Examples of melanomas diagnosed in follow-up (A-C) and melanomas referred for evaluation (D-F) with their clinical (top) and dermoscopic (bottom) images. A, In situ melanoma in an 83-year-old man with a history of personal melanoma (total dermoscopy score [TDS], 4.3). B, In situ melanoma arising on a melanocytic nevus in a 48-year-old man (TDS, 2.6). C, In situ melanoma in a 55-year-old man with a history of melanoma (TDS, 4.7). D, Superficial spreading melanoma, Breslow index 0.8 mm, in a 65-year-old man (TDS, 8.7). E, Superficial spreading melanoma, Breslow index 1.8 mm, in a 55-year-old man (TDS, 8.4). F, Superficial spreading melanoma, Breslow index 1.1 mm, in an 84-year-old man (TDS, 8.3).
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Salerni G, Lovatto L, Carrera C, Puig S, Malvehy J. Melanomas Detected in a Follow-up Program Compared With Melanomas Referred to a Melanoma Unit. Arch Dermatol. 2011;147(5):549–555. doi:10.1001/archdermatol.2010.430
Dermoscopy increases sensitivity in the clinical diagnosis of melanoma from 60% to 90%, with a specificity as high as 95%.1 This increase in diagnostic accuracy is reflected by a minor excision rate and a decrease in the benign to malignant ratio.2 Digital dermoscopy monitoring devices allow the follow-up of melanocytic lesions to detect changes over time, offering the double benefit of increasing the possibility that melanoma will not be overlooked with any or few specific criteria of malignancy and minimizing the excision of benign lesions.3
The efforts to improve melanoma prognosis have also been focused on the identification and follow-up of individuals with increased risk. Fair-skinned persons, persons who tan with difficulty, blond or red-haired persons, and persons with blue eyes have more risk of developing melanoma than the general population.4 The presence of many pigmented lesions, including freckles and clinically typical or atypical nevi; intermittent sun exposure and severe sunburns, especially during childhood; and exposure to artificial UV-A radiation have all been associated with an increased risk of melanoma. The history of a previous melanoma is associated with a high risk for the development of a second primary melanoma.4 Patients with a strong family history of melanoma and atypical mole syndrome (AMS) represent the population of persons who are at major risk of developing melanoma. Hereditary mutations in CDKN2A and CDK4 genes result in a 30% to 90% risk of melanoma throughout life.5-7
The aim of our study was to assess the clinical, dermoscopic, and histologic features of melanomas diagnosed in individuals included in follow-up programs in a specialized unit (follow-up melanomas [FUMMs]) and melanomas diagnosed in patients referred to the same unit for evaluation of suspicious lesions (referred melanomas [RMMs]) but not included in a specific follow-up program.
We conducted a retrospective analysis of clinical and dermoscopic characteristics of 215 melanomas consecutively excised and diagnosed in our unit over a 2-year period. The study included primary lesions with clinical and dermoscopic pictures of acceptable quality to allow reliable evaluation. Patients who were referred to our unit with a diagnosis of melanoma after excision or biopsy were excluded from the study (n = 302), as were melanoma recurrences or cutaneous metastases of prior melanomas (n = 9).
One of us (C.C.) collected all melanomas diagnosed between January 2007 and December 2008 that met inclusion criteria for the study from our database; clinical data such as age and sex of the patients and the location and size of the lesions were incorporated along with the clinical and dermoscopic images in a PowerPoint presentation (Microsoft Corp, Redmond, Washington). This collection was presented to 2 dermatologists with experience in dermoscopy (G.S. and L.L.) who performed both clinical and dermoscopic evaluation while blinded to the origin of the lesions (RMM or FUMM), identity of the patients, and histologic features of the lesions. For the clinical evaluation of the lesions, the ABCD clinical criteria for early detection of melanoma8 were used. The dermoscopic evaluation was performed using the ABCD rule of dermoscopy proposed by Stolz et al,9 which is based on the evaluation of 4 criteria: asymmetry (A), abrupt borders (B), colors (C), and differential dermoscopic structures (D). The total dermoscopy score (TDS) was calculated in each lesion.
