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Immune-Mediated Diseases and Immunodeficiencies Associated with Thymic Epithelial Neoplasms

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Abstract

Introduction

This retrospective study aimed to characterize the clinical hematological and immunological features of patients with thymic epithelial neoplasms.

Methods

From a cohort of 512 patients with thymic epithelial neoplasms, 79 patients diagnosed with autoimmune/immunodeficiency conditions or signs and/or symptoms suggesting an autoimmune or immunodeficiency state were evaluated by standard immunological and hematological testing.

Results

Elevated percentages of CD2+, CD3+, and CD8+ lymphocytes were observed in 44 (57.1%), 33 (41.8%), and 32 (40.5%) patients. Low CD4+ and CD19+ percentages were observed in 25 (31.6%) and 36 (46.2%), respectively; CD4+:CD8+ ratios were inverted in 18 (22.8%). IgG, IgA, and IgM levels were low in 12 (15.8%), 9 (11.7%) and 15 (19.7%) patients, respectively. Patients with immunodeficiency condition(s) were more likely to have high CD8+ percentages (p = 0.040), low CD19+ percentages (p = 0.025), and/or inverted CD4+/CD8+ ratios (p = 0.034). Patients with autoimmune condition(s) were more likely to have a high/normal CD4+ percentage (p = 0.038). High CD2+ percentages were associated with lower mean IgG and IgA levels (p = 0.030 and p = 0.017, respectively). High CD3+ and CD8+ percentages were associated with lower mean IgA levels (p = 0.046 and p = 0.013, respectively). Low CD19+ percentages were associated with lower mean IgG and IgA levels (p = 0.004 and p < 0.001, respectively).

Conclusion

Signs/symptoms and history of autoimmune and immunodeficiency conditions among patients with thymic epithelial neoplasms are associated with high frequencies of abnormalities in immunoglobulin levels and lymphocyte immunophenotypes, suggesting a role for their assessment.

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References

  1. Suster S, Moran CA. Thymoma, atypical thymoma, and thymic carcinoma. A novel conceptual approach to the classification of thymic epithelial neoplasms. Am J Clin Pathol. 1999;111:826–33.

    PubMed  CAS  Google Scholar 

  2. Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC. Pathology and genetics of tumors of the lung, pleura, thymus and heart. Lyon: IARC; 2004.

    Google Scholar 

  3. Suster S, Moran CA. Histologic classification of thymoma: the World Health Organization and beyond. Hematol Oncol Clin N Am. 2008;22(3):381–92.

    Article  Google Scholar 

  4. Masci AM, Palmieri G, Perna F, Montella L, Merkabaoui G, Sacerdoti G, et al. Immunological findings in thymoma and thymoma-related syndromes. Ann Med. 1999;31 Suppl 2:86–9.

    PubMed  Google Scholar 

  5. Barnes EW, Irvine WJ. Clinical syndromes associated with thymic disorders. Proc R Soc Med. 1973;66:151–4.

    PubMed  CAS  Google Scholar 

  6. Souadjian JV, Enriquez P, Silverstein MN, Pépin JM. The spectrum of diseases associated with thymoma. Coincidence or syndrome. Arch Intern Med. 1974;134:374–9.

    Article  PubMed  CAS  Google Scholar 

  7. Marx A, Schultz A, Wilisch A, Helmreich M, Nenninger R, Müller-Hermelink HK. Paraneoplastic autoimmunity in thymus tumors. Dev Immunol. 1998;6:129–40.

    Article  PubMed  CAS  Google Scholar 

  8. Evoli A, Minicuci GM, Vitaliani R, Battaglia A, Della Marca G, Lauriola L, et al. Paraneoplastic diseases associated with thymoma. J Neurol. 2007;254:756–62.

    Article  PubMed  Google Scholar 

  9. Nelson Jr RP, Pascuzzi RM. Paraneoplastic syndromes in thymoma: an immunological perspective. Curr Treat Options Oncol. 2008;9:269–76.

    Article  PubMed  Google Scholar 

  10. Tormoehlen LM, Pascuzzi RM. Thymoma, myasthenia gravis, and other paraneoplastic syndromes. Hematol Oncol Clin N Am. 2008;8:509–26.

    Article  Google Scholar 

  11. Rosenow EC, Hurley BT. Disorders of the thymus. A review. Arch Intern Med. 1984;144:763–70.

    Article  PubMed  Google Scholar 

  12. Kelesidis T, Yang O. Good's syndrome remains a mystery after 55 years: a systematic review of the scientific evidence. Clin Immunol. 2010;135:347–63.

