Review and proposal for classification of the congenital anomalies of thymus in children

Czech version

Authors: I. Varga ¹; L. Plank ²; V. Mešťanová ³; L. Zábojníková ⁴
Authors‘ workplace: Ústav histológie a embryológie, Lekárska fakulta, Univerzita Komenského, Bratislavaprednosta doc. MUDr. Š. Polák, CSc. ¹; Ústav patologickej anatómie, Jesseniova lekárska fakulta v Martine, Univerzita Komenského, Bratislavavedúci prof. MUDr. L. Plank, CSc. ²; Ústav histológie a embryológie, Jesseniova lekárska fakulta v Martine, Univerzita Komenského, Bratislavavedúci prof. MUDr. M. Adamkov, CSc. ³; Klinika detskej chirurgie, Detská fakultná nemocnica s poliklinikou a Lekárska fakulta, Univerzita Komenského, Bratislavaprednosta doc. MUDr. J. Trnka, CSc. ⁴
Published in: Čes-slov Pediat 2014; 69 (3): 178-190.
Category: Review

Overview

Thymus is a central lymphoid organ with an important endocrine function located in the superior mediastinum, but in newborns it caudally reaches to anterior mediastinum. Thymic morphology varies greatly even in the same age group. For instance, in young adults, it is typically bilobed and V-shaped, with two small processes extending into the neck. Anomalies of the thymic shape, size and localization are explained by the disruption of thymic primordia formation and/or disruption of its descent from the neck to the mediastinum. The most common thymic anomalies include anomalies in number of the thymic lobes, ectopic thymus, accessory thymic tissue, thymic aplasia, thymoparathyroid aplasia (DiGeorge syndrome), thymic hypoplasia and hyperplasia. In a case of ectopic thymus, the whole thymus is (most often) located in the midline neck, and no thymic tissue is located in the normal position in the mediastinum. The presence of accessory thymic tissue reflects a failed migration of the whole thymic primordia from the third pharyngeal pouches. It may be found at any level of the pathway of normal thymic descent, from the angle of the mandible to the superior mediastinum. The prevalence of foci of accessory thymic tissue varies according to several authors from 1.8% up to more than 50%.

A great controversy about the terms being used in the classification of thymic anomalies arises in current literature. Most of the recent articles use the term “ectopic thymus” in a confusing way, because they call cervical extension of the thymus, accessory cervical lobes of the thymus or accessory thymic tissue also “ectopic thymus”. The “genuine” ectopic thymus is a distinct entity from accessory thymic tissue localized in the neck. The term “ectopic thymus” should be reserved for states where only ectopic thymic tissue is present, while no thymus tissue is localized in the normal, mediastinal position. These two entities are differentiated also according to the recommendation of the Terminologia Embryologica (ectopia thymi versus textus thymicus accessorius). A cystic version of accessory thymic tissue localized in the neck is called “congenital cervical thymic cyst”. The cystic version of aberrant thymic tissue is more often described in the literature than the “classical” solid form. Thymopharyngeal duct cyst is another special and extremely rare variant of cystic accessory thymic tissue. Only circa 5 cases are described in the literature. Relatively common and asymptomatic anatomical variation is the fusion of thymus with one or more parathyroid glands - much common with the inferior due to common embryonic origin of both organs.

Key-words:
accessory thymic tissue, DiGeorge syndrome, ectopic thymus, embryonic development, human thymus, Terminologia Embryologica

Sources

1. Dorko F, Varga I. Vývin a inervácia týmusu. Týmus z pohľadu anatómie, histológie a embryológie. Bratislava: Asklepios, 2011: 1-136. ISBN 978-80-7167-156-5.

2. Polák Š, Varga I. Funkčná histológia, vývin a evolúcia lymfatického systému človeka (s klinicko - anatomickými koreláciami). Učebné texty pre pregraduálne a postgraduálne štúdium na lekárskych a prírodovedeckých fakultách. Bratislava: Univerzita Komenského, 2013: 1–130. ISBN 978-80-223-3358-0.

