Diagnosis Of Cutaneous Melanoma Research Articles

Dermatoscopia: o método de análise de padrões

A incidência do melanoma cutâneo tem aumentado mundialmente e, por tratar-se de neoplasia bastante agressiva e de difícil tratamento em estádios mais avançados, o diagnóstico precoce é fundamental para a cura do paciente. A dermatoscopia surgiu como exame auxiliar in vivo, que tem papel fundamental na realização do diagnóstico precoce e amplifica a acurácia diagnóstica do melanoma. Para a realização do método, é necessário utilizar o dermatoscópio, aparato que permite aumentar a lesão, no mínimo, 10 vezes. A imagem obtida é interpretada utilizando-se o método diagnóstico da preferência do examinador. O método de Análise de Padrões é atualmente o mais utilizado e o que possui maior acurácia para o diagnóstico do melanoma cutâneo, tendo-se demonstrado confiável para o ensino de residentes em dermatologia. Baseia-se em padrões globais e específicos que permitem diferenciar as lesões melanocíticas das não melanocíticas (também importantes no diagnóstico diferencial com o melanoma cutâneo), assim como identificar lesões melanocíticas consideradas benignas, suspeitas ou malignas.

Structural Correlations Between Dermoscopic Features of Cutaneous Melanomas and Histopathology Using Transverse Sections

Interpretation of dermoscopic features of cutaneous melanoma is based on histologic description of perpendicular sections of the lesions that does not reflect the overview achieved by epiluminescence. We describe the utilization of transverse sections as a tool to define the histopathology of features that are the dermoscopic hallmarks of cutaneous melanoma. From a collection of 23 pigmented lesions with the dermoscopic diagnosis of cutaneous melanoma submitted for surgical excision we selected, from each specimen, one dermoscopic feature (black dots and globules, brown dots, blues dots and globules, depigmentation, broadened network, radial streams or pseudopods) that was sampled with a 4-mm punch (specimen) to obtain perpendicular and transverse sections. Using this strategy, it was possible to correlate the histopathology of all features that are often used as criteria for diagnostic dermoscopy. The black dots were pigmented neoplastic cells at the dermal-epidermal junction (DEJ) and within the epidermis in heavily pigmented columns. Similar findings were seen in brown dots, however there was slightly less pigment. No statistical difference was observed between brown dots and black dots regarding size, area and number of atypical cellnests. Blue dots correlated to melanophages, surrounding the superficial vascular plexus. Depigmentation was characterized by intense fibrosis of the papillary dermis. The pigmented network showed atypical pigmented or non-pigmented melanocytes at the DEJ and epidermis as well as heavily pigmented keratinocytes in the basal cell layer. The radial streaming and pseudopods had neoplastic cells in nests, a stratified growth pattern arranged in centrifugal linear extensions, resembling a arborescent branching. The results represented herein, are an important tool for understanding histopathological alterations responsible for dermoscopic features and for improving the efficacy of this diagnostic method.

Cutaneous melanoma: making a clinical diagnosis, present and future

The minimum requirement for the general dermatologist for clinically assessing pigmented skin lesions is dermoscopy. In expert hands, this technique has been shown to improve both the sensitivity and specificity for the diagnosis of melanoma. This is also reflected by lower benign melanoma excision ratios and decreased excision rates. Evidence is mounting for the routine use of total body skin photography for patients with a very high risk of developing cutaneous melanoma. Both long-term (12 months) and short-term (3 months) digital dermoscopy monitoring has been shown to allow the detection of dermoscopically featureless melanoma and is central for the clinical assessment of melanocytic lesions at the Sydney Melanoma Diagnostic Center. The use of automated instruments for the diagnosis of cutaneous melanoma is still in an experimental phase, and its utility is dependent on the evidence that such instruments give a clinically useful expert second opinion. Currently, other noninvasive diagnostic techniques, such as in vivo confocal scanning laser microscopy, are reserved for clinical research settings.

