Management and dermoscopy of fast-growing nevi in pregnancy: case report and literature review

BACKGROUND: The relationship between pregnancy and a change in melanocytic nevi is still controversial. Moreover, management of the rapid evolution of a nevus in an unauspicious melanocytic lesion can be a clinical challenge in pregnancy. METHODS: This article examines a case of a fast-growing deep penetrating nevus in a pregnant woman and provides a literature review of articles relative to pregnancy and nevi change, the management of fast-growing pigmented lesions, and the role and usefulness of dermoscopy in these cases. RESULTS: Recent studies have documented that pregnancy is not associated with any significant change in the size of melanocytic nevi. The management of fast-growing melanocytic lesions during this period compulsorily leans toward excision. Dermoscopy can be useful, providing clinicohistopathologic correlations and a better assignment of the lesion. CONCLUSION: This case report and review provide important management considerations for nevi during pregnancy. Early intervention with aggressive treatment measures is the best management for fast-growing lesions, and epiluminescence dermoscopy can assist the management, although still remaining a second-level examination, useful for documentation and for a better classification of the lesion.     

Clinical and histopathologic analyses of pigmented macular lesions on the soles of Japanese--proposal of a clinical guideline for detection of early malignant melanoma on the sole

Of 92 pigmented macular lesions on the soles of Japanese, 88 lesions were histologically confirmed to be melanocytic: 65 ordinary acquired melanocytic nevi, 9 congenital melanocytic nevi, 5 dysplastic nevi, and 5 possible and 4 definite lesions of early malignant melanomas. None of the ordinary acquired melanocytic nevi were more than 7 mm in maximum diameter. Excluding congenital melanocytic nevi, there were 8 lesions whose greatest diameters were more than 7 mm: 2 dysplastic nevi, and 2 possible and 4 definite lesions of early malignant melanoma. Judging from the data obtained in this study, we propose the following clinical guideline for the detection of early lesions of malignant melanoma on the sole. If the pigmented lesions have no possibility of being congenital melanocytic nevus, black heel, lesions of Peutz-Jeghers syndrome, or 5-FU induced lesions, measure the maximum diameters. 1) Lesions with a diameter of more than 7 mm should be excised for histological evaluation. 2) Lesions with a diameter between 6 and 7 mm should be examined histologically when they show conspicuous irregularity in shape, color and/or border or are observed on the soles of a patient older than 50.     

Estrogen receptor beta expression in nevi during pregnancy

Abstract:  Estrogen levels increase during pregnancy and clinical evidence has long suggested that melanocytes are estrogen-responsive. We hypothesized that nevi from pregnant patients would exhibit increased expression of estrogen receptor β (ERβ) and thus enhanced potential to respond to altered estrogen levels. Normal, dysplastic and congenital nevi ( n  = 212) were collected from pregnant and non-pregnant women ranging from 18 to 45 years of age. Immunohistochemical staining was performed on these nevi using antibodies specifically directed against estrogen receptor α (ERα) and ERβ. ERα was not observed in any lesions; thus, ERβ was the predominant estrogen receptor in melanocytic cells from all types of nevi. Enhanced positivity for ERβ in normal nevi during pregnancy was noted, compared with non-pregnant controls including nevocytes residing in both the epidermal and dermal micro-environments ( P  = 0.005 and P  = 0.001 respectively). Nevi with increasingly melanocytic atypia showed increased ERβ in nevocytes nested within the epidermis. No additional increase in ERβ in atypical nevi was observed during pregnancy. For normal and congenital nevi, regardless of pregnancy status, dermally associated nevocytes tended to have greater ERβ immunoreactivity. Significant decreases in ERβ immunoreactivity were observed in congenital nevi from pregnant women compared with normal and dysplastic nevi from pregnant women. Our data suggest that nevi possess the capacity to be estrogen-responsive. Factors such as pregnancy and degree of atypia are associated with enhanced ERβ with the exception of congenital nevi where the melanocytes were unique in their response to pregnancy.     

