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Immunophenotypic Shifts in Primary Cutaneous γδ T-Cell Lymphoma Suggest Antigenic Modulation: A Study of Sequential Biopsy Specimens

Agbay, Rose Lou Marie C. MD; Torres-Cabala, Carlos A. MD; Patel, Keyur P. MD; Merril, Eric D. MS; Duvic, Madeleine MD; Quesada, Andres MD; Prieto, Victor G. MD; Aung, Phyu P. MD; Loghavi, Sanam MD; Young, Ken H. MD; Hu, Shimin MD; Ferrufino-Schmidt, Maria C. MD; Tetzlaff, Michael MD, PhD; Li, Shaoying MD; Medeiros, L. Jeffrey MD; Miranda, Roberto N. MD

The American Journal of Surgical Pathology: April 2017 - Volume 41 - Issue 4 - p 431–445
doi: 10.1097/PAS.0000000000000786
Original Articles

Primary cutaneous γδ T-cell lymphoma (PCGD TCL), an aggressive type of lymphoma, accounts for approximately 1% of all primary cutaneous lymphomas. We have occasionally observed changes in T-cell antigen expression (immunophenotypic [IP] shift) over time, a phenomenon that is considered rare in T-cell lymphoma including cutaneous T-cell lymphoma. Therefore, we assessed sequential biopsies of PCGD TCL for possible IP shifts of the lymphoma cells. We searched for cases of PCGD TCL with consecutive biopsies to perform a comprehensive immunohistochemical analysis of paired specimens. A median of 12 markers per case was tested. We evaluated the percentage of neoplastic lymphocytes and determined the differential expression of antigens (gain, loss, increase or decrease). We identified 9 patients with PCGD TCL with consecutive biopsies. All (100%) cases had IP shifts of at least 1 antigen, whereas overall 22 pairs of markers were shifted: gain of reactivity occurred in 7 (31.8%) and loss in 3 (13.6%); increased reactivity in 4 (18.2%) and decreased in 8 (36.4%). Molecular analysis of TCRγ showed identically sized monoclonal rearrangements between biopsy pairs in 4/4 (100%) patients. There was no correlation between IP shifts and the clinical appearance of lesions, histopathologic or cytologic features, or molecular rearrangements. IP shifts are common in PCGD TCL, occurring in all patients in this study and involving a variety of antigens. IP shifts do not seem to be linked to changes in the T-cell clone and are without obvious clinical or morphologic correlates. The occurrence of IP shifts in PCGD TCL suggests that antigen modulation may be involved in pathogenesis. IP shifts are somewhat frequent in T-cell lymphoma; however, it does not suggest a second neoplasm, and molecular studies can be used to determine clonal identity.

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Departments of *Hematopathology



Translational and Molecular Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX

§University of Missouri, Kansas City, MO

Departamento de Patologia, Universidad Peruana Cayetano Heredia, Lima, Peru

Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Roberto N. Miranda, MD, Department of Hematopathology, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 72, Houston, TX 77030 (e-mail:

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