Solar Elastosis Research Articles

A case of keratoacanthoma associated with Basal cell carcinoma.

Dear Editor: Keratoacanthoma is a relatively common epithelial tumor that originates in the pilosebaceous glands and bears a pathological resemblance to squamous cell carcinoma (SCC). Several cases of keratoacanthoma in association with other lesions such as SCC, nevus comedonicus, verrucous cell carcinoma, and cutaneous horn have been reported. Herein, we report a rare case of keratoacanthoma and basal cell carcinoma (BCC) present in a single tumor nest. A 46-year-old male patient presented with a rapidly growing lesion on his left cheek, which had developed 6 weeks previously. He had no relevant medical or family history. Physical examination revealed a 6-mm-sized, protruding verrucous papule on the cheek (Fig. 1A). The edges were raised and the central portion was crateriform with a keratin plug. A 4-mm punch biopsy was performed with a clinical impression of verruca vulgaris or keratoacanthoma. Biopsy specimen results were consistent with keratoacanthoma (Fig. 1B), without features of solar elastosis or basal layer dysplasia. Complete removal of the keratoacanthoma was performed by surgical excision. The excision specimens were composed of two sections. One section exhibited remnant keratoacanthoma, whereas the other section was consistent with BCC (Fig. 2). The BCC contained palisading basaloid cells and a cleft between the tumor nest and stroma. Fig. 1 (A) A 6-mm-sized, protruding, verrucous papule on the left cheek. (B) Central keratotic plug surrounded by epithelial proliferation (H&E, ×20). Fig. 2 Single tumor nest with abundant sebaceous glands and hair follicles (H&E, ×100). Basal cell carcinoma showing palisading basaloid cells with a cleft between the tumor nest and stroma (inset, ×200). A cutaneous collision tumor is the coexistence of more than one neoplasm in a single cutaneous specimen. In most instances, collision tumors are composed of two different tumor portions. To the best of our knowledge, there have been three previously reported cases of keratoacanthoma associated with BCC. In two reports, the keratoacanthoma and BCC lesions were distinct and separate in a single tumor nest1,2, which may be similar to our case. In another report, a histologic transition between the two lesions was observed3. The lesions reported in these three cases were located on the face, specifically on the eyelid, nose, and cheek. Given the small number of cases reported in the literature, the pathogenesis of collision tumors is controversial. One theory suggests that cumulative damages to the skin may induce the development of different neoplasms adjacent to each other4. Considering the risk factors for keratoacanthoma and BCC, we believe that in our case, the collision developed incidentally, due to chronic ultraviolet light exposure. The collision tumor in our case and those of the three previous reported cases1,2,3 were all located on the face. This also supports the above theory. As in our case, we believe that most cutaneous collision tumors are coincidental. However, there are other theories about collision tumor pathogenesis. One suggests that collision tumors may develop due to an interaction between the different tumor portions4. Another theory suggests that the different neoplasms of collision tumors may arise from multipotent stem cells5. In conclusion, we report a rare case of collision tumor composed of keratoacanthoma and BCC, although direct contact between the two lesions was not observed. Further studies will be needed to elucidate the pathogenesis of collision tumors.

Clinical manifestations of the skin photodamage as a result of a multi-course phototherapy of psoriasis patients

Goal. To study clinical manifestations and frequency of skin photodamage symptoms in psoriasis patients receiving a longterm multi-course phototherapy. Materials and methods. The study involved 106 patients suffering from psoriasis vulgaris and receiving a multi-course treatment by methods of the PUVA therapy, broadband medium-wave UV therapy and narrowband phototherapy with the wavelength of 311 nm. The average number of courses was 7 while the average number of treatment sessions was 141. Depending on the number of treatment sessions, the patients were divided into three groups: Group 1 (n = 33) - patients that received 50-100 phototherapy sessions, Group 2 (n = 58) - patients that received 101-200 treatment sessions, and Group 3 (n = 15) - patients that received over 200 treatment sessions. The control group comprised 20 psoriasis patients that did not receive any phototherapy before. Major results. The comparative analysis of the entire group of patients receiving a phototherapy revealed a statistically significant incidence of lentigo/sunspots, diffuse skin hyperpigmentation and actinic elastosis vs. the control group. The frequency of clinical manifestations characteristic of the skin photodamage grew as the number of treatment sessions increased. All of the symptoms except for guttate hypomelanosis and venous lakes demonstrated statistically significant dynamics. Conclusion. There is a dose-dependant increase in the frequency of skin photodamage symptoms in patients suffering from psoriasis vulgaris and receiving a long-term multi-course phototherapy.

