Successful Treatment of Giant Basal Cell Carcinoma with Topical Imiquimod 5% Cream with Long Term Follow-up.

The use of the topical Imiquimod 5% cream offers a noninvasive, nonsurgical, and an effective option for the treatment of primary small (<2 cm) superficial basal cell carcinoma (sBCC). However, reports about successful treatment of giant (>5 cm) BCC with topical Imiquimod 5% cream are rare. We present our experience in the treatment of two giant tumors (6 × 8 cm(2), 5.2 × 4.2 cm(2)) of BCC on the face with Imiquimod 5% cream, 2 to 3 days/week for 12 weeks. Both the tumors were cured with clinical and pathological evidence, one with 6-year follow-up and the other with 3.5-year follow-up.

What was known?

Topical Imiquimod 5% cream has been approved by the European Medicines Agency for the treatment of primary small (<2 cm) superficial BCC(sBCC)

Extensive excision will result in disfigurement of face and great pain, so surgical resection of giant basal cell carcinoma (<5 cm) on the face is imperfect.

Even the patients, who have undergone surgical removal has suffered the operation, they till have the risk of relapse of the tumor.

Introduction

Basal cell carcinoma (BCC) is the most common skin cancer in humans. The tumors rarely metastasize and are slow growing and usually encountered when they are small in size. The American Joint Committee on Cancer has defined Giant BCC as a tumor larger than 5 cm in diameter. Less than 1% of all BCCs reach this size.[1] Although, topical Imiquimod 5% cream has been approved by the European Medicines Agency for the treatment of primary small (<2 cm) superficial BCC (sBCC),[2] reports about successful treatment of giant BCC with topical Imiquimod 5% cream are rare. We report two cases of giant infiltrative BCC (6 × 8 cm2, 5.2 × 4.2 cm2) on the face successfully treated with Imiquimod 5% cream with 6-year and 3.5-year follow-up.

Case Reports

Patient 1

Six years ago, a 51-year-old man presented with a large asymptomatic red plaque on the right cheek. He complained of first noticing the lesion 15 years ago. The lesion started as a small plaque and gradually increased in size with no systemic symptoms. Local examination revealed a 6 × 8 cm2 erythematous, indurated, irregular plaque with a sharply demarcated red and scaly border [Figure 1]. The patient had a history of prolonged sun exposure due to farm activities for many years. The diagnosis of infiltrative BCC was made on the basis of skin biopsy which showed varying size of basaloid cells’ nests invading the deeper dermis. These histopathological findings correlated with the character of infiltrative BCC[3] [Figure 2]. Owing to the large size of the tumor on the face, we opted for the use of topical Imiquimod 5% cream for a total of 12 weeks. Every alternate night, before bedtime, a thin layer of the cream was applied uniformly over the lesion after washing face. The cream was left over the lesion for about 8-12 hours before washing it off. In addition to the skin lesion itself, a radius of 1 cm area extending beyond its visible margins was also treated with the topical cream as this area correlates to the site of subclinical tumor extensions. After one week of treatment, the plaque became painful, erythematous, and edematous with successive erosion followed by crusting. The treatment was withdrawn and prednisone 10 mg was given thrice daily for one week to reduce the inflammatory response. The erosion resolved and the cream was applied every three days per week for another 11 weeks. After total 13-weeks of treatment, the tumor had disappeared but left a vitiligo-like depigmentation [Figure 3]. Three years later, a repeat biopsy was performed from the border of the lesion that showed no evidence of recurrence [Figure 4]. Six years later, there was no clinical evidence of relapse.

