Cutaneous involvement by angioimmunoblastic T-cell lymphoma with remarkable heterogeneous Epstein-Barr virus expression

Introduction: Initially described as an abnormal immune reaction, most case s of angioimmunoblastic lymphadenopathy with dysproteinemia (ARD)-like T-ce ll infiltrates are now regarded as a peripheral T-cell lymphoma (AILD T-NHL ). AILD T-NHL is characterized clinically with constitutional symptoms, gen eralized lymphadenopathy, hepatosplenomegaly, skin rash, and polyclonal hyp ergammaglobulinemia. Epstein-Barr virus (EBV) is frequently detected in inv olved lymph nodes, but the presence of EBV in cutaneous infiltrates of AILD T-NHL has rarely been examined. We present a patient with AILD T-NHL with cutaneous involvement that shows marked heterogeneity of EBV expression in the lymph node and skin biopsies, and review the histological findings of A ILD T-NHL in the skin. Methods: Two skin biopsies of a diffuse maculopapular rash and a lymph node were examined and immunophenotyped. In situ hybridization for detection of EBV in the lymph node and skin biopsies was utilized. In order to attempt to delineate which lymphocytes were EBV positive, skin biopsies were dual l abeled with CD3, CD45RO, CD20 and EBV. The skin biopsies and lymph node wer e submitted for gene rearrangement studies by polymerase chain reaction (PC R). Capillary electrophoresis of fluorescently labeled PCR products was uti lized for PCR product quantitation. Results: The histological features of the lymph node were diagnostic of AIL D T-NHL and a T-cell clone was identified by PCR. The skin biopsies showed an atypical superficial and deep perivascular polymorphous infiltrate consi stent with cutaneous involvement by AILD T-NHL. Both skin biopsies showed t he same clonal T-cell receptor gene rearrangement as the lymph node. In sit u hybridization of the lymph node and one skin biopsy showed a few scattere d EBV-positive lymphocytes (<1% of the infiltrate). A second skin biopsy re vealed 40-50% of the lymphocytes as EBV positive. Dual staining for CD20 an d EBV identified a minority of EBV-infected lymphocytes as B-cells, but mos t of the EBV-positive cells lacked staining for CD3 and CD45RO. Conclusions: In our patient, the same T-cell receptor gene rearrangement wa s found by PCR in all three biopsy sites. Most cases of AILD T-NHL contain only a few EBV-positive cells, but in our patient the extent of EBV express ion ranged from <1% to 40-50% of the AIM T-NHL cutaneous infiltrate. To our knowledge, this case is the most extensive and heterogeneous expression of EBV in cutaneous AILD T-NHL to date.