Case-based experience in the use of 5-fluorouracil cream 0.5% as monotherapy and in conjunction with glycolic acid peels for the treatment of actinic keratosis

Abstract

Actinic keratosis, commonly indicative of photodamage, requires treatment secondary to the risk of progression to squamous cell carcinoma. A number of effective treatments for actinic keratosis are available, including topical and lesion-directed therapies. While lesion-directed therapies such as cryotherapy are appropriate for isolated lesions, topical 5-fluorouracil is an effective modality for the treatment of multiple facial actinic keratoses. 5-Fluorouracil, available in a number of formulations, offers patients the benefit of treating subclinical lesions and may help to improve the overall appearance of the skin. In many cases, combination therapy is a better treatment option than monotherapy. The cases presented here demonstrate the use of topical 5-fluorouracil cream 0.5% as monotherapy and in conjunction with glycolic acid peels to treat facial actinic keratoses in two patients with extensive histories of prior actinic keratosis and skin cancer.     

Caspase-3在皮肤鳞状细胞癌及光线性角化病中的表达

目的：检测Caspase-3在皮肤鳞状细胞癌及光线性角化病组织中的表达。方法： 应用免疫组化法检测16例皮肤鳞状细胞癌皮损、27例光线性角化病皮损及24例正常皮肤组织中Caspase-3蛋白的表达。结果：Caspase-3在皮肤鳞状细胞癌、光线性角化病及正常皮肤组织的表达率分别为37.50%,51.85%,79.17%,其表达含量在皮肤鳞状细胞癌、光线性角化病、正常皮肤组织逐渐增加。结论：Caspase-3蛋白表达下调可能参与皮肤鳞状细胞癌及光线性角化病的发病过程。     

Actinic Keratosis

Actinic keratoses are hyperkeratotic skin lesions that represent focal abnormal proliferation of epidermal keratinocytes. Some actinic keratoses evolve into squamous cell carcinoma of the skin, while others resolve spontaneously. The conversion rate of actinic keratosis to squamous cell carcinoma is not accurately known, but appears to be in the range of 0.25 to 1% per year. Although there is a low rate of conversion of actinic keratoses to squamous cell carcinoma, 60% of squamous cell carcinomas of the skin probably arise from actinic keratoses. The main cause of actinic keratoses in otherwise healthy Caucasians appears to be the sun. Therapy for actinic keratoses begins with prevention which starts with sun avoidance and physical protection. Sunprotection with sunscreens actually slows the return of actinic keratoses in patients already getting actinic keratoses. Interestingly, a few studies are available that demonstrate that a high fat diet is associated with the production of more actinic keratoses than is a low fat diet. One of the mainstays of therapy has been local destruction of the actinic keratoses with cryotherapy, and curettage and electrodesiccation. A new addition to this group of therapies to treat individual actinic keratoses is photodynamic therapy with topical aminolevulinic acid and light. In patients who have numerous actinic keratoses in an area of severely sun damaged skin, therapies which are applied to the whole actinic keratosis area are used. The goal of treating such an area of skin is to treat all of the early as well as the numerous clinically evident actinic keratoses at the same time. The classical approaches for treating areas of photodamaged skin without treating actinic keratoses individually include: the use of topically applied fluorouracil cream, dermabrasion, and cutaneous peels with various agents like trichloroacetic acid. Both topically as well as orally administered retinoids have been used to treat actinic keratoses but retinoids alone are probably not an optimal monotherapy. Photodynamic therapy with topical aminolevulinic acid and light is a new therapy for actinic keratoses. Aminolevulinic acid is a precursor of protoporphyrin IX (PpIX) which is synthesized in the actinic keratosis when it is treated with aminolevulinic acid, and the PpIX photosensitizes the actinic keratosis so that light exposure can lead to its destruction. Photodynamic therapy with topical aminolevulinic acid is approved in the US to treat multiple individual actinic keratoses on the face and scalp and has similar cure rates to those reported for cryotherapy and fluorouracil therapy.     

