Abstract
The chapter on Nonneoplastic Thymic Lesions will cover the epidemiological, etiological and clinicopathological features of common thymic lesions (congenital and acquired cysts, including dysplasia); thymic follicular, rebound and “true” hyperplasia) as well as rare or recently described non-neoplastic thymic alterations that may form mass lesions and can mimic thymic neoplasms (“Lesa-like thymic hyperplasia”; “Cholesteroloma”; Fibrosing mediastinitis, including IgG4-related disease). Criteria concerning the broad spectrum of differential diagnoses will be highlighted.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Kozu Y, et al. Single institutional experience with primary mediastinal cysts: clinicopathological study of 108 resected cases. Ann Thorac Cardiovasc Surg. 2014;20(5):365–9.
Esme H, et al. Primary mediastinal cysts: clinical evaluation and surgical results of 32 cases. Tex Heart Inst J. 2011;38(4):371–4.
Aydin Y, et al. Surgical treatment of mediastinal cysts: report on 29 cases. Acta Chir Belg. 2012;112(4):281–6.
Kelleher CM, et al. Case records of the Massachusetts general hospital. Case 10-2012. A 16-year-old boy with epigastric pain and a mediastinal mass. N Engl J Med. 2012;366(13):1241–9.
Takeda S, et al. Clinical spectrum of primary mediastinal tumors: a comparison of adult and pediatric populations at a single Japanese institution. J Surg Oncol. 2003;83(1):24–30.
Nam JG, et al. Age- and gender-specific disease distribution and the diagnostic accuracy of CT for resected anterior mediastinal lesions. Thorac Cancer. 2019;10(6):1378–87.
Rosai J, Levine GD. Tumors of the thymus. In: Firminger HI, editor. Atlas of tumor pathology, vol. 13. 2nd ed. Washington, D.C.: Armed Forces Institute of Pathology; 1976. p. 228.
Haro Estarriol M, et al. Spontaneous resolution of a primary thymic cyst. An Med Interna. 2003;20(10):552–3.
Schweigert M, et al. Thymoma within a giant congenital thymic cyst. Interact Cardiovasc Thorac Surg. 2011;13(4):442–3.
Kitami A, et al. Thymoma with intracystic dissemination arising in a unilocular thymic cyst. Gen Thorac Cardiovasc Surg. 2007;55(7):281–3.
Travis WD, et al. WHO classification of tumours of the lung, pleura, thymus and heart. In: Bosman FT, et al., editors. World health classification of tumours. 4th ed. Lyon: IARC; 2015.
Nakamura S, et al. Multilocular thymic cyst associated with thymoma: a clinicopathologic study of 20 cases with an emphasis on the pathogenesis of cyst formation. Am J Surg Pathol. 2012;36(12):1857–64.
Asma B, et al. Acute respiratory failure revealing a multilocular thymic cyst in an infant: a case report. Cases J. 2009;2:9109.
Mishalani SH, Lones MA, Said JW. Multilocular thymic cyst. A novel thymic lesion associated with human immunodeficiency virus infection. Arch Pathol Lab Med. 1995;119(5):467–70.
Nonaka D, Klimstra D, Rosai J. Thymic mucoepidermoid carcinomas: a clinicopathologic study of 10 cases and review of the literature. Am J Surg Pathol. 2004;28(11):1526–31.
Matsumoto S, et al. Multilocular thymic cyst associated with rheumatoid arthritis. Kyobu Geka. 2012;65(3):205–8.
Tamagno M, et al. Giant multilocular thymic cyst in an HIV-infected adolescent. J Pediatr Surg. 2011;46(9):1842–5.
Suster S, Rosai J. Multilocular thymic cyst: an acquired reactive process. Study of 18 cases. Am J Surg Pathol. 1991;15(4):388–98.
Izumi H, et al. Multilocular thymic cyst associated with follicular hyperplasia: clinicopathologic study of 4 resected cases. Hum Pathol. 2005;36(7):841–4.
