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Melanocytic nevi and risk of cutaneous malignant melanoma in southern Spain.

The main objective of this study was to assess whether cutaneous malignant melanoma (CMM) shows a stronger relation with the melanocytic nevi count at the site where CMM was diagnosed than with the melanocytic nevi count at other sites, stratifying by histologic CMM type, in a southern Mediterranean population. Cases and controls were selected from a population in southern Spain in 1988-1993. The study population included 116 incident cases with non-familial CMM (International Classification of Diseases 9th Revision (ICD-9) code 172), and 116 controls matched 1:1 for sex and age (+/- 4 years). Data were collected by personal interview, and melanocytic nevi were counted over the entire body surface by clinical skin examination performed by a dermatologist. Crude and multiple risk factor-adjusted odds ratios and 95% confidence intervals were computed by conditional logistic regression analysis. After adjustment by skin type, unexposed skin color, and sun exposure, CMM was found to occur significantly more frequently in individuals with a high number of melanocytic nevi at the same site where CMM originated (odds ratio (OR) for >8 nevi = 12.0, 95% confidence interval (CI) 1.3-108.2). The ability to predict the number of melanocytic nevi on different anatomic sites on CMM, but excluding the CMM cases on each corresponding site, was also examined. A significant trend with the number of nevi on the anterior surface of thighs was found (OR for >4 nevi = 4.5, 95% CI 1.4-14.9). Melanocytic nevi count on the melanoma site was the variable most closely related to superficial spreading melanoma subtype (SSM) (OR for >8 nevi = 82.19, 95% CI 2.72-2,454). On the other hand, the number of melanocytic nevi on the melanoma site was unrelated to risk of CMM subtypes other than SSM. These results support the hypothesis that nevi are an important risk factor for melanoma, especially SSM, in populations with a darker ethnic background.

Case-Control Studies↗

Giant nevi: a review.

Congenital nevi are benign neoplasms that are present at birth and composed of nevomelanocytes. Approximately 1-3% of all newborns have congenital pigmented nevi, and the number of nevi increases with age, peaking by late adolescence to 20-40 nevi in an individual. Giant congenital nevi are often defined as nevi that are greater than 20 cm in diameter in an adult, or nevi that occupy 2% or more of the body surface area. Histologically, nevi are transformed melanocytes, which are normally highly dendritic cells interspersed among basal keratinocytes. The genetic basis of these lesions is not known. Findings of a culture of melanocytes from such a lesion from a showed chromosome rearrangements involving 1p,12q, and 19p. The giant nevi might be associated to several diseases: neurocutaneous melanosis, diffuse lipomatosis, structural brain malformations, hypertrophy of skull bones, limb atrophy, skeletal asymmetry involving both soft tissue hyper-and hypoplasia, von Recklinghausen's disease and vitiligo. The risk of malignant change in giant nevi is probably the most contentious issue in its management. The consensus is that lesions are pre-malignant, but the purported incidence of malignancy varies wildly from 0-42%. Surgical excision remains the mainstay of treatment for large congenital melanocytic nevi, and most giant nevi are managed by staged excision and resurfacing with skin grafts or tissue expanders and flaps.

Humans↗

Chronic sun exposure and age are inversely associated with nevi in adult renal transplant recipients.

In 126 adult renal transplant recipients who had survived their transplantation for at least 8 years, we determined whether numbers of nevi and the presence of clinically atypical nevi were related to chronic sun exposure. On the basis of a skin examination, three groups were defined: patients with at least one clinically a typical nevus; patients with only clinically normal nevi: and patients without any nevi. The prevalence odds ratio of having any clinically atypical nevi as compared to having only clinically normal nevi was calculated in a logistic model, in relation to gender, skin type, age, sun exposure, and number of keratotic skin lesions present. Similarly, the prevalence odds ratio of having 30 or more nevi compared to fewer than 30 nevi was calculated. We found an inverse association between chronic sun exposure and age with numbers of nevi in adult renal transplant recipients. The presence of clinically atypical nevi was also inversely associated with chronic sun exposure, but this association disappeared after adjustment for age. We did not observe an association of nevi with the number of keratotic skin lesions, nor with humoral immune responses against human papillomavirus and the presence of certain HLA antigens, which are factors associated with nonmelanoma skin cancer in renal transplant recipients. Chronic sun exposure and age appeared to be strong determinants for decreased numbers of nevi in adult renal transplant recipients. Infection with human papillomaviruses does not appear to play an important role.

