Histological correlates of metastasis in primary invasive squamous cell carcinoma of the lip

The histological features of 66 cases of squamous cell carcinoma of the lip were studied in an attempt to define prognostic parameters. Features that correlated with an increased risk or metastasis included histological grade of the tumour at the base and the surface, the tumour thickness, presence of stromal sclerosis, and the presence of muscle and perineural invasion.     

Functional characterization of cancer-associated fibroblasts of human cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (SCC) is the second most common type of skin cancer in the Caucasian population worldwide, having a propensity for invasion, local recurrence and metastasis. Stromal cancer-associated fibroblasts (CAFs) are suspected to play an important role in SCC carcinogenesis. In this study, we characterized CAFs isolated from primary cutaneous SCCs and compared them to normal fibroblasts (NFs) isolated from healthy dermis. Human skin CAFs in monolayers displayed different morphology, increased proliferation and migration compared to NFs. CAFs caused strong contraction of collagen matrices in which they were seeded and released high levels of the extracellular matrix component pro-collagen I. CAFs decreased proliferation and differentiation in the epidermis of human skin equivalents (HSEs) seeded with SCC cell lines, without affecting basement membrane composition. Finally, CAFs significantly increased invasion and dermal-epidermal detachment of SCC cell lines SCC-12B2 and SCC-13, respectively, when cultured in HSEs. These distinct features of CAFs point out a specific role in cutaneous SCC development.     

Nicotinamide and the skin

Nicotinamide, an amide form of vitamin B3, boosts cellular energy and regulates poly‐ADP‐ribose‐polymerase 1, an enzyme with important roles in DNA repair and the expression of inflammatory cytokines. Nicotinamide shows promise for the treatment of a wide range of dermatological conditions, including autoimmune blistering disorders, acne, rosacea, ageing skin and atopic dermatitis. In particular, recent studies have also shown it to be a potential agent for reducing actinic keratoses and preventing skin cancers.     

Assessment of skin lesions and skin cancer using simple electrical impedance indices

Background/aims: Purpose of this investigation was to assess benign pigmented cellular nevus (BEN), basal cell carcinoma (BCC), dermatofibroma (DER), dysplastic nevus (DYS), and seborrheic keratoses (SEB) using in vivo non- invasive electrical impedance technique.
Methods: Electrical impedance was measured at 258 BEN, 34 BCC, 17 DER, 35 DYS, and 26 SEB lesions. Controls were measured at healthy skin close to the lesions. The impedance was measured between 1 kHz and 1 MHz at five depth settings. After the impedance measurements the lesions were histopathologically diagnosed. The impedance spectra were parameterized to four indices prior to the statistical analysis of the data.
Results: There were significant differences between the lesions and their controls for BEN ( P  < 0.001), BCC ( P  < 0.001), DYS ( P  < 0.01), and SEB ( P  < 0.01).
Conclusions: There are clear statistical differences between impedance of common lesions and control skin. With some further developments, the impedance technique can be useful as a diagnostic decision support tool for skin cancer assessment.     

Skin cancer chemoprophylaxis in renal transplant recipients: 5 years of experience using low-dose acitretin

Renal transplant recipients have an increased risk of developing skin cancers, which are often multiple and aggressive. Frequently, these tumours develop on a background of widespread epidermal dysplasia. Systemic retinoids are known inhibitors of skin cancer but reports of their use in renal transplant patients are limited. We describe our experience using 0.3 mg/kg daily of acitretin in 16 patients over a 5-year period. Overall, there was a significant reduction in the number of new tumours excised in 12 of 16 patients during treatment compared with the same pretreatment interval. A significant chemoprophylactic effect was shown for up to 4 years of treatment. Patients with five or more tumours prior to acitretin benefited most. Two patients discontinued treatment because of side-effects and two patients developed hyperlipidaemia. Two patients with end-stage graft failure proceeded to haemodialysis. The introduction of low-dose acitretin proved to be a useful strategy in the long-term reduction of skin cancer in renal transplant recipients with multiple skin cancers and extensive epidermal dysplasia.     

