Intralesional photodynamic therapy induces apoptosis in basal cell carcinoma and Bowen's disease through caspase 3 and granzyme B.

BACKGROUND: Photodynamic therapy (PDT) is used to treat cutaneous cancers. It may induce cell death through direct and indirect means, including apoptosis, inflammation and certain immune mechanisms, with the depth of penetration as a potential modifying factor. OBJECTIVES: To examine the pathways of apoptosis in the intralesional PDT of basal cell carcinoma (BCC) and intraepidermal squamous cell carcinoma (Bowen's disease). METHODS: Sixteen patients with superficial or nodular BCC and Bowen's disease were treated with intralesional aminolevulinic acid-PDT. Biopsies were taken at baseline and 24 h post-PDT, and sections were examined by immunohistochemistry for the expression of markers of apoptosis, such as caspase 3, involved in the intrinsic apoptotic pathway, granzyme B, a caspase-independent apoptotic mediator, and the proapoptotic markers BAX and BAK. RESULTS: Apoptotic cells stained with TUNEL showed statistically significant staining at 24 h post PDT (p < 0.01 in both BCC and Bowen's lesions). Caspase 3 (p < 0.01 in BCC and p < 0.05 in Bowen's) and granzyme B (p < 0.01 in BCC and p < 0.01 in Bowen's) were significantly increased at 24 h post-PDT. BAX expression was apparently increased compared to baseline in Bowen's lesions at 24 h post-PDT, whereas Bak was upregulated both in BCC and Bowen's disease at baseline and at 24 h post-PDT. CONCLUSION: Intralesional PDT induces apoptosis in BCC and Bowen's disease via common and alternative apoptotic pathways involving granzyme B. Proapoptotic factors Bak in both BCC and Bowen and Bax in Bowen's disease appear to increase by intralesional PDT at 24 h.

Delayed localized hypersensitivity reactions to COVID-19 mRNA vaccines: a 6-month retrospective study.

Several individuals have developed delayed localized cutaneous vaccine reactions to the two novel mRNA Covid-19 vaccines. Clinical and histopathologic results of this case series study confirm that the localized injection-site reactions to the mRNA COVID-19 vaccines are delayed hypersensitivity reactions that, unlike immediate hypersensitivity reactions, are not a contraindication to vaccination.

The peculiar dermatoscopic pattern of scalp melanoma.

BACKGROUND: Melanomas developing on anatomic sites other than the trunk and extremities have a special pathogenetic and mutational profile, morphologic characteristics and biologic behaviour. OBJECTIVE: By retrospectively screening the databases of our centres, we aimed to investigate the dermatoscopic morphology of early scalp melanoma, including in situ and invasive tumours with a Breslow thickness up to 1 mm. METHODS: The databases of three specialized centres for skin cancer diagnosis and management in Greece were retrospectively evaluated to retrieve dermatoscopic images of scalp melanomas. Patients' age and sex were recorded, as well as the precise location of the tumour, using 6 possible sub-locations: frontal, parietal, occipital, temporal, nuchal scalp and vertex. The dermatoscopic images were evaluated by 3 independent investigators for the presence of pre-defined criteria. The dermatoscopic criteria included in the evaluation were selected based on available literature and were categorized in 2 groups: 'classic melanoma criteria' and 'lentigo maligna (LM) criteria'. RESULTS: Of 38 melanomas, 37 (97.4%) displayed brown colour and 23 (60.5%) displayed additional grey or blue colour. The most frequent dermatoscopic criteria were regression (18/38, 47.4%), grey dots/globules (17/38, 44.7%), atypical network (16/38, 42.1%), obliterated follicles (16/38, 42.1%) and angulated lines (15/38, 39.5%). Of 38 melanomas, 28 (73.7%) displayed at least 1 classic melanoma criterion plus at least 1 LM criterion. Of the remaining melanomas, 8 (21.1%) displayed only classic melanoma criteria, 1 (2.6%) only LM criteria and 1 (2.6%) did not exhibit any of the evaluated criteria. CONCLUSIONS: This study demonstrates that early scalp melanoma combines classic with LM criteria in terms of colours and structures.

Clinical and dermatoscopic predictors of squamous cell carcinoma of the lips: a case-control, multicentric study.