Figure 1

Erythematous, indurated, irregular plaque 6 × 8 cm2 in size with a large ulcer in the middle and raised crustosus border on the right cheek

Figure 2

Varying size of basaloid cells nests with peripheral palisade cells and fissures can be seen between the tumor cells’ nests and stroma (H and E, ×400)

Figure 3

Twelve week's treatment left only a vitiligo-like depigmentation patching 4 years later

Figure 4

Evidence of histopathological cure of patient one. The epidermis is normal, and there is no carcinoma cell in the dermis except few perivascular lymphocytes infiltration (H and E, ×100)

Patient 2

Three point five years ago, a 43-year-old woman came to our department for the treatment of a red plaque on the bridge of her nose. A lesion of similar clinical and histological appearance to that of case one was also found in this patient with a tumor size 5.2 × 4.2 cm2 [Figure 5]. The biopsy confirmed the diagnosis of superficial-infiltrative BCC[3] [Figure 6]. After surgical consultation, our patient refused surgical operation and agreed to receive topical treatment, so we began with the same treatment plan as case one. Similar ASR (application site reaction) appeared over the lesion after two weeks of using Imiquimod every alternate night. Therefore, she was also given prednisone and the ASR reduced and Imiquimod was then added. After the continuous use of Imiquimod every alternate night for 10 weeks, the lesion became smooth and whitened. At present, there is only a vitiligo-like depigmentation present on her nose without any histological evidence of recurrence by biopsy 0.5 year after the treatment [Figures 7 and 8].

Figure 5

A red plaque on the bridge of the nose was about the size of 5.2 × 4.2 cm2

Figure 6

The multangular tumor islands vary in size connecting the epidermis and infiltrate into the middle line of the dermis. (H and E, ×40)

Figure 7

A vitiligo-like depigmentation patching left on the nose

Figure 8

Patient two was as same as the patient one, there was no carcinoma cell (H and E, ×100)

Discussion

Imiquimod 5% cream (Aldara™, 3M), a topical immune response modifier, which was approved by the US FDA in February 1997, for the treatment of genital and perianal warts, enhances both the innate and acquired immune responses, in particular, the cell-mediated immune pathways.[4] This stimulation of the innate and cell-mediated immune response leads to the generation of antitumor and antiviral activity,[5] and has therefore been studied for the treatment of sBCC, pigmented BCC and other cutaneous neoplasms.[678] Recently, it has been approved by the European Medicines Agency for the treatment of small (<2 cm) sBCC.[2]

Management is dependent upon a variety of factors, including the location of the lesion, the patient's age, co-morbidities and the type of tumor. Traditionally, Mohs micrographic surgery (MMS) or standard excision would be the gold-standard treatments for BCCs. Recent guidelines suggest the following as specific indications for MMS: Tumor site (especially central face), tumor size (any size, but especially > 2 cm), histological subtype, etc.[1] However, excision of large tumor may leave cosmetically disfiguring scar on the face. Often after serial excisions, tissue expanders and skin grafts are required. Furthermore, any kind of surgical management may leave unpredictable recurrence for such giant tumor.[9] Due to the possible outcomes of surgery and our patients’ rejection to surgical treatments, Imiquimod became our first-line treatment for them. At the beginning our patient had acute reactions such as erythema, edema, and pain but we agreed with the viewpoint that the severity of ASR as erythema, erosion, and scabbing/crusting correlated positively with the composite and histologic response rates.[10] After giving prednisone and stopping the use of Imiquimod for one week, these side effects reduced very quickly and patients continued the treatment. Depigmentation was also left on patient's faces, forming vitiligo-like lesions. Even though tumors in our cases were a little deeper than common superficial BCC, they were confirmed clinically to be cured after 6 years and 3 years after the treatment without recurrence.

Effective treatment with Imiquimod depends upon tissue penetration. It may be an alternative to surgery in patients who consider the underlying risk that are associated with the surgery with primary facial infiltrative BCC. To date, there are few cases documenting the use of topical Imiquimod in treating giant infiltrative BCC in China. A long-term follow-up of a larger number of cases is needed to establish its definite role in the management of giant superficial-infiltrative BCC.

What is new?

1. Report of successful nonoperative therapy for giant superficial-infiltrative basal cell carcinoma is rare.

The topical treatment of giant BCC with Imiquimod 5% cream left a residual vitiligo-like depigmentation on the face, with no recurrence.