Standardization of dermoscopic terminology and basic dermoscopic parameters to evaluate in general dermatology (non-neoplastic dermatoses): an expert consensus on behalf of the International Dermoscopy Society.

BACKGROUND: Over the last few years, several articles on dermoscopy of non-neoplastic dermatoses have been published, yet there is poor consistency in the terminology among different studies. OBJECTIVES: We aimed to standardize the dermoscopic terminology and identify basic parameters to evaluate in non-neoplastic dermatoses through an expert consensus. METHODS: The modified Delphi method was followed, with two phases: (i) identification of a list of possible items based on a systematic literature review and (ii) selection of parameters by a panel of experts through a three-step iterative procedure (blinded e-mail interaction in rounds 1 and 3 and a face-to-face meeting in round 2). Initial panellists were recruited via e-mail from all over the world based on their expertise on dermoscopy of non-neoplastic dermatoses. RESULTS: Twenty-four international experts took part in all rounds of the consensus and 13 further international participants were also involved in round 2. Five standardized basic parameters were identified: (i) vessels (including morphology and distribution); (ii) scales (including colour and distribution); (iii) follicular findings; (iv) 'other structures' (including colour and morphology); and (v) 'specific clues'. For each of them, possible variables were selected, with a total of 31 different subitems reaching agreement at the end of the consensus (all of the 29 proposed initially plus two more added in the course of the consensus procedure). CONCLUSIONS: This expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This tool, if adopted by clinicians and researchers in this field, is likely to enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology. What's already known about this topic? Over the last few years, several papers have been published attempting to describe the dermoscopic features of non-neoplastic dermatoses, yet there is poor consistency in the terminology among different studies. What does this study add? The present expert consensus provides a set of standardized basic dermoscopic parameters to follow when evaluating inflammatory, infiltrative and infectious dermatoses. This consensus should enhance the reproducibility and comparability of existing and future research findings and uniformly expand the universal knowledge on dermoscopy in general dermatology.

[Dermoscopy in special locations : Nails, acral skin, face, and mucosa]. / Dermatoskopie in Sonderlokalisationen : Nägel, akrale Haut, Gesicht und Mukosa.

The use of dermoscopy by dermatologists across Europe has become a standard examination for benign and malignant skin lesions and increasingly also for inflammatory skin diseases. However, based on the experience of the authors from numerous dermoscopy courses, knowledge about important dermoscopic features in special locations such as mucosa or nails is often limited. This may be explained by (1) a different anatomy of the skin and its adnexa in special locations in comparison to the remaining integument, (2) difficult technical access to special locations with a dermatoscope, and (3) a rather low incidence of malignant skin neoplasms in areas of special locations (with the exception of facial skin/scalp). This article aims at explaining dermoscopic characteristics and features of important benign and malignant lesions of nails, acral skin, face, and mucosa.

Dermoscopy and the diagnosis of primary cutaneous B-cell lymphoma.

BACKGROUND: Primary cutaneous B-cell lymphomas (PCBCLs) are frequently misdiagnosed, and a biopsy is needed to attain the correct diagnosis. OBJECTIVE: To characterize the dermoscopic features of PCBCL. METHODS: In this retrospective observational study, we analysed the pathology reports of 172 newly diagnosed PCBCL for the initial clinical differential diagnosis. The dermoscopic images of 58 PCBCL were evaluated for dermoscopic features. Two dermoscopy experts, who were blinded to the diagnosis and the study objective, evaluated images from 17 cases for a dermoscopic differential diagnosis. RESULTS: Of 172 biopsy-proven PCBCL lesions, cutaneous lymphoma was suspected by the clinician in 16.3%; the leading diagnosis was basal cell carcinoma in 17.4%, and other skin neoplasms in 21%. Studying 58 PCBCL dermoscopic images, we most frequently identified salmon-coloured background/area (79.3%) and prominent blood vessels (77.6%), mostly of serpentine (linear-irregular) morphology (67.2%). Dermoscopic features did not differ significantly by subtype or location. Blinded evaluation by dermoscopy experts raised a wide differential diagnosis including PCBCL, arthropod bite, basal cell carcinoma, amelanotic melanoma and scar/keloid. CONCLUSIONS: Two dermoscopic features, salmon-coloured area/background and serpentine vessels, are frequently seen in PCBCL lesions. These characteristic dermoscopic features, although not specific, can suggest a possible diagnosis of PCBCL.

