脂溢性角化病研究进展

文章综述了脂溢性角化病发病可能的相关因素如年龄、目光、血脂和乳头瘤病毒感染，以及脂溢性角化病细胞增殖、分化和凋亡异常，说明脂溢性角化病是介于正常与恶性肿瘤之间的一种皮肤病。     

临沧市佤族136例脂溢性角化病的临床病理分析

目的探讨临沧市佤族脂溢性角化病的临床和组织病理学特点。方法回顾性分析我院136例脂溢性角化病的临床表现及组织病理学资料。结果 136例脂溢性角化病患者病理分型主要为棘层肥厚型占44%、角化过度型占30%。患者男女比例为1.61∶1,发病年龄50岁以上占84.5%,头面颈部等暴光部位占发病部位的71.5%。结论年龄和日光照射可能是临沧市脂溢性角化病的重要致病因素。临床上典型的脂溢性角化病不难诊断,不典型者容易与日光性角化病、黑色素瘤、扁平疣等相混淆,临床表现与组织病理的结合有助于降低误诊率。     

裸鼠脂溢性角化病造模初探

目的:评价体外皮肤移植法建立脂溢性角化病动物模型的可行性.方法:在裸鼠背部一侧掀起约10 mm×10mm的全层皮瓣,将制备好的10 mm×10 mm的脂溢性角化病组织块移植于创面上.观察裸鼠移植的脂溢性角化病皮损的大体形态学变化,观察至1个月后将皮损切除行病理组织学检查,HE染色后观察皮损的组织形态学变化.结果:20只裸鼠中有15只出现了肉眼可见的脂溢性角化病样皮损(15/20,75％),组织学上与人脂溢性角化病的形态相一致.结论:体外脂溢性角化病皮损移植的裸鼠模型建模方法可靠,能比较真实地模拟脂溢性角化病的组织学形态,可为脂溢性角化病的研究提供平台.     

脂溢性角化病皮损表皮中负性调节因子Smad7的表达

目的：探讨负性调节因子Smad7在脂溢性角化病皮损中表达水平的变化及其意义。方法：采用实时定量（quantitative real-time）PCR和免疫组化技术分别检测脂溢性角化病皮损及正常对照皮肤中Smad7的表达。结果：Smad7在脂溢性角化病皮损中的表达较正常表皮显著升高（P〈0.01）。结论：脂溢性角化病皮损表皮中Smad7过度表达可能有助于表皮细胞的异常增生,促进脂溢性角化病的形成。     

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。     

脂溢性角化病231例临床及病理分析

脂溢性角化病是一种常见病，但临床上易与多种疾病相混淆，通过对西京医院皮肤科门诊1990年－2000年252例脂溢性角化病的临床及病理资料进行回顾分析，发现脂溢性角化病临床和病理诊断符合率仅为69．44％，结果显示：（1）脂溢性角化病可发生于任何年龄；（2）黑色丘疹性皮病不应看作独立疾病，而是早期发生的脂溢性角化病。     

克隆型脂溢性角化病4例皮肤镜及反射式共聚焦显微镜影像学特征及文献复习

目的探讨克隆型脂溢性角化病皮肤镜与反射式共聚焦显微镜(RCM)特征,提高临床医生无创诊断克隆型脂溢性角化病的水平。方法回顾性分析4例克隆型脂溢性角化病的皮肤镜及RCM特征,并结合文献讨论。结果皮肤镜下3例表现为球状结构,1例表现为黑褐色均质样结构,所有皮损边界清晰;RCM下发现表皮内高折光细胞巢。结论皮肤镜与RCM检查可能为克隆型脂溢性角化病的诊断提供参考依据。     

