Increased Melanocytic Nevi in Patients with Inherited Ichthyoses: Report of a Previously Undescribed Association

Abstract: Ichthyosis is a heterogeneous cornification disorder. Melanocytic lesions have not been previously described in association with ichthyosis. Their clinical importance lies in the fact that they may simulate melanoma clinically and dermoscopically, as seen in epidermolysis bullosa. The objective of this study was to evaluate the clinical, dermoscopic, and histopathologic features of nevi and lentigines in 16 patients with autosomal recessive congenital ichthyosis—lamellar ichthyosis and nonbullous ichthyosiform congenital erythroderma. Patients underwent general clinical examination dermoscopy. The more suspicious lesions were excised and to histopathologic examination. Most patients (n = 13) reported no personal or familial history of melanoma or atypical nevi. All of the patients had at least five atypical melanocytic lesions. Ten of the 16 patients had at least one atypical nevus or lentigo. This study suggests that increased atypical melanocytic nevi may be a feature of long‐standing congenital ichthyoses. Whether this finding is disease‐related or a coincidental observation is difficult to ascertain. As an unequivocal discrimination from malignant melanoma in vivo is not always possible, regular clinical follow‐up of patients with ichthyosis and increased or unusual nevi is recommended.     

Melasma and its association with different types of nevi in women: A case-control study

Background

Very little is known about possible association of nevi and melasma. The study objective was to determine if there is an association between melasma and existence of different kinds of nevi.

Methods

In a case-control study, 120 female melasma patients referred to dermatology clinic of Ardabil and 120 patients referred to other specialty clinics who lacked melasma were enrolled after matching for age. Number of different types of nevi including lentigines and melanocytic nevi were compared between case and control group patients. Data were entered into the computer and analyzed by SPSS 13 statistical software.

Results

Mean number of lentigines was 25.5 in melasma group compared to 8 in control group(P < 0.01). Mean number of melanocytic nevi was 13.2 in cases compared to 2.8 in control group(P < 0.001). Multivariate analysis showed that existence of freckles, lentigines and more than three melanocytic nevi were positively related to developing melasma. The chance of melasma increased up to 23 times for patients having more than three melanocytic nevi. Congenital nevi were observed among 10% both in case and control groups. Campbell de morgan angiomas were seen among 26 patients(21.8%) in case group compared to 6 patients(5%) in control group.

Conclusion

Existence of lentigines and melanocytic nevi increases chance of having melasma     

Genital lentigines and melanocytic nevi with superimposed lichen sclerosus: a diagnostic challenge

BACKGROUND: Benign pigmented lesions of the genitalia, such as genital lentigines and melanocytic nevi, often show clinical and histopathologic features highly suggestive of malignant melanoma (MM). Superimposed changes of lichen sclerosus (LS) may cause real concern and lead to an erroneous diagnosis of MM. OBJECTIVE: This study was performed to assess clinicopathologic characteristics of genital lentigines and melanocytic nevi with associated LS. METHODS: We performed a retrospective review of 5 cases. RESULTS: Histopathologic sections of the 2 cases of genital lentigines with concurrent changes of LS showed a lichenoid lymphocytic infiltrate and pigment incontinence with melanophages in a fibrosed papillary dermis, features reminiscent of completely regressed MM. The 3 cases of genital melanocytic nevi and superimposed LS were sharply circumscribed, relatively symmetric, but revealed confluent nests varying in size and shape and pagetoid upward spread of melanocytic nests and single melanocytes. Changes of LS extended beyond the melanocytic proliferation. CONCLUSION: Genital lentigines and melanocytic nevi with associated LS may show features that mimic MM.     

LEOPARD Syndrome: What Are Café Noir Spots?

