Dermatology Online Journal

Treatment of invasive squamous cell carcinoma with 5-percent imiquimod cream
M Konstantopoulou, MG Lord, AW Macfarlane
Dermatology Online Journal 12 (3): 10

Departments of Dermatology and Pathology, Ysbyty Gwynedd Hospital, Bangor, LL57 2PW, UK. Maria.Konstantopopoulou@nww-tr.wales.nhs.uk

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Abstract

Skin cancer is a major problem in the elderly. Squamous cell carcinoma (SCC), the second most common skin cancer, typically occurs in this age group. Despite a number of modalities readily available for treatment (depending on the tumor site, and depth of invasion) there remains the problem of individuals with multiple lesions who may be unsuitable for existing treatments for SCC, particularly surgery. Consequently, the search for novel treatments continues. To our knowledge, there are only 6 published reports of invasive SCC treated with 5-percent imiquimod cream.

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Skin cancer is a major problem in the elderly. Squamous cell carcinoma (SCC), the second most common skin cancer, typically occurs in this age group. Despite a number of modalities readily available for treatment (depending on the tumor site, depth of invasion) there remains the problem of individuals with multiple lesions who may be unsuitable for existing treatments for SCC, particularly surgery. Consequently, the search for novel treatments continues. To our knowledge, there are only 6 published reports of invasive SCC treated with 5-percent imiquimod cream [1, 2, 3, 4, 5, 6].

Clinical synopsis

An 89-year-old woman presented with three lesions on her lower limbs. She had previous treatments for multiple basal cell carcinomas, actinic keratoses, Bowen disease, and invasive SCCs at various sites. The new lesions were on the left foot (one) and right lower leg (two) (Figs. 1a and 1c), and all showed changes of poorly differentiated SCC histologically (Figs. 2a and 2c). She declined surgical excision; radiotherapy was felt to be a poor option.

Figure 1a	Figure 1b
Figure 1. (a) Dorsum, left foot before treatment and (b) after treatment.

Figure 1c	Figure 1d
Figure 1. (c) Outer aspect, right lower leg before treatment and (d) after treatment.

Figure 2a	Figure 2b
Figure 2. Histopathology. (a) Dorsum, left foot before treatment: markedly thickened epidermis with dysplastic squamous cells invading into superficial dermis. (b) After treatment: epidermis now shows only focus of dysplastic squamous cells with no invasion.

Figure 2c	Figure 2d
Figure 2: (c) Outer aspect, right lower leg before treatment: area of invasive squamous cell carcinoma composed of nests and cords of dysplastic squamous cells. (d) After treatment: epidermis shows hyperplastic changes only; mitotic figures but no significant cytological dysplasia.

She was treated with 5-percent imiquimod cream, initially to just the lesion on the dorsum of the foot, for 8-12 hours at night for three nights each week (3×/week). Treatment was well tolerated by week 2, so the frequency was increased to 5×/week and all three lesions treated. Gradually, two lesions diminished in size. Treatment was continued until there was no clinical evidence of residual tumor at these sites (19 weeks) (Figs. 1b and 1d); repeat biopsies showed only a focus of dysplastic cells with no invasion (dorsum, left foot), and epidermal hyperplasia with no significant cytological atypia (outer aspect, right lower leg) (Figs. 2b and 2d). Neither now showed evidence of invasive SCC. After 16 months there was no recurrence of either lesion. The third lesion (right lower leg, not illustrated) did not respond to topical imiquimod and was later surgically excised.

Discussion

Imiquimod is a topically applied imidazoquiline immunomodulator that enhances both innate and cell-mediated immunity [1, 2]. It may be effective in a wide range of infectious and neoplastic dermatologic conditions [2, 5]. It acts as an immune modulator via binding to toll-like receptor 7 present on dendritic cells, macrophages, and monocytes [4, 6], leading to the release of proinflammatory mediators, including interferon-α, interleukins 1, 6, 8, 12, and tumor necrosis factor-α among others [3, 4]. Imiquimod directly activates natural killers cells, effects proliferation of B cells, and enhances migration and antigen presentation by Langherhans cells [1, 4]. Direct antineoplastic activity via induction of apoptosis in tumor cells has been proposed [2, 4]. Local complications of topical imiquimod treatment are frequent; significant inflammation is inevitable [1, 5].

There are relatively few reports detailing the successful use topical imiquimod for treating invasive SCC and, as in our case, not all tumors seem to respond. Nevertheless, given the success in our case for two poorly differentiated invasive SCCs, we feel that it has a place in treatment. It may be of use in patients unsuitable for more invasive procedures or for selected early lesions. Careful clinical and histological followup is indicated.

References

1. Nouri K, O'Connell C, Rivas MP. Imiquimod for the treatment of Bowen's disease and invasive squamous cell carcinoma. J Drugs Dermatol.2003 Dec;2(6):669-673.

2. Martin-Garcia RF. Imiquimod: an effective alternative for the treatment of invasive cutaneous squamous cell carcinoma. Dermatol Surg.2005 Mar;31(3):371-4.

3. Oster-Schmidt C.Two cases of squamous cell carcinoma treated with topical imiquimod 5%. J Eur Acad Dermatol Venereol.2004 Jan;18(1):93-95.

4. Hengge UR, Schaller J. Successful treatment of invasive squamous cell carcinoma using topical imiquimod. Arch Dermatol.2004 Apr;140:404-406.

5. Flórez Á, Feal C, de la Torre C, Cruces M. Invasive squamous cell carcinoma treated with imiquimod 5% cream. Acta Derm Venereol.2004;84:227-8.

6. Oster-Schmidt C, Dirschka T. Therapy of cutaneous cell carcinoma in two retirement home residents. J Dtsch Dermatol.2005 Sep;3(9):705-8.

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