Merkel cell carcinoma: histopathologic and prognostic features according to the immunohistochemical expression of Merkel cell polyomavirus large T antigen correlated with viral load.

Merkel cell carcinoma (MCC) is a neuroendocrine skin malignancy frequently associated with Merkel cell polyomavirus (MCPyV), which is suspected to be oncogenic. In a series of MCC patients, we compared clinical, histopathologic, and prognostic features according to the expression of viral large T antigen (LTA) correlated with viral load. We evaluated the LTA expression by immunohistochemistry using CM2B4 antibody and quantified viral load by real-time polymerase chain reaction. We analyzed formalin-fixed, paraffin-embedded (FFPE) tissue samples (n = 36) and corresponding fresh-frozen biopsies when available (n = 12), of the primary tumor and/or metastasis from 24 patients. MCPyV was detected in 88% and 58% of MCC patients by real-time polymerase chain reaction and immunohistochemistry, respectively. The relevance of viral load measurements was demonstrated by the strong consistency of viral load level between FFPE and corresponding frozen tissues as well as between primary tumor and metastases. From FFPE samples, 2 MCC subgroups were distinguished based on a viral load threshold defined by the positivity of CM2B4 immunostaining. In the LTA-negative subgroup with no or low viral load (nonsignificant), tumor cells showed more anisokaryosis (P = .01), and a solar elastosis around the tumor was more frequently observed (P = .03). LTA-positive MCCs with significant viral load had a lower proliferation index (P = .03) and a longer survival of corresponding patients (P = .008). Depending on MCPyV involvement, 2 MCC subgroups can be distinguished on histopathologic criteria, and the CM2B4 antibody is able to differentiate them reliably. Furthermore, the presence of a significant viral load in tumors is predictive of better prognosis.

Solar elastosis and cutaneous melanoma: a site-specific analysis.

Cutaneous melanomas are postulated to arise through at least two causal pathways, namely the "chronic sun exposure" and "nevus" pathways. While chronic sun exposure probably causes many head/neck melanomas, its role at other sites is unclear. In a population-based, case-case comparison study conducted in Brisbane, Australia, we determined the prevalence and epidemiologic correlates of chronic solar damage in skin adjacent to invasive, incident melanomas on the trunk (n = 418) or head/neck (n = 92) among patients aged 18-79 in 2007-2010. Participants self-reported information about environmental and phenotypic factors, and a dermatologist counted nevi and actinic keratoses. Dermatopathologists assessed solar elastosis adjacent to each melanoma using a four-point scale (nil, mild, moderate, marked), and noted the presence or absence of adjacent neval remnants. We measured associations between various factors and solar elastosis using polytomous logistic regression. Marked or moderate solar elastosis was observed in 10% and 27%, respectively, of trunk melanomas, and 60% and 17%, respectively, of head/neck melanomas. At both sites, marked elastosis was positively associated with age (p(trend) < 0.0001) and inversely associated with neval remnants (p(trend) < 0.001). For trunk melanomas, marked elastosis was associated with highest quartiles of total sun exposure [odds-ratio (OR) = 5.47, 95% confidence interval (CI) = 1.08-27.60] and facial freckling (OR = 2.98, 95% CI = 1.17-7.56), and inversely associated with deeply tanning skin (OR = 0.29, 95% CI = 0.08-1.11) and high nevus counts (OR = 0.08, 95% CI = 0.01-0.66). Mostly similar associations were observed with moderate solar elastosis. About one in three trunk melanomas in Queensland have evidence of moderate-to-marked sun damage, and they differ in risk associations from those without.

