, Volume 74, Issue 5, pp 521–531 | Cite as

The enigmatic thymic myoid cells – their 130 years of history, embryonic origin, function and clinical significance

  • Ivan VargaEmail author
  • Ildikó Bódi
  • David Kachlík
  • Veronika Mešťanová
  • Martin Klein
Review Review


Thymic myoid cells form a part of the cellular microenvironment of the thymic medulla in fish, amphibians, reptiles, birds, and mammals, including humans. In lower vertebrates they resemble skeletal muscle fibers at the level of light and electron microscopy, in humans they are less noticable even though they contain proteins typically found in the muscle tissue including desmin, actin, acetylcholine receptor, myosin, troponin or myogenic transcription factor. Despite the discovery of thymic myoid cells by German histologist Sigmund Mayer employed at the Charles-Ferdinand University (now Charles University) in Prague, Czech Republic, occurred exactly 130 years ago, as of today, these cells have been mentioned neither in most of the histology textbooks, nor in the histological nomenclature Terminologia Histologica. Thus, we find it appropriate to call these cells “enigmatic.” In this narrative review, we focus on the historical background of the discovery of thymic myoid cells, and current opinions on their embryonic origin and functional significance during the maturation of T-lymphocytes within the thymus. Finally, we present the overview of the clinical importance of this cell population, including the notion of rare mediastinal rhabdomyomas and rhabdomyosarcomas probably originating from these cells. We also ponder over the possible connection between thymic myoid cells and the pathogenesis of autoimmune disease – myasthenia gravis.


Thymic myoid cells Thymus Functional histology Myasthenia gravis Terminologia Histologica Terminologica Embryologica 



This work was supported by Grant of The Slovak Research and Development Agency No. APVV- 14-0032.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.


