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  • Review Article
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Gamma-delta T-cell lymphomas

Nature Reviews Clinical Oncology volume 6, pages 707–717 (2009)Cite this article

Abstract

Peripheral T-cell lymphomas (TCLs) are uncommon neoplasms, accounting for about 12% of all lymphoid tumors worldwide. TCLs in which γδ T-cell receptors are expressed (γδ TCLs) are extremely aggressive and rare (<1% of lymphoid neoplasms). γδ TCLs originate from γδ T cells, a small subset of peripheral T cells with direct antigen recognition capability acting at the interface between innate and adaptive immunity. Two distinct γδ TCL entities are recognized: hepatosplenic T-cell lymphoma (HSTL) and primary cutaneous γδ T-cell lymphoma (PCGD-TCL). HSTL is a well-characterized extranodal lymphoma that has a disguised onset, secondary to intrasinusoidal infiltration of the spleen, liver and bone marrow, has a rapidly progressive course that is poorly responsive to chemotherapy, and often ensues in the setting of immune system suppression. PCGD-TCL can present with prominent epidermal involvement or with a panniculitis-like clinical picture that can be complicated by a concurrent hemophagocytic syndrome; the disease shows biological and phenotypic overlap with other extranodal γδ TCLs that involve the respiratory or gastrointestinal tract mucosa. The regular application of phenotypic and molecular techniques is crucial for the diagnosis of γδ TCLs. In this Review, we discuss the clinical and biological features, the diagnostic challenges and the therapeutic perspectives of HSTL and PCGD-TCL.

Key Points

  • T-cell lymphomas that bear γδ T-cell receptors are heterogeneous biological entities that share a very poor prognosis irrespective of their site of origin

  • The actual incidence of γδ lymphomas is probably underestimated because of difficulties in the identification of γδ T-cell receptors in routine biopsy specimens

  • In young patients who present with hepatosplenomegaly, jaundice, altered liver function parameters, thrombocytopenia, and fever, hepatosplenic T-cell lymphoma should be included in the differential diagnosis

  • The response of γδ T-cell lymphomas to standard chemotherapy regimens is poor

  • Cytarabine combined with platinum-containing chemotherapies consolidated with stem cell transplantation seems to be the best available therapeutic strategy for eligible patients on diagnosis

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Figure 1: Structure of the TCR.
Figure 2: A schematic overview of the presumptive pathogenesis of HSTL and PCGD-TCL, the two main γδ T-cell lymphoma entities.
Figure 3: Histological and immunophenotypical features of HSTL.
Figure 4: Histological and immunophenotypic features of PCGD-TCL.

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Acknowledgements

The authors are indebted to Dr. Mario Colombo of the IRCSS Istituto Nazionale dei Tumori, Milan, for helpful discussions. This manuscript was supported by grants from the Gruppo Italiano Studio Linfomi, Associazione Italiana per la Ricerca sul Cancro (Milan), BolognAIL (Bologna), Centro Interdipartimentale di Ricerca sul Cancro “G. Prodi” (Bologna), Fondazione Cassa di Risparmio in Bologna (Bologna).

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  1. Department of Human Pathology, University of Palermo, Palermo, Italy

    Claudio Tripodo, Ada Maria Florena & Vito Franco

  2. Department of Oncology, Unit of Hematology, University of Palermo, Palermo, Italy

    Emilio Iannitto

  3. Department of Biomedical Science and Technology, Immunology Section, University of Udine, Udine, Italy

    Carlo Ennio Pucillo

  4. Department of Hematology and Clinical Oncology “L. e A. Seràgnoli”, Bologna University School of Medicine, Bologna, Italy

    Pier Paolo Piccaluga & Stefano Aldo Pileri

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Tripodo, C., Iannitto, E., Florena, A. et al. Gamma-delta T-cell lymphomas. Nat Rev Clin Oncol 6, 707–717 (2009). https://doi.org/10.1038/nrclinonc.2009.169

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