Lesion classification using skin patterning

Background/aims: The observation that skin line patterning tends to be disrupted by malignant but not non‐malignant skin lesions suggests that this could be used as an aid to lesion differentiation. Since recognised differentiating features can be obtained from the simply‐captured white light optical image, the possibility of using such images for skin pattern disruption detection is worth exploring. Methods: The skin pattern has been extracted from optical images by high‐pass filtering and profiles of local line strength variation with the angle estimated using a new consistent high‐value profiling technique. The resultant profile images have been analysed using a novel region‐based agglomerative clustering technique (mRAC) and also a local variance measurement. A measure based on the relationship between the classification results and an intensity‐based segmentation was calculated, and this represented the disruption of the skin line patterning. Results: A set of images containing a variety of histologically confirmed malignant and non‐malignant lesions was analysed. The computed textural disruption figure was compared to both the histological diagnosis and to a visual estimate of patterning disruption for each image. It was demonstrated that lesion separation could be achieved by both analysis methods, with a good correlation with visual estimate of disruption and with mRAC providing the best performance. Conclusions: It was concluded that the acquisition and modelling of skin line patterning from clinical images of skin lesions had been successfully achieved and that the analysis of the resulting data provided an assessment of pattern disruption that is both consistent with visual inspection and effective in presenting information useful for discrimination between melanoma and benign naevi lesion examples.     

Quality of life issues in nonmetastatic skin cancer

Background Current knowledge of quality of life (QOL) issues affecting patients with nonmetastatic skin cancer is unsatisfactory, being based either on the use of QOL questionnaires derived from dermatology patients with predominantly benign lesions or inflammatory skin rashes, or on the use of general health QOL questionnaires. Objectives We sought to determine the impact of nonmetastatic skin cancer on patients’ lives by asking such patients for their written opinions. Methods An open‐ended ‘Skin Cancer Quality of Life Question Sheet’ was given to 100 consenting patients with nonmetastatic skin cancer [50 with malignant melanoma (MM) and 50 with nonmelanoma skin cancer (NMSC)]. Results In total, 82 ‘Skin Cancer Quality of Life Question Sheets’ were returned complete (40 MM and 42 NMSC). There were 44 different patient concerns voiced overall in the responses. The concerns were grouped into 10 main themes. Patients with MM were significantly more likely than those with NMSC to mention ‘a sense of relief/gratitude following treatment and/or a commitment to enjoy life here on’ (P = 0·001), ‘feelings of anxiety/depression/guilt/stress towards oneself or family/friends’ (P < 0·001) and ‘strengthening of emotional relationships with family and/or friends’ (P = 0·02). Patients with NMSC were significantly more likely than those with MM to mention ‘concern about the public’s lack of understanding and recognition of skin cancer’ (P = 0·02). The theme ‘realization of one’s mortality’ was commoner among patients with MM than with NMSC, while the theme ‘concern regarding possible scarring/disfigurement or the reaction of others’ was commoner among patients with NMSC than with MM, although neither of these two differences was statistically significant (P = 0·07 and P = 0·11, respectively). Conclusions QOL issues expressed by patients with nonmetastatic skin cancer highlight concerns we must address during their care. A disease‐specific QOL measure suitable for both nonmetastatic MM and nonmetastatic NMSC is needed. The psychosocial impact on patients with nonmetastatic MM must not be underestimated.     