  1. Alvarez R (1990) Thymus of Rana perezi: presence of interdigitating cells. J Morphol 204(3):305–312Google Scholar
  2. Ash JF, Morton DA, Scott SA (2013) The big picture: histology. The McGraw-Hill Companies, New YorkGoogle Scholar
  3. Balko J, Tonar Z, Varga I (2018) Memorix histology, 1st edn. Triton, PragueGoogle Scholar
  4. Bockman DE (1968) Myoid cells in adult human thymus. Nature 218(5138):286–287Google Scholar
  5. Bockman DE, Winborn WB (1969) Ultrastructure of thymic myoid cells. J Morphol 129(2):201–210Google Scholar
  6. Bódi I, Minkó K, Molnár D, Nagy N, Oláh I (2015) A novel aspect of the structure of the avian thymic medulla. Cell Tissue Res 359(2):489–501. Google Scholar
  7. Cao J, Chen Q, Lu M, Hu X, Wang M (2017) Histology and ultrastructure of the thymus during development in tilapia, Oreochromis niloticus. J Anat 230(5):720–733. Google Scholar
  8. Chan AS (1992) Association of nerve fibres with myoid cells in the chick thymus. J Anat 181(Pt 3):509–512Google Scholar
  9. Chetty R, Reddi A (2003) Rhabdomyomatous multilocular thymic cyst. Am J Clin Pathol 119(6):816–821. Google Scholar
  10. Clarke PG, Clarke S (2012) Nineteenth century research on cell death. Exp Oncol 34(3):139–145Google Scholar
  11. Cron MA, Maillard S, Villegas J, Truffault F, Sudres M, Dragin N, Berrih-Aknin S, Le Panse R (2018) Thymus involvement in early-onset myasthenia gravis. Ann N Y Acad Sci 1412(1):137–145. Google Scholar
  12. Cui D (2011) Atlas of histology with Functional & Clinical Correlations, 1st edn. Wolters Kluwer Lippincott Williams & Wilkins, BaltimoreGoogle Scholar
  13. Díaz-Flores L, Gutiérrez R, Varela H, Rancel N, Valladares F (1991) Microvascular pericytes: a review of their morphological and functional characteristics. Histol Histopathol 6(2):269–286Google Scholar
  14. Eroschenko VP (2012) diFiore’s atlas of histology with functional correlations, 12th edn. Wolters Kluwer Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  15. FIPAT, Federative International Programme on Anatomical Terminology (2008) Terminologia Histologica: international terms for human cytology and histology. Lippincott Williams & WilkinsGoogle Scholar
  16. FIPAT, Federative International Programme on Anatomical Terminology (2017) Terminologia Embryologica, 2nd Edition. Accessed 3 Nov. 2018
  17. Furuya A, Kobayashi T, Kameda N, Tsukagoshi H (1991) Human myasthenia gravis thymic myoid cells: de novo immunohistochemical and intracellular electrophysiological studies. J Neurol Sci 101(2):208–220Google Scholar
  18. Gannon BR, Dexter DF, Petsikas D, Isotalo PA (2007) Mediastinal thymolipoma: a rare occurrence with striated myoid cells. Tumori 93(2):198–200Google Scholar
  19. Gartner LP (2018) Color atlas and text of histology, 7th edn. Wolters Kluwer, PhiladelphiaGoogle Scholar
  20. Grim M, Naňka O, Černý K (2014) Anatomie od Vesalia po současnost (1517–2014). (monography in Czech; anatomy from Vesalius to nowadays). Grada publishing, PragueGoogle Scholar
  21. Gülmez N, Aslan Ş (1999) Histological and Histometrical investigations on Bursa of Fabricius and Thymus of native geese. Turk J Vet Anim Sci 23(2):163–171Google Scholar
  22. Hammar JA (1905) Zur Histogenese und Involution der Thymusdrüse. Anat Anz 37:41–89Google Scholar
  23. Hanzliková V (1979) Histochemical and ultrastructural properties of myoid cells in the thymus of the frog. Cell Tissue Res 197(1):105–112Google Scholar
  24. Hu B, Simon-Keller K, Küffer S, Ströbel P, Braun T, Marx A, Porubsky S (2016) Myf5 and Myogenin in the development of thymic myoid cells - implications for a murine in vivo model of myasthenia gravis. Exp Neurol 277:76–85. Google Scholar
  25. Iseki M, Tsuda N, Kishikawa M, Shimada O, Hayashi T, Kawahara K, Tomita M (1990) Thymolipoma with striated myoid cells. Histological, immunohistochemical, and ultrastructural study. Am J Surg Pathol 14(4):395–398Google Scholar
  26. Itoh T (1983) Establishment of a myoid cell clone from rat thymus. Cell Tissue Res 231(1):39–47Google Scholar
  27. Ito T, Hoshino T, Abe K (1969) The fine structure of myoid cells in the human thymus. Arch Histol Jpn 30(2):207–215Google Scholar
