Epidermodysplasia verruciformis with multiple mucosal carcinomas treated with pegylated interferon alfa and acitretin

Epidermodysplasia verruciformis (EV) is characterized by abnormal genetically-determined susceptibility to widespread and persistent infection of the skin with human papillomaviruses (HPV). The infection results in disseminated pityriasis versicolor-like lesions and flat warts. Skin malignant changes are very common and occur on sun-exposed areas. Several treatments have been used but without consistent benefit. Recently, retinoids and alpha-interferon, alone or in combination, have been reported to be of value in the therapy of EV lesions. We present the case of a 43-year-old white female affected by EV who developed multiple squamous cell carcinomas in the oral and genital mucosae during the previous four years. Both wart and cancer lesions harbored HPV24 along with the novel putative HPV type FA51. The patient was treated with a combination of acitretin (0.2 mg/kg per day) and peginterferon alfa-2b (1 microg/kg per week s.c.) for one year, with marked improvement of verrucous lesions and no recurrence of mucosal cancer. Thereafter, interferon was stopped whereas acitretin therapy was continued, but a new Bowen's disease developed in the perianal region, and the acitretin dose was increased at 0.5 mg/kg per day. At six-month follow-up, only a low number of flat warts persisted, and no clinical signs of cutaneous or mucosal carcinoma were evident.     

The effect of an intralesional sustained-release formulation of interferon alfa-2b on basal cell carcinomas

Intralesional interferon alfa-2b has been proven effective in the treatment of basal cell carcinomas. Because nine injections over a 3-week period have been necessary to produce clinically significant cure rates, a sustained-release protamine zinc chelate interferon formulation has been developed. In this study, 65 basal cell carcinomas were treated in one of two dosing schedules with intralesional sustained release interferon alfa-2b (10 million IU per injection). Thirty-three patients received a single injection and 32 patients received one injection per week for 3 weeks. At study week 16, 80% of evaluable tumors treated with three injections and 52% treated with one injection were cured histologically. Two patients discontinued injections because of side effects. A sustained-release protamine zinc preparation of interferon alfa-2b shows promise as a practical, effective, and cosmetically elegant treatment for basal cell carcinoma.     

The effect of intralesional interferon gamma on basal cell carcinomas

This open label study evaluated the effect of nine intralesional injections of two different doses of interferon gamma on basal cell carcinomas in 29 patients. One group of 15 patients received interferon gamma, 0.01 mg (20,000 IU), intralesionally three times a week for 3 weeks. Fourteen patients received interferon gamma, 0.05 mg (100,000 IU), intralesionally in the same dosage schedule. Excisional biopsy specimens 12 weeks after therapy showed no evidence of tumor remaining in 7 of 14 patients (50%) treated with the higher dose of interferon gamma, whereas only 1 of 15 patients (7%) treated with low-dose interferon gamma was cured according to histologic criteria (p = 0.025). Seventy-six percent of patients reported at least one adverse reaction, but most were considered mild by the patient and the investigator.     

Treatment of cutaneous squamous cell carcinomas by intralesional interferon alfa-2b therapy.

BACKGROUND AND DESIGN--Intralesional recombinant interferon alfa-2b has been shown to be effective in the treatment of actinic keratoses and basal cell carcinomas. This open-label study was designed to evaluate the effectiveness and cosmetic result of this therapy on actinically induced, primary cutaneous squamous cell carcinomas. Thirty-six squamous cell carcinomas (28 invasive lesions and 8 in situ lesions) ranging in size from 0.5 to 2.0 cm in the longest dimension were treated with interferon alfa-2b 1.5 million units injected intralesionally three times per week for 3 weeks. Eighteen weeks following therapy, the treatment sites were excised and examined for histologic evidence of remaining tumor. RESULTS--Thirty-three (97.1%) of 34 evaluable lesions revealed an absence of squamous cell carcinoma histologically after therapy, although three biopsy specimens (8.8%) obtained after treatment showed actinic keratoses, for an overall complete response rate of 88.2%. The lesion not eliminated after treatment was an invasive squamous cell carcinoma. The investigators and patients independently judged 93.9% of cases to have a very good or excellent cosmetic result. Adverse reactions were limited to those influenzalike symptoms well recognized to occur with interferon therapy and these were well tolerated. Only one patient discontinued therapy due to side effects. CONCLUSIONS--This trial demonstrates that intralesional interferon is effective in the treatment of small sun-induced squamous cell carcinomas with well-tolerated side effects and a highly acceptable cosmetic result.     

