Line-field confocal optical coherence tomography in dermato-oncology: A literature review towards harmonized histopathology-integrated terminology.

Non-invasive diagnostics like line-field confocal optical coherence tomography (LC-OCT) are being implemented in dermato-oncology. However, unification of terminology in LC-OCT is lacking. By reviewing the LC-OCT literature in the field of dermato-oncology, this study aimed to develop a unified terminological glossary integrated with traditional histopathology. A PRISMA-guided literature-search was conducted for English-language publications on LC-OCT of actinic keratosis (AK), keratinocyte carcinoma (KC), and malignant melanoma (MM). Study characteristics and terminology were compiled. To harmonize LC-OCT terminology and integrate with histopathology, synonymous terms for image features of AK, KC, and MM were merged by two authors, organized by skin layer and lesion-type. A subset of key LC-OCT image-markers with histopathological correlates that in combination were typical of AK, squamous cell carcinoma in situ (SCCis), invasive squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and MM in traditional histopathology, were selected from the glossary by an experienced dermatopathologist. Seventeen observational studies of AK (7 studies), KC (13 studies), MM (7 studies) utilizing LC-OCT were included, with 117 terms describing either AK, KC, or MM. These were merged to produce 45 merged-terms (61.5% reduction); 5 assigned to the stratum corneum (SC), 23 to the viable epidermis, 2 to dermo-epidermal junction (DEJ) and 15 to the dermis. For each lesion, mandatory key image-markers were a well-defined DEJ and presence of mild/moderate but not severe epidermal dysplasia for AK, severe epidermal dysplasia and well-defined DEJ for SCCis, interrupted DEJ and/or dermal broad infiltrative strands for invasive SCC, dermal lobules connected and/or unconnected to the epidermis for BCC, as well as single atypical melanocytes and/or nest of atypical melanocytes in the epidermis or dermis for MM. This review compiles evidence on LC-OCT in dermato-oncology, providing a harmonized histopathology-integrated terminology and key image-markers for each lesion. Further evaluation is required to determine the clinical value of these findings.

Dynamic optical coherence tomography unveils subclinical, vascular differences across actinic keratosis grades I-III.

Actinic keratosis (AK) classification relies on clinical characteristics limited to the skin's surface. Incorporating sub-surface evaluation may improve the link between clinical classification and the underlying pathology. We aimed to apply dynamic optical coherence tomography (D-OCT) to characterize microvessels in AK I-III and photodamaged (PD) skin, thereby exploring its utility in enhancing clinical and dermatoscopic AK evaluation. This explorative study assessed AK I-III and PD on face or scalp. AK were graded according to the Olsen scheme before assessment with dermatoscopy and D-OCT. On D-OCT, vessel shapes, -pattern and -direction were qualitatively evaluated at predefined depths, while density and diameter were quantified. D-OCT's ability to differentiate between AK grades was compared with dermatoscopy. Forty-seven patients with AK I-III (n = 207) and PD (n = 87) were included. Qualitative D-OCT evaluation revealed vascular differences between AK grades and PD, particularly at a depth of 300 µm. The arrangement of vessel shapes around follicles differentiated AK II from PD (OR = 4.75, p < 0.001). Vessel patterns varied among AK grades and PD, showing structured patterns in AK I and PD, non-specific in AK II (OR = 2.16,p = 0.03) and mottled in AK III (OR = 29.94, p < 0.001). Vessel direction changed in AK II-III, with central vessel accentuation and radiating vessels appearing most frequently in AK III. Quantified vessel density was higher in AK I-II than PD (p ≤ 0.025), whereas diameter remained constant. D-OCT combined with dermatoscopy enabled precise differentiation of AK III versus AK I (AUC = 0.908) and II (AUC = 0.833). The qualitative and quantitative evaluation of vessels on D-OCT consistently showed increased vascularization and vessel disorganization in AK lesions of higher grades.

An Update on Non-Invasive Skin Imaging Techniques in Actinic Keratosis-A Narrative Review.

