The causal effects of atopic dermatitis on the risk of skin cancers: A two-sample Mendelian randomization study.

BACKGROUND: Observational and epidemiological studies show conflicting results on the relationship between atopic dermatitis and skin cancer. Additionally, observational studies are susceptible to the reverse causation and confounders, thus, may not interpret true causal relationships. The causal effects of atopic dermatitis on the risk of skin cancers remains unclear. OBJECTIVES: To investigate the causal relationship between atopic dermatitis and skin cancer including cutaneous malignant melanoma, cutaneous squamous cell carcinoma, basal cell carcinoma and actinic keratosis. METHODS: We performed a two-sample Mendelian randomization analysis based on summary datasets of public genome-wide association studies of European ancestry. The inverse variance-weighted approach was applied as the main analysis. MR-Egger and weighted median methods were used to complement the inverse variance-weighted results. A series of sensitivity analyses were used to ensure the robustness of the causality estimates. RESULTS: Inverse variance-weighted method showed that genetically predicted dermatitis patients were significantly associated with an increased incidence of basal cell carcinoma (OR, 1.20; 95% CI, 1.10-1.31; p = 4.07E-05) and cutaneous squamous cell carcinoma (OR, 1.14; 95% CI, 1.10-1.19; p = 1.05E-11). However, we did not find a significant causality for atopic dermatitis on melanoma neither did we find actinic keratosis. Subsequent sensitive analyses supported these results. CONCLUSIONS: Our study identified the causality between atopic dermatitis basal cell carcinoma and squamous cell carcinoma. Accordingly, regular skin cancer screening is recommended for patients with atopic dermatitis.

Single-cell RNA-seq reveals actinic keratosis-specific keratinocyte subgroups and their crosstalk with secretory-papillary fibroblasts.

BACKGROUND AND AIM: Actinic keratosis (AK) represents an intraepidermal malignant neoplasm with the proliferation of atypical keratinocytes. AK lesions are regarded as early in situ squamous cell carcinomas (SCCs) having the potential to progress into invasive SCC (iSCC) and metastasize, causing death. This study aimed to investigate the heterogeneity of keratinocytes and how this heterogeneity promoted AK development and progression. METHODS: We employed single-cell RNA sequencing (scRNA-seq) to examine the heterogeneity of keratinocytes and dermal fibroblast clusters in AKs and adjacent normal skins. Cell clustering, pseudotime trajectory construction, gene ontology enrichment analysis, transcription factor network analysis, and cell-cell communication were used to investigate the heterogeneity of keratinocytes in AK. The cellular identity and function were verified by immunohistochemical and immunofluorescence staining. RESULTS: Using scRNA-seq, we revealed 13 keratinocyte subgroups (clusters 0-12) in AK tissues and characterized 2 AK-specific clusters. Cluster 9 displayed high levels of IL1R2 and WFDC2, and cluster 11 showed high levels of FADS2 and FASN. The percentages of cells in these two clusters significantly increased in AK compared with normal tissues. The existence and spatial localization of AK-specific IL1R2+WFDC2+ cluster were verified by immunohistochemical and immunofluorescence staining. Functional studies indicated that the genes identified in the IL1R2+WFDC2+ cluster were crucial for epithelial cell proliferation, migration, and angiogenesis. Further immunofluorescent staining revealed the interactions between AK-specific keratinocytes and secretory-papillary fibroblasts mainly through ANGPTL4-ITGA5 signalling pathway rarely seen in normal tissues. CONCLUSION: The findings of this study might help better understand AK pathogenesis.

The role of HPV in keratinocyte skin cancer development: A systematic review.

