Correspondence
Merkel-Cell Carcinomas in Patients Treated with Methoxsalen and Ultraviolet A Radiation
N Engl J Med 1998; 339:1247-1248October 22, 1998
- Article
To the Editor:
Merkel-cell carcinoma is a very rare small-cell carcinoma of the skin.1 Probably derived from Merkel cells, the mechanoreceptors located in the basal layer of the epidermis, these tumors are asymptomatic, solitary, small red-purple subcutaneous nodules.2 Most are found in elderly persons at sites exposed to the sun. The two-year survival rate is about 50 percent.3 As is the case for non-melanoma skin cancers, especially squamous-cell cancers, exposure to ultraviolet radiation and, possibly, ionizing radiation are risk factors for Merkel-cell carcinoma.
Since 1975, we have prospectively studied 1380 patients with psoriasis who were treated with oral methoxsalen (psoralen) and ultraviolet A photochemotherapy at 16 university centers to assess the long-term risks and benefits of ultraviolet A radiation.4 Merkel-cell carcinomas have developed in three of these patients (0.2 percent), suggesting that ultraviolet A photochemotherapy increases the risk of these rare tumors (Table 1Table 1
Characteristics of Three Patients with Merkel-Cell Carcinoma in the Follow-up Study of Ultraviolet A Photochemotherapy.). All three patients were elderly and had had non-melanoma skin cancers after exposure to ultraviolet A photochemotherapy. Only one patient reported exposure to ionizing radiation for the treatment of psoriasis. Two had received more than 300 treatments with ultraviolet A radiation. In two of the three, Merkel-cell carcinoma developed more than 20 years after they had started ultraviolet A photochemotherapy.In this cohort, the incidence of Merkel-cell carcinoma is about 100 times higher than that expected in the general population.1 Although we cannot exclude other causes of these tumors in the three patients, including exposure to other potential carcinogens for the treatment of psoriasis, our findings argue that long-term ultraviolet A photochemotherapy at high doses increases the risk of Merkel-cell carcinoma of the skin. In addition to melanoma and squamous-cell cancer, Merkel-cell carcinoma is yet another risk of ultraviolet A photochemotherapy that should be weighed against the benefits of this treatment.4,5
5 ReferencesElissa J. Lunder, M.D.
Robert S. Stern, M.D.
Beth Israel Deaconess Medical Center, Boston, MA 022151
The SEER histology monograph: supplemental tables. Histology of cancer incidence and prognosis. SEER population based data, 1973–1987. Version 1.0. Bethesda, Md.: National Cancer Institute, June 1995. (CD-ROM.)
2
Yiengpruksawan A ,Coit DG ,Thaler HT ,Urmacher C ,Knapper WK . Merkel cell carcinoma: prognosis and management. Arch Surg 1991;126:1514-1519
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Kokoska ER ,Kokoska MS ,Collins BT ,Stapleton DR ,Wade TP . Early aggressive treatment for Merkel cell carcinoma improves outcome. Am J Surg 1997;174:688-693
CrossRef | Web of Science | Medline4
Stern RS ,Laird N . The carcinogenic risk of treatments for severe psoriasis. Cancer 1994;73:2759-2764
CrossRef | Web of Science | Medline5
Stern RS ,Nichols KT ,Vakeva LH . Malignant melanoma in patients treated for psoriasis with methoxsalen (psoralen) and ultraviolet A radiation (PUVA). N Engl J Med 1997;336:1041-1045
Full Text | Web of Science | Medline
- Citing Articles (29)
Citing Articles
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David Schrama, Selma Ugurel, Jürgen C. Becker. (2012) Merkel cell carcinoma. Current Opinion in Oncology1
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Thai Yen Ly, Noreen M. Walsh, Sylvia Pasternak. (2011) The spectrum of Merkel cell polyomavirus expression in Merkel cell carcinoma, in a variety of cutaneous neoplasms, and in neuroendocrine carcinomas from different anatomical sites. Human Pathology
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Kelly G. Paulson, Jayasri G. Iyer, Paul Nghiem. (2011) Asymmetric lateral distribution of melanoma and Merkel cell carcinoma in the United States. Journal of the American Academy of Dermatology 65:1, 35-39