Upregulation of MMP12 and Its Activity by UVA1 in Human Skin: Potential Implications for Photoaging

UVA1 constitutes around 75% of the terrestrial UV radiation, and most of the output of artificial tanning sources. However, the molecular effects of UVA1 in human skin in vivo are surprisingly poorly understood. We have examined time-dependent whole-genome expression, along with mRNA and protein changes in the skin after one minimal erythema dose of spectrally pure UVA1 (50 J cm(-2)) and 300 nm UVB (30 mJ cm(-2)). After 24 hours, the genes induced to the greatest extent were those involved in extracellular matrix remodeling with both UVA1 (P=5.5e-7) and UVB (P=2.9e-22). UVA1 and UVB caused different effects on matrix metalloproteinase (MMP) expression: UVB induced MMP1, MMP3, and MMP10 mRNA at 24 hours to a much greater extent than UVA1. MMP12 induction by UVA1 at 6 hours is marked and much greater than that by UVB. We have found that MMP12 mRNA induction by UVA1 resulted in expression of MMP12 protein, which is functional as an elastase. This induction of elastase activity did not occur with UVB. We hypothesize that the UVA1 induction of MMP12 mediates some of its photoaging effects, particularly by contributing to elastin degeneration in late solar elastosis. MMP12 is a good marker of UVA1 exposure.

Sun exposure and melanoma survival: a GEM study.

We previously reported a significant association between higher UV radiation exposure before diagnosis and greater survival with melanoma in a population-based study in Connecticut. We sought to evaluate the hypothesis that sun exposure before diagnosis was associated with greater survival in a larger, international population-based study with more detailed exposure information. We conducted a multicenter, international population-based study in four countries-Australia, Italy, Canada, and the United States-with 3,578 cases of melanoma with an average of 7.4 years of follow-up. Measures of sun exposure included sunburn, intermittent exposure, hours of holiday sun exposure, hours of water-related outdoor activities, ambient ultraviolet B (280-320 nm) dose, histologic solar elastosis, and season of diagnosis. Results were not strongly supportive of the earlier hypothesis. Having had any sunburn in 1 year within 10 years of diagnosis was inversely associated with survival; solar elastosis-a measure of lifetime cumulative exposure-was not. In addition, none of the intermittent exposure measures-water-related activities and sunny holidays-were associated with melanoma-specific survival. Estimated ambient UVB dose was not associated with survival. Although there was an apparent protective effect of sunburns within 10 years of diagnosis, there was only weak evidence in this large, international, population-based study of melanoma that sun exposure before diagnosis is associated with greater melanoma-specific survival. This study adds to the evidence that sun exposure before melanoma diagnosis has little effect on survival with melanoma.

BRAFmutation status in primary and metastatic melanomas in two regions with differing potential ultraviolet radiation exposure

Melanoma is seen as a heterogeneous molecular entity, with solar ultraviolet radiation (UVR) and BRAF mutation status being important determinants. To study primary and metastatic melanomas from two UVR-distinct regions to elucidate correlations between prognostic predictors, UVR and BRAF mutation status. Extended BRAF testing for 9 mutations was obtained for 95 primary melanomas [Lebanon (LB) n=55, Pakistan (PK) n=40)] and 65 metastatic melanomas (LB n=36, PK n=29). Collected data included patient age and sex, melanoma size and anatomical location, prognostic parameters and solar elastosis grade for primary melanomas. For metastatic melanomas, site of metastasis, magnitude of necrosis and degree of pigmentation were assessed. Cumulative 21-year averages of potential UVR exposure for Lebanon (110 kJ/m(2) /year) and Pakistan (128kJ/m(2) /year) were derived from the National Center for Atmospheric Research databases. BRAF mutation status was obtained for 146/160 cases (91.3%). Overall mutation rate was 24/88 (27.3%) in primary and 25/58 (43.1%) in metastatic melanoma. V600E was the predominant mutation in 21/24 (87.5%) of primary and 23/25 (92%) of metastatic melanomas. A 60% discordant mutation rate was identified; of three patients, two lost the mutation in the metastasis and one gained it. The relative incidence of BRAF mutation with potential UVR exposure showed a similar trend in primary (low vs. high UVR: 32.1% vs. 20.0%) and metastatic (57.1% vs. 21.7%) melanomas (P<0.05). Predictors of BRAF mutations were trunk location and epithelioid and mixed cytology for primary and subcutaneous metastasis, low UVR exposure and absence of pigmentation for metastatic melanomas (P<0.05). BRAF-positive status in primary melanomas was predicted by multivariate binary logistic regression with reasonable accuracy (C-statistic=0.67, 95% CI 0.530-0.81 with one independent predictor, namely, epithelioid cytology (OR=5.11, 95% CI 1.38-8.88, P=0.01). In metastatic melanomas, high UVR (OR=0.21, 95% CI 0.06-0.07; P<0.01) was an independent negative predictor of BRAF mutation. We have documented the rate of different BRAF mutation types in a Lebanese and Pakistani cohort, and assessed correlations with prognostic markers and potential UVR exposure.