Abstract:  Lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome (multiple lentigines syndrome) is most often characterized by multiple lentigines and cardiac conduction defects. Café noir spot is a term proposed, by analogy to café au lait spots, for the larger and darkly pigmented patches that are frequently observed in patients with this syndrome. Although presumed by some authors to represent lentigines, the histologic features of café noir spots have not been well documented in the literature. Only two previous cases have been reported in which a biopsy of the café noir spots than melanocytic nevi. We describe the histologic characteristics of seven café noir spots in six patients with lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome. Three lesions represented melanocytic nevi (one with dysplastic features), and four were compatible with lentigo simplex. These findings help our understanding of the histologic spectrum of pigmented lesions in lentigines, electrocardiographic abnormalities, ocular hypertelorism, pulmonary stenosis, abnormalities of genitalia, retarded growth, and deafness syndrome.     

Congenital melanocytic nevi: clinical and histopathologic features, risk of melanoma, and clinical management

Congenital melanocytic nevi occur in approximately 1% of newborns and are usually classified according to their size. Giant congenital melanocytic nevi are most simply defined as melanocytic nevi that are greater than 20 cm in largest dimension; whereas small congenital nevi are defined as melanocytic nevi less that 1.5 cm in largest dimension. Congenital nevi can exhibit distinctive histologic features that can help in differentiating them from common acquired nevi. Giant congenital melanocytic nevi are associated with an increased risk of the development of melanoma. On the other hand, there is evidence of an increased melanoma risk in patients with small congenital nevi. Nevertheless, the risk of malignant transformation in small congenital nevi and the lifetime melanoma risk in patients with small congenital nevi remain controversial. In large part due to inconsistency in the reported literature describing patients with congenital melanocytic nevi, the risk of melanoma in these patients remains unclear and consistent guidelines for clinical management do not exist. We review the literature and comment on the course of management for these patients at the Massachusetts General Hospital Pigmented Lesion Clinic.     

Melanocytic lesions of the genital area with attention given to atypical genital nevi

Melanocytic lesions of the genital area are rare. They arise mainly in the vulva, although they can also occur less frequently in the perineum, mons pubis and male genitalia and represent 10-12% of pigmented lesions of White women. These pigmented lesions include melanocytic nevi, lentigines, melanocytic nevi with architectural disorder and atypia of melanocytes (dysplastic nevi) and melanomas with microscopic features similar to those seen elsewhere on the body. There is a small subset of benign nevi named atypical melanocytic nevi of the genital type (AMNGT) that occur in young women, with distinctive histologic features in some cases overlapping morphologically with those of melanoma. Thus, it is important to distinguish AMNGT from melanomas in terms of prognosis and treatment. We retrieved 58 cases of genital pigmented lesions diagnosed at our hospital from 1986 to 2008 to evaluate their clinicopathologic features with especial consideration to those cases with atypical features. Thirty-two cases (55%) were common nevi, 10 (17%) lentigines, 6 (10%) melanomas, 3 (5%) dysplastic nevi and 1 blue nevus. Six cases (10%) corresponded to AMNGT and were taken from women with a median age of 21 years. All cases showed symmetry, and the melanocytic proliferation was well demarcated at the lateral margins. The junctional component was very prominent and formed by round or fusiform nests with common retraction artifact and/or cellular dyshesion or as a single cell proliferation with mild (33%) to moderate (67%) cytologic atypia, focal pagetoid spread (17%) and a benign-appearing dermal component (83%) with maturation and dense eosinophilic fibrosis in the superficial dermis. Neither nuclear atypia of melanocytes in the superficial dermis nor dermal mitoses were observed. AMNGT were excised, and no recurrences were recorded in the follow up (median 10.5 years). Therefore, it seems that there is no evidence that AMNGT are precursors of dysplastic nevi or melanomas.     