成纤维细胞生长因子10mRNA在脂溢性角化病皮损中的表达

目的研究成纤维细胞生长因子10 mRNA在脂溢性角化病皮损中的表达,探讨其在脂溢性角化病发病中的作用机制。方法应用原位杂交法检测FGF10 mRNA正常皮肤组织和脂溢性角化病皮损中的表达和分布。结果28例脂溢性角化病皮损表皮的全层或中下层均可见FGF10 mRNA表达(100.0%);正常皮肤表皮的基底层或个别细胞内可见FGF10 mRNA的表达(3.57%);脂溢性角化病皮损表皮中FGF10 mRNA的表达明显高于正常对照组(P<0.05)。结论FGF10 mRNA在脂溢性角化病皮损中表达增高。     

脂溢性角化病128例临床病理分析

目的探讨脂溢性角化病的临床及组织病理学特点。方法对近10年来128例脂溢性角化病患者的临床及病理资料进行回顾性分析。结果六种类型脂溢性角化病的组织象均可见到,并以棘层肥厚型和角化过度型为主。51岁以上发病者占71.9%,头、面、颈等暴光部位发病者占53.9%,临床和病理诊断符合89例,临床误诊率30.47%。结论发病年龄虽有提前,但年龄的增加与脂溢性角化病的发病率仍成正比;暴露区域比非暴露区域更易患病,过度日光照射可能是其重要诱因;临床常易误诊,需与相关皮肤病鉴别。     

泛发性脂溢性角化病2例

脂溢性角化病泛发于青年患者较少见,现将我们所见的2例泛发性脂溢性角化病报道如下.     

Seborrheic keratosis

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.     

Are all seborrheic keratoses benign? Review of the typical lesion and its variants

BACKGROUND: Seborrheic keratosis (SK) is one of the more common benign epidermal neoplasms seen in adult and middle-aged patients. OBJECTIVE: As little is written in the literature about the variants of SK, this article aims to categorize and discuss the different subtypes and their important associations. METHODS: An in-depth literature search using OVID Medline and PubMed was conducted to classify the various subtypes of SK. Clinical variants were photographed and used to help document the subtypes. The pathology is described for each. RESULTS: Six subtypes of SK were identified: dermatosis papulosa nigra, stucco keratosis, inverted follicular keratosis, large cell acanthoma, lichenoid keratosis, and flat seborrheic keratosis. Although the etiology and pathogenesis of SKs are still largely debatable, several underlying mechanisms and contributing factors have been identified. All subtypes represent benign lesions, and treatment is usually done for cosmetic reasons. Several of the subtypes may act as cutaneous markers for internal malignancy and should be monitored closely for any atypical changes. CONCLUSION: Although all subtypes of SK are benign, their association with other malignant lesions and ability to serve as cutaneous markers of internal malignancy emphasize the importance of correctly identifying all variants.     

Enhanced expression of p16 in seborrhoeic keratosis; a lesion of accumulated senescent epidermal cells in G1 arrest

BACKGROUND: Seborrhoeic keratosis (SK) is a common skin disease associated with skin ageing and photoageing, but only limited studies have been performed on SK and the senescence of keratinocytes. OBJECTIVES: We sought to clarify the genetic basis of SK and the senescence of keratinocytes. METHODS: Expression of p16, cyclins A, D and E, p21, p53, retinoblastoma (Rb) gene product and telomerase-associated protein 1 (TP1) in SK was examined by immunohistochemistry. DNA fragmentation in SK was detected by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling method. We cultured keratinocytes from SK lesions and non-lesional epidermis and examined expression of p16, observed morphology of the cultured cells by light and electron microscopy and measured survival time. RESULTS: p16, a cyclin-dependent kinase inhibitor, was expressed in all cells from SK lesions, whereas normal keratinocytes expressed p16 only in the granular cells. Other factors such as cyclins A, D and E, p21, p53, Rb gene product, and TP1, were not expressed in SK cells. These results suggest that p16 expression is a marker of SK and that p16 has a role in the pathogenesis of SK. DNA fragmentation was not detected in four of five SK tissue samples; one of the SK tissue samples showed DNA fragmentation only in the superficial upper layer of an SK lesion, suggesting that apoptosis was inhibited in SK cells. In contrast, normal epidermis showed DNA fragmentation in the granular and squamous layers. Immunohistochemical examination of cultured SK cells also revealed the presence of p16. A greater number of SK cells survived after 3 weeks of culture in comparison with normal keratinocytes. Features of senescence, such as a balloon-like appearance after lengthy culture and increased amounts of tonofilaments in cytoplasm, were observed in SK cells in culture. CONCLUSIONS: These results suggest that SK is a benign neoplasm where keratinocytes in a senescent condition and G1 arrest are accumulated.     

