Newborn Skin: Part II. Birthmarks.

Birthmarks in newborns can be classified as vascular, melanocytic or pigmented, or markers of underlying developmental abnormalities of the nervous system. A nevus simplex is a benign capillary malformation. Newborns with a nevus flammeus can be safely treated before one year of age with a pulsed dye laser to reduce the visibility of lesions. Infantile hemangiomas should be treated with systemic beta blockers if there is a risk of life-threatening complications, functional impairment, ulceration, underlying abnormalities, permanent scarring, or alteration of anatomic landmarks. Dermal melanocytosis is a benign finding that is easily recognized and does not warrant further evaluation. A solitary congenital melanocytic nevus that is less than 20 cm in diameter may be observed in primary care; children with larger or multiple nevi should be referred to pediatric dermatology due to the risk of melanoma. Newborns with skin markers of occult spinal dysraphism (other than a simple, solitary dimple) should have lumbar spine imaging using ultrasonography or magnetic resonance imaging.

What are congenital melanocytic nevi?

Congenital melanocytic nevi (CMN) are special types of moles. CMN happen when extra pigment-making cells (melanocytes) grow in a baby's skin while the baby is forming before birth. They are not caused by anything their parent did or didn't do during pregnancy. These moles are there when the baby is born, stay on the skin for life, and grow as the child grows.

PRAME Expression in Melanocytic Proliferations in Special Sites.

The subset of nevi occurring at special sites (eg, acral skin, anogeni-tal region, breast, ear, flexural surfaces) have normal histologic variations that preclude the use of routinely used diagnostic criteria for malignancy. Suggested criteria for differentiating malignant special-site lesions from benign lesions have been described, but there is an unmet need for a validated test aiding in the delineation of benign and malignant lesions at special sites. Preferentially expressed antigen of melanoma (PRAME) expression has been characterized as a relatively specific marker of melanoma, but not within the specific population of special-site lesions. This study aimed to determine if PRAME may serve as a specific marker of melanoma within the population of special-sites lesions.

Perineural differentiation in neurotized nevi.

BACKGROUND: Perineuriomatous melanocytic nevi are rare and this may indicate the similar embryological source of melanocytes and peripheral nerves in the neural crest. Neurotized melanocytic nevi may resemble nerve sheath tumors histologically, and show schwannian differentiation. However, literature on whether neurotized nevi differentiate into perineural cells is controversial. We examined our cases of neurotized nevi for evidence of perineural differentiation. MATERIALS AND METHODS: A total of 100 benign nevi with large neurotized component (microscopically involved a low power field 4.2 mm in diameter) were prospectively evaluated in excisional biopsy samples. Immunohistochemical stainings for EMA, Claudin1, Glut1 and neurofilament were performed. RESULTS: Perineural differentiation was immunohistochemically detected in the neurotized component of the nevi in 61% of the cases with EMA and in all the cases with Glut1 and Claudin1. Axonal differentiation was not detected with neurofilament. The expression pattern, especially with Glut1, was usually in form of partial or complete staining surrounding the Meissner's corpuscle-like structure (MCLS). Also, a linear/curvilinear staining pattern was observed particularly with Claudin1. A diffuse staining pattern with EMA, Glut1 and Claudin1 was detected in a case with a microscopically distinct whorl structure, and in which spindle cells are separated from the superficial epithelioid melanocytes with an abrupt transition histologically. These findings of the case are compatible with previous reports of perineuromatous nevus. CONCLUSION: Perineural differentiation is not uncommon and immunohistochemically observed in all nevi with a relatively large component of neurotization. To prevent misdiagnosing desmoplastic melanoma and overtreating patients, it is crucial to be aware of perineuromatous nevi.

Digging into uncertainty: a case report on Spitz lesions.

Spitz lesions represent a spectrum of melanocytic proliferations, and they include Spitz nevi, atypical Spitz tumors, and Spitz melanomas. Atypical Spitz tumors are intermediate melanocytic lesions with features between benign Spitz nevi and malignant Spitz melanomas. They often present a diagnostic challenge to pathologists and dermatologists alike because they can mimic melanoma, especially high-grade atypical Spitz tumors. Importantly, they present a relevant clinical management challenge because definite recommendations for their management and treatment have not yet been established. Here we present the case of a young patient with a high-grade atypical Spitz tumor along with the diagnostic procedure and further management. We also review potential pitfalls in the literature that should alert clinicians to the more aggressive potential of the lesion, such as some BRAF fusions.

