Predicting Choroidal Nevus Transformation to Melanoma Using Machine Learning.

Purpose: To develop and validate machine learning (ML) models to predict choroidal nevus transformation to melanoma based on multimodal imaging at initial presentation. Design: Retrospective multicenter study. Participants: Patients diagnosed with choroidal nevus on the Ocular Oncology Service at Wills Eye Hospital (2007-2017) or Mayo Clinic Rochester (2015-2023). Methods: Multimodal imaging was obtained, including fundus photography, fundus autofluorescence, spectral domain OCT, and B-scan ultrasonography. Machine learning models were created (XGBoost, LGBM, Random Forest, Extra Tree) and optimized for area under receiver operating characteristic curve (AUROC). The Wills Eye Hospital cohort was used for training and testing (80% training-20% testing) with fivefold cross validation. The Mayo Clinic cohort provided external validation. Model performance was characterized by AUROC and area under precision-recall curve (AUPRC). Models were interrogated using SHapley Additive exPlanations (SHAP) to identify the features most predictive of conversion from nevus to melanoma. Differences in AUROC and AUPRC between models were tested using 10 000 bootstrap samples with replacement and results. Main Outcome Measures: Area under receiver operating curve and AUPRC for each ML model. Results: There were 2870 nevi included in the study, with conversion to melanoma confirmed in 128 cases. Simple AI Nevus Transformation System (SAINTS; XGBoost) was the top-performing model in the test cohort [pooled AUROC 0.864 (95% confidence interval (CI): 0.864-0.865), pooled AUPRC 0.244 (95% CI: 0.243-0.246)] and in the external validation cohort [pooled AUROC 0.931 (95% CI: 0.930-0.931), pooled AUPRC 0.533 (95% CI: 0.531-0.535)]. Other models also had good discriminative performance: LGBM (test set pooled AUROC 0.831, validation set pooled AUROC 0.815), Random Forest (test set pooled AUROC 0.812, validation set pooled AUROC 0.866), and Extra Tree (test set pooled AUROC 0.826, validation set pooled AUROC 0.915). A model including only nevi with at least 5 years of follow-up demonstrated the best performance in AUPRC (test: pooled 0.592 (95% CI: 0.590-0.594); validation: pooled 0.656 [95% CI: 0.655-0.657]). The top 5 features in SAINTS by SHAP values were: tumor thickness, largest tumor basal diameter, tumor shape, distance to optic nerve, and subretinal fluid extent. Conclusions: We demonstrate accuracy and generalizability of a ML model for predicting choroidal nevus transformation to melanoma based on multimodal imaging. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Oral sialadenoma papilliferum with kras mutation in a patient with linear nevus sebaceous syndrome.

Linear nevus sebaceous syndrome (LNSS) is a rare neurocutaneous syndrome part of the epidermal nevus syndromes group, characterized by the presence of sebaceous nevi and other extracutaneous lesions genetically related to RAS family gene mutations. Sialadenoma papilliferum (SP) is a rare benign intraoral neoplasm which is usually BRAF or HRAS mutated. We report a case of a young female girl diagnosed with a LNSS who developed a SP which had a KRAS mutation. This is the first case of SP with a KRAS mutation in the context of a LNSS.

Overlapping Large Facial Nevus Spilus and Nevus of Ota: A Case Report Diagnosed with Dermoscopy and Reflectance Confocal Microscopy.

We report a rare case of large facial hyperpigmentation in a 25-year-old female. Starting one month after birth, the patient developed a blue-brown patch on the right side of her face, interspersed with black macules and papules. As she aged, the lesion progressively enlarged and darkened, eventually covering the entire right side of her face. Dermoscopic and reflectance confocal microscopy examinations indicated nevus spilus in some areas and Nevus of Ota in others, leading to a definitive diagnosis of overlapping nevus spilus and Nevus of Ota. With no signs of malignant transformation on clinical or imaging examination, successful treatment was achieved using Q-switched alexandrite laser without any adverse effects. Our case underscores the critical value of dermoscopy and reflectance confocal microscopy in diagnosing rare facial pigmentary conditions, as we compare the imaging characteristics of nevus spilus, nevus of Ota, and similar conditions, alongside their clinical and histopathological correlations. Furthermore, our findings highlight the significant role of imaging examinations in monitoring malignancy and guiding treatment decisions.

