Seborrhoeic keratosis or occult malignant neoplasm of the skin?

BACKGROUND: Seborrhoeic keratosis is generally considered to be a benign lesion of the skin. OBSERVATION: We present the case of a 68-year-old male who presented with clinically typical seborrhoeic keratosis that later histological examination showed partially covered an occult basal cell carcinoma. OBJECTIVE: To have an indication of what percentage of clinically apparent seborrhoeic keratoses may be associated with some form of histologically proven skin malignancy. METHODS: We carried out a retrospective analysis of approximately 23,000 histopathological examinations done on specimens from dermatological lesions. RESULTS: Fifty-nine (11.9%) clinically apparent seborrhoeic keratoses were later histologically diagnosed as basal cell carcinomas, 17 (3.4%) as squamous cell carcinomas, and five (1.01%) as malignant melanomas. CONCLUSIONS: Although the association of seborrhoeic keratosis and skin malignancy appears to be relatively uncommon, the possibility of such an association cannot be ruled out.     

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.     

Photodynamic therapy: A targeted literature review focussing on outcomes and optimisation in solid organ transplant recipients

Squamous cell carcinoma incidence is 65- to 250-fold in solid organ transplant recipients, BCC is 10-fold and in Australia, rates of skin cancer in solid organ transplant recipients reach 70–82% prevalence within the first 20 years; hence, effective, evidence-based treatment of early and precancerous lesions is an essential tool in dermatological patient care. Photodynamic therapy is used to treat a range of conditions including actinic keratoses, squamous cell carcinoma in situ, superficial basal cell carcinoma and nodular basal cell carcinoma. A literature review was undertaken to examine the outcomes of photodynamic therapy in solid organ transplant recipients and methods of optimising outcomes in solid organ transplant recipients. Study sizes were small and protocols varied widely, so meta-analysis was not possible; however, photodynamic therapy appears to be an acceptable treatment for approved indications in solid organ transplant recipients in whom ongoing surveillance is maintained to ensure clearance and detect recurrence. Methods for improving efficacy were also reviewed for this population. Improved outcomes may be achieved by combining photodynamic therapy with other local methods such as 5-fluorouracil or ablative fractional laser.     

Dermatological feasibility of multimodal facial color imaging modality for cross‐evaluation of facial actinic keratosis

Background/Purpose: Digital color image analysis is currently considered as a routine procedure in dermatology. In our previous study, a multimodal facial color imaging modality (MFCIM), which provides a conventional, parallel‐ and cross‐polarization, and a fluorescent color image, was introduced for objective evaluation of various facial skin lesions. This study introduces a commercial version of MFCIM, DermaVision‐PRO, for routine clinical use in dermatology and demonstrates its dermatological feasibility for cross‐evaluation of skin lesions. Methods/Results: Sample images of subjects with actinic keratosis or non‐melanoma skin cancers were obtained at four different imaging modes. Various image analysis methods were applied to cross‐evaluate the skin lesion and, finally, to extract valuable diagnostic information. DermaVision‐PRO is potentially a useful tool as an objective macroscopic imaging modality for quick prescreening and cross‐evaluation of facial skin lesions. Conclusion: DermaVision‐PRO may be utilized as a useful tool for the cross‐evaluation of widely distributed facial skin lesions and as an efficient database management of patient information.     

