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.     

Accuracy of diagnosis of benign skin lesions in hospital practice: a comparison of clinical and histological findings

Demand for surgical removal of presumed benign skin lesions is increasing. Our aim was to see whether the practice of sending every skin specimen for histological review is necessary in a hospital-based dermatology department. We first reviewed the histological findings of 1000 lesion removed between 1990 and 1992 where a firm clinical diagnosis of a benign melanocytic naevus (BM; n = 250). seborrhoeic keratosis (SK: n = 250). viral wan (VW; n =250) or skin tag ( n = 250) had been made. Next, we perused the original clinical diagnosis made for all histologically proven malignant melanomas (MM) between 1968 and 1993, to see whether they had been misdiagnosed as one of the above four common benign lesions. Histology confirmed the clinical diagnosis in 89% of presumed BM. 89% of presumed SK, 83% of presumed VW and 81% of presumed skin tags. Common causes of misdiagnosis were other benign lesions: 52% of incorrectly diagnosed BM were SK and 30% of incorrectly diagnosed SK were BM, while 38% of incorrectly diagnosed VW were SK. A total of seven malignant tumours (six basal cell carcinomas, one squamous, cell carcinoma) were misdiagnosed clinically, one as BM, three as VW, and two as SK, but no malignant lesions were mistakenly diagnosed as skin lags. Review of 238 histologically proven malignant melanomas revealed a prior clinical diagnosis of BM in 9% and SK in 0.8%, but none were clinically misdiagnosed us skin tags or VW. Hence, in a hospital setting, a firm clinical diagnosis of u skin tag did not lead to missed malignancy, and routine histological confirmation of these lesions appears unnecessary. However, in the case of BM and SK. and where clinical doubt exists, histological review remains essential.     

Lichenoid keratosis is frequently misdiagnosed as basal cell carcinoma

Lichenoid keratosis (LK), also known as benign lichenoid keratosis or lichen planus‐like keratosis, is a solitary, pink to red‐brown scaly plaque representing a host immunological response to a variety of precursor lesions. LK is often misdiagnosed as a dermatological malignancy owing to its clinical resemblance to basal cell carcinoma (BCC) or Bowen disease. We performed a retrospective analysis of the pathology records of a series of LK lesions with reference to the demographic features and accuracy of clinical diagnosis. The pathology records from 2008 to 2009 of 263 consecutive patients with a histological diagnosis of LK from a specialized skin laboratory were retrieved. Data relating to clinical diagnosis, age, sex, anatomical location, time of year of presentation and any coexistent pathological lesions adjacent to the LK were recorded. Mean age at presentation was 64 years (range 34–96), and 58% of patients were female. The most common anatomical site was the chest/anterior torso, followed by the back and legs. The most common coexisting lesion was solar keratosis at 14%, followed by seborrhoeic keratosis (SK) at 7.8%. The correct clinical diagnosis of LK was made in 29.5% of cases. The most common clinical diagnosis was BCC (47%), while SK was the preferred diagnosis in 18%. A clinical diagnosis was not given in 5.5% of cases. In conclusion, it appears that LK is frequently misdiagnosed, with misdiagnosis occurring in > 70% of cases in this study.     

Seborrheic keratosis or verruca plana? A pilot study with confocal laser scanning microscopy

Background: Differentiation of some seborrheic keratosis (SK) and verruca plana (VP) lesions is a challenge. Confocal laser scanning microscopy (CLSM) has been proved to be useful in the diagnosis of skin diseases; however, to date, there is no report on the differential study of the two diseases with CLSM. Objectives: To obtain the CLSM image characteristics of SK and VP, and then test the differential ability of CLSM imaging. Methods: We recruited 10 patients with typical lesions of SK under CLSM images to validate the features reported. Another 10 patients with typical VP lesions were also recruited, imaged with CLSM and biopsied to obtain the features under CLSM images based on histology analysis. Then, we attempt to summarize and refine those characteristics collected to obtain the most significant ones. All the cases with lesions suggestive of SK or VP were advised to undergo imaging with CLSM, and if CLSM imaging reflected discordantly with the clinical diagnosis, a biopsy was suggested for the exact lesion imaged. Those cases with CLSM and histology results were collected. Finally, two clinical dermatologists, who had no previous experience with CLSM, were tested with the simplified features of CLSM images to differentiate the suspected lesions of SK and VP among the cases collected. Results: In total, there were 58 cases with CLSM images and histology results collected, in which, 40 cases were diagnosed as SK and 18 cases as VP by histology. The two blinded dermatologists' judgments were identical to histology analysis. Conclusion: CLSM proved to be valuable in the differential diagnosis of SK and VP. The simplified characteristics were easily understood and acceptable to those with no previous experience of CLSM.     

