Histopathology of skin melanocytic lesions.

Melanocytic lesions are instable tumors, the genome of which and its changes determinate their morphology and biological properties. Intermediate lesions share histomorphological features of both, nevi and melanoma. Melanocytomas represent a group of them separated on the basis of recent molecular-biological studies. The article summarizes benign, intermediate, malignant and combined melanocytic skin lesions and offers practical recommendations for diagnosis.

Dermoscopic-Guided Shave Removal of Acquired Facial Melanocytic Nevi in Dark-Skinned Individuals.

BACKGROUND: Acquired melanocytic nevi are common benign skin lesions that require removal under certain circumstances. Shave removal is a straightforward treatment modality with a risk of recurrence. OBJECTIVE: To evaluate the outcome of dermoscopy-guided shave removal of acquired melanocytic nevi in the face of dark-skinned individuals who are more liable to postsurgical complications. METHODS: The study was conducted on 64 patients with acquired facial melanocytic nevi. Serial shave removal using a razor blade guided by dermoscopic examination was done until nevus-free tissue was seen, followed by electrocauterization of the base. Cosmetic outcome, patients' satisfaction, and recurrence rate were evaluated during follow-up. RESULTS: Excellent cosmetic outcome was achieved in 54.69% of patients, while 39.06% had an acceptable outcome, and 6.25% of patients had poor cosmetic outcome. Meanwhile, the recurrence rate was noticed in 5 cases only (7.8%). CONCLUSION: Dermoscopic-guided shave removal provides an easy procedure of treating common melanocytic nevi with an acceptable cosmetic result and a lower rate of recurrence even in patients with darker skin phenotypes.

Trauma plays an important role in acral melanoma: A retrospective study of 303 patients.

INTRODUCTION: Acral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive. METHODS: A retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed. RESULTS: Traumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment. CONCLUSION: This study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.

The potential of facial nevi in personal identification.

Forensic anthropologists dealing with personal identification (PI) of human remains have recently stressed the need to explore the potential of "secondary identifiers" for identifying victims who died in particular events for whom images often represent the main antemortem data available. Being the face the part most exposed in images, characteristics as pigmented skin lesions (PSLs), can be crucial if combined with other input. Since no data is available on frequencies and distribution of facial PSLs in the general population, this study aims at systematically collecting such data to verify their potential in PI and to open a debate on the aid that "secondary identifiers", regardless of their specific nature, can give to the identification of the deceased in specific forensic contexts. A retrospective analysis on three-dimensional facial models of 1039 Italian subjects (from 4 to 84 years old) was conducted to examine the incidence of PSLs discriminated according to size and position in well-defined facial areas. From the collected data we developed a probabilistic approach providing the likelihood ratio (LR) for two settings: (1) the relative frequencies of nevi in the various facial areas, providing the deriving compound probability of owning a certain facial PSLs pattern; and (2) codes describing the facial nevi pattern of each individual of our population, thus testing their uniqueness and so their potential in PI. The calculated LRs mostly proved high identifying strength, particularly when provided by the compound probability-based approach. Data on incidence and position of facial nevi, their generated codes, and the probabilistic approach here presented, all constitute a starting point for advancing secondary identifiers. Nonetheless, although this preliminary study proved facial PSLs as valuable and potentially useful for identification, their significance and validity should be interpreted with caution as we are still at the first theoretical step clearly based on ideal conditions, and thus further investigations are due on the limitations of their use in practical identifying settings. Therefore, being this systematic study only a preliminary one in its nature, it is recommended not to use this kind of approach until further studies will test its validity in several practical conditions.

Thickness of melanocytes in giant congenital melanocytic nevus for complete surgical excision: clinicopathological evaluation of 117 lesions according to the area and size.