In vivo confocal laser scanning microscopy of melanocytic skin tumours: diagnostic applicability using unselected tumour images

BACKGROUND: In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool that allows the noninvasive examination of skin cancer morphology in real time at a 'quasi-histopathological' resolution viewing microanatomical structures and individual cells. OBJECTIVES: To validate diagnostic confocal examination of melanocytic skin tumours using unselected tumour images. METHODS: In the present study, we used a total of 3709 unselected CLSM tumour images obtained from 20 malignant melanomas and 50 benign naevi. The entire set of images derived from each tumour was evaluated by independent observers. Classification tree analysis based on a subsample of 857 tumour images was performed to develop a diagnostic algorithm. RESULTS: Overall, sensitivity and specificity of 97.5% and 99% could be achieved by the independent observers (positive predictive value 97.5%, negative predictive value 99%). Classification tree analysis yielded a three-step algorithm based on only three morphological CLSM features, facilitating a correct classification in 92.4% of the benign naevus images and 97.6% of melanoma images. CONCLUSIONS: In vivo CLSM augurs a sea change in the way we will view skin tumour processes clinically at the bedside and merits application for use as a screening tool in skin oncology.     

Diagnosis of cutaneous tumors with in vivo confocal laser scanning microscopy

In recent years, in vivo confocal laser scanning microscopy (CLSM) has become an established method for the non‐invasive examination of the skin. In vivo CLSM allows for real‐time imaging of micro‐anatomic cutaneous structures. It has been used to diagnose ambiguous skin tumors and to measure subclinical tumor spread prior to surgery. By additionally providing high power morphologic information, in vivo CLSM helps to reduce unnecessary biopsies. A multitude of diagnostic features for skin tumors has been published. Here we review published diagnostic in vivo CLSM features, and compare them to our own experience in 100 tumors. In combination with clinical examination and dermatoscopy, in vivo CLSM is a valuable additional tool for non‐invasive skin tumor diagnosis.     

Study design and preliminary results from the pilot phase of the PraKtis study: self-reported diagnoses of selected skin diseases in a representative sample of the Italian population

BACKGROUND: Few data are available on the prevalence of common skin disorders like actinic keratoses in the general population. Such data are mostly needed to better define health needs and to organize medical services. The Prevalence of Actinic Keratoses in the Italian Population Study (PraKtis) was designed to estimate the point prevalence of actinic keratoses and related disorders, e.g. photoaging, in a representative sample of the Italian population. Within the study, information on the history of relevant dermatological diagnoses was also collected. METHODS: The study was conducted in collaboration with DOXA, the Italian branch of the Gallup International Association. A representative sample of people aged 45 years or older was selected by picking them from the electoral rolls according to a stratified random sampling design involving a replacement procedure. A total of 180 interviewers specifically trained to collect data on skin diseases and to take photographs of representative lesions on the face and upper limbs, contacted and interviewed the sampled subjects and performed a face-to-face computer-assisted interview. A final sample of about 12000 subjects was foreseen. RESULTS: The pilot phase of the study was conducted between January 1 and June 30, 2003. A total of 3660 subjects were recruited and interviewed. Overall, an estimated 37% of Italian people reported having ever undergone a dermatological consultation in the past. An estimated 29% reported having ever received a specific dermatological diagnosis by a physician. The frequency of specifically enquired diagnoses, weighted according to the distribution of the Italian population, was as follows: atopic dermatitis 4.7%, other eczematous dermatitides 4.3%, urticaria 4.3%, psoriasis 3.1%, skin tumors 1.6%, vitiligo 0.7% and actinic keratoses 0.3%. CONCLUSION: Skin diseases are frequently reported. The prevalence of actinic keratoses according to self-reported diagnoses was lower than expected based on prevalence data obtained by directly examining people. These discrepancies may be due to underreporting and/or unawareness of lesions by affected people. More precise estimates will be obtained by direct examination of sampled people.     

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.     

Wavelength effects on contrast observed with reflectance in vivo confocal laser scanning microscopy

Background/purpose: The ability to optically section live biological tissue in vivo with laser light is made possible by confocal laser scanning microscopy (CLSM). In this work, the effects of changing the wavelength of incident light used for CLSM imaging of human skin are reported and analyzed.
Methods: Optical phantoms and the skin of eight human volunteers were imaged using CLSM systems having three different incident light wavelengths (405, 785, and 830 nm).
Results: Qualitative and quantitative differences were observed between images obtained at each wavelength, despite the proximity of the two near infrared 785 and 830 nm wavelengths. Furthermore, the penetration depth achieved with the 405 nm CLSM permitted imaging into the papillary dermis.
Conclusion: The laser wavelength used in CLSM reflectance imaging is important to properly understand and resolve different biological structures within human skin.     

