Melanocytic Tumors Research Articles

A-242 - BRCA1-associated-protein 1 tumour predisposition syndrome (BAP1-TPDS) presenting with multiple BAP1-inactivated melanocytic tumours – a rare hereditary tumour syndrome

A-242 - BRCA1-associated-protein 1 tumour predisposition syndrome (BAP1-TPDS) presenting with multiple BAP1-inactivated melanocytic tumours – a rare hereditary tumour syndrome

Minimally invasive differential diagnosis of melanocytic intraocular neoplasms

Purpose: to analyze the mutation frequency of the GNAQ/GNA11 gene in circulating tumor DNA and genotypes of the polymorphic marker C3435T of the ABCB1 gene in a large sample of patients with intraocular melanocytic neoplasms (IMN).Material and methods. In an open prospective study performed in 2015–2022, 272 IMN patients with intraocular melanocytic neoplasms aged 28 to 87 (ave. 58.3 ± 12.6), including 187 females (68.8 %) and 85 males (31.2 %), were divided into three groups depending on the nature of the tumor focus: Group I, n = 141, progressing choroidal melanomas; Group II, n = 67, stationary melanomas, and Group III, n = 64, choroidal nevi.Results. In Group I, at least one mutation in the GNAQ/GNA11 gene was detected in 134 patients (95.0 %). Of these, 35 patients (24.8 %) revealed two mutations, and 16 patients (11.3 %) had 3 mutations. In Group II, one mutation was detected in 49 patients (73.1 %), of which three patients (4.5 %) had two mutations. In Group III, one mutation in the GNAQ/GNA11 gene was detected in 13 patients (20.3 %). When comparing the overall frequency of mutations in the GNAQ/GNA11 genes in Groups I and II, significant differences were obtained (OR = 7.03 (2.77 to 17.86), F = 0.000015, ξ2 = 20.6), with Group I having mutations identified in 95 % of cases and Group II, in 73.1 %. Significant differences were also obtained when comparing the frequency of the studied mutations in Groups I and III (OR = 75.1 (28.36 to 198.86), F = 0.0000001, ξ2 = 121.15) with a frequency of 20.3 % in Group III. The frequency of mutations in the GNAQ/GNA11 genes was significantly higher in Group II than in Group III (OR = 10.68 (4.73 to 24.1), F = 0.0000001, ξ2 = 36.64). The frequencies of heterozygous mutations in all 4 exons were significantly higher in Group I than in Groups II and III, except for the GNAQ183 gene when comparing Groups I and II. Heterozygous mutations in all 4 exons were significantly more frequent in Group II than in Group III. Homozygous mutations were found only in Group I patients, but, in spite of this, no significant differences were detected when comparing them with other groups. The frequency of genotype CC of the polymorphic marker C3435T of ABCB1 gene was significantly lower in Group I as compared to Group II, whilst the frequency of genotype CT was significantly higher than in group II.Conclusion. The general analysis of molecular genetic studies of 272 patients with intraocular melanocytic neoplasms showed a direct correlation between the frequency of detection of mutations in genes and the size and source of the tumor. The obtained results substantiate both screening of patients from risk groups and differentiation of patients depending on the size and source of the tumor.

Sclerosing melanocytic tumors with MAP2K1 in-frame deletions and copy number gains in 15q: A distinctive pathway of nevogenesis.

Sclerosing melanocytic tumors with MAP2K1 in-frame deletions and copy number gains in 15q: A distinctive pathway of nevogenesis.

Programmed Cell Death-Ligand 1 (PD-L1) Immunohistochemical Expression in Equine Melanocytic Tumors.

Currently available treatments for equine melanocytic tumors have limitations, mainly due to mass localization and dimension, or the presence of metastases. Therefore, a search for new therapies is necessary. Programmed cell death-ligand 1 (PD-L1) is expressed by several tumors, blocking T cell-mediated elimination of the tumor cells by binding to programmed cell death protein 1 (PD-1). A novel therapeutic approach using PD-1/PD-L1 blockade in human melanoma resulted in tumor regression and prolonged tumor-free survival. This study aimed to evaluate the immunohistochemical expression of PD-L1 in equine melanocytic tumors. A total of 77 melanocytic tumors were classified as benign or malignant and evaluated by extension of labeling. A total of 59.7% of the tumors showed >50% of immunolabeled cells. Regarding malignant tumors, 24/38 tumors presented >50% of labeled cells, 13 tumors presented between 25-50% and one tumor presented <10%. Regarding benign tumors, 22/39 tumors presented >50% of labeled cells, nine tumors presented 25-50%, three tumors presented 10-25%, two tumors presented <10% and three tumors did not present expression. Our results suggest that PD-L1 blockade may be a potential target for immunotherapy in equine melanocytic tumors and that future clinical research trials into the clinical efficacy of the anti-PD-L1 antibody are necessary.