Somatic FGFR3 and PIK3CA mutations are present in familial seborrhoeic keratoses

Background  Seborrhoeic keratosis (SK) represents one of the most common benign skin tumours. Familial occurrence of multiple SKs has been reported, but the genetic basis of these SKs has not been investigated so far. We present a German family with at least seven affected members in two generations and occurrence of high numbers of SKs at an unusually young age, suggesting a hereditary background.
Objectives  Because FGFR3 and PIK3CA mutations have been reported to be involved in the pathogenesis of sporadic SK, we analysed five SKs of an affected family member for hotspot mutations of these genes.
Methods  A SNaPshot^® multiplex assay was used for analysis of 11 previously described FGFR3 hotspot mutations. In addition, exon 9 of PIK3CA was directly sequenced and the H1047R hotspot mutation in exon 20 was analysed by a SNaPshot^® assay.
Results  FGFR3 mutations were present in three of five SKs. One SK with a FGFR3 mutation additionally showed a hotspot PIK3CA mutation. None of these mutations was present in the germline.
Conclusions  The results show that this case of familial SK reveals the same mutational spectrum as sporadic SK. Because FGFR3 and PIK3CA germline mutations can be excluded as an underlying genetic basis, alternative mechanisms have to contribute to familial SK such as inherited susceptibility factors predisposing to the acquisition of somatic FGFR3 and PIK3CA mutations in skin, or increased exposure of the family members to yet unknown environmental risk factors causing these mutations.     

Dermoscopic features of hidroacanthoma simplex: Usefulness in distinguishing it from Bowen's disease and seborrheic keratosis

Hidroacanthoma simplex (HAS) is a rare benign eccrine adnexal tumor. HAS is sometimes clinically or pathologically misdiagnosed as squamous cell carcinoma in situ (Bowen's disease; BD), seborrheic keratosis (SK) or other adnexal tumor. To date, there has never been a report focusing on dermoscopic features to distinguish HAS from BD and SK. We found the following dermoscopic findings to be characteristic of HAS: fine black dots/globules (75% of cases) and fine scales arranged annularly (100% of cases). In contrast, glomerular vessels, which are typically observed in BD, were not seen in any of the four cases. Cerebriform appearance and milia‐like cysts, which are typically observed in SK, were also not seen in any of the four cases. The existence of “scattered fine black dots/globules” and “fine scales arranged annularly”, and the absence of the glomerular vessels, may contribute to precise diagnosis of HAS. Even though HAS resembles BD or SK clinically, it can be distinguished from these by the characteristic dermoscopic features.     

Clinical and Histopathological Investigation of Seborrheic Keratosis

BackgroundSeborrheic keratosis (SK) is one of the most common epidermal tumors of the skin. However, only a few large-scale clinicohistopathological investigations have been conducted on SK or on the possible correlation between histopathological SK subtype and location.ObjectiveThe aim of this study was to analyze the clinical and histopathological features of a relatively large number of cases of diagnosed SK.MethodsTwo hundred and seventy-one pathology slides of skin tissue from patients with clinically diagnosed SK and 206 cases of biopsy-proven SK were analyzed. The biopsy-proven cases of SK were assessed for histopathological subclassification. The demographic, clinical, and histopathological data of the patients were collected for analysis of associated factors.ResultsThe most frequent histopathological subtype was the acanthotic type, followed by mixed, hyperkeratotic, melanoacanthoma, clonal, irritated, and adenoid types; an unexpectedly high percentage (9.2%) of the melanoacanthoma variant was observed. The adenoid type was more common in sun-exposed sites than in sun-protected sites (p=0.028). Premalignant and malignant entities together represented almost one-quarter (24.2%) of the clinicopathological mismatch cases (i.e., mismatch between the clinical and histopathological diagnoses). Regarding the location of SK development, the frequency of mismatch for the sun-exposed areas was significantly higher than that for sun-protected areas (p=0.043).ConclusionThe adenoid type was more common in sun-exposed sites. Biopsy sampling should be performed for lesions situated in sun-exposed areas to exclude other premalignant or malignant diseases.     