Follicular mucinosis associated with nonlymphoid skin conditions.

Follicular mucinosis coexisting with lymphoproliferative disorders has been thoroughly debated. However, it has been rarely reported in association with inflammatory disorders. Thirteen cases have been retrieved, and those with cutaneous lymphoma or alopecia mucinosa were excluded. Follicular mucinosis was found in the setting of squamous cell carcinoma, seborrheic keratosis, simple prurigo, acne vulgaris, dextrometorphan-induced phototoxicity, polymorphous light eruption (2 cases), insect bite (2 cases), tick bite, discoid lupus erythematosus, drug-related vasculitis, and demodecidosis. Unexpectedly, our observations revealed a preponderating accumulation of mucin related to photo-exposed areas, sun-associated dermatoses, and histopathologic solar elastosis. The amount of mucin filling the follicles apparently correlated with the intensity of perifollicular inflammatory infiltrate, which was present in all cases. The concurrence of dermal interstitial mucin was found in 7 cases (54%). The concurrence of interstitial dermal mucinosis or the potential role of both ultraviolet radiation and the perifollicular inflammatory infiltrates in its pathogenesis deserves further investigations. Precise recognition and understanding of this distinctive, reactive histological pattern may prevent our patients from unnecessary diagnostic and therapeutic strategies.

Desmoplastic nevus of chronically sun-damaged skin: an entity to be distinguished from desmoplastic melanoma.

Desmoplastic (sclerotic) nevus (DSN) can often be difficult to differentiate from desmoplastic melanoma (DM). This can be especially difficult when DSNs occur in a background of heavy solar elastosis. We have observed numerous examples of DSNs occurring in chronically sun-damaged (CSD) skin. In a subset of these cases, we have observed notable pleomorphism and nuclear atypia raising concern for the possibility of DM. In this study, we evaluated the clinical, histopathologic, and immunohistochemical findings in 23 cases of DSN occurring in CSD skin and compared them with 10 cases of DM. DSN on CSD skin is seen in adults (mean, 53.2 years) with a female predominance (70%) and upper (57%) and lower (17%) extremity anatomic locations. Most DSNs present as small flesh-colored macules or papules. Typical histologic features include symmetry, limited junctional growth, presence of a lentiginous component often with focal and limited pagetoid spread (extension across only a few rete ridges), and lack of deep extension. DSN and DM had a statistically significant difference in immunohistochemical staining for Melan-A and p75. Melan-A was positive in 18 of 20 DSNs and only 2 out of 10 DMs, whereas p75 was positive in all DMs (10/10) and was weakly positive in 11 of 20 DSN cases. We believe that our study offers some useful clinical, histologic, and immunohistochemical clues to help differentiate DSNs on CSD skin from DMs.

Ultraviolet A-induced cathepsin K expression is mediated via MAPK/AP-1 pathway in human dermal fibroblasts.