Delivery management of pregnant blue rubber bleb nevus syndrome patients: a case report and literature review.

Blue rubber bleb nevus syndrome (BRBNS) is a rare systemic vascular disorder characterized by multifocal venous malformations (VMs). Little is known about the perinatal management of pregnant women with BRBNS owing to the limited number of reported cases. We present the case of a 36-year-old primigravida with BRBNS who underwent an uneventful cesarean section under spinal anesthesia for breech presentation. A thorough systemic examination revealed VMs in various organs, including the skin, conjunctiva, larynx, gastrointestinal tract, lungs, and vulva. Prior to spinal anesthesia, careful examination using imaging modalities was conducted to assess the spinal and epidural involvement of the VMs to avoid complications, including accidental puncture of the VMs, associated bleeding, and epidural hematoma. In pregnant women with BBNS, it is imperative to scrutinize the localization and distribution of VMs throughout the body to anticipate potential complications and select the appropriate delivery mode and anesthetic management.

Deep learning model shows pathologist-level detection of sentinel node metastasis of melanoma and intra-nodal nevi on whole slide images.

Introduction: Nodal metastasis (NM) in sentinel node biopsies (SNB) is crucial for melanoma staging. However, an intra-nodal nevus (INN) may often be misclassified as NM, leading to potential misdiagnosis and incorrect staging. There is high discordance among pathologists in assessing SNB positivity, which may lead to false staging. Digital whole slide imaging offers the potential for implementing artificial intelligence (AI) in digital pathology. In this study, we assessed the capability of AI to detect NM and INN in SNBs. Methods: A total of 485 hematoxylin and eosin whole slide images (WSIs), including NM and INN from 196 SNBs, were collected and divided into training (279 WSIs), validation (89 WSIs), and test sets (117 WSIs). A deep learning model was trained with 5,956 manual pixel-wise annotations. The AI and three blinded dermatopathologists assessed the test set, with immunohistochemistry serving as the reference standard. Results: The AI model showed excellent performance with an area under the curve receiver operating characteristic (AUC) of 0.965 for detecting NM. In comparison, the AUC for NM detection among dermatopathologists ranged between 0.94 and 0.98. For the detection of INN, the AUC was lower for both AI (0.781) and dermatopathologists (range of 0.63-0.79). Discussion: In conclusion, the deep learning AI model showed excellent accuracy in detecting NM, achieving dermatopathologist-level performance in detecting both NM and INN. Importantly, the AI model showed the potential to differentiate between these two entities. However, further validation is warranted.

Treatment of a Congenital Melocytic Giant Naevi at Age 39 Using Split-Thickness Skin Graft Over an Artificial Dermal Scaffold Through 2-Step Operation: A Novel Technique and Literature Review.

Congenital melanocytic nevus is a benign proliferation seen from birth. However, malignant transformation can be observed in later ages, so the removal of especially large and giant nevi is recommended during childhood. Nevertheless, there are no cases reported in the literature regarding excision of giant congenital melanocytic nevi in advanced age. This article presents the first case of a 39-year-old patient with a giant congenital melanocytic nevus covering 10% of the total body surface area, who underwent treatment with a 2-step operation. The nevus was located on the back, covering 10% of the total body surface area. The patient underwent en-bloc excision. A bilayer dermal matrix was applied over the fascia. Subsequently, a split-thickness skin graft was applied to the entire area. Full re-epithelialization was achieved within a total of 35 days. Thanks to the applied dermal scaffold, the area became pliable.

[Diagnosis of choroidal nevus following multiple intravitreal anti-VEGF injections (case study)]. / Diagnostika nevusa khorioidei posle mnogokratnykh intravitreal'nykh in"ektsii anti-VEGF-preparata (klinicheskoe nablyudenie).