Speckled lentiginous nevus: within the spectrum of congenital melanocytic nevi

BACKGROUND: Currently, there is disagreement as to whether speckled lentiginous nevi (nevi spili) are congenital or acquired pigmented lesions. Part of this controversy is related to the natural history of these lesions that often present at birth as hyperpigmented patches and then take several years to reach their more readily recognized spotted form. Arguments in favor of speckled lentiginous nevi as a subtype of congenital nevi include the following observations: multiple reports of lesions present at birth or noted soon thereafter; patterns of distribution reflecting embryonic development; hamartomatous behavior with various types of nevi (eg, junctional nevi, blue nevi, and Spitz nevi) presenting in the same lesion over time; and histologic features of congenital melanocytic nevi within the spots. Herein we present additional evidence for the congenital nature of speckled lentiginous nevi. OBSERVATIONS: Ten patients are described with congenital pigmented lesions that had the clinical appearance of speckled lentiginous nevi in whole or in part. These lesions either evolved and acquired an appearance more suggestive of "classic" congenital nevi, or they existed as "hybrid" lesions with portions appearing as classic congenital nevi adjacent to or admixed with portions appearing as speckled lentiginous nevi. On histologic examination, biopsy specimens from the spots within these lesions showed features of congenital melanocytic nevi. CONCLUSIONS: These 10 cases, along with the arguments outlined above, provide strong support for the hypothesis that speckled lentiginous nevi are a subtype of congenital melanocytic nevi.     

The histology of "congenital features" in early acquired melanocytic nevi

To test the specificity of certain histologic features claimed to be frequent in congenital melanocytic nevi, 66 of 313 consecutive newborn infants without congenital nevi (verified by perinatal examination) were addressed in a questionnaire 2 1/2 years after birth. Fifty children with acquired melanocytic nevi were reexamined clinically and biopsies were performed in 15. Congenital features were found in seven biopsy specimens from the indubitably acquired melanocytic nevi. These nevi were larger and more speckled in color than melanocytic nevi without "congenital features." It is concluded that the histologic features said to be specific for congenital nevi are, in fact, not specific. The possible relationship between these features and an increased melanoma risk cannot be refuted by the present study, but the risk of misinterpretation based on congenital features as the sole criterion in the prediction of the potential malignancy of melanocytic nevi is real.     

Meyerson Phenomenon in Children: Observation in Five Cases of Congenital Melanocytic Nevi

Abstract:   To describe the characteristics of five pediatric patients with the Meyerson phenomenon associated with congenital melanocytic nevi, five cases were reviewed to retrieve information relating to clinical presentation, treatment and evolution of the eczematous phenomenon and of the nevi. Three of five patients were male. Mean age at presentation of the Meyerson phenomenon was 23 months (range: 4 mos–4 yrs). Three patients presented with only one halo eczematous lesion, while two patients presented with more then one halo eczematous lesions. The halo eczematous lesions were located on the leg, arm, and trunk in four, two, and two patients, respectively. All were associated with congenital melanocytic nevi with overlying hypertrichosis. Four were treated with topical corticosteroids, and five developed some degree of hypopigmentation within the nevic lesion. In children with Meyerson phenomenon associated with congenital hairy melanocytic nevi, neither trigger to the eczematous eruption nor preferential gender or anatomical site location was identified. The Meyerson phenomenon evolved towards hypopigmentation of the congenital melanocytic nevic lesions in all patients but no other cutaneous changes were observed on follow-up.     

Chromosomal translocations as a mechanism of BRAF activation in two cases of large congenital melanocytic nevi

Genetic studies of melanocytic tumors have mainly demonstrated activation of oncogenes such as NRAS or BRAF through point mutations. In two cases of large congenital melanocytic nevi, we observed a chromosomal translocation involving the BRAF oncogene on chromosome 7q34, resulting in both cases in removal of the auto-inhibitory N-terminal regulatory domain (hence the Ras-guanosine triphosphate binding domain) of BRAF from its protein kinase domain. This is early evidence of BRAF activation through chromosomal translocation in melanocytic tumors. Because BRAF point mutations are rather rare in congenital melanocytic nevi and melanoma arising in non-sun-exposed area, the molecular mechanism of oncogenic activation as described here could be a recurrent molecular feature in these groups of melanocytic tumors.     

