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。     

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。     

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。     

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。     

Lewandowsky and lutz dysplasia: report of two cases in a family

Lewandowsky and Lutz dysplasia, also known as epidermodysplasia verruciformis (EV), is an inherited disorder in which there is widespread and persistent infection with human papilloma virus, defect in cell-mediated immunity and propensity for malignant transformation. Differential clinical and histopathologic evolutions of lesions in two cases of familial EV are compared and discussed in detail. Cases were followed up for 7 years. Detailed history, clinical features and investigations, including skin biopsy from different sites at different times, were examined. Generalized pityriasis versicolor like hypopigmented lesions in both the cases, together with variable pigmented nodular actinic keratosis like lesions on sun-exposed areas, were present. Multiple skin biopsies done from various sites on different occasions revealed features typical of EV along with lesions, i.e., actinic keratosis, Bowen's disease, basal and squamous cell carcinoma, in the elder sibling. However, skin biopsy of the other sibling showed features of EV and seborrheic keratosis only till date. This study reveals that the disease progression is variable among two individuals of the same family. Malignant lesions were seen only on sun-exposed areas and may be associated with other skin lesions or infections such as angiokeratoma of Fordyce and tinea cruris, as seen in this report.     

Pitfalls in the clinical and dermoscopic diagnosis of pigmented actinic keratosis

Pigmented actinic keratosis and melanoma may exhibit overlapping clinical features, thus representing a diagnostic challenge for dermatologists. Although the differentiation between these two entities is traditionally done by histopathology, dermoscopy has been utilized as a useful additional aid for improving the clinical diagnostic accuracy of such pigmented skin lesions. We report the clinical and dermoscopic features of two pigmented actinic keratoses to discuss the difficulties in their preoperative differential diagnosis.     

Chemokine receptor expression in non-melanoma skin cancer

Background:  Previous studies suggest that chemokines and chemokine receptors have a role in the metastatic process. A correlation exists between the specific expression of these chemoattractive, pro-inflammatory cytokines and the ability of cancer to disseminate. Prior studies have shown that in metastatic melanoma and squamous cell carcinoma of the head and neck upregulation of CXC (α) chemokine receptor (CXCR)4 and CC (β) chemokine receptor (CCR)7 expression is accompanied by downregulation of the chemokine receptor CCR6. However, the expression patterns of CCR6, CCR7 and CXCR4 in non-melanoma skin cancer have yet to be elucidated.
Methods:  The expression patterns of CCR6, CCR7 and CXCR4 were determined using an immunohistochemical approach on formalin-fixed, paraffin-embedded normal, pre-cancerous actinic (solar) keratosis, squamous cell carcinoma and basal cell carcinoma tissues.
Results:  Analysis of chemokine receptor expression showed downregulation of CCR6 and upregulation of CCR7 and CXCR4 in potentially metastatic non-melanoma skin cancer, invasive squamous cell carcinoma, but this pattern did not exist in non-melanoma skin cancer with no metastatic potential, basal cell carcinoma; or actinic keratosis, when compared with normal skin.
Conclusions:  Chemokine receptor expression may influence the biological behavior of non-melanoma skin cancer. The exact mechanism by which this occurs requires further study.     

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.     

The diagnostic concordance of actinic keratosis and squamous cell carcinoma

Diagnostic concordance of intraepithelial malignancy is generally only fair. Because the diagnosis of actinic keratosis (AK) and squamous cell carcinoma (SCC) is not uniform and because such terms are not consonant with the nomenclature of other human epithelial malignancies, nomenclature revisions have been attempted. One hundred dermatopathologists were solicited to review 15 tissue sections representing a spectrum of varying thickness epidermal malignancy and to choose either AK or SCC as the diagnosis. Among the 77 participating dermatopathologists, intraclass correlation was high for what was perceived as AK, SCC, and their differentiation. Development of a two-tiered diagnostic system that retains our present diagnostic capabilities, but better fits the pathobiology of superficial epidermal malignancy is suggested. Davis DA, Donahue JP, Bost JE, Horn TD. The diagnostic concordance of actinic keratosis and squamous cell carcinoma.     

