Intraepidermal distribution patterns of melanocytes in the melanocytic lesions on the sole: proposed criteria for histopathologic diagnosis of plantar malignant melanoma in situ

Eighty-eight melanocytic lesions on the soles of Japanese were histologically investigated. Increased numbers of solitary melanocytes above the basal layer of the epidermis were often found in the benign melanocytic nevi on the sole: in 5 lesions of 9 congenital melanocytic nevi, 22 of 65 acquired melanocytic nevi, and 1 of 5 dysplastic nevi. In addition, a moderate degree of nuclear atypia of proliferating melanocytes was frequently observed in the benign melanocytic nevi on the sole: in 3 lesions of 9 congenital melanocytic nevi, 17 of 65 acquired melanocytic nevi, and 2 of 5 dysplastic nevi. Therefore it cannot be said that increased numbers of solitary atypical melanocytes above the basal layer is a characteristic histologic feature of early malignant melanoma in situ. Combining the intraepidermal distribution patterns of melanocytes and maximum diameter of the lesion, we propose criteria for histopathologic diagnosis of plantar malignant melanoma in situ.     

Clinical guidelines for the early detection of plantar malignant melanoma

Of 144 pigmented lesions excised from the soles of Japanese patients, 140 were melanocytic. Apart from congenital melanocytic nevi, only a few benign acquired melanocytic nevi on the sole were more than 7 mm in maximum diameter and none exceeded 9 mm. In contrast, all plantar malignant melanomas, including malignant melanoma in situ, were 9 mm or more in maximum diameter. In addition, the majority of plantar melanocytic lesions excised from patients who were older than 50 years of age were malignant melanoma. On the basis of these data, we propose clinical guidelines for the early detection of plantar malignant melanoma.     

Dermoscopy of an acral congenital melanocytic nevus

Congenital melanocytic nevi carry a risk for malignant transformation into melanoma, therefore early detection of suspicious features is crucial to reduce mortality rates. Dermoscopy improves the early detection of melanoma while reducing the number of unnecessary excisions of benign pigmented skin lesions. Dermoscopically, congenital melanocytic nevi are often characterized by the presence of a cobblestone pattern, but to date, little is known about the dermoscopic features of acral congenital melanocytic nevi. We report an acral congenital melanocytic nevus typified by the presence of three different dermoscopic patterns that are commonly seen in acquired melanocytic nevi of palms and soles.     

EFFECTIVE DETECTION OF PLANTAR MALIGNANT MELANOMA

Background: As the sole of the foot is the most prevalent site of malignant melanoma in non-Caucasians, early detection of the neoplasm at this anatomical site is very important. In our previous study, we proposed a clinical guideline that acquired melanocytic lesions on the sole larger than 7 mm in maximum diameter should be examined histologically. Methods: Eighty-one Japanese patients with the complaint of plantar pigmented lesions were screened at our dermatology clinic during 3 years using the 7-mm criterion. Results: Of the total 80 melanocytic lesions on the sole, 14 lesions were larger than 7 mm in maximum diameter, excluding congenital lesions. Diagnoses of the 14 “large” lesions were as follows: advanced malignant melanoma, 8 lesions; early malignant melanoma (malignant melanoma in situ), 1 lesion; acquired melanocytic nevus, 4 lesions, and volar melanotic macule, 1 lesion. Conclusions: The present study confirmed the validity of the 7-mm criterion for the early effective detection of plantar malignant melanoma.     

Relation of maximum diameters of plantar malignant melanoma to various prognostic factors and prognosis of patients

The following factors were investigated in 43 cases of plantar malignant melanoma: maximum diameters of primary lesions, Clark's subtypes, clinical stages, UICC's stages, Clark's levels of invasion, Breslow's tumor thickness, and prognosis of patients. Relation of maximum diameter of primary lesions to various prognostic factors and prognosis of the patients was analysed. It was revealed that there were no statistically significant relationships between maximum diameters and other various factors. In our series, however, all patients with plantar malignant melanoma less than 14 mm in diameter are alive without metastasis. Judging from our previous and present studies, the following two points are the most important for improving the prognosis of patients with plantar malignant melanoma: 1) Catching all pigmented lesions on the sole that are more than 7 mm in diameter and examining them histologically, if they have no possibility of being congenital melanocytic nevus or black heel. 2) Treating plantar malignant melanomas adequately before they become 14 mm in maximum diameter.     

