Virchows Archiv

, Volume 465, Issue 6, pp 731–736 | Cite as

Primary γδ T cell lymphoma of the lung: report of a case with features suggesting derivation from intraepithelial γδ T lymphocytes

  • Ji-Young Choe
  • Bettina Bisig
  • Laurence de Leval
  • Yoon Kyung JeonEmail author
Case Report


T cell lymphoma of γδ T cell origin is a rare disease that mainly involves extranodal sites and shows aggressive clinical behavior. Here, we report a case of primary γδ T cell lymphoma of the lungs with epitheliotropism in the respiratory epithelium, a feature somewhat reminiscent of what is observed in enteropathy-associated T cell lymphoma. A 63-year-old man presented with chest pain and dyspnea on exertion, weight loss, and general weakness. On a positron emission tomography (PET) scan, multiple hypermetabolic lesions were found in both lungs. Microscopic examination of the wedge lung biopsy revealed nodular infiltration of monomorphic, medium- to large-sized atypical lymphocytes with round nuclei, coarse chromatin, and a variable amount of clear to eosinophilic cytoplasm. Of note, intraepithelial lymphocytosis by atypical lymphoid cells was observed in the respiratory epithelium within and around the nodule. Immunohistochemically, the tumor cells were CD3+, TCRβF1-, TCRγ+, CD5-, CD7+, CD20-, CD79a-, CD30-, CD4-, CD8-, CD10-, BCL6-, CD21-, CD56+, CD57-, and CD138-, and expressed cytotoxic molecules. Epstein–Barr virus (EBV) was not detected by an in situ hybridization assay for EBV-encoded RNA. Interestingly, CD103 was expressed by a subset of tumor cells, especially those infiltrating the epithelium. T cell clonality was detected by multiplex PCR analysis of TRG and TRD gene rearrangements. After 2 months of systemic chemotherapy, PET scan showed regression of the size and metabolic activity of the lesions. This case represents a unique γδ T cell lymphoma of the lungs showing epitheliotropism by CD103+ γδ T cells that is suggestive of tissue-resident γδ T cells as the cell of origin.


γδ T cell lymphoma Epitheliotropism CD103 Tissue-resident γδ T cell Pulmonary lymphoma 



This work was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (grant number: NRF-2013R1A1A2013210).

Conflict of interest

We declare that we have no conflict of interest.