Adult↗

Differentiation between Spitz nevi and malignant melanomas by interphase fluorescence in situ hybridization.

Spitz nevi are benign melanocytic neoplasias which have distinct pathological features that make the pathological differential diagnosis from malignant melanomas extremely difficult. The Spitz nevi may be misdiagnosed as malignant melanoma and vice versa. Therefore, interphase fluorescence in situ hybridization (I-FISH) was used for a possible discrimination between Spitz nevi and malignant melanomas on the basis of numerical aberrations of the chromosome complement in interphase nuclei of thin sections. Previous studies had shown changes in malignant melanomas which were not found at the same level in normal tissue or benign tumors. Thin sections of archival paraffin material from 42 Spitz nevi with different histological type and grade of anomaly were subjected to FISH-analyses using commercially available biotinylated and/or digoxigenated alphoid DNA probes of chromosomes 1, 6, 7, 9, 17 and 18, which were applied in combinations in a two- or three-color-FISH. Unaffected epithelial areas from the same sections served as. The obtained data were compared with those collected previously from thin sections of malignant melanomas prepared in the same way. Due to the sometimes limited nevus area investigated, the number of evaluable nuclei was lower than expected from previous experiences with malignant melanomas. Therefore, only 20 nevi could be reliably evaluated. The comparison of the group of Spitz nevi with the group of controls did not show any significant difference regarding chromosomes 1, 6, 7, 9 and 17 (Wilcoxon test). The method used to detect chromosomal loss or gain in the individual Spitz nevi demonstrated only two nevi (one of the spindle cell type with a low to middle grade of anomaly, the other of the epitheloid cell type with a middle grade of anomaly) with a gain of chromosome 7 and chromosome 17, respectively. So, with respect to the histological type and grade of anomaly, no numerical aberrations could be detected in Spitz nevi. The comparison of the group of Spitz nevi with subgroups of malignant melanomas (metastatic, non-metastatic, melanomas with a thickness <1.5 mm and melanomas with a thickness >2. 0 mm) and with the whole group of malignant melanomas showed significant differences concerning chromosome 9 (Mann-Whitney U test), signal indices, which were higher in the melanomas than in the Spitz nevi. Regarding chromosomes 6, 7 and 17 no significant differences could be shown, although a trend of gain in melanomas and of loss in Spitz nevi was observed of these chromosomes.

Adolescent↗

Cyclin D1 expression in dysplastic nevi: an immunohistochemical study.

OBJECTIVE: We previously surveyed cyclin D1 expression in common acquired nevi, Spitz nevi, and malignant melanomas and reported that benign nevi maintain a zonal pattern of cyclin D1 expression, in contrast with malignant melanomas. Our aim was to extend those observations by examining cyclin D1 expression in dysplastic nevi. METHODS: Cyclin D1 overexpression in 23 dysplastic nevi was detected by an immunohistochemical technique. The extent of atypia of the nevi was graded as mild, moderate, or severe, using previously established criteria. RESULTS: Cyclin D1 overexpression in dysplastic nevi maintained a zonal pattern, similar to Spitz nevi. Cyclin D1 overexpression was greatest in the region of the epidermal-dermal junction and was significantly less prominent in the papillary and reticular dermis, suggesting that cyclin D1 expression is under cell control and correlates with maturation of nevus cells. Cyclin D1 overexpression also correlated with cytologic atypia, as dysplastic nevi with moderate or severe cytologic atypia contained a greater percentage of cyclin D1-positive cells than did nevi with mild atypia. Six dysplastic nevi with many cyclin D1--positive cells were assessed by fluorescence in situ hybridization studies using cyclin D1--specific and chromosome 11 centromeric probes. In all cases, there was no evidence of 11q13 translocation, amplification, or trisomy of chromosome 11. CONCLUSIONS: Cyclin D1 may be involved in the pathogenesis of dysplastic nevi. Cyclin D1 overexpression does not appear to be explained by cyclin D1 locus amplification or translocation in most cases, and it may be a result of other cell abnormalities that up-regulate the protein level of cyclin D1.

