Imiquimod induced regression of clinically diagnosed superficial basal cell carcinoma is associated with early infiltration by CD4 T cells and dendritic cells.

Imiquimod is presumed to clear basal cell carcinoma (BCC) through apoptosis mediated by cytokines and lymphocytes, with erosion often observed correlating with complete clearance. The objective was to determine the cellular immune response early in the course of treatment in order to examine whether cell mediated immunity could be responsible for imiquimod mediated regression of BCC. Sixteen adults with clinically diagnosed BCC were openly assigned to 5 days per week of drug (1, 2 or 4 weeks) or placebo (2 weeks) in groups of four. No baseline biopsy was performed. Post-treatment excision specimens were examined by routine and immunohistochemical staining. Treatment was associated with the early appearance of CD4 cells, activated dendritic cells and macrophages, with later infiltration by CD8 T cells. Dendritic cells continually increased with time, while macrophages reached a maximum at 1 week and then declined slightly. There were comparatively few neutrophils or gammadelta T cells. Early infiltrates were most prominent in the tumour and upper dermis. The results are consistent with a cell mediated immune response being responsible for the clearance of the BCC. Several immune-mediated tumour destruction mechanisms are likely to be involved.

Increased Fas ligand expression by T cells and tumour cells in the progression of actinic keratosis to squamous cell carcinoma.

BACKGROUND: In the counterattack model of tumorigenesis, it has been proposed that tumours develop resistance to attack from Fas ligand (FasL)-expressing cytotoxic T cells by downregulating Fas (immune escape), while at the same time upregulating FasL expression to induce apoptosis in Fas-expressing T cells (counterattack). OBJECTIVES: The aim of this study was to examine Fas and FasL expression on tumour cells and infiltrating T cells during the progression of actinic keratoses (AK), the benign precursor lesion, to squamous cell carcinoma (SCC). PATIENTS AND METHODS: Samples of AK (n = 20) and SCC (n = 20) were collected from immunocompetent patients attending dermatology clinics. Double-label immunohistochemistry was performed on frozen sections using mouse monoclonal antibodies to Fas or FasL, simultaneously with a rabbit polyclonal antibody to either CD3 or cytokeratin, markers of T cells and keratinocytes, respectively. Cell densities and the optical density of tumour Fas expression were measured using image analysis. RESULTS: FasL-expressing T cells were observed in nine of 19 SCCs, compared with three of 20 AKs (P < 0.05). FasL-expressing tumour cells were found in nine of 18 SCCs, compared with only one of 20 AK specimens (P < 0.005). There was no difference in the number of Fas-expressing T cells infiltrating AK and SCC. Fas expression by keratinocytes, measured by optical density, was lower in SCC (range 0.1-40, median 17) compared with AK (range 4-62, median 25) (P < 0.05). CONCLUSIONS: These results suggest that the greater numbers of FasL-expressing T cells infiltrating into SCC compared with AK are targeting Fas-expressing tumour cells. As AK cells progress to SCC, they subvert this T-cell-mediated killing of tumour cells by downregulating their Fas expression (immune escape). Furthermore, tumour cells upregulate their expression of FasL, possibly as a counterattack measure to induce apoptosis in the increased number of tumour-infiltrating T cells. Thus changes in Fas/FasL-mediated interactions between T cells and tumour cells occur during the progression of AK into SCC.

Reactive perforating collagenosis: a condition that may be underdiagnosed.

Reactive perforating collagenosis is a perforating disorder developing in adults, usually in association with diabetes mellitus or renal failure. We present three cases diagnosed at the Royal Prince Alfred Hospital in a 5 month period. All three patients had long-standing diabetes mellitus, hypertension, hypercholesterolaemia and ischaemic heart disease. Each patient presented with generalized pruritus and a papular eruption across the trunk and limbs. More than one biopsy or multiple levels were needed before the diagnostic histological features were seen. The first patient responded to 0.5% phenol with 10% glycerine in sorbolene cream. The second patient did not respond to topical betamethasone diproprionate 0.5 mg/g cream and antihistamines (hydroxyzine 25 mg nocte) and required narrow-band ultraviolet (UV) B. The third patient, having failed to respond to topical betamethasone diproprionate 0.5 mg/g cream and wet dressings, antihistamines (hydroxyzine 25 mg tds and doxepin 50 mg nocte) and UVB required acitretin 25 mg orally per day. Because reactive perforating collagenosis responds to treatment, we believe this condition should be considered in patients with diabetes mellitus or renal failure presenting with pruritus and that biopsy of intact lesions may need multiple levels to help establish the diagnosis.

Menarcheal age among girls attending school in urban and rural Jamaica.

PIP: Data collected in 1978 on age a menarche among 1,148 schoolgirls in Jamaica are presented. Variations in age at menarche by rural or urban residence, socioeconomic status, and body weight are analyzed.^ieng