BackgroundCathepsin K (CatK), a cysteine protease with the potent elastolytic activity, plays a predominant role in intracellular elastin degradation in human dermal fibroblasts (HDFs), and contributes to solar elastosis. In previous studies, CatK expression was downregulated in photoaged skin and fibroblasts, but upregulated in acute UVA-irradiated skin and fibroblasts. The underlying mechanisms regulating UVA-induced CatK expression remain elusive.ObjectiveThis study investigates mechanisms involved in the regulation of UVA-induced CatK expression in HDFs.MethodsPrimary HDFs were exposed to UVA. Cell proliferation was analyzed using a colorimetric assay of relative cell number. Quantitative real-time RT-PCR and Western blot were performed to detect CatK expression in HDFs on three consecutive days after 10 J/cm2 UVA irradiation, or cells treated with increasing UVA doses. UVA-activated MAPK/AP-1 pathway was examined by Western blot. Effects of inhibition of MAPK pathway and knockdown of Jun and Fos on UVA-induced CatK expression were also measured by real-time RT-PCR and Western blot.ResultsUVA significantly increased CatK mRNA and protein expression in a dose-dependent manner. UVA-induced CatK expression occurred along with UVA-activated phosphorylation of JNK, p38 and Jun, UVA-increased expression of Fos. Inactivation of JNK and p38MAPK pathways both remarkably decreased UVA-induced CatK expression, which was suppressed more by inhibition of JNK pathway. Furthermore, knockdown of Jun and Fos significantly attenuated basal and UVA-induced CatK expression.ConclusionUVA is capable of increasing CatK expression in HDFs, most likely by activation of MAPK pathway and of AP-1, which has been shown to be the case for matrix metalloproteinases. As current strategies for selecting anti-photoaging agents focus on their ability to decrease MMPs' expression through inhibiting UV- activated MAPK pathway, future strategies should also consider their effect on CatK expression.

Macromelanosomes

Macromelanosomes are melanin-containing granules characterized by their large size and spherical or ellipsoidal morphology. They are reported to be present in a variety of pigmented skin lesions, including lentigines. However, there is limited information on macromelanosomes in malignant melanocytic proliferations. The margins of a lentigo maligna/malignant melanoma in situ (LM/MMIS) and solar lentigo share morphological similarities, including lentiginous proliferation of melanocytes, increased melanin in basal cell layer keratinocytes, and solar elastosis. This may represent a potential diagnostic pitfall, particularly in small biopsies. We sought to identify whether the presence of macromelanosomes at the lesional margins of LM/MMIS may represent a morphological clue in distinguishing between these 2 entities. Data were obtained from 2 different institutions between 2001 and 2010. 619 cases of solar lentigo and 117 cases of LM/MMIS were screened for the presence and distribution of macromelanosomes. 25 of 117 cases (21%) of LM/MMIS had macromelanosomes identified at the lesional margins, compared with 7 of 619 (1%) of solar lentigo cases (P < 0.0001). Our data demonstrate that the identification of macromelanosomes within a lentiginous melanocytic proliferation should prompt further evaluation to rule out the possibility of a contiguous LM/MMIS, particularly in a small biopsy.

Merkel cell Polyomavirus and p63 status in Merkel cell carcinoma by immunohistocnemistry: Merkel cell Polyomavirus positivity is inversely correlated with sun damage, but neither is correlated with outcome

The aim of this study was to determine the frequency of Merkel cell polyomavirus (MPyV) and p63 positivity by immunohistochemistry in a large cohort of primary Merkel cell carcinoma (MCC) from a region with high rates of actinic damage. We also aimed to determine whether there is any relationship between these markers and histological correlates of chronic sun exposure and to identify whether these markers have prognostic significance in our population. Ninety-five cases of primary cutaneous MCC were identified and stained with immunohistochemical markers for MPyV and p63. The presence of solar elastosis and squamous dysplasia in the overlying/adjacent skin were recorded as markers of actinic damage. Follow up data were obtained from the Western Australian Cancer Registry. MPyV was detected by immunohistochemistry in 23% of cases. There was a statistically significantly lower rate of positivity in tumours associated with markers of chronic sun damage as assessed by the presence of solar elastosis and squamous dysplasia. There was no association with overall or disease specific survival. p63 positivity was detected in 17% of cases. There was no association with markers of actinic damage or with overall or disease specific survival.Our data demonstrate a significant difference in rates of immunohistochemical positivity for MPyV between MCC in sun-damaged and non-sun-damaged sites. This may go some way to explaining previously identified geographical differences. When compared with a number of studies from Europe and North America, p63 positivity is less common in our population and does not show the strong prognostic significance that has been found in these other regions.