Chromosomes, Human, Pair 11↗

Is high mole count a marker of more than melanoma risk? Eczema diagnosis is associated with melanocytic nevi in children.

BACKGROUND: The number of melanocytic nevi is the best single marker of increased melanoma risk. In a previous study, adults with severe eczema were reported to have significantly fewer nevi than adults without eczema. OBSERVATIONS: In a nested case-control design within a randomized, controlled interventional trial of additional sun protection vs standard care in 269 children, a history of eczema was reported by the parents of 44 (16%) of the children. More nevi were found in children with a parental report of previous eczema diagnosis than in children without reported eczema (median, 7.5 nevi vs 5.0 nevi; P =.01). Eczema diagnosis was most significantly associated with more melanocytic nevi in children with lightly pigmented skin (8.5 nevi vs 6.0 nevi; P <.001). In multivariate logistical regression analysis, including assessment of hair color, sun protection practices, and study assignment (intervention vs standard care), eczema status remained significantly predictive of nevi number in children (P <.001). CONCLUSIONS: In contrast to a previous study that associated severe eczema with fewer nevi in adults, in the present study children with a reported history of eczema had more nevi than children without a reported history of eczema.

Case-Control Studies↗

The prevalence of common acquired melanocytic nevi and the relationship with skin type characteristics and sun exposure among children in Lithuania.

OBJECTIVE: To evaluate the prevalence of common acquired melanocytic nevi and its relationship with pigmentary characteristics and severe sunburns in children. DESIGN: Cross-sectional study. SETTING: Kaunas city, Lithuania (latitude of 55 degrees 55 minutes). PATIENTS: A random sample of 484 children aged 1 to 2 years, 4 to 5 years, and 9 to 10 years and adolescents aged 14 to 15 years. INTERVENTIONS: A questionnaire that provided information about the history of sunbathing and skin type. MAIN OUTCOME MEASURES: Atypical melanocytic nevi were defined according to the clinical criteria of the ABCDE rule. RESULTS: The median number of all common acquired melanocytic nevi was 12 in boys and 11 in girls; the median number of melanocytic nevi 2 mm or larger in boys and girls was 4. Twenty-seven percent of children experienced severe sunburns more than once. After adjustment for age and sex, it was found that children who had severe sunburns in summer and skin type I had a higher density of all melanocytic nevi and melanocytic nevi 2 mm or larger. The prevalence of atypical melanocytic nevi was 7% in all children and was age dependent (age 4-5 years, 1%; 9-10 years, 4%; 14-15 years, 16%). Three percent of children had congenital melanocytic nevi. CONCLUSIONS: The total number of common acquired melanocytic nevi in children increased with age. There was a positive association between severe sunburns, the tendency of the skin to burn, and the number of all melanocytic nevi and nevi 2 mm or larger.

Adolescent↗

Pigmented nevi of the oral mucosa: a clinicopathologic study of 36 new cases and review of 155 cases from the literature. Part II: Analysis of 191 cases.

Review and analysis of data on 191 cases of oral pigmented nevi from the literature and from two studies at the University of California, San Francisco, revealed that nevi of the intramucosal type are the most common, followed by the common blue nevus. Compound and junctional nevi are rare, and combined nevi are the rarest. The data on location, presence of clinical pigmentation, configuration, size, and duration of the nevi, as well as on the patient's age, sex, and race, are analyzed. Blue nevi were found mostly on the hard palate, whereas intramucosal nevi occurred on the buccal mucosa, on the gingiva, and on the lips as well as on the palate. Nonpigmented nevi were especially common (22%) in the intramucosal group. Most oral nevi are raised, which can be of help in the differential diagnosis. Oral nevi are small, most being between 0.1 and 0.6 cm at the largest dimension. Because the malignant potential of oral nevi is still uncertain and because preexisting macular pigmentation is present in about one third of all patients with oral melanoma, it is advisable to accurately diagnose all oral pigmented lesions, many of which will require microscopic examination.