Nonmelanocytic skin cancers (NMSCs) are currently the most common group of human cancers and include all tumors that are not melanomas. Increased exposure to sunlight over the past few years, the lack of regular and proper use of sunscreen, the aging of the population, and better screening techniques are the reasons for the escalation in their diagnosis. Squamous cell carcinoma (SCC) comprises nearly 37% of the tumors in this group and can originate from actinic keratosis (AK), which usually presents as pink, often scaly plaques, usually located on the face or scalp. Advances in dermatoscopy, as well as the development of other non-invasive skin imaging modalities such as high-frequency ultrasound (HFUS), reflectance confocal microscopy (RCM), and optical coherence tomography (OCT), have allowed for greatly increased sensitivity in diagnosing these lesions and monitoring their treatment. Since AK therapy is usually local, and SCCs must be removed surgically, non-invasive imaging methods enable to correctly qualify difficult lesions. This is especially important given that they are very often located on the face, and achieving an appropriate cosmetic result after treatments in this area is very important for the patients. In this review, the authors describe the use of non-invasive skin imaging methods in the diagnosis of actinic keratosis.

Artificial intelligence-based PRO score assessment in actinic keratoses from LC-OCT imaging using Convolutional Neural Networks.

BACKGROUND AND OBJECTIVES: The histological PRO score (I-III) helps to assess the malignant potential of actinic keratoses (AK) by grading the dermal-epidermal junction (DEJ) undulation. Line-field confocal optical coherence tomography (LC-OCT) provides non-invasive real-time PRO score quantification. From LC-OCT imaging data, training of an artificial intelligence (AI), using Convolutional Neural Networks (CNNs) for automated PRO score quantification of AK in vivo may be achieved. PATIENTS AND METHODS: CNNs were trained to segment LC-OCT images of healthy skin and AK. PRO score models were developed in accordance with the histopathological gold standard and trained on a subset of 237 LC-OCT AK images and tested on 76 images, comparing AI-computed PRO score to the imaging experts' visual consensus. RESULTS: Significant agreement was found in 57/76 (75%) cases. AI-automated grading correlated best with the visual score for PRO II (84.8%) vs. PRO III (69.2%) vs. PRO I (66.6%). Misinterpretation occurred in 25% of the cases mostly due to shadowing of the DEJ and disruptive features such as hair follicles. CONCLUSIONS: The findings suggest that CNNs are helpful for automated PRO score quantification in LC-OCT images. This may provide the clinician with a feasible tool for PRO score assessment in the follow-up of AK.

Dermoscopy and Reflectance Confocal Microscopy in Actinic Keratosis, Intraepithelial Carcinoma, and Invasive Squamous Cell Carcinoma.

BACKGROUND: Patients with multiple actinic keratosis (AK), have pre-neosplastic abnormalities, constituting the sites of new tumors, this region is called the cancerization field. Due to the risk of malignant transformation, rigorous evaluation, follow-up, and treatment of the cancerization field is proposed. Recently, non-invasive diagnostic technologies such as confocal reflectance microscopy (RCM), detect AK, intraepithelial carcinomas (IEC), and SCC, without the need of repeated biopsies. There are few reports of the progression of AK assessed by dermatoscopy and RCM concomitantly. OBJECTIVES: Define morphological patterns and clinical applicability of dermatoscopy and MCR examinations of the AK lesions and their degrees of progression to IEC and SCC. METHODS: A retrospective cross-sectional study of dermatoscopy and RCM examinations was performed in 30 patients with histopathological diagnosis of AK (20), IEC (6), and SCC (4). RESULTS: In the comparative analysis of the dermatoscopic features, erythema was present in 100% of the lesions, the red pseudo-network in 75% of the AK (P=0.007), and linear and irregular vessels in 90% of the lesions of IEC/SCC. In the RCM of AK, the most striking finding was the presence of atypical honeycomb in the spinous layer, but typical in the granular layer. While the IEC/SCC group presented irregular epidermal architecture and atypical honeycomb in all epider-mal layers, it also showed a higher prevalence of individual corneocytes and nucleated cells, cellular pleomorphism, and nuclear atypia in the dermal papillae, irregular vessels within papilla, and cells with bright edges and dark central nuclei in the dermis. CONCLUSION: Dermoscopy and RCM may be considered as auxiliary methods for assessing lesions resulting from ke-ratinocyte atypia. The results of this study are consistent with published studies and it was possible to propose, with literature support, a model of progression of AK to IEC and SCC. J Drugs Dermatol. 2022;21(3):259-268. doi:10.36849/JDD.5086.