Molecular targets in melanoma: Strategies and challenges for diagnosis and therapy

In coming years, we expect rapid advances in cutaneous melanoma diagnosis and therapy, because of the incorporation of new technologies into experimental and clinical research. Major discoveries in melanoma are often made by investigators outside the field, and the melanoma research community will need to develop a better means of incorporating these advances into their work, to capitalize on the promise they hold for patients. A far greater level of cooperation between labs and clinics will be to bring new technology-based discoveries from bench-to-bedside and back. Metastatic melanoma should become a treatable disease in the next few years, because specific inhibitors are expected for most major targets. However, major challenges lie ahead in securing funding, building infrastructure and gaining expertise in new technologies. To meet these challenges, multidisciplinary collaborations will be required all the more.

Cutaneous, ocular and visceral melanoma in African Americans and Caucasians

The incidence and age-specific rates of cutaneous, ocular and visceral melanoma were compared in blacks, whites and other ethnic groups using data obtained from the Surveillance, Epidemiology and End Results (SEER) Program of the National Cancer Institute for the years 1973-2001. As the SEER Program is now more mature and includes a larger proportion of minority populations, we thought it important to revisit these observations in more detail. Overall, the rate of cutaneous melanoma was higher in white males but, prior to 50 years of age, the rate was higher in white females. Compared with white males, white females and black males and females had proportionally higher rates of melanoma on the lower extremities. Cutaneous and ocular melanomas were, as expected, more common in whites than in blacks or in other groups. The age-specific rates for ocular and cutaneous melanoma were similar for blacks and other ethnic groups, but differed from those of whites. Patients with a previous diagnosis of cutaneous melanoma had a significantly higher probability of developing ocular melanoma than the general population. Age-specific rates were similar in all three groups for visceral melanoma. In all three racial/ethnic groups, age-specific rate patterns were different between cutaneous, ocular and visceral melanoma, suggesting a different pathogenesis. Visceral melanoma develops later in life, after the age of 60 years, compared with cutaneous or ocular melanomas.

Seasonal variation in the diagnosis of cutaneous melanoma and non-cutaneous malignancies: an Italian population-based study

The aim of the present study was to investigate whether or not the diagnosis of cutaneous melanoma and non-cutaneous tumours shows seasonal variations. Data from the Tuscany Cancer Registry, central Italy, for malignant cutaneous melanomas (no. 2062) and non-skin cancers (no. 114,755), diagnosed during 1985-2000, were used to evaluate the monthly variation in the number of diagnoses. The chi-squared test was used to evaluate the heterogeneity in the monthly number of cancer diagnoses throughout the year and to compare monthly proportions between groups. Poisson multivariate regression was used to estimate the monthly risk of cancer diagnosis. Clear monthly variations were evident for both melanoma and non-cutaneous cancers, but the monthly diagnosis distributions differed. Statistically significant peaks in June [relative risk (RR), 1.54] and July (RR, 1.40) and a lower risk for January (RR, 0.76), in comparison with the mean monthly value, were documented for melanoma. Monthly risks were similar for thin (< or =1 mm) and thick (>1 mm) melanomas and for males and females. A peak in May-June and October and significantly lower numbers of cases in August and December were detected for all non-skin cancers. The holiday periods may influence the seasonality in the diagnosis of melanomas and non-cutaneous cancers. However, the monthly fluctuation for melanoma differed from that for non-cutaneous cancers; the peak in July suggests an additional effect of summer clothing, with fewer clothes worn and more skin visible, on melanoma diagnosis.

Early Diagnosis of Cutaneous Melanoma

The incidence of cutaneous melanoma has increased over the past several decades, making its early diagnosis a continuing public health priority. The ABCD (Asymmetry, Border irregularity, Color variegation, Diameter >6 mm) acronym for the appraisal of cutaneous pigmented lesions was devised in 1985 and has been widely adopted but requires reexamination in light of recent data regarding the existence of small-diameter (< or =6 mm) melanomas. Cochrane Library and PubMed searches for the period 1980-2004 were conducted using search terms ABCD and melanoma and small-diameter melanoma. Bibliographies of retrieved articles were also used to identify additional relevant information. Available data do not support the utility of lowering the diameter criterion of ABCD from the current greater than 6 mm guideline. However, the data support expansion to ABCDE to emphasize the significance of evolving pigmented lesions in the natural history of melanoma. Physicians and patients with nevi should be attentive to changes (evolving) of size, shape, symptoms (itching, tenderness), surface (especially bleeding), and shades of color. The ABCD criteria for the gross inspection of pigmented skin lesions and early diagnosis of cutaneous melanoma should be expanded to ABCDE (to include "evolving"). No change to the existing diameter criterion is required at this time.