Adolescent↗

Typical, dysplastic, congenital, and Spitz nevi: a comparative immunohistochemical study.

Nevus cell components have been observed in up to 40% of melanomas, but little is known of the pathobiology of these components in relation to their malignant potential. We studied 44 nevi of the typical, dysplastic, congenital, and Spitz types with a battery of monoclonal and polyclonal antibodies that react on formalin-fixed, paraffin-embedded tissues (HMB.45, S-100 protein, RAP-5, epithelial membrane antigen [EMA], and neuron-specific enolase [NSE]) by avidin-biotin immunohistochemical methods. EMA and RAP-5 (which detects the ras oncogene-associated P21 protein) were negative in all cases. Melanoma-specific HMB.45 was strongly reactive with the epidermal component and had a weak to negative reaction with the dermal component in the typical nevi. However, the reaction seen with HMB.45 in the junctional component of dysplastic nevi, congenital nevi, and some Spitz nevi was heterogeneous. One Spitz nevi showed HMB.45 staining in a pattern near to that of melanoma. In contrast to HMB.45, S-100 protein labeled nevomelanocytes, regardless of whether they were within the epidermis or dermis, although, in half of the dysplastic nevi, the reaction was heterogeneous, with some atypical cells failing to stain. But, with cytologically atypical junctional component (dysplastic-appearing), congenital nevi also stained heterogeneously for S-100 protein compared with the dermal component. NSE stained the central component of some Spitz nevi more intensely than the lateral component. Junctional nevomelanocytic subsets of some congenital nevi revealed HMB.45 and S-100 reactivity similar to dysplastic nevi.

Antibodies, Monoclonal↗

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.

Adult↗

Small congenital nevocellular nevi and the risk of cutaneous melanoma.

The relative risk of melanoma associated with small congenital nevi was estimated by comparing the published frequency of histologically documented nevocellular nevi in newborn infants with the frequency of: (1) congenital nevi at the tumor site, ascertained by history in 134 patients with melanoma; and (2) tumor-associated nevi with congenital features in 234 melanoma specimens. A 21-fold increase in melanoma risk was estimated for persons with small congenital nevi when nevi were ascertained by history, and a three- to tenfold increase in risk when nevi were ascertained by histology. Based on these approximations of relative risk from historic and histologic methods of detection, persons with small congenital nevi who live to age 60 are estimated to have cumulative risks for melanoma of 4.9/100 and 0.8 to 2.6/100, respectively. The increased risk is related presumably to the markedly increased probability of melanoma arising in association with small congenital nevi. In other words, small congenital nevi may represent precursors for at least some cases of cutaneous melanoma. The estimated risk are highly dependent on the specificity of methods used for ascertainment of congenital nevi.

Adolescent↗

Comparative immunoreactivity of CD-68 and HMB-45 in malignant melanoma, neural tumors and nevi.