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Heli Kukko, Tom Böhling, Virve Koljonen, Erkki Tukiainen, Caj Haglund, Arun Pokhrel, Risto Sankila, Eero Pukkala. (2011) Merkel cell carcinoma – A population-based epidemiological study in Finland with a clinical series of 181 cases. European Journal of Cancer
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Piergiacomo Calzavara-Pinton, Paola Monari, Ausilia M Manganoni, Marco Ungari, MariaTeresa Rossi, Giulio Gualdi, Marina Venturini, Raffaella Sala. (2010) Merkel cell carcinoma arising in immunosuppressed patients treated with high-dose ultraviolet A1 (320-400 nm) phototherapy: a report of two cases. Photodermatology, Photoimmunology & Photomedicine 26:5, 263-265
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Kenneth B. Calder, Bruce R. Smoller. (2010) New Insights Into Merkel Cell Carcinoma. Advances in Anatomic Pathology 17:3, 155-161
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Jennifer G. Pryor, Rochelle A. Simon, Patricia A. Bourne, Betsy O. Spaulding, Glynis A. Scott, Haodong Xu. (2009) Merkel cell carcinoma expresses K homology domain–containing protein overexpressed in cancer similar to other high-grade neuroendocrine carcinomas. Human Pathology 40:2, 238-243
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Lars Alexander Schneider, Ralf Hinrichs, Karin Scharffetter-Kochanek. (2008) Phototherapy and photochemotherapy. Clinics in Dermatology 26:5, 464-476
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Michelle Heath, Natalia Jaimes, Bianca Lemos, Arash Mostaghimi, Linda C. Wang, Pablo F. Peñas, Paul Nghiem. (2008) Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features. Journal of the American Academy of Dermatology 58:3, 375-381
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Tony Y. Eng, Melisa G. Boersma, Clifton D. Fuller, Virginia Goytia, William E. Jones, Melissa Joyner, Dominic D. Nguyen. (2007) A Comprehensive Review of the Treatment of Merkel Cell Carcinoma. American Journal of Clinical Oncology 30:6, 624-636
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Christopher K. Bichakjian, Lori Lowe, Christopher D. Lao, Howard M. Sandler, Carol R. Bradford, Timothy M. Johnson, Sandra L. Wong. (2007) Merkel cell carcinoma: Critical review with guidelines for multidisciplinary management. Cancer 110:1, 1-12
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Vy Dinh, Lynn Feun, George Elgart, Niramol Savaraj. (2007) Merkel Cell Carcinomas. Hematology/Oncology Clinics of North America 21:3, 527-544
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E. Matichard, V. Descamps, M. Grossin, R. Genin, E. Bouvet, B. Crickx. (2002) Merkel cell carcinoma in a black human immunodeficiency virus-infected patient. British Journal of Dermatology 146:4, 671-673
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Hans Theodor Eich, Dorothee Eich, Susanne Staar, Cornelia Mauch, Hartmut Stützer, Wolfgang Groth, Thomas Krieg, Rolf-Peter Müller. (2002) Role of Postoperative Radiotherapy in the Management of Merkel Cell Carcinoma. American Journal of Clinical Oncology 25:1, 50-56
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Fernando Colombo, Leonard M. Holbach, Anselm G.M. J??nemann, Ursula Schl??tzer-Schrehardt, Gottfried O. H. Naumann. (2000) Merkel Cell Carcinoma: Clinicopathologic Correlation, Management, and Follow-up in Five Patients. Ophthalmic Plastic and Reconstructive Surgery 16:6, 453-458
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P. Ziprin, S. Smith, G. Salerno, R.D. Rosin. (2000) Two cases of Merkel cell tumour arising in patients with chronic lymphocytic leukaemia. British Journal of Dermatology 142:3, 525-528
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Nathalie C. Zeitouni, Richard T. Cheney, Mark D. Delacure. (2000) Lymphoscintigraphy, Sentinel Lymph Node Biopsy, and Mohs Micrographic Surgery in the Treatment of Merkel Cell Carcinoma. Dermatologic Surgery 26:1, 12-18
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