Evaluation of relationship between antihypertensive drug usage and dermatoscopic features in patients with keratinizing skin cancer.

Keratinizing skin cancers including actinic keratoses (AK), in situ squamous cell carcinoma/Bowen's disease/intraepidermal carcinoma (IEC), invasive cutaneous squamous cell carcinoma (cSCC) and keratoacanthoma share similar dermatoscopic features and also reveal different patterns that assist in their diagnosis. Recently epidemiological studies reveal the association between antihypertensive drugs and skin cancer risk, especially cSCC. This study aims to determine the dermatoscopic features of keratinizing skin cancer in patients using antihypertensive drug and compare with non-users. A total of 46 patients with 64 keratinizing skin cancer lesions were included in the study. The demographic, clinical characteristic of patients, the number, duration, localization and dermatoscopic features from each lesion were collected. First, we evaluated the dermatoscopic features according to the histopathologic diagnosis. Then, all patients were divided into two groups as users of antihypertensive drugs and non-users. The dermatoscopic features were compared in terms of antihypertensive drug usage and histopathologic diagnosis in antihypertensive drug users and non-users, separately. The users of anti-hypertensive drugs were 22 (47,8%) and non-users 24 (52,2%). Of the total 64 lesions including 47 AK, 5 IEC, 10 cSCC, and 2 keratoacanthoma were evaluated. White structureless area was found statistically significant in cSCC lesions of patients using antihypertensive drugs (P = .004). This finding in cSCC may be a clue for antihypertensive drug usage and these drugs may be a predisposan factor for dermal fibrosis. Regardless of histopathology, dermatoscopic features show no statistically difference between antihypertensive drug users and non-users (P > .05). Clearer results can be obtained by conducting more detailed and long-term studies.

Dermatoscopic findings and dermatopathological correlates in clinical variants of actinic keratosis, Bowen's disease, keratoacanthoma, and squamous cell carcinoma.

Non-melanoma skin cancer (NMSC), predominantly squamous cell carcinoma (SCC) and basal cell carcinoma, is increasing worldwide. Dermatoscopy, which is one of the non-invasive diagnostic techniques, is important for early diagnosis of NMSC. In this study we aimed to determine dermatoscopic features of keratinocyte derived tumors including actinic keratosis (AK), Bowen's disease (BD), keratoacanthoma (KA), and SCC and correlate the dermatoscopic findings with pathology. A total of 242 lesions from 169 patients were included in the study and dermatoscopic and dermatopathological findings of the lesions were retrospectively studied. Revised pattern analysis was used for the dermatoscopic evaluation. Among 242 lesions, 145 were clinically flat (86 AK, 30 BD, and 29 SCC). Presence of vessels, ulceration, fiber sign, keratin mass, and blood spots decreased the probability of a lesion being AK. When the differential diagnosis was considered between KA and SCC vs AK and BD; vessel presence, ulceration, fiber sign, blood spots, white structureless, keratin, and centred vessels favored the diagnosis of KA and SCC. Our results may contribute to the determination of the lesions to be biopsied in patients with multiple AK on chronically sun damaged skin. In non-pigmented lesions when a final diagnosis cannot be established, knowledge of dermatopathologic and dermatoscopic correlation may significantly assist interpretation of dermatoscopic patterns and clues.

Line-field confocal optical coherence tomography for actinic keratosis and squamous cell carcinoma: a descriptive study.

