Search Results (114)

Background: Melanoma is one of the most aggressive types of skin cancer. Its diagnosis appears to be challenging due to morphological similarities to benign melanocytic lesions. Even though histopathological evaluation is the diagnostic gold standard, immunohistochemistry (IHC) proves to be useful in challenging cases. Preferentially Expressed Antigen in Melanoma (PRAME) has emerged as a promising diagnostic, prognostic, and therapeutic marker in melanoma. Methods: This review critically examines the role of PRAME across clinical domains. It presents an evaluation of PRAME’s diagnostic utility in differentiating melanomas from benign nevi, its prognostic significance across melanoma subtypes, and therapeutic applications in emerging immunotherapy strategies. An extensive analysis of the current literature was conducted, with a focus on PRAME expression patterns in melanocytic lesions and various malignancies, along with its integration into IHC protocols and investigational therapies. Results: PRAME demonstrates high specificity and sensitivity in distinguishing melanoma from benign melanocytic proliferations, particularly in challenging subtypes such as acral, mucosal, and spitzoid lesions. Its overexpression correlates with poor prognosis in numerous malignancies. Therapeutically, PRAME’s HLA class I presentation enables T-cell-based targeting. Early-phase trials show promising results using PRAME-directed TCR therapies and bispecific ImmTAC agents. However, immune evasion mechanisms (i.e., heterogeneous antigen expression, immune suppression in the tumor microenvironment, and HLA downregulation) pose significant challenges to therapy. Conclusions: PRAME is a valuable biomarker for melanoma diagnosis and a promising target for immunotherapy. Its selective expression in malignancies supports its clinical utility in diagnostic precision, prognostic assessment, and precision oncology. Ongoing research aimed at overcoming immunological barriers will be essential for optimizing PRAME-directed therapies and establishing their place in the personalized management of melanoma. Full article

Background and Clinical Significance: Osteonevus of Nanta is a rare histological phenomenon characterized by bone formation within a benign melanocytic nevus, most commonly in intradermal nevi of the head and neck. Although osteonevus of Nanta is rare, ossification in a cellular blue nevus is even more uncommon. To date, only one case of a cellular blue nevus with ossification has been documented. This case report adds to the limited literature and emphasizes the clinical importance of recognizing this rare phenomenon, as osteonevus of Nanta has been potentially associated with malignant melanoma. Case Presentation: A 72-year-old woman presented with an asymptomatic, pigmented scalp lesion that had recently increased in size. On clinical examination, the tumor appeared as a well-demarcated, firm, and nodular mass with dark blueish to violet pigmentation that measured 15 × 12 × 7 mm. To ensure a definitive diagnosis and rule out malignancy, the lesion was excised with narrow margins. Histological examination revealed a cellular blue nevus with prominent osseous metaplasia. Due to the absence of clear margins, a wider re-excision was performed. No residual tumor was found, and the patient remained asymptomatic with no recurrence. Conclusions: This case represents only the second published example of a cellular blue nevus with ossification. While osteonevus of Nanta is benign, its potential association with malignant melanoma, as well as its clinical resemblance to malignant entities such as nodular melanoma, malignant blue nevus, and pigmented basal cell carcinoma, underscores the need for thorough clinical and histopathologic evaluation. Full article

Background and Clinical Significance: Blue nevi are a dubious pigmented lesion. While somewhat common throughout the population, they are significantly less common than other melanocytic neoplasms, and both their morphology and development bring them closer to true hamartomas than neoplasms. An exceedingly rare occurrence is the development of melanoma from a preexisting blue nevus. This nosological unit, defined as melanoma arising in a blue nevus, also known as malignant blue nevus, blue naevus–like melanoma, melanoma ex-blue naevus, and melanoma mimicking cellular blue naevus, is required to either originate from an area of previously excised blue nevus or have a blue nevus remnant adjacent to it. Due to the spindle cell morphology of melanoma arising in blue nevus, the terminology is often misused by some authors to include spindle cell melanomas, which exhibit a distinct pathogenesis and, although morphologically similar, have differing molecular profiles as well. Case presentations: The following manuscript discusses comparative morphological features in a case series of blue nevi and melanoma arising in blue nevi. Discussion: Blue nevi present with unique morphological features, with melanomas originating from them having a unique molecular pathology profile, which significantly differs from other cutaneous melanomas and is closer to that of uveal melanomas. Full article

Recently, there has been a rise in skin cancer cases, for which early detection is highly relevant, as it increases the likelihood of a cure. In this context, this work presents a benchmarking study of standard Convolutional Neural Network (CNN) architectures for automated skin lesion classification. A total of 38 CNN architectures from ten families (ConvNeXt, DenseNet, EfficientNet, Inception, InceptionResNet, MobileNet, NASNet, ResNet, VGG, and Xception) were evaluated using transfer learning on the HAM10000 dataset for seven-class skin lesion classification, namely, actinic keratoses, basal cell carcinoma, benign keratosis-like lesions, dermatofibroma, melanoma, melanocytic nevi, and vascular lesions. The comparative analysis used standardized training conditions, with all models utilizing frozen pre-trained weights. Cross-database validation was then conducted using the ISIC 2019 dataset to assess generalizability across different data distributions. The ConvNeXtXLarge architecture achieved the best performance, despite having one of the lowest performance-to-number-of-parameters ratios, with 87.62% overall accuracy and 76.15% F1 score on the test set, demonstrating competitive results within the established performance range of existing HAM10000-based studies. A proof-of-concept multiplatform mobile application was also implemented using a client–server architecture with encrypted image transmission, demonstrating the viability of integrating high-performing models into healthcare screening tools. Full article

