Optical coherence tomography for presurgical delineation of basal cell carcinomas on the face-A comparison with histopathology.

BACKGROUND: To minimize the risk of incomplete excision of basal cell carcinomas (BCC) the macroscopic tumor margins should be adequately defined. Optical coherence tomography (OCT) is a non-invasive imaging tool that can provide structural and vascular information about skin cancer lesions. The study objective was to compare the presurgical delineation of facial BCC by clinical examination, histopathology, and OCT imaging in tumors undergoing full excision. METHODS: Ten patients with BCC lesions on the face were examined clinically, with OCT and histopathology at 3-mm intervals, from the clinical lesion border and beyond the resection line. The OCT scans were evaluated blinded and a delineation estimate of each BCC lesion was made. The results were compared to the clinical and histopathologic results. RESULTS: OCT evaluations and histopathology were in agreement in 86.6% of the collected data points. In three cases the OCT scans estimated a reduction of the tumor size compared to the clinical tumor border set by the surgeon. CONCLUSION: The results of this study support the notion that OCT can have a role in the clinical daily practice by aiding clinicians in delineating BCC lesions before surgery.

One-day or two-day procedure for sentinel node biopsy in melanoma?

PURPOSE: We compared the outcome of a 1-day and a 2-day sentinel node (SN) biopsy procedure, evaluated in terms of lymphoscintigraphic, surgical and pathological findings. METHODS: We studied 476 patients with melanoma from two melanoma centres using static scintigraphy and blue dye. A proportional odds model was used for statistical analysis. RESULTS: The number of SNs visualized at scintigraphy increased significantly with time from injection to scintigraphy and activity left in the patient at scintigraphy, and depended on the melanoma location. The number of SNs removed at surgery increased with the number of SNs visualized at scintigraphy and time from injection to surgery. The frequency of nodal metastasis increased with increasing thickness and Clark level of the melanoma, and was highest for two SNs visualized at scintigraphy. CONCLUSION: This study showed that early vs. late imaging and surgery do make a difference on the outcome of the SN procedure and confirmed the importance of the scintigraphic visualization of all true SNs.

Pain induced by photodynamic therapy of warts.

BACKGROUND: Photodynamic therapy with topical 5-aminolevulinic acid (ALA), followed by irradiation with red light (ALA-PDT), is used for non-melanoma skin cancer and other dermatological diseases. Pain during and after light exposure is a well-known adverse advent that may be a limiting factor for treatment, particularly, in viral warts. METHODS: To assess the pain induced by ALA-PDT, we asked 45 patients enrolled in a randomized, placebo-controlled trial with six consecutive ALA- and placebo-PDT treatments for recalcitrant foot and hand warts to fill in questionnaires about pain immediately and 24 h after each treatment. RESULTS: Immediately and 24 h after each of the six treatments, pain intensity was significantly higher in warts treated with ALA-PDT than in warts treated with placebo-PDT (P<0.028). Severe or unbearable pain was reported from a median of 17% (6-31%) of the ALA -treated warts and from a median of 2% (0-15%) from the placebo-treated warts immediately after the treatments. With increasing treatments, no significant change in pain intensity was observed and no significant relation was found between the pain intensity and the relative change in wart area. The pain was primarily characterized as burning and shooting. The pain lasted about 30 h (range: 1-96 h). CONCLUSION: We conclude that pain induced by ALA-PDT is of such intensity in about one-fifth of the warts that pain relief is indicated.

Naevi as a risk factor for basal cell carcinoma in Caucasians: a Danish case-control study.

The number of melanocytic naevi in Caucasians is related to previous exposure to the sun and is a well-documented major risk factor for cutaneous malignant melanoma. Basal cell carcinoma, which is the most common form of skin cancer, has also been shown to be related to exposure to the sun. To investigate whether the number of common naevi is a risk factor for basal cell carcinoma in Caucasians we performed whole-body counting of naevi > or =2 mm in a Danish case-control study with 145 cases of primary basal cell carcinoma and 119 controls matched on age, gender and place of residence. Naevi were recorded according to size and body region and the skin phototype was assessed. There was no correlation between self-reported skin type and the number of naevi. Females with basal cell carcinoma had more naevi than did female controls (median number of naevi: 65 and 32, respectively) while males with basal cell carcinoma did not differ from male controls (median number of naevi: 48 and 43, respectively). Female cases had more small size naevi (2 mm), intermediate size naevi (3-4 mm) and large size naevi (> or =5 mm) than did female controls. Females with basal cell carcinoma had a substantially higher number of naevi on the arms and the legs than did female controls, but also had more naevi on the trunk. For females, the risk for basal cell carcinoma increased with increasing number of naevi. Naevi were not a risk factor for basal cell carcinoma in males.

