日光性角化病研究进展

日光性角化病的发病与炎症反应、氧化应激、免疫抑制等有关, 其组织病理表现为表皮结构异常和角质形成细胞发育不良,其他非侵入性的成像方法对诊断该病也有重要意义。治疗方法包括局部药物、光动力、冷冻、激光等。本文对日光性角化病的流行病学、发病机制、临床和组织学特征、诊断及治疗进行综述。     

Dermoscopic features of actinic keratosis

Actinic keratosis (AK) is a keratinocytic neoplasm that typically develops on sun‐damaged skin of elderly individuals. Only a few reports so far have described the dermoscopic diagnostic features of AK, mainly focusing on facial non‐pigmented AKs. A typical feature of facial non‐pigmented AK is a composite pattern named “strawberry pattern”, characterized by a background erythema/red pseudonetwork consisting of unfocused, large vessels located between the hair follicles, associated with prominent follicular openings surrounded by a white halo. Dermoscopic characteristics of pigmented AK on the face include multiple slate‐gray to dark‐brown dots and globules around the follicular ostia, annular‐granular pattern and brown to gray pseudonetwork. Recognizing specific dermoscopic features of AK can be useful in guiding the clinician in the differential diagnosis of AK with melanocytic skin lesions such as LM and non‐melanocytic lesions. Histopathologic examination should be performed whenever clinical and/or dermoscopic differential diagnosis is inconclusive.     

Current therapies for actinic keratosis

Actinic keratosis (AK) is a very common skin disease caused by chronic sun damage, which in 75% of cases arises on chronically sun-exposed areas, such as face, scalp, neck, hands, and forearms. AKs must be considered an early squamous cell carcinoma (SCC) for their probable progression into invasive SCC. For this reason, all AK should be treated, and clinical follow-up is recommended. The aims of treatment are: (i) to clinically eradicate evident and subclinical lesions, (ii) to prevent their evolution into SCC, and (iii) to reduce the number of relapses. Among available treatments, it is possible to distinguish lesion-directed therapies and field-directed therapies. Lesion-directed treatments include: (i) cryotherapy; (ii) laser therapy; (iii) surgery; and (iv) curettage. Whereas, field-directed treatments are: (i) 5-fluorouracil (5-FU); (ii) diclofenac 3% gel; (iii) chemical peeling; (iv) imiquimod; and (v) photodynamic therapy (PDT). Prevention plays an important role in the treatment of AKs, and it is based on the continuous use of sunscreen and protective clothing. This review shows different types of available treatments and describes the characteristics and benefits of each medication, underlining the best choice.     

Expression of p53 and p16 in actinic keratosis,bowenoid actinic keratosis and Bowen's disease

Introduction Bowen's disease (BD) and bowenoid actinic keratosis (bAK) have traditionally been differentiated according to the presence or absence of dysplasia in the follicular epithelium. p16 has been suggested to be a useful tool to make the differential diagnosis between BD and AK and as a marker of bad prognosis. Materials Five biopsies of BD, five of AK and five of bAK where stained for p53 and p16. Results All lesions showed positive immunostaining of p53, affecting to the lower two thirdss of the epidermis in BD and bAK, and only the basal layer in non‐bAK. All the BD and bAK cases were positive for p16, showing a similar immunostaining pattern, whereas no staining was observed in non‐bAK. Discussion and conclusion These findings suggest a common pathogenic mechanism for BD and bAK. bAK might have worse prognosis than AK. p16 might not be useful as a tool for differential diagnosis between AK and BD because bAK and BD show an extremely similar immunohistochemical pattern.     