Differential expression of ezrin in epithelial skin tumors: cytoplasmic ezrin immunoreactivity in squamous cell carcinoma

Background Ezrin is a cytoskeleton linker protein that is actively involved in regulating the growth and metastatic capacity of cancer cells. The purpose of the study was to assess the expression pattern of ezrin in normal skin and various epithelial neoplasms. Methods We used immunohistochemical techniques to examine the expression of ezrin in paraffin‐embedded tissues of squamous cell carcinoma (n = 23), basal cell carcinoma (n = 10), Bowen’s disease (n = 10), actinic keratosis (n = 10), keratoacanthoma (n = 9), seborrheic keratosis (n = 5), psoriasis vulgaris (n = 5), and normal control skin (n = 5). Results In Bowen’s disease, actinic keratosis, keratoacanthoma, and seborrheic keratosis, ezrin was dominantly expressed in the cell membrane except for the cornified layer. In squamous cell carcinoma (SCC) specimens, the percentage of ezrin‐positive cells was increased compared with Bowen’s disease, actinic keratosis, keratoacanthoma, and seborrheic keratosis. Especially in SCC samples, ezrin expression was markedly expressed in the cytoplasm. In addition, there was a correlation between the pattern of ezrin expression and tumor differentiation in SCC. Basal cell carcinoma showed intense and diffuse staining especially in the solid growth pattern. Conclusions Our findings suggest that dysregulation of ezrin may be important in the development of cutaneous epithelial malignancies and tumor grade. We suggest that the cytoplasmic localization of ezrin may be useful in the diagnosis of skin SCC.     

Immunohistochemical Detection of Ki-67 in Epithelial Skin Tumors in Formalin-fixed Paraffin-embedded Tissue Sections Using a New Monoclonal Antibody (MIB-1)

The expression of the Ki-67 antigen was investigated in 44 epithelial skin tumors using an immunohistochemical technique on formalin-fixed, paraffin-embedded tissue sections. Microwave oven heating was employed for retrieval of the antigen in these tissue sections. The staining patterns varied among the epithelial skin tumors. The assessment of immunohistochemical staining was based upon the growth fraction (GF), defined as the number of Ki-67 positive cells divided by the total number of tumor cells counted and expressed as a percentage. GF was 9.7 ± 3.1% in seborrheic keratosis, 19.5 ± 2.9% in keratoacanthoma, 23.1 ± 4.9% in basal cell carcinoma, 18.5 ± 6.3% in actinic keratosis, 37.1 ± 6.0% in Bowen's disease, and 32.9 ± 10.5% in squamous cell carcinoma. There was a significant difference in GF between the keratoacanthoma and squamous cell carcinoma (p<0.01). Actinic keratosis showed a relatively low GF, whereas Bowen's disease showed a high one. Furthermore, the GF tended to increase with tumor cell differentiation in squamous cell carcinoma: 23.7% (±5.0) in well-differentiated, 35.0% (±6.2) in moderately-differentiated, and 47.6% (±4.5) in poorly-differentiated squamous cell carcinomas. Immunohistochemistry with MIB-1 may give useful additional information in the differential diagnosis of KA and SCC.     

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.     

Family with MSH2 mutation presenting with keratoacanthoma and precancerous skin lesions

Muir–Torre syndrome (MTS) is a familial cancer syndrome characterized by a predisposition to keratoacanthoma (KA) and sebaceous tumors. Although MTS and hereditary non‐polyposis colorectal cancer (HNPCC) share the same genetic alterations in mismatch repair (MMR) genes, the other skin lesions in MTS or HNPCC have been only rarely reported. We report a family with an MSH2 mutation c.1126_1127delTT (p.Leu376Thrfs*12). A 46‐year‐old male proband developed KA with sebaceous differentiation, colon cancer and gastric cancer, and fulfilled the diagnostic criteria for MTS. His 80‐year‐old mother, diagnosed with HNPCC, presented with multiple gastrointestinal tract cancers, Bowen's disease and actinic keratosis. Immunostaining revealed attenuated MSH2 protein expression in KA, as well as in Bowen's disease and actinic keratosis lesions. These findings suggest that MMR gene abnormality is also critical in the development of benign or malignant cutaneous tumors such as actinic keratosis and Bowen's disease in MTS/HNPCC patients.     