The monoclonal antibody CD 68 (KP 1) reacts with fibrohistiocytic and some epithelial neoplasms; its reactivity compared with that of HMB 45 in malignant melanoma (MM) and neural tumors needs further elucidation. Using a streptavidin-biotin-immunoperoxidase procedure, we examined the reactivity of 65 MM (46 conventional, 1 polypoid, 6 desmoplastic [DMM], and 12 metastatic), 21 neurofibromas, 1 neurofibrosarcoma, 10 schwannomas, 1 perineurioma, 2 neurothekeomas, and 14 blue and 26 other nevi for CD-68, HMB-45-defined antigen, S 100 and neurofilament protein. A positive staining for CD 68 was observed in 38 of 42 primary, 5 of 6 DMM, and 11 of 12 metastatic melanomas; 6 of 10 schwannomas; 5 of 10 nevi with junctional component and all 14 blue nevi. All 21 neurofibromas, 1 each neurofibrosarcoma and perineurioma, both neurothekeomas, and all 12 nevi with dermal component were CD 68-negative. HBM 45 was expressed by all 44 primary, none of 6 DMM, and 7 of 12 metastatic melanomas; by none of 10 schwannomas, 6 neurofibromas, 1 neurofibrosarcoma, 1 perineurioma and 2 neurothekeomas. Both junctional nevi, 8 of 10 nevi with junctional components, 1 of 10 dermal components of junctional nevi, and 11 of 13 blue nevi were also HMB 45 positive. Except for 1 perineurioma, S 100 decorated all tumors examined. NF was immunoreactive in 1 of 45 conventional melanomas, 2 of 21 neurofibromas, 2 of 10 schwannomas, and 3 of 10 blue nevi; it was non-reactive in all polypoid, desmoplastic and metastatic melanomas; neurofibrosarcoma, perineurioma, neurothekeoma and other nevi. We conclude that the CD-68-reactivity in primary melanomas, neurofibromas, neurofibrosarcomas, perineuriomas, and nevi was similar to that of HMB 45. The significantly higher CD 68-positivity than of HMB 45 in metastatic and desmoplastic melanomas and schwannomas may be of diagnostic value.

Antigens, CD↗

Deep shave excision of macular melanocytic nevi with the razor blade biopsy technique.

BACKGROUND: Shave excision is an established surgical method for removing benign skin lesions for cosmetic and functional reasons. Usually superficial shave excision is performed with a common scalpel blade for the removal of papular nevi. However, there is little known about deep shave excision of macular melanocytic nevi with the razor blade technique. OBJECTIVE: The present study was undertaken to evaluate the cosmetic outcome of deep shave excision of macular melanocytic nevi with the razor blade technique. Moreover, its potency for sufficient removal of these lesions was investigated. METHODS: Within routine skin cancer screening 45 outpatients with a total of 77 macular melanocytic nevi were prospectively recruited. Deep shave excisions of these lesions were performed with a double-edged razor blade followed by chemical hemostasis. Histologically all specimens were processed and evaluated in a routine manner. After 6 months the physician and patients evaluated the shave sites for cosmetic outcome with a score graded from 1 to 4 (1 = excellent; 2 = good; 3 = moderate; 4 = poor). RESULTS: Histologically 88% (68 of 77) of the melanocytic lesions were described as completely excised and 60% (46 of 77) were diagnosed as atypical melanocytic nevi; 12% (9 of 77) of the nevi were incompletely excised on the depth. On average, the deep margin of the specimens (n = 77) was 0.5 mm (range 0-1.8 mm) and the lateral margin was 2 mm (range 0.3-8.2 mm). After 6 months 56 shave sites could be reassessed. We observed mild hypopigmentation in 52% (29 of 56), hyperpigmentation in 32% (18 of 56), and erythema in 23% (13 of 56). Recurrent nevi occurred in 13% (7 of 56). The evaluation of the cosmetic outcome by the patients (mean score 1.7) achieved better results than the evaluation by the physician (mean score 2.5). The cosmetic results showed no significant (P >.05) differences in various anatomic sites. CONCLUSION: Our data confirm that deep razor blade excision presents a highly useful and inexpensive method for the removal of macular melanocytic nevi that yields adequate specimens for pathologic interpretation. We consider that shave excision with the razor blade technique is potentially much less scarring than full-thickness scalpel excisions of nevi. In particular, this is of great significance for patients with multiple nevi, such as dysplastic nevi syndrome.

Adolescent↗

Management of dysplastic nevi: a survey of fellows of the American Academy of Dermatology.