Ultraviolet exposure and risk of melanoma and basal cell carcinoma in Ulm and Dresden, Germany

There is a perpetuating increase in melanoma and basal cell carcinoma (BCC) incidence in Europe. Few studies are evaluating various risk factors for both tumours. This pre-planned additional analysis directly compared occupational and past-time ultraviolet exposure behaviour, and examined the effects of sun sensitivity between melanoma and sporadic BCC, and assessed its importance for the two entities. The study included 503 patients (melanoma, n=291 and BCC, n=212), and 329 controls from Germany. In all, 244 (49%) of the cases and 165 (50%) of the controls were male (median age melanoma, 55years; BCC, 69years; and controls, 57years). Selection of important risk factors was performed by backward elimination in a polytomous logistic regression. When directly comparing melanoma and sporadic BCC, actinic elastosis (OR 48.83; 95% CI 17.87, 133.40) and site were associated with a higher risk of melanoma, whereas mountaineering in childhood, sunburn 20years before diagnosis, farming full time, sunbed use in general, seborrheic keratosis, actinic cheilitis, actinic keratosis and age were associated with a higher risk of sporadic BCC. Gardening 20years before melanoma, hair colour and solar lentigo were risk factors for both entities. A re-evaluation of the data excluding lentiginous melanoma entities (i.e. acro-lentiginous and lentigo-maligna melanoma) resulted in selection of the same factors. However, compared to controls, atopy evolved as a protective factor for melanoma (OR 0.29; 95% CI 0.15, 0.57) and BCC (OR 0.41; 95% CI 0.17, 0.99), respectively, but was associated with a higher risk of sporadic BCC compared to melanoma. The odds for having clinical actinic elastosis was lower in BCC compared to melanoma. In contrast, various factors associated with chronic UV exposure and age had higher odds for sporadic BCC, rather than melanoma. Further research is required to set the context for these findings, especially regarding, atopy in non-lentiginous vs. lentiginous forms of melanoma, and possible molecular pathways involved.

Exploring the prevalence of skin tears and skin properties related to skin tears in elderly patients at a long‐term medical facility in Japan

The identification of appropriate skin tear prevention guidelines for the elderly requires clinicians to focus on local risk factors such as structural alterations of the epidermis and dermis related to skin tears. The aim of this cross-sectional study is to explore the prevalence of skin tears and to explore skin properties related to skin tears in elderly Japanese patients at a long-term medical facility. After doing the prevalence study, 18 participants with skin tears and 18 without were recruited and an evaluation of their skin properties using 20-MHz ultrasonography, skin blotting and also Corneometer CM-825, Skin-pH-meterPH905, VapoMeter, Moisture Meter-D and CutometerMPA580 was undertaken. A total of 410 patients were examined, the median age was 87 years and 73·2% were women. The prevalence of skin tears was 3·9%, and 50% of skin tears occurred on the dorsal forearm. The changes in skin properties associated with skin tears included increased low-echogenic pixels (LEP) by 20-MHz ultrasonography, decreased type IV collagen and matrix metalloproteinase-2, and increased tumour necrosis factor-α by skin blotting. In conclusion, this study suggests that increased dermal LEP, including solar elastosis, may represent a risk factor for skin tears; this indicates that skin tear risk factors might not only represent chronological ageing but also photoageing.

Histological comparison of two cryopeeling methods for photodamaged skin.