Recalcitrant hand and foot warts successfully treated with photodynamic therapy with topical 5-aminolaevulinic acid: a pilot study.

The purpose of this pilot study was to determine if photodynamic therapy with topical application of 5-aminolaevulinic acid followed by irradiation with incoherent filtered and unfiltered light (ALA-PDT) is an effective therapy for recalcitrant hand and foot warts. In 30 patients with recalcitrant warts, 49 regions with a total of 250 warts were randomized to one of the following five treatments: (i) ALA-PDT with white light applied three times within 10 days (W3); (ii) ALA-PDT with white light applied once (W1); (iii) ALA-PDT with red light applied three times within 10 days (R3); (iv) ALA-PDT with blue light applied three times within 10 days (B3), and (v) cryotherapy applied up to four times within 2 months (CRYO). The ALA-PDT treatment modality was repeated in case of partially responding warts. Significantly more warts were completely healed after W3 and W1 than after R3, B3 and CRYO (P < 0.01): 73% of the warts treated with W3 were completely healed, 71% after W1, 42% after R3, 23% after B3 and 20% after CRYO. No scars were observed in the ALA-PDT treated areas and patients treated for foot warts were all able to walk after the treatment. No recurrences in completely responding ALA-PDT treated warts were observed after 12 months of follow-up. In conclusion, photodynamic therapy with topical 5-aminolaevulinic acid followed by irradiation with white light is a promising treatment for recalcitrant hand and foot warts.

Eye and hair colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma. A Danish case-control study.

To assess the importance of hair and eye colour, skin type and constitutive skin pigmentation as risk factors for basal cell carcinoma and cutaneous malignant melanoma in fair-skinned Caucasians, we conducted two identical case-control studies in Denmark. We studied 145 cases with basal cell carcinoma and 174 matched controls, and 168 cases with cutaneous malignant melanoma and 176 matched controls. Controls were matched on age, gender and place of residence. Subjects indicated their hair colour before 7 years of age, and at 25 years of age and their skin phototype. Interviewers assessed the present hair colour and eye colour, and the constitutive skin pigmentation was measured objectively by skin reflectance of UV unexposed buttock skin. There were no differences between basal cell carcinoma cases and controls in hair colour or eye colour or constitutive skin pigmentation, but more cases were of skin type II than skin type IV; skin type 11 was a risk factor for basal cell carcinoma with an odds ratio (OR) of 2.3. For cutaneous malignant melanoma, more cases than controls were red-haired or blond and of skin type II, but there was no difference in constitutive skin pigmentation. Hair colour and skin type were found to be independent risk factors for cutaneous malignant melanoma; red hair vs. black/brown: OR >9.7, blond hair vs. brown/black: OR = 2.4, and skin type 11 vs. type IV: OR=2.0. There were no gender-related differences in risk factors for basal cell carcinoma and cutaneous malignant melanoma.

Urocanic acid isomers in patients with basal cell carcinoma and cutaneous malignant melanoma.

Urocanic acid (UCA) is a major chromophore for ultraviolet (UV) radiation in the skin. On UV exposure, the naturally occurring trans-isomer converts to the cis-isomer in a dose-dependent manner. Accumulating evidence indicates that cis-UCA acts as an initiator of the UV-induced suppression of certain skin immune functions. This immunomodulation is recognized as an important factor in the development of skin cancer. In this study, pigmentation and UCA isomers were measured in 29 patients with previous basal cell carcinoma (BCC), 23 patients with previous cutaneous malignant melanoma (MM), and 32 healthy controls. Measurements were performed on UV-exposed (forehead, upper back) and UV non-exposed (buttock) skin. No significant differences in pigmentation percentage, total UCA concentration, relative (%) or absolute (nmol/cm2) cis-UCA concentration were observed between the groups in any of the body sites studied. The net production of cis-UCA after irradiation with a single test UV dose was evaluated. The relative production of cis-UCA following irradiation was significantly higher in both cancer groups when compared with the control group, while no significant difference was found between the BCC and the MM patients.

Facultative skin pigmentation in caucasians: an objective biological indicator of lifetime exposure to ultraviolet radiation?