Understanding the anatomy of dermoscopy of melanocytic skin tumours: Correlation invivo with line-field optical coherence tomography.

Early melanoma detection is the main factor affecting prognosis and survival. For that reason, non-invasive technologies have been developed to provide a more accurate diagnosis. Recently, line-field confocal optical coherence tomography (LC-OCT) was developed to provide an invivo, imaging device, with deep penetration and cellular resolution in three dimensions. Combining the advantages of conventional OCT and reflectance confocal microscopy, this tool seems to be particularly suitable for melanocytic lesions. The objective of this study was to identify and describe the correlation between specific dermoscopic criteria and LC-OCT features in three dimensions associated with melanocytic lesions. Dermoscopic and LC-OCT images of 126 melanocytic lesions were acquired in three different centres. The following dermoscopic criteria have been considered: reticular pattern, dots and globules, structureless areas, blue-whitish veil, regression structures, negative network, homogeneous pattern, streaks and blotches. 69 (55%) benign and 57 (45%) malignant lesions were analysed. A regular reticular pattern was found associated in the 75% of the cases with the presence of elongated rete ridges with pigmented cells along the basal layer, while atypical reticular pattern showed an irregular organization of rete ridges with melanocytic hyperplasia, broadened and fused ridges and elongated nests. Both typical and atypical dots and globules were found associated with melanocytic nests in the dermis or at the dermoepidermal junction (DEJ), as well as with keratin cysts/pseudocysts. Grey globules corresponded to the presence of melanin-containing dermal inflammatory cells (melanophages) within the papillae. Structureless brown/black areas correlated with alterations of the DEJ. We observed the same DEJ alterations, but with the presence of dermal melanophages, in 36% of the cases of blue/white/grey structureless areas. A description of each LC-OCT/dermoscopy correlation was made. LC-OCT permitted for the first time to perform an invivo, 3D correlation between dermoscopic criteria and pathological-like features of melanocytic lesions.

Subtypes of Melanomas Associated with Different Degrees of Actinic Elastosis in Conventional Histology, Irrespective of Age and Body Site, Suggesting Chronic Ultraviolet Light Exposure as Driver for Lentigo Maligna Melanoma and Nodular Melanoma.

(1) Background: Ultraviolet (UV) radiation and sunburns are associated with an increased incidence of acquired nevi and melanomas. However, the data are controversial as to whether chronic UV exposure or high intermittent UV exposure is the major carcinogenic factor in melanocytic tumors. In this study, we compared the degree of actinic elastosis (AE) as a surrogate for lifetime UV exposure in nevi and different clinical melanoma subtypes (i.e., superficial spreading melanoma (SSM), nodular malignant melanoma (NMM), acral lentiginous melanoma (ALM), and lentigo maligna melanoma (LMM)) with respect to clinical variables (age, sex, and body site). (2) Methods: We defined a semi-quantitative score for the degree of AE ranging from 0 = none to 3 = total loss of elastic fibers (basophilic degeneration) and multiplied it by the perilesional vertical extent (depth), measured histometrically (tumor-associated elastosis grade (TEG)). We matched the TEG of n = 595 melanocytic lesions from 559 patients with their clinical variables. (3) Results: The TEG was correlated with age and UV-exposed body sites. Furthermore, the TEG was significantly higher in LMM than in all other types of melanomas and the TEG in NMM was higher than in SSM, irrespective of patient age and tumor site. (4) Conclusions: High cumulative UV exposure is more strongly associated with LMM and NMM than with other melanoma subtypes.

A Comparison of Preferentially Expressed Antigen in Melanoma Immunohistochemistry and Diagnostic Gene Expression-Profiling Assay in Challenging Melanocytic Proliferations.