3. Polák Š, Varga I. Lymphatic tissue and organs. In: Adamkov M (Ed). Introduction to Functional Histology. Martin: P+M Turany, 2013: 271–300. ISBN 978-80--89410-25-5.

4. Varga I, Mikušová R, Pospíšilová V, et al. Morphologic heterogeneity of human thymic nonlymphocytic cells. Neuroendocrinol Lett 2009; 30 (3): 275–283.

5. Rezzani R, Nardo L, Favero G, et al. Thymus and aging: morphological, radiological, and functional overview. Age (Dordr) 2014. 36 (1):313–351.

6. Rezzani R, Bonomini F, Rodella LF. Histochemical and molecular overview of the thymus as site for T-cells development. Prog Histochem Cytochem 2008; 43: 73–120.

7. Manley NR, Richie ER, Blackburn CC, et al. Structure and function of the thymic microenvironment. Front Biosci (Landmark Ed) 2011; 16: 2461–2477.

8. Ventevogel MS, Sempowski GD. Thymic rejuvenation and aging. Curr Opin Immunol 2013; 25 (4): 516–522.

9. Wolf E, Milazzo S, Boehm K, et al. Thymic peptides for treatment of cancer patients. Cochrane Database Syst Rev 2011; (2): CD003993.

10. Lunin SM, Novoselova EG. Thymus hormones as prospective anti-inflammatory agents. Expert Opin Ther Targets 2010; 14 (8): 775–786.

11. Bodey B. Thymic reticulo-epithelial cells: key cells of neuroendocrine regulation. Expert Opin Biol Ther 2007; 7 (7): 939–949.

12. Weerkamp F, De Haas EFE, Naber BAE, et al. Age related changes in cellular composition of the thymus in children. J Allergy Clin Immunol 2005; 115 (4): 834–840.

13. Bodey B, Bodey B Jr, Siegel S, Keiser HE. Involution of the mammalian thymus, one of the leading regulators of aging. In Vivo 1997; 11: 421–440.

14. Kendall MD, Johnson HR, Singh J. The weight of the human thymus gland at necropsy. J Anat 1981; 131: 483–485.

15. Steinmann GG. Changes in the human thymus during aging. In: Müller-Hermelink HK (Ed). The Human Thymus. Histophysiology and Pathology. Berlin: Springer-Verlag, 1986: 43–88. ISBN 3-540-15311-X.

16. Dorko F, Kluchová D, Boleková A, et al. Influence of surgical and chemical orchidectomy on weight and distribution of AChE-nerve fibres in thymuses of adult rats. Eur J Histochem 2011; 55 (3): e22.

17. Pazirandeh A, Jondal M, Okret S. Glucocorticoids delay age-associated thymic involution through directly affecting the thymocytes. Endocrinol 2004; 145 (5): 2392–2401.

18. Varga I, Uhrinova A, Toth F, Mistinova J. Assessment of the thymic morphometry using ultrasound in full-term newborns. Surg Radiol Anat 2011; 33 (8): 689–-695.

19. Nasseri F, Eftekhari F. Clinical and radiologic review of the normal and abnormal thymus: pearls and pitfalls. Radiographics 2010; 30 (2): 413–428.

20. Pospíšilová V, Varga I, Gálfiová P, Polák Š. Morfologický pohľad na ontogenézu týmusu človeka. Čes-slov Pediat 2008; 63 (4): 201–208.

21. Gordon J, Manley NR. Mechanisms of thymus organogenesis and morphogenesis. Development 2011; 138 (18): 3865–3878.

22. Bodey B, Siegel SE, Kaiser HE. Embryology of the mammalian thymus. In: Bodey B, Siegel SE, Kaiser HE. Immunological Aspects of Meoplasia – The Role of the Thymus. Dordrecht: Kluwe Academic Publishers, 2004: 5–14. ISBN 1-4020-2184-4.

