliferation and apoptosis of human uterine leiomyoma. Oncology. 1999;57(Suppl 2):49–58.

    Article  CAS  PubMed  Google Scholar 

  23. Wang L, Mou X, Xiao L, Tang L. T-cadherin expression in uterine leiomyoma. Arch Gynecol Obstet. 2013;288(3):607–14.

    Article  CAS  PubMed  Google Scholar 

  24. Mäkinen N, Mehine M, Tolvanen J, Kaasinen E, Li Y, Lehtonen HJ, et al. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science. 2011;334(6053):252–5.

    Article  PubMed  Google Scholar 

  25. Mittal P, Shin YH, Yatsenko SA, Castro CA, Surti U, Rajkovic A. Med12 gain-of-function mutation causes leiomyomas and genomic instability. J Clin Invest. 2015;125(8):3280–4.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Croce S, Chibon F. MED12 and uterine smooth muscle oncogenesis: state of the art and perspectives. Eur J Cancer. 2015;51(12):1603–10.

    Article  CAS  PubMed  Google Scholar 

  27. Vergara D, Greco M. Genetics and genomics of uterine myomas. In: Tinelli A, Malvasi A, editors. Uterine myoma, myomectomy and minimally invasive treatments. Cham: Springer Publisher; 2015. p. 12–25.

    Google Scholar 

  28. Mäkinen N, Vahteristo P, Bützow R, Sjoberg J, Aaltonen LA. Exomic landscape of MED12 mutation-negative and -positive uterine leiomyomas. Int J Cancer. 2014;134(4):1008–12.

    Article  PubMed  Google Scholar 

  29. Ono M, Yin P, Navarro A, Moravek MB, Coon JS 5th, Druschitz SA, et al. Paracrine activation of WNT/β-catenin pathway in uterine leiomyoma stem cells promotes tumor growth. Proc Natl Acad Sci U S A. 2013;110(42):17053–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Karra L, Shushan A, Ben-Meir A, Rojansky N, Klein BY, Shiveiky D, et al. Changes related to phosphatidylinositol 3-kinase/Akt signaling in leiomyomas: possible involvement of glycogen synthase kinase 3alpha and cyclin D2 in the pathophysiology. Fertil Steril. 2010;93(8):2646–51.

    Article  CAS  PubMed  Google Scholar 

  31. Munro MG, Critchley HO, Broder MS, Fraser IS. FIGO working group on menstrual disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age. Int J Gynaecol Obstet. 2011;113(1):3–13.

    Article  PubMed  Google Scholar 

  32. Worhunsky DJ, Gupta M, Gholami S, Tran TB, Ganjoo KN, van de Rijn M, et al. Leiomyosarcoma: one disease or distinct biologic entities based on site of origin? J Surg Oncol. 2015;111(7):808–12.

    Article  PubMed  Google Scholar 

  33. Hodge JC, Morton CC. Genetic heterogeneity among uterine leiomyomata: insights into malignant progression. Hum Mol Genet. 2007. 16 Spec No 1:R7-13.

    Google Scholar 

  34. Robboy SJ, Bentley RC, Butnor K, Anderson MC. Pathology and pathophysiology of uterine smooth-muscle tumors. Environ Health Perspect. 2000;108(Suppl 5):779–84.

    Article  PubMed  Google Scholar 

  35. Clement PB, Young RH. Atlas of gynecologic surgical pathology. 3rd ed. Philadelphia: Saunders; 2013.

    Google Scholar 

  36. Tinelli A, Sparic R, Kadija S, Babovic I, Tinelli R, Mynbaev OA, et al. Myomas: anatomy and related issues. Minerva Ginecol. 2016;68(3):261–73.

    PubMed  Google Scholar 

  37. Ito F, Kawamura N, Ishimura T, Tsujimura A, Ishiko O, Ogita S. Ultrastructural comparison of uterine leiomyoma cells from the same myoma nodule before and after gonadotropin-releasing hormone agonist treatment. Fertil Steril. 2001;75(1):l25–30.

    Article  Google Scholar 

  38. Dapunt O. Studies on the structure of the myoma capsule. Arch Gynakol. 1965;202:492–4.

    Article  CAS  PubMed  Google Scholar 

  39. Fox H, Buckley CH. Benign neoplasms of the female genital tract. In: Pathology for gynaecologists. London: Arnold Edts; 1982. p. 91–7.

    Google Scholar 

  40. Vizza E, Motta PM. The skeleton fibrous and muscolar of the uterus. In: Atti LXXVII Congresso SIGO. Rome: CIC Edit Int; 2001. p. 47–9.

    Google Scholar 

  41. Kurjak A, Jurkovic D, Alfirevic Z, Zalud I. Transvaginal color Doppler imaging. J Clin Ultrasound. 1990;18(4):227–34.