To investigate age and gender trends in facultative and constitutive skin pigmentation we measured skin pigmentation non-invasively and objectively by skin reflectance spectroscopy in 653 caucasians (336 females and 317 males; mean age 38 years, range 0-85) who were not using artificial tanning devices. In all subjects, measurements were performed in the late winter and pre-spring period at five sites exposed to ultraviolet (UV) radiation: the forehead, the upper chest, the upper back and the lateral and medial aspects of the upper arm, and in UV-unexposed buttock skin. Constitutive pigmentation at the buttocks was highest in the first years of life and then decreased substantially during the first two decades of life (P < 0.01). After the age of 25 years, buttock pigmentation remained at a constant level (P = 0.20). There was no gender difference in constitutive pigmentation. Facultative skin pigmentation increased with age for all the measured sites with the highest levels found at the lateral aspect of the upper arm. Based on observations in this study we propose the idea of a 'sun exposure index' (SEI) for individuals, based on objective measurements of skin pigmentation. The SEI is calculated as the increase in facultative pigmentation above the constitutive level and is expressed as a percentage of the constitutive level. The SEI appeared to be related to cumulative lifetime UV exposure and may be used in epidemiological research as an objective estimate of UV exposure at different body sites in caucasians.

Skin pigmentation in Caucasian babies is high and evenly distributed throughout the body.

To investigate if Caucasian babies have particular sun sensitive skin and if skin pigmentation before any sun exposure is uniform throughout the body, we measured skin pigmentation objectively by skin reflectance spectroscopy in 10 anatomical sites in 20 healthy Caucasian babies (mean age 5 months, range 1 to 10 months) that had not been sun exposed previously. We found that skin pigmentation at all the measured sites was significantly higher than the constitutive pigmentation in Caucasian adults (P < 0.01). Furthermore, the level of skin pigmentation in all the 10 measured sites in the babies was statistically not different (P < 0.31) and there was no gender differences in pigmentation for any site.

Interdependence of eye and hair colour, skin type and skin pigmentation in a Caucasian population.

Eye colour, hair colour and skin colour are important risk factors for malignant melanoma and non-melanoma skin cancers. There are few studies in which the distribution of these pigmentary factors in risk populations has been assessed. The purpose of this study was to investigate the prevalence of the major eye and hair colours and the distribution of skin types and skin pigmentation in a Caucasian population. In 892 Danish Caucasians, eye colour, hair colour and skin type were assessed and facultative and constitutive skin pigmentation were measured objectively using skin reflectance spectroscopy. Blue eye colour and blond hair colour and skin type II were the most frequent (60%, 67% and 33% of subjects, respectively). All four major eye colours and four major hair colours (with the exception of red hair colour) were found within skin types I-IV and we could not predict the skin type or the constitutive skin pigmentation. Skin type could not be taken to classify individuals reliably according to their facultative or constitutive skin pigmentation.

The measurement of constitutive and facultative skin pigmentation and estimation of sun exposure in Caucasians with basal cell carcinoma and cutaneous malignant melanoma.

In two identical and simultaneously performed case-control studies of basal cell carcinoma (BCC) and cutaneous malignant melanoma (CMM) with age-matched, sex-matched and residence-matched controls, skin pigmentation was measured objectively by skin reflectance spectroscopy in 145 BCC patients and 174 matched controls and in 168 CMM patients and 176 matched controls. Measurements were performed at the forehead, the upper chest, the upper back, the lateral and medial aspects of the upper arm, and the buttocks. Self-estimation of sun exposure in childhood, in youth and in adulthood was performed by all subjects. There were no statistically significant differences in constitutive skin pigmentation at the buttocks between BCC patients and controls (P = 0.96) or between CMM patients and controls (P = 0.13). Facultative skin pigmentation in ultraviolet-exposed sites was not significantly different between BCC patients and controls except that women patients had higher pigmentation at the lateral side of the upper arm. For CMM, men patients had higher pigmentation at the lateral side of the upper arm. Self-estimations of sun exposure did not show differences between patients and controls but indicated high exposure levels in childhood and youth and in adult leisure time. Sun exposure estimated by increase in facultative pigmentation above the constitutive level (the Sun Exposure Index) was not significantly different between BCC patients and controls, whereas CMM men patients had higher estimates for the lateral side of the upper arm, the chest and the back.

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.

Epidermal thickness measured by light microscopy: a methodological study.

