Pralatrexate-induced tumor cell apoptosis in the epidermis of a patient with HTLV-1 adult T-cell lymphoma/leukemia causing skin erosions by Alexander G.

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Pralatrexate-induced tumor cell apoptosis in the epidermis of a patient with HTLV-1 adult T-cell lymphoma/leukemia causing skin erosions by Alexander G. Marneros, Marc E. Grossman, David N. Silvers, Sameera Husain, Gerard J. Nuovo, Barbara MacGregor-Cortelli, Ellen Neylon, Molly Patterson, Owen A. O'Connor, and Jasmine M. Zain Blood Volume 113(25):6338-6341 June 18, 2009 ©2009 by American Society of Hematology

Pralatrexate induces skin erosions limited to areas affected by ATLL Pralatrexate induces skin erosions limited to areas affected by ATLL. (A) ATLL skin lesions with confluent erythematous papules of the dorsal hands with areas of sparing over knuckles (*). Pralatrexate induces skin erosions limited to areas affected by ATLL. (A) ATLL skin lesions with confluent erythematous papules of the dorsal hands with areas of sparing over knuckles (*). Pompholyx-like lesions on digits. Pictures were taken 3 days after the first dose of pralatrexate was given. (B) Skin erosions within affected areas 6 days after the first dose of pralatrexate was administered. (C) Resolution of rash with postinflammatory hyperpigmentation 3 months later. (D) Higher magnification of skin erosions (arrow) on the right leg 6 days after the first dose of pralatrexate. (E) In situ hybridization for HTLV-1 shows positive signal within atypical lymphocytes in the epidermis (bold arrow), whereas red counterstain is observed in dermal fibroblast (→; original magnification ×40). (F) Immunohistochemistry for HTLV-1 shows positive signal in atypical lymphocytes in Pautrier microabscesses (; original magnification ×40). Alexander G. Marneros et al. Blood 2009;113:6338-6341 ©2009 by American Society of Hematology

Pralatrexate induces tumor cell lysis within epidermal Pautrier microabscesses without affecting keratinocytes. 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). Alexander G. Marneros et al. Blood 2009;113:6338-6341 ©2009 by American Society of Hematology