    Article  CAS  PubMed  Google Scholar 

  42. Tinelli A, Malvasi A, Rahimi S, Negro R, Cavallotti C, Vergara D, et al. Myoma pseudocapsule: a distinct endocrino-anatomical entity in gynecological surgery. Gynecol Endocrinol. 2009;25(10):661–7.

    Article  PubMed  Google Scholar 

  43. Malvasi A, Tinelli A, Rahimi S, D’Agnese G, Rotoni C, Dell’Edera D, et al. A three-dimensional morphological reconstruction of uterine leiomyoma pseudocapsule vasculature by the Allen-Cahn mathematical model. Biomed Pharmacother. 2011;65(5):359–63.

    Article  PubMed  Google Scholar 

  44. Mettler L, Tinelli A, Hurst BS, Teigland CM, Sammur W, Dell’Edera D, et al. Neurovascular bundle in fibroid pseudocapsule and its neuroendocrinologic implications. Expert Rev Endocrinol Metab. 2011;6(5):715–22.

    Article  Google Scholar 

  45. Malvasi A, Cavallotti C, Morroni M, Lorenzi T, Dell’Edera D, Nicolardi G, et al. Uterine fibroid pseudocapsule studied by transmission electron microscopy. Eur J Obstet Gynecol Reprod Biol. 2012;162(2):187–91.

    Article  PubMed  Google Scholar 

  46. Wei JJ, Zhang XM, Chiriboga L, Yee H, Perle MA, Mittal K. Spatial differences in biologic activity of large uterine leiomyomata. Fertil Steril. 2006;85(1):179–87.

    Article  CAS  PubMed  Google Scholar 

  47. Tinelli A, Malvasi A, Hurst BS, Tsin DA, Davila F, Dominguez G, et al. Surgical management of neurovascular bundle of uterine fibroid pseudocapsule during myomectomy. JSLS. 2012;16(1):119–29.

    Google Scholar 

  48. Tinelli A, Hurst BS, Mettler L, Tsin DA, Pellegrino M, Nicolardi G, et al. Ultrasound evaluation of uterine healing after laparoscopic intracapsular myomectomy: an observational study. Hum Reprod. 2012;27(9):2664–70.

    Article  PubMed  Google Scholar 

  49. Di Tommaso S, Massari S, Malvasi A, Bozzetti MP, Tinelli A. Gene expression analysis reveals an angiogenic profile in uterine leiomyoma pseudocapsule. Mol Hum Reprod. 2013;19(6):380–7.

    Article  PubMed  Google Scholar 

  50. Di Tommaso S, Tinelli A, Malvasi A, Massari S. Missense mutations in exon 2 of the MED12 gene are involved in IGF-2 overexpression in uterine leiomyoma. Mol Hum Reprod. 2014;20(10):1009–15.

    Article  PubMed  Google Scholar 

  51. Malvasi A, Tinelli A, Cavallotti C, Morroni M, Tsin DA, Nezhat C, et al. Distribution of substance P (SP) and vasoactive intestinal peptide (VIP) neuropeptides in pseudocapsules of uterine fibroids. Peptides. 2011;32(2):327–32.

    Article  CAS  PubMed  Google Scholar 

  52. Malvasi A, Cavallotti C, Nicolardi G, Pellegrino M, Dell’Edera D, Vergara D, et al. NT, NPY and PGP 9.5 presence in myomeytrium and in fibroid pseudocapsule and their possible impact on muscular physiology. Gynecol Endocrinol. 2013;29(2):177–81.

    Article  PubMed  Google Scholar 

  53. Malvasi A, Cavallotti C, Nicolardi G, Pellegrino M, Vergara D, Greco M, et al. The opioid neuropeptides in uterine fibroid pseudocapsules: a putative association with cervical integrity in human reproduction. Gynecol Endocrinol. 2013;29(11):982–8.

    Article  CAS  PubMed  Google Scholar 

  54. Rowe MK, Kanouse DE, Mittman BS, Bernstein SJ. Quality of life among women undergoing hysterectomies. Obstet Gynecol. 1999;93:915–21.

    CAS  PubMed  Google Scholar 

  55. Munro MG, Lukes AS, Abnormal Uterine Bleeding and Underlying Hemostatic Disorders Consensus Group. Abnormal uterine bleeding and underlying hemostatic disorders: report of a consensus process. Fertil Steril. 2005;84(5):1335–7.

    Article  PubMed  Google Scholar 

  56. Wegienka G, Baird DD, Hertz-Picciotto I, Harlow SD, Steege JF, Hill MC, et al. Self-reported heavy bleeding associated with uterine leiomyomata. Obstet Gynecol. 2003;101(3):431–7.

    PubMed  Google Scholar 

  57. Parker WH. Uterine fibroids: clinical features. In: Tinelli A, Malvasi A, editors. Uterine myoma, myomectomy and minimally invasive treatments. Cham: Springer Publisher; 2015. p. 39–52.