  1. 1.
    Carding SR, Egan PJ (2002) Gammadelta T cells: functional plasticity and heterogeneity. Nat Rev Immunol 2(5):336–345. doi: 10.1038/nri797 PubMedCrossRefGoogle Scholar
  2. 2.
    Komori HK, Meehan TF, Havran WL (2006) Epithelial and mucosal gamma delta T cells. Curr Opin Immunol 18(5):534–538. doi: 10.1016/j.coi.2006.06.001 PubMedCrossRefGoogle Scholar
  3. 3.
    Hayday A, Theodoridis E, Ramsburg E, Shires J (2001) Intraepithelial lymphocytes: exploring the third way in immunology. Nat Immunol 2(11):997–1003. doi: 10.1038/ni1101-997 PubMedCrossRefGoogle Scholar
  4. 4.
    Tripodo C, Iannitto E, Florena AM, Pucillo CE, Piccaluga PP, Franco V, Pileri SA (2009) Gamma-delta T-cell lymphomas. Nat Rev Clin Oncol 6(12):707–717. doi: 10.1038/nrclinonc.2009.169 PubMedCrossRefGoogle Scholar
  5. 5.
    Garcia-Herrera A, Song JY, Chuang SS, Villamor N, Colomo L, Pittaluga S, Alvaro T, Rozman M, de Anda Gonzalez J, Arrunategui AM, Fernandez E, Gonzalvo E, Estrach T, Colomer D, Raffeld M, Gaulard P, Campo E, Jaffe ES, Martinez A (2011) Nonhepatosplenic gammadelta T-cell lymphomas represent a spectrum of aggressive cytotoxic T-cell lymphomas with a mainly extranodal presentation. Am J Surg Pathol 35(8):1214–1225. doi: 10.1097/PAS.0b013e31822067d1 PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Arnulf B, Copie-Bergman C, Delfau-Larue MH, Lavergne-Slove A, Bosq J, Wechsler J, Wassef M, Matuchansky C, Epardeau B, Stern M, Bagot M, Reyes F, Gaulard P (1998) Nonhepatosplenic gammadelta T-cell lymphoma: a subset of cytotoxic lymphomas with mucosal or skin localization. Blood 91(5):1723–1731PubMedGoogle Scholar
  7. 7.
    Chan JK, Chan AC, Cheuk W, Wan SK, Lee WK, Lui YH, Chan WK (2011) Type II enteropathy-associated T-cell lymphoma: a distinct aggressive lymphoma with frequent gammadelta T-cell receptor expression. Am J Surg Pathol 35(10):1557–1569. doi: 10.1097/PAS.0b013e318222dfcd PubMedCrossRefGoogle Scholar
  8. 8.
    Delabie J, Holte H, Vose JM, Ullrich F, Jaffe ES, Savage KJ, Connors JM, Rimsza L, Harris NL, Muller-Hermelink K, Rudiger T, Coiffier B, Gascoyne RD, Berger F, Tobinai K, Au WY, Liang R, Montserrat E, Hochberg EP, Pileri S, Federico M, Nathwani B, Armitage JO, Weisenburger DD (2011) Enteropathy-associated T-cell lymphoma: clinical and histological findings from the international peripheral T-cell lymphoma project. Blood 118(1):148–155. doi: 10.1182/blood-2011-02-335216 PubMedCrossRefGoogle Scholar
  9. 9.
    van Dongen JJ, Langerak AW, Bruggemann M, Evans PA, Hummel M, Lavender FL, Delabesse E, Davi F, Schuuring E, Garcia-Sanz R, van Krieken JH, Droese J, Gonzalez D, Bastard C, White HE, Spaargaren M, Gonzalez M, Parreira A, Smith JL, Morgan GJ, Kneba M, Macintyre EA (2003) Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 17(12):2257–2317. doi: 10.1038/sj.leu.2403202 PubMedCrossRefGoogle Scholar
  10. 10.
    Mueller SN, Gebhardt T, Carbone FR, Heath WR (2013) Memory T cell subsets, migration patterns, and tissue residence. Annu Rev Immunol 31:137–161. doi: 10.1146/annurev-immunol-032712-095954 PubMedCrossRefGoogle Scholar
  11. 11.
    Gebhardt T, Mackay LK (2012) Local immunity by tissue-resident CD8(+) memory T cells. Front Immunol 3:340. doi: 10.3389/fimmu.2012.00340 PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Witherden DA, Havran WL (2013) Cross-talk between intraepithelial gammadelta T cells and epithelial cells. J Leukoc Biol 94(1):69–76. doi: 10.1189/jlb.0213101 PubMedCentralPubMedCrossRefGoogle Scholar
  13. 13.
    Havran WL, Jameson JM, Witherden DA (2005) Epithelial cells and their neighbors. III. Interactions between intraepithelial lymphocytes and neighboring epithelial cells. Am J Physiol Gastrointest Liver Physiol 289(4):G627–G630. doi: 10.1152/ajpgi.00224.2005 PubMedGoogle Scholar
  14. 14.
    Agace WW (2008) T-cell recruitment to the intestinal mucosa. Trends Immunol 29(11):514–522. doi: 10.1016/ PubMedCrossRefGoogle Scholar
  15. 15.
    Goto E, Kohrogi H, Hirata N, Tsumori K, Hirosako S, Hamamoto J, Fujii K, Kawano O, Ando M (2000) Human bronchial intraepithelial T lymphocytes as a distinct T-cell subset: their long-term survival in SCID-Hu chimeras. Am J Respir Cell Mol Biol 22(4):405–411. doi: 10.1165/ajrcmb.22.4.3861 PubMedCrossRefGoogle Scholar
  16. 16.
    Piet B, de Bree GJ, Smids-Dierdorp BS, van der Loos CM, Remmerswaal EB, von der Thusen JH, van Haarst JM, Eerenberg JP, ten Brinke A, van der Bij W, Timens W, van Lier RA, Jonkers RE (2011) CD8(+) T cells with an intraepithelial phenotype upregulate cytotoxic function upon influenza infection in human lung. J Clin Investig 121(6):2254–2263. doi: 10.1172/JCI44675 PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Ji-Young Choe
    • 1
  • Bettina Bisig
    • 2
  • Laurence de Leval
    • 2
  • Yoon Kyung Jeon
    • 1
    Email author
  1. 1.Department of PathologySeoul National University HospitalSeoulRepublic of Korea
  2. 2.Institute of PathologyCentre Hospitalier Universitaire Vaudois - CHUV (University Hospital Lausanne)LausanneSwitzerland

Personalised recommendations