Keratinocyte skin cancers are the most frequent malignancy, accounting for approximately 30% of all cancers. Although beta genus HPV are the main etiologic agents for squamous cell carcinoma development in patients with epidermodysplasia verruciformis and organ transplant recipients, their role in non-melanoma skin cancer (NMSC) progression in the general population remains controversial. The aim of our review is to summarize current scientific data and to systematically analyse evidence regarding the role of HPV in keratinocyte skin cancers. A total of 2284 patients were included, of which 724 with actinic keratoses, 290 with Bowen's disease, 949 with cutaneous squamous cell carcinomas and 321 with keratoacanthomas. In the case of actinic keratoses, the majority were positive for beta (n = 372, 58.49%) and gamma HPV (n = 256, 40.25%) and only a few (n = 6, 0.94%) were positive for alpha subtypes. Similarly, most of the cutaneous squamous cell carcinomas were positive for beta (n = 248, 55.98%) and gamma HPV (n = 172, 33.82%) and 23 cases (2.42%) were positive for alpha subtypes. Bowen's disease lesions were mostly positive for beta (n = 43, 55.84%) and alpha HPV (n = 30, 38.96%), in contrast to the gamma genus (n = 4, 5.19%). Keratoacanthomas showed a high distribution among beta genus (n = 79, 50.31%) and an equal proportion between alpha (n = 39, 24.84%) and gamma (n = 39, 24.84%) genera. Studies published so far identifying HPV in keratinocyte skin cancers reflect the difference in detection methods rather than a type-specific tendency towards either actinic keratoses, Bowen's disease, squamous cell carcinoma or keratoacanthoma. On the other hand, recent evidence regarding the role of HPV vaccination in patients with non-melanoma skin cancer brings into perspective the idea of a beta-HPV vaccine or a combined alpha and beta-HPV vaccine that could be used as an adjuvant treatment measure in patients with recalcitrant non-melanoma skin cancer.

Pulse rate and blood pressure changes during low-irradiance PDT compared with conventional PDT in the treatment of facial actinic keratoses: A retrospective study.

BACKGROUND: Conventional photodynamic therapy (c-PDT) is a highly effective treatment for actinic keratoses. Besides pain as the main side effect, blood pressure (BP) increases and hypertensive crises may occur during treatment. Reducing the irradiation intensity while keeping the total dose constant (low-irradiance PDT) can achieve a clinically relevant reduction in pain. This study aimed to evaluate the influence of li-PDT on the BP and pulse (PR) during therapy and the incidence of post-interventional hypertension compared with c-PDT. METHODS: We retrospectively analyzed the treatment data of 79 patients (39 c-PDT and 40 li-PDT). BP and PR measurements were performed in all patients before PDT, at mid-exposure, and immediately after PDT. In addition, the pain was assessed by using the visual analog scale. RESULTS: Patients treated with li-PDT reported significantly lower pain than those receiving c-PDT (p < .0005). Additionally, they showed less systolic (SBP) and diastolic (DBP) BP increase (∆SBP: p < .0005, ∆DBP: p = .015) and overall lower absolute BP values (SBP: p < .0005, DBP: p = .008) compared with c-PDT. They were also significantly less likely to develop post-interventional hypertension (p = .037) or higher stages of arterial hypertension. Regarding PR, there was no difference in absolute values between both groups, but the increase from onset to half irradiation duration was significantly higher in c-PDT (p = .013). CONCLUSIONS: Li-PDT is an excellent option to reduce the elevation of arterial BP and decrease the incidence of post-interventional hypertension and hypertensive crisis. This finding has considerable relevance, especially with the risk profile of many PDT patients in mind (advanced age and cardiovascular history).

De Novo Skin Neoplasms in Liver-Transplanted Patients: Single-Center Prospective Evaluation of 105 Cases.