Digital image analysis for diagnosis of cutaneous melanoma. Development of a highly effective computer algorithm based on analysis of 837 melanocytic lesions

Digital image analysis has been introduced into the diagnosis of skin lesions based on dermoscopic pictures. To develop a computer algorithm for the diagnosis of melanocytic lesions and to compare its diagnostic accuracy with the results of established dermoscopic classification rules. In the Department of Dermatology, University of Tuebingen, Germany, 837 melanocytic skin lesions were prospectively imaged by a dermoscopy video system in consecutive patients. Of these lesions, 269 were excised and examined by histopathology: 84 were classified as cutaneous melanomas and 185 as benign melanocytic naevi. The remaining 568 lesions were diagnosed by dermoscopy as benign. Digital image analysis was performed in all 837 benign and malignant melanocytic lesions using 64 different analytical parameters. For lesions imaged completely (diameter < or = 12 mm), three analytical parameters were found to distinguish clearly between benign and malignant lesions, while in incompletely imaged lesions six parameters enabled differentiation. Based on the respective parameters and logistic regression analysis, a diagnostic computer algorithm for melanocytic lesions was developed. Its diagnostic accuracy was 82% for completely imaged and 84% for partially imaged lesions. All 837 melanocytic lesions were classified by established dermoscopic algorithms and the diagnostic accuracy was found to be in the same range (ABCD rule 78%, Menzies' score 83%, seven-point checklist 88%, and seven features for melanoma 81%). A diagnostic algorithm for digital image analysis of melanocytic lesions can achieve the same range of diagnostic accuracy as the application of dermoscopic classification rules by experts. The present diagnostic algorithm, however, still requires a medical expert who is qualified to recognize cutaneous lesions as being of melanocytic origin.

Management of cutaneous melanoma.

Cutaneous melanoma remains a management challenge. This year an estimated 55,000 Americans will receive a diagnosis of cutaneous melanoma, and 7900 will die from the disease. The authors of this review discuss the pathogenesis and management of cutaneous melanoma and provide perspective on treatment options.

Germline CDKN2A mutations are rare in child and adolescent cutaneous melanoma.

Early-onset melanoma under the age of 20 years is still a rare disease but has an increasing incidence. The aim of this study was to determine whether CDKN2A germline mutations are present in patients diagnosed with childhood/adolescent melanoma. From the Swedish Cancer Register we identified 60 patients with a diagnosis of cutaneous malignant melanoma before the age of 20 years. A medical history including information on self-reported melanoma heredity was obtained, a physical examination was performed by a dermatologist, and the histopathology slides were reviewed. A blood test was obtained for analysis of germline CDKN2A exon 1 and exon 2 mutations by DNA sequencing. We found only one germline CDKN2A mutation with functional significance, which was an exon 1 missense mutation resulting in a proline-to-leucine substitution in codon 48. This mutation was seen in a patient belonging to a previously reported kindred with hereditary melanoma where this particular germline CDKN2A mutation had been identified. Thus, in the large majority of cutaneous melanoma in childhood/adolescence, any underlying genetic alterations have yet to be identified.