Acquired unilateral melanocytic nevi in otherwise normal skin

We describe a case with numerous melanocytic nevi in otherwise normal skin. A 5-year-old girl presented with more than 100 small pigment lesions on her left arm, shoulder and upper back without underlying light brown macule. The pigment lesions were first found on her left forearm at 3 months old and gradually increased along with her growth. Skin biopsy from a pigmented lesion shows a pathological change in compound-type melanocytic nevus without any atypical changes. Speckled lentiginous nevus is known to have multiple melanocytic lesions on the underlying brown macule from birth. Partial unilateral lentiginosis is characterized by unilateral lentigines with histopathological changes in lentigo but not melanocytic proliferation in the dermis. Agminated melanocytic nevi tend to be clustered together in a circumscribed area, whereas in the present case melanocytic nevi were segmentally arranged but not agminated. We consider that this is an unusual type of mosaicism of melanocytic disorders.     

Neurocutaneous melanosis

Neurocutaneous melanosis (NCM) is a rare congenital disorder characterized by the presence of large or multiple congenital melanocytic nevi in association with benign or malignant proliferation of melanocytes in the leptomeninges. NCM is believed to occur as a consequence of an error in morphogenesis in neural ectoderm in the developing embryo. Animal models suggest that aberrant expression of the hepatocyte growth factor/scatter factor (HGF/SF) may be involved in the pathogenesis in the NCM. While the majority of patients with NCM have large congenital melanocytic nevi in a posterior axial distribution, a significant proportion of patients present with multiple smaller nevi in the absence of a single larger lesion. Neurologic manifestations generally occur within the first two years of life, and are often related to increased intracranial pressure. Associated structural anomalies of the CNS have been reported in NCM, particularly the Dandy-Walker complex. The long-term clinical significance of characteristic magnetic resonance findings in neurologically asymptomatic patients is unclear. Approximately half of NCM patients develop CNS melanoma. The prognosis of symptomatic patients remains poor.     

Inflammatory cellular infiltrates in melanocytic nevi.

We examined 1,054 melanocytic nevi [137 (13%) simple lentigines, 158 (15%) junctional nevi, 337 (32%) compound nevi, and 422 (40%) dermal nevi] for the presence of lymphohistiocytic infiltrates. The following criteria were evaluated: age and sex of the patient, location, histological type, horizontal and vertical diameter, increase of melanocytes in the basal layer of the epidermis, increase of melanophages in the papillary dermis, melanin content of keratinocytes, and melanin content of nevus cells. Lymphohistiocytic infiltrates were measured semiquantitatively; their presence within the center, in the lateral margins, or both was also determined. The results were analyzed statistically by means of chi-square tests and univariate and multivariate analyses. We found that 824 lesions (78%) were associated with a lymphohistiocytic infiltrate; whereas 230 (22%) were not. This infiltrate was weak in 273 cases (33%), moderate in 411 cases (50%), pronounced in 130 cases (16%), and very strong in 10 cases (1%). Multivariate analyses revealed that the only criteria associated with the presence of lymphohistiocytic infiltrates were the increase of melanocytes in the basal layer and the vertical thickness in compound nevi. All other parameters were statistically insignificant. We conclude that melanocytic nevi with a junctional hyperplasia of melanocytes--i.e., mostly early stages such as simple lentigines, junctional nevi, and superficial compound nevi--are often associated with a moderate to pronounced cellular stromal reaction. Their presence may reflect the appearance of antigens on proliferating melanocytes. It may also represent a stromal reaction to necrotic tumor cells and keratinocytes within the dermoepidermal junction. These findings rule out any relationship to an increase of melanin pigment.(ABSTRACT TRUNCATED AT 250 WORDS)     

Histologic features of melanocytic nevi seen in association with mycosis fungoides