Prognostic relevance of lactate dehydrogenase and serum S100 levels in stage IV melanoma with known BRAF mutation status.

BACKGROUND: Activating mutations of BRAF provide an important treatment target in patients with melanoma. The prognostic role of several biochemical markers in relation to mutation status is not clear. OBJECTIVES: To analyse the prognostic significance of BRAF mutation in patients with melanoma and correlate it to different markers. METHODS: In total, 162 patients with stage IV melanoma and known BRAF mutation status were included. Clinical, histopathological and laboratory information was collected and compared between patients with BRAF mutant (BRAFm) and wild-type (BRAFwt) melanoma at the time of first distant metastasis. RESULTS: In total, 88 patients (54%) had BRAFm melanoma (V600E/V600K). At the first distant metastasis, S100B levels in BRAFm patients were more frequently elevated (P = 0·01) and significantly higher (P = 0·02). Median overall survival (mOS) was significantly longer in BRAFwt patients with normal compared with patients with elevated S100B levels (P < 0·01). In BRAFm melanoma, elevated S100B levels showed no prognostic influence (P = 0·18). Elevated lactate dehydrogenase (LDH) levels had a significantly negative impact on mOS in both groups. mOS was increased for BRAFm patients treated with a BRAF inhibitor (BRAFi) compared with BRAFm patients not receiving BRAFi (P = 0·01). No difference in mOS between BRAFm patients who did not receive BRAFi treatment and BRAFwt patients was observed. CONCLUSIONS: Better mOS was observed in BRAFm patients treated with BRAFi. BRAFm patients not treated with BRAFi show similar survival curves to BRAFwt patients. Elevated LDH is a BRAF-independent prognostic parameter; S100B has prognostic significance in BRAFwt melanoma only.

Spectophotometric intracutaneous analysis: an investigation on photodamaged skin of immunocompromised patients.

BACKGROUND: SIAscopy (Spectrophotometric Intracutaneous Analysis) enables non-invasive analysis of the skin. OBJECTIVE: We wanted to determine whether SIAscopy is able to detect and differentiate the skin chromophores melanin, collagen and haemoglobin and the influence of immunosuppressive drugs and other known risk factors for non-melanoma skin cancer (NMSC). METHODS: Volunteers and patients were measured by SIAscopy at six spots on sun-exposed and two spots on sun-protected skin. Measurements were transformed by SIAmetrics into arbitrary units and statistically analysed. RESULTS: Melanin was shown to be higher with age (+1.73759 a.u.; P < 0.0001), sun exposure (+47.03998 a.u.; P < 0.0001), immunosuppression (+10.48526 a.u.; P < 0.0001) and lower in males (-26.50952 a.u.; P < 0.0001). Collagen was lower with increasing age (-0.29162 a.u.; P < 0.0001) and sun exposure (-6.85586 a.u.; P < 0.0001) but higher with male sex (+8.34251 a.u.; P < 0.0001) and immunosuppression (+5.79171 a.u.; P = 0.0001). Haemoglobin was lower with increasing age (-0.23833 a.u.; P = 0.0005), but higher with male sex (+18.51976 a.u.; P < 0.0001) and sun exposure (+13.74523 a.u.; P < 0.0001). Haemoglobin content was not associated to immunosuppression. CONCLUSION: Our results encourage the use of SIAscopy as a tool to better gauge an individual patient's NMSC risk factors. Further studies should help to better delineate SIAscopy as a prognostic tool.

A multifaceted intervention: no increase in general practitioners' competence to diagnose skin cancer (minSKIN) - randomized controlled trial.