Diagnostic applicability of in vivo confocal laser scanning microscopy in melanocytic skin tumors

In vivo confocal laser scanning microscopy (CLSM) represents a novel imaging tool that allows the examination of skin morphology in real time at a resolution equal to that of conventional microscopes. The aim of the study was to test the applicability of CLSM to the diagnostic discrimination of benign nevi and melanoma. five independent observers without previous experience in CLSM received a standardized instruction about diagnostic CLSM features. Subsequently, 117 melanocytic skin tumors (90 benign nevi and 27 melanoma), imaged using a commercially available, near-infrared, reflectance confocal laser scanning microscope, were evaluated by each observer. Overall, sensitivity of 88.15% and specificity of 97.60% was achieved by the five observers. Logistic regression analysis revealed that mainly cytomorphology, architecture and keratinocyte cell borders should be taken into account for diagnostic decisions. Remarkably, using the presence or absence of monomorphic melanocytes as a single diagnostic criterion, the classification results with a sensitivity of 98.15% and a specificity of 98.89% were superior to the intuitive, integrative judgement of the observers. This first sensitivity and specificity study with CLSM has yielded promising results. CLSM provides new and useful information to the clinician diagnosing melanocytic skin tumors.     

Squamous-cell carcinoma arising in solar keratosis of a leprosy patient: relationship with positive skin smear examination.

A 70-year-old Japanese female with lepromatous leprosy developed squamous-cell carcinoma within a long standing area showing solar keratoses on her head. Alopecia had been present at least for the preceding 34 years on her forehead and frontal area of the head, and solar keratoses had existed at least for the previous 9 years. Skin smear examination for acid-fast bacilli which had continually been negative for the previous 2 years (during which 8 examinations were done) became positive. We assume that there may be some relationship between the onset of the tumor and the positive skin smear examination, although the exact connection remains unclarified.     

Detection of human papillomavirus DNA in nongenital seborrhoeic keratoses

The histological similarities of seborrhoeic keratoses and common warts led to the investigation of the possible occurrence of human papillomavirus DNA (HPV-DNA) in a large number of nongenital seborrhoeic keratoses using the in situ hybridization technique. All specimens derived from normal skin (n=173) were negative for the applied HPV-DNA probe, whereas the HPV genome was detected in 34 of 173 seborrhoeic keratosis specimens (19.65%). Of 34 HPV-positive specimens, 15 contained types 6/11 and 14 types 31/33/35, and 5 showed no positive reaction to the applied types. These results suggest that a considerable percentage of nongenital seborrhoeic keratoses may be related to an HPV infection.Dedicated to Professor Dr. H. Ippen on the occasion of his 70th birthday     

Nicotinamide and the skin

Nicotinamide, an amide form of vitamin B3, boosts cellular energy and regulates poly‐ADP‐ribose‐polymerase 1, an enzyme with important roles in DNA repair and the expression of inflammatory cytokines. Nicotinamide shows promise for the treatment of a wide range of dermatological conditions, including autoimmune blistering disorders, acne, rosacea, ageing skin and atopic dermatitis. In particular, recent studies have also shown it to be a potential agent for reducing actinic keratoses and preventing skin cancers.     

