Background/Objectives
Lichen planus‐like keratoses (LPLK) are benign skin lesions that can mimic malignancy; the clinical and dermoscopic features distinguishing lichen planus‐like keratoses from ...skin tumors have not been extensively studied. The objective of this study was to identify dermoscopic features that may prevent unnecessary biopsies of lichen planus‐like keratoses.
Methods
Retrospective, single‐center, observational study of biopsied skin lesions at a tertiary center. We compared 355 lichen planus‐like keratoses to 118 non‐lichen planus‐like keratoses lesions with lichen planus‐like keratosis in the differential diagnosis biopsied from August 1, 2015, to December 31, 2016. The investigators were blinded to the diagnosis of the lesions.
Results
Lichen planus‐like keratoses were most frequently non‐pigmented (61.7%), truncal (52.1%), and on sun‐damaged skin (69.6%); the majority occurred in Whites (95.5%) and females (62.8%). Dermoscopically, lichen planus‐like keratoses were more likely than non‐lichen planus‐like keratoses to have scale (42.5% vs 31.4%, P = 0.03) and orange colour (8.2% vs 0.9%, P = 0.01). Among lesions with peppering (n = 76; 63 lichen planus‐like keratoses and 13 non‐lichen planus‐like keratoses), coarse ± fine peppering (73% vs 38.5%, P = 0.02) and peppering as the only feature (34.9% vs 0%, P = 0.01) were associated with lichen planus‐like keratoses.
Conclusions
Lichen planus‐like keratoses can be challenging to distinguish from benign and malignant skin tumors. The presence of dermoscopic scale and orange colour may aid in the recognition of lichen planus‐like keratosis. Coarse peppering and the presence of peppering as the only dermoscopic feature may further aid the identification of pigmented lichen planus‐like keratoses.
Background
The risk of cutaneous squamous cell carcinoma (cSCC) is significantly increased in organ transplant recipients (OTRs). Clearance of actinic keratoses (AKs) is generally regarded as a ...surrogate biomarker for cSCC prevention. OTR‐cSCC chemoprevention with topical AK treatments has not been investigated in randomized controlled trials (RCTs), although there is evidence that 5% 5‐fluorouracil (5‐FU) may be chemoprotective in immunocompetent patients.
Objectives
To assess the feasibility, activity and evaluation outcomes relevant to the design of a future phase III RCT of topical cSCC chemoprevention in OTRs.
Methods
OTRs with 10 or more AKs in predefined areas were randomized 1 : 1 : 1 to topical 5‐FU, 5% imiquimod (IMIQ) or sunscreen (sun‐protective factor 30+) in a phase II, open‐label RCT over 15 months. Feasibility outcomes included proportions of eligible OTRs randomized, completing treatment and willing to be re‐treated. AK activity AK clearance, new AK development, patient‐centred outcomes (toxicity, health‐related quality of life, HRQoL) and evaluation methodology (clinical vs. photographic) were assessed.
Results
Forty OTRs with 903 AKs were randomized. All feasibility outcomes were met (56% of eligible OTRs were randomized; 89% completed treatment; 81% were willing to be re‐treated). AK activity analyses found 5‐FU and IMIQ were superior to sunscreen for AK clearance and prevention of new AKs. 5‐FU was more effective than IMIQ in AK clearance and prevention in exploratory analyses. Although toxicity was greater with 5‐FU, HRQoL outcomes were similar.
Conclusions
Trials of topical AK treatments in OTRs for cSCC chemoprevention are feasible and AK activity results support further investigation of 5‐FU‐based treatments in future phase III trials.
What is already known about this topic?
Cutaneous squamous cell carcinoma (cSCC) is significantly more common in immunocompromised individuals including organ transplant recipients (OTRs) compared with immunocompetent populations.
cSCC chemoprevention activity of sunscreen and 5‐fluorouracil‐based (5‐FU) actinic keratosis (AK) treatments has been demonstrated in randomized controlled trials (RCTs) in immunocompetent populations but not in OTRs.
AKs are cSCC precursors and their clearance and prevention are generally regarded as surrogate endpoint biomarkers for potential cSCC chemoprevention activity.
What does this study add?
SPOT (SCC Prevention in OTRs using Topical treatments) has confirmed that RCTs of OTR‐cSCC chemoprevention with topical AK treatments are feasible.
It also suggests that topical 5‐FU may be superior to 5% imiquimod and sunscreen in AK clearance and prevention.
Together with recent evidence from several RCTs in the general population, these data provide a compelling rationale for further studies of intervention with 5‐FU‐based topical chemoprevention approaches in OTR‐cSCC prevention.
Clearance of actinic keratoses (AK) is generally regarded as a surrogate biomarker for CSCC prevention. Our aim is to assess feasibility, activity and evaluation outcomes relevant to design of a future phase III RCT of topical CSCC chemoprevention in OTRs. We have concluded that trials of topical AK treatments in OTRs for CSCC chemoprevention are feasible and AK activity results support further investigation of 5‐FU‐based treatments in future phase III trials.
Linked Comment: M. Samimi. Br J Dermatol 2022; 187:281–282.