梅花针叩刺增强氨基酮戊酸光动力治疗光线性角化病、基底细胞癌、鳞状细胞癌的研究

目的 探讨梅花针叩刺预处理对氨基酮戊酸光动力（ALA-PDT）治疗光线性角化病、基底细胞癌、鳞状细胞癌的疗效影响,以及梅花针叩刺预处理的安全性。 方法 通过病例对照研究,对6例光线性角化病,3例结节型基底细胞癌,3例原位鳞状细胞癌进行梅花针叩刺 ＋ ALA-PDT治疗,同时选取皮损类型及分期类似的患者仅单纯ALA-PDT治疗作为对照组。 结果 梅花针叩刺 ＋ ALA-PDT治疗组单次治疗对光线性角化病的完全缓解率明显高于单纯ALA-PDT组［1级皮损12/12比10/14,2级皮损79.5%（31/39）比57.9%（22/38）,3级皮损36.6%（15/41）比17.0%（7/41）,均P ＜ 0.05］。梅花针叩刺 ＋ ALA-PDT治疗组中光线性角化病获得完全缓解所需的治疗次数有所减少,3级皮损平均治疗1.9次获得完全缓解;单纯ALA-PDT组3级皮损平均2.6次获得完全缓解。梅花针叩刺 ＋ ALA-PDT治疗原位皮肤鳞状细胞癌（皮损厚度超过0.3 mm）,获得完全缓解治疗次数少于单纯ALA-PDT组。结节型基底细胞癌在增加梅花针叩刺后治疗效果亦增强。梅花针叩刺患者疼痛无明显增加。 结论 梅花针叩刺可增强ALA-PDT治疗光线性角化病,基底细胞癌,鳞状细胞癌的疗效,而不增加不良反应。     

光线性角化病159例与皮肤鳞状细胞癌51例临床病理特征分析

目的了解滇东地区光线性角化病与鳞状细胞癌的疾病构成比、一般情况和临床病理特征。方法采用回顾性研究方法对曲靖市第一人民医院皮肤科2014年1月-2018年12月共5年行病理检查确诊的光线性角化病和皮肤鳞状细胞癌患者的临床和病理检查资料进行分析。结果159例光线性角化病(AK)与51例(SCC)鳞状细胞癌患者中女性多于男性,光线性角化病和鳞状细胞癌的发病平均年龄分别为(66.32±14.63)岁和(65.00±16.26)岁。光线性角化病和鳞状细胞癌患者皮损发生于曝光部位的分别占98.11%和78.43%。51例鳞状细胞癌患者中,有3例均是光线性角化病继发鳞状细胞癌,均为女性,年龄均>70岁,发病部位均为曝光部位。5年确诊光线性角化病患者占总病检患者的构成比相对稳定,其中鳞状细胞癌有所波动。AK病理分型分为肥厚型98例(61.64%)、萎缩型26例(16.35%)、棘层松解型12例(7.55%)、色素型9例(5.66%)、苔藓样型9例(5.66%)、鲍温样型5例(3.14%);SCC病理分级Ⅰ级39例(76.47%)、Ⅱ级11例(21.57%)、Ⅲ级1例(1.96%)、Ⅳ级0例。光线性角化病与鳞状细胞癌中临床诊断与病理诊断符合率分别为61.00%和56.86%,易被误诊为其他疾病。结论滇东地区光线性角化病与鳞状细胞癌以中老年女性为主,主要位于头面颈部等曝光部位,与紫外线关系密切,其中发生于曝光部位、皮损多样、病程长的老年女性光线性角化病患者易继发鳞状细胞癌,但临床病理诊断符合率较低,需引起重视。     

The development of actinic keratosis into invasive squamous cell carcinoma: evidence and evolving classification schemes

Actinic keratosis is an incipient form of cutaneous squamous cell carcinoma. Consequently, actinic keratoses must be treated expeditiously to forestall their downward growth. Several classification schemes have been proposed to better categorize actinic keratoses, and to guide their diagnosis and treatment. Among these approaches is the "keratinocyte intraepithelial neoplasia" (KIN) system developed by Cockerell; Goldberg's concept of the "proliferative actinic keratosis" (PAK), and Berhane's emphasis on the "inflamed actinic keratosis" (IAK). In the future, disparate classification schemes may be unified into a single pragmatic approach which accurately reflects the biological process whereby actinic keratoses devolve into invasive squamous cell carcinoma.     

S3-Leitlinie “Aktinische Keratose und Plattenepithelkarzinom der Haut“ – Update 2023, Teil 2: Epidemiologie und Ätiologie,Diagnostik, Therapie des invasiven Plattenepithelkarzinoms der Haut,Nachsorge und Prävention

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutaneous squamous cell carcinoma in situ (Bowen's disease) and actinic cheilitis. The guideline is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC. A separate guideline exists for patients and their relatives. In this part, we will address aspects relating to epidemiology and etiology, diagnostics, surgical and systemic treatment of cutaneous squamous cell carcinoma (cSCC), surveillance and prevention.     