This article describes a clinical case of a female patient with choroidal nevus, who was previously diagnosed in another clinic with "subretinal neovascular membrane as a result of central serous chorioretinopathy" and subsequently underwent multiple intravitreal anti-VEGF injections. Based on the analysis of OCT angiography images, the macular changes in this case were interpreted as a polypoidal form of neovascularization in a patient with subfoveolar choroidal nevus.

Additional treatments after curettage of congenital melanocytic nevi in the craniofacial region: A report from a single center in Japan.

BACKGROUND: Congenital melanocytic nevus (CMN) is a benign skin lesion present from birth, which may present with a risk of malignant transformation if extensive. Curettage, a treatment method involving the removal of the superficial layer of the nevus, is often used in the early stages of life. However, recurrence of the nevus and postoperative scarring may present as problems. Additional treatments, such as resection and/or laser treatment, are regularly required after curettage, particularly in the craniofacial region. However, no systematic treatment strategy has been reported. This study investigated additional treatments used after curettage to treat CMN in the craniofacial region and compared the frequency of treatments with respect to specific sites. METHODS: CMN cases involving curettage as an initial treatment were retrospectively reviewed at Kyoto University Hospital between May 2019 and April 2022. RESULTS: This study comprised 23 cases. Curettage was performed at a mean of 3.8 (1-10) months of age. No additional treatments were provided for 80% of head CMN. Additional treatments were performed in all cases, including the forehead and cheek. Laser treatment was performed in 86% of eyelid CMN and 75% of nasal CMN. Tissue expansion and flap closure were used in 33% of forehead CMN and 33% of cheek CMN. CONCLUSIONS: Additional treatments used for CMN in the craniofacial region varied in accordance with the lesion site.

A Case Report and an Overview of the Differential Diagnosis of Pigmented Lesions of the Conjunctiva: Just a Freckle or Something to Heckle?

A 42-year-old darkly pigmented woman presented at our emergency department with complaints of pruritus, foreign body sensation, and blurry vision. Besides findings compatible with mild dry eye disease, anterior segment examination revealed dark pigmented, ill-defined areas of the conjunctiva surrounding the temporal limbus and temporal bulbar conjunctiva in the left eye and involving the superior and inferior tarsal conjunctiva in both eyes. The patient reported no recent changes in these lesions. A diagnosis of complexion-associated melanosis in the palpebral conjunctiva of both eyes and primary acquired melanosis in the bulbar conjunctiva of the left eye was assumed, and the patient was placed under regular follow-up. Preservative-free tears were also recommended for her dry eye condition. Conjunctival pigmented lesions are a common finding during ophthalmologic evaluations. They pose a significant diagnostic challenge due to the wide array of differential diagnoses and the concern of misdiagnosing melanoma. A comprehensive clinical history and multidisciplinary evaluation are crucial in managing these cases.

MPATH-Dx Version 2.0 Schema for Melanocytic Lesions: A Robust Tool for Standardized Diagnostic Reporting.

The new revised MPATH-Dx (Version 2.0) reporting schema for melanocytic lesions is presented herein. Principal changes include the simplification of the previous five-class Version 1.0 to a four-class hierarchy of melanocytic lesions to improve diagnostic agreement and to provide more explicit guidance in the management of patients. Version 2.0 also has clearly defined histopathological criteria for classification of Class I and II lesions now designated as low-grade (mild to moderate) atypia and high-grade (high-end moderate to severe) atypia, respectively. This new revised schema, also includes specific provisions for the less common WHO pathways to melanoma, provides guidance for classifying "intermediate" Class II tumors (melanocytomas), and recognizes a subset of pT1a melanomas with very low risk and possible eventual reclassification as a neoplasm falling short of fully-evolved melanoma.

Malignant blue melanoma.