Trends of skin diseases in organ‐transplant recipients transplanted between 1966 and 2006: a cohort study with follow‐up between 1994 and 2006

Background Skin diseases are frequently observed in organ‐transplant recipients (OTRs). Objectives To count the registered skin diseases in all 2136 OTRs who had been transplanted in a single centre between 1966 and 2006 and to calculate their relative contribution in relation to the number of years after transplantation. Methods All registered skin diseases which were entered into a computerized system between 1994 and 2006 at the Leiden University Medical Centre were counted and their relative contributions were calculated. Results Between 1994 and 2006, 2408 skin diseases were registered in 801 of 1768 OTRs who were at risk during this specific time period. The most commonly recorded diagnoses were skin infections (24·0%) followed by benign skin tumours (23·3%) and malignant skin lesions (18·2%). The relative contributions of infectious and inflammatory disorders decreased with time after transplantation, whereas the contribution of squamous cell carcinomas strongly increased with time. Conclusions This study gives a systematic overview of the high burden of skin diseases in OTRs. The relative distributions of skin diseases importantly changed with time after transplantation, with squamous cell carcinoma contributing most to the increasing burden of skin diseases with increasing time after transplantation.     

Basal cell carcinoma of the scrotum

An 80-year-old man with a 7 year history of a slowly enlarging, asymptomatic scrotal nodule is presented. He had a negative history for sexually transmitted disease, trauma to the area, radiotherapy and chemical or arsenic exposure. The lesion was excised with a margin of 0.8 cm of normal skin. Examination of the specimen revealed a basal cell carcinoma.     

Incidence of skin cancer in 5356 patients following organ transplantation

BACKGROUND: Skin cancer following solid organ transplantation is an important cause of morbidity in long-term survivors. This risk is well known but imprecisely quantified. OBJECTIVES: We aimed to determine: (i) the skin cancer risks in transplant patients more precisely; (ii) whether the risk of malignant melanoma is altered; and (iii) whether the risk of epithelial cancers occurring at non-exposed sites is comparable with that seen in sun-exposed sites. METHODS: We linked a population-based cohort of 5356 patients who had received organ transplants in Sweden between 1970 and 1994 with the compulsory Swedish Cancer Registry, to identify all cancer cases except basal cell carcinomas, which are not registered. RESULTS: After a mean follow-up of 5.6 years post-transplantation, 172 of 5356 patients developed 325 non-melanoma skin cancers (excluding basal cell carcinomas) and six malignant melanomas. The relative risk of non-melanoma skin cancer was 108.6 [95% confidence interval (CI) 94.6-123.1] for men and 92.8 (95% CI 73.2-116.0) for women. The highest risks were noted for upper limbs, and the risk increased with time. No significant increase in malignant melanomas was noted: the relative risk was 1.6 (95% CI 0.5-3.7) for men and 0.5 (95% CI 0. 0-2.6) for women. Except for the lip, which is also sun-exposed, other epithelial sites did not show comparable increases in cancer risk. CONCLUSIONS: We conclude that organ transplant recipients are at a highly increased risk for non-melanoma skin cancer and must be closely followed throughout their lives. Cancer risk associated with transplantation is higher for sun-exposed than for non-sun-exposed epithelial tissues, even among populations living in regions with low solar insolation.     

An open-label, pilot study examining the efficacy of curettage followed by imiquimod 5% cream for the treatment of primary nodular basal cell carcinoma

SUMMARY The short-term efficacy of imiquimod 5% cream for the treatment of primary superficial basal cell carcinoma has been established. This study investigated its efficacy following curettage (without electrodesiccation) for the treatment of primary nodular basal cell carcinoma on the trunk and limbs. Seventeen patients with a total of 34 lesions were enrolled. Curettage was used to de-bulk the lesion and confirm suitable histology. Lesions displaying more aggressive subtypes (such as micronodular or morpheoic components) were excluded. Lesions were treated daily for 6 to 10 weeks with imiquimod 5% cream. Three months post treatment all lesions were excised, and 32 of 34 treated lesions (94%) were histologically clear of basal cell carcinoma. Fourteen of 17 patients rated the cosmetic outcome of treatment as excellent or good. Curettage followed by imiquimod 5% cream is effective for the treatment of primary nodular basal cell carcinoma on the trunk and limbs, and most patients are pleased with the cosmetic outcome.     