Background and Objectives: Solid-organ transplant recipients (SOTRs) are notably considered at risk for developing cutaneous malignancies. However, most of the existing literature is focused on kidney transplant-related non-melanoma skin cancers (NMSCs). Conflicting data have been published so far on NMSC incidence among liver transplant recipients (LTRs), and whether LTRs really should be considered at lower risk remains controversial. The aim of the present study was to prospectively collect data on the incidence of cutaneous neoplasms in an LTR cohort. Materials and Methods: All LTRs transplanted at the Hepato-Pancreato-Biliary Surgery and Liver Transplantation Unit of Modena University Hospital from October 2015 to June 2021 underwent a post-transplant periodic skin check at the Dermatology Unit according to our institutional integrated care pathway. Data on the presence of cutaneous malignant and premalignant lesions were collected at every timepoint. Results: A total of 105 patients were enrolled in the present study. Nearly 15% of the patients developed cutaneous cancerous and/or precancerous lesions during the follow-up period. Almost half of the skin cancerous lesions were basal cell carcinomas. Actinic keratoses (AKs) were observed in six patients. Four patients developed in situ squamous cell carcinomas, and one patient was diagnosed with stage I malignant melanoma. Otherwise, well-established risk factors for the occurrence of skin tumors, such as skin phototype, cumulative sun exposure, and familial history of cutaneous neoplasms, seemed to have no direct impact on skin cancer occurrence in our cohort, as well as an immunosuppressive regimen and the occurrence of non-cutaneous neoplasms. Conclusions: Close dermatological follow-up is crucial for LTRs, and shared protocols of regular skin checks in this particular subset of patients are needed in transplant centers.

Actinic keratosis: where do we stand and where is the future going to take us?

Introduction: Actinic keratosis (AK) is a chronic disease which is mainly located across areas of sun-exposed skin. Clinical and subclinical lesions coexist across a large area resulting in a field cancerization. As these lesions have the potential to transform into invasive squamous cell carcinoma (iSCC), treatment is crucial. With global prevalence increasing, AK is expected to be the most common in situ carcinoma of the skin.Areas covered: In this article, we cover the established algorithm of treating AK and give an insight into the drugs under development. There are six compounds under development covering different treatment angles, from Sinecatechin a Polyphenon E which targets the link between HPV infection and development of AK, over Tirbanibulin which targets the SRC proto-oncogene and fast proliferating cells, to Tuvatexib a small-molecule dual VDAC/HK2 modulator that has shown that it can compete with the established therapies.Expert opinion: These new treatment options are moving us further toward a more individually tailored treatment for each patient considering his abilities, the size and location of his lesions but also the genetic bases as well as individual risk of transforming into a iSCC and possibly other factors contributing to each patients individual AK lesions.

An Investigation of the Stability of Patients' Treatment Preferences Over the Course of a Clinical Trial.

OBJECTIVES: The usefulness of discrete choice experiments (DCEs) to inform clinical guidelines rests on the assumption that patients facing the same treatment choice at different points in time will express the same preferences. This study provides the first investigation, to our knowledge, to specifically focus on the stability of patients' treatment preferences over the course of a clinical trial. METHODS: The same DCE was completed by participants at baseline and final post-treatment assessment in a trial of the efficacy of alternative topical treatments for actinic keratosis as a means for the prevention of skin cancer. The study assesses both the consistency of stated treatment choices and the stability of population-level preference parameter estimates and analyzes how the former is influenced by design aspects of the DCE. RESULTS: No evidence was found of population-level preference parameter instability over the course of the trial despite only a moderate strength of choice consistency. Choice consistency is negatively related to task difficulty with weak evidence of the existence of ordering effects over the sequence of choice tasks. CONCLUSIONS: The results provide no evidence that the timing of a DCE within a clinical trial significantly influences population-level treatment preference estimates.

Squamous cell carcinoma: pain as a clue to increased tumour diameter, increased invasion depth, the grade of differentiation, acantholysis and perineural invasion.

