T. Forschner

Actinic keratosis is an early in situ squamous cell carcinoma: A proposal for reclassification

Summary The term actinic keratosis (AK) describes a sun‐induced, clinical erythematous lesion covered with scale, but does not provide an understanding of the biology or histopathology of the lesion. Cousequeutly, several classification systems for AK have been suggested, but as yet no cousensus has been reached. These systems strive to correlate the pathological and clinical features to better provide physcians with the most accurate information to enable correct decisions to be made regarding treatments, Prognosis and metastatic potential. AK is a clinical description that has a histological diagnosis consistent with squamous cell carcinoma (SCC) in situ. We recommend an AK classification system that describes these lesions as squamous cell carcinomas (SCCs), using the terminology ‘early in situ SCC Type AK I’, ‘early in situ SCC type AK II’ and ‘in situ SCC Type AK III’, there by giving clinicians better guidance for diagnosis and specific treatment recommendations.

Identification of differentially expressed genes in cutaneous squamous cell carcinoma by microarray expression profiling

BackgroundCarcinogenesis is a multi-step process indicated by several genes up- or down-regulated during tumor progression. This study examined and identified differentially expressed genes in cutaneous squamous cell carcinoma (SCC).ResultsThree different biopsies of 5 immunosuppressed organ-transplanted recipients each normal skin (all were pooled), actinic keratosis (AK) (two were pooled), and invasive SCC and additionally 5 normal skin tissues from immunocompetent patients were analyzed. Thus, total RNA of 15 specimens were used for hybridization with Affymetrix HG-U133A microarray technology containing 22,283 genes. Data analyses were performed by prediction analysis of microarrays using nearest shrunken centroids with the threshold 3.5 and ANOVA analysis was independently performed in order to identify differentially expressed genes (p < 0.05). Verification of 13 up- or down-regulated genes was performed by quantitative real-time reverse transcription (RT)-PCR and genes were additionally confirmed by sequencing. Broad coherent patterns in normal skin vs. AK and SCC were observed for 118 genes.ConclusionThe majority of identified differentially expressed genes in cutaneous SCC were previously not described.

Photodynamic therapy with methyl aminolevulinate for prevention of new skin lesions in transplant recipients: a randomized study.

Background. Organ transplant recipients on long-term immunosuppressive therapy are at increased risk of non-melanoma skin lesions. Repeated field photodynamic therapy using topical methyl aminolevulinate (MAL) may have potential as a preventive treatment. Methods. This open randomized, intrapatient, comparative, multicenter study included 81 transplant recipients with 889 lesions (90% actinic keratoses (AK)]. In each patient, the study treatment was initially administered to one 50 cm2 area on the face, scalp, neck, trunk, or extremities (n=476 lesions) twice (1 week apart), with additional single treatments at 3, 9, and 15 months. On each occasion, the area was debrided gently and MAL cream (160 mg/g) applied for 3 hr, before illumination with noncoherent red light (630 nm, 37 J/cm2). The control, 50 cm2 area (n=413 lesions) received lesion-specific treatment (83% cryotherapy) at baseline and 3, 9, and 15 months. Additionally, all visible lesions were given lesion-specific treatment 21 and 27 months in both treatment and control areas. Results. At 3 months, MAL photodynamic therapy significantly reduced the occurrence of new lesions (65 vs. 103 lesions in the control area; P=0.01), mainly AK (46% reduction; 43 vs. 80; P=0.006). This effect was not significant at 27 months (253 vs. 312; P=0.06). Hypopigmentation, as assessed by the investigator, was less evident in the treatment than control areas (16% vs. 51% of patients; P<0.001) at 27 months. Conclusion. Our results suggest that repeated field photodynamic therapy using topical MAL may prevent new AK in transplant recipients although further studies are needed.