Malignant blue melanomas (MBMs) arise from blue nevi and all related intradermal melanocytic proliferations. They harbor specific, mutually exclusive mutations in the G-coupled protein pathway, mainly involving GNAQ or GNA11. Other rare genetic drivers include CYSLTR2 or PCLB4 mutations. PKC and GRM1-gene fusions have been recently added to this list. MBMs have a predilection for the scalp area, presenting as rapidly growing nodules within a pre-existing lesion. Histopathologically, these tumors are located in the dermis and subcutaneous fat and consist of large nodules or expanding dense sheets. Tumor necrosis is commonly seen. Large spindle-shaped and epithelioid melanocytes with high-grade cytological atypia and frequent mitotic figures are at higher magnification. A benign blue nevus or intermediate-grade blue melanocytoma is frequently found on the side of the central mass. Loss of nuclear BAP1 immunoreactivity is a poor prognostic factor.

Clinicopathological and molecular spectrum of patients with germline SUFU mutations: A case series.

BACKGROUND: One of the hereditary syndromes associated with multiple early-onset basal cell carcinomas (BCCs) is basal cell nevus syndrome (BCNS), of which a minority is caused by germline SUFU mutations. Germline SUFU mutations show a spectrum of phenotypes, of which multiple hereditary infundibulocystic basal cell carcinoma syndrome (MHIBCC) is one. Patients with MHIBCC develop multiple basaloid skin tumors from middle age onwards. METHODS: Three patients presenting with an MHIBCC phenotype were tested for a germline SUFU mutation. Skin biopsies were assessed by two dermatopathologists. RESULTS: Our study adds three new pathogenic SUFU variants, including a mosaic, to the current literature. Literature suggests a spectrum of phenotypes of patients carrying the same SUFU mutation, which ranges from the MHIBCC phenotype, to BCNS, to patients that develop life-threatening brain tumors. This last risk is significantly higher in germline SUFU mutation carriers when compared to BCNS patients carrying germline PTCH1 mutations. CONCLUSIONS: Germline SUFU mutation carriers should be recognized as a distinct group of patients carrying specific health risks, independent of meeting the BCNS criteria. Phenotypic prediction based on the specific SUFU mutation seems unfeasible. It is of utmost importance that the less apparent MHIBCC phenotype is recognized, to provide (second generation) germline SUFU mutation carriers appropriate healthcare.

Reflectance Confocal Microscopy and Dermoscopy for the Diagnosis of Solitary Hypopigmented Pink Lesions: A Narrative Review.

Diagnosing solitary pink skin lesions poses a significant challenge due to the scarcity of specific clinical and dermoscopic criteria. Several benign lesions, such as cherry angioma, clear cell acanthoma, dermal nevus, keloid, hypertrophic scar, and Spitz nevus, often exhibit similar clinical and dermoscopic features. This similarity extends to some malignant lesions, including basal cell carcinoma, actinic keratosis, and amelanotic melanoma, making differentiation difficult. Recent studies highlight the enhanced diagnostic accuracy of reflectance confocal microscopy (RCM), which offers increased sensitivity and specificity compared to dermoscopy alone for diagnosing skin cancer. This study aims to summarize the application of dermoscopy and RCM in distinguishing between benign and malignant pinkish-reddish skin lesions. The integration of RCM with traditional dermoscopic techniques improves the ability to accurately identify and differentiate these lesions. However, it is crucial to note that for any suspicious lesions, a final diagnosis must be confirmed through surgical excision and histopathological evaluation. This comprehensive approach ensures accurate diagnosis and appropriate treatment, highlighting the importance of combining advanced imaging techniques in clinical practice.

Expression of LOXL3, NES, and SNAI1 in Melanoma Genesis and Progression.

Melanoma is the most severe type of skin cancer and among the most malignant neoplasms in humans. With the growing incidence of melanoma, increased numbers of therapeutic options, and the potential to target specific proteins, understanding the basic mechanisms underlying the disease's progression and resistance to treatment has never been more important. LOXL3, SNAI1, and NES are key factors in melanoma genesis, regulating tumor growth, metastasis, and cellular differentiation. In our study, we explored the potential role of LOXL3, SNAI1, and NES in melanoma progression and metastasis among patients with dysplastic nevi, melanoma in situ, and BRAF+ and BRAF- metastatic melanoma, using immunofluorescence and qPCR analysis. Our results reveal a significant increase in LOXL3 expression and the highest NES expression in BRAF+ melanoma compared to BRAF-, dysplastic nevi, and melanoma in situ. As for SNAI1, the highest expression was observed in the metastatic melanoma group, without significant differences among groups. We found co-expression of LOXL3 and SNAI1 in the perinuclear area of all investigated subgroups and NES and SNAI1 co-expression in melanoma cells. These findings suggest a codependence or collaboration between these markers in melanoma EMT, suggesting new potential therapeutic interventions to block the EMT cascade that could significantly affect survival in many melanoma patients.

