Characterisation of the inflammatory response triggered by topical ingenol mebutate 0.05% gel in basal cell carcinoma.

BACKGROUND/OBJECTIVE: Ingenol mebutate gel is approved for actinic keratosis field therapy, but little has been published as a treatment of basal cell carcinoma (BCC). Our objective is to characterise the histopathological changes and the infiltrating cell populations to better understand its mechanism of action. METHODS: Sixteen patients with various BCC subtypes were prospectively evaluated and treated once daily for two consecutive days with ingenol mebutate gel 0.05% under occlusion. Patients were randomised to two arms: the first arm was biopsied between the third and the tenth day after treatment initiation ('early immune response'), and the second arm was biopsied at day 30 after treatment initiation ('late immune response'). The immunopathology was evaluated by immunohistochemistry: anti-CD3, anti-CD4, anti-CD8, anti-CD20, anti-CD56, anti-CD68, anti-Bcl-2, anti-CASP3, anti-FoxP3, anti-GrzB and anti-TIA-1. RESULTS: Ten BCCs were in complete remission after 2 years of follow-up. The early immune response was characterised by a quick recruitment of T lymphocytes, macrophages and natural killer cells. At later time-points, T-regulatory cells and some pro-apoptotic markers were detected. Treatment-related adverse events were described. CONCLUSION: Ingenol mebutate gel produces a transient immuno-inflammatory response and an important necrosis reaction in BCCs. Larger studies will be required to determine the maximum effective tolerated dose of ingenol mebutate gel for BCC.

Cytokeratin Profile of Basal Cell Carcinomas According to the Degree of Sun Exposure and to the Anatomical Localization.

Basal cell carcinoma (BCC) seems to originate from ultraviolet light-induced mutations involving the bulge or the outer sheath of the hair follicle cells. However, the etiopathogenic mechanisms involved in the development of these tumors in nonphotoexposed and in hairless areas remain unclear. The cytokeratin (CK) profile (including CK5/6, CK7, CK14, CK15, CK17, and CK19) from a series of different BCC subtypes developing in sun-exposed and non-sun-exposed areas, including hairless regions, was evaluated. The authors have observed that CK7 expression in BCC is associated with the anatomical localization of the tumor and its sun-exposition, but not with other factors such as histological subtype. The expression of this CK is higher in BCCs located in non-sun-exposed and nonhairy areas, such as the vulvar semimucosa and the nipple. Because CK7 is a marker of simple glandular epithelia, the authors suggest a glandular origin for BCCs located in hairless and nonphotoexposed areas.

Vulvar Basal Cell Carcinoma: Four Case Reports With Immunohistochemical Study.

Basal cell carcinomas (BCC) are the most frequent tumours in humans and normally appear in photoexposed areas of the skin. It is widely accepted that BCCs originate at follicular stem cells and consequently are very rare in nonhairy areas. Here, we report 4 cases of vulvar BCC, 3 of which were located in a vulvar semimucous area, a nonphotoexposed area, and a nonhairy area. We have determined the CK7 and CK19 profile of all cases; both are markers of simple epithelium with glandular differentiation. Interestingly, all cases were positively stained for CK7 and CK19. Considering that the vulvar region is rich in sebaceous and apocrine units, we hypothesise a glandular origin of BCCs situated in the vulvar region.