BACKGROUND: General practitioners (GPs) play crucial roles in early detection of skin cancer. A pilot-study found a positive short-term effect of a 1-day dermatologic education programme on GPs' diagnostic competence. OBJECTIVE: To determine effects of a multifaceted intervention, including technical equipment and continuing feedback by a dermatologist, on GPs' diagnostic skills regarding skin cancer. METHODS: Randomized controlled trial with 78 GPs of the Canton of Zurich, Switzerland. INTERVENTION: GPs in intervention group received a 1-day training, a Lumio (magnifying glass with polarized light, 3Gen), a Nikon digital camera and - during 1 year - feedback on skin lesion pictures sent to the dermatologist. GPs in control group only received the 1-day training. PRIMARY OUTCOME: structured assessment of GP's diagnostic skills in correctly diagnosing images of skin lesions regarding skin cancer. At baseline prior to intervention (T0), after the full-day training course in both groups (T1), and after 1 year of continuing feedback (T2) to the intervention group. MEASURES: Non-parametric unpaired (Wilcoxon-Mann-Whitney) tests were used to compare numbers of correctly classified skin lesions between both groups at T2 and for the change between T1 and T2. RESULTS: At T0, both groups classified a median of 23 skin lesions of the 36 images correctly. This value rose to 28 for both groups at T1 and fell to 24 for both groups at T2. No difference between control and intervention group at T2. Furthermore, we compared differences in the sum scores per GP between T1 and T2 for each group. Also in this comparison, no difference between control and intervention group was found. CONCLUSION AND RELEVANCE: No long-term effect of the multifaceted intervention was found on the competence to diagnose skin cancer by GPs. The positive short-term effect of the 1-day dermatologic education programme did not persist over 12 months.

Agreement of dermatopathologists in the evaluation of clinically difficult melanocytic lesions: how golden is the 'gold standard'?

BACKGROUND: The 'gold standard' for the diagnosis of melanocytic lesions is dermatopathology. Although most of the diagnostic criteria are clearly defined, the interpretation of histopathology slides may be subject to interobserver variability. OBJECTIVES: The aim of this study was to determine the variability among dermatopathologists in the interpretation of clinically difficult melanocytic lesions. METHODS: This study used the database of MelaFind®, a computer-vision system for the diagnosis of melanoma. All lesions were surgically removed and sent for independent evaluation by four dermatopathologists. Agreement was calculated using kappa statistics. RESULTS: A total of 1,249 pigmented melanocytic lesions were included. There was a substantial agreement among expert dermatopathologists: two-category kappa was 0.80 (melanoma vs. non-melanoma) and three-category kappa was 0.62 (malignant vs. borderline vs. benign melanocytic lesions). The agreement was significantly greater for patients ≥40 years (three-category kappa = 0.67) than for younger patients (kappa = 0.49). In addition, the agreement was significantly lower for patients with atypical mole syndrome (AMS) (kappa = 0.31) than for patients without AMS (kappa = 0.76). LIMITATIONS: The data were limited by the inclusion/exclusion criteria of the MelaFind® study. This might represent a selection bias. The agreement was evaluated using kappa statistics. This is a standard method for evaluating agreement among pathologists, but might be considered controversial by some statisticians. CONCLUSIONS: Expert dermatopathologists have a high level of agreement when diagnosing clinically difficult melanocytic lesions. However, even among expert dermatopathologists, the current 'gold standard' is not perfect. Our results indicate that lesions from younger patients and patients with AMS may be more problematic for the dermatopathologists, suggesting that improved diagnostic criteria are needed for such patients.

Clinical and dermoscopic characteristics of amelanotic melanomas that are not of the nodular subtype.

BACKGROUND: Amelanotic melanomas remain challenging to diagnose. OBJECTIVE: To analyze and describe the clinical and dermoscopic characteristics of amelanotic melanomas that are not of the nodular subtype. PATIENTS/METHODS: We conducted a retrospective review of 20 consecutively diagnosed amelanotic melanomas. The clinical and dermoscopic images of pathologically confirmed amelanotic melanomas that were not of the nodular subtype were analyzed. In addition, the clinical diagnosis and the reasons why these lesions were biopsied were examined. RESULTS: All 20 amelanotic melanomas were erythematous and lacked any of the clinical ABCD features commonly attributed to melanoma. The lesions appeared clinically to be relatively symmetric with regular borders and manifesting a circular to oval morphology. Dermoscopically, all lesions manifested polymorphous vascular pattern. CONCLUSIONS: Amelanotic melanomas that are not of the nodular subtype often present as clinically symmetric erythematous lesions. Therefore, it is important to consider AMs in the differential diagnosis of isolated and persistent erythematous outlier lesions, even if they are symmetric in appearance. Additionally, the presence of a polymorphous vascular pattern seen with dermoscopy can facilitate in correctly identifying these melanomas.

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 of scalp tumours: a multi-centre study conducted by the international dermoscopy society.

