Correspondence
Cutaneous Squamous-Cell Carcinoma
N Engl J Med 2001; 345:296-297July 26, 2001
- Article
To the Editor:
In their excellent review article on cutaneous squamous-cell cancers (March 29 issue),1 Alam and Ratner mention sunscreen use but not the prevention of these cancers in certain populations of patients at high risk. Among recipients of solid-organ transplants, the incidence of cutaneous squamous-cell carcinoma may be more than 100 times the incidence in the general population.2 Moreover, as many as 6 percent of renal-allograft recipients with skin cancer may die of metastases.
Prophylactic measures, including the daily use of topical tretinoin, enhance the number and function of dendritic cells within the skin, a change seen in association with a decrease in the formation of new skin cancers.3,4 In selected patients, the addition of oral retinoids may provide further benefit.4 However, we have observed acute allograft rejection during the use of high doses of oral retinoids, a problem that may be due to the ability of these agents to induce interferon-γ production,5 which may play a part in abrogating allograft tolerance. We advocate the use of 13-cis-retinoic acid at a dose of 10 mg every day or every other day as an adjunct to the use of topical tretinoin; adverse effects have not been observed at this dose. In the future, novel topical agents with potent local immune-enhancing effects, such as resiquimod, may prove to be of even greater benefit.
5 ReferencesAlain H. Rook, M.D.
Michael Shapiro, M.D.
University of Pennsylvania School of Medicine, Philadelphia, PA 19104
arook@mail.med. upenn. edu 1
Alam M ,Ratner D . Cutaneous squamous-cell carcinoma. N Engl J Med 2001;344:975-983
Full Text | Web of Science | Medline2
Penn I . Cancer is a long-term hazard of immunosuppressive therapy. J Autoimmun 1988;1:545-558
CrossRef | Web of Science3
Chen G ,Kang K ,Kang S , et al. Differential induction of IL-12 p40 and IL-10 mRNA in human Langerhans' cells and keratinocytes by in vivo occlusion, vehicle, and all-trans retinoic acid. J Cutan Med Surg 1996;1:74-804
Rook AH ,Jaworsky C ,Nguyen T , et al. Beneficial effect of low-dose systemic retinoid in combination with topical tretinoin for the treatment and prophylaxis of premalignant and malignant skin lesions in renal transplant recipients. Transplantation 1995;59:714-719
CrossRef | Web of Science | Medline5
Fox FE ,Kubin M ,Cassin M , et al. Retinoids synergize with interleukin-2 to augment IFN-γ and interleukin-12 production by human peripheral blood mononuclear cells. J Interferon Cytokine Res 1999;19:407-415
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To the Editor:
With regard to the article by Alam and Ratner on cutaneous squamous-cell carcinoma, I would like to draw attention to the depiction of skin carcinogenesis in Figure 1. Actinic keratoses do not begin in the upper layers of the epidermis, but within the basal layer — that is, within the only layer where cells replicate. Suprabasal keratinocytes cannot replicate. Keratinocytes acquire ultraviolet-induced p53 mutations while they are within the basal layer. In conventional immunohistochemical sections, they can be seen in the upper layers as a consequence of upward migration — a feature common to all keratinocytes.
Lorenzo Cerroni, M.D.
University of Graz, A-8036 Graz, Austria
lorenzo.cerroni@kfunigraz. ac. at To the Editor:
As a radiation oncologist, I generally see patients with skin cancer of the head and neck, where surgery can be disfiguring. The majority of patients are elderly, and thus do not face the theoretical risk (probably no greater than 1 to 2 percent over a period of 30 years) of a secondary cancer. However, the review article does little to reassure practitioners that radiotherapy is a reasonable and very effective alternative to surgery. A previous review article1 stated that “radiation therapy maximizes tissue preservation,” that it “is especially advantageous in elderly, debilitated, or other patients at higher risk of surgical complications,” and that it “is most appropriate for lesions at sites where tissue preservation is essential.” Another review article on curative radiotherapy for skin cancers reported a 95 percent rate of local control for eyelid tumors and a 93 percent rate of local control for tumors of the nose.2 Other studies have reported excellent local control, in excess of 90 percent, with radiotherapy for squamous-cell tumors of the pinna and medial fleshy canthus.3
3 ReferencesJondavid Pollock, M.D., Ph.D.
Schiffler Cancer Center, Wheeling, WV 26003
jpollock@wheelinghosp.com 1
Preston DS ,Stern RS . Nonmelanoma cancers of the skin. N Engl J Med 1992;327:1649-1662
Full Text | Web of Science | Medline2
Morrison WH ,Garden AS ,Ang KK . Radiation therapy for nonmelanoma skin carcinomas. Clin Plast Surg 1997;24:719-729
Web of Science | Medline3
Petrovich Z ,Kuisk H ,Langholz B , et al. Treatment results and patterns of failure in 646 patients with carcinoma of the eyelids, pinna, and nose. Am J Surg 1987;154:447-450
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Author/Editor Response
The authors reply:
To the Editor: We agree with Rook and Shapiro that the prevention of squamous-cell carcinoma in patients who have received a solid-organ transplant is an essential part of management. Topical and systemic retinoids are certain to have an increasing role in tumor prophylaxis in these patients, and we look forward to the development of new topical immunomodulatory agents to treat patients with human papillomavirus-associated and non–human papillomavirus-associated squamous-cell carcinoma.
Cerroni is correct in stating that actinic keratoses begin in the basal layer of the epidermis as a result of p53 mutations induced by ultraviolet radiation. We tried to simplify this concept in our diagram, but unfortunately, the cells with dysfunctional p53 genes are shown too high in the epidermis. The abnormal cell population should instead be shown initially in the basal layer. After ultraviolet radiation, these cells undergo clonal expansion into the upper portions of the epidermis, instead of exhibiting downward growth.
We disagree with Pollock's assertion that our article “does little to reassure practitioners that radiotherapy is a reasonable and very effective alternative to surgery.” In fact, we state that radiation as a primary treatment “may provide favorable functional and cosmetic results” for properly selected patients with squamous-cell carcinoma and that radiation may be used in combination with other types of therapy to treat aggressive or recurrent lesions. It is important to note that nonmelanoma skin cancer, which is discussed in a previous review article, consists principally of basal-cell carcinomas.1 Although radiation therapy may be useful to treat primary basal-cell carcinomas in elderly or debilitated patients or in other patients at increased risk for surgical complications, basal-cell carcinomas and squamous-cell carcinomas have far different rates of metastasis. Although both populations of tumors may become more aggressive if they recur after radiation therapy, recurrent squamous-cell carcinomas carry a much greater risk of metastasis than recurrent basal-cell carcinomas and are also associated with a higher mortality rate.2
2 ReferencesDésirée Ratner, M.D.
Murad Alam, M.D.
Columbia Presbyterian Medical Center, New York, NY 10032
dr221@columbia.edu 1
Preston DS ,Stern RS . Nonmelanoma cancers of the skin. N Engl J Med 1992;327:1649-1662
Full Text | Web of Science | Medline2
Johnson TM ,Rowe DE ,Nelson BR ,Swanson NA . Squamous cell carcinoma of the skin (excluding lip and oral mucosa). J Am Acad Dermatol 1992;26:467-484
CrossRef | Web of Science | Medline
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