Pralatrexate induces tumor cell lysis within epidermal Pautrier microabscesses without affecting keratinocytes. Apoptosis of atypical lymphocytes is demonstrated with staining for activated caspase 3. (A,B) First skin biopsy of papule 2 months before initiation of pralatrexate therapy. Pautrier microabscess in epidermis is seen. No staining for activated caspase 3 is observed (original magnifications: A, ×10; B, ×10). (C,D) Skin biopsy 3 days after the first dose of pralatrexate was given shows atypical cells within epidermal Pautrier microabscesses undergoing apoptosis, whereas no activated caspase 3 staining is observed in adjacent keratinocytes (original magnifications: C, ×10; D, ×20). (E,F) Skin biopsy of skin erosion 6 days after pralatrexate therapy was initiated. Necrosis and cellular debris are seen within epidermal Pautrier microabscesses accompanied by positive staining for activated caspase 3. No necrosis is seen in adjacent keratinocytes (*, original magnifications: E, ×10; F, ×20). Slides were viewed with a Zeiss Axio Scope light microscope using N-ACHROPLAN objectives (10×/0.25, 20×/0.45, and 40×/0.65), and images were acquired with an AxioCam HR camera (Carl Zeiss AG). Images were processed using Image-Pro Plus version 5.0 (Media Cybernetics).