Differentiating Dysplastic Nevi From Melanoma-Reply
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As Dr Whitmore notes, for any individual pigmented lesion on the skin, the final diagnosis can only be made after biopsy of the lesion. Clinically diagnosed dysplastic nevi span a continuum from minimally abnormal nevi that barely fulfill criteria for diagnosis of dysplastic nevi to markedly abnormal nevi that cannot clinically be distinguished from early melanoma and need to be biopsied to rule out either in situ or invasive melanoma. At either end of the spectrum, the clinical diagnosis is difficult. In selecting the photographs, we chose representative samples of all of the types of nevi (in the middle of the spectrum clinically). Patients with florid dysplastic nevi may have many, sometimes hundreds, of abnormal-appearing nevi. At the time of initial examination, of course, any lesion that is suspicious for melanoma should be removed. Removal of all unusual-appearing nevi is not recommended, however, because (1) the chance of any 1Keywords:
Dysplastic nevus
Melanoma diagnosis
To the Editor: I thank Stewart Cramer, M.D., for his comments on my article “Atypical Histologic Features in Melanocytic Nevi”(1). Dr. Cramer agrees that the histologic features proposed as diagnostic of dysplastic nevus are not specific. He also agrees that a new diagnostic approach (analytic diagnosis, i.e., to diagnose nevi as junctional, compound and dermal, reporting any atypical characteristics (2) and the class number) may be opportune. However, Dr. Cramer disagrees with the conclusion that dysplastic nevus is not a distinct histologic entity. I believe that dysplastic nevus cannot be considered a distinct histologic entity because its “left border” is not defined. If we imagine melanocytic lesions as lying on a continuum, dysplastic nevus, which has intermediate histologic characteristics, is located between “common” nevus and melanoma. To be considered a distinct histologic entity, dysplastic nevus should be distinguished clearly from “common” nevi and from melanoma (i.e., its “histologic borders”(3) should be well defined). Actually, although the “right border” of dysplastic nevus (facing melanoma) is rather well defined (4), the “left border” (facing common nevus) is not, because nevi do not form two distinct classes of lesions (common nevi with no atypical features and dysplastic nevi with all atypical features), but they form a complex spectrum of lesions with a progressively increasing incidence of atypical features. However, the fact that dysplastic nevus is not a distinct histologic entity does not imply that all nevi are equal in terms of risk for melanoma (at contiguous and noncontiguous sites) (5). The problem is to identify lesions implying an increased risk, if they exist and if they are histologically recognizable. I believe that they may exist, because a conspicuous proportion of melanomas seems to arise in a preexisting nevus. I am not sure that nevi implying an increased risk for melanoma are recognizable. I believe, however, we can try to identify them. I agree with Dr. Cramer that size of nevi may be an important parameter, although nevi smaller than 5 mm seem to have the same histologic characteristics of nevi greater than 5 mm. I also agree that in the spectrum of nevi, lesions showing a high number of atypical features (Class 5 nevi, and Class 6 nevi, which I have also observed in another series of nevi) may be potential candidates to be lesions implying an increased risk for melanoma. Of course, further studies are needed. First of all, however, it is necessary to diagnose nevi more accurately and to stratify them histologically in objectively defined classes of lesions. Then, it will be possible to investigate the obtained different classes of nevi at all levels and to study corresponding patients clinically and epidemiologically. Carmelo Urso, M.D.
Dysplastic nevus
Melanocytic nevus
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A lack of consensus as to the clinical and histologic characteristics of dysplastic nevi has resulted in the recommendation to abandon the term dysplastic nevus for the more descriptive atypical nevus or atypical mole. The significance of the presence of one or more such lesions, histologic features notwithstanding, has not been carefully examined. The risk of melanoma was assessed in individuals with atypical nevi monitored regularly in our Pigmented Lesion Clinic. Any patient enrolled in this subspecialty clinic between 1980 and 1985 without the diagnosis of melanoma who had at least one sufficiently atypical-appearing nevus and who was followed up for a minimum of 5 years was entered in the study.A total of 155 such individuals were identified. The mean (+/- SEM) age of the patients at first evaluation was 26 +/- 1 years. The group was followed for 7 +/- 1 years. The male-female ratio was 1:1. A family history of melanoma was present in 71 subjects (46%). Of the 155 patients, two developed melanoma. The thickness of the tumors in both patients was less than or equal to 0.8 mm. Twenty-five patients (16%), including the two with melanoma, had at least one nevus removed that showed "severe nuclear atypia."The risk of melanoma in individuals with atypical nevi is significantly greater than expected. The elevated risk was demonstrated even though careful, regular evaluations and removal of more atypical lesions were performed. This study provides evidence that, compared with no surveillance, the meticulous monitoring of patients with clinically atypical nevi is more likely to result in the detection of melanoma at thin stages, with an attendant improved prognosis.