BACKGROUND: Giant congenital melanocytic nevi (GCMN) are usually defined as nevi that exceed 20 cm in maximal diameter or 15% of the total body surface area. There have been reports of life-long malignant change risks arising from GCMN, leading to surgical excision of GCMN. This study aims to evaluate the thickness of melanocytes based on clinical factors in order to provide objective information for the complete resection of the lesion. METHODS: Overall, 75 patients diagnosed with GCMN between 2000 and 2021 were included, and their clinical records were collected retrospectively. 117 pathologic slides obtained during excision were reviewed to measure nevus thickness. Clinical factors were assessed with a generalized estimated equation model for association with nevus thickness. RESULTS: The thickness of nevus was significantly associated with the location and size. Nevus thickness was more superficial in the distal extremity than in the head and trunk (P = 0.003 [head]; P < 0.001 [trunk]; P = 0.091 [Proximal extremity]). Nevi sized 60 cm or more were significantly deeper than those measuring 20-29.9 cm (P = 0.035). An interaction between size and location existed (P < 0.001). Trunk and distal extremity lesions consistently exhibited uniform thickness regardless of lesion size, whereas head and proximal extremity lesions showed variations in thickness based on lesion size. CONCLUSION: GCMNs have differences in thickness according to location and size. Therefore, it is necessary to devise an approach optimized for each patient to treat GCMN. In the study, it was emphasized that the thickness of GCMN is correlated with clinical factors, specifically the location and size of the nevus. Consequently, these findings underscore the need for individualized treatment plans for effective surgical intervention.

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.

Multispectral Fundus Photography of Choroidal Nevi With Trans-Palpebral Illumination.

Purpose: The purpose of this study was to investigate the spectral characteristics of choroidal nevi and assess the feasibility of quantifying the basal diameter of choroidal nevi using multispectral fundus images captured with trans-palpebral illumination. Methods: The study used a widefield fundus camera with multispectral (625 nm, 780 nm, 850 nm, and 970 nm) trans-palpebral illumination to examine eight subjects diagnosed with choroidal nevi. Geometric features of nevi, including border clarity, overlying drusen, and lesion basal diameter, were characterized. Clinical imagers, including scanning laser ophthalmoscopy (SLO), autofluorescence (AF), and optical coherence tomography (OCT), were utilized for comparative assessment. Results: Fundus images depicted nevi as dark regions with high contrast against the background. Near-infrared (NIR) fundus images provided enhanced visibility of lesion borders compared to visible fundus images and SLO images. Lesion-background contrast measurements revealed 635 nm SLO at 11% and 625 nm fundus at 42%. Significantly enhanced contrasts were observed in NIR fundus images at 780 nm (73%), 850 nm (63%), and 970 nm (67%). For quantifying the diameter of nevi, NIR fundus images at 780 nm and 850 nm yielded a deviation of less than 10% when compared to OCT measurements. Conclusions: NIR fundus photography with trans-palpebral illumination enhances nevi visibility and boundary definition compared to SLO. Agreement in diameter measurements with OCT validates the accuracy and reliability of this method for choroidal nevi assessment. Translational Relevance: Multispectral fundus imaging with trans-palpebral illumination improves choroidal nevi visibility and accurately measures basal diameter, promising to enhance clinical practices in screening, diagnosis, and monitoring of choroidal nevi.

Review: Are moles senescent?

Melanocytic nevi (skin moles) have been regarded as a valuable example of cell senescence occurring in vivo. However, a study of induced nevi in a mouse model reported that the nevi were arrested by cell interactions rather than a cell-autonomous process like senescence, and that size distributions of cell nests within nevi could not be accounted for by a stochastic model of oncogene-induced senescence. Moreover, others reported that some molecular markers used to identify cell senescence in human nevi are also found in melanoma cells-not senescent. It has thus been questioned whether nevi really are senescent, with potential implications for melanoma diagnosis and therapy. Here I review these areas, along with the genetic, biological, and molecular evidence supporting senescence in nevi. In conclusion, there is strong evidence that cells of acquired human benign (banal) nevi are very largely senescent, though some must contain a minor non-senescent cell subpopulation. There is also persuasive evidence that this senescence is primarily induced by dysfunctional telomeres rather than directly oncogene-induced.