BACKGROUND: Many different tumors have been reported to occur simultaneously as collision lesions. To date, no such events have been reported between mycosis fungoides (MFs) and melanocytic neoplasms. METHODS: Two cases are presented in which patches of MF were superimposed on melanocytic nevi. In addition, 967 biopsies of MF from 411 patients were identified in an 8-year retrospective database search. Patient pathology history summaries were reviewed to identify inflamed nevi, atypical nevi, and melanoma submitted for histologic evaluation from this population. RESULTS: The occurrence of MF in a congenital nevus was associated with a halo phenomenon restricted to the affected region of the nevus in one patient. In the other patient, nests of two morphologies (lymphocytic and melanocytic) in the same biopsy presented a potentially confusing histologic picture. No other cases of MF superimposed on a nevus were identified in 967 biopsies from 411 patients with a histological diagnosis of MF seen over the past 8 years. In this population, 57 biopsies of melanocytic lesions were identified from 28 patients, including three atypical nevi and three melanomas. CONCLUSIONS: The presence of MF superimposed on a nevus is rare and may lead to confounding histologic features or the development of a halo nevus phenomenon.     

Numerous,small, darkly pigmented melanocytic nevi: the cheetah phenotype

BACKGROUND: The presence of multiple atypical nevi or numerous melanocytic nevi increases the risk for the development of cutaneous melanoma. OBJECTIVE: We sought to describe a distinct clinical phenotype characterized by numerous (>100), small (< or =4 mm), darkly pigmented melanocytic nevi that are uniform in color. METHODS: Biopsy specimens from 6 patients (3 men and 3 women; age range, 44 to 81 years) with this clinical phenotype were reviewed and compared with a database of melanocytic lesions analyzed by the Yale Dermatopathology Laboratory (YDL) in the year 2000. RESULTS: Of the 6 patients, 4 had multiple primary melanomas develop (n = 2-4), ranging from in situ to 1.0 mm in depth. The other 2 patients each had 1 nevus with severe cytologic atypia. When compared with the YDL database, our patients were more likely to have the following pigmented lesions: junctional melanocytic nevi, junctional lentiginous nevi, junctional nevi with cytologic atypia, and simple lentigines (P <.001). CONCLUSIONS: The longitudinal evaluation of patients with this phenotype can be challenging because similar-appearing pigmented lesions (small and uniformly dark-brown to black) had a range of histologic diagnoses from simple lentigo to junctional lentiginous nevus to thin melanoma.     

The relationship between melanocytes and peripheral nerve sheath cells (Part I): melanocytic nevus (excluding so-called "blue nevus") with peripheral nerve sheath differentiation

Among thousands of specimens of melanocytic nevi, not including giant congenital melanocytic nevus or blue nevus, 42 melanocytic nevi that showed peripheral nerve sheath differentiation were collected. The patterns of melanocytic nevi with peripheral nerve sheath differentiation may be classified into three groups: 1) "neurotized and neural nevi" with nests of "neuroid cords" and "nevic corpuscles" (the most common pattern); 2) nerve fascicle-like structures with no relation to neurotized and neural nevi; and 3) palisading melanocytes of a nevus in nests of conventional melanocytic nevi (a rare pattern). Each pattern may represent a different expression of nerve sheath differentiation in melanocytic nevi. Some melanocytic nevi with nerve fascicle-like structures show discrete structures closely resembling authentic nerve fascicles, confirming a close relationship between melanocytes and peripheral nerve sheath cells (Schwann cells and probably perineurial cells in part) and suggesting derivation of the two types of cells from common precursor cells of the neural crest and their de novo development in the dermis rather than by Abtropfung of melanocytes from the epidermis. In addition, the high prevalence of Unna, Miescher, and superficial congenital nevi in melanocytic nevi with peripheral nerve sheath differentiation suggests a different character or process for these congenital melanocytic nevi than for Clark and Spitz nevi (junctional and compound types).     

