Rapid deterioration in a patient with primary aggressive cutaneous epidermotropic CD8+ cytotoxic T-cell (‘Berti’) lymphoma after administration of adalimumab
Authors: Sarah M. Jacks, Brent R. Taylor, Raford P. Rogers, Jonathan S. Ralston, John S. Metcalf, John Lazarchick
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Primary aggressive cutaneous epidermotropic CD8+ cytotoxic T-cell lymphoma, a World Health Organization provisional entity here referred to as "Berti lymphoma," comprises less than 1% of cutaneous T-cell lymphomas (CTCLs).1Willemze R. Meijer C.J. Classification of cutaneous T-cell lymphoma: From Alibert to WHO-EORTC.J Cutan Pathol. 2006; 33: 18-26Crossref PubMed Scopus (93) Google Scholar Berti lymphoma classically presents as eruptive hyperkeratotic plaques or nodules with a phase of ulceration and necrosis.2Willemze R. Jaffe E.S. Burg G. Cerroni L. Berti E. Swerdlow S.H. et al.WHO-EORTC classification for cutaneous lymphomas.Blood. 2005; 105: 3768Crossref PubMed Scopus (3266) Google Scholar The epidermis exhibits epidermotropism of atypical pleomorphic lymphocytes and occasional necrotic keratinocytes.2Willemze R. Jaffe E.S. Burg G. Cerroni L. Berti E. Swerdlow S.H. et al.WHO-EORTC classification for cutaneous lymphomas.Blood. 2005; 105: 3768Crossref PubMed Scopus (3266) Google Scholar Dissemination to lung, testis, central nervous system, and oral mucosa with sparing of lymph nodes is common.3Berti E. Tomasini D. Vermeer M.H. Meijer C.J. Alessi E. Willemze R. Primary cutaneous CD8-positive epidermotropic cytotoxic T cell lymphomas: a distinct clinicopathological entity with an aggressive clinical behavior.Am J Pathol. 1999; 155: 483-492Abstract Full Text Full Text PDF PubMed Scopus (369) Google Scholar We present a case of Berti lymphoma that arose following a trial of adalimumab in the setting of a long-standing spongiotic and psoriasiform dermatitis clinically suggestive of psoriasis. A 35-year-old African American woman had a 10-year history of nonspecific "dermatitis." In the year before her death, she was admitted to her local hospital several times for shortness of breath and dermatitis and was repeatedly treated with prednisone. Skin biopsies from this period showed a nonspecific spongiotic and psoriasiform dermatitis. Immunohistochemical analysis failed to demonstrate any concerning atypical or CD8+ epidermotropic infiltrate. She was seen by a local dermatologist as an outpatient, psoriasis was diagnosed, and a single loading dose of adalimumab (80 mg) was administered. She presented 2 days later to her local hospital for respiratory decline and rapidly developing cutaneous ulceration. On transfer to our institution's intensive care unit 6 days later, examination revealed skin ulcers localized primarily to the trunk as well as serpiginous to arcuate scaly plaques and erosions on the extremities (Fig 1). A biopsy on an ulcer edge revealed an epidermotropic infiltrate of atypical CD8+ cells consistent with a diagnosis of Berti lymphoma (Fig 2). Atypical cells stained diffusely positive by immunohistochemistry for CD3, CD8, granzyme B, and TIA-1, with 70% of cells proliferating by Ki-67. A subpopulation of atypical cells were CD56 positive. Atypical cells were negative for CD4, CD5, CD7, CD20, CD30, CD57, CD99, HSV, and TdT. Flow cytometry of peripheral blood was normal, and HTLV I/II and EBV were negative. Left upper and lower lung biopsies revealed focal involvement by CD8+ and CD56+ atypical large lymphocytes consistent with pulmonary lymphoma. Respiratory function deteriorated, and she died 2 months after admission.Fig 2Biopsy of an ulcer on the chest exhibited an epidermotropic CD8+ infiltrate of atypical T-cells. (Hematoxylin-eosin stain; original magnification ×10.)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Adalimumab, a human tumor necrosis factor (TNF)-alpha monoclonal antibody, is indicated to treat a range of autoimmune diseases including psoriasis.4Dalle S. Balme B. Berger F. Hayett S. Thomas L. Mycosis fungoides-associated follicular mucinosis under adalimumab.Br J Dermatol. 2005; 153: 207-208Crossref PubMed Scopus (36) Google Scholar Whether TNF-alpha blockade is associated with development of lymphomas is controversial, but rapid and fatal progression of lymphomas after TNF-alpha blockade has been reported.4Dalle S. Balme B. Berger F. Hayett S. Thomas L. Mycosis fungoides-associated follicular mucinosis under adalimumab.Br J Dermatol. 2005; 153: 207-208Crossref PubMed Scopus (36) Google Scholar, 5Adams A.E. Zwicker J. Curiel C. Kadin M.E. Falchuk K.R. Drews R. et al.Aggressive cutaneous T-cell lymphomas after TNFalpha blockade.J Am Acad Dermatol. 2004; 51: 660-662Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar TNF-alpha blockade likely inhibits both innate and acquired immunity and may compromise immune surveillance for malignancy.5Adams A.E. Zwicker J. Curiel C. Kadin M.E. Falchuk K.R. Drews R. et al.Aggressive cutaneous T-cell lymphomas after TNFalpha blockade.J Am Acad Dermatol. 2004; 51: 660-662Abstract Full Text Full Text PDF PubMed Scopus (78) Google Scholar The relation between our patient's dermatitis and her Berti lymphoma is unclear. Her dermatitis may have represented a smoldering CTCL that transformed into Berti lymphoma, or the latter may have developed anew in the setting of immunosuppression. This case suggests that corticosteroid-refractory, histologically nonspecific dermatitis should be evaluated carefully and managed cautiously. Not all psoriasiform dermatitis is psoriasis or is safely treated as such. A high suspicion for possible CTCL and a low threshold for repeat biopsies to establish a diagnosis should be maintained when considering immunomodulatory therapy.