Alterations in the inflammatory cells infiltrating basal cell carcinomas during immunocryosurgery.

Immunocryosurgery, the combination modality of a cryosurgery session at day 14 of a 5-week daily imiquimod treatment cycle, has shown remarkable efficacy in the treatment of basal cell carcinoma (BCC). The modality was designed to exploit synergy of antitumor effects, including the induction of immune responses, elicited by imiquimod and cryosurgery. Herein, we report on the infiltration of the BCC by selected inflammatory cell species during an immunocryosurgery treatment cycle. The density of tissue infiltrating CD68+, CD3+ and Foxp3+ cells was studied by immunohistochemistry in 56 BCC biopsies from 28 treated sites (26 patients) at baseline and at days 12, 16 or 28 during treatment. Immunocryosurgery induces statistically significant alterations in all three cell species (p < 0.003): The density of CD68+ increased already by day 12 and remained at a higher level during the treatment thereafter. The density of CD3+ cells increased significantly between days 12 and 16 of treatment. The density of Treg (Foxp3+) cells increased in the early phase of treatment (highest at day 12) to decrease significantly already 2 days after the cryosurgery session (day 16) and thereafter up to day 28 of the treatment cycle (p = 0.033). Within the tumor tissue, these alterations result in an abrupt increase in the CD3+/Foxp3+ ratio, a finding suggesting that the cryosurgical perturbation may probably play a decisive modulating role in the cellular composition of the inflammatory infiltrate during immunocryosurgery, eventually heralding the induction of an effective tumor-destructing immune response.

Immunocryosurgery for basal cell carcinoma: results of a pilot, prospective, open-label study of cryosurgery during continued imiquimod application.

BACKGROUND/AIM: Theoretical considerations support the combination of cryosurgery and topical imiquimod to treat basal cell carcinomas (BCC). The aim of the present study was to test the feasibility and efficacy of 'cryosurgery during continued imiquimod application' ('immunocryosurgery') to treat 'high-risk-for-recurrence' BCCs. METHODS: Thirteen patients with 21 biopsy-proven tumours (4 of 21 relapses after prior surgery) were included. After 2-5 weeks (median, 3) of daily 5% imiquimod cream application, the tumours were treated by liquid N(2) cryosurgery (spray, two cycles, 10-20 s) and imiquimod was continued for additional 2-12 weeks (median, 4). The outcome after at least 18 months of follow-up (18-24 months) is currently reported. RESULTS: Nineteen of 21 tumours responded promptly to immunocryosurgery; two tumours required additional treatment cycles to clear. Thus, the clinical clearance rate was 100%. Only 1 of 21(5%) tumour relapsed after at least 18 months of follow-up (cumulative efficacy: 95%). CONCLUSIONS: 'Immunocryosurgery' is a promising non-surgical combination modality to treat 'high-risk-for-recurrence BCCs'. Initial evidence is suggestive of an at least additive effect of the two combined modalities. Further studies comparing immunocryosurgery directly with cryosurgery and imiquimod monotherapies will confirm the reported results.

Cryosurgery during topical imiquimod: a successful combination modality for lentigo maligna.

BACKGROUND: Either cryosurgery or topical imiquimod have been used to treat patients with lentigo maligna in cases where surgery is not feasible. METHODS: We report a patient with lentigo maligna, who was treated with the combination of topical imiquimod and cryosurgery, and review the rationale, which led us to design the present combined cryo-immunological treatment modality. RESULTS: Sustained clearance of lentigo maligna to date (26 months after treatment). The successful treatment of this patient was based on the following rationale: A cryosurgery session during continuing imiquimod application may: (i) reinforce apoptosis of tumor cells; (ii) strengthen antiangiogenesis in the treated tumor; and (iii) build-up a potent tumor-destructive immune response by a cascade of events starting with imiquimod-promoted attraction of immature dendritic antigen-presenting cells (DCs) into the tumor. DCs further mature within the tumor-antigen-rich environment of subsequently cryo-destructed tumor and upon imiquimod-driven migration into the peripheral lymph nodes can stimulate a specific antineoplastic cell-mediated immunity. Finally, continuing imiquimod application after cryosurgery may increase recruitment of activated effector cells into the tumor tissue leading to its destruction. CONCLUSION: Cryosurgery during continued topical imiquimod seems to be a promising treatment for lentigo maligna.

Eruptive pseudoangiomatosis: report of an adult case and unifying hypothesis of the pathogenesis of paediatric and adult cases.

One month after the onset of immunosuppressive treatment with corticosteroids and mycophenolate mofetil for a newly diagnosed pemphigus vulgaris, a 50-year-old female patient developed a new eruption clinically and histomorphologically consistent with eruptive pseudoangiomatosis (EP). Its self-limited course further confirmed this diagnosis. Although initially described as a paediatric eruption, meanwhile more adult cases of EP (30 out of a total of 53 cases identified by a Medline search) are reported in the literature. The review of adult cases of EP disclosed some common clinical and epidemiological characteristics: adult EP cases tend to cluster in the Mediterranean region of Europe, develop during the summer months, sometimes in the form of limited micro-epidemics, affect immunocompromised individuals and have lesions confined to the exposed skin sites. These characteristics, together with the exanthematic nature of the disease in children, point to some vector-transmitted infectious agent as the cause of this probably underdiagnosed disease.