Current topical agents for field therapy of actinic keratoses have single mechanisms of action and must be applied for weeks. Ingenol mebutate gel, a novel drug for field therapy of actinic ...keratoses, appears to have a dual mechanism of action: (1) rapid lesion necrosis and (2) specific neutrophil-mediated, antibody-dependent cellular cytotoxicity. Because of the rapid destruction of actinic keratosis lesions after application of ingenol mebutate gel, treatment is necessary for only 2 or 3 days. The subsequent immune-mediated response targets any residual dysplastic epidermal cells. This dual mechanism of action should provide efficacy equivalent to that of current topical agents with a substantially shorter treatment period.
There is lack of uniformity in reflectance confocal microscopy (RCM) terminology for nonmelanocytic lesions (NMLs).
To review published RCM terms for NMLs and identify likely synonymous terms.
We ...conducted a systematic review of original research articles published up to August 19, 2017, adhering to Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines. Two investigators gathered all published RCM terms used to describe basal cell carcinoma (BCC), squamous cell carcinoma (SCC), and seborrheic keratosis/solar lentigo/lichen planus–like keratosis (SK/SL/LPLK). Synonymous terms were grouped on the basis of similarity in definition and histopathologic correlates.
The inclusion criteria was met by 31 studies. Average frequency of use per term was 1.6 (range 1-8). By grouping synonymous terms, the number of terms could be reduced from 58 to 18 for BCC, 58 to 36 for SCC, 23 to 12 for SK/SL/LPLK, and from 139 to 66 terms (52.5% reduction) in total. The frequency of term usage stratified by anatomic layer (suprabasal epidermis vs epidermal basal layer, dermoepidermal junction, and superficial dermis) was 27 (25.7%) versus 78 (74.2%) for BCC; 60 (64.5%) versus 33 (34.5%) for SCC, and 15 (45.4%) versus 18 (54.5%) for SK/SL/LPLK, respectively.
Articles that were not peer reviewed were excluded.
Systematic review of published RCM terms provides the basis for future NMLs terminology consensus.
Seborrheic keratosis Barthelmann, Sara; Butsch, Florian; Lang, Berenice M. ...
Journal der Deutschen Dermatologischen Gesellschaft,
March 2023, 2023-03-00, 20230301, Letnik:
21, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Summary
Seborrheic keratosis (SK) is the most common benign epidermal tumor in clinical dermatological practice. This review summarizes current knowledge about the clinical and histological ...appearance, epidemiology, pathogenesis, and treatment of SK. There are different subtypes of SK based on clinical presentation and histologic findings. Several factors, including age, genetic predisposition, and possibly also exposure to ultraviolet radiation, are thought to contribute to the development of SK. The lesions can occur on all areas of the body except for the palms and soles, but the most common sites are the face and upper trunk. The diagnosis is usually made clinically, and in some cases by dermatoscopy or histology. Many patients prefer to have the lesions removed for cosmetic reasons although there is no medical indication. Treatment options include surgical therapy, laser therapy, electrocautery, cryotherapy, and topical drug therapy, which is currently in development. Treatment should be individualized depending on the clinical picture and patient preference.
The precursor of most cutaneous invasive squamous cell carcinomas (iSCCs) is intraepithelial UV‐induced damage, known as field cancerization, which can eventually transform into actinic keratosis ...(AK). Although AK is the most common precursor of iSCC, many AKs will either persist in the same stage or regress, while only a few will progress into iSCC. Nevertheless, because the progression of individual AKs cannot be predicted, it has been proposed that all AKs, regardless of the grade, should be carefully monitored and appropriately treated in clinical practice. Modern imaging techniques such as dermatoscopy, reflectance confocal microscopy (RCM) and high‐definition optical coherence tomography (HD‐OCT) may have potential to monitor the evolution of actinic field damage. Dermatoscopy can be used to differentiate between AK, intraepidermal carcinoma (IEC) and SCC which may help clinicians to diagnose in situ or invasive lesions at an earlier stage. HD‐OCT and RCM can be used to detect cellular and histological changes characteristic of subclinical lesions, allowing visualization of previously invisible lesions. As development of invasive AK directly from the cancer field cannot be ruled out, the ideal treatment should be able to eradicate AK lesions and reverse the underlying field cancerization.
Cutaneous squamous cell carcinoma (cSCC) is the second most frequent of the keratinocyte-derived malignancies with actinic keratosis (AK) as a precancerous lesion. To comprehensively delineate the ...underlying mechanisms for the whole progression from normal skin to AK to invasive cSCC, we performed single-cell RNA sequencing (scRNA-seq) to acquire the transcriptomes of 138,982 cells from 13 samples of six patients including AK, squamous cell carcinoma in situ (SCCIS), cSCC, and their matched normal tissues, covering comprehensive clinical courses of cSCC. We identified diverse cell types, including important subtypes with different gene expression profiles and functions in major keratinocytes. In SCCIS, we discovered the malignant subtypes of basal cells with differential proliferative and migration potential. Differentially expressed genes (DEGs) analysis screened out multiple key driver genes including transcription factors along AK to cSCC progression. Immunohistochemistry (IHC)/immunofluorescence (IF) experiments and single-cell ATAC sequencing (scATAC-seq) data verified the expression changes of these genes. The functional experiments confirmed the important roles of these genes in regulating cell proliferation, apoptosis, migration, and invasion in cSCC tumor. Furthermore, we comprehensively described the tumor microenvironment (TME) landscape and potential keratinocyte-TME crosstalk in cSCC providing theoretical basis for immunotherapy. Together, our findings provide a valuable resource for deciphering the progression from AK to cSCC and identifying potential targets for anticancer treatment of cSCC.
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