4 Pitfalls in the diagnosis of cutaneous melanoma and its prognostic indicators

Imperial College London, Division of Investigative Science and the Melanoma Unit, Charing Cross Hospital, London, UK Abstract section INVITED SPEAKERS

Current technologies for the in vivo diagnosis of cutaneous melanomas

The rising incidence of cutaneous malignant melanoma has been observed in the past decades. 1,2 Currently, there is no cure for metastatic melanoma; only early diagnosis followed by prompt excision of cutaneous lesions ensures a good prognosis. The clinical ABCD rule 3 is created as a framework for differentiating melanomas from benign pigmented skin lesions, and it serves as the basis for current clinical diagnosis. The ABCD rule relies on four simple clinical morphologies of melanoma: 1) Asymmetry, 2) Border irregularity, 3) Color variegation, and 4) Diameter greater than 6 mm. Although it is valuable, it has its limitations. Currently, the diagnostic accuracy for physicians is about 65%. 4 This statistic implies that 1) melanomas with subtle signs are missed as benign lesions, and 2) benign lesions are over diagnosed as melanomas, which lead to unnecessary biopsies.

Seasonal variations in the diagnosis of cutaneous melanoma

Seasonal patterns in diagnosis were examined in 7836 patients with cutaneous melanoma (clinical stage I and II) documented at the Department of Dermatology and Allergology at Ludwig-Maximilian-University in Munich, Germany, between 1977 and 2000. Of these patients, 2362 were first given a diagnosis in the summer months (June-August) and 1757 were first given a diagnosis in the winter months (December-February). A summer-to-winter ratio was determined for sex, age, anatomic tumor site, histopathologic subtype, and tumor thickness. The summer-to-winter ratio was 1.34 (95% confidence interval: 1.27-1.43) for all patients, with a ratio of 1.22 (95% confidence interval: 1.12-1.33) for men and 1.47 (95% confidence interval: 1.35-1.60) for women. The frequency of diagnosis of cutaneous melanoma was seasonal for all age classes, for all anatomic tumor sites, for all histopathologic subtypes except acrolentiginous melanomas, and for melanomas with a tumor thickness <3.0 mm. Comparing supgroups of the above-mentioned clinical and histopathologic parameters, significant differences could be observed for sex and anatomic tumor site. On the basis of this data, possible explanations for the diagnostic summer peak may be a greater awareness as a result of clothing habits in summertime or because of incurred sunburns in patients with skin type I and II, and the influence of public-health campaigns usually performed at the beginning of summer.

High prevalence of hypothyroidism among patients with cutaneous melanoma

We have previously reported a high prevalence of hypothyroidism among patients with uveal melanoma. The objectives of the present study were to determine if a similar pattern of thyroid pathology exists among patients with cutaneous melanoma as well. To address this question, the medical records of all patients registered at the University of Texas M.D. Anderson Cancer Center with a diagnosis of cutaneous melanoma during the years 1997 and 1998 were examined for a history of overt hypothyroidism, defined as a requirement for thyroid hormone replacement. Data regarding stage and site of the primary tumor were obtained for these patients and for age/gender matched euthyroid controls from the same melanoma study population. Among 1,580 cutaneous melanoma patients (948 M/632 F), 111 (7.0%) gave a history of hypothyroidism [23/948 M (2.4%) and 88/632 F (13.9%)]. The prevalences of hypothyroidism for both males and females were significantly higher than those reported for the general population. Characteristics of the primary tumor did not differ between cases and controls, although there was a trend for a lower rate of primary tumor ulceration among the hypothyroid case subjects. We conclude that hypothyroidism of varied etiologies is common among patients with cutaneous melanoma. These data suggest that melanoma may be responsive to hormones of the thyroid hormone control loop, raising many questions of clinical and biologic importance.

Early diagnosis of malignant melanoma: Proposal of a working formulation for the management of cutaneous pigmented lesions from the Melanoma Cooperative Group

Epiluminescence microscopy (ELM) strongly improves the separation of different types of cutaneous pigmented lesions (CPL) and facilitates the early diagnosis of cutaneous melanoma (CM). ELM alone is not 100% accurate in routine diagnosis, and should not be considered the only criterion in the diagnosis of high-risk skin lesions. We have however, demonstrated close agreement between ELM classification criteria and histology in 2,731 cutaneous lesions. In the past five years, our Melanoma Cooperative Group has evaluated 61,000 skin lesions from 30,000 individuals and identified 478 cutaneous melanomas. Most newly diagnosed patients had very early stage melanoma [299 (62%) were Stage I (203 Stage IA and 96 Stage IB), by the American Joint Committee on Cancer (AJCC) criteria]. We have compared data from the patient histories and clinical evaluations with ELM-based morphological patterns to better characterize skin lesions and minimize interpretative problems. From these comparisons, we propose new guidelines for the management of CPL to provide a standard diagnostic and therapeutic approaches and to foster the early identification of lesions at risk for malignant transformation.