脂溢性角化病的研究进展

脂溢性角化病是老年人常见的表皮良性肿瘤,50岁后80%以上患病。近年的研究认为,日光和人类乳头瘤病毒感染与该病的发生密切相关,但确切机制不明。该病皮损绝大部分颜色较深,研究认为,是增生的角质形成细胞产生内皮素作用于黑素细胞所致。分子生物学方面的研究发现该病皮损中p53、Bcl-2、p73及p16等生物分子表达异常,引起细胞的分化、增殖、凋亡及细胞周期紊乱,从而参与疾病的发生。     

Cytokeratin 10-negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease

Background: The histopathologic pattern of clonal seborrheic keratosis (SK) is quite similar to the nested pattern of pagetoid Bowen's disease [squamous cell carcinoma in situ (SCCIS)], and differentiation between the two can be challenging, especially when only small pieces are available for interpretation. Methods: Eleven examples of clonal SK and 13 examples of pagetoid SCCIS were examined histopathologically (tabulating necrotic keratinocytes, suprabasal mitoses, infiltrate, parakeratosis housing plump nuclei, crowding of nuclei) and immunohistochemically (using Ki‐67, bcl‐2, cytokeratin 7 and cytokeratin 10). Sensitivity, specificity, p‐values (Fisher's exact test, two‐tailed) and positive/negative likelihood ratios (+LR/?LR) were calculated. Results: Significant differences were seen with regard to crowding (p = 0.0009) and mitoses (p = 0.0006); however, only complete absence of necrotic keratinocytes or of crowding appeared to be diagnostically convincing for a diagnosis of clonal SK (?LR < 0.01). Significant differences were also seen with bcl‐2 (p = 0.0005) and cytokeratin 10 antibodies (p < 0.00001). Both markers displayed a typical nested pattern in clonal SK, nests being bcl‐2‐positive and cytokeratin 10‐negative. Cytokeratin 10‐negative nests were the most convincing criterion for differentiation between clonal SK and pagetoid SCCIS (+LR > 10, ?LR < 0.01). Conclusions: The most reliable marker to distinguish clonal SK from pagetoid SCCIS is cytokeratin 10 when it spares nests. Other criteria that assist in the differential diagnosis are bcl‐2 expression, absence of crowding and of mitoses. Böer‐Auer A, Jones M, Lyasnichaya OV. Cytokeratin 10‐negative nested pattern enables sure distinction of clonal seborrheic keratosis from pagetoid Bowen's disease.     

脂溢性角化病96例和日光性角化病28例临床与病理分析

目的观察脂溢性角化病(SK)与日光性角化病(AK)的临床及病理差异。方法回顾性分析本科门诊2006年1月-2011年7月经病理确诊的96例SK和28例AK患者的临床及病理资料,对数据用Excel整理与分析。结果①SK好发于中老年人,而AK好发于老年人;②SK皮损好发于头面、躯干及四肢,而AK好发于头、面和颈等光暴露部位;③组织病理:SK以角化型和棘层肥厚型为主,而AK以原位癌型和萎缩型为主;④SK临床与组织病理的诊断符合率为70.83%,而AK临床与组织病理的诊断符合率仅为46.43%,临床上易将AK误诊为SK。结论 AK发病晚于SK,临床上AK误诊率高于SK,两者鉴别诊断主要依赖组织病理。