BACKGROUND: Squamous cell carcinoma of the lip accounts for 20% of all oral carcinomas. Its diagnosis may be challenging because it clinically resembles actinic cheilitis and inflammatory lesions of the lips. OBJECTIVES: To determine clinical and dermatoscopic predictors of squamous cell carcinoma of the lip vs. other lip lesions. METHODS: Multicentre retrospective morphological study, including histologically confirmed cases of squamous cell carcinoma of the lip and controls consisting of actinic cheilitis and inflammatory lesions of the lips. Clinical and dermatoscopic images were evaluated for the presence of predefined criteria. Crude and adjusted odds ratios and corresponding 95% confidence intervals were calculated by univariate and multivariate logistic regression respectively. RESULTS: A total of 177 lip lesions were evaluated, 107 (60.5%) were squamous cell carcinomas and 70 (39.5%) were controls. The most frequent dermatoscopic criteria of lip squamous cell carcinoma were scales (100%), white halos (87.3%) and ulceration (79.4%). The majority of squamous cell carcinomas displayed polymorphic vessels (60.8%), with linear (68.6%) and hairpin (67.6%) being the most frequent types. Multivariate logistic regression analysis showed that clinical predictors of lip squamous cell carcinoma were exophytic appearance and clinical hyperkeratosis, with 43-fold and 6-fold higher probability respectively. White clods and ulceration in dermoscopy presented a 6-fold and 4-fold increased risk for squamous cell carcinoma respectively. CONCLUSIONS: A scaly lesion with exophytic growth, dermatoscopically displaying white clods, ulceration and linear and hairpin vessels is very likely a squamous cell carcinoma of the lip.

Is apremilast for psoriasis as effective and safe as reported in clinical trials? Five-year experience from a Greek tertiary hospital: long-term real-life efficacy and safety of apremilast in Greece.

Apremilast has been approved as an effective and safe treatment for psoriasis, but clinical trial results may differ from real-life data. This retrospective cross-sectional study evaluated the long-term efficacy and safety of apremilast in a Greek cohort of adult patients with psoriasis who had received at least one dose of apremilast between March 2016 and January 2021. The primary endpoint was the percentage of patients who achieved 75% reduction in Psoriasis Area Severity Index (PASI75) at Week 16. Absolute PASI, PASI90 (90% reduction) and adverse events were also recorded at various timepoints. In total, 102 patients (29.4% women, 70.6% men) with a mean ± SD age 55.94 ± 15.21 years were included. PASI75 and PASI90 were achieved by 20.8% and 1.98% of patients, respectively, at Week 16. According to our results, PASI90 achievement was significantly lower than that reported in clinical trials. The efficacy of apremilast increased gradually until Week 24, with further improvement noted in good responders up to Week 52.

Short incubation fractional CO2 laser-assisted photodynamic therapy vs. conventional photodynamic therapy in field-cancerized skin: 12-month follow-up results of a randomized intraindividual comparison study.

BACKGROUND: Topical methyl aminolevulinate photodynamic therapy (MAL-PDT) with 3 h incubation is recommended as a field directed treatment. Skin pretreatment with ablative CO2 fractional laser (AFXL) prior to MAL-PDT enhances drug penetration and could minimize incubation time. OBJECTIVES: To evaluate and compare the safety and the preventive effect in the development of new non-melanocytic skin cancers (NMSCs) of AFXL-assisted MAL-PDT with 1-h incubation with that of conventional MAL-PDT in patients with clinical and histological signs of field cancerization. METHODS: Forty-two patients with two mirror cancerized areas of face or scalp were randomized to field treatment with 1-h incubation AFXL-assisted PDT or conventional PDT (CPDT). All patients underwent two treatment sessions 1 week apart. Irradiation was performed using a red light-emitting diode lamp at 37 J/cm2 . Patients were followed up at 3, 6, 9 and 12 months for the evaluation of development of new NMSCs lesions. RESULTS: All patients completed the study. There was no statistically significant difference with respect to the total number of new actinic keratoses at any point of follow-up as well as to the mean time of occurrence of new lesions between treatment fields. Both treatment regimens were safe and well tolerated. CONCLUSION: Ablative CO2 fractional laser pretreatment may be considered as an option for reducing photosensitizer occlusion time while providing the same preventative efficacy as CPDT in patients with field-cancerized skin.

