Gamma-delta T-cell lymphomas

• Published in: Nature reviews. Clinical oncology Vol. 6; no. 12; pp. 707 - 717
• Main Authors: Tripodo, Claudio, Iannitto, Emilio, Florena, Ada Maria, Pucillo, Carlo Ennio, Piccaluga, Pier Paolo, Franco, Vito, Pileri, Stefano Aldo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-12-2009; Nature Publishing Group
• Subjects: Cell receptors; Clinical Trials as Topic; Diagnosis; Gene Rearrangement, delta-Chain T-Cell Antigen Receptor - genetics; Gene Rearrangement, gamma-Chain T-Cell Antigen Receptor - genetics; Humans; Lymphoma, T-Cell, Cutaneous - diagnosis; Lymphoma, T-Cell, Cutaneous - genetics; Lymphoma, T-Cell, Peripheral - diagnosis; Lymphoma, T-Cell, Peripheral - genetics; Medicine; Medicine & Public Health; Oncology; Physiological aspects; Receptors, Antigen, T-Cell, gamma-delta - genetics; review-article; Risk factors; T cell lymphoma; T cells; Italy
• ISSN: 1759-4774; 1759-4782
• DOI: 10.1038/nrclinonc.2009.169

Gamma-delta lymphomas are rare and aggressive lymphomas with a poor prognosis. The authors of this Review discuss the clinical and biological features of the two types of such lymphomas and the diagnostic challenges associated with these still insufficiently known diseases.
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