Most melanocytic tumors are classified as benign or malignant based on clinical morphology, histology, and immunohistochemical (IHC) analysis. A subset of more challenging cases with ambiguous features may require further evaluation with established ancillary diagnostic molecular studies, including fluorescence in situ hybridization and/or single nucleotide polymorphism array, to increase diagnostic certainty. More recently, a diagnostic gene expression-profiling (GEP) assay and an IHC stain for the detection of PRAME (PReferentially expressed Antigen in MElanoma) have been developed. The use of PRAME IHC has been validated in cases of unequivocal and ambiguous melanocytic proliferations via comparing results with fluorescence in situ hybridization and/or single nucleotide polymorphism array. A study comparing performance metrics of PRAME IHC and diagnostic GEP has not been previously published. Herein, we evaluated the use of PRAME IHC in 55 melanocytic tumors with challenging histomorphology by comparing the results with diagnostic GEP and final histomorphologic diagnosis. Intertest agreement occurred in 88% of cases. PRAME IHC supported the final diagnosis in 89% of cases with a sensitivity of 79%, specificity of 95%, and positive predictive value of 88.2%. GEP agreed with the final diagnosis in 88% of cases with a sensitivity of 65%, 97% specificity, and positively predicted melanoma in 91.7% of cases. Because the results of this study align with past publications evaluating the performance metrics of PRAME IHC, showing it to be as sensitive as and more cost effective than all other ancillary molecular tests, we propose the use of PRAME IHC as the optimal first-line diagnostic tool for ambiguous melanocytic proliferations.

Clear Cell Sarcoma masquerading as Malignant Melanoma: A Case Report

Abstract Introduction/Objective Clear cell sarcoma (CCS) is a rare and diagnostically challenging soft tissue tumor that can mimic other malignancies with melanocytic differentiation. Histologically it shows diffuse sheets of clear cells with scattered melanin pigment in a subset of cases. Other morphologies have been described but contain atleast a portion of clear cell features. We report a case of CCS with unusual histomorphology, highlighting the importance of incorporating cytogenetic and immunohistochemical studies to accurately diagnose this tumor. Methods/Case Report We present a case of a 49-year-old male with a left lateral knee mass associated with pain and swelling for one year. A core biopsy revealed a diffuse proliferation of pleomorphic spindle and atypical epithelioid cells. These atypical cells exhibited intranuclear vacuoles, variable prominent nucleoli, abundant dusky cytoplasm, and increased mitotic activity. Immunohistochemical studies were positive for S100, SOX10, and Melan-A (patchy), suggesting a melanocytic differentiation. However, no expression of Preferentially Expressed Antigen in Melanoma (PRAME) or BRAF V600E mutation was noted. Given the clinical history and lack of cutaneous melanocytic lesion, clear cell sarcoma was considered in the differential diagnosis. Fluorescence in situ hybridization (FISH) studies revealed Ewing sarcoma region 1 (EWSR1) gene rearrangement in neoplastic cells, confirming the diagnosis of CCS. Results (if a Case Study enter NA) NA Conclusion The tumor lacked definitive histologic features including clear cell features, demonstrating the variability in histomorphology that can be encountered with CCS. Distinction of CCS from melanoma is of clinical significance as treatment significantly differs. Accurate diagnosis requires the incorporation of cytogenetic and immunohistochemical studies to differentiate it from melanocytic neoplasms. Variability in histomorphology of CCS can pose, as is evident in our case, as a diagnostic pitfall, and CCS should be considered in the differential diagnosis of unusual non-cutaneous melanocytic proliferations that lack clear cell features and show compelete spindle and epithelioid morphology.

S100 Protein Expression in Primary and Metastatic Neuroendocrine Neoplasms: A Specific Marker of Pancreatic Origin.

Neuroendocrine neoplasms can arise in a wide variety of anatomic sites including the gastrointestinal tract, pancreas, and lung, among others. Here, we report on the expression of S100 protein in a tissue microarray composed of 919 distinct primary and metastatic neuroendocrine neoplasms from 548 patients. S100 protein is a commonly used marker in many laboratories for the identification of neural and melanocytic neoplasms and occasionally used in the workup for neuroendocrine neoplasms when the diagnosis of paraganglioma is being considered. We show that strong S100 protein expression is highly specific to well-differentiated neuroendocrine tumors of pancreatic origin. This finding suggests potential diagnostic utility of this marker in cases of tumors of unknown origin, and emphasizes that S100 protein expression should not be an unexpected finding in neuroendocrine tumors of pancreatic origin.