Accuracy of dermoscopic criteria for the differentiation between superficial basal cell carcinoma and Bowen's disease.

BACKGROUND: The dermoscopic features of superficial basal cell carcinoma (sBCC) and Bowen's disease (BD) have been extensively investigated, and dermoscopy was shown to significantly improve their recognition. However, incorrectly diagnosed cases still exist, with a considerable number of sBCCs dermoscopically interpreted as BD. Our aim was to investigate the dermoscopic variability in sBCC and BD on different anatomic sites, to identify potent dermoscopic predictors for each diagnosis and to investigate the potential source of the inaccurate clinico-dermoscopic diagnosis of some sBCCs. METHODS: Dermoscopic images of histopathologically diagnosed sBCC and BD were evaluated by three independent investigators for the presence of predefined criteria. Subsequently, three independent investigators with expertise in dermoscopy classified the tumours as sBCC or BD based on the dermoscopic image. Diagnostic accuracy scores were calculated and crude and adjusted odds ratios, and 95% confidence intervals were calculated by univariate and conditional multivariate logistic regression, respectively. RESULTS: A total of 283 lesions were included in the study (194 sBCCs and 89 BD). The main dermoscopic predictors of BD were dotted vessels (7.5-fold) and glomerular vessels (12.7-fold). The presence of leaf-like areas/spoke-wheel areas/concentric structures (OR = 0.027) and arborizing vessels (OR = 0.065) has predicted sBCC. Multivariate risk factors for sBCC misclassification were the location on lower extremities (OR = 5.5), the presence of dotted vessels (OR = 59.5) and the presence of large ulceration (OR = 6.4). In contrast, the presence of brown-coloured pigmentation was a protective predictor for misdiagnosis (OR = 0.007). Finally, a subgroup analysis of lesions located on lower extremities revealed two additional potent predictors of sBCC: superficial fine telangiectasia (SFT) and whity shiny blotches/strands. CONCLUSIONS: Dotted and glomerular vessels are strong predictors of BD. When located on the lower extremities, sBCC may also display dotted vessels, rendering its recognition problematic. On the latter anatomic site, clinicians should consider SFT and whity shiny blotches/strands as additional sBCC predictors.

Dermoscopic features of melanocytic skin lesions in Greek children and adolescents and their association with environmental factors and skin types.

BACKGROUND: Acquired naevi often present in childhood and increase in number and size during early and middle life. As naevi represent potential mimickers of melanoma, the knowledge of their epidemiologic and morphologic characteristics is essential. OBJECTIVE: In this study, we intend to determine the prevalence of dermoscopic patterns of naevi, as well their association with environmental and constitutional factors. METHODS: Cross-sectional data derived from a population-based cohort of children and adolescents aged 6-18 years, from 12 different schools in Thessaloniki, Greece. For each participant, a consent form and a questionnaire were completed, which included data on age, sex, phototype, sun sensitivity, sun exposure, sunscreen use and previous sunburn history. All naevi, their body distribution, and their dermoscopic patterns were recorded. RESULTS: Two thousand and five hundred and five (2505) subjects were enrolled into the study (47.8% males and 52.2% females). The mean number of MN counted in a single person was 29.11 (SD = ±23.863). TNC increased continuously with higher age. Males were found to have a significantly increased number on the trunk (11.7 ± 11.2 and 10.0 ± 8.7, respectively, P < 0.001) and face and neck (6.2 ± 5.3 and 5.1 ± 4.3, respectively, P < 0.001) while females on the upper (10.3 ± 10.1 and 9.3 ± 9.4, respectively, P = 0.008) and lower extremities (2.8 ± 3.4 and 2.5 ± 3.2, respectively, P = 0.008). Globular pattern was the most frequent dominant pattern in lower age groups, and its percentage fell as age increased. On the contrary, the reticular pattern was more often documented in individuals in adolescence. CONCLUSION: This first study of MN in our young population aims to be the basis of further investigation for the MM preventive policy of our state.