p16INK4a expression in actinic keratosis and Bowen's disease

BACKGROUND: Progression of cutaneous squamous neoplasms from actinic keratosis (AK) to Bowen's disease (BD; squamous cell carcinoma in situ) has important implications for clinical management and treatment, thus requiring accurate diagnosis. p16INK4a is a cell cycle regulatory tumour suppressor protein that negatively regulates D-type cyclins in the G1 cell cycle phase via intimate interplay with the retinoblastoma gene. Expression of a paraffin-reactive p16INK4a marker has recently been shown to increase in cervical squamous neoplasms as lesions progress from low-grade dysplasia to squamous cell carcinoma in situ. p16INK4a expression in the progression of squamous cutaneous neoplasia, however, has not been evaluated. OBJECTIVES: To evaluate p16INK4a expression in the progression of squamous cutaneous neoplasia. METHODS: Biopsies of 203 squamous cutaneous neoplasms with unequivocal features of AK (n = 87) and BD (n = 116) as well as a benign squamous control group (verruca vulgaris: n = 10; seborrhoeic keratosis: n = 11; scar tissue: n = 8) obtained between January and December 2001 at Henry Ford Hospital (Detroit, MI, U.S.A.) were immunostained for p16INK4a (Dako; clone E6H4; dilution 1 : 50) using large core (1.5 mm) tissue microarray analysis. Nuclear/cytoplasmic immunoreactivity in > 10% of neoplastic cells was considered positive. RESULTS: Of 203 cases, 166 (81.8%) were interpretable (AK 59; BD 107). Mean patient age was 71.0 years (range 33-93); 57% were male. Sites of involvement were: head and extremities 75.9%, trunk/buttocks 21.7%, genital region 2.4%. p16INK4a immunostaining was positive in 90 of 107 (84.1%) BD cases, four of 59 (6.8%) AK cases and none of 29 benign squamous controls. The sensitivity and specificity of p16INK4a for a diagnosis of BD (vs. benign squamous controls/AK) was 84.1% and 95.5%, respectively (P < 0.0001, Fisher's exact test, two-sided). CONCLUSIONS: p16INK4a is a sensitive and specific marker for distinguishing BD from AK/benign squamous cutaneous lesions and may be helpful as an adjunct to histomorphology in the diagnosis and appropriate clinical management of these lesions.     

Sebaceous carcinoma arising on actinic keratosis

We report two cases of sebaceous carcinoma arising on actinic keratosis. The first patient, a 75-year-old female, had a granuloma pyogenicum-like tumor on her left temple, and the second patient, an 81-year-old female, developed a tumor with erythema on her left cheek. In both cases, histopathological examination revealed findings typical of sebaceous carcinoma in the center of the tumors, and in the periphery, actinic elastosis and intraepidermal proliferation of squamoid atypical cells without vacuolation was observed. Immunohistochemical examinations using six antibodies also revealed that neoplastic cells of both cases demonstrated sebaceous differentiation. These cases suggest that extraocular sebaceous carcinoma may arise from actinic keratosis.     

Standardized AgNOR analysis in actinic keratosis.

To assess if the quantity of silver-stained nucleolar organizer region (AgNOR) proteins predicts the behavior of actinic keratosis (AK), we performed a standardized AgNOR analysis on 51 cases of AK; in addition, 10 cases of squamous cell (SCC) and 10 cases of basal cell (BCC) carcinomas and 10 normal skin samples were also studied. AgNOR analysis was performed on formalin-fixed and paraffin-embedded sections according to the guidelines of the Committee on AgNOR Quantification (1995), evaluating the mean area (microm(2)) of AgNORs per nucleus (NORA). A highly significant P value (< 0.001) was found in the comparison among NORA values of normal skin (1.869 microm(2); SD + 0.332), AK (3.988 microm(2); SD + 0.914), BCC (3.044 microm(2); SD + 0.254), and SCC (5.286 microm(2); SD + 0.920). In AK, a progressive increase of mean NORA values was observed moving from Stage I (3.161 microm(2); SD + 0.600) to Stage II (3.455 microm(2); SD + 0.562), Stage III (4.360 microm(2); SD + 0.295), and Stage IV (5.168 microm(2); SD + 0.694); highly significant differences (P < 0.001) were noted when Stages I or II were compared with Stage III or Stage IV or between these latter stages. The AgNOR quantity may identify AKs with high proliferative activity and increased tendency to develop into invasive SCC.     