Dysplastic nevus: the eye of the hurricane

Dysplastic nevi were generally recognized, thanks to the contributions of Clark et al. in 1978. These lesions were described in a familial context, which was called the 'B-K mole syndrome'. However, it is worth noting that this was not the first time that these nevi had been described in the literature. If we look back in history, we can find that in 1820, Norris had already described some very similarly pigmented lesions, also in a familial context, just as Cawley subsequently did in 1952. Clark coined the term of dysplastic nevi for lesions presenting in patients with personal and family histories of malignant melanoma, having from 10 to 100 nevus lesions of a certain size, irregular shape and variable pigmentation of more than 5 mm. In addition, he pointed out that histologically, such lesions were principally characterized by the presence of atypical melanocytic hyperplasia.     

Significant melanocytic lesions in infancy, childhood, and adolescence

Malignant melanoma is diagnosed yearly in approximately 300 persons under age 20 in the United States. Relatively recent advances in dermatology include the recognition of lesions felt to be potential precursors of malignant melanoma. Small congenital melanocytic nevi, present in 1 per cent of all newborn infants, may have a small but definite potential for developing malignant melanoma. Furthermore, despite inconclusive data, many leading dermatologists now advocate removal of these small congenital lesions. Giant congenital melanocytic nevi, with their strong predilection for undergoing malignant change, are removed surgically at an early age, often in multistaged procedures. Dermabrasion, once felt to have a role in the treatment of giant congenital nevi, does not remove the malignant potential of these lesions. The dysplastic nevus syndrome, recognized in 1976, identifies individuals at increased risk for developing melanoma. Adolescents who have the dysplastic nevus syndrome or who are members of families with the syndrome require close medical supervision and patient education. The benign Spitz nevus, with its histologic similarity to malignant melanoma, continues to challenge the dermatopathologist and clinician. These lesions--the Spitz nevus, dysplastic nevus, congenital melanocytic nevus, and malignant melanoma--must all be actively considered when regarding the many other benign melanocytic lesions found in infancy, childhood, and adolescence.     

Childhood melanoma

Pediatric melanoma is rare but increasing in incidence. Because early diagnosis and treatment improves prognosis, clinicians need to include it as a possible diagnosis when evaluating a pigmented lesion in a pediatric patient. Some risk factors for melanoma include xeroderma pigmentosum, giant congenital melanocytic nevi, dysplastic nevus syndrome, atypical nevi, many acquired melanocytic nevi, family history of melanoma, and immunosuppression. Definitive treatment is with surgical excision. Adjuvant therapies such as chemotherapy, immunotherapy, and radiation therapy can be used in advanced cases.     

Benign melanocytic lesions: Risk markers or precursors of cutaneous melanoma?

Background: The role of benign melanocytic lesions as precursors and not only as risk markers for the development of cutaneous melanoma is controversial.Objective: The purpose of the study was to assess the frequency of the histologic association of benign melanocytic lesions with cutaneous melanoma of a maximum thickness of 1.00 mm. The possibility that the spatial association of benign lesions with melanoma may be co-incidental was also investigated.Methods: The study subjects representing 289 cases of cutaneous melanoma of maximum thickness 1.00 mm (or less) were examined histologically for the presence of an associated benign melanocytic lesion(s), including lentiginous melanocytic proliferation; junctional, compound, or intradermal nevus; dysplastic nevus; and congenital nevus contiguous with or adjacent to the melanoma. The effects of age, tumor thickness, level of invasion, histologic type, and anatomic site on the association of benign melanocytic lesions with melanoma were assessed. In the control subjects 40 basal cell carcinomas and 38 compound nevi (not dysplastic) randomly chosen and matched for age (±1 year) and site (head/neck, trunk, upper and lower limbs) with a melanoma case were examined to assess the proportion of these cases associated with benign lesions compared with the matched melanoma cases.Results: A nevus was associated with melanoma in 51% of cases (n = 147). Of these, 82 (56%) were dysplastic nevi, 61 (41%) were common acquired nevi, and 4 (3%) were congenital nevi. Lentiginous melanocytic proliferation was present in the epidermis adjacent to 219 melanomas (75%) and in 44% of these cases (n = 97) a coexisting nevus was also present.Conclusion: The results of this study lend further support to the concept of common acquired nevi and dysplastic nevi as precursors of cutaneous melanoma. In addition, lesions diagnosed clinically as simple lentigo and solar lentigo may be important as potential precursors of melanoma, particularly in the elderly.     