BACKGROUND: Pain may be associated with actinic keratosis (AK), intraepidermal carcinoma (IEC) and invasive squamous cell carcinoma (SCC), which may all display high-risk features. AIM: To examine variation in pain frequency associated with these three conditions, and assess their invasive SCC surface diameter, invasion depth, grade of differentiation, presence of acantholysis and perineural invasion (PNI). METHODS: Pain was prospectively recorded for consecutive cases of AK, IEC and SCC from three institutions in Australia during the period 2016-2018. RESULTS: Pain with palpation was recorded with 15.8% of AK (n = 30/190), 15.1% of IEC (n = 345/299) and 29.0% invasive SCC (n = 247/853). Pain without palpation was respectively 1.1% (2/190), 4.0% (12/299) and 6.7% (57/853). Invasive SCC with increased surface diameters and deeper invasion recorded increased pain frequency. Pain did not vary significantly by the grade of differentiation in males. In females, well-differentiated SCC recorded more pain (45.4%; n = 473) than poorly differentiated SCC (9.1%; n = 11). Acantholytic SCC recorded more pain 48.7% (n = 29) than nonacantholytic SCC 35.2% (n = 824). Three out of five cases of PNI recorded pain. Pain intensity was not recorded, which was a limitation. CONCLUSION: Pain presence increases from AK to invasive SCC. Pain was more frequent in invasive SCC with increased surface diameter, deeper invasion, acantholysis and PNI. Pain frequency did not vary between the grades of differentiation in males. In females, pain was less frequent in poorly differentiated than in well-differentiated SCC.

Drug-Related Cutaneous Adverse Events in Philadelphia Chromosome-Negative Myeloproliferative Neoplasms: A Literature Review.

Since myeloproliferative neoplasms (MPN) pose a significant risk for vascular and thrombotic complications, cytoreductive therapies, such as hydroxyurea (HU), interferon (IFN) inhibitors, and Janus kinase (JAK) inhibitors are recommended for patients at high risk. However, these agents also place patients at increased risk for drug-related cutaneous adverse events. Herein, we review the literature on skin toxicity related to the use of drugs for the treatment of MPN. Overall, the cytoreductive agents used for MPN are generally well tolerated and considered to be safe, except IFN, for which dropout rates as high as 25% have been reported. While IFN is known to give rise to flu syndrome, it rarely leads to hematological alterations. The most common hematological side effects of HU are mild and include granulocytopenia, anemia, and thrombocytopenia. The JAK inhibitor ruxolitinib has been associated with cytopenia and a higher incidence of viral infections, as well as increased risk for basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Based on the present analysis, it can be concluded that cutaneous toxicity is not a negligible complication of commonly used treatments for MPN. While further research is needed, patients on these agents, and especially those with a history of cutaneous malignancies, should undergo thorough skin examination before and during therapy. In addition, detailed history is critical since many patients who develop non-melanoma skin cancer have multiple preexisting risk factors for cutaneous carcinogenesis.

Occurrence of newly discovered human polyomaviruses in skin of liver transplant recipients and their relation with squamous cell carcinoma in situ and actinic keratosis - a single-center cohort study.

To date 14 human polyomaviruses (HPyVs) have been identified. The newly found HPyVs have not been examined with regard to post-transplant skin carcinogenesis. To determine the occurrences in skin and possible pathological associations of the HPyVs, we studied their genoprevalences in squamous cell carcinoma (SCC) in situ or actinic keratosis and benign skin in liver transplant recipients (LiTRs); and of healthy skin in immunocompetent adults. We used highly sensitive and specific HPyV PCRs of two types. Overall, Merkel cell polyomavirus (MCPyV), human polyomavirus 6 (HPyV6), human polyomavirus 7 (HPyV7), trichodysplasia spinulosa polyomavirus (TSPyV), and Lyon IARC polyomavirus (LIPyV) were found in 58/221 (26.2%) skin biopsies. MCPyV DNA was detected in 5/14 (35.7%) premalignant vs. 32/127 (25.2%) benign skin of LiTRs, and in 12/80 (15%) healthy skin of immunocompetent adults, with no statistically significant difference in viral DNA prevalence or load. TSPyV DNA was found in a single skin lesion. LIPyV, HPyV6 and HPyV7 DNAs occurred exclusively in benign skin. Overall, the viral findings in premalignant versus benign skin were alike. The occurrences of HPyVs in skin of LiTRs and immunocompetent individuals speak against a role for any of the 14 HPyVs in SCC development.