BACKGROUND/AIMS: Epidermal thickness is frequently measured by light microscopy. The preservation and staining methods may alter the proportions of the specimens and thereby influence the measurements. The aim of the present study was to describe: 1) a standardized light microscopic method to quantify the thicknesses of the stratum corneum and the cellular epidermal layers, 2) the variations according to preparation and staining techniques, and 3) the observer variability. METHODS: One hundred and sixty skin biopsies from 67 human volunteers were included. The cellular epidermis and the stratum corneum were estimated in sections preserved by freezing and subsequent preparation with cryostat or formalin-paraffin techniques. The slides were stained with haematoxylin-eosin or er-ythrocin, and thicknesses of the stratum corneum and the cellular epidermis were measured by a calibrated ruler and an ocular grid, respectively. RESULTS: The formalin fixation gave slightly higher values for the cellular epidermis than the cryostat technique. In comparison to erythrocin staining, haematoxylin-eosin gave a significantly thinner stratum corneum. No significant inter- or intra-observer variation was found for the thickness of the stratum corneum assessed twice by two experienced observers. However, the two observers differed slightly from each other on the thickness of the cellular epidermis. CONCLUSION: It is found that thickness measurements of the stratum corneum and the cellular epidermis are reliably performed on cryostatic cut sections stained with haematoxylin-eosin.

Sunscreens used at the beach do not protect against erythema: a new definition of SPF is proposed.

Since sunscreens are recommended by doctors and used all over the world to protect against sun induced erythema, it is important to evaluate if sunscreens are used as recommended and if the intended effect is achieved. We refer to the findings of several studies performed on people at risk of sun-burning at beaches in the vicinity of Copenhagen, Denmark. On a sunny day at the beach 65% of the sunbathers used one or more sunscreens. Of these, 46% used the sunscreen all over the body and a median sun protection factor (SPF) of 5-6 was used. The sunbathers used 0.5 mg/cm2 of sunscreen independent of skin type. Of the sunscreen users, 43% applied the sunscreen after arriving at the beach and 43% reapplied the sunscreen after swimming. The sun exposure time and the sun exposure dose were almost identical among sunscreen users and non-users. Self-assessed redness of the skin demonstrated that more sunscreen users than non-users reported to be red the day after sun exposure, 42 and 34%, respectively. Theoretical calculations support this findings and show a drastic reduction in the achieved photoprotection if a thinner layer than in the test situation is used. Sunscreens do not protect against erythema if not used as intended. Instead of changing people's habits, we suggest modifying the test method by adjusting the amount of sunscreen to that used in real life situations, 0.5 mg/cm2.

Epidermal thickness, skin pigmentation and constitutive photosensitivity.

The important factors for UV sensitivity in humans are considered to be the skin pigmentation and the epidermal thickness. In this study on 73 Caucasians (age 20-85 years), we investigated in UV unexposed buttock skin the relationship between the UV sensitivity and constitutive skin pigmentation and thickness of the stratum corneum and the cellular part of the epidermis, in 34 normal people and in 39 skin cancer patients (20) patients with cutaneous malignant melanoma and 19 patients with basal cell carcinoma of the skin). Skin pigmentation was measured by skin reflectance spectroscopy, and UV sensitivity by phototest with a solar simulator. Thicknesses of the stratum corneum and the cellular part of the epidermis were determined by light microscopic evaluation of skin biopsies from the phototest areas. We found that epidermal thickness was independent of skin type and was not correlated to constitutive skin pigmentation. Thickness of the stratum corneum was statistically not different in normal persons and in skin cancer patients (P = 0.41) and was independent of gender (P = 0.61) and age (P = 0.56), while thickness of the cellular epidermis decreased with age (P < 0.01). Stratum corneum thickness was found to be of minor importance for the constitutive UV sensitivity (accounting for on average 11% of the total photoprotection), which was mainly determined by the constitutive skin pigmentation (goodness-of-fit for correlation r = 0.83). A theoretical model for the relationship of UV dose to induction of clinical erythema grade and skin pigmentation and thickness of the stratum corneum was developed. Objective measurements of skin pigmentation in UV unexposed skin by skin reflectance spectroscopy in Caucasians, normal people and people with cutaneous malignant melanoma and basal cell carcinoma of the skin predicts the constitutive UV sensitivity with a high degree of precision.

Seasonal variation of skin pigmentation.

We measured skin pigmentation by skin reflectance monthly from May 1992 to April 1993 in 36 healthy Caucasians. Pigmentation was measured at four UV-exposed sites at the forehead, the upper chest, the inside of the upper arm, and at the upper back. The pigmentation and UV sensitivity were simultaneously measured at UV-protected buttock skin. The results showed a considerable seasonal variation for skin pigmentation at the UV-exposed sites. Buttock skin had a pigmentation and UV sensitivity that varied only marginally. We recommend that measurements of genetically controlled skin pigmentation and constitutive UV sensitivity should be performed at UV-unexposed skin on the buttocks, except in persons that expose this site to artificial or natural sunlight.

