Original ArticlesNonhepatosplenic γδ T-cell Lymphomas Represent a Spectrum of Aggressive Cytotoxic T-cell Lymphomas With a Mainly Extranodal PresentationGarcia-Herrera, Adriana MD*; Song, Joo Y. MD†; Chuang, Shih-Sung MD‡; Villamor, Neus MD, PhD*; Colomo, Luis MD, PhD*; Pittaluga, Stefania MD, PhD†; Alvaro, Tomas MD§; Rozman, Maria MD, PhD*; de Anda Gonzalez, Jazmin MD∥; Arrunategui, Ana Maria MD¶; Fernandez, Eva BSc*; Gonzalvo, Elena BSc*; Estrach, Teresa MD, PhD♯; Colomer, Dolors PhD*; Raffeld, Mark MD†; Gaulard, Philippe MD**; Campo, Elias MD, PhD*; Jaffe, Elaine S. MD†; Martinez, Antonio MD, PhD*Author Information *Department of Pathology, Hospital Clinic, IDIBAPS ♯Department of Dermatology, Hospital Clinic, University of Barcelona, Barcelona §Department of Pathology, Hospital Verge de la Cinta, Tortosa, Spain †Hematopathology Section, Laboratory of Pathology, National Cancer Institute, Bethesda, MD ‡Department of Pathology, Chi-Mei Medical Center, Tainan and Taipei Medical University, Taipei, Taiwan ∥Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico D.F., Mexico ¶Fundación Valle del Lili, Cali Colombia **Department of Pathology, INSERM U955, Hospital Henri Mondor, University of Paris Est, Créteil, France Conflict of Interest and Sources of Funding: Supported by Instituto de Salud Carlos III, Fondo de Investigación Sanitaria) PI080095 (AM) and PI050458 (TE). The Spanish Comisión Interministerial de Ciencia y Tecnología (CICYT) SAF08-3630 (EC), Red Temática de Investigación Cooperativa del Cáncer (RTICC) RD06/0020/0039 (EC), AGH is a fellow supported by the Instituto de Salud Carlos III. This study was also supported by the Intramural Research Program of the Center for Cancer Research, National Cancer Institute. For the remaining authors none were declared. Supplemental Digital Content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website, www.ajsp.com. Correspondence: Antonio Martinez, MD, PhD, Hematopathology Section, Laboratory of Pathology, Hospital Clinic Villarroel 170 E3-P5, 08036 Barcelona, Spain (e-mail: [email protected]).> The American Journal of Surgical Pathology: August 2011 - Volume 35 - Issue 8 - p 1214-1225 doi: 10.1097/PAS.0b013e31822067d1 Buy SDC Metrics Abstract γδ T cells represent a minor T-cell subset that is mainly distributed in mucosal surfaces. Two distinct lymphomas derived from these cells have been recognized: hepatosplenic γδ T-cell lymphoma (HSTL) and primary cutaneous γδ T-cell lymphoma (PCGD-TCL). However, whether other anatomic sites may also be involved and whether they represent a spectrum of the same disease are not well studied. The lack of T-cell receptor (TCR)β expression has been used to infer a γδ origin when other methods are not available. We studied 35 T-cell tumors suspected to be γδ TCL using monoclonal antibodies reactive with TCR δ or γ in paraffin sections. We were able to confirm γδ chain expression in 22 of 35 cases. We identified 8 PCGD-TCLs, 6 HSTLs, and 8 γδ TCLs without hepatosplenic or cutaneous involvement involving mainly extranodal sites. Two such cases were classified as enteropathy-associated T-cell lymphoma, type II. The other γδ TCL presented in the intestine, lung, tongue, orbit, and lymph node. In addition, we observed 13 cases with mainly extranodal involvement that lacked any TCR expression (“TCR silent”). In all cases, a natural killer cell origin was excluded. In conclusion, the lack of TCRβ expression does not always predict γδ-T-cell derivation, as TCR silent cases may be found. The recognition of γδ TCL presenting in extranodal sites other than skin and liver/spleen expands the clinical spectrum of these tumors. However, non-HSTL γδ TCL do not seem to represent a single entity. The relationship of these tumors with either HSTL or PCGD-TCL requires further study. © 2011 Lippincott Williams & Wilkins, Inc.