The global pattern classification was made according to the subtypes proposed in the pattern analysis10 for the evaluation of melanocytic lesions and their differentiation between benign and malignant. These global patterns are reticular, globular, homogeneous, “starburst,” parallel, multicomponent, and unspecific.
Our Melanoma Unit, which is composed of a multidisciplinary team, belongs to the Dermatology Department of the Hospital Clinic of Barcelona, Barcelona, Spain. The hospital is a tertiary and high-complexity center that provides service for the public health system in Catalonia (population of about 7 million), where a network of melanoma centers is integrated by main hospitals. Almost 30% of melanomas in Catalonia are attended directly in our unit. Patients who have been examined by primary care physicians and/or area dermatologists are referred according to a specific derivation protocol that includes filling out a referral form and a schedule of visits within 48 hours for the evaluation of highly suspicious lesions or within 2 months for their incorporation in a follow-up program once they have been identified as high-risk individuals. The criteria for inclusion in our follow-up program include moderate to severe AMS, presence of a congenital nevus of medium to giant size, AMS and previous melanoma, familial melanoma, presence of genetic mutations related to melanoma risk, and syndromes associated with melanoma risk.
As standard practice in our unit, at every visit the patients undergo a complete clinical examination with a handheld dermoscope (Dermlite DL100 and Dermlite II Pro Hybrid; 3Gen LLC, Dana Point, California).When necessary, a digital record of atypical lesions is performed with a digital dermoscopic device (MoleMax II; Derma Medical Systems, Vienna, Austria) to assess whether follow-up should be short, medium, or long term, according to the judgment of the evaluator. High-risk patients are included in a follow-up program with total-body photographs and digital dermoscopy, according to the 2-step method previously described,11 with follow-up visits once or twice a year. In our study, 8 and 32 patients were scheduled for follow-up once and twice a year, respectively. Once a suspicious lesion is identified, a high-resolution dermoscopic photograph (Dermlite Foto; 3Gen LLC) is taken before surgical excision.
Because this was a retrospective study and had no influence on the established clinical treatment of patients, no ethics committee approval was required. Each patient's written consent was obtained for all invasive procedures.
Analysis of variables included clinical information about the patient (sex, age at diagnosis, personal and familial history of melanoma, nevi count, presence of AMS, skin phototype, hair and eye color, degree of lentiginosis, presence of solar elastosis, and personal history of basal cell carcinoma); clinical information about the lesion (clinical ABCD, clinical stage at diagnosis); dermoscopic features (ABCD rule of dermoscopy, TDS, global pattern); and histologic characteristics (histological subtype, Breslow index, Clark level, association with melanocytic nevus, and presence of ulceration).
The χ2 test was used to compare qualitative variables, applying Fisher correction when needed because of the small sample size in tables of 2 × 2, and the t test was used to compare means. Differences were considered to be statistically significant at P ≤ .05.
Of the melanomas diagnosed in 2007 and 2008 in our Melanoma Unit, 215 fulfilled the inclusion criteria of the study, 50 (23.3%) corresponded to clinical suspicious lesions diagnosed in follow-up in our unit (FUMMs), and 165 (76.7%) corresponded to clinically suspicious lesions referred for evaluation (RMMs).
Of the 201 patients (105 men and 96 women) who were diagnosed as having melanoma in the study, 40 were included in the follow-up program in our unit, and 161 were referred for evaluation. The distribution according to sex was homogeneous in both groups. The mean age of the patients with FUMMs was significantly lower (49.9 years vs 61.7 years) than that of the patients with RMMs (P < .001).