Multiple basal cell carcinomas in xeroderma pigmentosum treated with imiquimod 5% cream

Abstract:  We report successful treatment of multiple basal cell carcinomas with imiquimod 5% cream in a 16-year-old boy with xeroderma pigmentosum and review the possibility of prophylactic role of imiquimod in the disease. Imiquimod cream was applied uniformly over all the basal cell carcinoma lesions and background pigmented skin, once at bedtime on every alternate day for 12 weeks. Besides the basal cell carcinomas, the background hyperpigmentation and keratotic papules also cleared, and the skin texture improved. The lesions did not recur at the treated sites during the follow up of 1 year.     

Acrochordon-like basal cell carcinomas in patients with basal cell nevus syndrome

Basal cell nevus syndrome is an autosomal dominant disorder characterized by multiple basal cell carcinomas, along with numerous other documented clinical features. Acrochordons (or skin tags) are common benign neoplasms that are appropriately left untreated in most patients. We describe two patients with known BCNS who were found to have multiple BCCs that clinically resembled acrochordons. Our findings support the biopsy of acrochordon-like growths in patients with basal cell nevus syndrome to rule out basal cell carcinoma.     

Evidence of increased apoptosis and reduced proliferation in basal cell carcinomas treated with tazarotene

A preliminary clinical experience suggested tazarotene, a new acetylenic retinoid, as an effective alternative topical treatment of basal cell carcinomas (BCC). The mechanisms of action of this synthetic retinoid, however, have not been yet clarified. In this work we assessed the in vivo effects of daily application of tazarotene for 24 wk, on 30 small superficial and nodular BCC, and the in vitro effects of tazarotene on immortalized basal and squamous tumor epidermal cells. Cellular proliferation, apoptosis and changes in expression of retinol and retinoic acid receptors (RAR), p53, bcl-2, and bax were studied by immunohistochemistry, western blotting and PCR. Overall, 76.7% of treated tumors showed >50% regression. Complete healing was observed in 46.7% of all treated BCC, without recurrences at 2-y observation. Regression was associated with reduced proliferation and increased apoptosis, demonstrated by Ki-67- and TdT-mediated dUTP-biotin nick-end labelling-positive nuclear staining, and with enhanced RAR-beta and bax expression, with RAR-alpha and -gamma expression unchanged. In vitro, tazarotene induced a concentration-dependent increase of RAR-beta and bax associated with a greater rate of apoptosis and growth inhibition in basaloid tumor cells compared with squamous tumor cells. Our studies provide convincing evidence that tazarotene induces BCC regression possibly by synergistic RAR-beta-dependent anti-proliferative and pro-apoptotic pathways.     

Long-term follow-up of leucoderma patients treated with transplants of autologous cultured melanocytes,ultrathin epidermal sheets and basal cell layer suspension

BACKGROUND: In vitiligo and piebaldism the lack of melanin in the epidermis is due to the fact that melanocytes are missing. The patients suffer psychologically and the white areas have lost the part of the skin barrier protection normally provided by the melanocytes. Medical treatments are ineffective in many of the patients, and surgical methods have therefore been developed. OBJECTIVES: It is important to investigate the long-term results and factors that might influence the outcome of melanocyte transplantations in order to form a basis for guidance in the selection of patients who will benefit most from the treatments. METHODS: A follow-up of 132 patients who had been treated by transplantation on 176 occasions in total, 1-7 years previously, was carried out by questionnaires and clinical examinations. We investigated the responses in five types of leucoderma to three different transplantation methods: autologous cultured melanocytes, ultrathin epidermal sheets and basal layer cell suspension. RESULTS: Stable types of leucoderma, i.e. segmental vitiligo and piebaldism, responded in most cases with 100% repigmentation, regardless of the surgical method used. For these types of leucoderma surgery seems to be the method of choice. The largest group, vitiligo vulgaris, was thoroughly scrutinized and three statistical models were used to analyse the data. The ultrathin epidermal sheet method gave somewhat better overall results, but was the method that gave the worst outcome in knee and elbow areas, emphasizing the importance of the right choice of method depending on the anatomical location to be treated. Irrespective of the method, fingers and elbows were the most difficult areas to repigment. The trunk and the arms and legs (not including elbows and knees) responded best. Patients with increasing and/or extensive vitiligo vulgaris more often showed incomplete repigmentation. They also had a lower chance of retaining their repigmentation compared with those with less extensive vitiligo. Patients in whom untreated white lesions had increased in recent years tended to respond less well to transplantation compared with patients with unchanged or decreased lesions. Within the vitiligo vulgaris group, patients with short disease duration or with small total vitiligo area responded best to transplantation. The subgroup of vitiligo vulgaris patients with hypothyroidism tend to respond less well to the transplantation and they were generally older at vitiligo onset. This information is of great importance for the selection of patients and when informing about the chances of improvement after transplantation. Slight hyperpigmentation was common, especially when ultrathin epidermal sheets had been used. No scars or indurations were seen in treated areas. CONCLUSIONS: Transplantations are the methods of choice in stable types of leucoderma. Progressive, widespread vitiligo vulgaris should never be selected for transplantation.     