TERT promoter mutations in atypical melanocytic lesions: A series of seven cases with adverse melanoma-specific outcome.

The majority of melanocytic proliferations can be readily categorized as benign or malignant based on histologic assessment under the microscope by a trained dermatopathologist. However, a subset of lesions, termed Atypical Melanocytic Proliferations (AMPs), are histologically ambiguous, leading to possible diagnostic error and suboptimal treatment. Mutations in the promoter region of the catalytic subunit of telomerase, telomerase reverse transcriptase (TERT), are commonly found in melanomas but are rare in melanocytic nevi. In this study, we aimed to determine the prevalence of hot spot TERT promoter (TERT-p) mutations in AMPs with adverse melanoma-specific outcome. Studies were approved by respective institutional review boards. Using a multi-center database, we identified seven cases of melanocytic proliferations with a clinical follow-up period of at least 4 years, which were initially diagnosed as AMPs, and which recurred either as melanoma at site of prior biopsy or as metastatic melanoma. Sequencing of the TERT-p region showed hotspot mutations in three cases (43 %), suggesting that TERT-p mutations are enriched and could aid in the identification of AMPs with adverse outcome. In comparison with existing ancillary techniques for prognostication of AMPs, TERT-p mutation analysis may have advantages in terms of cost effectiveness and turnaround time, and is a promising diagnostic parameter with potential widespread utility.

Ganglioneuroma Arising in Congenital Melanocytic Nevus in a Patient with Cardiac Anomalies: A Case Report.

A congenital melanocytic nevus is a benign melanocyte proliferation, that may be complicated by malignant transformation. We are reporting a three-year-old girl, who had a giant congenital melanocytic nevus on her back, that was treated by serial surgical excisions with tissue expander insertion. Histopathological examination confirmed the diagnosis of congenital melanocytic nevus with ganglioneuroma. Out of approximately 250 case reports on congenital melanocytic nevus, we identified only two reports of medium/large congenital melanocytic nevus with cutaneous ganglioneuroma. Due to the potential malignant transformation of congenital melanocytic nevus, reporting the features and characteristics of such rare findings may help in further understanding congenital melanocytic nevus, its associations, and prognosis.

A clinical and biologic review of congenital melanocytic nevi.

Congenital melanocytic nevi (CMN) are the result of aberrations in the mitogen-activated protein kinase signal transduction pathway caused by postzygotic somatic mutations. The estimated incidence of newborns with CMN is 1%-2%. The main complications of CMN include proliferative nodules, melanomas, and neurocutaneous melanosis, and the latter two are the most troublesome issues to address. Treatments are primarily taken into account for aesthetic purposes and the reduction of melanoma risk. Due to the much lower incidence of malignant transformation observed in recent studies than in previous data, clinical management paradigms for CMN patients have gradually shifted towards conservative observation and close monitoring. Surgery and lasers are still the main treatments, and targeted therapy may be a promising strategy to help manage complications. With the increase in awareness of mental health, increasing focus has been placed on the quality of life (QoL) and psychological issues of both CMN patients and their parents. Recent studies have revealed that families coping with CMN might endure intense pressure, a major loss in QoL, and psychological problems after diagnosis and during treatment. Here, we sought to present an overview of genetic basis, complications, treatments, and psychological issues related to CMN and hope to provide better management for patients with CMN.

"THE DANGEROUS BRASSIERE" AND THE NEVUS ASSOCIATED POLYPOID MELANOMA: CONNECTION SEEMS PLAUSIBLE?