Dysplastic nevus
Atypia
Melanocytic nevus
Nuclear atypia
Nodular melanoma
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Dysplastic nevus
Melanocytic nevus
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Dysplastic nevus
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Congenital melanocytic nevus
Melanocytic nevus
Superficial spreading melanoma
Nodular melanoma
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Dysplastic nevus
Atypia
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Melanoma diagnosis
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Previous studies have shown that congenital as well as acquired melanocytic naevi indicate an increased risk for developing melanoma in individual patients. Most studies stress the importance of melanocytic naevi as melanoma markers, while in some studies they are considered to be direct melanoma precursors. The latter opinion is favoured by the common co-occurrence of melanoma and naevus within one biopsy. The present study examines the question of whether the co-occurrence of melanoma and naevus is a random event or whether melanomas significantly co-localize with pre-existent naevi, which would suggest a precursor role for these naevi. Seven hundred biopsies of primary melanoma were examined for the presence of congenital or acquired naevi according to standard histological criteria. A naevus was found in 143 of the 700 biopsies (20.4%), of which 90 were acquired (12.9%) and 53 were congenital (7.6%). Within each biopsy the exact location of the melanoma and the naevus was determined using an ocular micrometer at a final magnification of 20 x. From these data the frequency of finding a naevus with increasing distance from the melanoma margin was calculated. The frequency of finding a naevus decreased from 2.6% immediately at the melanoma border to 0.3% at a distance of 4.5 mm and 0% at a distance of 5.0 mm. This decrease was statistically highly significant (P<0.001). Similar results were obtained when congenital and acquired naevi were evaluated separately. These data strongly indicate that melanoma and naevi are non-randomly distributed and that both congenital and acquired naevi may be precursors of melanoma.
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We describe a case in which a "punch biopsy" specimen of a conventional melanoma on the cheek of a 25-year-old man led to a problem in differentiating a desmoplastic malignant melanoma from cicatrix. The circumstances of this case raise the issue of whether desmoplastic melanoma can arise at the site of trauma within a pre-existing melanoma.
Melanoma diagnosis
Cheek
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An excess of intracellular beta-catenin protein is triggered by various genetic alterations in melanoma cell lines, and has been suggested to play a role in melanoma tumorigenesis.To investigate the role played in vivo by beta-catenin in melanoma tumorigenesis, we compared the cytoplasmic detection of beta-catenin in benign melanocytic cells vs. malignant melanoma cells presumably generated from these benign melanocytic cells. For this purpose, melanocytic naevi occurring in association with melanoma, which were suggested to be melanoma precursors, were compared with their associated melanoma for beta-catenin cytoplasmic immunoreactivity.Fifty-seven consecutive cases of primary cutaneous melanoma were considered, and 15 of them were found to be associated with a melanocytic naevus portion. The naevus portion showed features of acquired melanocytic naevus (total 12 cases: five dysplastic, seven intradermal) or congenital growth pattern naevus (total three cases: one superficial, two deep). All specimens were immunohistochemically investigated for beta-catenin.Virtually all primary cutaneous melanomas, including those associated with a naevus portion, showed cytoplasmic beta-catenin positivity. However, the intradermal naevus portion was consistently cytoplasmic beta-catenin negative, while both the dysplastic and the congenital naevus portions were cytoplasmic beta-catenin positive.Beta-catenin excess may play a role in melanoma tumorigenesis, because beta-catenin cytoplasmic reactivity was found in primary cutaneous melanoma but not in its associated intradermal naevus precursor. As, however, beta-catenin cytoplasmic reactivity was detected not only in primary cutaneous melanoma but also in its associated dysplastic/congenital naevus precursors, beta-catenin stabilization alone is not sufficient to play a decisive role for melanoma onset.
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