Oligoclonal Peripheral T-Cell Lymphocytosis as a Result of Aberrant T-Cell Development in a Cortical Thymoma

  • Daphne De Jong
  • Dick Richel
  • Cees Schenkeveld
  • Lucie Boerrigter
  • Laura van’ t Veer


A 42 year old man presented with a locally invasive cortical thymoma. Before chemotherapy was commenced 36 months after presentation, a peripheral lymphocytosis of 19×109/1 had slowly developed over time. After the first course of chemotherapy, the lymphocytosis showed a sharp decline to normal absolute cell numbers and subsequently remained at normal levels. Currently, the patient is in stable partial remission and doing well.

Immunophenotypic analysis showed 95% CD3+ve cells; 36% CD4+ve and 56% CD8+ve cells with a mature T-cell phenotype. 78% of the T-cells expressed TcR-aß and 16% TcR-γδ as assessed by immunocytochemistry. No CD4/CD8 double positive population was detected. 4% CD16/CD56+ve NK-cells could be demonstrated. Southern blot analysis of peripheral blood mononuclear cells before chemotherapy showed a striking oligoclonal pattern with 13–20 rearranged fragments of different intensity for theTcRß-gene. TcRγ also showed a pattern compatible with a oligoclonal proliferation with 6 of the 8 theoretically possible rearranged fragments in EcoRI-digested DNA. After treatment, when absolute blood counts had returned to normal, the distribution of subsets still showed a slightly aberrant pattern with a CD4/CD8 ratio of 3.25 and 80%TcR-aß and 16% TcR-γδ expressing cells. Immunophenotypic analysis of a blood sample taken 6 months later, also at normal absolute cell counts, showed an aberrant phenotype of late thymocytes (CD34, TdT, CD1+, CD4/CD8 single positive) and of mature T-cells (CD1). TcRß- and TcRγ-gene rearrangment of the same sample showed a polyclonal pattern.

Thymomas may rarely be associated with peripheral lymphocytosis. Immunophenotypic analysis showed a T-cell phenotype in all reported cases. We describe a patient with a locally invasive cortical thymoma, who presented with an oligoclonal peripheral lymphocytosis of mature T-cell phenotype and subsequent polyclonal emergence of late thymocytes. These findings may be interpreted as the result of aberrant positive and negative selection and development of thymocytes in the microenvironment of neoplastic thymic epithelial cells and clonal selection through continuous peripheral stimulation.


