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Eruptive keratoacanthoma following topical imiquimod for in situ squamous cell carcinoma of the skin in a renal transplant recipient

2008; Elsevier BV; Volume: 59; Issue: 5 Linguagem: Inglês

10.1016/j.jaad.2008.06.018

1097-6787

Amanda Marcollo Pini, Simon Koch, Leo Schärer, Lars E. French, Severin Läuchli, Günther F.L. Hofbauer,

Cutaneous lymphoproliferative disorders research

To the Editor: Keratoacanthoma is an epithelial skin tumor characterized by rapid growth and spontaneous involution within months, with a typical clinical and histopathologic picture, with 90% of keratoacanthomata arising on sun-exposed skin.1Pattee S.F. Silvis N.G. Keratoacanthoma developing in sites of previous trauma: a report of two cases and review of the literature.J Am Acad Dermatol. 2003; 48: S35-S38Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar Keratoacanthoma is believed to be an abortive form of squamous cell carcinoma of the skin.2Watanabe D. Tachi N. Tomita Y. Keratoacanthoma centrifugum marginatum arising from a scar after skin injury.J Dermatol. 1999; 26: 541-543PubMed Google Scholar Immunosuppressed patients show a higher incidence of keratoacanthomata.3Dessoukey M.W. Omar M.F. Abdel-Dayem H. Eruptive keratoacanthomas associated with immunosuppressive therapy in a patient with systemic lupus erythematosus.J Am Acad Dermatol. 1997; 37: 478-480Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar Eruption after excision of squamous cell carcinomas has been observed under immunosuppression.4Washington Jr., C.V. Mikhail G.R. Eruptive keratoacanthoma en plaque in an immunosuppressed patient.J Dermatol Surg Oncol. 1987; 13: 1357-1360Crossref PubMed Scopus (18) Google Scholar Here, we report a case of eruptive keratoacanthoma in a renal transplant recipient following topical therapy with imiquimod. An 80-year-old female presented to a dermatologist 20 years after renal transplantation with Bowen disease and a 3-month history of multiple actinic keratoses on her lower legs and the dorsal surfaces of her hands. Topical imiquimod 5% was prescribed twice weekly over 3 months. Erythema, edema, and erosion developed with the clinical clearance of actinic keratoses and Bowen disease. One month before admission, under continued imiquimod treatment, several rapidly growing tumors appeared in the treatment area. Ten erythematous papules and nodules with teleangiectasia and a partially seen central keratin plug were observed on the dorsal surface of her hands and her lower legs in the imiquimod-treated areas (Fig 1). Tumors from the dorsal surface of her left hand and left lower leg were excised and histologically showed a keratin-filled crater (Fig 2, A) lined by a proliferating squamous epithelium, large eosinophilic nucleoli, and some mitotic figures at the periphery of lobules (Fig 2, B). A diagnosis of multiple eruptive keratoacanthomata was established. After surgical removal, no skin tumors recurred up to her death 6 months later from unrelated cardiac failure.Fig 2A, Symmetric tumor with keratin-filled crater lined by a proliferating squamous epithelium. B, Partial view of keratin-filled crater with proliferating squamous epithelium. The cells have large vesicular nuclei, large eosinophilic nucleoli, and irregularly distributed chromatin. Many mitotic figures are present at the peripheries of lobules. (Hematoxylin–eosin stain; original magnification: A, ×20; B, ×100.)View Large Image Figure ViewerDownload Hi-res image Download (PPT) Imiquimod may have triggered keratoacanthoma; lesions appeared only under continued imiquimod treatment with the clearance of actinic keratosis and Bowen disease.5D'Addario S. Carrington P.R. Multiple keratoacanthomas as an untoward response to imiquimod therapy for actinic keratoses.Acta Derm Venereol. 