Performance of the 23-gene Expression Profile (23-GEP) Test by Histopathological Evaluation in an Independent, Multi-Center Performance Cohort of Cutaneous Melanocytic Neoplasms

Histopathologic evaluation can effectively diagnose most melanocytic neoplasms; however, lesions considered to be difficult-to-diagnose pose challenges for accurate classification of malignant potential, which can lead to over- or under-treatment. Ancillary testing to provide additional information is available for such cases. The validated diagnostic 23-GEP test provides an objective result of benign, malignant, or intermediate. In this large, independent cohort, the performance of the 23-GEP in its current laboratory is presented. Lesions from patients ≥18 years old were enrolled from eight centers or from melanoma cases clinically submitted for prognostic 31-GEP testing. Lesions were independently reviewed by 3–5 dermatopathologists and included in the study if they were fully concordant or non-concordant without conflicting diagnoses (i.e., both benign and malignant designations) or majority of unknown malignant potential designations, resulting in a cohort (n=2512) of benign nevi (n=1140) and malignant melanomas (n=1372). Accuracy metrics and two-tailed 95% confidence intervals (CIs) were calculated using resampling x10,000 iterations to establish a balanced number of benign versus malignant samples. The 23-GEP performance within this cohort was 91.3% (95% CI, 89.2–93.2%) sensitivity, 91.9% (89.8–93.8%) specificity, 92.2% (9.30–94.0%) positive predictive value, and 91.0% (89.0–92.9%) negative predictive value; 7.8% of lesions received an intermediate result. These metrics do not deviate significantly from previously published studies. These data demonstrate that the 23-GEP has an overall accuracy of 91.6% (90.1–93.0%), further supporting its use as an ancillary test that can be integrated with clinical and histopathologic information to guide final diagnosis.

NIMG-77. EARLY DIAGNOSIS OF NEUROCUTANEOUS MELANOSIS MASQUERADING AS SUBARACHNOID HEMORRHAGE

Abstract A 50-year-old male presented to the emergency room with a sudden onset right upper limb facial numbness and dysphasia, soon followed by full-recovery. Brain computed tomography revealed hyperdense lesions within the left frontal sulcus, highly suspicious of subarachnoid hemorrhage. T1-weighted magnetic resonance imaging showed multiple leptomeningeal enhancement in the left frontal area.The digital subtraction angiography indicated an absence of vascular lesions. One-month after, the lesions progressed in the occipital area, when left sixth nerve palsy developed. Multiple giant nevus over the legs, trunk, and scalp had attracted attention. Owing to the suspicious symptomatic leptomeningeal lesions, open biopsy was performed. Surprisingly, diffuse, thick, black-colored tissue infiltration of the subarachnoid space, involving prominent cortical vessels, was noted. Pathology confirmed meningeal melanocytosis. Neurocutaneous melanosis is characterized by giant congenital or multiple satellite nevi and melanocytic tumors of the leptomeninges. Early disease diagnosis is crucial. Once the patient develops neurological symptoms, prognosis could quickly worsen.

Immunohistochemistry for PRAME in Dermatopathology.

Preferentially expressed antigen in melanoma (PRAME) is a tumor-associated antigen first identified in a melanoma patient and found to be expressed in most melanomas as well as in variable levels in other malignant neoplasms of epithelial, mesenchymal, or hematolymphoid lineage. Detection of PRAME expression in formalin-fixed paraffin-embedded tissue is possible by immunohistochemistry (IHC) with commercially available monoclonal antibodies. In situ and invasive melanoma frequently show a diffuse pattern of nuclear PRAME immunoreactivity which contrasts with the infrequent and typically nondiffuse staining seen in nevi. In many challenging melanocytic tumors, results of PRAME IHC and other ancillary tests correlate well, but not always: The tests are not interchangeable. Most metastatic melanomas are positive for PRAME, whereas nodal nevi are not. Numerous studies on PRAME IHC have become available in the past few years with results supporting the value of PRAME IHC as an ancillary tool in the evaluation of melanocytic lesions and providing insights into limitations in sensitivity and specificity as well as possible pitfalls that need to be kept in mind by practicing pathologists.

Utility of Immunohistochemistry With Antibodies to SS18-SSX Chimeric Proteins and C-Terminus of SSX Protein for Synovial Sarcoma Differential Diagnosis.