Clinical diagnosis of early malignant melanomas

Criteria for the clinical diagnosis of early malignant melanomas were sought. A total of 213 pigmented tumors, clinically suspected of being early malignant melanomas, were measured, described, photographed, and classified histologically: 40 proved to be definitely malignant, 49 possibly malignant ("dysplastic"), and 124 definitely benign (mostly melano-/nevocytic nevi, spindle-cell nevi, and Spitz nevi). Malignant melanomas had a horizontal diameter of greater than 5 mm, the patients were older than 18 years, and 62.5% were females. A combination of criteria allowed a clinical diagnosis to be made with an accuracy of 76.2%. The criteria of a horizontal diameter of greater than 5 mm, irregular configuration, and uneven pigmentation permitted 80% of all melanomas to be identified. Histologically atypical, dysplastic nevi could not be diagnosed clinically. They probably constitute a heterogeneous group and only some of them appear to be very early, histologically not clearly recognizable, malignant melanomas.     

Melanocytic nevi and malignant melanoma

It has been known for a long time that melanoma can have its origin in congenital or acquired melanocytic nevi. In regard to congenital nevi, there is sufficient evidence to state that large lesions (those greater than 20 cm in diameter) have a significant risk factor that is several-fold greater than for common acquired nevi. Prophylactic excision of such lesions should be strongly considered when it is feasible, but individual circumstances must be taken into account. The risk factors for small and medium-sized congenital nevi have not been accurately determined; therefore, no uniform recommendation can be made regarding their management. There is no objective evidence to indicate that common acquired nevi in any particular anatomic sites, such as volar or genital skin, are at greater risk for the development of melanoma than are any others. Patients with familial dysplastic nevus syndrome must be identified and followed carefully in order to recognize and eradicate evolving and early melanomas. The concept of the sporadic dysplastic nevus syndrome is intriguing and deserves careful study to further define the clinical and histologic diagnostic criteria that will enable accurate determination of its prevalence and risk factors.     

Age distribution and histologic patterns of dysplastic nevi

A total of 676 dysplastic moles collected from 487 patients over a 1-year period were reviewed together with demographic data. The associated nevus in 642 cases (95%) had a superficial, or "acquired," pattern within the papillary dermis, in comparison with the nevus in the remaining 34 cases (5%), which showed a deep, or "congenital," pattern. The dysplasia was graded in severity as mild, moderate, or severe (on a scale of 1 to 3). When patients with mild to severe dysplastic melanocytic nevi were compared with those patients showing atypical intraepidermal melanocytic hyperplasia (also called in situ malignant melanoma) or early invasive malignant melanoma associated with dysplasia, a progression of ages was noted. The average ages in the five diagnostic groups were as follows: 34.8 years, mild dysplasia (group 1); 35.1 years, moderate dysplasia (group 2); 41.5 years, severe dysplasia (group 3); 44.4 years, in situ malignant melanoma (group 4), and 46.9 years, early invasive malignant melanoma (group 5). Statistical analysis revealed that the two younger groups differed significantly in age from the three older groups. Men and women had an equal proportion of acquired and congenital pattern nevi, but men were older in each category and had more severe dysplasia, a greater tendency toward truncal lesions, and more regressive changes. Biopsy of trunk lesions was done in 275 cases (80%), of extremity lesions in 60 cases (17%), and in head and neck sites in 9 cases (3%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Melanocytic proliferations associated with lichen sclerosus.

OBJECTIVES: To describe the clinicopathologic features of melanocytic proliferations associated with lichen sclerosus (LS) and to compare these findings with those in controls. DESIGN: Cohort study. SETTING: Academic and private practice dermatology and dermatopathology services. PATIENTS: Cases of melanocytic proliferations associated with LS and consecutive controls with persistent (recurrent) melanocytic nevi, persistent malignant melanomas, and compound melanocytic nevi. MAIN OUTCOME MEASURES: Diagnostic criteria and disease recurrence. RESULTS: Eleven patients, all female, with a mean age of 40 years (range, 8-83 years), presented with pigmented lesions clinically suspected to be malignant melanoma or atypical melanocytic nevi affecting the vulva (7 patients), perineum (3 patients), or chest (1 patient). Lichen sclerosus was first identified in the biopsy specimen and subsequently confirmed clinically. In 10 cases, a melanocytic nevus was superimposed on LS (overlying or entrapped by sclerosis), whereas LS was found at the periphery of vulvar malignant melanoma. After complete excision, no recurrences have been reported for the melanocytic nevi in LS (mean follow-up, 29 months; range, 4-60 months). Compared with control lesions, the LS melanocytic nevi most closely resembled persistent melanocytic nevi and could be distinguished from persistent malignant melanoma histologically. Melanocytes, nevoid or malignant, proliferating contiguously with fibrotic or sclerotic collagen, contained abundant melanin, diffusely expressed HMB-45, and had a higher Ki-67 labeling index than ordinary melanocytic nevi. However, persistent malignant melanoma exhibited mitotic figures, significantly higher Ki-67 labeling index, and deep dermal HMB-45 expression compared with LS melanocytic nevi and persistent melanocytic nevi. CONCLUSIONS: Melanocytic nevi occurring in LS have features in common with persistent melanocytic nevi and can mimic malignant melanoma. An "activated" melanocytic phenotype is seen in LS melanocytic nevi, implicating a stromal-induced change.     