The limitations of dermoscopy: false-positive and false-negative tumours.

Dermoscopy has been documented to increase the diagnostic accuracy of clinicians evaluating skin tumours, improving their ability to detect skin cancer and better recognize benign moles. However, dermoscopically 'false-positive' and 'false-negative' tumours do exist. False-positive diagnosis usually leads to unnecessary excisions. False-negative diagnosis is much more dangerous, as it might result in overlooking a cancer, with severe undesirable consequences for the patient and the physician. Therefore, management strategies should mainly focus on addressing the risk of dermoscopically false-negative tumours. The most frequent benign tumours that might acquire dermatoscopic characteristics suggestive of malignancy are seborrhoeic keratosis (SK), including solar lentigo, melanoacanthoma, irritated, clonal and regressive SK, angioma (mainly thrombosed angioma and angiokeratoma), dermatofibroma, benign adnexal tumours and naevi (Clark, Spitz, recurrent, combined, sclerosing). The most useful clues to recognize these tumours are the following: solar lentigo - broad network; melanoacanthoma - sharp border; irritated SK - regularly distributed white perivascular halos; clonal SK - classic SK criteria; regressive SK - remnants of SK; targetoid haemosiderotic haemangioma - dark centre and reddish periphery; thrombosed angioma - sharp demarcation; angiokeratoma - dark lacunae; atypical dermatofibromas - palpation; follicular tumours - white colour; sebaceous tumours - yellow colour; Clark naevi - clinical context; Spitz/Reed naevi - age; combined naevi - blue central area; recurrent naevi - pigmentation within the scar; sclerosing naevi - age and location on the upper back; blue naevi - history. Malignant tumours that might mimic benign ones and escape detection are melanoma (in situ, nevoid, spitzoid, verrucous, regressive, amelanotic), squamous cell carcinoma (mainly well-differentiated variants) and rarely basal cell carcinoma (non-pigmented variants). The most useful clues to recognize the peculiar melanoma subtypes are as follows: melanoma in situ - irregular hyperpigmented areas; nevoid melanoma - history of growth; spitzoid melanoma - age; verrucous melanoma - blue-black sign; regressive melanoma - peppering or scar-like depigmentation; amelanotic melanoma - pink colour, linear irregular vessels, dotted vessels. In this article, we summarized the most frequent dermoscopic variations of common skin tumours that are often misinterpreted, aiming to assist clinicians to reduce the number of false diagnoses.

Conventional vs. daylight photodynamic therapy for patients with actinic keratosis on face and scalp: 12-month follow-up results of a randomized, intra-individual comparative analysis.

INTRODUCTION: Daylight PDT (DLPDT) is a new PDT procedure. Several trials demonstrate that DLPDT achieves similar response rates with conventional PDT (CPDT) in the treatment of non-hyperkeratotic actinic keratoses (AKs) in a nearly painless way. It seems that DLPDT represents a more convenient and equally effective treatment modality. Data on long-term efficacy of DLPDT are limited. OBJECTIVE: To compare short- and long-term efficacy, safety and tolerability of DLPDT with that of CPDT in face and scalp AKs. METHODS: The study, an intra-individual right-left comparison study, was conducted in three centres in North, Center and South Greece. Eligible patients received either DLPDT or CPDT randomly allocated to alternate sides of face or scalp. Patients were evaluated at baseline, 3 and 12 months after treatment. Assessments included lesion response at 3 and 12 months, PDT-associated pain during PDT session, local skin reactions 3 days after treatment as well as patients' preference 3 months after treatment. RESULTS: A total of 46 patients completed the study. Three months after treatment, the overall lesion complete response rate was 78% for DLPDT and 80.6% for CPDT. At the 12-month follow-up, response rate decreased to 71.8% and 73.7% for DLPDT and CPDT accordingly. Regarding response based on lesion grade, response rates obtained in grade-I lesions were higher with DLPDT, while treatment with CPDT resulted to higher rates of cured grade-II lesions at both follow-up visits. Results were not supported by statistical significance. DLPDT was associated with significantly lower pain and reduced severity of local skin reactions. Patients' preference favoured DLPDT. CONCLUSIONS: Our study demonstrated that DLPDT is similar to CPDT in terms of long-term efficacy and recurrence rates in the treatment of face and scalp AKs. DLPDT demonstrated a better tolerability profile as it was associated with lower pain and less severe adverse events.