Treatment of basal cell carcinomas in patients with nevoid basal cell carcinoma syndrome

Background  Nevoid basal cell carcinoma syndrome (NBCCS) is characterized by the development of multiple basal cell carcinomas (BCCs). A major problem for these patients is the enormous amount of BCCs which can invade in the deep underlying structures, especially in the face. Different treatment modalities are used in these patients; surgical excision, Mohs micrographic surgery, cryotherapy, photodynamic therapy, ablative laser therapy and topical 5% imiquimod. There is no evidence based advice how to treat a NBCCS patient.
Objective  To give a review of the literature about the possible treatment modalities for the multiple BCCs in NBCCS patients.
Results  Literature consists mainly of case reports; no evidence based advice how to treat a NBCCS patient exists. Multiple treatments are available (surgical and non-surgical), and a lot of them can be combined. Treatment in a megasession is an option to diminish the medical and social inconvenience for the patient.

Conflicts of interest

None declared     

Multiple basal cell carcinomas associated with hairy cell leukaemia

We report the case of a caucasian woman who, between the ages of 49 and 51 years, developed multiple (> 20) basal cell carcinomas (BCC). There was no family history of BCC. No abnormalities in the human homologue of the Drosophila segment polarity gene patched (PTCH), glutathione S-transferases T1 and M1, or cytochrome P450 1A1 were detected by polymerase chain reaction (PCR)-based molecular analysis. There was, however, actinic damage of the skin in sun-exposed areas. The patient was diagnosed as having hairy cell leukaemia (HCL) at the age of 51 years, based upon leucocyte morphology as assessed by light and electron microscopy, tartrate-resistant acid leucocyte phosphatase (TRAP) staining, fluorescence activated cell scanning of peripheral blood leucocytes and bone marrow histology. As the leukaemia slowly progressed over a 3-month period, the patient developed four further BCCs. Given that HCL is characterized by a profound defect in T-cell function, it is conceivable that T-cell immune dysregulation can contribute to the pathogenesis of BCC, possibly enhancing the aetiological effect of ultraviolet irradiation.     

Management of basal cell carcinomas with positive margins

A common problem in day-to-day practice is the approach to take following resection of basal cell carcinoma with positive margins. In such cases, it is important to decide whether we should take a wait-and-see approach or consider re-excision or radiotherapy. To make this decision, 4 key points need to be clarified: the significance of positive margins; whether positive margins are equivalent to tumor persistence; whether negative margins equate with complete excision; and the rate of recurrence in cases of re-excision compared in those in which a wait and see approach is taken. Having addressed each of these points, the approach will depend on the characteristics of the individual case. Based on the evidence presented, an aggressive approach involving re-excision would seem indicated in aggressive cases, whereas a flexible strategy combining observation, surgery, and radiotherapy (or other treatments) can be used in less aggressive cases.     

Treatment of basal cell carcinoma with intralesional interferon

Eight patients with basal cell carcinomas were treated with recombinant alpha-2 interferon. Each patient had a biopsy-proved basal cell carcinoma of the nodular or superficial type that was injected intralesionally three times a week for 3 weeks (9 total injections) with 1.5 X 10(6) IU (0.15 ml) of alpha-2 interferon per injection (total dose, 13.5 X 10(6) IU). Excisional biopsy 2 months after completion of therapy revealed no evidence of basal cell carcinoma in any patient. Minimal side effects were observed. In these eight patients alpha-2 interferon was therefore an effective and safe modality of treatment. The encouraging results of this pilot study suggest that additional evaluation of interferon in the treatment of basal cell carcinoma is warranted.