The clinico-pathological spectrum of plaque-type blue naevi and their potential for malignant transformation.

AIMS: Plaque-type blue naevi are rare melanocytic tumours presenting as large, pigmented plaques at birth or during childhood. There is a risk for malignant transformation, but no larger comprehensive studies exist and the diagnosis is challenging, especially on limited biopsy material. The aim is to describe the clinicopathological features and behaviour of the disease more comprehensively. METHODS AND RESULTS: We retrieved eight plaque-type blue naevi, presenting as large, pigmented plaques (median = 7 cm; range = 3-26) most frequently affecting the scalp (four) followed by the cheek, arm, abdominal wall and gluteal cleft (one each), with a slight female predilection. Median age at time of biopsy was 39.5 years (range = 15-90), but three tumours had been present at birth and one since childhood. Histopathologically, the tumours were poorly circumscribed and composed of cellular fascicles of uniform spindle cells in a background of variably prominent pigmented dendritic cells affecting dermis and subcutaneous tissues. The majority had mutations in GNAQ. One tumour showed malignant transformation, characterised by an expansile nodule of pleomorphic epithelioid melanocytes with rhabdoid morphology, high mitotic activity and areas of necrosis. This patient developed metastatic melanoma to lymph nodes. All patients are alive with a median follow-up of 60 months. CONCLUSION: Plaque-type blue naevi are diagnostically challenging tumours with risk for malignant transformation. Awareness and familiarity with the salient clinicopathological features are necessary for reliable diagnosis, and long-term clinical follow-up is required to monitor for malignant transformation.

Neonatal cutaneous melanoma with cutaneous metastasis: a case report and review of literature.

Malignant melanoma, a rare skin cancer in children, primarily affects individuals over 10 years old. Giant congenital nevi, found in about 1% of newborns, increases the risk. However, the development of melanoma from a pre-existing giant congenital nevus diagnosed during the neonatal period is exceptionally rare. We present a case of congenital melanoma in a newborn, where nodules grew on an existing nevus on the baby's back. Literature on managing such cases was reviewed. This case highlights the importance of considering malignant transformation in congenital nevi and the challenges in their management. Due to limited reported cases over 80 years, conclusive findings on survival and treatment options are difficult to provide. Clinicians should report outcomes to develop a management algorithm for neonatal melanoma. Further studies are needed to enhance understanding of causes and treatment for patients with congenital giant hairy nevi and associated melanoma.

Metabolomic analysis reveals the biological characteristics of giant congenital melanocytic nevi.

Giant congenital melanocytic nevi (GCMN) is a congenital cutaneous developmental deformity tumor that usually occurs at birth or in the first few weeks after birth, but its pathogenesis is still unclear. In this study, nuclear magnetic resonance-based metabolomics strategy was employed to evaluate the metabolic variations in serum and urine of the GCMN patients in order to understand its underlying biochemical mechanism and provide a potential intervention idea. Twenty-nine metabolites were observed to change significantly in serum and urine metabolomes, which are mainly involved in a variety of metabolic pathways including glyoxylate and dicarboxylate metabolism, TCA cycle and metabolisms of amino acids. The substantial cores of all the disturbed metabolic pathways are related to amino acid metabolism and carbohydrate metabolism and regulate the physiological state of the GCMN patients. Our results provide the physiological basis and physiological responses of GCMN and will be helpful for better understanding the molecular mechanisms of GCMN in future research.

Frequency of naevus cells in lymph nodes of melanoma and breast cancer patients.