Modified ABC-point list of dermoscopy: A simplified and highly accurate dermoscopic algorithm for the diagnosis of cutaneous melanocytic lesions

Background: The use of dermoscopy (epiluminescence microscopy, surface microscopy, dermatoscopy) improves clinical diagnostic sensitivity by 10% to 27%, particularly achieved by different algorithms or scores. Objective: We sought to develop a simplified and highly accurate dermoscopic-point list for cutaneous melanocytic lesions. Method: We studied consecutive patients with suspicious melanocytic lesions, which were excised and histopathologically examined at our institution. On the basis of the ABCD rule of Stolz, Menzies score, and the modified ABCD rule of Kittler, a simplified ABC-point list was developed. Simple points were given for the following: asymmetry of outer shape (A) or differential structures inside the lesion in at least 1 axis ((A)); the abrupt cutoff of network at the border in at least one quarter of circumference (B); 3 or more colors (C); 3 or more differential structures (D); or noticed change (evolution) in the last 3 months (E). Using 20-fold magnification of computer dermoscopy, the sensitivity, specificity, and diagnostic accuracy were examined in 269 cutaneous melanocytic lesions. Of these, 84 (31.2%) were cutaneous melanomas. Also, the sensitivity, specificity, and diagnostic accuracy were investigated with a 7-point checklist and the 7 features for melanoma. Results: With the ABC-point list for the diagnosis of cutaneous melanoma, sensitivity was 90.5%, specificity was 87%, and diagnostic accuracy was 88.1%, confirmed by cross-validation. The ABCD rule resulted in 90.5%, 72.4%, and 78.1%; Menzies score in 95.2%, 77.8%, and 83.3%; 7-point checklist in 90.5%, 87%, and 88.1%; and 7 features for melanoma in 94%, 74.6%, and 80.7%, respectively, Conclusions: The ABC-point list is simpler than the already established algorithms. Despite its simplicity, a high sensitivity, specificity, and diagnostic accuracy was achieved. This simplified approach in dermoscopic diagnostics may contribute to further spread and enable to learn and use this method more easily. (J Am Acad Dermatol 2003;48:672-8.)

A two-year regional program for the early detection of cutaneous melanoma.

A regional program for the early diagnosis of cutaneous melanoma involving general practitioners was effective in 1997-1998 in the Friuli Venezia Giulia region in Northern Italy. The aim of the 2-year program was to evaluate the role of a skin examination performed by general practitioners in people older than 18 years without known skin lesions and spontaneously presenting to their offices for any reason, with referral of suspect cases to a pre-identified regional dermatology or plastic surgery institution. In the preparatory phase (late 1995 and 1996), all general practitioners operating in the Friuli Venezia Giulia region (n = 1,038) were asked to participate in the program. Support from all regional dermatology, pathology and plastic surgery institutions was obtained. Operational procedures for the management of referred people were defined, and educational meetings directed to general practitioners interested in the program were held. Skin examinations by general practitioners started at the end of 1996 and took place during 1997 and 1998. Subsequently, information was obtained from participating general practitioners and from pathology institutions about the number and thickness of diagnosed melanomas, as well as the number of diagnosed skin carcinomas and dysplastic nevi. In addition, the thickness distribution of all melanomas diagnosed in the Friuli Venezia Giulia region before and during the program was obtained. A total of 153 general practitioners participated in the program, but only 74 were active and assessable. A total of 11,040 skin examinations was performed by these 74 general practitioners (median, 75 per general practitioner). In all, 820 people (7.4%) were referred for dermatological evaluation (median, 8 per general practitioner). Among these 820 people, at least 38 melanomas (4.6% of referred cases) were detected (18 < or = 1.5 mm, 11 > 1.5 mm thick, unknown in 9). The dermatological examinations/diagnosed melanomas ratio was 21. In addition, 94 skin carcinomas and 50 dysplastic nevi were detected. At the regional level, the percentage of thin melanomas rose from 65.3% in 1995-96 to 72.2% in 1997-98 (P = 0.04), whereas the number of thick melanomas declined. In our study, only a few general practitioners chose, in the absence of incentives, to participate in the study. However, the yield of melanomas, most of which were thin, was considerably high and the workload was acceptable. This compares favorably to experiences where dermatologists were involved directly without a filter work by general practitioners.