抗增殖蛋白2在皮肤鳞状细胞癌中的表达及其对A431细胞增殖的影响

目的：观察抗增殖蛋白2在皮肤鳞状细胞癌、鲍温病、日光性角化病组织中的表达情况及其对A431细胞增殖作用的影响。方法：采用免疫组织化学方法检测抗增殖蛋白2在40例皮肤鳞状细胞癌、18例鲍温病、17例日光性角化病组织以及9例正常皮肤组织中的表达水平。采用CRISPR-Cas9法构建两组靶向敲除抗增殖蛋白2的皮肤鳞状细胞癌A431细胞模型（KO299组及KO320组）,使用Western印迹法证实其敲除效果,通过CCK8法及细胞克隆形成实验分析其对细胞增殖的影响。使用Western印迹法对AKT蛋白表达及其ser473位点磷酸化产物水平进行分析。 结果：抗增殖蛋白2在皮肤鳞状细胞癌(90.00％)、鲍温病(66.70％)、日光性角化病(41.18％)的表达高于正常组织(0.00％)（均P<0.05）,皮肤鳞状细胞癌抗增殖蛋白2表达高于日光性角化病(P<0.05)。在不同性别、年龄、部位、病程、肿瘤直径、浸润深度、分化、Broder分级的皮肤鳞状细胞癌组织中抗增殖蛋白2的表达差异无统计学意义（均P>0.05）。两组抗增殖蛋白2敲除组A431细胞的蛋白表达水平、细胞活力、克隆形成数显著低于对照组 (均P<0.05)。p-AKT表达随抗增殖蛋白2表达水平的降低而显著下调（均P<0.01）。结论：抗增殖蛋白2的表达可能促进了皮肤鳞状细胞癌的发生,并且其机制可能与促癌基因AKT蛋白活化相关。     

Reflectance confocal microscopy criteria of lichen planus‐like keratosis

Background Lichen planus‐like keratosis (LPLK) may be difficult to differentiate from melanoma and other skin cancers on sun‐damaged skin based on clinical and dermoscopic examination. Reflectance confocal microscopy (RCM) allows evaluation of skin lesions at high resolution. Objectives The aim of this study was to identify criteria for specific diagnosis of LPLK using in vivo RCM. Methods Lesions included in the study were derived from patients presenting for skin examination at a private dermatology practice specializing in skin cancer. We retrospectively analysed RCM features of 28 biopsy‐proven LPLK and compared them to RCM findings in skin cancers on sun‐damaged skin, including five in situ squamous cell carcinomas, six actinic keratoses, seven superficial basal cell carcinomas and eight melanomas. Results The main RCM features of LPLK and their relative frequencies were: (i) typical honeycomb pattern of the spinous layer (78.6%); (ii) elongated cords and/or bulbous projections at the dermal‐epidermal junction (75%); and (iii) numerous plump‐bright cells and/or bright stellate spots in the superficial dermis (92.9%). These RCM features correlated with the following histopathological findings respectively: (i) spinous‐granular layers without significant atypia of keratinocytes; (ii) elongated, bulbous rete ridges; and (iii) dense infiltration of melanophages and lymphocytes in superficial dermis. We propose diagnostic criteria that classify correctly 71.4% of LPLK, while avoiding misclassification of any of the skin cancers in the present series as LPLK. Conclusions We identified RCM criteria for diagnosis of LPLK that correlate well with histopathological findings and that allow differentiation of LPLK from skin cancer.     

Dermoscopy in the diagnosis and management of non-melanoma skin cancers

Over the past two decades, dermoscopy has remarkably enhanced the diagnostic accuracy of pigmented skin lesions and, more recently, of non-pigmented skin disorders, including skin cancers, inflammatory and infectious diseases. With respect to non-melanoma skin cancers (NMSC), dermoscopy is an effective diagnostic tool for the clinical assessment of basal cell carcinoma, Bowen's disease, actinic keratosis and squamous cell carcinoma. Besides its relevance for diagnostic purposes, further applications of dermoscopy in the management of NMSC have been suggested in the preoperative evaluation, in monitoring the outcome of topical, light-based or laser treatments and in the post-treatment follow-up. This article summarizes the dermoscopic diagnostic criteria of NMSC and provides a review of the published literature as well as of our own experience on the usefulness of dermoscopy in monitoring surgical and medical treatment of NMSC.     