BACKGROUND: Little is known about the dermoscopic features of scalp tumours. Objective To determine the dermoscopic features of scalp tumours. METHODS: Retrospective analysis of dermoscopic images of histopathologically diagnosed scalp tumours from International Dermoscopy Society members. RESULTS: A total of 323 tumours of the scalp from 315 patients (mean age: 52 years; range 3-88 years) were analysed. Scalp nevi were significantly associated with young age (<30 years) and exhibited a globular or network pattern with central or perifollicular hypopigmentation. Melanoma and non-melanoma skin cancer were associated with male gender, androgenetic alopecia, age >65 years and sun damage. Atypical network and regression were predictive for thin (≤1 mm) melanomas, whereas advanced melanomas (tumour thickness > 1 mm) revealed blue white veil, unspecific patterns and irregular black blotches or dots. CONCLUSIONS: The data collected provide a new knowledge regarding the clinical and dermoscopy features of pigmented scalp tumours.

Diagnostic pitfall: pigmented lesion of the nipple--correlation between dermoscopy, reflectance confocal microscopy and histopathology.

We present an unusual case of a nevus of the nipple changing during pregnancy which caused a diagnostic pitfall. Nevi on the nipple and areola are infrequent, and diagnostic criteria for clinical, dermoscopy or reflectance confocal microscopy examination for nevi in this 'special location' are still missing. We comment on the literature on dermoscopic findings in mammary lesions and their management during pregnancy, as well as the challenging histopathology of nevi along the milk line. Finally, we focus on two main limitations of reflectance confocal microscopy: the misinterpretation of dendritic cells and the limitation of the imaging depth.

Dermoscopy patterns of nevi associated with melanoma.

It is well known that dermoscopy improves the diagnostic accuracy of pigmented skin lesions. Many dermoscopic criteria can be found both in nevi and in melanoma. For the correct interpretation of those criteria, formal training and clinical experience in dermoscopy is needed. This paper reviews the global and local dermoscopic features seen both in nevi and melanoma and focuses on the interpretation of those findings in order to differentiate between benign and malignant melanocytic skin tumors.

Dermoscopy of superficial spreading melanoma.

Knowledge and insights gained over the past few decades pertaining to the clinical and dermoscopic primary morphology of melanoma has greatly increased the authors' appreciation of the varied faces of this malignancy. This knowledge has improved their ability to detect early melanoma and may in part explain the observed increase in the percentage of thin melanomas being diagnosed today as compared to the past. The authors have previously published in this journal an article on the dermoscopic patterns of melanoma. In this review they will focus on specific dermoscopic structures that are frequently observed in the most common subtype of melanoma, the superficial spreading melanoma.

[Follow-up of melanoma lesions]. / Surveillance des lésions mélanocytaires.

Due to the early diagnosis, melanomas can be diagnosed in early stages. Most melanomas tend not to show morphological criteria of malignancy in the very early stages. They rather resemble benign moles. For patients with hundreds of atypical lesions, follow-up examinations using digital dermoscopy are very helpful. This technique enables the physician to monitor lesions and to detect microscopic change. Lesions with microscopic change are thought to be high risk lesions and should be removed this will represent important savings for the health system because this will allow to make the diagnosis of melanoma in earlier stages and to save costs for unnecessary surgery. In this article we are going to review the technique.

The immunogenic properties of poly(dI).poly(dC) and poly(rI). poly(dC)--analysis by monoclonal antibodies.

Eight monoclonal antibodies were prepared from a C57/black mouse which had been immunized with poly(rI).poly(dC). Two of the antibodies were specific for the RNA-DNA duplex but bound about 100-fold better to poly(rI).poly(dC) than to poly(rA).poly(dT). The other six antibodies were single-strand specific and bound to poly(rI) and in most cases to poly(dI) as well, but not to other single-stranded nucleic acids. Similarly, 10 monoclonal antibodies were produced from mice immunized with poly(dI).poly(dC). Nine of these were specific for poly(dI) while the other had a strong preference for poly(dC). Thus, in contrast to poly(rI).poly(dC), the all DNA duplex poly(dI). poly(dC) only elicits duplex specific antibodies at very low frequency, if at all.

Specificity of monoclonal antibodies produced against phosphorothioate and ribo modified DNAs.