Solar keratoses: analysis in a dermatological practice in Australia

Two hundred consecutive patients with solar keratoses (SK) seen in a private dermatology practice had on average 61.9 SK compared with eight reported in the general population. Non-melanoma skin cancer was present in 41% of patients and 17% had squamous cell carcinoma (SCC). The ratio of basal cell carcinoma to SCC in the cohort was 1.7:1. The commonest site of SK was the upper limbs but the greatest density of lesions was on the face, particularly the nose. Squamous cell carcinomas were most commonly found on the upper and lower limbs. Basal cell carcinomas were most common on the head and neck.     

German-Austrian-Swiss Consensus Conference on clinical practice in chronic graft-versus-host disease (GVHD): guidance for supportive therapy of chronic cutaneous and musculoskeletal GVHD

Supportive therapy plays a central role in the management of cutaneous and musculoskeletal manifestations of chronic graft-versus-host disease (cGVHD), either alone or in combination with systemic approaches. We present results from the German-Austrian-Swiss Consensus Conference on clinical practice in cGVHD, held in Regensburg, Germany, in November 2009. The intention was to achieve a consensus on current evidence-based treatment options as well as to provide guidelines for daily clinical practice. Skin is the most common organ involved in cGVHD. Its clinical presentation varies considerably. Patients may have pruritus, rash, pain, dyspigmentation and fibrotic or sclerodermatous lesions, often leading to contractures. Treatment options for supportive therapy in cutaneous cGVHD include topical therapies such as topical steroids and topical calcineurin inhibitors, as well as phototherapy and physiotherapy. The most relevant manifestation in musculoskeletal cGVHD is fasciitis which must be distinguished from sclerodermatous skin cGVHD. Physiotherapy is the mainstay of supportive treatment in fasciitis in cGVHD. Successful therapy of cutaneous and musculoskeletal cGVHD depends on interdisciplinary management to improve patients' quality of life.     

Treatment of Cutaneous Warts

Cutaneous warts are common skin lesions caused by human papillomavirus infection. Treatment is aimed at relieving the patient's physical and psychological discomfort and at preventing the spread of infection by autoinoculation. Among the available medical and destructive therapeutic options for cutaneous warts, none is uniformly effective or virucidal. Moreover, in most cases their safety and efficacy has not been assessed in double-blind, controlled clinical trials, so that the reproducibility of many of the listed treatments is difficult to evaluate and a possible placebo effect cannot be ruled out. The aim of this article is to describe the outcome of current therapies for each clinical wart type according to evidence-based medicine studies published in the literature. For each clinical form, the existing treatments are classified as first-, second-, and third-line therapy. First-line therapy includes medical treatments (salicylic acid, silver nitrate, glutaraldehyde) that are useful to treat a single wart or a few and/or small common warts of short duration (less than 1 year). If these treatments have failed or are contraindicated, cryotherapy may be considered as second-line therapy. For recurrent or difficult-to-treat lesions, third-line therapy includes a variety of alternative therapeutic options (topical, intralesional, systemic, and physical destruction) that are generally off-label (not US FDA approved), and whose use is limited by drawbacks or adverse effects. From pooled evidence-based medicine data, it is possible to conclude that significantly higher remission rates may be expected only with cryotherapy and salicylic acid used in combination.     