23. Varga I, Pospíšilová V, Gmitterová K, Gálfiová P, Polák Š, Galbavý Š. The phylogenesis and ontogenesis of the human pharyngeal region focused on the thymus, parathyroid, and thyroid glands. Neuroendocrinol Lett 2008; 29 (6): 837–845.

24. Varga I, Pospisilova V, Jablonska V, Gálfiová P, Polak S. The thymus: Picture review of human thymus prenatal development. Bratisl lek Listy 2011; 112 (7): 368–372.

25. Varga I, Jablonska-Mestanova V, Galfiova P, Polak S, Adamkov M. Some aspects of early development of thymus: embryological basis for ectopic thymus and thymopharyngeal duct cyst. Rev Arg de Anat Clin 2011; 3 (1): 22–31.

26. Boehm T. Thymus development and function. Curr Opin Immunol 2008; 20: 178–184.

27. Manley NR, Blackburn CC. A development look at thymus organogenesis: where do the non-hematopoietic cell in the thymus come from? Curr Opin Immunol 2003; 15 (2): 225–232.

28. Shashiraj, Aggarwal A. Undescended thymus presenting as midline neck swelling. Indian J Pediatr 2005; 72 (1): 86.

29. Liu D, Kitajima M, Awai K, et al. Ectopic cervical thymus in an infant. Radiat Med 2006; 24 (6): 452–455.

30. Wurdak H, Ittner LM, Sommer L. DiGeorge syndrome and pharyngeal apparatus development. Bioessays 2006; 28 (11): 1078–1086.

31. Gennery AR. Immunological aspects of 22q11.2 deletion syndrome. Cell Mol Life Sci 2012; 69 (1): 17–27.

32. Carneiro-Sampaio M, Moraes-Vasconcelos D, Kokron CM, et al. Primary immunodeficiency diseases in different age groups: a report on 1,008 cases from a single Brazilian reference center. J Clin Immunol 2013; 33 (4): 716–724.

33. Fomin AB, Pastorino AC, Kim CA, et al. DiGeorge Syndrome: a not so rare disease. Clinics (Sao Paulo) 2010; 65 (9): 865–869.

34. Varga I, Pospíšilová V, Tóth F, et al. Factors affecting child thymus size and involution. Čes-slov Pediat 2008; 93 (4): 209–214.

35. Zajratjanc OV, Serov VV, Kuzmenko LG. The pathogenesis of congenital thymus hyperplasia in children with immune defects. Zentralbl Allg Pathol 1990; 136 (7–8): 689–702.

36. Zaĭrat‘iants OV. The thymo-lymphatic system in congenital thymomegaly (clinico-morphological study). Arkh Patol 1988; 50 (4): 17–25.

37. Tertychnyĭ AS, Talalaev AG, Zaĭrat‘iants OV. Syndrome of enlarged thymus gland in children with congenital heart defects. Arkh Patol 2001; 63 (2): 39–43.

38. Jacobs MT, Frush DP, Donelly LF. The right place at the wrong time: historical perspective of the relation of the thymus gland and pediatric radiology. Radiology 1999; 210: 11–16.

39. Nishino M, Ashiku SK, Kocher ON, Thurer RL, Boiselle PM, Hatabu H. The thymus: a comprehensive review. RadioGraphics 2006; 26: 335–348.

40. Choyke PL, Zeman RK, Gootenberg JE, et al. Thymic atrophy and regrowth in response to chemotherapy: CT evaluation. Am J Roentgenol 1987; 149 (2): 269–272.

41. Yarom N, Zissin R, Apter S, et al. Rebound thymic enlargement on CT in adults. Int J Clin Pract 2007; 61 (4): 562–568.

42. Scheinpflug K, Schmitt J, Jentsch-Ullrich K, et al. Thymic hyperplasia following successful treatment for nodular-sclerosing Hodgkin‘s disease. Leuk -Lymphoma 2003; 44 (9): 1615–1617.

43. Federative International Programme on Anatomical Terminology. Terminologia Embryologica: International Anatomical Terminology. Thieme, 2013: 1–312. ISBN-10: 3131701412.