A large number of phosphorothioate DNAs and mixed ribo/deoxyribo duplexes were prepared and their immunogenicity was studied in mice. Only those polymers which were nuclease-resistant were immunogenic and in these cases monoclonal antibodies were prepared. The specificity of the antibodies was measured by direct and competitive Solid Phase Radioimmune Assay (SPRIA) and on this basis four types of antibody could be identified. Type I antibodies are specific for the immunizing polymer and show very limited crossreactivity. For example, Jel 384 binds only to poly(dsA).poly(dT); Jel 453 and 462 bind only to poly(dsG).poly(dC) and poly(dsG).poly(dm5C). Type II antibodies bind to most polymers containing the appropriate modification but will not bind to unmodified DNAs. For example, Jel 343 binds to most thio DNAs regardless of sequence; Jel 346 binds well to most ribose-containing polymers and may be a useful reagent for the detection of the 'A' family of conformations. Type III antibodies bind to most nucleic acids whether modified or not. Their specificities are similar to autoimmune antibodies. Type IV antibodies are single strand-specific such as Jel 383 which binds to poly(dT). There were no examples of antibodies which bound specifically to the immunizing DNA and the unmodified polymer. Thus, modified DNAs cannot be used to prepare sequence-specific reagents. Also, the immunogenicity of modified nucleic acids may limit their usefulness in antisense technologies.

Immunization of neonates with DNA encoding a bovine herpesvirus glycoprotein is effective in the presence of maternal antibodies.

Neonates generally display low immune responsiveness to conventional vaccines, which may be due to the immaturity of their immune system and interference by maternal antibodies. Because of the unique capacity of plasmid DNA for the production of low doses of antigen over extended periods of time, we used DNA immunization as an approach to induce immunity in neonates. Previously, we demonstrated that a plasmid encoding a truncated secreted version of bovine herpesvirus-1 gD (tgD) induces protective immunity in adult animals. For the present study, 3-day-old lambs were immunized intradermally with the tgD-expressing plasmid. The lambs developed antibody as well as T-cell responses to the tgD glycoprotein, which clearly demonstrates the ability of the animals to respond to vaccination at this age. Furthermore, lambs born to tgD-hyperimmunized ewes, thus containing high levels of passively acquired serum antibodies, responded to the tgD DNA vaccine in a similar manner, which shows that the maternal antibodies did not inhibit the development of an immune response. These results indicate that DNA immunization might be a useful approach to vaccinate neonates that possess high levels of maternal antibodies.

The use of a juvenile hormone binding protein for the quantitative assay of juvenile hormone.

The suitability of the haemolymph juvenile hormone binding protein (JHBP) of Locusta migratoria for use in a competition assay for juvenile hormone (JH) III has been investigated, and a simple quantitative assay procedure using this protein has been developed. JHBP partially purified from haemolymph of precocene treated adult locusts gives rapid and stable binding of [3H]10R-JH III, and can be separated from the unbound hormone with hydroxylapatite (HAP). The sensitivity of the method is such that 0.15 pmol (40 pg) 10R-JH III gives 50% displacement of [3H]10R-JH III from the binding protein. Competition by JH II is about 5 times less and JH I about 10 times less than that by JH III, JH III diol and acid compete at least 1000 times less strongly. A procedure for extraction and assay of JH from 50 microliters haemolymph samples is described, the interference by non-specific haemolymph components is shown to be relatively small, and some data on JH III titres in maturing adult locusts are presented.

Hypoluminescence microscopy of pigmented skin lesions.

Since the 'renaissance' of epiluminescence microscopy (ELM), histological correlation of ELM structures has been the subject of many investigations. Direct correlation is difficult because of the methodological differences between ELM and histopathology. In order to further understand the features of pigmented skin lesions (PSLs), we studied whether hypoluminescence microscopy (HLM) had any advantages over ELM. Twenty pigmented skin lesions scheduled for surgical excision were chosen randomly for this study. After excision, the lesions were studied using standard ELM and an HLM technique. For the latter, illumination was performed from the dermal side. The HLM pattern was clearly different from that of ELM. In all lesions the 'deeper' (dermal) structures became more visible. Some structures already visible in ELM appeared more visible, particularly structures apparently localized in deeper layers of the PSL. For highly pigmented lesions the difference in the two approaches was striking. With the HLM technique details became visible, and structures which were hardly or not visible with the classic ELM approach could be easily distinguished and evaluated. In conclusion, HLM is a simple, easy to use, reproducible ex vivo technique that is able to provide additional information to the conventional ELM technique.