Synovial sarcoma is a relatively common soft tissue tumor characterized by highly specific t(X;18)(p11;q11) translocation resulting in the fusion of SS18 with members of SSX gene family. Typically, detection of SS18 locus rearrangement by fluorescence in situ hybridization or SS18 :: SSX fusion transcripts confirms the diagnosis. More recently, immunohistochemistry (IHC) for SS18-SSX chimeric protein (E9X9V) and C-terminus of SSX (E5A2C) showed high specificity and sensitivity for synovial sarcoma. This study screened a cohort of >1000 soft tissue and melanocytic tumors using IHC and E9X9V and E5A2C antibodies. Three percent (6/212) of synovial sarcomas were either negative for SS18-SSX or had scattered positive tumor cells (n=1). In these cases, targeted RNA next-generation sequencing detected variants of SS18 :: SSX chimeric transcripts. DNA methylation profiles of 2 such tumors matched with synovial sarcoma. A few nonsynovial sarcoma tumors (n=6) revealed either focal SS18-SSX positivity (n=1) or scattered positive tumor cells. However, targeted RNA next-generation sequencing failed to detect SS18 :: SSX transcripts in these cases. The nature of this immunopositivity remains elusive and may require single cell sequencing studies. All synovial sarcomas showed positive SSX IHC. However, a mosaic staining pattern or focal loss of expression was noticed in a few cases. Strong and diffuse SSX immunoreactivity was also seen in epithelioid sclerosing osteosarcoma harboring EWSR1 :: SSX1 fusion, while several sarcomas and melanocytic tumors including cellular blue nevus (5/7, 71%) revealed focal to diffuse, mostly weak to intermediate SSX staining. The SS18-SSX and SSX IHC is a useful tool for synovial sarcoma differential diagnosis, but unusual immunophenotype should trigger molecular genetic testing.

Cytologic features of mesenchymal, melanocytic and haematolymphoid tumours of the central nervous system and metastases.

The current World Health Organization (WHO) classification of central nervous system (CNS) tumours includes several neoplasms that, while occurring in this location, are more frequently seen extracranially. These include mesenchymal, melanocytic and haematolymphoid neoplasms, as well as metastases. A few of these entities are exclusive of the CNS and have no extracranial counterpart. Despite their diverse histogenesis, these neoplasms share a peculiar predilection for involving meningeal structures. In fact, in the context of an intraoperative pathologic consultation of a meningeal tumour, virtually all these entities should be considered as potential diagnoses. Metastases in the CNS are very common. Most are carcinomas that cytologically resemble their site of origin. Loss of differentiation with cell dissociation and anaplasia and presence of accompanying fibrillary brain parenchyma can be a source of diagnostic problems. In this review, we intend to show the most relevant cytologic features of these tumours, and it is especially aimed at their analysis during intraoperative studies.

Glial and Melanocytic Tumors of the Retina and Optic Disc

In this review, solitary limited retinal astrocytic proliferation, retinal astrocytic hamartoma, acquired retinal astrocytoma, optic disc melanocytoma and optic disc melenoma, which are glial and melanocytic tumors of the retina and optic disc, are discussed. The point that makes these diseases important is the necessity of making the differential diagnosis. Because while there are retinal tumors that can show complete regression in this group of diseases, there are also tumors where more severe clinical conditions can be seen that can lead to vision loss and even systemic metastatic spread. In addition, serious retinal and optic nerve complications can be observed in some tumors, which can lead to vision loss. Another important point is the malignant transformation that can be observed in tumors such as melanocytoma, although it is rare. For this reason, periodic follow-up of these cases in the presence of an experienced ophthalmologist is very important. This review aimed to summarize the clinical and histopathological features that may be important in the diagnosis and follow-up of these tumors.

Choroidal Nevus; Clinical Findings, Imaging Findings and Diagnosis

Choroidal nevus is a benign melanocytic tumor that is often incidentally detected during ophthalmic examinations. It is typically located behind the equator of the eye and appears as a flat or slightly elevated lesion with indistinct borders. The shape of the nevus can be round or oval, and its color varies from brown to dark gray, depending on the amount of pigment present. Most nevi are asymptomatic. However, if choroidal neovascularization or serous retinal detachment develops, it can lead to a decrease in vision and become symptomatic. Fundus photography, B-mode ultrasonography, and optical coherence tomography are useful imaging techniques for clinical monitoring. Differential diagnosis between choroidal nevus and melanoma is important. Risk factors for the development of melanoma include a thickness greater than 2 mm, a basal diameter larger than 6 mm, the presence of lipofuscin pigment accumulation on the surface, proximity to the optic disc within 3 mm, serous retinal detachment, and visual impairment. These factors require further investigation.

