Primary Cutaneous γδ T-Cell Lymphoproliferative Disorder Following a Stingray Puncture: A Case Report

Introduction: Primary cutaneous γδ T-cell lymphoma (PCGD-TCL) is a rare neoplasm, of unknown etiology, composed of mature, activated, γδ T cells with a cytotoxic phenotype, usually presenting as plaques or nodules with ulceration. PCGD-TCL, which has been classified as a distinct entity in the 2008 World Health Organization classification, often fails to respond to polychemotherapy and radiation therapy with a poor prognosis although some cases demonstrate relatively indolent behavior.

Objective: We report a case of cutaneous γδ T-Cell lymphoproliferative disorder following a stingray puncture and mimicking PCGD-TCL.

Case report: A 33-year-old man was referred for a generalized skin rash of seven years duration. In 2007, a stingray punctured his right ankle and one week later he developed cellulitis that responded to IV antibiotics. Five months later, multiple small, red spots appeared at the site of the puncture first and then on both ankles and gradually spread to the lower legs and torso. In 2011, arthralgias in knees and hands were successfully treated with oral prednisone, and his rash also improved transiently. Eosinophilia of up to 31% fell to 10% on prednisone but persisted. At presentation to MDACC in Dec 2012, on physical exam there was a red capillaritis-like fixed exanthem from the waist down. Small nodules were present on his right lower leg and back. Flow cytometry of peripheral blood showed CD8+ T cells with partial loss of CD5 and CD7, and partial expression of CD56 and CD57. Bone marrow was negative. PET scan showed a few small skin nodules without lymphadenopathy. Increased serum beta-2-microglobulin (2.6 mg/L) and lactate dehydrogenase (680 IU/L) were noted. Multiple biopsies from capillaritis and nodules showed perivascular, periadnexal, and subcutaneous infiltrates of small to medium sized CD8+ T cells, eosinophils, and CD68+/S100+ histiocytes. Anti-CD1a staining highlighted scattered, small clusters of dendritic cells with a small subset of Langerin+ cells. There were scattered mast cells as highlighted by anti-tryptase. Molecular studies showed T-cell receptor γ chain gene rearrangements identical in skin and peripheral blood.

Discussion : This patient developed generalized capillaritis, arthralgias, and neuropathy following a stingray puncture, an injury occurring in approximately 2000 people annually in the USA. In one other patient with a stingray puncture, a skin biopsy taken four days later showed central hemorrhagic necrosis with surrounding infiltrate of eosinophils and lymphoid cells, which were mainly CD3+, CD4+ and TIA+. Both cases suggest a host immunological reaction with eosinophils to stingray toxin venom. In particular, stingray venom contains tetraspanins which are known to activate macrophages and induce chemotaxis of eosinophils. The presence of CD68+/S100+ histiocytes and CD1a+/Langerin+ cells in our patient suggests activation of the classic macrophage- maturation pathway, leading to proliferation of CD8+ T-cells and promotion of anti-tumor immunity. Human Vδ1+ γδ T cells are known to recognize phospholipid antigens presented by CD1a+ cells. We hypothesize that tetraspanins in stingray toxin may have induced chemotaxis for eosinophils and promoted CD8+ immunosurveillance by controlling the antigen presentation process and macrophage activation.

Summary: Although this patient's skin lesions had several poor prognostic factors (monoclonal TCR γ in skin and peripheral blood, elevated lactic dehydrogenase and beta-2-microglobulin, and CD8+ cytotoxic markers), unlike PCGD-TCL his clinical course was indolent over 7 years and his lesions responded to oral prednisone. Therefore, we conclude that this patient developed a PCGD-TCL- like immune reaction to stingray venom similar to that reported against tetraspanins. Further studies are needed to confirm this mechanism.