Suster S, et al. Multilocular thymic cysts with pseudoepitheliomatous hyperplasia. Hum Pathol. 1991;22(5):455–60.
Osaki T, Nakagawa M. Multilocular mediastinal cyst with rim calcification: report of a case. Surg Today. 2008;38(1):52–5.
Shen X, et al. Thymoma and thymic carcinoma associated with multilocular thymic cyst: a clinicopathologic analysis of 18 cases. Diagn Pathol. 2018;13(1):41.
Weissferdt A, Moran CA. Thymic carcinoma associated with multilocular thymic cyst: a clinicopathologic study of 7 cases. Am J Surg Pathol. 2011;35(7):1074–9.
Moran CA, et al. Carcinomas arising in multilocular thymic cysts of the neck: a clinicopathological study of three cases. Histopathology. 2004;44(1):64–8.
Huang WL, Tseng YL. Rare presentation of giant isolated enteric cyst in anterior mediastinum. Ann Thorac Surg. 2019;107(6):e417–9.
Salyer DC, Salyer WR, Eggleston JC. Benign developmental cysts of the mediastinum. Arch Pathol Lab Med. 1977;101(3):136–9.
Schweigert M, et al. The tale of spring water cysts: a historical outline of surgery for congenital pericardial diverticula and cysts. Tex Heart Inst J. 2012;39(3):330–4.
Park JG, et al. Mediastinal lymphangioma: Mayo clinic experience of 25 cases. Mayo Clin Proc. 2006;81(9):1197–203.
Kadota Y, et al. Lymphatic and venous malformation or “lymphangiohemangioma” of the anterior mediastinum: case report and literature review. Gen Thorac Cardiovasc Surg. 2011;59(8):575–8.
Moran CA, Suster S. Thymoma with prominent cystic and hemorrhagic changes and areas of necrosis and infarction: a clinicopathologic study of 25 cases. Am J Surg Pathol. 2001;25(8):1086–90.
Suster S, Rosai J. Thymic carcinoma. A clinicopathologic study of 60 cases. Cancer. 1991;67(4):1025–32.
Suster S, Rosai J. Cystic thymomas. A clinicopathologic study of ten cases. Cancer. 1992;69(1):92–7.
Rieker RJ, et al. Cystic thymoma. Pathol Oncol Res. 2005;11(1):57–60.
Brown JG, et al. Thymic basaloid carcinoma: a clinicopathologic study of 12 cases, with a general discussion of basaloid carcinoma and its relationship with adenoid cystic carcinoma. Am J Surg Pathol. 2009;33(8):1113–24.
Moser B, et al. Adenocarcinoma of the thymus, enteric type: report of 2 cases, and proposal for a novel subtype of thymic carcinoma. Am J Surg Pathol. 2015;39(4):541–8.
Weissferdt A, Kalhor N, Moran CA. Cystic well-differentiated squamous cell carcinoma of the thymus: a clinicopathological and immunohistochemical study of six cases. Histopathology. 2016;68(3):333–8.
Lindholm KE, Moran CA. Cystic and encapsulated atypical thymoma (World Health Organization Type B3). Am J Clin Pathol. 2019;152(4):512–6.
Betts G, Beckett E, Nonaka D. GATA3 shows differential immunohistochemical expression across thyroid and parathyroid lesions. Histopathology. 2014;65(2):288–90.
Tulay CM. Primary mediastinal hydatid cysts. Ann Thorac Cardiovasc Surg. 2014;20(4):316–9.
Sabzi F, Faraji R. A rare case of anterior mediastinal mass caused by Brucella infection. Asian Cardiovasc Thorac Ann. 2017;25(3):222–5.
Mao JC, et al. Craniocervical necrotizing fasciitis with and without thoracic extension: management strategies and outcome. Am J Otolaryngol. 2009;30(1):17–23.
Strobel P, et al. The ageing and myasthenic thymus: a morphometric study validating a standard procedure in the histological workup of thymic specimens. J Neuroimmunol. 2008;201–202:64–73.