Number of melanocytic nevi as a major risk factor for malignant melanoma

A study of 121 melanoma patients and 139 control subjects from the University of California, San Francisco clinics was conducted among whites to examine the relationship between number of melanocytic nevi and cutaneous melanoma. Nevi that measured 2 mm or more in diameter were counted over the body by a dermatologist and a dermatology fellow. The average number of nondysplastic melanocytic nevi that were 2 mm or greater in diameter was 97 for melanoma patients and 36 for control subjects (p less than 0.001). Relative risks were 1.6 (p = 0.43) for 11 to 25 nevi, 4.4 (p = 0.01) for 26 to 50 nevi, 5.4 (p = 0.008) for 51 to 100 nevi, and 9.8 (p = 0.001) for more than 100 nondysplastic melanocytic nevi. Relative risks were 3.8 (p = 0.001) for 1 to 5 dysplastic nevi and 6.3 (p = 0.003) for 6 or more of these lesions. Report of blistering sunburns or of a previous skin cancer and having red or blond hair at the age of 20 were also independently associated with an increased risk of cutaneous melanoma. If confirmed in larger studies, the results presented on number of nevi and melanoma risk suggest a readily identifiable melanoma-prone group that could be followed to detect early malignant melanoma.     

Solitary small active junctional nevi in juvenile patients

Solitary small very dark and papular pigmented nevi, less than 4 mm, are seen commonly in the second decade of life and have a distinctive histologic pattern. Microscopically these lesions show abundant intraepidermal melanin, included within the keratin layer, and proliferating single melanocytes or nevus cell nests. Prominent nucleoli in the melanocytic cells, occasional mitoses, and the invariable presence of moderate numbers of dermal melanophages and lymphocytes indicated the activity of the pathologic process. The benignity of the lesions in nine patients is supported by a benign course over a one- to three-year evaluation period after limited excisional biopsy procedures. The clinical and pathologic evidence of activity in these nevi suggests yet another possible precursor of malignant melanoma. The B-K mole syndrome and the dysplastic nevi syndrome differ from these cases both clinically and histologically.     

Incidence of congenital melanocytic nevi in newborn babies in Denmark

Three hundred fourteen unselected babies were examined within 96 hours of delivery. Three (1%) of the infants had clinically recognizable pigmented lesions. Two of the lesions (mean, 0.6%; range, 0.1%-2.3%; 95% confidence limits) proved histologically to be compound melanocytic nevi. The histology displayed almost identical patterns, with large nests of melanocytes at the dermoepidermal junction and only few nevus cells in the papillary dermis. A 0.6% incidence rate corresponds to 330 congenital melanocytic nevi in Denmark each year (range, 55-1265; 95% confidence limits). Because histology does not seem to be an accurate diagnostic tool to sort out the malignant potential of the small congenital melanocytic nevi, prospective studies are needed to characterize the premalignant melanocytic nevi, whether congenital or acquired.     

Number of acquired melanocytic nevi in patients with melanoma and control subjects in Japan: Nevus count is a significant risk factor for nonacral melanoma but not for acral melanoma

BACKGROUND: Epidemiologic studies have suggested that number of acquired melanocytic nevi is a risk factor for melanoma development in Japanese as it is in white populations. However, there are only a few population-based studies on acquired nevi in Asian populations, and no epidemiologic study on relationship between number of acquired nevi and melanoma in Japanese populations has been reported. OBJECTIVE: The purpose of this study was to assess number, size, and distribution of acquired melanocytic nevi in a Japanese population. Particular attention was paid to evaluation of relationship between number of acquired nevi and development of nonacral or acral malignant melanoma. METHODS: In all, 82 patients with malignant melanoma and 600 control subjects were included in this study. All participants were Japanese. The number of acquired melanocytic nevi, 2 mm or larger in diameter, on the whole body except the scalp and genital areas was counted by experienced dermatologists. The participants were divided into 5 age categories (0-19, 20-39, 40-59, 60-79, and >80 years old) for the statistical analyses. This categorization adjusted the age and sex distribution between patients with melanomas and control subjects in 40- to 59-, 60- to 79-, and over 80-year-old groups. RESULTS: In the control Japanese population, the number of acquired melanocytic nevi on the whole body increased with age in 0- to 19-year-old age group and reached the highest number, 6.7 +/- 8.1/person, in 20- to 39-year-old group. In patients with nonacral melanoma, the number of acquired nevi on the whole body in 40- to 59- and 60- to 79-year-old groups was significantly higher than that of the corresponding control group. In contrast, the rate of individuals who had acquired nevi on soles, palms, and nail apparatus was not significantly different between acral melanoma group and the control group in 40- to 59- and 60- to 79-year-old groups. CONCLUSION: This study has revealed that a large number of acquired melanocytic nevi is a risk factor for the development of nonacral melanoma in Japanese and white populations. However, acquired nevi on soles, palms, and nail apparatus do not seem to be a risk factor for acral melanoma in Japanese populations.     