Thymic Carcinoma Immunophenotypic Analysis Thymic Epithelial Tumor Thymic Epithelium Invasive Thymoma 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Marino M, Müller-Hermelink HK. Thymoma and thymic carcinoma. Relation of thymoma epithelial cells to the cortical and medullary differentiation of thymus. Virchows Arch. (Pathol.Anat) 1985; 407:119–149.CrossRefGoogle Scholar
  2. 2.
    Müller-Hermelink HK, Marino M, Palestro G. Pathology of thymic epithelial tumors. In Müller-Hermelink HK ed. Current Topics in Pathology: The human thymus. Berlin: Springer-Verlag 1986:208–268.Google Scholar
  3. 3.
    Kirchner T, Müller-Hermelink HK. New approaches to the diagnosis of thymic epithelial tumors Prog.Surg.Pathol. 1989; 10:167–189.Google Scholar
  4. 4.
    Pescarmona E, Rendia EA, Venuta F, Ricci C, ruco LP, Baroni CD. The prognostic implication of thymoma histologic subtyping. Am.J.Clin.Pathol. 1990; 93:190–195.PubMedGoogle Scholar
  5. 5.
    Quintanilla-Martinez L, Wilkins EW, Ferry JA, Harris NL. Thymoma-morfologic subclassification correlates invasiveness and immunohistologic features. A study of 122 cases. Hum.Pathol. 1993; 24:958–969.PubMedCrossRefGoogle Scholar
  6. 6.
    Kuo TT, Lo SK. Thymoma: astudy of the pathologic classificaion of 71 cases with evaluation of the Müller-Hermelink system. hum.Pathol. 1993; 24:766–771.PubMedCrossRefGoogle Scholar
  7. 7.
    Müller-Hermelink HK, Marx A, Geuder K, Kirchner T. The pathological basis of thymoma-associated myasthenia gravis. Ann N Y Acad Sci. 1993; 681:56–65.PubMedCrossRefGoogle Scholar
  8. 8.
    Gilhus NE, Willcox N, Harcourt G, Nagvekar N, Beeson D, Vincent A, Newsom-Davis J. Antigen presentation by thymoma epithelial cells from myastenia gravis patients to potentially pathogenic cells. J.Neuroimmunol. 1995; 56:65–76.PubMedCrossRefGoogle Scholar
  9. 9.
    Arntzenius AB, Bieger R. Disappearance of autoantibody-induced haemolysis after excision of a malignant thymoma. Neth J Med. 1991; 38:117–21.PubMedGoogle Scholar
  10. 10.
    Doll DC, Landreneau RJ, List AF. Malignant thymoma associated with peripheral T-cell lymphocytosis. Med.Pediatric Oncol. 1991: 19;496–498.CrossRefGoogle Scholar
  11. 11.
    Medeiros LJ, Bhagat SKM, Naylor P, Fowler D, Jaffe ES, Stetler-Stevenson M. Malignant thymoma associated with T-cell lymphocytosis. Arch.Pathol.Lab.Med. 1993; 117:279–283.PubMedGoogle Scholar
  12. 12.
    Handa SI, Schofield KP, Sivakumaran M, Short M, Pumphrey RS. Pure red cell aplasia associated with malignant thymoma, myasthenia gravis, polyclonal large granular lymphocytosis and clonal thymic T cell expansion. J Clin Pathol. 1994; 47:676–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Lishner M, Ravid M, Shapira J, Radnay J, Amiel A, Leytn V, Shapiro C, Klein A. Delta-T lymphocytosis in a patient with thymoma. Cancer 1994; 74:2924–2929.PubMedCrossRefGoogle Scholar
  14. 14.
    Smith GP, Perkins SL, Segal GH, Kjeldsberg CR. T-cell lymphocytosis associated with invasive thymomas. Am.J.Clin.Pathol. 1994; 102:447–453.PubMedGoogle Scholar
  15. 15.
    Yoshioka K, Terasaki J. CD7+, CD5+, CD4−, CD8−, and CD3− T-cell malignancy of the spleen after remission of invasive thymoma. Am.J.Hematol. 1995; 48:141–142.PubMedCrossRefGoogle Scholar
  16. 16.
    Macon WR, Rynalski TH, Swerdlow SH, Cousar JB. T-cell lymphoblastic leukemia/lymphoma presenting in a recurrent thymoma. Mod Pathol. 1991; 4:524–8.PubMedGoogle Scholar
  17. 17.
    Friedman HD, Inman DA, Hutchison RE, Poiesz BJ. Concurrent invasive thymoma and T-cell lymphoblastic leukemia and lymphoma. A case report with necropsy findings and literature review of thymoma and associated hematologic neoplasm. Am J Clin Pathol. 1994; 101:432–7.PubMedGoogle Scholar
  18. 18.
    Fujii Y, Okumura M, Inada K, Nakahara K. Lymphocytes in thymomas are tolerant to self-MHC. Cell Immunol. 1991; 137:438–47.PubMedCrossRefGoogle Scholar
  19. 19.
    Willcox N, Baggi F, Batocchi AP, Beeson D, Harcourt G, Hawke S, Jacobson L, Matsuo H, Moody AM, Nagvekar N et al. Approaches for studying the pathogenic T cells in autoimmune patients. Ann N Y Acad Sci. 1993; 681:219–37.PubMedCrossRefGoogle Scholar
  20. 20.
    Takeuchi Y, Fujii Y, Okumura M, Inada K, Nakahara K, Matsuda H. Accumilation of immature CD3-CD4+CD8− single positive cells that lack CD69 in epithelial cell tumors of the human thymus. Cell.Immunol. 1995; 161:181–187.PubMedCrossRefGoogle Scholar
  21. 21.
    Spits H, Lanier LL, Phillips JH. Development of human T and natural killer cells. Blood 1995; 85:2654–2670.PubMedGoogle Scholar
  22. 22.
    Anderson G, Owen JJT, Moore NC, Jenkinson EJ. Thymic epithelial cells provide unique signal for positive selection of CD4+CD8+ thymocytes in vitro. J.Ex.Med. 1994; 179:2027–2031.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1997

Authors and Affiliations

  • Daphne De Jong
    • 1
  • Dick Richel
    • 2
  • Cees Schenkeveld
    • 3
  • Lucie Boerrigter
    • 1
  • Laura van’ t Veer
    • 1
  1. 1.Department of PathologyNetherlands Cancer Institute/Antoni van LeeuwenhoekziekenhuisAmsterdamThe Netherlands
  2. 2.Department of Internal MedicineEnschedeThe Netherlands
  3. 3.Clinical ChemistryMedisch Spectrum TwenteEnschedeThe Netherlands

Personalised recommendations