The actinic dysplasia syndrome - diagnostic approaches defining a new concept in field carcinogenesis with multiple cSCC.

Usually, SCC lesions are surrounded by a number of clinically visible and non-visible (subclinical) areas of actinically damaged skin containing cells with dysplasia, and thus may be designated actinic dysplasia syndrome. The epithelial damage is caused mainly by UV radiation, inducing mutations in keratinocytes that may confer growth advantages resulting in preneoplastic fields. The development of visible dysplastic lesions (actinic keratosis - AK) and subsequent progression to invasive SCC requires further mutations in cancer-associated genes, like tumour suppressor genes and cell cycle regulators. Reflectance confocal microscopy (RCM) and optical coherence tomography (OCT) represent a considerable advantage for the investigation of field cancerization. In addition, imaging allows the non-invasive monitoring of topical treatments for AKs. RCM provides in vivo horizontal skin sections with a high, 1-µm lateral resolution (similar to histopathology) but with a limited penetration (about 200 µm), which can hamper the visualization of important areas such as the dermal-epidermal junction. Conventional OCT has better penetration (1-2 mm) at the expense of a more limited resolution (much lower than histopathology). Line-field confocal OCT (LC-OCT) combines the high precision of RCM and the good penetration of OCT in a single device and therefore appears to be very useful in diagnosing/managing AKs.

Distribution of high-risk α-genus human papillomavirus genotypes impacts cutaneous neoplasms.

BACKGROUND: High-risk α-genus human papillomaviruses (α-HPVs) are linked to cervical and genital carcinomas; however, their correlation with cutaneous squamous cell carcinoma (cuSCC) or premalignant skin lesions remains controversial. OBJECTIVE: We evaluated the contribution of high-risk α-HPV to the occurrence of cuSCC, Bowen's disease and actinic keratosis (AK), and the distribution of high-risk α-HPV genotypes in these cutaneous tumours. METHODS: HPV genotypes were determined using a commercial PCR-based microarray on skin tissue samples collected from 76 [38 young (<60 years) and 38 elderly (>60 years)] cuSCC, 34 Bowen's disease, 48 AK patients and 10 young controls. Associations between α-HPV prevalence and relevant risk factors were analysed. RESULTS: High-risk α-HPV was more frequently detected in cuSCC patients (57.9%) than in the patients with Bowen's disease (38.2%), AK (0.0%) and control patients (10.0%). The high-risk α-HPV prevalence was higher in young than in elderly cuSCC patients (65.8% vs. 50.0%, P = 0.031). The most common HPV type was 16, present in 90.9% of all HPV-carrying cuSCC patients. Multiple infections with different high-risk α-HPV types were found in 20.5% of HPV-related cuSCC, whereas only single infection with type 16 was found in Bowen's disease. Although sun exposure is known as a major risk factor for cuSCC, high-risk α-HPVs were more frequently found in non-exposed sites rather than in sun-exposed sites of cuSCC. CONCLUSION: Multiple infections, as well as single infection with high-risk α-HPV may link to cuSCC. In spite of the involvement of high-risk α-HPV at high levels in cuSCC and Bowen's disease, no high-risk α-HPV was detected in AK patients, suggesting that Bowen's disease rather than AK might be involved in the development of HPV-related cuSCC as a precursor.

Prevalence, Discontinuation Rate, and Risk Factors for Severe Local Site Reactions with Topical Field Treatment Options for Actinic Keratosis of the Face and Scalp.