  28. Iwakami N, Kikuchi A, Kunishita T, Yamamoto H, Nonaka I, Kamo I (1996) Analysis of lymphoproliferative cytokines produced by thymic myoid cells. Immunology 87(1):108–112Google Scholar
  29. Jablonska-Mestanova V, Sisovsky V, Danisovic L, Polak S, Varga I (2013) The normal human newborns thymus. Bratisl Lek Listy 114(7):402–408Google Scholar
  30. Kamo I, Tada-Kikuchi A, Furukawa S, Iwasaki Y, Nonaka I, Satoyoshi E, Itoh T (1985) Effects of thymic myoid cell culture supernatant on cells from lymphatic tissues. Cell Immunol 94(2):587–597Google Scholar
  31. Kamo I, Kunishita T, Kikuchi A, Nonaka I, Komiyama A (1993) Characterization of a macrophage lineage cell colony-stimulating factor produced by thymic myoid cells. Immunology 79(1):103–106Google Scholar
  32. Katoh Y, Ito T, Shimada Y, Ohnuma-Koyama A, Takahashi N, Okazaki Y, Shiga A, Kuwahara M, Yoshida T, Harada T (2018) Spontaneous malignant myoid thymoma in an aged female Fischer 344 rat. J Toxicol Pathol 31(2):135–139. Google Scholar
  33. Kierszenbaum AL, Tres LL (2016) Histology and cell biology. An Introduction to Pathology, 4th edn. Elsevier Saunders, PhiladelphiaGoogle Scholar
  34. Kirchner T, Hoppe F, Schalke B, Müller-Hermelink HK (1988) Microenvironment of thymic myoid cells in myasthenia gravis. Virchows Arch B Cell Pathol Incl Mol Pathol 54(5):295–302Google Scholar
  35. Lambropoulou M, Tamiolakis D, Venizelos I, Alexiadis G, Limberis V, Galazios G, Tsikouras P, Karamanidis D, Koutsougeras G, Nikolaidou S, Petrakis G, Papadopoulos H, Papadopoulos N (2007) A stromal myoid cell line provokes thymic T-cell immigration at the second and third gestational trimesters. Rev Med Chir Soc Med Nat Iasi 111(3):710–716Google Scholar
  36. Le Panse R, Berrih-Aknin S (2005) Thymic myoid cells protect thymocytes from apoptosis and modulate their differentiation: implication of the ERK and Akt signaling pathways. Cell Death Differ 12:463–472. Google Scholar
  37. Le Panse-Ruskoné R, Berrih-Aknin S (2003) Human myoid cells protect thymocytes from apoptosis. Ann N Y Acad Sci 998:266–269Google Scholar
  38. Leboffe MJ (2013) A photographic atlas of histology, 2nd edn. Morton Publishing, EnlewoodGoogle Scholar
  39. Leite MI, Jones M, Ströbel P, Marx A, Gold R, Niks E, Verschuuren JJ, Berrih-Aknin S, Scaravilli F, Canelhas A, Morgan BP, Vincent A, Willcox N (2007) Myasthenia gravis thymus: complement vulnerability of epithelial and myoid cells, complement attack on them, and correlations with autoantibody status. Am J Pathol 171(3):893–905. Google Scholar
  40. Liu D, Ellis H (2016) The mystery of the thymus gland. Clin Anat 29(6):679–684. Google Scholar
  41. Lowe JS, Anderson PG (2015) Stevens & Lowe’s human histology, 4th edn. Elsevier Mosby, PhiladelphiaGoogle Scholar
  42. Lüllmann-Rauch R (2009) Taschenlehrbuch Histologie, 3. Auflage. Georg Thieme Verlag, StuttgartGoogle Scholar
  43. Marx A, Osborn M, Tzartos S, Geuder KI, Schalke B, Nix W, Kirchner T, Müller-Hermelink HK (1992) A striational muscle antigen and myasthenia gravis-associated thymomas share an acetylcholine-receptor epitope. Dev Immunol 2(2):77–84Google Scholar
  44. Marx A, Pfister F, Schalke B, Saruhan-Direskeneli G, Melms A, Ströbel P (2013) The different roles of the thymus in the pathogenesis of the various myasthenia gravis subtypes. Autoimmun Rev 12(9):875–884. Google Scholar
  45. Marx A, Porubsky S, Belharazem D, Saruhan-Direskeneli G, Schalke B, Ströbel P, Weis CA (2015) Thymoma related myasthenia gravis in humans and potential animal models. Exp Neurol 270:55–65. Google Scholar
  46. Matsumoto MY, Matsuo H, Oka T, Fukudome T, Hayashi K, Shiraishi H, Motomura M, Shibuya N, Ayabe H (2004) Thymic myoid cells as a myasthenogenic antigen and antigen-presenting cells. J Neuroimmunol 150(1–2):80–87Google Scholar
  47. Mayer S (1886) Die sogennanten Sarkoplasten. Anat Anz 1(9):231–235Google Scholar
  48. Mayer S (1888) Zur Lehre von der Schilddrüse und Thymus bei Amphibien. Anat Anz 3:97–103Google Scholar
  49. Mescher AL (2016) Junqueira’s basic histology. Text and Atlas, 14th edn. McGraw Hill Education, New YorkGoogle Scholar