INTRODUCTION: We aimed to study the frequency (prevalence) and histology of benign melanocytic naevus cells in regional lymph nodes in relation to age and sex and nodal location. MATERIAL AND METHODS: Histopathology reports of sentinel lymph node (SLN) biopsies from melanoma patients, 2002 - 2014, and from breast cancer patients, 2010- 2019, were obtained from records of a single hospital in England. All sections were similarly processed and examined. For standardisation, presence of naevus cells was assessed in a single node per patient: the first SLN biopsied (melanoma) or the node nearest the first SLN (breast cancer). RESULTS: Associations were tested using Fisher's exact test. Naevus cells were found in 10% (60/585) of melanoma patients' index SLNs. Frequency varied significantly by anatomic region: 13% in axillary to 0% cervical SLNs (p = 0.03), but not by sex or age. Within nodes, naevus cells were present in capsular or pericapsular tissue (93%), or trabeculae (7%). In breast cancer patients' index axillary nodes, 6% (11/196) contained naevus cells, all intracapsular. In the predominant 40-69 years age-group, prevalence was similar in breast cancer (7%) and female melanoma (9%) patients, but in those aged 70-100, prevalence was lower in breast cancer (2%) than in female melanoma (15%) patients (p = 0.05). CONCLUSIONS: Standard methods of assessment yielded no clear pattern of naevus cell frequency in lymph nodes by age or sex, but confirmed naevus cell location as mostly intracapsular.

Clinical characteristics of intradermal nevus in the external auditory canal.

Melanocytic nevus occurring in the external auditory canal (EAC) is uncommon. Therefore, in the absence of sufficient clinical experience, this disease may be challenging to be suspected even with a physical examination. Herein, clinical and demographic features of intradermal nevus in the EAC were investigated. Patients with an intradermal nevus on histopathological examination (n = 15; 2 men and 13 women; P = .005) were included from a pool of patients who underwent surgical resection for EAC tumors between November 2011 and March 2022. Data were retrospectively collected on their sex, appearance of the lesions, surgical method, and outcomes. Nine patients had a dome shape and 6 patients had a papillomatous shape. Ten patients had dark colors and 5 patients had pale colors. All pale colors appeared only in the dome-shaped nevus, and only dark colored papillomatous nevi were observed. A significant difference was noted in terms of the frequency of occurrence by colors (dark or pale) according to shape (dome or papillomatous) (P = .044). No patient showed recurrence or EAC stenosis after circumferential excision. In women, a dome-shaped or papillomatous mass with dark color in the EAC may likely be predicted as the nevus. However, it can also occur in men, and even if it is a pale color, in the case of a dome shape, taking the nevus into account is important. Moreover, successful treatment outcomes were achieved through circumferential excision.

Clinical features and management of eyelid margin nevi.

PURPOSE: Acquired melanocytic nevi are common eyelid lesions; however, their clinical presentation is not well documented. METHODS: In this retrospective study, clinical records were reviewed in patients evaluated between 2005 and 2022. RESULTS: Eyelid margin nevi (n = 150) were more commonly excised in female (78%) and Caucasian (86%) patients. Change in appearance/size were frequent presenting complaints, and 17% experienced ocular symptoms. Referring diagnosis included other benign lesions (11.3%), and concern for malignancy (16.7%). Many individuals (38.7%) noted their lesion for ≤5 years. Nevi were distributed across the 4 margins (9% peripunctal), and 88% had a regular base. Visible pigmentation was more common in non-Caucasians (95.2%) than Caucasians (41.1%). Lashes grew through 60.7% of nevi and were often misdirected.Nevi were treated with superficial excision and cauterization. Histologic subtypes included: dermal (86.6%), compound (9.4%), blue (2.7%), junctional (0.7%), lentiginous dysplastic (0.7%). An irregular base (p=0.042) and pigmentation (p=0.056) were more common in compound than dermal nevi. Lash line quality and appearance were improved in the majority of patients returning for follow-up, although postoperative trichiasis, marginal erythema, and residual pigmentation were observed. CONCLUSIONS: Melanocytic nevi commonly involve the eyelid margins and have a variety of presentations and appearances. Existing nevi can change, and new lesions appear throughout adulthood. Stable, benign appearing nevi can be observed. Shave excision provides a diagnosis and improved appearance for symptomatic or suspicious lesions, with few serious complications. Malignant transformation is rare, although evidence for recurrence warrants further evaluation.