不同孕期治疗妊娠梅毒对妊娠结局的影响

目的:明确不同孕期妊娠梅毒患者的治疗对妊娠结局的影响。方法:共124例妊娠梅毒妇女接受了驱梅治疗,包括孕早期42例,孕中期40例,孕晚期42例。结果:124例妊娠梅毒患者中不良妊娠33例,包括流产死产14例,先天性梅毒患儿19例。孕早期不良妊娠率为7.14%,孕中期为22.5%,孕晚期为50%,三组比较差异有统计学意义(P0.05)。结论:妊娠梅毒患者治疗越早,不良妊娠发生率越低。     

Pointillist nevi

BACKGROUND: Atypical melanocytic nevi and cutaneous melanoma are often marked by variation in color. However, there are examples of "benign" explanations for irregularities in pigmentation, such as perifollicular hypopigmentation or hyperpigmentation. OBJECTIVE: The purpose of this study was to correlate the clinical and histologic features of 3 unusual melanocytic nevi consisting exclusively of multiple, tiny, dark brown to black dots on a skin-colored background, which we have termed pointillist nevi. METHODS: Histologic examination was performed of the single pointillist nevus from each of 3 patients (all women; aged 28, 39, and 47 years). RESULTS: The diameters of the pointillist nevi were 2, 3.5, and 5.5 mm. Individual dots were approximately 0.1-0.25 mm. Each of the 3 nevi showed a different histologic correlate for the dots, either (1) discrete, densely pigmented, junctional melanocytic nests; (2) isolated dermal pigmented melanocytic nests; or (3) discrete clusters of melanophages in the papillary dermis. CONCLUSION: Pointillist nevi are benign melanocytic nevi with histologic correlates similar to those of the "brown globules" observed by dermoscopy in uniformly pigmented nevi. However, the dots seen in pointillist nevi can be visualized without magnification. The clinical and histologic features of pointillist nevi add to the spectrum of unusual patterns of pigmentation that may be encountered in benign melanocytic lesions.     

Phosphoinositide 3-kinase is not overexpressed in melanocytic lesions

BACKGROUND: Although various studies have stressed the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN)-PI3K-AKT pathway in the progression of melanocytic lesions, little is known about the expression pattern of PI3K in these lesions. OBJECTIVE: To investigate the expression pattern of PI3K in benign and dysplastic nevi, primary melanomas, and metastatic melanomas and the role of PTEN and PI3K in melanocytic tumor progression. METHODS: Tissue microarrays were constructed using formalin-fixed, paraffin-embedded archival tissue blocks from 89 melanocytic lesions: 17 benign nevi, 18 dysplastic nevi, 23 primary melanomas, and 31 metastatic melanomas. Expression of PTEN and PI3K (p85 and p110 subunits) was evaluated immunohistochemically, and the number of cells and labeling intensity were assessed semiquantitatively. RESULTS: Both benign and dysplastic nevi showed strong cytoplasmic staining with PTEN, which was subsequently less in melanomas and completely lost in the metastatic lesions. Eleven of 17 (64%) benign nevi, seven of 10 (70%) dysplastic nevi, four of 23 (17%) primaries, and one of 31 (3%) visceral or lymph node metastasis showed strong positivity. Loss of PTEN expression from benign and dysplastic nevi to melanoma was statistically significant (p=0.001). Although few cells showed reactivity for phosphoinositide 3-kinase (PI3 kinase)-p85 subunit, strong positivity was not detected in the cytoplasm of benign, malignant, or metastatic lesions, except for a single visceral metastasis. Three of 13 (23%) nevi showed positivity for the p110 subunit. No positivity was observed in the dysplastic nevi. Two of 22 (9%) melanomas, one of 14 (7%) visceral metastasis, and three of 12 (25%) lymph node metastasis showed strong positivity. There was no statistical difference in PI3 kinase expression in benign and malignant melanocytic lesions (p=0.2). CONCLUSION: PI3K is not overexpressed in melanocytic lesions.     

Digital computer analysis of dermatoscopical images of 260 melanocytic skin lesions; perimeter/area ratio for the differentiation between malignant melanomas and melanocytic nevi

BACKGROUND: Digital computer analysis of dermatoscopical images has been reported to facilitate the differential diagnosis of pigmented skin lesions in recent years. OBJECTIVE: The aim of our study was to perform digital computer analysis of a set of different melanocytic lesions and compare the objective results. METHODS: The set of 260 melanocytic lesions (150 excised difficult cases (46 melanomas, 47 atypical nevi, 57 common nevi and 110 unexcised common nevi) was automatically analysed by the digital dermatoscopical system microDERM. We searched for differences in asymmetry, size, compactness and colour distribution. Perimeter/area ratio was calculated. RESULTS: The perimeter/area ratio was detected as the most important criterion for differentiation between malignant and benign melanocytic lesions (sensitivity 91.3% and specificity 90.7% for malignant melanomas vs. all benign nevi; sensitivity 91.3% and specificity 80.8% for melanomas vs. clinically atypical nevi). Differences in size of the lesion, shape and asymmetry of colour were found and statistically verified. Using step-wise logistic regression the formula for calculation of probability of malignant nature of every analysed lesion was constructed. CONCLUSION: The perimeter/area ratio is a simple parameter for the differential diagnosis of melanocytic skin lesions.     