  50. Mesnard-Rouiller L, Bismuth J, Wakkach A, Poëa-Guyon S, Berrih-Aknin S (2004) Thymic myoid cells express high levels of muscle genes. J Neuroimmunol 148(1–2):97–105. Google Scholar
  51. Mikušová R, Mešťanová V, Polák Š, Varga I (2017) What do we know about the structure of human thymic Hassall's corpuscles? A histochemical, immunohistochemical, and electron microscopic study. Ann Anat 211:140–148. Google Scholar
  52. Miller JF (1961) (1961) immunological function of the thymus. Lancet. 2(7205):748–749Google Scholar
  53. Mills SE (ed) (2012) Histology for pathologists, 4th edn. Wolter Kluwer Lippincott Williams & Wilkins, PhiladelphiaGoogle Scholar
  54. Mohammad MG, Chilmonczyk S, Birch D, Aladaileh S, Raftos D, Joss J (2007) Anatomy and cytology of the thymus in juvenile Australian lungfish, Neoceratodus forsteri. J Anat 211(6):784–797. Google Scholar
  55. Nakamura H, Ayer-Le Liére C (1986) Neural crest and thymic myoid cells. Curr Top Dev Biol 20:111–115Google Scholar
  56. Nishijima Y, Hirato J, Fukuda T (2017) Pleomorphic rhabdomyosarcoma arising in the anterior mediastinum: a case report with cytological features of imprint and liquid-based cytology specimens. Diagn Cytopathol 45(4):333–338. Google Scholar
  57. Oka T, Hayashi K, Nakaoka Y, Ohtsuki Y, Akagi T (2000) Differentiation of rat thymic myoid progenitor cell line established by coculture with human T-lymphotropic virus type-I-producing human T cells. Cell Tissue Res 300(1):119–127Google Scholar
  58. Oláh I, Röhlich P, Töró I (1975) Ultrastructure of lymphoid organs. An electron-microscopic atlas. Akadémia Kiadó, BudapestGoogle Scholar
  59. Ovalle WK, Nahirney PC (2013) Netter’s essential histology, 2nd edn. Elsevier Saunders, PhiladelphiaGoogle Scholar
  60. Pagel CN, Morgan JE, Gross JG, Partridge TA (2000) Thymic myoid cells as a source of cells for myoblast transfer. Cell Transplant 9(4):531–538Google Scholar
  61. Pensa A (1902) Osservazioni a propostio di una particolarità di struttura del Timo. Nota preventive. Bolletino della Società medico-chirurgica di PaviaGoogle Scholar
  62. Pensa A (1904) Ancora a proposito di una particolarità distruttura del timo ed osservazioni sullo sviluppo del timo negli Anfibi Anuri. Boll. Soc. med.-chir. PaviaGoogle Scholar
  63. Pensa A (1905) Osservazioni sulla struttura del timo. Anat Anz 27:529–541Google Scholar
  64. Puchtler H, Meloan SN, Branch BW, Gropp S (1975) Myoepithelial cells in human thymus: staining, polarization and fluorescence microscopic studies. Histochemistry 45(2):163–176Google Scholar
  65. Raviola E, Raviola G (1967) Striated muscle cells in the thymus of reptiles and birds: an electron microscopic study. Am J Anat 121(3):623–645Google Scholar
  66. Roche PA, Furuta K (2015) The ins and outs of MHC class II-mediated antigen processing and presentation. Nat Rev Immunol 15(4):203–216. Google Scholar
  67. Ross MH, Pawlina W (2016) Histology. A text and atlas with correlated cell and molecular biology, 7th edn. Wolter Kluwer Health, PhiladelphiaGoogle Scholar
  68. Roxanis I, Micklem K, McConville J, Newsom-Davis J, Willcox N (2002) Thymic myoid cells and germinal center formation in myasthenia gravis; possible roles in pathogenesis. J Neuroimmunol 125(1–2):185–197Google Scholar
  69. Saad AH, Zapata A (1992) Reptilian thymus gland: an ultrastructural overview. Thymus 20(3):135–152Google Scholar
  70. Sato T, Tamaoki N (1989) Myoid cells in the human thymus and thymoma revealed by three different immunohistochemical markers for striated muscle. Acta Pathol Jpn 39(8):509–519Google Scholar
  71. Schaffer G (1893) Über den feineren Bau der Thymus und deren Beziehungen zur Blutbildung. Vorläufige Mitteilung. Sitzungsber. D. Math.-Naturw. Klasse d. Kais. Akad. D. Wiss., Bd. CII, Abt. III, WienGoogle Scholar
  72. Schluep M, Willcox N, Vincent A, Dhoot GK, Newsom-Davis J (1987) Acetylcholine receptors in human thymic myoid cells in situ: an immunohistological study. Ann Neurol 22(2):212–222. Google Scholar