Real-world experience of implementing the MOLES score in a virtual choroidal naevi clinic at a tertiary referral centre.

INTRODUCTION: The MOLES score has been validated to clinically differentiate choroidal naevi from melanomas by ocular oncologists and community optometrists. However, its utility in a virtual choroidal naevi clinic at a tertiary eye hospital without specialist ocular oncology services has not yet been evaluated. METHODS: A retrospective case review of 385 choroidal lesions in the virtual choroidal naevus clinic at Bristol Eye Hospital during January-March 2020 and April-August 2021 was performed. Choroidal lesions were assessed using the TFSOM-UHHD risk factor index and MOLES score, respectively. For both study periods, clinical outcome and adherence data were analysed. RESULTS: Choroidal lesions scored higher with the TFSOM-UHHD index (median 2) compared to the MOLES score (median 0; p < 0.001). Median required follow-up duration was 2 years for lesions assessed with the TFSOM-UHHD index, and 0 years for those graded with the MOLES score. Overall, 215 patients were appropriately discharged to community optometrists based on their MOLES score. Imaging requirements for the TFSOM-UHHD index and MOLES score protocols were met in 69.1% and 94.8% of cases, respectively. CONCLUSION: The MOLES score was easily implemented in a virtual choroidal naevus clinic, with good adherence. It increased clinic capacity by facilitating appropriate discharges of low-risk naevi to community monitoring, allowing finite and specialist hospital-based services to monitor higher-risk naevi more closely.

Melanoma Arising on a Nevus After Tattooing.

The pathogenetic relationship between tattooing and the development of malignant melanoma has not been demonstrated yet, but there are numerous instances documented in the literature where both benign and malignant lesions have developed on tattoos. We report the case of a 39-year-old man with a melanoma that arose on a nevus on the back after tattooing. Since the identification of melanocytes lesions can be heavily hindered by large tattoos, implementing a dedicated screening process with regular monitoring of the tattooed region could be necessary to prevent potential diagnostic delays.

Concordance of in vivo reflectance confocal microscopy and horizontal-sectioning histology in skin tumours.

BACKGROUND: In vivo reflectance confocal microscopy (RCM) enables the study of architectural and cytological aspects in horizontal sections, which closely correlate with histologic features. However, traditional histopathological vertical sections cannot totally reproduce the image of the in vivo RCM horizontal section. OBJECTIVE: To evaluate the concordance between in vivo RCM and histopathologic transverse sections for melanocytic lesions, basal cell carcinoma and seborrheic keratoses. METHODS: Prospectively collected benign melanocytic and non-melanocytic tumours diagnosed by dermoscopy were evaluated for common RCM features and compared to histopathology in horizontal sections with haematoxylin and eosin staining. RESULTS: A total of 44 skin tumours including 19 melanocytic lesions (nine compound, five junctional and five intradermal nevi), 12 basal cell carcinomas and 13 seborrheic keratoses were collected in the Department of Dermatology of Hospital Clinic of Barcelona. The RCM features that had statistically significant agreement with the histopathological horizontal sections were the preserved and visible honeycomb pattern, well defined DEJ, small bright particles, dermal nests, tumour islands and dark silhouettes, clefting, collagen bundles, thickened collagen bundles and cytologic atypia. CONCLUSIONS: Histopathology evaluation of horizontal sections of skin tumours can be correlated with main RCM findings. The results of this study have improved the understanding and interpretation of RCM features in relation to skin tumours, thus reinforcing the utility of RCM as a diagnostic tool.