Middleton G, Schoch EM. The prevalence of human thymic lymphoid follicles is lower in suicides. Virchows Arch. 2000;436(2):127–30.
Marx A, et al. Thymus pathology observed in the MGTX trial. Ann N Y Acad Sci. 2012;1275:92–100.
Alpert LI, et al. A histologic reappraisal of the thymus in myasthenia gravis. A correlative study of thymic pathology and response to thymectomy. Arch Pathol. 1971;91(1):55–61.
Koneczny I, et al. Characterization of the thymus in Lrp4 myasthenia gravis: four cases. Autoimmun Rev. 2019;18(1):50–5.
Zisimopoulou P, et al. A comprehensive analysis of the epidemiology and clinical characteristics of anti-LRP4 in myasthenia gravis. J Autoimmun. 2014;52:139–45.
Leite MI, et al. Fewer thymic changes in MuSK antibody-positive than in MuSK antibody-negative MG. Ann Neurol. 2005;57(3):444–8.
Dalla Costa M, Mangano FA, Betterle C. Thymic hyperplasia in patients with Graves’ disease. J Endocrinol Investig. 2014;37(12):1175–9.
Hofmann WJ, Moller P, Otto HF. Thymic hyperplasia. II. Lymphofollicular hyperplasia of the thymus. An immunohistologic study. Klin Wochenschr. 1987;65(2):53–60.
Meyer A, Levy Y. Geoepidemiology of myasthenia gravis [corrected]. Autoimmun Rev. 2010;9(5):A383–6.
Maniaol AH, et al. Late onset myasthenia gravis is associated with HLA DRB1∗15:01 in the Norwegian population. PLoS One. 2012;7(5):e36603.
Seldin MF, et al. Genome-wide association study of late-onset myasthenia gravis: confirmation of TNFRSF11A and identification of ZBTB10 and three distinct HLA associations. Mol Med. 2016;21(1):769–81.
Chuang WY, et al. Late-onset myasthenia gravis - CTLA4(low) genotype association and low-for-age thymic output of naive T cells. J Autoimmun. 2014;52:122–9.
Giraud M, et al. An IRF8-binding promoter variant and AIRE control CHRNA1 promiscuous expression in thymus. Nature. 2007;448(7156):934–7.
Gregersen PK, et al. Risk for myasthenia gravis maps to a (151) Pro-->Ala change in TNIP1 and to human leukocyte antigen-B∗08. Ann Neurol. 2012;72(6):927–35.
Renton AE, et al. A genome-wide association study of myasthenia gravis. JAMA Neurol. 2015;72(4):396–404.
Gradolatto A, et al. Both Treg cells and Tconv cells are defective in the Myasthenia gravis thymus: roles of IL-17 and TNF-alpha. J Autoimmun. 2014;52:53–63.
Vincent A, et al. In-vitro synthesis of anti-acetylcholine-receptor antibody by thymic lymphocytes in myasthenia gravis. Lancet. 1978;1(8059):305–7.
Wakkach A, et al. Expression of acetylcholine receptor genes in human thymic epithelial cells: implications for myasthenia gravis. J Immunol. 1996;157(8):3752–60.
Kao I, Drachman DB. Thymic muscle cells bear acetylcholine receptors: possible relation to myasthenia gravis. Science. 1977;195(4273):74–5.
Leite MI, et al. Myasthenia gravis thymus: complement vulnerability of epithelial and myoid cells, complement attack on them, and correlations with autoantibody status. Am J Pathol. 2007;171(3):893–905.
Hohlfeld R, Wekerle H. Reflections on the “intrathymic pathogenesis” of myasthenia gravis. J Neuroimmunol. 2008;201–202:21–7.
Wolfe GI, et al. Long-term effect of thymectomy plus prednisone versus prednisone alone in patients with non-thymomatous myasthenia gravis: 2-year extension of the MGTX randomised trial. Lancet Neurol. 2019;18(3):259–68.