  73. Shahzad A, Khan A, Khan MZ, Mahmood F, Gul ST, Saleemi MK (2015) Immuno-pathologic effects of oral administration of chlorpyrifos in broiler chicks. J Immunotoxicol 12(1):16–23Google Scholar
  74. Sidhu JS, Nicolas MM, Taylor W (2002) Mediastinal rhabdomyoma: a case report and review of the literature. Int J Surg Pathol 10(4):313–318. Google Scholar
  75. Standring S (Ed) (2016) Gray’s anatomy. The anatomical basis of clinical practice, Forty-first ed. ElsevierGoogle Scholar
  76. Starost MF, Tsang K, Zerfas PM, Stratakis CA (2010) A rhabdomyoma within a multilocular thymic cyst in a p53-null mouse. Vet Pathol 47(1):132–136. Google Scholar
  77. Strauss AJ, Kemp PG, Douglas SD (1966) Myasthenia gravis. Lancet 1(7440):772–773Google Scholar
  78. Sugimura M (1972) Myoid cells in the calf's thymus. Jpn J Vet Res 20(1):1–6Google Scholar
  79. Suster S, Moran CA, Koss MN (1994) Rhabdomyosarcomas of the anterior mediastinum: report of four cases unassociated with germ cell, teratomatous, or thymic carcinomatous components. Hum Pathol 25(4):349–356Google Scholar
  80. Tamiolakis D, Venizelos J, Kotini A, Karamanidis D, Boglou P, Papadopoulos N (2004) A stromal myoid cell line provokes thymic erythropoiesis between 16th to 20th weeks of intrauterine life. East Afr Med J 81(2):78–81Google Scholar
  81. Töró I, Oláh I, Röhlich P, Virágh S (1969) Electron microscopic observations on myoid cells of the frog's thymus. Anat Rec 165(3):329–341Google Scholar
  82. Van de Velde RL, Friedman NB (1966) The thymic "myoidzellen" and myasthenia gravis. JAMA 198(3):287–288Google Scholar
  83. Van de Velde RL, Friedman NB (1970) Thymic myoid cells and myasthenia gravis. Am J Pathol 59(2):347–368Google Scholar
  84. Varga I, Mikusova R, Pospisilova V, Galfiova P, Adamkov M, Polak S, Galbavy S (2009) Morphologic heterogeneity of human thymic nonlymphocytic cells. Neuro Endocrinol Lett 30(3):275–283Google Scholar
  85. Varga I, Blankova A, Konarik M, Baca V, Dvorakova V, Musil V (2018) The Terminologia Histologica after 10 years: inconsistencies, mistakes, and new proposals. Ann Anat 219:65–75Google Scholar
  86. Wakkach A, Poea S, Chastre E, Gespach C, Lecerf F, de la Porte S, Tzartos S, Coulombe A, Berrih-Aknin S (1999) Establishment of a human thymic myoid cell line. Phenotypic and functional characteristics. Am J Pathol 155(4):1229–1240Google Scholar
  87. Weissenberg R (1907) Über die quergestreiften Zellen der Thymus. Arch Mikrosk Anat 70:193–226Google Scholar
  88. Wekerle H, Ketelsen UP (1977) Intrathymic pathogenesis and dual genetic control of myasthenia gravis. Lancet 1(8013):678–680Google Scholar
  89. Wekerle TH, Paterson B, Ketelsen U, Feldman M (1975) Striated muscle fibres differentiate in monolayer cultures of adult thymus reticulum. Nature 256(5517):493–494Google Scholar
  90. Wekerle H, Ketelsen UP, Zurn AD, Fulpius BW (1978) Intrathymic pathogenesis of myasthenia gravis: transient expression of acetylcholine receptors on thymus-derived myogenic cells. Eur J Immunol 8(8):579–582Google Scholar
  91. Young B, O’Dowd G, Woodford P (2014) Wheater’s functional histology. A Text and Colour Atlas, 6th edn. Elsevier Churchill Livingstone, PhiladelphiaGoogle Scholar
  92. Zolota V, Tzelepi V, Charoulis N, Apostolakis E, Dougenis D (2006) Mediastinal rhabdomyoma: case report and review of the literature. Virchows Arch 449(1):124–128. Google Scholar

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© Institute of Molecular Biology, Slovak Academy of Sciences 2019

Authors and Affiliations

  • Ivan Varga
    • 1
    Email author
  • Ildikó Bódi
    • 2
  • David Kachlík
    • 3
  • Veronika Mešťanová
    • 4
  • Martin Klein
    • 1
  1. 1.Institute of Histology and Embryology, Faculty of MedicineComenius University in BratislavaBratislavaSlovakia
  2. 2.Department of Anatomy, Histology, and Embryology, Faculty of MedicineSemmelweis UniversityBudapestHungary
  3. 3.Department of Anatomy, Second Faculty of MedicineCharles UniversityPrahaCzech Republic
  4. 4.Institute of Histology and Embryology, Jessenius Faculty of Medicine in MartinComenius University in BratislavaMartinSlovakia

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