Photodynamic therapy for non-melanoma skin cancer

Photodynamic therapy is a treatment modality that has been shown to be effective mainly for the dermato-oncologic conditions: actinic keratosis, Bowen's disease, in situ squamous cell carcinoma and basal cell carcinoma. Recent work has focused on the development and evaluation of topical photosensitizers like the haem precursor 5-aminolevulinic acid or its methyl ester, both inducing photosensitizing porphyrins. These drugs do not induce strong generalized cutaneous photosensitization, unlike the systemically applied porphyrins or their derivatives. For dermatological purposes incoherent lamps or light-emitting diode arrays can be used for light activation. Cure rates reported for very superficial lesions (tumour thickness <2-3 mm) are comparable to those achieved by other therapeutic modalities. Photodynamic therapy is a minimally invasive therapy associated with excellent cosmetic results. For actinic keratosis and basal cell carcinoma, methyl aminolevulinate-photodynamic therapy is already approved in Europe, Australia and New Zealand, and is now also approved for actinic keratosis in the US.     

Realizing the cosmetic potential of topical photodynamic therapy

Several open studies report the efficacy of topical photodynamic therapy (PDT) for non-melanoma skin cancer (NMSC) and precursor lesions. PDT may also be effective in various inflammatory and infectious dermatoses. As a tissue sparing modality, PDT may be preferable for large and/or multiple lesions and those in sites where disfigurement or poor healing from conventional therapies is a particular risk. Limited comparison data confirms that topical PDT achieves superior cosmesis to conventional therapies in actinic keratoses, squamous cell carcinoma in-situ and basal cell carcinoma. This review assesses the current data and proposes potential future applications for topical PDT including the treatment of photo-damaged skin.     

Solar keratoses: Photodynamic therapy,cryotherapy, 5-fluorouracil,imiquimod, diclofenac,or what? Facts and controversies

Actinic keratosis is a common dermatologic condition that may regress, remain stable, or progress to squamous cell carcinoma. Some question whether all actinic keratoses should be routinely treated, whereas others contend that the unpredictable natural history of this disease necessitates treatment to prevent malignant transformation. Available treatments include photodynamic therapy, cryotherapy, 5-fluorouracil, imiquimod, and diclofenac. Each of these options has its advantages and disadvantages, although they all have a place in the management of actinic keratosis. An overview of these treatment modalities is presented, as are the controversies surrounding the treatment of actinic keratosis.     

中国光线性角化病临床诊疗专家共识（2021）

【摘要】 光线性角化病是一种慢性进行性癌前病变,可进展为皮肤鳞状细胞癌。随着中国患病人数逐渐增多,亟须建立合适的诊断及治疗规范。中国康复医学会皮肤病康复专业委员会、中华医学会皮肤性病学分会联合中国医学装备协会皮肤病与皮肤美容分会组织光线性角化病相关领域部分专家,在国内外文献数据、国际指南和专家临床经验的基础上,结合我国诊疗现状,制定中国光线性角化病临床诊疗专家共识。本共识从光线性角化病的流行病学、发病因素及临床转归、临床表现及分级、诊断及鉴别诊断、治疗策略和患者教育管理等方面进行阐述,诊断方面包含了皮肤镜、反射式共聚焦显微镜和皮肤病理等手段,治疗策略涵盖了常见局部治疗和系统治疗方法,局部治疗包括光动力治疗、外用药物、物理治疗和手术切除,且按照证据等级给予推荐级别,为皮肤科医师诊疗工作提供参考。     

Muir-torre syndrome with intriguing squamous lesions: a case report and review of the literature

Muir-Torre syndrome (MTS) is an autosomal, dominantly inherited disorder characterized by sebaceous neoplasms and visceral malignancies. We report a 56-year-old woman who underwent resections of extraocular sebaceous carcinoma, sebaceous epithelioma, actinic keratosis, and keratoacanthoma (KA)-like squamous cell carcinoma (SCC) with venous invasion metachronously over a 9-year period. Because of the mixed, unusual features of the skin lesions, and her history of endometrial and colorectal cancers that had been resected 12 years and 1 year, respectively, before the present event, a possible diagnosis of Muir-Torre syndrome was suggested. Immunohistochemical studies revealed loss of hMSH2 expression in all the cutaneous lesions including the actinic keratosis, and also in the endometrial and colorectal cancers. This patient presented with intriguing squamous lesions including keratoacanthoma-like squamous cell carcinoma that showed venous invasion and actinic keratosis, and associated loss of hMSH2 expression, in addition to the sebaceous neoplasms typical of Muir-Torre syndrome.     

