Paraneoplastic pemphigus due to natural‐killer/T‐cell lymphoma

Abstract

A 70-year-old woman presented with a 4-month history of right leg ulcers (upper left panel). Biopsy showed infiltration by abnormal medium to large size lymphoid cells (upper left middle panel, haematoxylin eosin). There was no obvious angiocentricity or angioinvasion. The abnormal lymphoid cells were positive for cytoplasmic CD3 epsilon (upper right middle panel, immunoperoxidase), CD56 (upper right panel), and T-cell intracellular antigen-1. In-situ hybridization for EpsteinBarr virus encoded RNA was positive. Overall features were consistent with extranodal natural killer (NK)/T-cell lymphoma, nasal type. She was treated with chemotherapy. After the second course, blistering skin eruptions occurred over the trunk, buttocks and legs (lower left panel). A skin biopsy revealed erythema multiforme-like areas with scattered cytoid bodies (white arrow) throughout all levels of the epidermis, and areas with pemphigus vulgaris-like changes showing early suprabasal acantholysis (black arrow) (lower right panel). Direct immunofluorescence studies showed weak intercellular and basement membrane staining with both C3 and IgG, confirming the diagnosis of paraneoplastic pemphigus (PNP). She deteriorated progressively and died 3 months after presentation despite immunosuppression and further chemotherapy. Paraneoplastic pemphigus characteristically presents as painful oral and mucosal ulcerations, with concomitant skin involvement simulating pemphigus vulgaris or erythema multiforme. Bronchiolitis obliterans may occur and can be fatal. PNP is caused by serum autoantibodies against epithelial proteins, particularly the plakin family, leading to epithelial injury in the skin, and mucosal and bronchial linings. Therefore, the underlying neoplasms are almost exclusively of B-cell lineage. However, T-cells and CD56+ NK cells have also been postulated to be effectors of PNP. This case illustrated the rare association between NK cell lymphoma and PNP, suggesting therefore that NK cells might be involved in the pathogenesis of PNP. Clinicians should also be alert to the possibility of PNP in lymphomas not of B-cell lineage.