Daylight photodynamic therapy vs. Conventional photodynamic therapy as skin cancer preventive treatment in patients with face and scalp cancerization: an intra-individual comparison study.

BACKGROUND: Individuals with medical history of non-melanoma skin cancers (NMSCs) usually develop multiple and/or recurrent malignant lesions around the site of the primary neoplasm. The latter represents the clinical expression of the 'field cancerization' theory; supporting the presence of multiple malignant clones of dysplastic keratinocytes over the entire epithelium that potentially can progress into clinical lesions. Taking into consideration that the burden of NMSCs on public health and health-care cost is high, adequate control of recurrences and management of field change is challenging. OBJECTIVES: To compare the safety and efficacy of daylight photodynamic therapy (DL-PDT) vs. conventional photodynamic therapy (C-PDT) in the prevention of occurrence of new NMSCs in patients with clinical and histological signs of actinic field damage. METHODS: Twenty-six patients, with personal history of NMSCs on the face or scalp and actinic keratosis (AK) on the same fields, were randomized for DL-PDT on one side and C-PDT on the other. For a 12-month period, individuals were clinically evaluated for development of new NMSCs. RESULTS: The total number of new AKs and the mean time of their development did not significantly differ between the treated sides. Local adverse events were more intense with C-PDT, and patients' preference was more for DL-PDT compared to C-PDT. CONCLUSIONS: The current findings suggest equal preventive potential of DL-PDT vs. C-PDT against the formation of new NMSCs in patients exhibiting actinic field damage.

Tinea capitis: a retrospective epidemiological comparative study.

BACKGROUND: Currently, a wide spectrum of retrospective studies regarding the incidence of TC among children and adults are available in the world literature, but none of them are comparative, aiming to distinguish etiological diversity depending on the different geographic areas. OBJECTIVE: This study aimed to investigate the epidemiology of TC in Plovdiv, Bulgaria and Thessaloniki, and Greece, and to compare the results and predominant etiological agents using retrospective comparative analysis for an 11-year time period. MATERIALS AND METHODS: The subjects included were selected from archives of the Mycological Laboratory of the University Dermatologic Clinic, University Hospital "St. George" Plovdiv, Bulgaria, and the Mycological Laboratory of the First Dermatology Department of Aristotle University Thessaloniki, Greece, by retrospective analysis of data from an 11-year time period (2004-2014). A total count of 374 children aged 0-18, with confirmed diagnosis of TC via direct mycological examination and culture were included (128 children from Plovdiv, Bulgaria, and 246 children from Thessaloniki, Greece). Samples were plated on Sabouraud agar, followed by species identification of the isolated colonies. RESULTS: Our results demonstrate that the incidence of TC in the region of Bulgaria and Thessaloniki for the investigated period was lower than for the previously reported period. In Plovdiv, Bulgaria, it was 1.20 ± 0.09 % (n = 172 from a total count of 14,278 cases of mycoses), as the disease accounts for 23.10 ± 1.79 % of all mycological infections among the pediatric population and 0.36 ± 0.05 % (n = 49 from a total count of 13,724) among the adults patients in Plovdiv, Bulgaria. The incidence of the disease during the period 2004-2014 in Thessaloniki was 2.49 ± 0.15 % (n = 253 cases of TC from a total count of 10,168 mycoses), as it accounts for approximately 27.06 ± 1.47 % of mycological infections among the pediatric population in Thessaloniki, Greece, and 0.08 ± 0.03 % (n = 7 from a total count of 9259) of the population of adult patients with mycoses. Our study confirmed the presumption that M. canis is the leader among the causative agents in TC in children in both of the included countries, but its presence in the etiology of disease in adult patients was very low and nonsignificant. We categorically identified dominance of the female gender among the children with TC in Plovdiv, Bulgaria; while in Thessaloniki, Greece, the gender distribution had an almost equal ratio of males to females. CONCLUSION: Our results suggest that the gender predisposition depends also on the investigated geographic region and the time of the study, rather than only on the causative pathogen and age.