The role of apoptosis in therapy and prophylaxis of epithelial tumours by nonsteroidal anti‐inflammatory drugs (NSAIDs)

Summary In addition to having anti‐inflammatory activities, nonsteroidal anti‐inflammatory drugs (NSAIDs) also inhibit neoplastic cell proliferation by inducing apoptosis. Diclofenac is the anti‐neoplastic compound in diclofenac 3% gel (SolarazeTM) used for topical treatment of actinic keratosis (AK). Main target of NSAIDs seems to be the inhibition of cyclo‐oxygenase‐2 (COX‐2), which is overexpressed in several epithelial tumours and catalyses the synthesis of prostaglandins. The precise mechanism of action of diclofenac in cutaneous cells is still unclear, but induction of apoptosis is a key effect of anti‐neoplastic drugs, including NSAIDs.

Apoptosis pathways as promising targets for skin cancer therapy

Summary Apoptosis pathways provide efficient safeguard mechanisms against cancer that are mediated via cell‐intrinsic responses and immune‐mediated extrinsic signals. Intrinsic pro‐apoptotic pathways are largely controlled by p53 and Bcl‐2 proteins, whereas the extrinsic induction of apoptosis is initiated by death ligands, such as tumour necrosis factor‐alpha (TNF‐α), CD95L/FasL and TNF‐related apoptosis‐inducing ligand (TRAIL), or by granzyme B. Initiation of these pathways results in the induction of a caspase cascade leading to cell death.

Current state of vitiligo therapy--evidence-based analysis of the literature.

Vitiligo is a skin disease with a worldwide prevalence ranging from 0.5% to 4%. Conservative therapies include photochemotherapy, phototherapy with UVB radiation (broadband UVB 290–320 nm, narrow band UVB 311 nm), systemic steroids and pseudocatalase. Modern therapeutic options include treatment with topical immunomodulators (tacrolimus, pimecrolimus), analogues of vitamin D3, excimer laser and surgery/transplantation. Our analysis compares these therapies for vitiligo and the evidence levels supporting their effectiveness.

Treatment of multiple actinic keratoses with topical diclofenac 3% gel in organ transplant recipients: a series of six cases

Summary Background  Non‐melanoma skin cancer (NMSC) represents a significant cause of morbidity in organ transplant patients; the relative risk of squamous cell carcinoma and actinic keratosis (AK) is 100 and 250 times higher, respectively, compared with immunocompetent patients.

Differentiation between actinic keratoses and disseminated superficial actinic porokeratoses with reflectance confocal microscopy

Summary Background  Clinical differentiation between actinic keratosis (AK) and disseminated superficial actinic porokeratosis (DSAP) may pose a significant challenge, and histological evaluation is often also required for diagnosis. Distinct morphological features can be distinguished upon histopathological examination, but the use of non‐invasive tools, such as reflectance confocal microscopy (RCM), may be an eligible alternative for confirmation of diagnosis.

Skin infections in organ transplant recipients

In contrast to the well‐described high risk of skin cancer in organ transplant recipients, skin infections in these patients are not as well explored.Skin infections caused by viruses, bacteria or fungi represent a growing diagnostic and therapeutic challenge in the dermatological aftercare of organ transplant recipients. Differing immunosuppressive drugs and their variable dosage in chronologic sequence after transplantation probably influence the type and appearance of skin infections.

Management of actinic cheilitis using diclofenac 3% gel: a report of six cases

Summary Background  Actinic cheilitis is a frequent manifestation of actinic dysplasia and requires early therapy to prevent its progression into invasive squamous cell carcinoma (SCC). Several therapies are used, ranging from unspecific lesion‐adapted destructive techniques (i.e. laser) to ambitious surgical field‐management (vermillionectomy). There is increasing awareness of the effectiveness of field adapted, non destructive therapies, such as photodynamic therapy or 5% imiquimod. Diclofenac 3% gel is used in the treatment of actinic keratosis (AK), but it has not been evaluated for the treatment of actinic cheilitis.