Diagnostic imaging in Merkel cell carcinoma: lessons to learn from 16 cases with correlation of sonography, CT, MRI and PET.

OBJECTIVE: The authors report imaging findings in a series of 16 patients with MCC, a rare tumour which is often managed primarily by a dermatologist. To our knowledge, no equivalent series of MCC has been described in the nuclear medicine literature. MATERIAL AND METHODS: In this IRB-approved retrospective noncomparative case series 16 patients with biopsy-proven Merkel cell carcinoma were included between January 1999 and October 2007. Twenty-nine whole body PET scans (18F-FDG n=24, 18F-FDOPA n=5) in 16 patients were retrospectively reviewed with regard to tracer uptake in six anatomical sites per patient. For 127/144 of FDG-PET evaluated regions and 68/144 of regions depicted by conventional imaging methods, a valid standard of reference could be obtained. A combined standard of reference was applied, which consisted of histopathology (lymphadenectomy or biopsy) or clinical or radiological follow-up for at least 12 months. RESULTS: the mean FDG uptake over the clinicopatholigical verified FDG avid areas was 4.7 SUV (1.5-9.9 SUV). The region based assessment of diagnostic value, in consideration of the standard of reference, resulted in a sensitivity of 85.7% and a specificity of 96.2% of FDG-PET (n=127) and in a combined sensitivity of 95.5% and a specificity of 89.1% for morphological imaging methods (n=68). Differences between methods did not reach statistical significance (p=1.00, p=0.18). CONCLUSIONS: FDG-PET is a highly useful whole body staging method of comparable value compared to conventional imaging methods with restricted field of view. The lessons learned from case series are discussed.

The PKC inhibitor AEB071 may be a therapeutic option for psoriasis.

PKC isoforms tau, alpha, and beta play fundamental roles in the activation of T cells and other immune cell functions. Here we show that the PKC inhibitor AEB071 both abolishes the production of several cytokines by activated human T cells, keratinocytes, and macrophages in vitro and inhibits an acute allergic contact dermatitis response in rats. To translate these findings into humans, single and multiple ascending oral doses of AEB071 were administered to healthy volunteers and patients with psoriasis, respectively. AEB071 was well tolerated with no clinically relevant laboratory abnormalities. Ex vivo stimulation of lymphocytes from subjects exposed to single doses of AEB071 resulted in a dose-dependent inhibition of both lymphocyte proliferation and IL2 mRNA expression. Clinical severity of psoriasis was reduced up to 69% compared with baseline after 2 weeks of treatment, as measured by the Psoriasis Area Severity Index (PASI) score. The improvement in psoriasis patients was accompanied by histological improvement of skin lesions and may be partially explained by a substantial reduction of p40+ dermal cells, which are known to mediate psoriasis. These data suggest that AEB071 could be an effective novel treatment regimen for psoriasis and other autoimmune diseases, and that AEB071 warrants long-term studies to establish safety and efficacy.

Efficacy and safety of pimecrolimus cream 1% in adult patients with vitiligo: results of a randomized, double-blind, vehicle-controlled study.

BACKGROUND: Vitiligo is an acquired, pigmentary skin disorder which is disfiguring and difficult to treat. In an earlier open label study in adult patients with vitiligo, pimecrolimus cream 1% was reported to have similar efficacy as clobetasol propionate 0.05%. We performed a double-blind, intrapatient comparison of pimecrolimus cream 1% with placebo cream. PATIENTS AND METHODS: Twenty adult Caucasians with symmetrical vitiligo (predominantly on extremities, none in the face) were treated b.i.d. for 6 months left/right with pimecrolimus/vehicle (N = 10) or vehicle/pimecrolimus (N = 10), respectively. Primary efficacy endpoint was the size of the target lesion at month 6 and secondary efficacy endpoint was re-pigmentation. RESULTS: Treatment with pimecrolimus cream 1% or vehicle resulted in no significant change in mean target lesion size. Modest repigmentation (1-25%) was noted with pimecrolimus at month 2 in 12 of 17 patients (vehicle: 9 of 17 patients). Afterwards, the number of patients who experienced an improvement of pigmentation steadily decreased (3 of 14 patients with pimecrolimus and 2 of 14 with placebo at month 6). Treatment was well tolerated. There were no treatment-related adverse events, no induction of skin atrophy nor any other application site side effects. CONCLUSION: In this group of adult patients with symmetrical vitiligo, treatment of body lesions (except face) with pimecrolimus cream 1% could not be shown to be effective.

Identification of clinically featureless incipient melanoma using sequential dermoscopy imaging.

OBJECTIVES: To examine the role of sequential dermoscopy imaging in detecting incipient melanoma and to elucidate the impact of length of follow-up on the relevance of observed changes. DESIGN: Baseline and follow-up images of melanomas and melanocytic nevi excised only because of changes across time were inspected on a computer screen and assessed according to prospectively defined criteria. Lesions were stratified into 3 groups according to the length of follow-up. SETTING: Three hospital-based referral centers in Europe and Australia. Patients Four hundred sixty-one patients selected for digital dermoscopy monitoring. MAIN OUTCOME MEASURES: Description and comparison of dermoscopy features and changes in melanomas and melanocytic nevi at baseline and after follow-up. RESULTS: We inspected baseline and follow-up images of 499 melanocytic skin lesions from 461 patients. The histopathologic diagnosis was melanoma in 91 cases and melanocytic nevus in 408. Most melanomas (58.2%; n = 53) were in situ, and the median thickness of invasive melanomas was 0.38 mm. Dermoscopy features of melanomas and nevi did not differ significantly at baseline. After follow-up of 1.5 to 4.5 months, 61.8% of the melanomas showed no specific dermoscopy features for melanoma. This value declined to 45.0% after follow-up of 4.5 to 8.0 months and to 35.1% after more than 8.0 months. We could not differentiate melanomas and changing nevi by means of observed changes or dermoscopy features when follow-up was shorter than 4.5 months. With longer follow-up, melanomas tended to enlarge asymmetrically with architectural and color changes, and nevi tended to enlarge symmetrically without architectural and color changes. CONCLUSIONS: Sequential dermoscopy imaging detects incipient melanomas when they are still featureless. Interpretation of changes observed during follow-up depends on the length of follow-up.