Dermoscopic Predictors of Benignity and Malignancy in Equivocal Lesions Predominated by Blue Color.

BACKGROUND: Blue color in dermoscopy can be seen in a wide range of benign and malignant lesions, melanocytic or not. Some blue-colored dermoscopic criteria have been associated with specific tumors, such as blue-white veil with melanoma and homogeneous blue with blue nevi. However, when blue color occupies a large part of the lesion's surface, the dermoscopic assessment might be particularly challenging. OBJECTIVE: To identify dermoscopic predictors associated with benignity and malignancy in tumors characterized by a predominant dermoscopic presence of blue color. METHODS: We retrospectively screened our institutional database for tumors exhibiting blue color in at least 50% of their surface with available histopathologic diagnosis. Lesions with blue color covering less than 50% of their extent and lesions not histopathologically assessed were excluded. The dermoscopic images were evaluated for the presence of predefined criteria, including the characteristics of the blue color, coexisting colors, and the vascular structures. RESULTS: Of 91 included tumors, 53 were benign (35 blue nevi, 10 angiomas, and 8 seborrheic keratoses) and 38 malignant (12 melanomas and 26 basal cell carcinomas). Our analysis revealed 3 potent dermoscopic predictors of benignity: extension of blue color in more than 75% of the surface, diffuse distribution of blue color, and absence of vessels, posing a 2.3-fold, 5.6-fold, and 6.7-fold increased probability of benignity, respectively. In contrast, asymmetric distribution of blue color, blue clods, coexistence of gray color and linear vessels were significantly predictive of malignancy, posing a 8.9-fold, 2.8-fold, 13.5-fold, and 10.4-fold increased probability, respectively. CONCLUSION: In predominantly blue tumors, the probability of malignancy is high when blue color is seen in clods or is asymmetrically distributed and when gray color or linear vessels coexist. In contrast, a diffuse distribution of blue color, its expansion in more than 75% of the surface, and the absence of vessels are highly suggestive of a benign tumor.

Agminated blue nevi: a case series and updated dermoscopic review.

Blue nevi, usually presenting as solitary, bluish, asymptomatic macules or nodules, are formed by collections of dermal melanocytes that failed to complete their migration from the neural crest to the dermo-epidermal junction. The term "agminated blue nevi" refers to multiple lesions grouped, linear, or arranged in a blashkoid distribution. It is a relatively rare phenomenon with less than 35 cases reported in the literature, but only 14 cases with dermoscopic features. We report another 4 cases along with an updated dermoscopic review.

Generalized congenital epithelioid blue nevi (pigmented epithelioid melanocytomas) in an infant: Report of case and review of the literature.

The epithelioid blue nevus (EBN) is a variant of the blue nevus characterized by heavily pigmented epithelioid melanocytes and lightly or nonpigmented spindle cells. It may be associated with Carney complex, a multiple neoplasia syndrome. Congenital cases of EBN not associated with Carney complex are rarely reported. We herein describe an infant who presented with multiple blue-gray nodules and papules involving the head, trunk, and extremities at birth, the corresponding histopathologic findings, and genetic testing results.

Blue nevus and "malignant blue nevus:" A concise review.

Blue nevi are a heterogeneous group of lesions that can display a variety of different clinicopathological characteristics. Although attempts are made to classify each lesion into defined subtypes, there can be overlap between the subtypes. The clinical and histolopathologic features of common blue nevi and cellular blue nevi are discussed, as well as blue nevi with atypical features and malignant lesions with features of blue nevi.

Giant Blue Nevus: A New Association to Nevus of Ota.

Nevus of Ota, also known as oculodermal melanocytosis, is a congenital pigmentary condition that can affect structures in the distribution of the ophthalmic and maxillary divisions of the trigeminal cranial nerve. Malignant transformation, although rare, may occur within nevus of Ota and result in uveal, cutaneous, orbital or even dural melanoma. We present a new association of Nevus of Ota complicated with a giant orbital Blue Nevus in a young white male and the management of this tumor.

Disseminated Eruptive Blue Nevi in a Young Adult Patient.

Common blue nevi tend to be singular or localized, with multiple eruptive blue nevi being a rare occurrence. We report the case of a young adult who presented with multiple asymptomatic lesions that had appeared gradually over a few years. Physical examination revealed 30 distinct, blue-gray macules diffusely over the medial buttocks, lower back, and dorsal arms. Histopathology showed pigmented dendritic melanocytes with associated melanophages, features characteristic of blue nevus. This case demonstrates that eruptive blue nevi can present as numerous, disseminated lesions over multiple anatomic sites. Recognition of the various patterns of eruptive blue nevi and their benign nature can reduce unnecessary biopsies and work-up.

Melanocortin 1 receptor (MC1R) polymorphisms' influence on size and dermoscopic features of nevi.