    Google Scholar 

  58. Murase E, Siegelman ES, Outwater EK, Perez-Jaffe LA, Tureck RW. Uterine leiomyomas: histopathologic features, MR imaging findings, differential diagnosis, and treatment. Radiographics. 1999;19(5):1179–97.

    Article  CAS  PubMed  Google Scholar 

  59. Gaym A, Tilahun S. Torsion of pedunculated subserous myoma—a rare cause of acute abdomen. Ethiop Med J. 2007;45(2):203–7.

    PubMed  Google Scholar 

  60. Olive DL. Review of the evidence for treatment of leiomyomata. Environ Health Perspect. 2000;108(Suppl 5):841–3.

    Article  PubMed  Google Scholar 

  61. Langer R, Golan A, Neuman M, Schneider D, Bukovsky I, Caspi E. The effect of large uterine fibroids on urinary bladder function and symptoms. Am J Obstet Gynecol. 1990;163(4 Pt 1):1139–41.

    Article  CAS  PubMed  Google Scholar 

  62. Peddada SD, Laughlin SK, Miner K, Guyon JP, Haneke K, Vahdat HL, et al. Growth of uterine leiomyomata among premenopausal black and white women. Proc Natl Acad Sci U S A. 2008;105(50):19887–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Parker W, Fu Y, Berek J. Uterine sarcoma in patients operated on for presumed leiomyoma and rapidly growing leiomyoma. Obstet Gynecol. 1994;83(3):414–8.

    CAS  PubMed  Google Scholar 

  64. Boutselis J, Ullery J. Sarcoma of the uterus. Obstet Gynecol. 1962;20:23–35.

    Article  CAS  PubMed  Google Scholar 

  65. Brooks SE, Zhan M, Cote T, Baquet CR. Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989–1999. Gynecol Oncol. 2004;93(1):204–8.

    Article  PubMed  Google Scholar 

  66. Quade BJ, Wang TY, Sornberger K, Dal Cin P, Mutter GL, Morton CC. Molecular pathogenesis of uterine smooth muscle tumors from transcriptional profiling. Genes Chromosomes Cancer. 2004;40(2):97–108.

    Article  CAS  PubMed  Google Scholar 

  67. Carlson KJ, Miller BA, Fowler FJ Jr. The Maine Women’s Health Study: II. Outcomes of nonsurgical management of leiomyomas, abnormal bleeding, and chronic pelvic pain. Obstet Gynecol. 1994;83(4):566–72.

    Article  CAS  PubMed  Google Scholar 

  68. Sparic R, Nejkovic L, Mutavdzic D, Tinelli A. Conservative surgical treatment of uterine fibroids. Acta Chir Iugosl. 2014;61(4):11–6.

    Article  Google Scholar 

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Authors and Affiliations

  1. Division of Experimental Endoscopic Surgery, Imaging, Technology and Minimally Invasive Therapy, Department of Obstetrics and Gynecology, Vito Fazzi Hospital, Lecce, Italy

    Andrea Tinelli MD, PhD

  2. Laboratory of Human Physiology, Department of Applied Mathematics, Moscow, Institute of Physics and Technology (State University), Moscow Region, Russia

    Andrea Tinelli MD, PhD

  3. Section of Pathological Anatomy, Department of Emergency and Organ Transplantation (DETO), University of Bari, Bari, Italy

    Leonardo Resta MD, PhD

  4. Clinic for Gynecology and Obstetrics, Clinical Centre of Serbia, Višegradska 26, 11000, Belgrade, Serbia

    Radmila Sparić MD & Aleksandar Stefanović MD, PhD

  5. Medical Faculty, University of Belgrade, Doktora Subotića 8, 11000, Belgrade, Serbia

    Radmila Sparić MD & Aleksandar Stefanović MD, PhD

  6. International Translational Medicine and Biomodelling Research Group, Department of Applied Mathematics, Moscow, Institute of Physics and Technology (State University), Moscow Region, Russia

    Antonio Malvasi MD

  7. Department of Obstetrics and Gynecology, GVM Care and Research, Santa Maria Hospital, Bari, Italy

    Antonio Malvasi MD

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  1. Andrea Tinelli MD, PhD
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  2. Leonardo Resta MD, PhD
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  3. Radmila Sparić MD
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  4. Aleksandar Stefanović MD, PhD
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  5. Antonio Malvasi MD
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Corresponding author

Correspondence to Andrea Tinelli MD, PhD .

Editor information

Editors and Affiliations

  1. Minimally Invasive Gynecologic Surgery, Department of Obstetrics and Gynecology, University of Florida, Gainesville, Florida, USA

    Nash S. Moawad

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Tinelli, A., Resta, L., Sparić, R., Stefanović, A., Malvasi, A. (2018). Pathogenesis, Classification, Histopathology, and Symptomatology of Fibroids. In: Moawad, N. (eds) Uterine Fibroids. Springer, Cham. https://doi.org/10.1007/978-3-319-58780-6_1

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