2006; 86: 366-367Crossref PubMed Scopus (17) Google Scholar Triggering of keratoacanthoma after imiquimod treatment has been reported.1Pattee S.F. Silvis N.G. Keratoacanthoma developing in sites of previous trauma: a report of two cases and review of the literature.J Am Acad Dermatol. 2003; 48: S35-S38Abstract Full Text Full Text PDF PubMed Scopus (80) Google Scholar, 2Watanabe D. Tachi N. Tomita Y. Keratoacanthoma centrifugum marginatum arising from a scar after skin injury.J Dermatol. 1999; 26: 541-543PubMed Google Scholar, 3Dessoukey M.W. Omar M.F. Abdel-Dayem H. Eruptive keratoacanthomas associated with immunosuppressive therapy in a patient with systemic lupus erythematosus.J Am Acad Dermatol. 1997; 37: 478-480Abstract Full Text Full Text PDF PubMed Scopus (21) Google Scholar, 4Washington Jr., C.V. Mikhail G.R. Eruptive keratoacanthoma en plaque in an immunosuppressed patient.J Dermatol Surg Oncol. 1987; 13: 1357-1360Crossref PubMed Scopus (18) Google Scholar, 6Weiss G. Shemer A. Trau H. The Koebner phenomenon: review of the literature.J Eur Acad Dermatol Venereol. 2002; 16: 241-248Crossref PubMed Scopus (253) Google Scholar, 7Gewirtzman A. Meirson D.H. Rabinovitz H. Eruptive keratoacanthomas following carbon dioxide laser resurfacing.Dermatol Surg. 1999; 25: 666-668Crossref PubMed Scopus (36) Google Scholar, 8Janik J.P. Bang R.H. Traumatic keratoacanthoma arising in a 15-year-old boy following a motor vehicle accident.Pediatr Dermatol. 2006; 23: 448-450Crossref PubMed Scopus (15) Google Scholar, 9Tamir G. Morgenstern S. Ben-Amitay D. Okon E. Hauben D.J. Synchronous appearance of keratoacanthomas in burn scar and skin graft donor site shortly after injury.J Am Acad Dermatol. 1999; 40: 870-871Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar Imiquimod activates the Toll-like receptor 7 leading to the expression of interferon alfa and a range of cytokines and chemokines. CD3+, CD4+, and CD8+ lymphocytes in treated lesions and T-cell–restricted intracellular antigen-1 positive granzyme B+ cytotoxic T cells and CD123+ plasmacytoid dendritic cells are increased.10Schwartz R.A. Keratoacanthoma: a clinico-pathologic enigma.Dermatol Surg. 2004; 30: 326-333Crossref PubMed Google Scholar Such triggering resembles koebnerization, typically seen in psoriasis, by epidermal cell injury and dermal inflammation.6Weiss G. Shemer A. Trau H. The Koebner phenomenon: review of the literature.J Eur Acad Dermatol Venereol. 2002; 16: 241-248Crossref PubMed Scopus (253) Google Scholar Basic fibroblast growth factor (b-FGF) is released from traumatized keratinocytes and stimulates the proliferation of endothelial cells, which may lead to the development of a tumor in predisposed patient.6Weiss G. Shemer A. Trau H. The Koebner phenomenon: review of the literature.J Eur Acad Dermatol Venereol. 2002; 16: 241-248Crossref PubMed Scopus (253) Google Scholar However, the application of imiquimod in melanoma metastasis led to reduced FGF-2 expression.11Hesling C. D'Incan M. Mansard S. Franck F. Corbin-Duval A. Chevenet C. et al.In vivo and in situ modulation of the expression of genes involved in metastasis and angiogenesis in a patient treated with topical imiquimod for melanoma skin metastases.Br J Dermatol. 2004; 150: 761-767Crossref PubMed Scopus (75) Google Scholar A direct induction of bFGF by imiquimod seems thus rather unlikely. In summary, we report keratoacanthoma development under imiquimod treatment, suggesting imiquimod as potential trigger with involvement of the Toll-like receptor 7 pathway.