The melanocortin 1 receptor (MC1R) is a highly polymorphic gene. The loss-of-function MC1R variants ("R") have been strongly associated with red hair color phenotype and an increased melanoma risk. We sequenced the MC1R gene in 175 healthy individuals to assess the influence of MC1R on nevus phenotype. We identified that MC1R variant carriers had larger nevi both on the back [p-value = .016, adjusted for multiple parameters (adj. p-value)] and on the upper limbs (adj. p-value = .007). Specifically, we identified a positive association between the "R" MC1R variants and visible vessels in nevi [p-value = .033, corrected using the FDR method for multiple comparisons (corrected p-value)], dots and globules in nevi (corrected p-value = .033), nevi with eccentric hyperpigmentation (corrected p-value = .033), a high degree of freckling (adj. p-value = .019), and an associative trend with presence of blue nevi (corrected p-value = .120). In conclusion, the MC1R gene appears to influence the nevus phenotype.

Nevus azul celular parotídeo, una tumoración inusual / Parotid cellular blue nevi, an unusual mass

Introducción: el nevus azul celular es una tumoración melanocítica dérmica benigna. En ocasiones, puede ser falsamente diagnosticada como lesiones malignas, entre ellas, el melanoma. Caso clínico: se trata de una mujer de 37 años que presentó una masa parotídea izquierda de cuatro meses de evolución correspondiente con un nevus azul celular. Discusión: la región de la cabeza y cuello es la tercera en frecuencia, tras la sacrococcígea y las extremidades. Ante una tumoración melanocítica, es importante la confirmación diagnóstica, debido a las similitudes, tanto clínicas como anatomopatológicas, del nevus azul celular con el melanoma maligno. Conclusiones: es muy importante el diagnóstico diferencial correcto, para lo cual es de ayuda el uso de las tinciones inmunohistoquímicas. El tratamiento de esta tumoración es la exéresis quirúrgica con márgenes, esto presenta un comportamiento benigno y baja tasa de recidiva.

Introduction: Cellular blue nevi is a benign dermal melanocytic tumor. Occasionally, it can be falsely diagnosed as malignant lesions, including melanoma. Clinical case: This is a 37-year-old woman who presented with a left parotid mass of four months of evolution, corresponding with a cellular blue nevi. Discussion: The region of the head and neck is the third in frequency, after the sacrococcygeal and the extremities. During the study of a melanocytic tumor, diagnostic confirmation with a biopsy is important, due to the similarities, both clinical and pathological, of cellular blue nevi with malignant melanoma. Conclusions: the correct differential diagnosis is very important, for which immunohistochemical study is helpful. The treatment of this tumor is the surgical excision with margins, presenting benign behaviour and low recurrence rate.

Reticulin immunostaining revisited.

INTRODUCTION: Reticulin staining has been suggested as an inexpensive tool in the differential diagnosis of melanoma versus benign nevi. In the present study, reticulin immunostaining patterns in malignant melanomas, benign intradermal nevi, and blue nevi were observed. The concordance in evaluation of the pattern between observers was also done. MATERIALS AND METHODS: A retrospective search was performed in the computer database of the Ackerman Academy of Dermatopathology for "melanoma," "melanocytic nevus," and "blue nevus". Fifty-six melanomas (30 of nodular subtype and 26 of superficial spreading subtype), 54 benign compound nevi, and 27 blue nevi were selected for the study. Patterns of reticulin staining in the dermis and the basement membrane in these melanocytic lesions were evaluated and the concordance between the two groups of authors was assessed. Statistical evaluation was performed with the Statistica(®) 10 program, Tulsa, OK. Concordance of the pattern evaluation was evaluated using Cohen's kappa coefficient. RESULTS: Melanomas show a variable basement membrane pattern some of which show flat, thin and smooth pattern. Benign nevi almost never showed this flat pattern at the basement membrane zone. In the dermis, melanomas showed reticulin fibers surrounding groups of melanocytic cells while nevi predominantly had reticulin fibers around individual cells. There was greater agreement in evaluating the dermal component compared to the basement membrane pattern. CONCLUSION: The dermal reticulin staining pattern may be of some value in the diagnosis of melanocytic lesions, but poor concordance in evaluation of the basement membrane zone pattern limits its usefulness.

Molecular alterations in malignant blue nevi and related blue lesions.