    Article  PubMed  CAS  Google Scholar 

  13. Castro KG, Ward JW, Slutsker L, Buehler JW, Jaffe HW, Berkelman RL, et al. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep. 1992;41(RR-17):1–19.

    Google Scholar 

  14. Jones JL, Hanson DL, Dworkin MS, Alderton DL, Fleming PL, Kaplan JE, et al. Surveillance for AIDS-defining opportunistic illnesses, 1992–1997. MMWR CDC Surveill Summ. 1999;48(2):1–22.

    PubMed  Google Scholar 

  15. Baker CJ, Kasper DL, Edwards MS, Schiffman G. Influence of preimmunization antibody levels on the specificity of the immune response to related polysaccharide antigens. N Engl J Med. 1980;303(4):173–8.

    Article  PubMed  CAS  Google Scholar 

  16. Engels EA, Pfeiffer RM. Malignant thymoma in the United States: demographic patterns in incidence and associations with subsequent malignancies. Int J Cancer. 2003;105(4):546–51.

    Article  PubMed  CAS  Google Scholar 

  17. Salyer WR, Eggleston JC. Thymoma: a clinical and pathological study of 65 cases. Cancer. 1976;37(1):229–49.

    Article  PubMed  CAS  Google Scholar 

  18. Rubin M, Straus B, Allen L. Clinical disorders associated with thymic tumors. Arch Intern Med. 1964;114:389–98.

    Article  PubMed  CAS  Google Scholar 

  19. Ammus SS, Yunis AA. Acquired pure red cell aplasia. Am J Hematol. 1987;24(3):311–26.

    Article  PubMed  CAS  Google Scholar 

  20. Yip D, Rasko JE, Lee C, Kronenberg H, O'Neill B. Thymoma and agranulocytosis: two case reports and literature review. Br J Haematol. 1996;95(1):52–6.

    Article  PubMed  CAS  Google Scholar 

  21. Kelleher P, Misbah SA. What is Good's syndrome? Immunological abnormalities in patients with thymoma. J Clin Pathol. 2003;56(1):12–6.

    Article  PubMed  CAS  Google Scholar 

  22. Tarr PE, Sneller MC, Mechanic LJ, Economides A, Eger CM, Strober W, et al. Infections in patients with immunodeficiency with thymoma (Good syndrome). Report of 5 cases and review of the literature. Medicine (Baltimore). 2001;80(2):123–33.

    Article  CAS  Google Scholar 

  23. Miyakis S, Pefanis A, Passam FH, Christodulakis GR, Roussou PA, Mountokalakis TD. Thymoma with immunodeficiency (Good's syndrome): review of the literature apropos three cases. Scand J Infect Dis. 2006;38(4):314–9.

    Article  PubMed  Google Scholar 

  24. Di Renzo M, Pasqui A, Bruni F, Voltolini L, Rottoli P, Perali G, et al. Thymoma and immunodeficiency. N Z Med J. 2004;117(1188):U750.

    PubMed  Google Scholar 

  25. Vitiello L, Masci AM, Montella L, Perna F, Angelini DF, Borsellino G, et al. Thymoma-associated immunodeficiency: a syndrome characterized by severe alterations in NK, T and B-cells and progressive increase in naive CD8+ T cells. Int J Immunopathol Pharmacol. 2010;23(1):307–16.

    PubMed  CAS  Google Scholar 

  26. Tarr PE, Lucey DR. Good's syndrome: the association of thymoma with immunodeficiency. Clin Infect Dis. 2001;33(4):585–6.

    Article  PubMed  CAS  Google Scholar 

  27. Del Pozo N, Sarmiento E, Lanio N, Gallego A, Largo J, Carbone J. Immunophenotypic abnormalities of CD8+ T-cell subsets in a patient with unusual Good's syndrome. Allergol Immunopathol (Madr). 2010;38(2):102–5.

    Article  Google Scholar 

  28. Baumert E, Schlesier M, Wolff-Vorbeck G, Peter HH. Alterations in lymphocyte subsets in variable immunodeficiency syndrome. Immun Infekt. 1992;20(3):73–5.

    PubMed  CAS  Google Scholar 

  29. Hanafusa T, Umegaki N, Yamaguchi Y, Katayama I. Good’s syndrome (hypogammaglobulinemia with thymoma) presenting intractable opportunistic infections and hyperkeratotic lichen planus. J Dermatol. 2010;37(2):171–4.