BACKGROUND: Early and accurate diagnosis of cutaneous squamous cell carcinomas (SCCs) and actinic keratoses (AK) is fundamental to reduce their associated morbidity and to select the correct treatment. Line-field confocal optical coherence tomography (LC-OCT) is a new imaging device that can characterize healthy skin and basal cell carcinoma, but no large studies on keratinocyte cell tumours have yet been published. AIM: To identify and describe LC-OCT criteria associated with SCC and AK, and to compare LC-OCT findings in these tumours. METHODS: A retrospective observational multicentre study was conducted. Lesions were imaged with the LC-OCT device before surgery and examined histologically. LC-OCT criteria for AK/SCC were identified and their presence was evaluated in all study lesions. Univariate and multivariate analyses were performed to compare AK and SCCs, and to investigate differences between in situ and invasive tumours. RESULTS: In total, 158 patients with 50 AK and 108 SCCs (62 in situ and 46 invasive) were included. Cytological and architectural alterations were found in most lesions, and differences were found between AK and SCCs. Although the visualization of the dermoepidermal junction (DEJ) was often hampered by hyperkeratosis and acanthosis, an outlined DEJ without broad strands was observed in almost all AK and almost all in situ SCCs, but in only three invasive SCCs (P < 0.001) when the DEJ was detectable. CONCLUSION: Our results suggest that LC-OCT can help clinicians in the identification of AK and SCC and their differentiation, providing a real-time and noninvasive examination. Further studies are needed to confirm our data.

In vivo reflectance confocal microscopy for monitoring actinic keratosis treated with 5-aminolevulinic acid photodynamic therapy.

BACKGROUND: Actinic keratosis (AK) occurs frequently in sun-exposed skin while its diagnosis and treatment were still in exploration. MATERIALS AND METHODS: Thirty two patients with facial AK lesions were selected and examined with reflective confocal microscopy (RCM) firstly, followed by biopsy at the same site. RCM was used to observe AK lesions before 5-aminolevulinic acid photodynamic therapy (ALA-PDT) treatment, after the first treatment, after 4 treatments, and at 1 and 6 months follow-up. Retrospective analysis of RCM images was performed. RESULTS: Thirty two AK cases showed initial RCM microscopic features including disorderly arranged epidermal cells (100%), atypical keratinocytes (100%), and blurry border between the epidermis and dermis (100%). 4 patients quitted trail. After treatments, 24 cases showed basically regular arrangement of epidermal cells, absent atypical keratinocytes, and clear border between epidermis and dermis, while 4 cases improved little. At 1 and 6 months follow-up, 23 cases remained relapse-free while 1 case developed recurrent symptoms. Effective rate of 4 ALA-PDT treatments for AK was 100%; recurrence and cure rates were 4.2% and 82.1%, respectively. CONCLUSION: ALA-PDT is effective to treat AK, while RCM can be recommended for in vivo evaluating and monitoring the effect of ALA-PDT on AK.

The diagnostic value of in vivo reflectance confocal microscopy in actinic keratosis.

BACKGROUND: Actinic keratosis (AK) is a pre-neoplastic skin damage caused by sun exposure with a risk of transforming squamous cell carcinoma (SCC) ranging from 0.1%-20%, while it should be differentiated with many diseases such as seborrheic keratosis (SK), discoid lupus erythematosus (DLE), Bowen's disease, and basal cell carcinoma(BCC) et al. Reflectance confocal microscopy (RCM) as a non-invasive method is showing an increasing diagnostic accuracy. Currently, there are a few studies that summarized the characteristics of AK with RCM. AIM: The study aimed to find the diagnostic value of diagnosing actinic keratosis by reflectance confocal microscopy. METHODS: A total of 92 patients with clinical suspicious diagnosis of actinic keratosis were enrolled in this study, and RCM device imaged their lesions. Fifty-three of these patients underwent skin biopsies to confirm the diagnosis. We retrospectively analyzed the results of RCM and histological diagnosis and then summarized the RCM characteristics of biopsy-confirmed lesions. RESULTS: Based on RCM images, 76 of 92 (82.6%) patients were diagnosed with AK, 9 of 92 (9.8%) patients could not be diagnosed by the dermatologist according to RCM. Of all 53 biopsied lesions, 42 (79.2%) were AK, 1 was seborrheic keratosis, 3 were basal cell carcinoma, three were discoid lupus erythematosus, 1 was Bowen's disease, and three were squamous cell carcinoma. CONCLUSION: The value of RCM in the diagnosis and differential diagnosis of AK is good and worthy of clinical application.