44. Anastasiadis K, Ratnatunga C (eds). The thymus gland. Diagnosis and surgical treatment. Berlin: Springer--Verlag, 2007: 1–112. ISBN 978-3-540-33425-5.

45. Jaretzki A 3rd. Thymectomy for myasthenia gravis; analysis of controversies regarding technique and results. Neurology 1997; 48 (Suppl 5): S52–S63.

46. Durmaz E, Barsal E, Parlak M, et al. Intrathyroidal ectopic thymic tissue may mimic thyroid cancer: a case report. J Pediatr Endocrinol Metab 2012; 25 (9–10): 997–1000.

47. Sapthavee A, Kulbersh B, Maddalozzo J, Bogard A. Pathology quiz case 1: ectopic intrathyroidal thymic tissue. JAMA Otolaryngol Head Neck Surg 2013; 139 (1): 87–88.

48. Kim HG, Kim MJ, Lee MJ. Sonographic appearance of intrathyroid ectopic thymus in children. J Clin Ultrasound 2012; 40 (5): 266–271.

49. Yerly S, Lobrinus JA, Bongiovanni M, et al. A carcinoma showing thymus-like elements of the thyroid arising in close association with solid cell nests: evidence for a precursor lesion? Thyroid 2013; 23 (4): 511–516.

50. Roka S, Kornek G, Schüller J, et al. Carcinoma showing thymic-like elements - a rare malignancy of the thyroid gland. Br J Surg 2004; 91 (2): 142–145.

51. Nolder AR, Agarwal A, Howard E, Richter GT. Ectopic thymus presenting as a retropharyngeal mass: surgical approach. Ear Nose Throat J 2013; 92 (1): 41–43.

52. Park JJ, Kim JW, Kim JP, et al. Two cases of ectopic cervical thymus: case reports and a review of the literature. Auris Nasus Larynx 2006; 33 (1): 101–105.

53. Saggese D, Ceroni Compadretti G, Cartaroni C. Cervical ectopic thymus: a case report and review of the literature. Int J Pediatr Otorhinolaryngol 2002; 66: 77–80.

54. Mizia-Malarz A, Sobol G, Maldyk J, et al. Cervical ectopic thymus in a 9-month-old girl: diagnostic difficulties. J Pediatr Hematol Oncol 2009; 31 (8): 599–601.

55. Bistritzer T, Tamir A, Oland J, et al. Severe dyspnea and dysphagia resulting from an aberrant cervical thymus. Eur J Pediatr 1985; 144: 86–87.

56. Felgentreff K, Schupp W, Otten JE, et al. Inspiratory stridor and dysphagia in two newborn infants caused by ectopic thymus tissue. Eur J Pediatr 2009; 168 (9): 1141–1145.

57. Shah SS, Lai SY, Ruchelli E, et al. Retropharyngeal aberrant thymus. Pediatrics 2001; 108: 94–97.

58. Prasad TRS, Chui CH, Ong CL, Meenakshi A. Cervical ectopic thymus in an infant. Singapore Med J 2006; 47: 68–70.

59. Conwell LS, Batch JA. Aberrant cervical thymus mimicking a cervical mass. J Paediatr Child Health 2004; 40: 579–580.

60. Pai I, Hegde V, Wilson PO, et al. Ectopic thymus presenting as a subglottic mass: diagnostic and management dilemmas. Int J Pediatr Otorhinolaryngol 2005; 69 (4): 573–576.

61. Jiang L, Sun B, Zheng Y, Du L. Posterior mediastinal thymus: case report and literature review. Iran J Pediatr 2011; 21 (3): 404–408.

62. Cigliano B, Baltogiannis N, De Marco M, et al. Cervical thymic cysts. Pediatr Surg Int 2007; 23 (12): 1219–1225.

63. Meyer E, Mulwafu W, Fagan JJ, et al. Ectopic thymic tissue presenting as a neck mass in children: a report of 3 cases. Ear Nose Throat J 2010; 89 (5): 228–231.