    Article  PubMed  Google Scholar 

  30. Jaffe JS, Eisenstein E, Sneller MC, Strober W. T-cell abnormalities in common variable immunodeficiency. Pediatr Res. 1993;33 Suppl 1:24–7.

    Article  Google Scholar 

  31. Burbelo PD, Browne SK, Sampaio EP, Giaccone G, Zaman R, Kristosturyan E, et al. Anti-cytokine autoantibodies are associated with opportunistic infection in patients with thymic neoplasia. Blood. 2010;116(23):4848–58.

    Article  PubMed  CAS  Google Scholar 

  32. Nagvekar N, Moody AM, Moss P, Roxanis I, Curnow J, Beeson D, et al. A pathogenetic role for the thymoma in myasthenia gravis. Autosensitization of IL-4- producing T cell clones recognizing extracellular acetylcholine receptor epitopes presented by minority class II isotypes. J Clin Invest. 1998;101:2268–77.

    Article  PubMed  CAS  Google Scholar 

  33. Okereke IC, Kesler KA, Morad MH, Mi D, Rieger KM, Birdas TJ, et al. Prognostic indicators after surgery for thymoma. Ann Thorac Surg. 2010;89(4):1071–9.

    Article  PubMed  Google Scholar 

  34. Mateo-Montoya A, Stanescu D, Wolff B, Sahel JA, Bonnel S. Cytomegalovirus retinitis associated with Good's syndrome. Eur J Ophthalmol. 2010;20(2):479–80.

    PubMed  Google Scholar 

  35. Squintani G, Ferrari S, Bazzoli E, Eleopra R, La Monaca C, Cagliari E, et al. Progressive multifocal leukoencephalopathy in a patient with Good's syndrome. Int J Infect Dis. 2010;14(5):e444–7.

    Article  PubMed  Google Scholar 

  36. Kuribayashi K, Fujimi A, Kobune M, Takimoto R, Kikuchi S, Iyama S, et al. Pure red cell aplasia associated with Good's syndrome accompanied by decreased stem cell factor production in the bone marrow. Intern Med. 2010;49(5):377–82.

    Article  PubMed  Google Scholar 

  37. Marx A, Hohenberger P, Hoffmann H, Pfannschmidt J, Schnabel P, Hofmann HS, et al. The autoimmune regulator AIRE in thymoma biology: autoimmunity and beyond. J Thorac Oncol. 2010;5(10 Suppl 4):S266–72.

    Article  PubMed  Google Scholar 

  38. Ströbel P, Helmreich M, Menioudakis G, Lewin SR, Rüdiger T, Bauer A, et al. Paraneoplastic myasthenia gravis correlates with generation of mature naive CD4(+) T cells in thymomas. Blood. 2002;100(1):159–66.

    Article  PubMed  Google Scholar 

  39. Ströbel P, Bauer A, Puppe B, Kraushaar T, Krein A, Toyka K, et al. Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis. J Clin Oncol. 2004;22(8):1501–9.

    Article  PubMed  Google Scholar 

  40. Ströbel P, Murumägi A, Klein R, Luster M, Lahti M, Krohn K, 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.

    Article  PubMed  Google Scholar 

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Conflicts of Interest

The authors declare that they have no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Muhammad Rizwan Khawaja

  2. Division of Hematology and Oncology, Department of Medicine, Indiana University School of Medicine, Melvin and Bren Simon Cancer Center, Indianapolis, IN, 46202, USA

    Robert P. Nelson Jr., Nicholas Miller, Elizabeth Loehrer & Patrick J. Loehrer Sr.

  3. Department of Pathology, Indiana University School of Medicine, Indianapolis, IN, USA

    Sunil S. Badve & Magdalena Czader

  4. Department of Biostatistics, Indiana University School of Medicine, Indianapolis, IN, USA

    Susan M. Perkins

  5. Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

    Kenneth Kesler

  6. Department of Laboratory Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Sunil S. Badve & Magdalena Czader

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  1. Muhammad Rizwan Khawaja
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  2. Robert P. Nelson Jr.
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Correspondence to Robert P. Nelson Jr..

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Khawaja, M.R., Nelson, R.P., Miller, N. et al. Immune-Mediated Diseases and Immunodeficiencies Associated with Thymic Epithelial Neoplasms. J Clin Immunol 32, 430–437 (2012). https://doi.org/10.1007/s10875-011-9644-1

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  • DOI: https://doi.org/10.1007/s10875-011-9644-1

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