Suster S, Moran CA. Micronodular thymoma with lymphoid B-cell hyperplasia: clinicopathologic and immunohistochemical study of eighteen cases of a distinctive morphologic variant of thymic epithelial neoplasm. Am J Surg Pathol. 1999;23(8):955–62.
Weissferdt A, Moran CA. Micronodular thymic carcinoma with lymphoid hyperplasia: a clinicopathological and immunohistochemical study of five cases. Mod Pathol. 2012;25(7):993–9.
Weissferdt A, Moran CA. Thymic hyperplasia with lymphoepithelial sialadenitis (LESA)-like features: a clinicopathologic and immunohistochemical study of 4 cases. Am J Clin Pathol. 2012;138(6):816–22.
Marchevsky A, et al. Policies and reporting guidelines for small biopsy specimens of mediastinal masses. J Thorac Oncol. 2011;6(Suppl 3):S1724–9.
Inagaki H, et al. Primary thymic extranodal marginal-zone B-cell lymphoma of mucosa-associated lymphoid tissue type exhibits distinctive clinicopathological and molecular features. Am J Pathol. 2002;160(4):1435–43.
Aoki M, et al. A case of resected plasma cell type castleman’s disease with intramediastinal lymph nodes spread. Ann Thorac Cardiovasc Surg. 2014;20:682–5.
Tani T, et al. A case of true thymic hyperplasia showing slow growth as revealed by chest X-ray. Nihon Kyobu Shikkan Gakkai Zasshi. 1994;32(2):194–8.
Judd RL. Massive thymic hyperplasia with myoid cell differentiation. Hum Pathol. 1987;18(11):1180–3.
Eifinger F, et al. True thymic hyperplasia associated with severe thymic cyst bleeding in a newborn: case report and review of the literature. Ann Diagn Pathol. 2007;11(5):358–62.
Strobel P, et al. Deficiency of the autoimmune regulator AIRE in thymomas is insufficient to elicit autoimmune polyendocrinopathy syndrome type 1 (APS-1). J Pathol. 2007;211(5):563–71.
Marx A, et al. The 2015 World Health Organization classification of tumors of the thymus: continuity and changes. J Thorac Oncol. 2015;10(10):1383–95.
Adam P, et al. Thymoma with loss of keratin expression (and giant cells): a potential diagnostic pitfall. Virchows Arch. 2014;465(3):313–20.
Balbach ST, et al. Proposal of a genetic classifier for risk group stratification in pediatric T-cell lymphoblastic lymphoma reveals differences from adult T-cell lymphoblastic leukemia. Leukemia. 2016;30(4):970–3.
Burkhardt B, Hermiston ML. Lymphoblastic lymphoma in children and adolescents: review of current challenges and future opportunities. Br J Haematol. 2019;185(6):1158–70.
Oschlies I, et al. Diagnosis and immunophenotype of 188 pediatric lymphoblastic lymphomas treated within a randomized prospective trial: experiences and preliminary recommendations from the European childhood lymphoma pathology panel. Am J Surg Pathol. 2011;35(6):836–44.
Pilozzi E, et al. Gene rearrangements in T-cell lymphoblastic lymphoma. J Pathol. 1999;188(3):267–70.
den Bakker MA, Oosterhuis JW. Tumours and tumour-like conditions of the thymus other than thymoma; a practical approach. Histopathology. 2009;54(1):69–89.
Shimosato Y, Mukai K, Matsuno Y. Tumors of the mediastinum. Washington, DC: American Registry of Pathology; 2010.
Tabarin A, et al. Paraneoplastic Cushing’s syndrome. Pseudotumors of the thymus occurring after correction of hypercorticism. 3 cases. Presse Med. 1993;22(38):1908–10, 1915.
Chertoff J, Barth RA, Dickerman JD. Rebound thymic hyperplasia five years after chemotherapy for Wilms’ tumor. Pediatr Radiol. 1991;21(8):596–7.
Kissin CM, et al. Benign thymic enlargement in adults after chemotherapy: CT demonstration. Radiology. 1987;163(1):67–70.