Dermoscopy of facial nonpigmented actinic keratosis

BACKGROUND: The accuracy of clinical diagnosis of nonpigmented, facial actinic keratosis (AK) is often suboptimal, even for experienced clinicians. OBJECTIVES: To investigate the dermoscopic features of nonpigmented AK located on the head/neck that may assist the clinical diagnosis. METHODS: Forty-one nonpigmented AKs on facial sites were examined by dermoscopy for any consistent underlying features. Lesions were gathered from skin cancer centres in Australia, Austria, Italy and the U.S.A. All cases were diagnosed histopathologically. RESULTS: Four essential dermoscopic features were observed in facial AK: (i) erythema, revealing a marked pink-to-red 'pseudonetwork' surrounding the hair follicles (95%); (ii) white-to-yellow surface scale (85%); (iii) fine, linear-wavy vessels surrounding the hair follicles (81%); and (vi) hair follicle openings filled with yellowish keratotic plugs (66%) and/or surrounded by a white halo (100%). These features combined, in 95% of cases, to produce a peculiar 'strawberry' appearance. CONCLUSIONS: A dermoscopic model of 'strawberry' pattern is presented, which may prove helpful in the in vivo diagnosis of nonpigmented, facial AK. A limitation of this study is the lack of testing of the specificity of the described dermoscopic criteria in differentiating nonpigmented AKs from other nonpigmented skin lesions at this site.     

The reliability of counting actinic keratosis

Many epidemiological studies and clinical trials have been performed concerning actinic keratoses. The most eligible endpoint in the majority of articles is counting of actinic keratoses before and after treatments, nevertheless some authors support that this is not a reliable form of evaluation. The aim of this study was to evaluate the actinic keratoses counting by various raters and suggest approaches to increase the reliability. Cross-sectional study: forty-three patients were evaluated by four raters (inter- and intra-rater assessment) on the face and forearms. The mean actinic keratoses counts on the face and forearms were 7.7 and 9.1. The overall agreement among the raters for the facial and forearm actinic keratoses was 0.74 and 0.77. The intra-rater assessment showed high rates of agreement for the face (ICC = 0.93) and forearms (ICC = 0.83). Higher agreement occurred when counting up to five lesions. Four raters led to increased measurement variability and loss of reliability. Higher rates of agreement may be achieved with small number of lesions, limitation and/or segmentation of body areas to reduce their number, in AK prevention designs, are strategies that may lead to a greater reliability of these measurements.     

光线性角化病发病机制及治疗进展

光线性角化病是一种发生于曝光部位的表浅性皮肤病,其发病与长期紫外线照射所造成的基因突变,氧化应激,炎症反应,免疫抑制,细胞凋亡受损,细胞生长、增殖及组织重塑功能失调相关.光线性角化病目前治疗主要是针对皮损治疗和区域性治疗,针对皮损治疗包括冷冻、切除术、激光术,区域性治疗包括外用氟尿嘧啶、咪喹莫特、双氯芬酸、巨大戟醇甲基丁烯酸酯、维A酸及光动力治疗.     

Radiation therapy for extensive actinic keratosis

Actinic keratosis in the most common premalignant keratotic tumour of sun-exposed skin. A 66-year-old man developed a large actinic keratosis on his scalp, which did not respond to conventional treatment. Fractionated radiotherapy with a cumulative dose of 28 Gy resulted in complete remission without relapse during a 14-month follow-up. In older subjects in whom conventional treatment fails, low-dose fractionated radiation therapy is an effective alternative method.     

光线性角化病的皮肤镜特征研究进展

光线性角化病(AK)是皮肤长期暴露于日光下所引起的一种癌前病变,有发展为鳞癌的风险,皮肤镜已广泛应用于AK的诊断与鉴别诊断,其皮肤镜特征包括:基底假网状红斑、毛囊口周围白晕、毛囊口黄色角栓等,本文对AK的皮肤镜表现及鉴别诊断进行了综述.