The sirtuin 6: An overture in skin cancer

In the recent past, the sirtuins have been under intense investigation for their roles in biology and disease, including cancer. The sirtuin SIRT6 is comparatively a lesser studied member of this family of seven proteins. Like certain other sirtuins, SIRT6 is emerging to have an oncogenic function as well as tumor suppressor roles in cancer. Limited studies have been conducted assessing the role and functional significance of SIRT6 in melanoma and non-melanoma skin cancers. In this review, we have attempted to critically dissect the potential role and significance of SIRT6 in skin carcinogenesis. With limited available information to date, SIRT6 appears to have a pro-proliferative function in non-melanoma skin cancers (NMSCs), including squamous cell carcinoma (SCC) and basal cell carcinoma (BCC). In addition, SIRT6 is also emerging to have an oncogenic function in melanoma. Moreover, we have provided information regarding the available SIRT6 inhibitors. Conclusively, it appears that additional comprehensive studies are needed to establish the role of SIRT6 in skin biology and skin diseases, including cancer. Further, concerted efforts are needed to characterize the stage-specific role of SIRT6 in skin cancers.     

Skin temperature of UV-induced erythema correlated to laser Doppler flowmetry and skin reflectance measured redness

Background/aims: The sensitivity of human skin to UV radiation is investigated by visual grading of the resulting erythema reactions 24 h after exposure to a series of increasing UV doses. Visual erythema assessment is, however, subjective and depends on pigmentation and redness of the adjacent un-irradiated skin and can be aided by skin reflectance spectroscopy and laser Doppler blood flow measurements. Erythema is accompanied by a raised skin temperature, and this reaction might be utilised as a simple objective measurement of UV sensitivity. Methods: Sixteen patients with cutaneous malignant melanoma, 16 patients with basal cell carcinoma, and 36 healthy people were phototested with simulated sunlight on previously UV un-exposed buttock skin. The resulting erythema reactions were graded visually 20-24 h post-exposure and measured by skin reflectance spectroscopy and laser Doppler flowmetry, and the surface skin temperature was determined in the erythema reactions and in adjacent un-irradiated skin by a contact thermometer. Results: Skin surface temperature in UV-induced erythema reactions was dose dependent, was statistically identical in skin cancer patients and in healthy people, and was age independent. The average temperature increase in barely perceptible erythema was 0.7°C (SD=1.1°C), and in bright red erythema it was 3.5°C (SD=2.0°C). Skin surface temperature increases were correlated to measurements by skin reflectance spectroscopy and by laser Doppler flowmetry. Conclusions: Skin surface temperature changes can be used as a simple objective measurement of UV sensitivity in healthy people and in skin cancer patients and may be particularly useful in heavily pigmented people where visual assessment of erythema is difficult or impossible.     

Safety and efficacy of a bilayered skin construct in full-thickness surgical wounds

This was a prospective, randomized, controlled clinical trial assessing the safety and efficacy of a living bilayered skin construct (BSC; Organogenesis, Canton, MA) in treating full-thickness surgical excision wounds. We enrolled 31 patients needing excision of a non-melanoma skin cancer. The patients consisted of 18 females and 13 males, with an average age of 67 years (range: 44 to 84 years). Patients were randomized to either receive a single application of BSC or to heal by secondary intention. Endpoints to assess efficacy included time to complete wound closure, intensity and duration of post-operative pain, cosmetic appearance, patient satisfaction, and quality of the healed wound. Endpoints to assess safety included infection at the wound site and rejection of the BSC. Findings indicate that BSC is safe in the post-operative treatment of acute surgical wounds for removal of non-melanoma skin cancer. The data also suggest that BSC may facilitate management by decreasing post-operative pain. It is unclear whether or not BSC decreases healing time of acute wounds or results in a better cosmetic outcome.