Clinical Characteristics of Cutaneous Melanoma and Second Primary Malignancies in a Dutch Hospital-Based Cohort of Cutaneous Melanoma Patients

The increasing number of living cutaneous melanoma patients and the increased risk of developing a second primary tumour incited us to analyse the clinical characteristics of cutaneous melanoma and define the frequency, site, and type of second primary cancers in cutaneous melanoma patients. We collected data on patients who visited the Department of Dermatology at the Radboud University Nijmegen Medical Centre and were newly diagnosed with cutaneous melanoma or metastasis of melanoma with unknown primary localization between 2002 and 2006. A total of 194 cases were included; eleven patients developed a subsequent melanoma, 24 had at least one basal cell carcinoma, three had at least one squamous cell carcinoma, and 21 patients had a second non-cutaneous primary malignancy. In conclusion, 48 patients developed a subsequent malignancy. As nonmelanoma skin cancer is the most frequent second malignancy, our results subscribe to the necessity of follow-up by a dermatologist

Standard step sectioning of skin biopsy specimens diagnosed as superficial basal cell carcinoma frequently yields deeper and more aggressive subtypes

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Maturation of dendritic cells is a prerequisite for inducing immune responses in advanced melanoma patients

We have investigated the capacity of immature and mature monocyte-derived DCs pulsed with melanoma-associated peptides (gp100 and tyrosinase) to induce a primary cytotoxic T-lymphocyte response in vivo. Advanced HLA-A2.1(+) melanoma patients were vaccinated with peptide- and keyhole limpet hemocyanin (KLH)-pulsed DCs, either immature (9 patients) or matured by monocyte-conditioned medium/tumor necrosis factor alpha/prostaglandin E(2) (10 patients). All patients vaccinated with mature DCs showed a pronounced proliferative T-cell and humoral response against KLH. By contrast, KLH responses were absent in most of the patients vaccinated with immature DCs. Delayed-type hypersensitivity (DTH) reactions against antigen-pulsed DCs were only observed in patients vaccinated with mature DCs and not in patients vaccinated with immature DCs. MHC-peptide tetramer staining of DTH-derived T cells revealed the presence of specific T cells recognizing the melanoma-associated peptides in 1 patient. In a second patient, DTH-derived T cells showed specific lysis of tumor cells expressing the antigens used for DC pulsing. Only patients vaccinated with mature DCs showed objective clinical responses. Interestingly, both patients with long-term progression-free survival (22 and >40 months) were both vaccinated with mature DCs and demonstrated antigen-specific T-cell reactivity of DTH-derived T cells. We conclude that mature DC are superior to immature DC in the induction of immunological responses in melanoma patients, which may translate into improved clinical result

Correlation between macroscopic fluorescence and protoporphyrin IX content in psoriasis and actinic keratosis following application of aminolevulinic acid.

Contains fulltext : 49155.pdf (publisher's version ) (Closed access)In fluorescence diagnosis with 5-aminolevulinic acid (ALA)-induced porphyrins (FDAP), protoporphyrin IX (PpIX) accumulation can be macroscopically visualized. Interpretation of these data is still problematic because of the low reproducibility of the procedure and poor understanding of the mechanisms involved in PpIX tumor selectivity. In this study, PpIX accumulation is investigated in patients with psoriasis and actinic keratosis (AK) following FDAP. For this purpose, desquamated lesional and non-lesional skin were incubated with 20% ALA ointment for 3 h, FDAP was performed, and highly fluorescing lesional skin and non-lesional skin were biopsied. In extracts from these biopsies, PpIX, protein, and dsDNA were quantified by spectrofluorometry. Digital images acquired with FDAP were analyzed using image analysis software. PpIX per biopsy in lesional skin in both psoriasis and AK was significantly higher than in non-lesional skin (p < 0.05). When corrected for epidermal involvement, only lesional psoriatic skin showed significantly higher PpIX levels than non-lesional skin. The PpIX-ratio lesional:non-lesional skin (mean(pmol per mL)+/-SEM) was 4.12+/-0.91 in psoriasis and 1.96+/-0.24 in AK. In FDAP, the ratio of lesional:non-lesional skin was 1.77+/-0.06 in psoriasis and 1.37+/-0.07 in AK. Macroscopic fluorescence and PpIX content appeared to be well correlated (r = 0.73), thus making FDAP a good predictor of PpIX content