Background. Cryopeeling is a technique that uses cryotherapy not only on actinic keratoses lesions, but also all over the photodamaged skin. Objectives. To investigate the histological changes induced by two cryopeeling methods (liquid nitrogen (LN) and portable system (PS)). Methods. Sixteen patients (n = 16) with multiple actinic keratoses on the forearms were treated with cryopeeling technique using LN for one forearm and PS for the other, randomly. Skin biopsies were taken before and after the procedures. Results. There was no statistical difference between the epidermal and Grenz zone thicknesses or density of elastic fibers after treatments. The amount of melanin pigment was lower after PS treatment (P < 0.05). In a blind analysis of paired pre- and postprocedure slides, it was not possible to identify cases which underwent treatment, both in global analysis of quality of the skin and in specific analysis (considering only the aspect of stratum corneum). Discussion. The results indicate the inconsistency of histological improvement after treatments, and, likely, since the method causes superficial exfoliation, a reliable marker was not found in the analysis. Conclusions. Despite cosmetic benefits on photodamaged skin and efficient treatment of actinic keratoses lesions, cryopeeling was not able to induce measurable histological changes in solar elastosis, epidermal organization, or epidermal and Grenz zone thicknesses. One should keep in mind the possibility of hypopigmentation risk of the method.

Comparison of 5-aminolevulinic acid photodynamic therapy and red light for treatment of photoaging

The aim of this pilot study was to compare the efficacy of ALA-PDT and red light alone in the treatment of photoaging. A total of 14 adults with photoaging skin were recruited. ALA-PDT or red light alone was applied to the forearm extensor. Before and after treatment, the treated sites were examined by dermoscopy, the changes in straum corneum (SC) hydration, transepidermal water loss (TEWL), and the L*a*b* values were measured, and microscopic examination of collagens and elastins was performed. After ALA-PDT or red light illumination, the appearance of photoaging lesions improved, SC hydration increased and TEWL decreased. These changes in the ALA-PDT group were more obvious than those in the red light group. No significant change was noticed in the L*a*b* values in both groups. The signs of typical solar elastosis damage were improved in both groups. ALA-PDT showed better skin rejuvenation effect than red light alone.

Cutis rhomboidalis protects skin from malignant epithelial tumors

Cutis rhomboidalis nuchae is a skin alteration which comes from chronic sun exposure and it integrates the solar elastosis group, acquiring a coriaceous aspect, with a yellowish and grooved surface. There is the occurrence of elastic and collagen fibers degeneration found in the dermis caused by ultraviolet radiation [1]. Another group of skin diseases which has solar exposure as a determining factor is the group of actinic keratoses, the non-melanoma malignant epithelial tumors {basal cell carcinoma (CBC) and squamous cell carcinoma (CEC)} [2].However, the occurrence of actinic keratoses, CBCs or CECs on the area of cutis rhomboidalis is infrequent in dermatology clinical practice. The authors do not know why people with neoplasias and pre neoplastic lesions in some areas with chronic photo damage amendments (face and upper limbs), do not present the same pre and neoplastic lesions in areas with similar appearance of chronic sun damage (nape). The authors seek to understand why the nape is protected for pre and neoplastic lesions. We suggest that cutis rhomboidalis protects skin from malignant epithelial tumors in nuchae.

Elastofibromatous Lesion in The Oral Mucosa

Elastofibromas are tumor-like lesions composed of elastic and fibrous connective tissue and often associated with local trauma. Although solar elastosis is routinely seen in actinic cheilitis cases, intraoral trauma-induced elastosis, usually referred as elastofibromatous lesions, is rarely reported. Woman, 63, was referred for management of a lesion located in the right buccal mucosa that had been detected during routine oral examination. The patient reported no local trauma or prior surgery. Intraoral examination disclosed a whitish-translucent plaque.