A Spitzoid Tumor dataset with clinical metadata and Whole Slide Images for Deep Learning models

Spitzoid tumors (ST) are a group of melanocytic tumors of high diagnostic complexity. Since 1948, when Sophie Spitz first described them, the diagnostic uncertainty remains until now, especially in the intermediate category known as Spitz tumor of unknown malignant potential (STUMP) or atypical Spitz tumor. Studies developing deep learning (DL) models to diagnose melanocytic tumors using whole slide imaging (WSI) are scarce, and few used ST for analysis, excluding STUMP. To address this gap, we introduce SOPHIE: the first ST dataset with WSIs, including labels as benign, malignant, and atypical tumors, along with the clinical information of each patient. Additionally, we explain two DL models implemented as validation examples using this database.

One step at a time: Melanocytic differentiation in fusion-driven cutaneous neoplasms.

As dermatopathologists, we routinely diagnose melanocytic nevi, melanomas, and occasionally melanocytomas in our daily clinical practice. However, it is now clearly established that the presence of melanocytic differentiation in a tumor does not necessarily indicate any of the aforementioned diagnoses. Tumors such as clear cell sarcoma, malignant melanotic nerve sheath tumor, PEComa, melanotic neuroectodermic tumor of infancy, and even certain translocation-associated renal cell carcinomas all share the common characteristic of melanin synthesis. Over the past two decades, with the advent of molecular diagnostics, there has been an explosion of new data and discoveries in this field. Examples such as CRTC1::TRIM11 cutaneous tumors and MITF pathway-activated melanocytic tumors (ACTIN::MITF and MITF::CREM) have been incorporated into the latest edition of the WHO classification of skin tumors (5th ed). In a recent issue, Alexandrescu et al. reported another case of a dermal/subcutaneous melanocytic tumor harboring a MITF::CREM1 translocation. In a separate paper within the current issue, Li et al. present a case of clear cell sarcoma with the rare EWSR1::CREM fusion, which had initially been misdiagnosed as melanoma with regional and distant metastases. We warmly welcome these two very interesting and high-quality articles to our journal, and we eagerly anticipate what the future holds for this fascinating category of tumors.

PRAME immunohistochemistry compared to traditional FISH testing in spitzoid neoplasms and other difficult to diagnose melanocytic neoplasms.

PRAME (PReferentially expressed Antigen in Melanoma) is a gene first identified in melanoma. It has been proposed as a useful marker to differentiate melanoma from benign melanocytic neoplasms. Recently genomic testing using fluorescence in situ hybridization has been used to aid in the diagnosis of difficult melanocytic neoplasms. We have compared PRAME staining to FISH testing results in 83 difficult to classify melanocytic neoplasms which showed spitzoid histologic features. A relatively low sensitivity of 29.6% and high specificity of 76.8% is seen with PRAME staining as compared to genomic testing with fluorescence in situ hybridization. This study highlights the limitations of PRAME staining in spitzoid neoplasms.

A novel method to assess copy number variations in melanocytic neoplasms: Droplet digital PCR for precise quantitation of MYC and MYB genes.

While most melanocytic neoplasms can be classified as either benign or malignant by histopathology alone, ancillary molecular diagnostic tests can be necessary to establish the correct diagnosis in challenging cases. Currently, the detection of copy number variations (CNVs) by fluorescence in situ hybridization and chromosomal microarray (CMA) are the most popular methods, but remain expensive and inaccessible. We aim to develop a relatively inexpensive, fast, and accessible molecular assay to detect CNVs relevant to melanoma using droplet digital polymerase chain reaction (ddPCR) technology. In this proof-of-concept study, we evaluated CNVs in MYC and MYB genes from 73 cases of benign nevi, borderline melanocytic lesions, and primary and metastatic melanoma at our institution from 2015 to 2022. A multiplexed ddPCR assay and CMA were performed on each sample, and the results were compared. Concordance analysis of ddPCR with CMA for quantification of MYC and MYB CNVs revealed a sensitivity and specificity of 89% and 86% for MYC and 83% and 74% for MYB, respectively. We demonstrate the first use of a multiplexed ddPCR assay to identify CNVs in melanocytic neoplasms. With further improvement and validation, ddPCR may represent a low-cost and rapid tool to aid in the diagnosis of histopathologically ambiguous melanocytic tumors.