BACKGROUND: Opinions concerning the significance of dysplastic nevi and their management vary among dermatologists. OBJECTIVE: The purpose of this study was to assess how fellows of the American Academy of Dermatology (AAD) perceive and manage dysplastic nevi. METHODS: Questionnaires were sent to 1216 fellows of the AAD; 456 questionnaires were returned. RESULTS: Almost all respondents (98%) accept the dysplastic nevus, or atypical mole, as an entity. Seventy-five percent of respondents perform follow-up total cutaneous examinations on all their patients with dysplastic nevi, and another 22% on some of them; 86% usually intend to do total removals when they perform biopsies of dysplastic nevi; 75% use margins of 2 mm or less when removing dysplastic nevi; 49% order baseline total-cutaneous photographs of some or all of their patients with multiple dysplastic nevi, although only 12% do so routinely; 67% prefer to re-excise dysplastic nevi when margins are positive, some using histologic atypia as a criterion; 60% recommend an ophthalmologic examination for at least some of their patients with many dysplastic nevi, although only 3% do so routinely; 12% always recommend cutaneous examinations of blood relatives of their patients with dysplastic nevi and another 81% recommend such examinations for at least some of their patients with dysplastic nevi; 23% use dermoscopy; 99% recommend self-examination; almost 100% recommend sunscreen use and 93%, sun avoidance. CONCLUSION: Most respondents, in agreement with the literature, accept the concept that patients with dysplastic nevi are at increased risk for melanoma and that methods for prevention and early detection of melanomas are appropriate for these patients.

Attitude of Health Personnel↗

Neurofibromas and neurotized melanocytic nevi are immunohistochemically distinct neoplasms.

Neurofibromas are often clinically, as well as histologically, indistinguishable from completely neurotized melanocytic nevi. We tested the hypothesis that immunologic markers would differentiate the perineural fibroblasts and Schwann cells of neurofibromas from the neurotized cells of melanocytic origin. We examined eight partially neurotized acquired melanocytic nevi, three partially neurotized congenital melanocytic nevi, and five neurofibromas, with antibodies directed against S-100 protein, Leu-7(HNK-1), glial fibrillary acid protein (GFAP), and myelin-basic protein (MBP). A histologic diagnosis of neurofibroma was based on identification of a dermal proliferation of spindle-shaped cells with wavy nuclei, in a background of loose reticulated collagen. Neurotized nevi were diagnosed upon recognition of scattered nests of type A or B nevus cells, surrounded by basement membrane, present in the papillary dermis of lesions otherwise indistinguishable from neurofibromas. The congenital nevi were all large melanocytic nevi known to be present at birth. S-100 stained the majority of neoplastic cells in all neurofibromas, neurotized acquired nevi, and neurotized congenital nevi. Neurofibromas showed focal staining for Leu-7, GFAP, and MBP. In contrast, neurotized acquired and congenital nevi failed to express these markers. We believe that Leu-7, GFAP, and MBP may be helpful in differentiating neurofibromas from completely neurotized melanocytic nevi. The differences in the immunohistochemical profiles of neurofibromas and neurotized nevi support the concept that these neoplasms are histogenically distinct, despite their similar histologic appearance.

Antigens, Differentiation↗

Atypical histologic features in melanocytic nevi.

The atypical histologic features considered to be specific to dysplastic (atypical) nevi have been reported to occur in nevi that are common nevi by all other clinical and histologic features. The distribution and mutual relations among such features in nevi need to be further studied. Six histologic features (dimension > 5 mm, lentiginous proliferation, disordered nested pattern, melanocytic dyskaryosis, dermal lymphocytic infiltrate, suprabasal melanocytes) were analyzed in 253 melanocytic nevi with different clinical appearances. Atypical histologic features, found in 72% of nevi, occurred singly or formed numerous and highly variable combinations. Nevi formed a complex histologic spectrum comprising lesions showing a progressively increasing incidence of atypical features rather than two classes (common and dysplastic nevi). To divide the investigated lesions in objectively defined groups, we used a scoring system. In each nevus, a numeric value of 1 was assigned when each of the studied parameters was present and a value of 0 was assigned when each of these parameters was absent; on the basis of the final scores, nevi were divided in six different classes (classes 0-5). Diagnostic categories such as dysplastic nevi and common nevi seem to be inappropriate, as they do not reflect the real histologic complexity of such lesions.