High-frequency ultrasound in the diagnosis of the spectrum of cutaneous squamous cell carcinoma: Noninvasively distinguishing actinic keratosis, Bowen's Disease, and invasive squamous cell carcinoma.

OBJECTIVE: To evaluate high-frequency ultrasound (HFUS) features for diagnosing cutaneous squamous cell carcinoma (cSCC) as a spectrum of progressively advanced malignancies, including precursor actinic keratosis (AK), Bowen's disease (BD), and invasive squamous cell carcinoma (iSCC). METHOD: In this retrospective study, 160 skin lesions diagnosed histopathologically (54 AK, 54 BD, and 52 iSCC) in 160 patients were included. The HFUS features of AK, BD, and iSCC were analyzed. The obtained data were evaluated using univariate and forward multivariate logistic regression analyses. RESULTS: The most significant HFUS features in AK were regular surface (odds ratio [OR], 8.42) and irregular basal border (OR, 6.36). The most significant HFUS features in BD were crumpled surface (OR, 19.62) and layer involvement confined to the epidermis (OR, 3.96). The most significant HFUS features in iSCC were concave surface (OR, 27.06), stratum corneum (SC) detachment (OR, 14.41), irregular basal border (OR, 4.01), and convex surface (OR, 3.73). The characteristics of surface features, basal border, and layer involvement could be valuable HFUS clues in the discrimination of AK, BD, and iSCC. CONCLUSION: High-frequency ultrasound is valuable for the differentiation of AK, BD, and iSCC, which may allow dynamic and noninvasive monitoring in the spectrum of cSCC.

Line-field confocal optical coherence tomography for the in vivo real-time diagnosis of different stages of keratinocyte skin cancer: a preliminary study.

BACKGROUND: The treatment of keratinocyte cancers (KC) strictly depends on their differentiation and invasiveness. Non-invasive diagnostic techniques can support the diagnosis in real time, avoiding unnecessary biopsies. This study aimed to preliminarily define main imaging criteria and histological correlations of actinic keratosis (AK), Bowen's disease (BD) and squamous cell carcinoma (SCC) using the novel device line-field confocal optical coherence tomography (LC-OCT). METHODS: Dermoscopy and LC-OCT images of 73 histopathologically confirmed lesions (46 AKs, 11 BD and 16 SCCs) were included in the study. Exemplary lesions (10 AKs, 5 BD and 5 SCCs) were additionally investigated with optical coherence tomography and reflectance confocal microscopy. RESULTS: Most common LC-OCT findings of KC in the descriptive statistics were hyperkeratosis/parakeratosis, disruption of stratum corneum, broadened epidermis, basal and suprabasal keratinocyte atypia, dilated vessels/neoangiogenesis and elastosis/collagen alterations. In the univariate multinomial logistic regression, a preserved DEJ was less common in SCC compared with AK and BD, BD displayed marked keratinocyte atypia involving all epidermal layers (bowenoid pattern), while SCC showed ulceration, increased epidermal thickness, keratin plugs, acantholysis, not visible/interrupted DEJ and epidermal bright particles. LC-OCT increased the diagnostic confidence by 24.7% compared with dermoscopy alone. CONCLUSIONS: Our study describes for the first time specific LC-OCT features of different stages of KC and their histopathological correlates, focusing on keratinocyte morphology and architecture of the epidermis and DEJ. LC-OCT may open new scenarios in the bedside diagnosis, treatment planning and follow-up of KC.

Histopathological predictor of the progression from actinic keratosis to squamous cell carcinoma: quantitative computer-aided image analysis.