Smad7在脂溢性角化病、日光性角化病及基底细胞癌中的表达

目的： 检测Smad7在脂溢性角化病、日光性角化病以及基底细胞癌中的表达。方法：对脂溢性角化病、日光性角化病及基底细胞癌标本（各30例）和30例正常标本进行免疫组化染色。结果：23例脂溢性角化病标本、23例日光性角化病标本和28例基底细胞癌标本中Smad7染色阳性,阳性细胞率分别为（31.0±23.0）%,（32.7±26.3）%和（62.6±32.1）%,均显著高于正常组织的（6.7±5.0%）。结论： Samd7可能与脂溢性角化病、日光性角化病以及基底细胞癌的发病有关。     

Ber EP4与EMA染色在皮肤基底细胞上皮瘤和鳞状细胞癌诊断中的意义

目的 观察BerEP4和EMA染色在皮肤基底细胞上皮瘤和鳞状细胞癌诊断中的意义.方法 用免疫组化SP法检测BerEP4和EMA在皮肤基底细胞上皮瘤、鳞状细胞癌、光线性角化病、Bowen病、脂溢性角化病、寻常疣和基底鳞状细胞癌皮损肿瘤成分及周围组织、皮肤附属腺体中的表达.结果 所有基底细胞上皮瘤和基底鳞状细胞癌肿瘤细胞呈BerEP4阳性,而鳞状细胞癌、光线性角化病、Bowen病、脂溢性角化病和寻常疣呈BerEP4阴性;多数鳞状细胞癌、Bowen病和部分光线性角化病肿瘤细胞及病变区域呈EMA阳性,而基底细胞上皮瘤、基底鳞状细胞癌、脂溢性角化病和寻常疣呈EMA阴性.结论 联合使用BerEP4和EMA能很好地协助诊断皮肤基底细胞上皮瘤、基底鳞状细胞癌、癌前病变及一些良性增生性皮肤病.     

Actinic keratosis among seafarers

The aim of this study was to assess the prevalence of UV-induced actinic keratosis and further skin lesions. A newly developed questionnaire about lifetime UV radiation exposure was completed by 514 seafarers. An experienced dermatologist inspected the whole-body skin status of all participants. The questionnaire revealed a pre-employment UV radiation exposure in 104 seafarers, sunbed use in 26 subjects and a median work-related UV radiation exposure at sea of 20 years. The diagnosis of actinic keratoses was made in 94 seafarers and the clinical diagnosis of skin cancers in 48 seafarers (28 basal cell carcinoma, 11 squamous cell carcinoma, 9 malignant melanoma). After age standardisation according to a European reference population, the male European seafarers in this study had a 1.80-fold increased risk of actinic keratosis. Actinic keratoses [OR 1.03 (1.01–1.05)] and squamous cell carcinoma [OR 1.07 (1.01–1.13)] were related to the duration of seafaring time in years. A significant association was also found between actinic keratosis/squamous cell carcinoma and sunlight exposure during home leave [OR 1.67 (1.03–2.81) and OR 6.19 (1.18–32.40)]. Furthermore, the engine room personnel—especially the technical officers—were at higher risk of developing actinic keratosis. Due to the high prevalence of actinic keratosis especially among older seafarers with fair skin, with longer duration of seafaring employment at sea and with higher UV exposure during home leave, more intensive advice should be given on sun protection both at sea and ashore.     

Bowen病的治疗现状及进展

Bowen病是一种表皮内鳞状细胞癌,可逐渐发展为侵袭性鳞状细胞癌.Bowen病的治疗方法包括手术和非手术疗法.手术治疗包括单纯切除、莫氏显微外科治疗、切削电灼法,非手术治疗包括药物治疗、放射疗法、冷冻疗法、光动力疗法及其他综合疗法等.手术是治疗Bowen病的首选方法,对于不适合手术的患者或特殊部位的病变可考虑药物治疗、光动力治疗等.     