Reliability of solar keratosis clinical diagnosis: A prospective study

Usually solar keratoses (SK) are diagnosed clinically. However other diseases may clinically present as erythematous macules, papules or patches on sun‐exposed areas; therefore the histopathology remains the gold standard diagnostic tool. Our study, which assessed the efficacy of photodynamic therapy (PDT), showed that one in 20 clinically diagnosed SK lesions grade I–II identified by board‐certified dermatologists were rosacea and only one in 40 were malignant lesions. These findings should be considered by clinicians who treat clinically diagnosed grade I–II SK without response to treatment or diagnose the recurrence of SK after PDT.     

Distinct profile of the mitochondrial DNA common deletion in benign skin lesions

Mutations of mitochondrial (mt) DNA, particularly the 4977 bp long common deletion, are increased in aging tissues and preferentially found in chronologically and photoaged skin. Mutations of human mitochondrial DNA (mtDNA) have also been identified in malignant tumors of the skin and of other organs. However, benign skin lesions have not yet been investigated. We analyzed the frequency of the common deletion in 27 benign skin lesions [8 seborrheic keratoses (SK), 5 epidermal nevi (EN), 14 solar lentigos (SL)] by quantitative real-time PCR, because SK and especially SL have been related to (photo)aged skin. All SK and four of five EN displayed reduced common deletion levels compared with adjacent normal skin. In contrast, 50% of SL revealed a higher percentage of the common deletion than the adjacent normal skin, and some SL showed very high absolute common deletion levels up to 14% of total mtDNA. Our results show that the amount of the common deletion is significantly different in benign skin lesions and raise further questions regarding the pathogenesis of SL and its possible role as a precursor lesion of SK.     

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。     

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。     

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.     

Management of Cutaneous Warts

Cutaneous warts are benign epidermal proliferations caused by human papillomavirus infection. Treatment aims to cure the patient's physical and psychological discomfort, and to prevent the spread of infection by contact with other body areas or with other individuals. Among the available medical and destructive therapeutic options for cutaneous warts, none is uniformly effective or virucidal. Moreover, in most cases the safety and efficacy of these treatment options has not been assessed in randomized controlled trials, so that the reproducibility of many of the listed treatments is difficult to evaluate and a possible placebo effect cannot be ruled out. This article provides indications for the management of patients with cutaneous warts through an evidence-based approach, considering a first-, second-, and third-line therapy for each clinical form. The first line includes medical treatments useful to cure single, or few, and/or small common warts of short duration (<1 year). If these treatments have failed or are contraindicated, cryotherapy may be considered as second-line therapy. For recurrent or difficult-to-treat lesions, a third-line of therapy includes a variety of alternative therapeutic options that are in clinical use but are not necessarily approved by the US FDA, and their use may be further limited by adverse effects.     

Sporotrichoid cutaneous infection by Mycobacterium haemophilum in an AIDS patient

We report a case of primary cutaneous infection by Mycobacterium haemophilum after the bite of an aquarium fish in a severely immunodepressed AIDS patient. Clinical features consisted in nodular and ulcerative lesions that followed a sporotrichoid pattern. Histological study of nodular lesions showed a granulomatous dermatitis with numerous acid-fast bacilli. The mycobacterium was identified 3 months later by genetic hybridization from a cultive in solid medium. Combined therapy with isoniazid, rifampin, clarithromycin, ethambutol, amikacin and ciprofloxacin resulted in complete resolution of the lesions. Infection by Mycobacterium haemophilum is a rare mycobacteriosis that usually affects immunodepressed patients. The most common clinical manifestations are cutaneous lesions but the development of sporotrichoid nodular lymphangitis is exceptional.     