Actinic keratoses (AKs) are common lesions on chronically sun damaged skin, which are morphologically characterized by lower third to full thickness atypia of epidermal keratinocytes. These lesions carry a risk of progression towards invasive squamous cell carcinoma (SCC); therefore, treatment of visible lesions and the field in case of field cancerization is recommended. Treatment of AK includes the destruction of atypical keratinocytes that clinically presents with various degrees of erythema, scaling, crusting, erosion, and other visible and subjective symptoms. Such inflammatory reactions may have an impact on the patient's social life and have shown to decrease compliance and adherence to therapy. Additionally, as various topical treatments have been proven to be effective in treating AK, tolerability of local site reactions (LSRs) might drive the decision for appropriate treatment in an individual scenario. Therefore, we aimed to review prevalence of severe LSRs among various topical treatments for AK. In addition, we summarized discontinuation rates due to LSRs and possible therapy-unrelated risk factors for the development of LSRs with increased severity.

Validity and Reliability of the Dutch Adaptation of the Actinic Keratosis Quality of Life Questionnaire (AKQoL).

BACKGROUND: The Actinic Keratosis Quality of Life Questionnaire (AKQoL) is a disease-specific instrument to measure the impact of actinic keratosis (AK) on patients' lives. OBJECTIVE: To validate and test the psychometric properties of the AKQoL translated into the Dutch language (AKQoL-NL). METHODS: All new patients ≥50 years of age with untreated AK in a university medical center and a general hospital between August 2014 and August 2015 were eligible. The AKQoL was obtained and repeated after 2 weeks. The feasibility was tested by missing responses and response distribution. The internal consistency reliability of each domain was investigated with the Cronbach alpha, and test-retest reliability and validity with the Spearman correlation coefficient. AKQoL scores were compared to the Skindex-17 for convergent validity and to the Groningen Frailty Indicator scores for divergent validity. RESULTS: A total of 153 of 190 eligible patients consented to participate. Feasibility analysis showed that none of the items missed ≥10% of responses but 5 of the 9 items showed floor effect. The AKQoL subscales showed a moderate internal consistency (Cronbach α = 0.235-0.468) and an excellent test-retest reliability (interclass correlation coefficient = 0.997-1). The AKQoL correlated poorly with the symptom component and moderately with the psychosocial component of the Skindex-17 (ρ = -0.015 to 0.346 and 0.324 to 0.501, respectively), which is less than expected. The AKQoL scored poorly in both of the Groningen Frailty Indicator (GFI) components (ρ = -0.97 to 0.12 and 0.185 to 0.276, respectively), as expected. CONCLUSION: The AKQoL-NL is a feasible, moderately valid, and moderately reliable health-related quality of life questionnaire.

Swiss (German) Version of the Actinic Keratosis Quality of Life questionnaire.

BACKGROUND: Actinic keratosis (AK) is a sun-induced skin lesion that may progress to invasive squamous cell carcinoma of the skin. Recently, the Actinic Keratosis Quality of Life questionnaire (AKQoL) was designed for patients with AK in Denmark as a specific quality of life instrument for AK patients. OBJECTIVE: The objective of this study was to adapt the AKQoL for the German language region of Switzerland and to evaluate its psychometric properties (validity, reliability). METHODS: Translation and cultural adaptation of the questionnaire were assessed by using the technique of cognitive interviewing. During the translation process, 34 patients with AK from the Department of Dermatology, University Hospital Zurich, were interviewed in 3 sessions of cognitive interviewing. The translated questionnaire was then distributed together with the Dermatology Life Quality Index (DLQI) to a second group of 113 patients for validation and reliability testing. Within this group, we measured the internal consistency by the Cronbach coefficient α and Spearman correlation coefficient between the AKQoL and the DLQI. RESULTS: The problems encountered during the translation process led to changes in 5 categories as described by Epstein: stylistic changes, change in breadth, change in actual meaning, change in frequency and time frame, change in intensity. We found a Cronbach α of 0.82, an acceptable internal consistency. The Spearman correlation coefficient between total scores of AKQoL and DLQI was 0.57. CONCLUSION: We culturally adapted and validated a Swiss (German) version of the AKQoL questionnaire applicable for the population of a university center in Switzerland to measure and monitor the quality of life in patients with AK.