CD163~+肿瘤相关巨噬细胞在常见上皮性皮肤肿瘤中的分布

目的:检测CD163+肿瘤相关巨噬细胞在皮肤鳞状细胞癌、基底细胞癌、鲍温病、日光性角化病中的分布。方法:采用免疫组织化学法(Max Vision法)检测CD163标记的肿瘤相关巨噬细胞在正常皮肤、鳞状细胞癌、基底细胞癌、鲍温病、日光性角化病中的分布。结果:每高倍镜视野下正常皮肤、鲍温病、日光性角化病真皮浅层中CD163+巨噬细胞个数为(9.5000±1.71594)、(43.9200±9.98716)和(49.4000±8.73830)个;基底细胞癌肿瘤间质中为(42.1724 1±11.73234),鳞状细胞癌的肿瘤间质中及肿瘤实质内为(65.8421±14.05649)。结论:CD163+肿瘤相关巨噬细胞可能与皮肤上皮性肿瘤的发生、发展相关。     

Cornu cutaneum

We report on 62 cases of cornu cutaneum. In contrast to the general opinion that the majority of these lesions arise on the basis of an underlying actinic keratosis or a squamous cell carcinoma, on histological examination we found actinic keratoses in only 25% and squamous cell carcinomas in only 3.2% of cases; 58% of all lesions were identified as common warts. We therefore recommend removal of these skin lesions by the shaving technique followed by electrodesiccation of the base. This has the advantage of supplying the histopathologist with a representative specimen for histological examination and avoiding an unnecessarily large surgical excision. In the rare cases of histologically confirmed squamous cell carcinoma, these lesions can be excised in a second session.     

Intraepithelial Elastic Fibers and Intracytoplasmic Glycogen: Diagnostic Aids in Differentiating Keratoacanthoma from Squamous Cell Carcinoma

A significant statistical difference was found between the incidence of intraepithelial elastic fibers in keratoacanthoma and squamous cell carcinoma arising in actinic keratosis ( P < 0.001). There was no significant difference when keratoacanthoma was compared to adenoid squamous cell carcinoma ( P =0.13) and de novo squamous cell carcinoma ( P =0.73). However, in keratoacanthoma intraepithelial elastic fibers were found in areas of pseudoepitheliomatous hyper-plasia and in the central keratin plug, as well as in areas of infiltrating, peripheral keratinocytes. In adenoid squamous cell carcinoma and de novo squamous cell carcinoma, the intraepithelial elastic fibers were found only in areas of atypical epithelial cells at the margin of the neoplasm. Intracytoplasmic glycogen was found to be statistically more abundant in keratoacanthoma than in squamous cell carcinoma arising in actinic keratosis ( P < 0.001), adenoid squamous cell carcinoma ( P < 0.001), and in de novo squamous cell carcinoma ( P < 0.001).     

P27 and mib1 expression in actinic keratosis, Bowen disease, and squamous cell carcinoma

The histologic boundary between actinic keratosis, Bowen disease, and invasive squamous cell carcinoma is not clear in many cases. We determined nuclear expression of p27 (a protein associated with cellular quiescence) and Ki-67 (a marker of proliferation) immunohistochemically in actinic keratosis, Bowen disease, and squamous cell carcinoma to see if differential patterns of expression for p27 exist and how these might correlate with Ki-67 expression. We determined a labeling index for p27-stained nuclei and assessed the pattern of Ki-67 expression. The student's t test was used to evaluate the p27 labeling index. The p27 labeling index was decreased in invasive aggregates of squamous cell carcinoma (76.9+/- 1.1%) when compared with those of normal epidermis (97.2+/- 2.4%), actinic keratosis (95.3 +/- 1.4%), and Bowen disease (98.0+/- 0.5%). Ki-67 was expressed in a scattered to confluent linear pattern in the basal/parabasal cell layer of normal epidermis and actinic keratosis. Keratinocytes in squamous cell carcinoma exhibited Ki-67 in the peripheral layers of the neoplasm and frequently within the tumor aggregates. Ki-67 was observed in nuclei throughout the full thickness of the epidermis in Bowen disease. The staining pattern of Ki-67 in Bowen disease separated this entity from others under study. The combination pattern of p27 and Ki-67 staining can be used to support differentiation of actinic keratosis, Bowen disease, and squamous cell carcinoma.