The development of cutaneous melanoma of the skin based on dysplastic nevus is not uncommon. The causes of the progression of nevi to melanomas are numerous and not well understood at present. Certain genetic and epigenetic factors have a major influence on this evolution. We describe a 46-year-old female patient with multiple dermal melanocytic nevi who developed a polypoid melanoma in one of them. After a carefully performed anamnesis, the mole that developed into melanoma was found to be localized in the dorsal area adjacent to the brassiere and underwent permanent and daily mechanical irradiation during the last 6-7 years. Around this mole there were 5 other moles with similar clinical and dermatoscopic morphology, which did not transform into melanomas and were not subjected to mechanical irritation. The patient had a dermatological examination 6 years ago and it was suggested that this lesion has to be surgically removed, which she declined. The patient was treated surgically and the lesion suspicious for cutaneous melanoma was removed in two stages according to the generally accepted AJCC/EJC recommendations. In parallel, 5 additional melanocytic nevi were removed, which histologically had features of dysplastic dermal melanocytic nevi but no signs of progression to melanoma. This article discusses the causes of nevus -associated melanomas and emphasizes the thesis of potential malignant transformation through mechanical irritation - in this case that of the brassiere. The moles localized in this area, although clinically and dermatoscopically inapparent, should be treated surgically. This painless, short-term manipulation has a preventive effect on the future development of cutaneous melanomas.

Incidence of neurocutaneous melanosis in Japanese pediatric patients with congenital melanocytic nevi.

Neurocutaneous melanosis (NCM) is a rare, non-hereditary neurocutaneous disorder characterized by excessive melanocytic proliferation in the skin and central nervous system. As no major studies have covered the incidence of NCM among Japanese patients with congenital melanocytic nevi (CMN), we prospectively investigated the incidence of NCM among Japanese patients who underwent initial treatment for CMN. The relationship of CMN and NCM was also investigated. Japanese pediatric patients with CMN under 1 year of age were included between January 2020 and November 2022, and all patients underwent brain MRI to check for NCM in this study. NCM lesions were most frequently seen in the amygdala, followed by the cerebellum, brainstem, and cerebral hemispheres. NCM was diagnosed on brain MRI in 31.6% of the 38 patients with CMN and in 25.0% of patients with no prior examination or treatment. Distribution and size of CMN, number of satellite nevi, rugosity and nodules were strongly associated with the existence of NCM, and these findings may guide a future registry study with a large cohort of CMN patients.

Acquired Melanocytic Nevi Mimicking Acral Lentiginous Melanoma in a Patient Taking a BRAF Inhibitor.

This case report describes a patient in their 60s with metastatic colon cancer who developed multiple new dark nevi within 2 months of initiating encorafenib and panitumumab therapy.

Refining the application of PRAME-a useful marker in high CSD and acral melanoma subtypes.

Pathologic discordance affecting patient management may approach 20% in melanocytic cases following specialist review. The diagnostic utility of PRAME has been highlighted in several studies but interpretative challenges exist including its use in severely dysplastic compound nevi showing progression to melanoma in situ, nevoid melanoma, and coexisting nevi with melanoma. We examine the PRAME status of a broad spectrum of melanocytic lesions including challenging, dysplastic nevi with severe atypia from a large Irish patient cohort. Retrospective review of the dermatopathology database was conducted to evaluate the PRAME staining characteristics of two hundred and twenty-one melanocytic lesions using a commercially available PRAME antibody (EPR20330). The proportion of nuclear labeling and intensity of staining was recorded. The sensitivity and specificity of PRAME for in situ and malignant melanocytic lesions was 77% and 100%, respectively. Virtually all of our melanoma in situ from high-cumulative sun damaged (CSD) skin (22/23) and all acral lentiginous melanoma (5/5) were PRAME positive while 80% (8/10) of our lentigo maligna melanoma showed diffuse expression. None of our benign subgroup showed diffuse immunoexpression (0/82), including thirty-seven moderate or severely dysplastic nevi. In all cases of melanoma in situ arising in association with a dysplastic compound nevus (0/10), no immunoexpression was observed in the nevic component while in five cases of melanoma in situ with coexistent, intradermal nevus immunostaining was confined to the in situ component. A total of 100% (2/2) of desmoplastic melanomas and 50% (4/8) of nodular melanomas were PRAME positive. PRAME is a sensitive and highly specific immunostain in the diagnosis of in situ and invasive melanoma and we emphasize its application in the evaluation of high CSD and acral melanoma subtypes as well as in challenging threshold cases.