BACKGROUND: The current histopathological classifications for actinic keratosis (AK) are subjective, and histopathological factors predicting the progression into invasive squamous cell carcinoma (SCC) remain unclear. OBJECTIVES: To quantitatively assess the histopathological findings of AK and to investigate the predisposing factors for malignant transformation of AK. METHODS: A total of 502 AK specimens were retrospectively reviewed. The AK lesions were divided into the atrophic, intermediate, hypertrophic and bowenoid types. Histopathological features were quantitatively analysed using computer-aided image analysis. RESULTS: The epidermal thickness excluding the horny layer increased with statistical significance (P < 0.001) in order of atrophic, intermediate, hypertrophic and bowenoid type. The proportion of keratinocytic atypia was not significantly different among subtypes, except for the bowenoid type. Five of 498 cases were confirmed to develop into SCC. Bowenoid type, epidermal thickening and higher proportion of keratinocytic atypia were significantly associated with progression to invasive SCC in univariate analysis (OR = 12.571, 95% CI: 1.392-113.57; OR = 1.004, 95% CI: 1.001-1.007; OR = 1.069, 95% CI: 1.011-1.130, respectively). In multivariate analysis, only the proportion of keratinocytic atypia was an independent predisposing factor for progression to invasive SCC (OR = 1.069; 95% CI: 1.011-1.130). CONCLUSIONS: Histopathological subtypes based on the essential change of the epidermis well correlated with the actual epidermal thickness excluding the horny layer. The overall severity of keratinocytic atypia might be an independent risk factor for malignant transformation of AK.

Perilesional sun damage as a diagnostic clue for pigmented actinic keratosis and Bowen's disease.

BACKGROUND: Chronic sun damage in the background is common in pigmented actinic keratoses and Bowen's disease (pAK/BD). While explainable artificial intelligence (AI) demonstrated increased background attention for pAK/BD, humans frequently miss this clue in dermatoscopic images because they tend to focus on the lesion. AIM: To analyse whether perilesional sun damage is a robust diagnostic clue for pAK/BD and if teaching this clue to dermatoscopy users improves their diagnostic accuracy. METHODS: We assessed the interrater agreement and the frequency of perilesional sun damage in 220 dermatoscopic images and conducted a reader study with 124 dermatoscopy users. The readers were randomly assigned to one of two online tutorials; one tutorial pointed to perilesional sun damage as a clue to pAK/BD (group A) the other did not (group B). In both groups, we compared the frequencies of correct diagnoses before and after receiving the tutorial. RESULTS: The frequency of perilesional sun damage was higher in pAK/BD than in other types of pigmented skin lesions and interrater agreement was good (kappa = 0.675). The diagnostic accuracy for pAK/BD improved in both groups of readers (group A: +16.1%, 95%-CI: 9.5-22.7; group B: +13.1%; 95%-CI: 7.1-19.0; P for both <0.001), but the overall accuracy improved only in group A from (59.1% (95%-CI: 55.0-63.1) to 63.5% (95%-CI: 59.5-67.6); P = 0.002). CONCLUSION: Perilesional sun damage is a good clue to differentiate pAK/BD from other pigmented skin lesions in dermatoscopic images, which could be useful for teledermatology. Knowledge of this clue improves the accuracy of dermatoscopy users, which demonstrates that insights from explainable AI can be used to train humans.

[Advances in optical coherence tomography]. / Neues von der optischen Kohärenztomographie.

Optical coherence tomography (OCT) has been able to establish itself in recent years not only in academic-scientific, but also in everyday dermatological practice. Its focus lies on epithelial tumors of the skin, which can be diagnosed intuitively and within a few seconds. Thus, basal cell carcinomas, actinic keratoses, and different stages of field cancerization can be diagnosed and monitored for response to therapy or possible recurrence. This often helps to avoid invasive sample extraction. Recently, the field of OCT and its latest advancement, dynamic OCT (D-OCT), has been expanded to include non-oncologic dermatological diseases. This encompasses inflammatory dermatoses and the analysis of physiological skin parameters such as hydration. Thanks to automated vascular imaging and the measurement of objective parameters such as epidermal thickness, blood flow at depth, optical attenuation coefficient, and skin roughness, more and more characteristics of the skin can be studied in a noninvasive and standardized way. New potential areas of application are eczema, contact allergic dermatitis, psoriasis, rosacea, telangiectasia, acute and chronic wounds, melasma and nevus flammeus but also melanocytic lesions.