Dysplastic Nevus Syndrome↗

Giant congenital nevi: a 20-year experience and an algorithm for their management.

A variety of treatment options exists for the management of giant congenital nevi. Confusion over appropriate management is compounded because not all giant congenital nevi are pigmented, and malignant potential varies between different types. The present study sought to define factors in the presentation of giant congenital nevi that could provide an algorithm for their management, with respect to both the extent of resection and subsequent reconstructive options.A retrospective review of all patients who presented with a congenital nevus of 20 cm2 or greater since 1980 was performed, distinguishing among nevi involving the head and neck, the torso, and the extremities. Sixty-one patients with giant congenital nevi were evaluated (newborn to age 16 years), of which 60 nevi in 55 patients have been operated on. Giant congenital nevi having malignant potential were pigmented nevi (53 patients) and nevus sebaceus (four patients). Those not having malignant potential were verrucous epidermal nevi (three patients) and a woolly hair nevus (one patient). Of the 60 giant congenital nevi operated on, expanded flaps were used in 25, expanded full-thickness skin grafts were used in 10, split-thickness or nonexpanded full-thickness skin grafts were used in 13, and serial excision was used in 30. After 1989, operations tended to use multimodality treatment plans, with an increased use of expanded full-thickness grafts and immediate serial tissue expansion. The use of serial excision, particularly in the extremities, also increased after 1989. Serial excision was the treatment of choice when it could be completed in two procedures or less, which occurred in more than 80 percent of cases using serial excision alone. Expanded flaps were the most common mode of reconstruction in the head and neck region and were used in 49 percent of these procedures. Serial excision was the most common form of treatment in the extremities, used in 50 percent of procedures. Tissue expansion in the extremities was infrequently used to provide an expanded flap (8 percent of procedures), whereas it was frequently used to provide expanded full-thickness skin grafts harvested from the torso (used in 31 percent of procedures). On the basis of these data, algorithms for the extent of resection and subsequent reconstructive options for giant congenital nevi were developed. Their management should be formulated relative to pigmentation, malignant potential, and anatomic location of the respective lesions.

Adolescent↗

S100A6 protein expression is different in Spitz nevi and melanomas.

The Spitz nevus is a benign melanocytic lesion that can be identified reliably in many cases by conventional histopathological criteria. However, there are subsets of Spitz nevi and of malignant melanoma that closely resemble each other and represent diagnostic challenges. S100 proteins are of interest because of their involvement in neoplastic processes and their genes are clustered in chromosome 1q21. Chromosome 1 contains mutations in several types of tumors, including melanomas. The expression of different S100 proteins (A2, A6 and A8/A9 or A12) was examined in 42 Spitz nevi, 105 melanomas, and 73 melanocytic nevi to test the hypothesis that their expression differs among these entities and may contribute to the distinction between these entities. The results showed an up-regulation of S100A6 protein in Spitz nevi, melanomas, and melanocytic nevi but with a different percentage of positivity and pattern of immunoreactivity. The differences between these three entities were statistically significant (P <.001). All 42 Spitz nevi (100%) showed strong and diffuse S100A6 protein expression, both in junctional and in dermal components of the nevi. Thirty-three percent of melanomas expressed S100A6 (35/105). The expression was mainly weak (30/35) and patchy in the dermal component and was negative or minimal in the junctional component. Fifty-six percent of different subtypes of melanocytic nevi (41/73) expressed S100A6, almost all of them weakly (40/41) and in the dermal component. Normal intraepidermal melanocytes were negative. The melanocytic cells in these three entities did not express S100A2, S100A8/A9 or A12. However, an up-regulation of S100A2 and S100A8/A9 or A12 proteins was observed in normal keratinocytes in the epidermis overlying Spitz nevi and melanomas, without differences. In summary, a simple immunohistochemical test for S100A6 protein differentiated between Spitz nevi, melanomas, and melanocytic nevi. This marker could be used when the distinction is very difficult or controversial in routine studies, especially when there is a junctional component. Further molecular analyses of the S100A6 protein and gene should be performed to study the underlying genetic bases for such differences.

Cell Count↗