64. Saad AH, Zapata A. Reptilian thymus gland: an ultrastructural overview. Thymus 1992; 20 (3): 135–152.

65. Bigaj J, Plytycz B. Cytoarchitecture of the thymus gland of the adult frog (Rana temporaria). Folia Histochem Cytobiol 1984; 22 (1): 63–69.

66. Ors U, Dagdeviren A, Kaymaz FF, Muftuoglu SF. Cysts in human thymus: maturational forms of Hassal´s corpuscles? Okajimas Folia Anat Jpn 1999; 76: 61–69.

67. Burton EM, Mercado-Deane MG, Howell CG, et al. Cervical thymic cysts: CT appearance of two cases including a persistent thymopharyngeal duct cyst. Pediatr Radiol 1995; 25: 363–365.

68. Zarbo RJ, McClatchey KD, Areen RG, Baker SB. Thymopharyngeal duct cyst: a form of cervical thymus. Ann Otol Rhinol Laryngol 1983; 92: 284–289.

69. Kaufman MR, Smith S, Rothschild MA, Som P. Thymopharyngeal duct cyst: an unusual variant of cervical thymic anomalies. Arch Otolaryngol Head Neck Surg 2001; 127: 1357–1360.

70. Noussios G, Anagnostis P, Natsis K. Ectopic parathyroid glands and their anatomical, clinical and surgical implications. Exp Clin Endocrinol Diabetes 2012; 20 (10): 604–610.

71. Hojaij F, Vanderlei F, Plopper C, et al. Parathyroid gland anatomical distribution and relation to anthropometric and demographic parameters: a cadaveric study. Anat Sci Int 2011; 86 (4): 204–212.

72. Yamashita H, Murakami N, Noguchi S, et al. Cervical thymoma and incidence of cervical thymus. Acta Pathol Jpn 1983; 33 (1): 189–194.

73. Tabatabaie SA, Hashemi SM, Sanei B, Sanei MH. The frequency of ectopic thymic tissue in the necks of patients without any thymic disease. Med Sci Monit 2007; 13 (6): CR283–285.

74. Jaretzki A 3rd, Wolff M. „Maximal“ thymectomy for myasthenia gravis. Surgical anatomy and operative technique. J Thorac Cardiovasc Surg 1988; 96 (5): 711–716.

75. Ashour M. Prevalence of ectopic thymic tissue in myasthenia gravis and its clinical significance. J Thorac Cardiovasc Surg 1995; 109 (4): 632–635.

76. Fukai I, Funato Y, Mizuno T, et al. Distribution of thymic tissue in the mediastinal adipose tissue. J Thorac Cardiovasc Surg 1991; 101 (6):1099–1102.

77. Zieliński M, Kuzdzal J, Szlubowski A, Soja J. Comparison of late results of basic transsternal and extended transsternal thymectomies in the treatment of myasthenia gravis. Ann Thorac Surg 2004; 78: 253–258.

78. De Foer B, Vercruysse JP, Mariën P, et al. Cervical ectopic thymus presenting as a painless neck mass in a child. JBR-BTR 2007; 90 (4): 281–283.

79. Clark JJ, Johnson SM. Solid cervical ectopic thymus in an infant. J Pediatr Surg 2009; 44 (7): e19–21.

80. Wang J, Fu H, Yang H, et al. Clinical management of cervical ectopic thymus in children. J Pediatr Surg 2011; 46 (8): e33–36.

Labels

Neonatology Paediatrics General practitioner for children and adolescents

Diagnostic monitoring and RSV infection epidemiology in Slovakia

The incidence of anaemia and the use of the ELISA method for measuring hepcidin levels in children with inflammatory bowel disease

Cholesteryl Ester Storage Disease (CESD): clinical, laboratory and histological characteristics in 6 patients

Hypertension-associated asymptomatic hyperuricaemia in the adolescents

Methotrexate update 2014: 70 years in autoimmunity and cancer treatment

Article was published in

Czech-Slovak Pediatrics

2014 Issue 3