Treatment monitoring of 5-fluorouracil 0.5%/salicylic acid 10% lesion-directed therapy for actinic keratosis using dermoscopy and in-vivo reflectance confocal microscopy.

Recently, 5-fluorouracil 0.5%/salicylic acid 10% (5-FU/SA) topical solution has been included in the National Italian portfolio for lesion-directed treatment of grade I/II actinic keratosis (AKs) located on the face or scalp. To describe the utility of dermoscopy and RCM in treatment response monitoring of a series of AKs treated with 5-FU/SA as lesion-directed therapy. Consecutive patients were prospectively treated for a maximum of 12 weeks with 5-FU/SA for AKs located on the face or scalp. Clinical, dermoscopic, and confocal images of one index AK were acquired at each visit and pre-specified criteria were evaluated. Clinical, dermoscopic, and confocal responses were evaluated at last follow-up visit. Fourteen patients were enrolled, of which five were treated for 12 weeks, seven for 8, and two for 4 weeks. At a median follow up of 30 weeks, 64.3% (9/14) index AKs achieved complete clinical, 50% (7/14) complete dermoscopic and 42.9% (6/14) complete confocal clearance. Local skin reaction was mild and significantly decreased during therapy administration. Although the small number of cases, our study underlines the utility of both dermoscopy and in-vivo RCM in 5-FU/SA treatment response monitoring for AKs located on the face or scalp.

Evaluation of diagnostic criteria of actinic keratosis through reflectance confocal microscopy.

BACKGROUND: The diagnosis of actinic keratosis (AK) is based on clinical evaluation and confirmed by histopathological analysis (HA). The challenge is to establish the correct diagnosis with a minimally invasive assessment. The aim of this study is to validate the analysis of AK by reflectance confocal microscopy (RCM), a cellular resolution, noninvasive imaging method and to determine the relevant parameters for diagnosis, compared to HA, by calculating the sensitivity (S), specificity (E), positive predictive value (PPV), and negative predictive value (NPV) of each criterion. MATERIALS AND METHODS: Through clinical examination, 25 AKs were selected for dermoscopy and RCM evaluation followed by shaving excision for HA. Statistical analysis was done by hypothesis tests (McNemar for binary and Wilcoxon for continuous variables). RESULTS: There was no significant difference between RCM and HA for 5 of the 6 parameters analyzed. The criteria that were statistically relevant were as follows: parakeratosis (p-value 0.449690; S 90%; PPV 78.26%), hyperkeratosis (p-value 0.248213; S 87.5%; E 100%; PPV 100%; NPV 25%), dyskeratosis (p-value 0.617075; S 85.71%; E 75%; PPV 94.74%; NPV 50%), spinous layer keratinocyte atypia classified as mild, moderate or severe (P-value 0.145032) and inflammation in epidermis (P-value 1.000000; S 75%; E 20%; PPV 78.95%; NPV 16.67%). RCM could not adequately measure inflammation in dermis (P-value 0.013328), despite good sensitivity (68%) and PPV (100%). CONCLUSION: RCM proved to be an effective method for the diagnosis of AK, contributing to the selection of the most appropriate treatment option.

Reflectance confocal microscopy in actinic keratosis-Comparison of efficacy between cryotherapy protocols.

BACKGROUND: Actinic keratosis (AK) incidence is increasing. Due to the risk of progression to squamous cell carcinoma, early detection and treatment are essential. The method stated in the European Consensus is cryotherapy, but there is no standard protocol defined for better results. OBJECTIVES: To compare two different cryotherapy protocols for AK using reflectance confocal microscopy (RCM) as a noninvasive imaging method for evaluation. METHODS: A self-controlled clinical trial was proposed to compare the efficacy of cryotherapy in two different application protocols. Grade II AKs in the forearms were submitted to freezing and thawing time of 10 seconds for 1 cycle (group A) or 2 cycles (group B). At baseline and 4 weeks after treatment, the same dermatologists assessed RCM evaluation (thickness of horny layer, parakeratosis, dyskeratosis, atypia in spinous layer, fibrosis, and presence of inflammatory cells in epidermis and dermis). RESULTS: We examined 24 AK lesions in each group. Statistical evaluation of the results evidenced superior response after 2 cycles of cryotherapy in parakeratosis and number of inflammatory cells in epidermis. CONCLUSION: Both protocols are effective in clearing clinical AK. Two cycles are not generating more side effects (fibrosis) and could reduce the risk of recurrence (better "clearance" of parakeratosis).