Assessment of the Effect of 3% Diclofenac Sodium on Photodamaged Skin by Means of Reflectance Confocal Microscopy.

Treatment of actinic keratosis with 3% diclofenac sodium w/w in hyaluronic acid is associated with a concomitant improvement in signs of photodamaged skin. However this effect has not yet been examined in depth. Twenty patients with actinic keratosis and signs of photodamaged skin were studied. They received treatment with diclofenac sodium w/w in hyaluronic acid for 2 months. Clinical and reflectance confocal microscopy assessment on signs of photodamaged skin were performed. Regarding reflectance confocal microscopy, the most common descriptors were: irregular honeycomb pattern in 18/20 patients (90%), mottled pigmentation in 17/20 (85%), coarse collagen structures in all patients, and huddled collagen and curled bright structures in 16/20 (77.8%). After treatment, significant improvement in clinical parameters: irregular pigmentation and coarseness, and confocal parameters: irregular honeycomb pattern and mottled pigmentation, were noted. Reflectance confocal microscopy is a useful tool in monitoring changes in photodamaged skin after treatment. The use of diclofenac sodium w/w in hyaluronic acid is associated with an improvement in some clinical and reflectance confocal microscopy parameters of photodamaged skin.

The depth of follicular extension in actinic keratosis correlates with the depth of invasion in squamous cell carcinoma: implication for clinical treatment.

BACKGROUND: Actinic keratosis (AK) may show extension down follicles, not only in cases with full-thickness epidermal atypia ('bowenoid' AK), but also in cases with atypia limited to the epidermal basalis. Previous studies have demonstrated that, in bowenoid AK, follicular extension is usually superficial, being limited to the upper follicular segment. Little is known about the depth of follicular involvement in cases of invasive squamous cell carcinoma of the skin (iSCC) arising from AK and the role of the follicle in iSCC pathogenesis. OBJECTIVE: This study investigated the relationship between follicular extension of atypical keratinocytes in an AK and the development of iSCC from the follicular wall. The depth of follicular extension was correlated with the depth invasion of iSCC. Differences between the differentiated and classical pathways of iSCC were also examined. METHODS: We performed a retrospective histologic review of 193 biopsy specimens of iSCC with an associated AK. We assessed the presence and depth of follicular extension of atypical keratinocytes in the AK, using tumour (Breslow) thickness and the follicular unit level (infundibular, isthmic and subisthmic), as well as iSCC being present directly adjacent to the follicular basalis. RESULTS: Follicular extension was present in 25.9% of the cases (50 cases), usually extending into the lower follicular segment. The iSCC was present directly adjacent to the follicular basalis in 58% of the cases (29 cases), correlating highly with the depth of follicular extension (infundibular: 3/12; isthmic: 21/33; subisthmic 5/5). CONCLUSION: The depth of follicular extension of atypical keratinocytes in an AK correlates with the development of depth of invasion of an associated iSCC, irrespective of the pathway of origin. It is therefore important to note the presence and the depth of follicular extension when diagnosing an AK, as follicular extension likely accounts for a significant proportion of recurrent AK and the development of iSCC following superficial treatment modalities.

Outcomes of two surgical techniques for major trichiasis treatment.