Clinical diagnosis of dysplastic melanocytic nevi: A clinicopathologic correlation

A prospective, community practice-based, clinicopathologic correlation was undertaken in 165 melanocytic nevi excised from a group of forty-three patients, each patient having previously had at least one clinically suspected and histologically confirmed dysplastic melanocytic nevus. Eighty-two percent of seventy-two lesions with histologic evidence of mild dysplasia had been diagnosed correctly as such clinically. The accuracy of clinical diagnosis of moderate dysplasia was low (20%); however, all cases of severe dysplasia with or without in situ melanoma were diagnosed correctly. In 75% of all cases in which dysplasia of any degree was diagnosed clinically, histologic evidence of dysplasia was found. In order to investigate further the clinical features of these nevi, 175 color enlargements of histologically confirmed dysplastic melanocytic nevi were examined. The following clinical features were found to be most common: ill-defined border (90%), irregularly distributed pigmentation (84%), maximum diameter greater than 5.0 mm (72%), erythema (64%), and accentuated skin markings (63%). Increasing darkness and confluence of pigmentation in these dysplastic melanocytic nevi correlated with increasing severity of dysplasia. We conclude that careful clinical examination of individual melanocytic nevi will separate severe dysplasia with or without in situ melanoma from low-grade (mild or moderate) dysplasia in a high percentage of nevi from patients with the dysplastic nevus syndrome. Clinical examination will yield a diagnosis of dysplasia in approximately 75% of nevi from such patients in whom histologic evidence of dysplasia is present. Clinical examination constitutes a practical and sufficiently reliable method for the assessment of melanocytic nevi in patients with the dysplastic nevus syndrome.     

DNA aneuploidy in congenital melanocytic nevi: suggestive evidence for premalignant changes

Nuclei with abnormal (aneuploid) DNA content were detected by flow cytometric analysis in 4 of 39 congenital melanocytic nevi and in 0 of 62 acquired nevi. Three of the 4 nevi with DNA-aneuploidy were greater than 20 cm in their largest diameter. We suggest that DNA aneuploidy is an indicator of a premalignant condition in congenital nevi in cases where histologic examination does not reveal any evidence for malignant melanoma. Cells with abnormal DNA content (aneuploid cells) are not uniformly distributed in giant congenital nevi: in one lesion we observed an area with a high percentage of cells with DNA aneuploidy, areas with a low percentage of aneuploid cells, and parts that were found to be normal by flow cytometric analysis. Nuclear pleomorphism was found histologically in the area with the high percentage of aneuploid cells while the areas with the low percentage of aneuploid cells were histologically normal. Thus, flow cytometry seems to be an additional sensitive method for the detection of nuclear abnormalities that are not always apparent by conventional histology. Increase in the relative amount of growth phase (S-phase cells), indicating elevated proliferative activity, was detected in 6 of 39 congenital pigmented nevi and in 6 of 62 acquired nevi.     

The relationship between melanocytic nevi and malignant melanoma

In conclusion, although there are data, some quite convincingly implicating dysplastic nevi and congenital nevi (particularly "giant") as "precursors" of malignant melanomas, our ability to predict the magnitude of these associations is lacking. Thus, until additional basic and clinical research data are forthcoming, any recommendation to prophylactically remove all congenital nevi or all dysplastic nevi in order to decrease the incidence of malignant melanoma is premature. In regard to congenital nevi, evidence exists that giant (larger than 20 cm in diameter) congenital nevi may have a significant risk factor so as to warrant, when feasible, prophylactic excision of such lesions. In our opinion, no uniform recommendation can be made at this time for the management of small and medium-sized congenital nevi. Patients with familial dysplastic nevus syndrome should be followed carefully and educated concerning the early detection of malignant melanoma. Patients with sporadic dysplastic nevus syndrome deserve further study to enable us to accurately determine their risk of developing malignant melanoma.