Effects of MAL-PDT, ingenol mebutate and diclofenac plus hyaluronate gel monitored by high-frequency ultrasound and digital dermoscopy in actinic keratosis - a randomized trial.

BACKGROUND: The efficacy for actinic keratosis (AK) clearance of field-directed treatments has been investigated in randomized studies against placebo, but the comparison of results is difficult for several methodological reasons. OBJECTIVES: The present study aims to compare efficacy of MAL-photodynamic therapy (MAL-PDT), ingenol mebutate gel (IMB) and diclofenac plus hyaluronate gel (DHA) on multiple AKs assessing a new performance index of efficacy, the cumulative AK area and evaluating dermoscopical and high-frequency ultrasound (HFUS) changes. METHODS: Patients with ≥5 Olsen II AKs in a 25 cm2 area of the scalp and face were enrolled and randomized to one of the treatment choices. Number of AKs and cumulative area were assessed before and after treatment. Dermoscopy and HFUS were performed on a single AK and surrounding photo-damaged skin in the treatment area. RESULTS: Cumulative AKs area reduced significantly more with PDT compared to other treatment options and with IMB in comparison to DHA. PDT was also the only treatment option that increased at a significant level the dermal density in both target AK and the surrounding skin and decreased significantly the SLEB thickness in the perilesional skin at HFUS. CONCLUSIONS: MAL-PDT is more effective than IMB and DHA for reducing the cumulative AK area which is calculated digitally from 3D pictures and should be the preferred performance index for the evaluation of the efficacy of treatments for AKs, rolling out clinical and dermoscopy evaluation. MAL-PDT improves all HFUS features of chronic photodamages of the dermis of the skin underlying and surrounding the AK spots.

Digital follow-up by means of dermatoscopy and reflectance confocal microscopy of actinic keratosis treated with Imiquimod 3.75% cream.

BACKGROUND: Imiquimod 3.75% cream (Zyclara® Meda, Stockholm, Sweden) is a new field-directed therapy for actinic keratosis (AK). OBJECTIVES: The aim is to evaluate efficacy and the morphologic dynamic changes induced by this treatment by means of dermatoscopy and reflectance confocal microscopy (RCM) of imiquimod 3.75% cream for the treatment of AKs of the face or scalp and to evaluate. METHODS: Thirty-two patients were treated with Imiquimod 3.75% cream. Demographic parameters, AK-FAS and AKASI scores and side-effects were collected. RCM and dermatoscopy on one target AKs were performed at each visit. We collected images at baseline (T0), after 1 week from the end of the first 2-week cycle (T1), after 1 week from the end of the entire treatment (T2) and 2 months after the end of treatment (T3). RESULTS: One target representative AK in the selected area of treatment of each patient was analysed. All dermoscopic and confocal parameters were reduced 2 months after the end of the therapy (T3) with a substantial reduction of AKASI and AK-FAS scores, and 17 cases (54.8%) were completely solved. Confocal microscopic analysis showed a reduction of keratinocytes disarray in 77.4% of cases; none showed crusts and parakeratosis. Inflammation was considerably decreased and was observed only in 12.9% of patients at the last visit. This improvement was not assessed on dermatoscopy because of inflammation and background erythema, which adversely influenced the assessments. LSRs were observed in almost all the patients during treatment being more severe after the first cycle of treatment (T1). CONCLUSIONS: Imiquimod 3.75% cream is effective in treating clinical and subclinical AKs with an easy management of side-effects. Dermatoscopy and mostly RCM allow non-invasive monitoring of treatment response in vivo.