Malignant blue nevi (MBN) are extremely rare dermal melanocytic tumors that arise in association with atypical cellular blue nevi (ACBN), cellular blue nevi (CBN), common blue nevi (BN), or de novo. The frequency of BRAF, NRAS, and KIT mutations in malignant melanoma varies according to histological subtype and localization. These mutations are rarely observed in blue nevi, which have recently been shown to carry activating mutations in GNAQ/GNA11 genes. Only few small molecular studies of MBN have been published. The aim of the present study was to analyze in MBN and related blue lesions such as ACBN, CBN, and BN the prevalence of BRAF, NRAS, KIT, GNAQ, and GNA11 gene mutations and their association with clinicopathological features. We included in our study 12 MBN, 6 ACBN, 29 CBN, and 35 common BN diagnosed between 1996 and 2014. Sanger sequencing method was used for mutation analysis. Overall, GNAQ exon 5 mutation was the most frequent alteration (46 %), in 2 of 12 (17 %) MBN, 1 of 6 (17 %) ACBN, 22 of 29 (76 %) CBN, and 13 of 35 (37 %) common BN. BRAF V600E and GNA11 exon 5 mutations were respectively detected in 3 of 12 (25 %) and in 2 of 12 (17 %) MBN while none in ACBN, CBN, and common BN. None of the cases harbored NRAS exon 2/3, KIT exon 9/11/13/17/18, or GNAQ/GNA11 exon 4 mutations. GNAQ gene exon 5 mutations are rare in MBN and ACBN but frequent in CBN and common BN. Remarkably, BRAF V600E and GNA11 exon 5 mutations were only detected in MBN, whereas none were found in ACBN, CBN, or common BN. Our data contribute new elements to the limited data on molecular alterations in MBN.

Genetics of melanocytic nevi.

Melanocytic nevi are a benign clonal proliferation of cells expressing the melanocytic phenotype, with heterogeneous clinical and molecular characteristics. In this review, we discuss the genetics of nevi by salient nevi subtypes: congenital melanocytic nevi, acquired melanocytic nevi, blue nevi, and Spitz nevi. While the molecular etiology of nevi has been less thoroughly studied than melanoma, it is clear that nevi and melanoma share common driver mutations. Acquired melanocytic nevi harbor oncogenic mutations in BRAF, which is the predominant oncogene associated with melanoma. Congenital melanocytic nevi and blue nevi frequently harbor NRAS mutations and GNAQ mutations, respectively, while Spitz and atypical Spitz tumors often exhibit HRAS and kinase rearrangements. These initial 'driver' mutations are thought to trigger the establishment of benign nevi. After this initial phase of the cell proliferation, a senescence program is executed, causing termination of nevi growth. Only upon the emergence of additional tumorigenic alterations, which may provide an escape from oncogene-induced senescence, can malignant progression occur. Here, we review the current literature on the pathobiology and genetics of nevi in the hope that additional studies of nevi promise to inform our understanding of the transition from benign neoplasm to malignancy.

Blue lesions.

Blue color is found in a wide range of malignant and benign melanocytic and nonmelanocytic lesions and in lesions that result from penetration of exogenous materials, such as radiation or amalgam tattoo or traumatic penetration of particles. Discriminating between different diagnostic entities that display blue color relies on careful patient examination and lesion assessment. Dermoscopically, the extent, distribution, and patterns created by blue color can help diagnose lesions with specificity and differentiate between benign and malignant entities. This article provides an overview of the main diagnoses whereby blue color can be found, providing simple management rules for these lesions.

Lack of GNAQ and GNA11 Germ-Line Mutations in Familial Melanoma Pedigrees with Uveal Melanoma or Blue Nevi.

Approximately 10% of melanoma cases are familial, but only 25-40% of familial melanoma cases can be attributed to germ-line mutations in the CDKN2A - the most significant high-risk melanoma susceptibility locus identified to date. The pathogenic mutation(s) in most of the remaining familial melanoma pedigrees have not yet been identified. The most common mutations in nevi and sporadic melanoma are found in BRAF and NRAS, both of which result in constitutive activation of the MAPK pathway. However, these mutations are not found in uveal melanomas or the intradermal melanocytic proliferations known as blue nevi. Rather, multiple studies report a strong association between these lesions and somatic mutations in Guanine nucleotide-binding protein G(q) subunit alpha (GNAQ), Guanine nucleotide-binding protein G(q) subunit alpha-11 (GNA11), and BRCA1-associated protein-1 (BAP1). Recently, germ-line mutations in BAP1, the gene encoding a tumor suppressing deubiquitinating enzyme, have been associated with predisposition to a variety of cancers including uveal melanoma, but no studies have examined the association of germ-line mutations in GNAQ and GNA11 with uveal melanoma and blue nevi. We have now done so by sequencing exon 5 of both of these genes in 13 unique familial melanoma pedigrees, members of which have had either uveal or cutaneous melanoma and/or blue nevi. Germ-line DNA from a total of 22 individuals was used for sequencing; however no deleterious mutations were detected. Nevertheless, such candidate gene studies and the discovery of novel germ-line mutations associated with an increased MM susceptibility can lead to a better understanding of the pathways involved in melanocyte transformation, formulation of risk assessment, and the development of specific drug therapies.