Twenty-four patients (60%) included in the follow-up were diagnosed as having melanoma before our study began, compared with only 8 of the patients (5.0%) who were referred to our unit (P < .001). Atypical mole syndrome was more frequent among patients in follow-up, who also had a higher nevi count (P < .001). Three patients with xeroderma pigmentosum were followed up in our unit, and 1 patient with albinism was referred for evaluation. No significant differences between the 2 groups were observed in skin phototype (P = .59), hair and eye color (P = .64), degree of lentiginosis (P = .65), presence of solar elastosis (P = .10), or personal history of basal cell carcinoma (P = .86). Patients in follow-up had more family histories of melanoma and AMS than patients referred for assessment (P < .001). Data related to the study population are summarized in Table 1.
Most of the lesions in both groups were clinically asymmetrical: 142 of the RMMs (86.0%) and 35 of the FUMMs (70%) (P = .18). Irregular borders, multiple colors, and a diameter larger than 6 mm were found more frequently in RMMs than in FUMMs; these differences were statistically significant (P = .02, P < .001, and P < .01). Only 12% of the FUMMs (n = 6) fulfilled the 4 ABCD criteria, while the number was 63.6% in the RMM group (Table 2).
The FUMMs were less asymmetrical than the RMMs (P < .001), with fewer abrupt borders (P = .003) and less variety of colors (P < .001), and they displayed fewer dermoscopic structures (P = .002). The TDS was significantly lower in the group of FUMMs (mean value, 5.04 vs 6.39) (P < .009). Eighteen of the FUMMs (36%) were misclassified as benign according to the TDS value, whereas this misclassification happened in only 11 of the RMMs (6.6%). All these differences were statistically significant (Table 3). In the FUMM group, 19 melanomas (38%) were diagnosed because of changes in digital follow-up, since they had no specific criteria for malignancy at the time of excision (Figure).
In the FUMM group, the reticular pattern was the most frequent, observed in 32 melanomas (64%), followed by an unspecific and a multicomponent pattern in 8 cases each (16%) and by a parallel and a globular pattern in 1 case each (2%).The starburst pattern was not observed in the FUMM group. In the RMM group, the most frequent global pattern was the multicomponent pattern, with 102 cases (61.8%), followed by the reticular pattern in 32 cases (19.3%), an unspecific pattern in 24 cases (14.5%), the starburst and the globular pattern in 3 cases each (1.8%), and the parallel pattern in 1 case (0.6%). These differences were statistically significant (P < .001).
Two different dermatopathologists reviewed all the histopathology slides. When there was discordance between the clinical-demoscopic presumptive diagnosis and the histopathologic report, cases were discussed in dermatopathologic conference. A consensus diagnosis was reached in all cases.
Among all melanomas, the most frequent histologic subtype was the superficial spreading type, with 149 cases (69.3%); followed by the lentigo maligna type, with 43 cases (20.0%); the acral lentiginous type, with 18 cases (8.4%); and the nodular type, with 5 cases (3.0%). Except for the nodular melanomas, all of which were RMMs, the distribution of histologic subtypes in both groups was similar, and the differences were not statistically significant (P = .19).
Of the FUMMs, 35 (70%) were in situ, while only 46 of the RMMs (27.9%) were in situ. A significantly lower proportion of melanomas in the FUMM group were Clark II or III than in the RMM group, and none of the FUMMs were Clark IV or V (P < .001). Among invasive melanomas, the Breslow index was significantly lower in the FUMM group, with a mean (range) of 0.53 (0.25-0.90) mm compared with 1.74 (0.25-13.00) mm in the RMM group (P < .001). Histologic ulceration was observed in 23 RMMs (14.1%); none of the FUMMs were ulcerated (P = .003). Sixteen of the RMMs (9.7%) and 10 of the FUMMs (20%) developed in association with a preexistent melanocytic nevus (P = .80) (Table 4).