Conjunctival blue nevus in a child - Case report and review of literature.

Purpose: To report a rare case of a conjunctival blue nevus in a child. Observations: A 10-year-old girl underwent an excisional biopsy for an atypical growing melanocytic conjunctival lesion. The diagnosis of a conjunctival blue nevus was confirmed on histopathology. We describe the histopathology and the anterior segment optical coherence tomography features of a blue nevus in a 10-year-old child along with a review of literature. Conclusion and importance: Conjunctival blue nevus is rare and has rarely been reported in a child. Multimodal imaging may help document lesion progression. This condition should remain in the differential for a growing, pigmented conjunctival lesion.

Nevi and Melanoma in Children: What to Do in Daily Medical Practice: Encyclopedia for Pediatricians and Family Doctors.

Melanocytic nevi, commonly known as moles, are benign skin lesions that often occur in children and adolescents. Overall, they are less common in children compared to adults. Understanding the diagnosis and management of melanocytic nevi and risk factors for melanoma development is crucial for their early detection and appropriate treatment. This paper presents children's most common melanocytic nevi, including their epidemiology, morphology, diagnostic methods, and treatment.

PRAME Immunohistochemistry in Thin Melanomas Compared to Melanocytic Nevi.

PRAME (PReferentially expressed Antigen in Melanoma) immunohistochemistry has proven helpful in distinguishing malignant from benign melanocytic tumors. We studied PRAME IHC expression in 46 thin melanomas and 39 melanocytic nevi, mostly dysplastic nevi. Twenty-six percent (26.09%) of the melanomas showed diffuse PRAME staining in over 76% of the tumor cells (4+), and 34.78% of the melanomas showed PRAME expression in over 51% of the tumor cells (3+ or 4+), while 8% were entirely negative for PRAME. No melanocytic nevi were PRAME 4+ or 3+. More than half of the nevi (64%) were entirely negative for PRAME staining, and 36% of the nevi showed staining expression in 1-25% (1+) or 26-50% of the cells (2+). No nevi were stained with a color intensity of 3, while 16.67% of the melanomas were stained with this color intensity. Most nevi (78.57%) were stained with an intensity of 1. With a lower positivity threshold, sensitivity increases with still reasonable specificity. The best accuracy was obtained for the 2+ positivity threshold. In conclusion, PRAME staining helps distinguish thin melanomas from dysplastic nevi. However, the threshold of positivity should be lowered in order not to miss thin melanomas.

Ophthalmologic manifestations of organoid nevus syndrome: A series of 13 cases.

Background: The organoid nevus syndrome is a rare neurocutaneous syndrome typified by cutaneous sebaceous nevus, seizures and epibulbar choristomas. The condition is associated with multiple ocular abnormalities. Herein, the authors aim to study and report the ophthalmic features of cases diagnosed with organoid nevus syndrome. Methods: The authors retrospectively evaluated the records of patients with the organoid nevus syndrome who had presented to a tertiary care eye hospital in northern India. The ocular features were studied and entered in MS excel and the data were evaluated. Results: Data of 13 patients with the organoid nevus syndrome were found. All 13 patients had cutaneous features in the form of Sebaceous nevus of Jadasson, 8 patients had alopecia of the scalp area, 2 had history seizures and 10 had arachnoid cysts on neuroimaging of the head. All 13 patients had a complex choristoma involving the ocular surface. Conclusions: We conclude that the most common ophthalmologic features associated with organoid nevus are complex choristoma of the bulbar surface, scleral coat calcification and upper eyelid coloboma.