No abstract

Purpose: Nonmelanoma skin cancer is the most common cancer and comprises basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The incidence of SCC increases drastically in immunosuppressed individuals, suggesting a critical role of the immune system in controlling SCC. To find an explanation for the selective immunosurveillance of SCC, we investigated the expression of cancer-testis (CT) antigens and MHC class I (MHC-I) and the infiltration by immune cells in BCC and SCC.Experimental Design: We determined the expression of 23 different CT-antigens in 63 BCC and 40 SCC biopsies of immunocompetent and in 20 biopsies of immunosuppressed SCC patients by reverse transcription-PCR and immunohistochemistry. IgG responses to 36 tumor antigens were measured by Western blotting and ELISA. MHC-I expression and CD8 + T-cell infiltration were analyzed by immunohistochemistry in BCC and SCC of immunocompetent and immunosuppressed patients and in imiquimodtreated BCC patients.Results: We found expression of at least one CT-antigen in 81% of BCC and in 40% of SCC. We did not detect CT-antigen-specific serum IgG. Most SCC, but not BCC, expressed MHC-I and were infiltrated with CD8 + cells. Imiquimod-treated BCC expressed MHC-I and were infiltrated by CD8 + T cells.

The development of cancer immunotherapy and targeted therapy has reached an important inflection point in the history of melanoma. Immune checkpoint inhibitors and kinase inhibitors are today’s standard of care treatments in advanced melanoma patients. Treatment-related toxicities can be very intriguing and quite challenging. Sarcoidosis is a multisystemic granulomatous disease characterized by an aberrant immune response to unknown antigens, whereas sarcoid-like reactions (SLRs) refer to localized clinical features. We carried out a single-center observational study in patients with stage IIB–IV melanoma treated with BRAF/MEK inhibitors and immune checkpoint inhibitors. A description of the sarcoidosis-related manifestations was provided from patients’ records. We observated eight cases of SLRs in a cohort of 200 patients. The clinical courses were characterized by a variety of symptoms, accompanied by cutaneous signs and extracutaneous manifestations such as bilateral, hilar lymphadenopathy. We identified a histologically granulomatous inflammation involving the skin, the lungs, and the lymph nodes. Two patients presented with cutaneous lesions only, and three patients had lung involvement only. Three patients achieved complete and partial response of the melanoma disease, and three patients had stable disease. Disease progression was documented in two patients. The reported immune-related adverse events were mild to severe and in most of the cases were continued without any treatment cessation. SLRs appear during treatment with both kinase and immune checkpoint inhibitors. Awareness of these can avoid misdiagnosis of disease progression and unnecessary treatment changes.

Topical therapy with timolol is effective for infantile hemangiomas, but systemic absorption occurs. Serum levels in our patients were low, suggesting that using timolol for small hemangiomas is safe, but caution is advised when treating ulcerated or large hemangiomas, very young infants, or concomitantly using systemic propranolol.

Background: Surgical excision is the gold standard for cutaneous squamous cell carcinoma (cSCC), however its application is limited in specific cases. Superficial radiotherapy (RTx) is an alternative treatment option, but long-term follow-up data are limited. Objective: To determine the outcome of superficial RTx of cSCC in correlation to histological differentiation grade and tumor localization. Methods: The outcome of 180 large cSCCs after superficial RTx between 1960 and 2004 was retrospectively reviewed. Results: Mean tumor size was 3.5 cm² (SD 7.5) and mean follow-up period was 4.9 years (SD 4.7). Relapse-free survival was 95.8 and 80.4% after 1 and 10 years. Two-year relapse-free survival was 94.8% for good, 88.9% for moderate and 85.7% for poor differentiated tumors. Five-year relapse-free survival was highest in cSCCs located around the eyes (100%) and cheeks (90.9%). Conclusion: Superficial RTx is an effective alternative for cSCC if surgery is difficult due to localization or concomitant disease.

We have investigated the staining patterns of primary and metastatic melanoma lesions using F8, L19 and F16. These three clinical-stage antibodies are currently being studied in clinical trials for the pharmacodelivery of cytokines or therapeutic radionuclides to neoplastic sites in patients with cancer. Frozen sections of 24 primary and 29 metastatic melanoma lesions were stained, using immunofluorescence procedures, with biotinylated preparations of the F8, L19 and F16 antibodies, which are specific to the alternatively spliced extra domain A and extra domain B domains of fibronectin and A1 domain of tenascin-C, respectively. Blood vessels were costained using von Willebrand factor-specific antibodies. In primary cutaneous melanoma lesions, F16 and F8 (but not L19) strongly stained the basal lamina at the interface between epidermis and dermis, with a strikingly complementary pattern. By contrast, metastatic melanoma lesions displayed a strong and diffuse pattern of immunoreactivity with all three antibodies. It was found that the extracellular matrix in melanoma undergoes extensive remodelling during the transition from primary to metastatic lesions. The intense staining of metastatic melanoma lesions by the F8, L19 and F16 antibodies provides a strong rationale for the use of these antibodies and their derivatives for the treatment of melanoma patients and possibly for the personalized choice of the best performing antibody in individual patients.

Background: Split-thickness skin graft (STSG) donor sites sometimes cause more postoperative morbidity for patients than the wound covered with the graft. Yet, there is no consensus on which dressings are best suited to treat these donor sites. Objective: To evaluate two commonly used modern wound dressings in the postoperative healing of STSG donor sites in a prospective randomized controlled trial. Methods: 38 patients were randomly assigned to treatment of an STSG donor site with an alginate dressing or a polyurethane film dressing. The primary outcome measures were postoperative pain scores, secondary outcome variables were time to epithelialization, dressing changes and complications. Results: Postoperative pain on day 1 was significantly lower in the polyurethane film group (2.05 vs. 0.79, p = 0.035) as compared to the alginate group. This difference was not detected on day 5 (0.89 vs. 0.53, p = 0.52). Time to epithelialization did not differ significantly between the two dressing groups. There were more dressing changes in the polyurethane film group and problems with leakage. Conclusion: Whereas film dressings resulted in initially lower pain scores, alginate dressings caused fewer additional dressing changes and less leakage.

Ultraviolet (UV) radiation has both beneficial and harmful effects on the human body. Its most important beneficial effect may be vitamin D production in the skin, also known as vitamin D photosynthesis. This is of particular interest for the elderly who often show vitamin D-deficiency. Intentional UV exposure has been recommended by different institutions in order to increase vitamin D levels. Nevertheless, UV radiation directly causes DNA damage and is verifiably responsible for carcinogenesis, potentially resulting in lethal skin cancers. Unfortunately, skin cancer incidence is rising worldwide, and there is still a lack of appropriate treatment for metastasized types. The only proven and avoidable risk factor is UV radiation. It has been shown that the earlier UV protection is started, the greater the benefit in terms of skin cancer prevention. Nevertheless, even if UV protection is started at older ages, individuals will benefit measurably. Because UV radiation is neither a reliable nor a safe method of achieving healthy vitamin D levels, intentional UV radiation is not recommended to increase vitamin D levels. In order to prevent skin cancer, UV protection is to be conducted as commonly recommended, by minimizing sun exposure, and especially sunburn, with appropriate sun protective behaviors, e.g. usage of sunscreen and clothing (hat, sunglasses, long sleeves, and pants). Infants must be protected with extra care. Tanning beds must be avoided.