Jeon TJ, et al. Rebound thymic hyperplasia detected by 18F-FDG PET/CT after radioactive iodine ablation therapy for thyroid cancer. Thyroid. 2014;24(11):1636–41.
Priola AM, et al. Nonsuppressing normal thymus on chemical-shift MR imaging and anterior mediastinal lymphoma: differentiation with diffusion-weighted MR imaging by using the apparent diffusion coefficient. Eur Radiol. 2018;28(4):1427–37.
Richmond BW, et al. Genome-wide association study of 58 individuals with Fibrosing Mediastinitis reveals possible underlying genetic susceptibility. Am J Respir Crit Care Med. 2018;197(9):1219–20.
Flieder DB, Suster S, Moran CA. Idiopathic fibroinflammatory (fibrosing/sclerosing) lesions of the mediastinum: a study of 30 cases with emphasis on morphologic heterogeneity. Mod Pathol. 1999;12(3):257–64.
Takanashi S, et al. IgG4-related fibrosing mediastinitis diagnosed with computed tomography-guided percutaneous needle biopsy: two case reports and a review of the literature. Medicine (Baltimore). 2018;97(22):e10935.
Giorgadze T, et al. Postradiation-associated sclerosing mediastinitis diagnosed in fine needle aspiration specimen: a cytological-pathological correlation. Ann Diagn Pathol. 2017;27:43–7.
Peikert T, et al. Fibrosing mediastinitis: clinical presentation, therapeutic outcomes, and adaptive immune response. Medicine (Baltimore). 2011;90(6):412–23.
Zhou Y, et al. Pulmonary vascular involvement of IgG4-related disease: case series with a PRISMA-compliant systemic review. Medicine (Baltimore). 2019;98(6):e14437.
Peikert T, et al. Histopathologic overlap between Fibrosing Mediastinitis and IgG4-related disease. Int J Rheumatol. 2012;2012:207056.
Sfyroeras GS, et al. A review of open and endovascular treatment of superior vena cava syndrome of benign aetiology. Eur J Vasc Endovasc Surg. 2017;53(2):238–54.
Weissferdt A, Moran CA. The impact of neoadjuvant chemotherapy on the histopathological assessment of thymomas: a clinicopathological correlation of 28 cases treated with a similar regimen. Lung. 2013;191(4):379–83.
Weissferdt A, Kalhor N, Moran C. Primary thymic cholesteroloma: a clinicopathological correlation of four cases of an unusual benign lesion. Virchows Arch. 2015;467(5):609–11.
Ezzat TF, Alowami S. Cholesterol granuloma of the anterior mediastinum with osseous metaplasia. Rare Tumors. 2012;4(4):e47.
Krishnan TR, Sinha SK, Kejriwal NK. A rare case of cholesterol granuloma in the anterior mediastinum. Heart Lung Circ. 2013;22(4):303–4.
Fujimoto K, et al. Focal cholesterol granuloma in the anterior mediastinum: [18F]-fluoro-2-deoxy-D-glucose-positron emission tomography and magnetic resonance imaging findings. J Thorac Oncol. 2007;2(11):1054–6.
Luckraz H, Coulston J, Azzu A. Cholesterol granuloma of the superior mediastinum. Ann Thorac Surg. 2006;81(4):1509–10.
Hamza A, Weissferdt A. Non-neoplastic and benign tumoral lesions of the thymic gland: a review and update. Adv Anat Pathol. 2019;26(4):257–69.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2020 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Marx, A. (2020). Pathology of Nonneoplastic Thymic Lesions. In: Jain, D., Bishop, J.A., Wick, M.R. (eds) Atlas of Thymic Pathology. Springer, Singapore. https://doi.org/10.1007/978-981-15-3164-4_5
Download citation
DOI: https://doi.org/10.1007/978-981-15-3164-4_5
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-3163-7
Online ISBN: 978-981-15-3164-4
eBook Packages: MedicineMedicine (R0)