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.     

Nevi and melanoma in pregnancy

The influence of pregnancy on melanocytic nevi and malignant melanoma (MM) continues to be a controversial issue. Over the past 50 years, case reports and uncontrolled studies have suggested that nevi are more likely to become malignant during pregnancy, and MM diagnosed during pregnancy has a poor prognosis. Clinical and laboratory observations suggested that pregnancy-associated hormones may influence nevi and MM. Recent clinical and laboratory evidence suggests, however, that pregnancy does not influence the prognosis of MM, nor does it seem to cause significant changes in nevi. A clear link between hormones and MM has not been established. An analysis of this evidence is presented along with practical recommendations for the patient.     

Melanocytic nevi of the breast: a histologic case-control study

BACKGROUND: Melanocytic nevi in the genital, acral, and flexural sites often display clinical and histologic features that may simulate melanoma. We verified whether this is the case also for nevi of the breast. METHODS: Eleven dermatopathologists, from nine Italian Institutions, collected the specimens of melanocytic lesions from the breast and other body sites, excluding the acral, genital, and flexural areas, as controls. Cases and controls were matched for sex and age. All nevi were observed 'blindly' and simultaneously by all participants. For each lesion, 10 histological parameters were analyzed: asymmetry, absence of lateral demarcation of melanocytes, lentiginous proliferation, nested and dyshesive pattern, intraepidermal melanocytes above the basal layer, involvement of the hair follicle, absence of maturation of dermal melanocytes, melanocytic atypia, fibroplasia of the papillary dermis, and lymphocytic dermal infiltrate. Each parameter was scored 2 when present and 1 when absent or not valuable. A total score was calculated for each lesion. Results were statistically analyzed by the chi-square test and the Mann-Whitney U-test. RESULTS: One hundred and one nevi came from the breast area and 97 from elsewhere. Breast nevi exhibited significantly more atypical features than nevi from other sites. In particular, breast nevi with intraepidermal melanocytes, melanocytic atypia, and dermal fibroplasia were significantly more numerous. We did not find any sexual difference. CONCLUSIONS: To avoid undue concerns, dermatopathologists should be aware that melanocytic nevi of the breast may show a high degree of atypical features.     

Clinically unapparent melanocytic nevi on the prepuce

Background:  Melanocytic nevi from the genitalia are uncommon. Nevi on the vulva are much better described than nevi on male genitalia. To our knowledge, a systematic study of preputial melanocytic nevi has not been reported.
Objective:  To investigate the frequency of clinically unapparent melanocytic nevi on a series of preputial excisions.
Materials and Methods:  We undertook a prospective histologic study of the prepuce obtained in a series of 372 consecutive circumcisions for phimosis performed during the period between January 2000 and December 2002.
Results:  Incidental preputial melanocytic nevi were detected in four (1.1%) patients. Lesions were dermal in nature, most of them showed pigment in superficial dermal nests and had pseudovascular spaces. There were no cytologic atypia, mitotic figures, architectural disorder or inflammatory infiltrate. The mean (standard deviation, SD) of the maximum diameter was 1.08 (0.85) mm (range 0.34–1.79 mm). The mean age (SD) of the patients was 41.5 (4.95) years (range 29–58).
Conclusions:  Incidental melanocytic nevi, although uncommonly, can be observed in the prepuce. They are detected in adults and may pose a diagnostic challenge when they are detected in the setting of concurrent malignant melanoma.     

Hormones, nevi, and melanoma: an approach to the patient

For many years, clinicians have been concerned about a potential adverse effect of pregnancy-associated hormones and exogenous hormones on melanocytic nevi and malignant melanoma. Today, these issues are more significant as women have delayed childbearing into their 30's and 40's, and the likelihood of diagnosis with melanoma during pregnancy is enhanced. More recent clinical, epidemiologic, and laboratory studies have shed some light on the relationship among hormones, nevi, and melanoma in pregnancy.     