Key points in dermoscopic differentiation between lentigo maligna and solar lentigo

A clinical diagnosis of lentigo maligna at an early stage is often difficult even for experienced dermatologists. Differential diagnoses would include solar lentigo, early lesions of seborrheic keratosis, lichen planus-like keratosis, pigmented actinic keratosis and melanocytic nevus. Dermoscopy has been shown to have higher diagnostic accuracy, especially in the diagnosis of pigmented skin lesions, in the past two decades. To aim of the present study was to review the diagnostic key points on dermoscopy in the published work to differentiate lentigo maligna from other differential diagnoses and reassess these important features on dermoscopy for specificity by describing the findings in detail. Diagnostic key points for lentigo maligna/lentigo maligna melanoma on dermoscopy are asymmetrical pigmented follicular openings, rhomboidal structures, annular-granular structures and gray pseudo-network. Lentigo maligna, at first, seems to occur as asymmetrical pigmented follicular openings and/or annular-granular structures, then expand and develop into the rhomboidal structures. Annular-granular structures and gray pseudo-network seem to be observed also in regressive areas of solar lentigo/initial seborrheic keratosis, lichen planus-like keratosis and pigmented actinic keratosis. The four important criteria on dermoscopy for the diagnosis of lentigo maligna have been reviewed, and the former two criteria seem to be more specific, but it might be difficult to recognize these findings without misinterpretation. The latter two seem to be not so specific as they would also be demonstrated in other pigmented epidermal lesions, although the distribution of the structures in these disorders would be inclined to be more homogeneous than that of lentigo maligna.     

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.     

5-氨基酮戊酸乳膏光动力疗法治疗皮肤癌前病变和皮肤原位癌

目的 探讨5-氨基酮戊酸光动力疗法(ALA-PDT)治疗皮肤癌前病变和皮肤原位癌的疗效.方法 对15例光线性角化病、3例Queyrat增生性红斑和8例Bowen病患者进行ALA-PDT治疗.结果 15例光线性角化病患者的17个皮损获得完全缓解,2例复发,复发率13.33%;3例Queyrat增生性红斑除1例无效外,另2例患者的皮损获完全缓解,无复发;8例Bowen病除1例获得部分缓解外,其他7例完全缓解,1例复发.结论 ALA-PDT是一种疗效好、无明显痛苦、无瘢痕形成、复发率低、美容效果好的治疗皮肤癌前病变和皮肤原位癌的新疗法;特别适合于头面部及外生殖器部位的多发性、较大面积皮损.     

Diagnostic accuracy in skin cancer clinics: the Australian experience

BACKGROUND: Australia, with the world's highest incidence of skin cancer, has witnessed the emergence of "open access" skin cancer clinics during the past decade. These clinics are becoming increasingly popular destinations for the diagnosis and treatment of skin cancers, yet little is known about the diagnostic performance of practitioners in this setting. We sought to measure the accuracy of clinical diagnosis in this setting. METHODS: Clinical and histological data were obtained from 199 consecutive patients undergoing biopsy or excision for 287 skin lesions. We measured the sensitivity, specificity and predictive value of the clinical diagnoses compared with histological diagnoses. RESULTS: Of 287 biopsied or excised lesions, the most common were benign nevi (24%) and basal cell carcinomas (22%), followed by actinic keratoses (11%), dysplastic nevi (11%) and squamous cell carcinomas (7%). Sensitivity was highest for diagnosing BCC (0.89, 95%CI 0.78-0.95) and dysplastic nevi (0.80, 95%CI 0.61-0.93), and lowest for actinic keratoses and the group of benign lesions. Specificity was greater than 0.93 for all diagnoses except BCC (0.76, 95%CI 0.70-0.81). Treating clinicians perceived moderate to strong pressure to excise 49% of lesions overall, but in particular for benign nevi (73%). CONCLUSIONS: Australian family practitioners in open access skin cancer clinics diagnose a wide range of skin lesions with high specificity and moderate to high sensitivity. Benign nevi are accurately diagnosed and often excised because of patient pressure.