UV induced erythema evaluated 24 h post-exposure by skin reflectance and laser Doppler flowmetry is identical in healthy persons and patients with cutaneous malignant melanoma and basal cell cancer.

Twenty-one patients with invasive cutaneous malignant melanoma and 19 patients with basal cell skin cancer and 29 healthy volunteers were phototested on non-UV exposed buttock skin to examine their 24 h reaction to a series of increasing doses of simulated sunlight with 25% dose increments. Skin pigmentation at the phototest sites was determined by skin reflectance before testing to assure an equal level of constitutive skin pigmentation in the 3 groups. Erythema reactions were scored visually 24 hours post-exposure and objective measurements of erythema were performed by skin reflectance and laser Doppler flowmetry. In adjacent non-irradiated skin the redness was also quantified to determine the increase in redness in irradiated skin compared to non-irradiated skin. Constitutional skin pigmentation correlated well to UV sensitivity (r = 0.75) and skin redness measured by skin reflectance technique correlated to laser Doppler flowmetry (r = 0.86). No significant differences in UV doses to barely perceptible erythema or to the higher erythema grades were found between the two skin tumour groups and the control group, and no significant differences were found in skin reflectance measured redness or in laser Doppler flowmetry of any erythema reactions between the 3 groups. The 24 h erythema reaction to sunlight can therefore not be used to distinguish patients with invasive cutaneous malignant melanoma or basal cell carcinoma from normal persons.

Skin temperature and phototest evaluation.

The degree of erythema following UV irradiation is known to depend upon skin temperature at the time of UV exposure. We investigated whether changes in skin temperature at the time of erythema assessment influenced the level of erythema. Twenty-two healthy people (mean age 26 years) were irradiated with solar stimulated radiation on previously UV un-exposed buttock skin. The erythematous reactions were evaluated 20-24 h after irradiation by visual scoring and by measurements of skin reflectance and laser Doppler flowmetry. The readings were done at the baseline level at 21 degrees C room temperature where skin temperature was 30.0 +/- 1.7 degrees C and subsequently after skin warming to 37.2 +/- 2.5 degrees C and after cooling to 22.8 +/- 2.6 degrees C. After skin warming, a clinically evaluated erythema grade [0, (+), +, ++, + + +] was scored higher for at least one reaction in 10 of 22 individuals (45%). In the same proportion of subjects, changes to lower erythema grades were detected upon cooling. Skin warming caused an increase in laser Doppler blood flux, but skin cooling did not have a significant effect on cutaneous perfusion. Skin redness measured by skin reflectance was relatively stable during the cooling phase, but a significant increase in skin redness was noted for 0 reaction upon skin warming. For ++ and + + + reactions a small but significance decrease in reflectance was noted. Our results indicate that alterations in skin temperature, especially a temperature increase, modulates the degree of UV-induced erythema moderately. The temperature-dependent changes as an assessment of the (+) reaction are of practical significance, since this reaction is used for the assessment of cutaneous photosensitivity.

Threshold level for measurement of UV sensitivity: reproducibility of phototest.

The ultraviolet (UV) sensitivity is determined by a phototest where the skin is exposed to well-defined doses of UV radiation and the resulting erythema is graded by visual scoring after 20-24 h. In this study we wanted to estimate the reproducibility of erythema assessment in phototesting. Twenty-one healthy Caucasians with skin types I to IV were phototested on UV un-exposed buttock skin using a xenon lamp solar simulator. Twenty-four hours after UV exposure eight physicians independently graded the erythema reactions two times. Data were analysed using inter- and intra-observer agreement and kappa statistics, which adjusts for agreement that could be caused by chance alone. Observed agreement and kappa statistics were found to decrease with increasing intensity of erythema and to be lower for skin types III and IV compared to skin types I and II. Intra-observer agreement was uniformly better than inter-observer agreement. The difference between observers assessment could be as much as three clinical erythema grades. Physicians's previous experience with phototesting only had a minor influence on agreement. In conclusion, phototesting is based on subjective assessment of erythema and is not as precise and reproducible as expected. Agreement was better for barely perceptible erythema than for erythema with a well-defined border and we therefore recommend that the barely perceptible erythema reaction should be used for measurement of the minimal erythema dose.