Targeted therapy of oral hairy leukoplakia with gentian violet

Oral hairy leukoplakia (OHL) is a common oral manifestation of HIV infection. Clinically, these lesions appear as white plaques on the edges of the tongue. Pathophysiologically, these lesions occur because of infection of oral epithelium with Epstein-Barr virus (EBV). No universally effective therapy exists for OHL. We have previously shown that EBV infection and EBV viral products induce the generation of reactive oxygen. We have also demonstrated that the Food and Drug Administration-approved over-the-counter medication gentian violet is a potent inhibitor of reactive oxygen species. We thus chose to treat a patient with biopsy-proven OHL with topical gentian violet. Gentian violet solution was applied topically to the tongue of a patient with OHL. Complete clinical resolution was noted after three treatments. Treatment with topical gentian violet resulted in resolution of the lesions. Further studies with larger numbers of patients are required. The application of gentian violet can be used as a method to OHL treatment. Gentian violet is an inexpensive and safe therapy and, given that it inhibits reactive oxygen, this old therapy is now a targeted novel therapy.     

脂溢性角化病的病因与治疗进展

脂溢性角化病是一种良性表皮角质形成细胞肿瘤.其病因尚不清楚,可能与遗传因素密切相关,流行病学研究显示年龄和紫外线暴露是本病独立的危险因素,细胞因子及感染可能与其发病有一定的关系.脂溢性角化病的治疗以冷冻、激光为主,但近年来也出现一些新的疗法,如局部外用三氯乙酸,系统应用阿维A等.     

Imported Tropical Infectious Ulcers in Travelers

Skin ulcers are a commonly encountered problem at departments of tropical dermatology in the Western world. Furthermore, the general dermatologist is likely to be consulted more often for imported chronic skin ulcers because of the ever-increasing travel to and from tropical countries. The most common cause of chronic ulceration throughout the world is probably pyoderma. However, in some parts of the world, cutaneous leishmaniasis is one of the most prevalent causes. Mycobacterium ulcerans is an important cause of chronic ulcers in West Africa. Bacterial infections include pyoderma, mycobacterial infections, diphtheria, and anthrax. Pyoderma is caused by Staphylococcus aureus and/or beta-hemolytic streptococci group A. This condition is a common cause of ulcerative skin lesions in tropical countries and is often encountered as a secondary infection in travelers. The diagnosis is often made on clinical grounds. Antibacterial treatment for pyoderma should preferably be based on culture outcome. Floxacillin is generally active against S. aureus and beta-hemolytic streptococci. Infection with Mycobacterium ulcerans, M. marinum, and M. tuberculosis may cause ulcers. Buruli ulcers, which are caused by M. ulcerans, are endemic in foci in West Africa and have been reported as an imported disease in the Western world. Treatment is generally surgical, although a combination of rifampin (rifampicin) and streptomycin may be effective in the early stage. M. marinum causes occasional ulcerating lesions in humans. Treatment regimens consist of combinations containing clarithromycin, rifampin, or ethambutol. Cutaneous tuberculosis is rare in travelers but may be encountered in immigrants from developing countries. Treatment is with multiple drug regimens consisting of isoniazid, ethambutol, pyrazinamide, and rifampin. Cutaneous diphtheria is still endemic in many tropical countries. Cutaneous diphtheria ulcers are nonspecific and erythromycin and penicillin are both effective antibacterials. Antitoxin should be administered intramuscularly in suspected cases. Anthrax is caused by spore-forming Bacillus anthracis. This infection is still endemic in many tropical countries. Eschar formation, which sloughs and leaves behind a shallow ulcer at the site of inoculation, characterizes cutaneous anthrax. Penicillin and doxycycline are effective antibacterials. Cutaneous leishmaniasis is caused by different species belonging to the genus Leishmania. The disorder is one of the ten most frequent causes of skin diseases in travelers returning from (sub)tropical countries. The clinical picture is diverse, ranging from a painless papule or nodule to an ulcer with or without a scab. Treatment depends on the clinical manifestations and the species involved.Sporotrichosis, chromo(blasto)mycosis, and mycetoma are the most common mycoses that may be accompanied by ulceration. Infections are restricted to certain regions and often result from direct penetration of the fungus into the skin. Anti-mycotic treatment depends on the microorganism involved. The most common causes of infectious skin ulceration encountered in patients from tropical countries who present at a department of tropical dermatology are reviewed in this article.     

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.