The clinical stage of the melanomas was classified according to the American Joint Committee on Cancer staging system.12 Of the FUMMs, 35 (70%) presented as stage 0 at diagnosis and 15 (30%) as stage IA. Of the RMMs, 46 (27.9%) presented as stage 0 at diagnosis, 62 (37.6%) as stage IA, 21 (12.7%) as stage IB, and 18 (10.9%) as stage II; 14 (8.5%) and 4 (2.4%) presented as stage III and IV, respectively. These differences were statistically significant (P < .01).
Over the last few decades, efforts in secondary prevention of melanoma have been focused on early recognition and prompt derivation of suspicious lesions. In 1985, the ABCD acronym was designed8 to provide simple parameters for the detection of suspicious pigmented skin lesions that might require evaluation by a specialist. The sensibility and specificity of these criteria may vary when they are used separately or in combination, and sensitivity decreases as specificity increases.13 The addition of E, for evolution, has substantially improved the ability of clinicians and the general population to detect melanomas at an early stage by recognizing their natural dynamics. The latter criterion is especially important for the diagnosis of nodular melanoma, which frequently, at least initially, is symmetrical, with regular borders and few colors.14-19 The following EFG acronym has been suggested for the recognition of nodular melanoma: E for elevation, F for firm, and G for growth. Although 35 of 50 of FUMMs were clinically asymmetrical, just 27 of 50 had irregular borders, 23 had multiple colours or 22 a diameter greater than 6 mm, and only 6 fulfilled the 4 ABCD clinical criteria, which raises the question of their usefulness in the recognition of early malignant lesions. In our study, 28 of the lesions in the FUMM group (56%) had a diameter equal to or less than 6 mm, which supports the current main critique of the ABCD clinical system by pointing out that a significant proportion of malignant melanomas may be less than 6 mm in diameter and that they have different aspects and begin as small lesions. No nodular melanoma was diagnosed in patients included in follow-up during the study; this may be explained by the small sample size and the relatively short term of follow-up, which was not sufficient to include the possibility of the occurrence of an early nodular melanoma.
The FUMMs had a lower TDS than the RMMs (5.00 vs 6.42) according to the ABCD rule of dermoscopy proposed by Stolz et al,9 since they were less asymmetrical, with fewer abrupt edges, fewer colors, and fewer dermoscopic structures. In our study, only 50% of the FUMMs but almost 90% of the RMMS were correctly classified as malignant according to the TDS value, which indicates that melanomas that are difficult to diagnose even with dermoscopy can be detected during follow-up. Furthermore, it should be noted that more than half of FUMMs were small lesions (≤6 mm in diameter); in 2001, Pizzichetta et al20 reported that the ABCD rule did not seem useful in managing small melanocytic skin lesions, in which specific criteria for melanoma might not yet be present. Whether structured algorithms might be more useful in the assessment of these early lesions is a matter for further analysis.
The multicomponent pattern is defined by the combination of 3 or more distinctive dermoscopic structures within a given lesion.10 This pattern was observed in more than 60.0% of RMMs but in only 16% of FUMMs; in the latter group, the reticular pattern was the most frequent (64%). If we consider that in the patients under surveillance malignant melanomas are diagnosed in an early phase of tumor progression, when lesions are smaller and display fewer structures and thus have a lower TDS value, it is reasonable to expect that incipient lesions preserve their original structures and that with tumor progression other features of malignant melanomas may appear, elevating the TDS value.
The inclusion of high-risk patients in specific digital programs has proved to be useful as a strategy in early melanoma detection, not only allowing the diagnosis of lesions with a low index of suspicion but also leading to a reduction in the biopsy rates and improving the benign to malignant ratio of the excised lesions.3,21-24 Most melanomas diagnosed in patients under surveillance in a digital program were in situ; they were thinner among invasive ones; and none were ulcerated. None of the 50 FUMMs required sentinel lymph node biopsy.