Clinical, Radiologic, and Histopathologic Features that Distinguish a Pigmented Plexiform Neurofibroma from a Congenital Melanocytic Nevus.

A 13-year-old Hispanic boy with no significant medical etymology presented with a chief complaint of widespread brown macules and patches. He had a large and evenly pigmented brown patch, with a centrally located 2.2 cm × 1.2 cm soft and darkly pigmented plaque, which became more apparent with tension applied to the surrounding skin (Figure 1). The patient's mother stated that the plaque was present since birth and had increased in size over time. The clinical differential diagnoses included a congenital melanocytic nevus (CMN), a large café au lait macule (CALM), and a Becker's nevus with a congenital smooth muscle hamartoma.

Differentiating between early melanomas and melanocytic nevi: A state-of-the-art review.

Clinicians and dermatologists are challenged by accurate diagnosis of melanocytic lesions, due to melanoma's resemblance to benign skin conditions. Several methodologies have been proposed to diagnose melanoma, and to differentiate between a cancerous and a benign skin condition. First, the ABCD rule and Menzies method use skin lesion characteristics to interpret the condition. The 7-point checklist, 3-point checklist, and CASH algorithm are score-based methods. Each of these methods attributes a score point to the features found on the skin lesion. Furthermore, reflectance confocal microscopy (RCM), an integrated clinical and dermoscopic risk scoring system (iDscore), and a deep convoluted neural network (DCNN) also aids in diagnosis. RCM optically sections live tissues to reveal morphological and cellular structures. The skin lesion's clinical parameters determine iDscore's score point system. The DCNN model is based on a detailed learning algorithm. Therefore, we discuss the conventional and new methodologies for the identification of skin diseases. Moreover, our review attempts to provide clinicians with a comprehensible summary of the wide range of techniques that can help differentiate between early melanomas and melanocytic nevi.

Giant Congenital Melanocytic Nevus of the Male External Genitalia: A Pediatric Case Report of Diagnosis, Evaluation and Management.

Congenital melanocytic nevi are present at birth or develop within the first few months of life. Giant congenital melanocytic nevi are a rare variant and may involve the external genitalia with a confluent "bathing trunk" distribution. Rapid growth of proliferative nodules of melanocytic cells may cause disfigurement and anatomical distortion resulting in psychological distress and loss of functionality. We report the case of a neglected 17-year-old nonverbal male who received a resection of a Giant Congenital Melanocytic Nevi (GMN) engulfing the penis and scrotum with final resected dimensions of 36.0×20.0×8.0 cm.

Targetoid haemosiderotic nevus: four cases and a literature review.

BACKGROUND: Targetoid haemosiderotic nevus (THN), a distinct clinical form of melanocytic nevus, is characterized by the sudden development of a purpuric halo surrounding a pre-existing nevus, easily mistaken for melanoma. OBJECTIVES: To summarise the clinical, dermoscopic and histopathological findings of THN in order to better recognize and manage this condition. MATERIALS & METHODS: We describe four cases and provide a review of the literature based on a search in PubMed. Overall, the clinical, dermoscopic and pathological findings of 15 THN cases are summarised. RESULTS: THN was characterized by a sudden onset of a purpuric halo surrounding a pre-existing nevus without any apparent trigger which occurred mainly in young females. Dermoscopically, the central nevus showed a black-brown, globular or homogeneous pattern, possibly interspersed with reddish, purple, or black structureless areas and comma-shaped vessels. The peripheric purpuric halo had two patterns: one with homogeneous reddish or purplish red areas, and another with an inner pale and outer homogeneous reddish or purplish red zone. The pathological findings showed an intradermal or compound nevus, dilated vessels, and extravasated erythrocytes, possibly accompanied by perivascular inflammatory infiltration and fibrin and hemosiderin deposits. CONCLUSION: THN is a benign lesion that usually requires no intervention other than follow-up observation. Dermoscopy is a useful non-invasive diagnostic tool, and biopsy can be avoided. The purpuric halo resolves spontaneously within two to four weeks with rare recurrence.