The purpose of this article is to analyze the outcomes of two surgical techniques to treat major trichiasis. A retrospective chart review of 67 patients (89 eyelids) with major trichiasis was performed who underwent surgical treatment using one of two techniques: intermarginal split lamella with graft (ISLG group) or lid lamella resection (LLR group). There were 30 lids in the ISLG group with mean patient age of 71.8 years and 63.3% were females. There were 59 lids in the LLR group with mean patient age of 72.5 years and 52.5% were female. The minimum postoperative follow up was six months. Statistical analysis included descriptive measures, Goodman association test for contrasts between and within multinomial populations and nonparametric Mann-Whitney test for comparison between groups. P < 0.05 was considered statistically significant. The underlying causes of trichiasis were blepharitis (37.07%), chronic meibomitis (21.3%), multiple causes (20.2%), ectropion (11.2%), actinic keratosis (6.7%), or prior ocular surgery (3.3%). Postoperatively, in the ISLG group, there were 20% lids with complete success, 50% underwent laser or electrolysis, 16.7% required further surgery, and 13.3% were unsuccessful. Postoperatively, in the LLR group, there were 47.5% eyelids with complete success, 46.7% underwent laser or electrolysis, 6.8% required further surgery, and 5.1% were unsuccessful. There was a higher statistical chance of complete success with LLR (P < 0.05). LLR is superior to ISLG surgery for the treatment of major trichiasis. There is a greater chance of success with LLR and it is technically simpler.

[Rapidly growing squamous cell carcinoma after ingenol mebutate treatment]. / Carcinome épidermoïde de croissance rapide après traitement par mébutate d'ingénol.

INTRODUCTION: Ingenol mebutate is an actinic keratosis treatment, which has a dual action mechanism. It allows a rapid cellular death and a severe inflammation. OBSERVATION: We report the case of a 75 years old patient with a rapidly growing tumor 5 weeks after application of ingenol mebutate on typical actinic keratosis. Histological analysis after surgical excision showed an invasive squamous cell carcinoma (SCC); with aggressiveness signs: perineural infiltration and vascular permeation. DISCUSSION: Ingenol mebutate's common side effects are benign and regressive within 2 to 4 weeks. There are erythema, edema, crusts, and ulcerations/erosions. Squamous cell carcinoma development was rarely reported. We have tried to collect other cases in the literature and in pharmacovigilance centres: three similar cases were recently published in the literature, 21 cases were notified to the European Medicines Agency and we asked French pharmacovigilance centres and found 5 cases of SCC after ingenol mebutate application. The role of the molecule in SCC development is currently unknown. Induced inflammation could take part in the development of these tumors. We compare this case with other situations of inflammation, such skin graft donor site or surgical incision, complicated of rapidly growing SCC. Our case, literature's and pharmacovigilance's cases encourage us to follow ingenol mebutate's side effects. Careful follow-up and registration of such cases are important to gain further insight on this topic.

Clinical efficiency of dynamic observation of patients with epidermal dysplasia of the skin.

OBJECTIVE: Introduction: Non-melanoma skin cancer is the most common type of cancer among the population of Ukraine. The aim: The study of clinical efficacy of dynamic observation of patients with epidermal dysplasia of the skin. PATIENTS AND METHODS: Materials and methods: To study epidermal dysplasia of the skin there was used identifying information of patients, who were under dynamic observation of dermatologists of the State Scientific Institution "Research and Practical Centre of Preventive and Clinical Medicine" of the State Administration in 2013-2017. RESULTS: Results: In 2013-2017, under our supervision there were 245 patients with epidermal dysplasia of the skin, including 66 (27.0%) patients with invasive squamous cell carcinoma, 71 (29.0%) patients with squamous cell carcinoma in situ and 108 (44.0%) patients with actinic keratosis. It has been established that the level of annual progression of epidermal dysplasia of the skin in patients with actinic keratosis was 1.4%, in patients with squamous cell carcinoma in situ and invasive squamous cell carcinoma - 3.22% and 0.86%, respectively. CONCLUSION: Conclusions: It has been found that the level of annual progression of epidermal dysplasia of the skin in patients with a combined course of the above listed pathology of the skin was significantly (p≤0.05) higher and amounted to 8.8%.