New strategies to slow down the photoaging of the human skin

Previous reports indicate that inflammatory and proliferating skin conditions like acne and psoriasis are also associated with decreased ATP and cyclic nucleotides (cAMP) in blood and epidermal cells. In the late 80’s we noticed that psoriatic skin lesions significantly respond to supplementation with energy generating compounds and melanin promoters. In clinical studies, topically applied energy generating compounds like AMP, ADP and NAD normalized the cell replication rate in psoriatic skin, (CELL ENERGY) diminished the acne pustulae and induced a significant improvement of skin structure and wrinkles (anti-aging-effect). The photoaging process of the human skin in the presence of natural sunlight or artificial UV-sources is closelyy related to a strong generation of free radicals, lipid peroxidation, collagenase activation, glycation/ oxidation of proteins (AGE products), activation of p53 transcription factors, low DNA repair capacity and cumulative DNA mutations. Clinically, the adverse effects of natural sunlight and other UV-sources on normal human skin may vary from sunburn with erythema, oedema and DNA damage (12-24 hrs. after UV-exposure) to polymorphic light reaction (eczema solare), solar actinic elastosis and actinic hyperkeratosis (as common precancerous condition), up to different skin cancer forms like basal cell carcinoma (BCC), squamous cell carcinoma (SCC) or malignant melanoma (MM). The study of the lipid, protein and DNA oxidative damage triggered by the free radical attack subsequent to sunlight exposure has conducted to appropriate strategies to slow down or block these reactions making possible the design of innovative skin care formulations. In this respect, a new German photoaging defence formula (SOLARIS SPF 25) combines for the first time the double UVA + UVB protection (SPF 25) with melanin promoting aminoacids directly enhancing the natural tanning process. Free radical blocking agents like Vit. E, carrot oil and metal chelators are preventing the sun exposure side-effects together with immune stimulating plant extracts (β-glucans) with anti-herpes virus activity. To slow down the photoaging related wrinkle formation efficiently, a new collagen synthase stimulating formula offers a synergistic anti-aging combination of UV-light blockers, free radical quenchers (Vit. E, Coenzyme Q10) and collagen/ elastin synthesis promoters like hydroxyprolin and plant bioflavonoids (ENERGO Repair)). The active ingredients are incorporated in liposomes containing skin identical phospholipids and ceramides by means of the patented DMS® nanoparticle technology. A rapid uptake in the epidermis cells is thus granted. The use of the described hypoallergenic topical products results in a significant improvement of the skin structure and appearance within 30 days, as documented with the standardized Surface Evaluation of Living Skin (SELS) methodology in a group of 35 women aged 40 to 63 years. Our recent research shows that appropriate combinations of hypoallergenic protein hydrolysates with sugar alcohols and omega-3 polyunsaturated fatty acids (EQUIDERM PLUS) are showing a remarkable free radical quenching and anti-inflammatory activity leading to a significant symptom alleviation in skin and geriatric patients. Finally, with the emergence of affordable microarray gene expression profiling methods we had the opportunity to test several oral and i.v. nutraceutical combinations (NUTRIGEN PA, NUTRIGEN PS ) for their silencing ability on inflammatory genes (nutrigenomic evaluation) and correlate the “ex in vivo” results in blood cells with their “ in vivo” clinical efficacy.

Clinicopathologic Findings and BRAF Mutation in Cutaneous Melanoma in Young Adults

Cutaneous melanoma in young patients is rare with increasing incidence. It is not clear whether the etiology and clinical outcome are similar to cutaneous melanoma in the elderly. Mutations in BRAF gene in patients with cutaneous melanoma, in general, range in frequency from 20% to 80%; however, the status and clinical significance of BRAF mutations in the young population have not been evaluated. We investigated 132 cases of primary cutaneous melanoma in patients aged between 18 and 30 years with emphasis on clinical characteristics, pathologic features, and molecular evaluation of mutation in the BRAF gene (BRAF(V600E)). It was predominantly seen in female individuals (61.4%), trunk was the most common site of involvement (40.4%), and superficially spreading melanoma was the predominant histologic type (79.5%). Mutation in BRAF(V600E) was analyzed successfully in 93 cases using an RT-PCR. The BRAF(V600E) mutation was identified in 38.7% (36/93) and was associated with vertical growth phase (P=0.01) and mild inflammatory infiltrate (P=0.02). No case of melanoma with regression phenomenon presented with BRAF(V600E) mutation (P<0.05). There was no significant association between BRAF(V600E) mutation and sex, histologic type, the Clark level, the Breslow index, solar elastosis, angiolymphatic and perineural invasion, satellitosis, and coexisting nevus. As in melanomas in older patients, these results probably indicate that BRAF mutation may not be the only key factor in melanoma tumorigenesis, and that there should be multiple alternative genetic pathways related to melanoma.