Epidermolysis bullosa nevus: an exception to the clinical and dermoscopic criteria for melanoma

BACKGROUND: Large acquired melanocytic nevi that occur in patients with epidermolysis bullosa (EB), referred to as EB nevi, may pose a diagnostic challenge because of their clinical and dermoscopic resemblance to melanoma. These unconventional melanocytic nevi have been encountered in all categories of hereditary EB, most of them in childhood. Although some of the reported cases have an alarming clinical appearance that is indistinguishable from melanoma, long-term follow-up has confirmed the benign nature of these rarely encountered melanocytic lesions. The histopathologic patterns of these nevi range from a banal congenital pattern to the problematic persistent pseudomelanoma pattern. OBSERVATION: We describe the clinical, dermoscopic, and histopathologic features of a large EB nevus in a toddler. Clinically, the lesion was markedly asymmetrical and irregularly pigmented with foci of stippled pigmentation and scarring, which easily fulfilled the ABCD criteria for melanoma. Accordingly, a false-positive score resulted when dermoscopy was performed. Histopathologically, a pattern of persistent melanocytic neoplasm was observed. In the following 18 months, dynamic changes of the lesion included near-complete disappearance of the pigment, which was replaced by scar, milia, and areas of healing ulcers. CONCLUSION: Epidermolysis bullosa nevi are dynamic melanocytic lesions that may simulate melanoma.     

Genetic alterations in melanocytic tumors

In the last decade, significant progress has been made in our understanding of the genetic alterations in melanocytic tumors. The most exciting finding is the discovery of oncogenic BRAF mutations in both malignant melanoma and melanocytic nevi. This finding indicates that activation of the mitogen-activated protein kinase pathway may be a critical initiating step of melanocytic neoplasia, and that the fundamental difference between melanoma and nevi may lie in the inhibitory machinery for this oncogenic signaling. In addition, different genetic alterations identified in melanomas at different sites and with different levels of sun exposure have been shown, indicating that there are several distinct genetic pathways in the development of melanoma. Different patterns of genetic alterations have also been identified among different kinds of melanocytic nevi. While acquired nevi and small congenital nevi show a high frequency of BRAF mutations regardless of their anatomic localization, the mutations were rare in medium-sized congenital nevi and giant congenital nevi. Spitz nevi show no BRAF mutations, while a subset of cases show HRAS mutations, often associated with a copy number increase of chromosome 11p. The clear differences in genetic aberration patterns have significant clinical implications in the diagnosis and treatment of melanocytic tumors.     

Neurocutaneous melanosis in association with proliferative skin nodules

We report the case of a 15-year-old boy with giant congenital melanocytic nevi on his back, buttocks, and rear of the two proximal thirds of his thighs, and neurocutaneous melanosis, diagnosed when he was 3 years old. Three melanocytic nodules were present in the giant nevi that were suspected to have malignant degeneration. A biopsy of these nodules was carried out, and histological study revealed benign proliferative melanocytic nodules within the giant congenital melanocytic nevi.     

Histologic characteristics of vulvar nevocellular nevi

Reports in the literature stress the premalignant potential of vulvar melanocytic lesions and the unusual histologic features associated with some vulvar nevi in premenopausal women. We examined biopsies of 85 pigmented vulvar lesions taken from women 13 to 73 years of age. There were 59 nevocellular nevi, 16 lentigines, 4 melanomas, and 6 miscellaneous lesions. The nevocellular nevi were compared to a control series of 200 nevi from the torsos of women 20 to 60 years old. Three vulvar nevi were considered to be unusual, but not dysplastic. These histologically unusual nevi occurred in women 20 to 30 years old. The lesions exhibited notable enlargement of junctional melanocytic nests with variability in the size, shape and position of the nests. Similar changes were not observed in the control group. There was a significant association (p less than 0.05) between the occurrence of these unusual lesions and their presentation on the vulva; however, these lesions showed no predilection for any particular site on the vulva. There was no evidence of an increased incidence of vulvar dysplastic nevi when compared with the control series.