Limitations of dermoscopy in the recognition of melanoma

OBJECTIVE: To compare dermoscopic features of melanocytic nevi with those of early melanomas that were not excised initially because of their uncharacteristic clinical and dermoscopic appearance. DESIGN: Retrospective study of the baseline images of 325 melanocytic skin lesions that were observed by digital dermoscopy and finally excised because of changes over time. SETTING: A dermatologic clinic and a dermatologic department at a university hospital. MAIN OUTCOME MEASURES: Comparison of baseline images of melanomas and melanocytic nevi by pattern analysis, the ABCD rule of dermoscopy, and the 7-point checklist. RESULTS: Baseline dermoscopic images of 262 melanocytic nevi and 63 melanomas from 315 patients were included in the analysis. The patterns of dermoscopic features observed in the baseline images of melanocytic lesions finally diagnosed as melanomas during follow-up did not differ substantially from the patterns observed in the baseline images of melanocytic nevi. Pattern analysis, the ABCD rule of dermoscopy, and the 7-point checklist failed to achieve adequate diagnostic accuracy for melanoma. In retrospect, no dermoscopic feature or pattern of features could be identified that reliably differentiated between melanomas and melanocytic nevi at the time of the first presentation. CONCLUSION: Dermoscopy depends on the appearance of classic dermoscopic features and is therefore limited in the diagnosis of very early and mainly featureless melanomas.     

The risk of melanoma and neurocutaneous melanosis associated with congenital melanocytic nevi

Congenital melanocytic nevi are commonly encountered in clinical practice. Although the development of malignant melanoma arising in small and intermediate congenital melanocytic nevi is rare, there is a significant risk of malignant degeneration associated with large congenital melanocytic nevi, in particular those that arise on the torso in the so-called "bathing trunk" distribution, where the risk is estimated to be about 2.5% to 5%. The risk of malignant melanoma arising within a large congenital melanocytic nevus is highest in the first 5 to 10 years of life and carries a significant mortality. Large congenital melanocytic nevi, in particular those overlying the posterior axis and occurring in the context of multiple satellite melanocytic nevi, are also associated with the development of neurocutaneous melanosis, which may result in neurologic and neurodevelopmental sequelae and is associated with a significant risk of primary central nervous system melanoma and death.     

Unna's and Miescher's nevi: two different types of intradermal nevus: hypothesis concerning their histogenesis

In 1991, we tentatively introduced the classification of Ackerman and Magana-García for acquired melanocytic nevi in our laboratory. We soon realized that every acquired intradermal melanocytic nevus might be easily classified into either Unna's or Miescher's patterns and that this classification had both clinical implications and significant histological differences. The decisive discriminative feature between Unna's and Miescher's nevi is that Unna's nevus is an almost purely adventitial lesion confined to expanded papillary dermis and, many times, to the perifollicular dermis too. In Miescher's nevus melanocytes diffusely infiltrate both adventitial and reticular dermis in a wedge-shaped pattern. With these concepts in mind, every acquired intradermal melanocytic nevus can be easily classified as either Unna's or Miescher's. We studied 751 acquired melanocytic nevi; 458 (61%) of them were intradermal; of these, 234 were Unna's nevi and 224 were Miescher's nevi. Eighty- three per cent of the nevi from the head and neck were intradermal nevi, whereas on the trunk and limbs junction and compound nevi were the most frequent (56%). When intradermal nevi were divided into Unna's and Miescher's patterns, it resulted that 91% of Miescher's nevi located on the face and 94% of intradermal nevi on the face were Miescher's nevi. In contradistinction, 87% of the Unna's nevi located on the neck, trunk, and limbs, and 96% of intradermal nevi from these locations were Unna's nevi. Only on the scalp was there no clear predominance of one type of intradermal nevus. A series of other histological characteristics were significantly predominant (P = 0.000) in either Unna's or Miescher's nevi. Unna's nevi had more: junctional nests above the intradermal component (40% versus 20%), a radial pattern of intradermal nests (38% versus 0%), vascular-like clefts lined by nevus cells (48% versus 4%), and in depth maturation (94% versus 0%). Miescher's nevi had more: pilosebaceous follicles within the nevus (100% versus 51%), subnevis folliculitis (12% versus 1%), large isolated melanocytes along the basal epidermal layer (47% versus 11%), multinucleated nevocytes (89% versus 44%), and adipocytes within the nevus (53% versus 11%). In conclusion, Unna's and Miescher's nevi are 2 subsets of acquired melanocytic nevus with clinical implications and significant histological differences. A histogenetic hypothesis is proposed on the basis of their histological structure.     