Delay in the diagnosis of cutaneous melanoma: an analysis of 233 patients.

Knowledge of factors associated with the detection of cutaneous malignant melanomas and reasons for delay in diagnosis are essential for the improvement of secondary prevention of cutaneous melanoma. For this reason, the extent and consequence of patient and professional delay in diagnosis and treatment was investigated in 233 patients with histologically proven primary cutaneous melanomas seen at the Department of Dermatology and Allergology at the Ludwig-Maximilians-University, Munich, Germany, between January 1999 and January 2001. Personal interviews were conducted by two physicians to obtain information on patients' knowledge of melanoma symptoms, sun behaviour, delay in seeking medical attention, professional delay and related factors. The main component of delay was patient related. Nearly one-third (29.2%) of all patients reported a delay interval of more than 12 months from the onset of an observed change in a pigmented lesion or first detection of a pigmented lesion to the first visit to a physician. The delay interval from the first visit to a physician to surgical treatment was shorter (< 1 month) in most of our patients (74.7%). The predominant symptoms of melanoma detected by patients were a change in colour and an increase in size or elevation. Most patients had obtained knowledge about cutaneous melanomas from television and magazines. A delay in diagnosis and a history of many sunburns and outdoor leisure time activities were not associated with a greater tumour thickness. However, fairer skin types, lower education levels and lack of knowledge about cutaneous melanoma were associated with a greater tumour thickness. Further efforts are necessary to improve public and medical education about early detection and prompt surgical treatment, which is known to be the most effective treatment modality for cutaneous melanomas.

A simple classification of the resolution and depth of imaging systems for pigmented skin lesions.

The resolving power of imaging systems used in the diagnosis of cutaneous malignant melanoma is usually presented in the literature in terms of numerical values, yet it is often difficult for the reader to ascertain what tangible information these systems are extracting. This paper presents a classification system of two aspects of imaging systems that allows rapid appraisal of the resolution of the different imaging systems used in the diagnosis of melanoma and the additional clinical information they reveal.

Confocal scanning laser microscopy of benign and malignant melanocytic skin lesions in vivo

Background: The ability of physicians for early diagnosis of cutaneous melanomas is less than perfect, prompting research into noninvasive methods for diagnosis. Objective: Our purpose was to evaluate confocal scanning laser microscopy (CSLM) for noninvasive imaging of benign and malignant melanocytic lesions in vivo. Methods: Forty pigmented skin lesions (including adjacent normal skin as control) in vivo were imaged with near-infrared CSLM. The confocal images were correlated to histopathology. Results: Nuclear, cellular, and architectural detail in the epidermis and superficial dermis is imaged with high resolution and contrast. Melanin causes the cytoplasm of pigmented cells to appear bright. Melanocytic nevi had cohesive nests of uniformly circular cells and increased microvascular blood flow. Melanomas had a polymorphous cytologic structure, containing atypical, pleomorphic cells in disarray and irregular dendritic cells. Conclusion: CSLM is capable of identifying distinct patterns and cytologic features of benign and malignant pigmented skin lesions in vivo. CSLM may be useful to noninvasively discriminate benign and malignant lesions in vivo. (J Am Acad Dermatol 2001;45:365-76.)