Imaging actinic keratosis by high‐definition optical coherence tomography. Histomorphologic correlation: a pilot study

With the continued development of non‐invasive therapies for actinic keratosis such as PDT and immune therapies, the non‐invasive diagnosis and monitoring become increasingly relevant. High‐definition optical coherence tomography is a high‐resolution imaging tool, with micrometre resolution in both transversal and axial directions, enable to visualize individual cells up to a depth of around 570 μm filling the imaging gap between conventional optical coherence tomography and reflectance confocal microscopy. We sought to determine the feasibility of detecting and grading of actinic keratosis by this technique using criteria defined for reflectance confocal microscopy compared to histology. In this pilot study, skin lesions of 17 patients with a histologically proven actinic keratosis were imaged by high‐definition optical coherence tomography just before excision and images analysed qualitatively. The surrounding normal looking skin has been used as control group. In lesional skin, dyskeratotic and atypical keratinocytes could be noticed with this new technique. An atypical honeycomb pattern in variable degree or a disarranged epidermal pattern could be observed. A good correlation between the dimension of atypia and/or disarrangement of the spinous–granular layer on en face images and the histopathological grading could be demonstrated. Relevant cross‐sectional imaging criteria could be defined for the different histopathological variants of actinic keratoses. The surrounding skin displayed features of photodamage. Using features already suggested by reflectance confocal microscopy, the study implies that high‐definition optical coherence tomography facilitates in vivo diagnosis of actinic keratosis and allows the grading of different actinic keratosis lesions for increased clinical utility.     

In vivo imaging of intradermal tattoos by confocal scanning laser microscopy

BACKGROUND/AIMS: In vivo confocal laser scanning microscopy (CLSM) is a new method for high-resolution imaging of intact skin in situ. Horizontal mapping of the outer skin is provided (magnification x 1000). OBJECTIVES: Tattooing is popular all over the world; however, tattooed skin has not been studied in using CLSM. RESULTS: Tattoos in two volunteers were studied using the Vivascope1500 of Lucid Inc. Subepidermal massive deposits of dense, clustered pigment granules up to about 3 mum in size corresponding to black tattoos, and more scarce and diffuse deposits, corresponding to red, blue and green tattoos, were observed. Diffuse pigment granules tended to accumulate in the outer dermis underneath the level of the basement membrane zone. CONCLUSIONS: Dermal pigments from tattoos can be imaged in vivo using CLSM. This application of CLSM has an important future potential for pre-evaluation of tattoos before laser removal, predicting good or poor outcome of laser removal.     

In vivo characterization of minipig skin as a model for dermatological research using multiphoton microscopy

Minipig skin is one of the most widely used non-rodent animal skin models for dermatological research. A thorough characterization of minipig skin is essential for gaining deeper understanding of its structural and functional similarities with human skin. In this study, three-dimensional (3-D) in vivo images of minipig skin was obtained non-invasively using a multimodal optical imaging system capable of acquiring two-photon excited fluorescence (TPEF) and fluorescence lifetime imaging microscopy (FLIM) images simultaneously. The images of the structural features of different layers of the minipig skin were qualitatively and quantitatively compared with those of human skin. Label-free imaging of skin was possible due to the endogenous fluorescence and optical properties of various components in the skin such as keratin, nicotinamide adenine dinucleotide phosphate (NAD(P)H), melanin, elastin and collagen. This study demonstrates the capability of optical biopsy techniques, such as TPEF and FLIM, for in vivo non-invasive characterization of cellular and functional features of minipig skin, and the optical image-based similarities of this commonly utilized model of human skin. These optical imaging techniques have the potential to become promising tools in dermatological research for developing a better understanding of animal skin models, and for aiding in translational pre-clinical to clinical studies.     

5% fluorouracil chemowraps in the management of widespread lower leg solar keratoses and squamous cell carcinoma

Elderly patients with extensive hypertrophic solar keratoses and squamous cell carcinoma on the lower legs can pose significant management challenges. Typically these patients require surgical treatment which is complicated by comorbidities and poor background lower leg skin. 5% fluorouracil chemowraps provides a useful alternative technique for the management of diffuse hypertrophic solar keratoses and as an adjuvant, and in some situations as a palliative treatment, for squamous cell carcinomas on the lower legs.