Spectrophotometric analysis of melanocytic naevi during pregnancy

Malignant melanoma is the most common cancer during pregnancy, but it is unknown whether melanocytic naevi in general are activated. A total of 381 melanocytic naevi in 34 Caucasian primigravidae were examined using spectrophotometric intracutaneous analysis (SIAscopy) technology in early pregnancy and prior to delivery. The Siagraphs of each naevus were then compared in order to evaluate changes over time. A total of 163 melanocytic naevi in 21 nulliparous women served as an additional control group. At the first visit none of the Siagraphs examined for the case or control groups aroused suspicion of dysplastic naevus or melanoma and no significant structural changes were noted during the observation period. However, 2.1% of the melanocytic naevi in the pregnant group increased and 1.3% decreased in size. Corresponding figures in the non-pregnant group were 1.8% and 0%, respectively. Only one naevus in a pregnant woman increased slightly in epidermal pigmentation, and a decrease in pigmentation was noted in 3.7% of the melanocytic naevi in the cases and 1.8% in the controls. None of the differences within or between the groups was statistically significant. We conclude that pregnancy does not influence the appearance of pigmented naevi. A changing naevus during pregnancy should be examined carefully and considered for excision and histopathology.     

BRAF mutation: a frequent event in benign, atypical, and malignant melanocytic lesions of the skin

BRAF mutations have recently been detected with a high frequency (66%) in cutaneous melanoma. All those mutations are activating, with a single substitution (T1796A) at codon 599 (V599E) accounting for over 90%. To investigate the stage in which those mutations occur in the currently proposed sequential malignant transformation of melanocytes, 22 benign melanocytic nevi, 23 melanocytic atypical nevi, and 25 primary cutaneous melanoma from 63 different patients were examined for BRAF mutations using DNA extracted from microdissected formalin-fixed and paraffin-embedded tissues, and a two-round PCR-RFLP-based strategy. A subset of samples was sequenced for mutation confirmation. Sixteen benign (73%) and eleven atypical (52%) melanocytic nevi, and thirteen melanoma (56%) demonstrated BRAF mutations at codon 599, and no statistically significant differences were detected among all three types of lesions. No mutations were demonstrated in microdissected epidermal keratinocytes adjacent to melanocytic lesions having BRAF mutations. No correlation was detected between BRAF mutational status and age, sun exposure, and Clark's level in malignant melanoma. However, comparing only atypical nevi and melanoma lesions the frequency of BRAF mutation is significantly greater in male (78%) than female (35%) patients (P = 0.0194). The previously described T1796A point mutation was detected in 17 of 18 mutated samples, and a novel mutation consisting of a substitution of valine for lysine (GT1795-96AA) was detected in one melanoma case. Our findings of a high frequency of BRAF mutations at codon 599 in benign melanocytic lesions of the skin indicate that this mutation is not sufficient by itself for malignant transformation.     

Melanoma in association with acquired melanocytic nevus in Japan: a review of cases in the literature

Background Malignant melanomas clinically and/or histologically associated with melanocytic nevi have been reported worldwide. Approximately 20% of malignant melanomas in Caucasians, most of which are found on the trunk and proximal extremities, develop in association with pre‐existing melanocytic nevi. In Japan, however, over half of all melanomas are acral lentiginous melanomas (ALMs) on the hands and feet; melanomas on sun‐exposed areas are seen less frequently in Japanese people than in Caucasians. As ALMs are not usually accompanied by melanocytic nevi and there have been no reviews of the literature or statistical data regarding Japanese cases of melanomas with melanocytic nevi, dermatologists in Japan have few opportunities to see melanomas associated with pre‐existing melanocytic nevi. Methods Here we report a case of a superficial spreading melanoma that was formed on a melanocytic nevus on the trunk, and we review for the first time the case reports from the Japanese literature. Results and Conclusions With regard to the reported cases, melanomas associated with melanocytic nevi were mainly superficial spreading melanomas and nodular melanomas on the trunk or extremities; ALMs were rarely associated with nevi, indicating a trend similar to that observed in Caucasians. These findings suggest that the low frequency of associations between melanomas and melanocytic nevi in Japan reflects racial differences in the frequencies of each type of melanoma.     

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.