Gamma-delta t-cell lymphomas

Eur J Haematol. 2015 Mar;94(3):206-18. doi: 10.1111/ejh.12439. Epub 2014 Oct 1.

Abstract

Gamma-delta T-cell lymphomas are aggressive and rare diseases originating from gamma-delta lymphocytes. These cells, which naturally play a role in the innate, non-specific immune response, develop from thymic precursor in the bone marrow, lack the major histocompatibility complex restrictions and can be divided into two subpopulations: Vdelta1, mostly represented in the intestine, and Vdelta2, prevalently located in the skin, tonsils and lymph nodes. Chronic immunosuppression such as in solid organ transplanted subjects and prolonged antigenic exposure are probably the strongest risk factors for the triggering of lymphomagenesis. Two entities are recognised by the 2008 WHO Classification: hepatosplenic gamma-delta T-cell lymphoma (HSGDTL) and primary cutaneous gamma-delta T-cell lymphoma (PCGDTL). The former is more common among young males, presenting with B symptoms, splenomegaly and thrombocytopenia, usually with the absence of nodal involvement. Natural behaviour of HSGDTL is characterised by low response rates, poor treatment tolerability, common early progression of disease and disappointing survival figures. PCGDTL accounts for <1% of all primary cutaneous lymphomas, occurring in adults with relevant comorbidities. Cutaneous lesions may vary, but its clinical behaviour is usually aggressive and long-term survival is anecdotal. Available literature on gamma-delta T-cell lymphomas is fractioned, mostly consisting of case reports or small cumulative series. Therefore, clinical suspicion and diagnosis are usually delayed, and therapeutic management remains to be established. This review critically analyses available evidence on diagnosis, staging and behaviour of gamma-delta T-cell lymphomas, provides recommendations for therapeutic management in routine practice and discusses relevant unmet clinical needs for future studies.

Keywords: T-cell lymphoma; extranodal lymphoma; gamma-delta T lymphocytes; hepatosplenic gamma-delta T-cell lymphoma; primary cutaneous gamma-delta T-cell lymphoma.

MeSH terms

  • Antineoplastic Agents / therapeutic use*
  • Carcinogenesis / chemically induced
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology
  • Delayed Diagnosis
  • Disease Management*
  • Hematopoietic Stem Cell Transplantation
  • Humans
  • Immunosuppressive Agents / adverse effects
  • Intestines / drug effects
  • Intestines / pathology
  • Lymph Nodes / drug effects
  • Lymph Nodes / pathology
  • Lymphoma, T-Cell / classification*
  • Lymphoma, T-Cell / diagnosis*
  • Lymphoma, T-Cell / mortality
  • Lymphoma, T-Cell / therapy
  • Palatine Tonsil / drug effects
  • Palatine Tonsil / pathology
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / metabolism*
  • Skin / drug effects
  • Skin / pathology
  • Survival Analysis
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / pathology

Substances

  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Receptors, Antigen, T-Cell, gamma-delta