In a similar study held in New Zealand, Barker et al25 compared melanomas referred by general practitioners and those identified in specialist clinics. They found 49% in situ melanomas and a mean Breslow index of 0.57 mm among melanomas detected at plastic surgery or dermatology clinics and 33% in situ melanomas and a mean Breslow index of 1.45 mm among melanomas referred by general practitioners. Recently, in our region, Marcoval et al26 conducted a study to analyze the changes in incidence of melanoma. They found 30.94% in situ melanomas and a mean Breslow index of 1.86 in the melanomas diagnosed between 1998 and 2006 in another tertiary-level hospital in Catalonia; both values are very similar to those found in the group of melanomas referred to our unit.
Beyond the differences in personal and family history in the risk for melanoma, the mean age of patients diagnosed as having melanoma during follow-up was significantly lower than that of the patients referred to our unit, a finding that could have 2 possible explanations: first, the presence of high risk for melanoma could be associated with the occurrence of melanoma at an earlier age, and second, surveillance aids in the the early diagnosis of melanoma, when the patients are younger and the lesions are diagnosed at initial stages.
Our study does not lack limitations because lesions referred for assessment in our unit were suspicious enough to justify their derivation. Furthermore, an inestimable number of melanomas might not have been referred because they were not clinically or dermoscopically suggestive of melanoma or because they were thin melanomas that were excised without derivation to a referral center. The age of the 2 groups was not equal; it was higher in the RMM group, which could also make a difference in the 2 population groups.
The present study shows the increasing trend in the diagnosis of thin melanomas in our population. This increase is attributable to the early recognition and identification of high-risk individuals. Otherwise, those melanomas will evolve and will be diagnosed as thick and evolved lesions, with positive ABCD clinical criteria.
The inclusion of patients who are high risk for melanoma in follow-up programs allows the detection of melanomas in early stages, with good prognosis, even in the absence of clinical and dermoscopic features of melanoma. In the general population without specific surveillance, melanoma continues to be diagnosed at more advanced stages. Our findings suggest that current efforts in public and medical education might have no substantial effect in this group. Further strategies and educational programs may be needed to improve the early detection of these lesions. We believe that high-risk individuals, whenever proper resources are available, should be referred to melanoma centers or qualified institutions for regular follow-up.
Correspondence: Susana Puig, MD, PhD, Melanoma Unit, Dermatology Department, Hospital Clinic Barcelona, Villarroel 170, 08036 Barcelona, Spain (firstname.lastname@example.org; email@example.com)
Accepted for Publication: November 2, 2010.
Published Online:January 17 2011 doi:10.1001/archdermatol.2010.430
Author Contributions: Drs Salerni, Puig, and Malvehy had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Salerni, Puig, and Malvehy. Acquisition of data: Salerni, Lovatto, Carrera, Puig, and Malvehy. Analysis and interpretation of data: Salerni, Lovatto, Carrera, Puig, and Malvehy. Drafting of the manuscript: Salerni, Lovatto, and Puig. Critical revision of the manuscript for important intellectual content: Carrera, Puig, and Malvehy. Statistical analysis: Salerni and Puig. Study supervision: Puig and Malvehy.
Financial Disclosure: None reported.
Funding/Support: The work at the Melanoma Unit is partially funded by grants 03/0019, 05/0302, and 06/0265 from Fondo de Investigaciones Sanitarias and from the Centros de Investigacion Biomedica en Red de Enfermedades Raras of the Instituto de Salud Carlos III.
Role of the Sponsors: The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; or in the preparation, review, or approval of the manuscript.
Additional Contributions: This work was performed with the participation of the following members of the Melanoma Unit: Llúcia Alós, Ana Arance, Pedro Arguís, Antonio Campo, Teresa Castel, Carlos Conill, Daniel Ga briel, Pablo Iglesias, Jaime Jimeno, Jose Palou, Ramon Rull, Marcelo Sánchez, Sergi Vidal-Sicart, Antonio Vilalta, and Ramon Vilella. We are grateful to all the clinicians who sent the patients to us and to those patients who kindly agreed to allow us to image their tumors and to use the images for scientific purposes.