Amelanotic melanocytic nevi of the oral cavity are uncommon lesions that often present a diagnostic challenge for clinicians, primarily due to their nonspecific clinical appearance and the broad spectrum of possible differential diagnoses. These lesions can mimic a variety of benign and malignant conditions, requiring precise histopathological confirmation. The primary objective of this article is to present a comprehensive case report—tracing the course from initial presentation through diagnostic workup to final diagnosis—and to provide an overview of the current literature on oral amelanotic melanocytic nevi. We report the case of a 27-year-old female who presented with a small, exophytic mass located in the anterior mandibular gingival region. The lesion was asymptomatic and lacked pigmentation, adding to the diagnostic uncertainty. A range of differential diagnoses was considered, including pyogenic granuloma, peripheral ossifying fibroma, and squamous cell carcinoma. Due to the lesion’s limited size and accessibility, an excisional biopsy was performed under local anesthesia. Histopathological examination revealed an amelanotic melanocytic nevus, a rare variant characterized by the absence of melanin pigment, further complicating the clinical impression. The diagnosis was confirmed through immunohistochemical staining, which demonstrated melanocytic markers consistent with a nevus. The patient was followed up with for six months postoperatively, with no evidence of recurrence or malignant transformation. This case highlights the critical role of biopsy in achieving a definitive diagnosis, especially in lesions with atypical clinical presentations. It also underscores the importance of considering amelanotic melanocytic nevi in the differential diagnosis of nonpigmented oral lesions, as well as maintaining vigilance regarding the rare possibility of amelanotic melanoma. Full article

Background/Objectives: Telomerase plays a vital role in preserving telomere length, a key process in cancer development. Human telomerase reverse transcriptase (hTERT) is commonly expressed in various cancers, including melanoma. This study evaluated hTERT protein expression in melanomas compared to melanocytic nevi. Methods: In total, we examined 75 melanocytic lesions using TERT immunohistochemistry on paraffin-embedded tissues; 36 of them were thin melanomas (Breslow index ≤ 1 mm) and 39 melanocytic nevi. Results: The TERT expression differed with statistical significance between the two studied groups, melanomas and melanocytic nevi, in all three aspects examined: percentage of staining (p = 0.006), intensity of staining (p = 0.035), and localisation of staining (p = 0.012). Three quarters of the melanomas stained in over 50% of the cells at cytoplasmic level, 52.78% of the melanomas exhibited an intensity of 3+, and all melanomas were stained at the cytoplasmic level, except for the two negative cases. The values were lower in the melanocytic nevi group. Still, the diagnostic values were relatively low (sensitivity = 75%, specificity = 58.97%, PPV = 62.79%, NPV = 71.88%, and ACC = 66.67%). Conclusions: TERT immunohistochemistry differed between the two studied groups; however, the diagnostic utility is low in our study. Combining with other immunohistochemical antibodies would probably increase the diagnostic power. Full article

Congenital melanocytic nevi (CMN) are benign tumors present at birth or arising in the first few months of life. A small subset of these nevi present with mild atypical features and heterogeneous differentiation, including Schwannian differentiation. We present a case of a 3-week-old with a 7 cm red/purple scalp nodule consistent with CMN with mild atypical heterogeneous areas. On histology, there were dermal nests of spindle cells in a fibrillar matrix, with increased vessels and clusters of small round melanocytes interspersed between collagen bundles and around adnexal structures. The lesion also exhibited rare pagetoid ascent of melanocytes as single cells and nests. Overall, these features were consistent with a CMN with nodular proliferative neurocristic cutaneous hamartoma (NCH) with a component of a compound mild atypical melanocytic proliferation. Next generation sequencing (NGS) identified a novel SH2B1::BRAF fusion. This case highlights the diagnostic challenges of heterogeneous differentiation within CMN in young children. Full article

Background: Spitz tumors (STs) are a diverse group of melanocytic lesions that range from benign to malignant. STs pose significant classification challenges due to overlapping histological and immunohistochemical (IHC) features among the STs with different malignant potential. This study aimed to assess the diagnostic value of a melanoma-specific next-generation sequencing (NGS) panel (MelArray) combined with IHC analysis to improve the assessment of diagnostically challenging ST cases. Methods: Patients with STs and available MelArray results were included in this retrospective analysis. Molecular analysis (genetic alterations, tumor mutational burden (TMB), and copy number variations (CNV)), clinical data (demographics and clinical course), and IHC data (scores for markers such as p16, Ki-67, HMB45, PRAME, and Melan A) were evaluated in conjunction and correlated with patient outcomes. Results: Atypical Spitz tumors (ASTs, n = 20) predominantly exhibited heterozygous deletions in melanoma-relevant genes, but these were not accompanied by the multiple damaging mutations commonly associated with melanoma. IHC scores were higher in ASTs compared to Spitz nevi (SN, n = 3), suggesting an intermediate biologic potential. SN exhibited minimal genetic alterations and low IHC scores, reflecting a benign profile. Genetic analysis of the Spitz melanoma (SM, n = 1) revealed a distinct molecular profile with damaging mutations affecting the key regulatory pathways involved in tumor progression, along with a high TMB, and an IHC score comparable to ASTs. During a median follow-up of 36 months (range: 6–48 months, n = 23), no recurrences, distant metastases, or tumor-related deaths were observed. Conclusions: The integration of NGS analysis with the MelArray panel, histology, and immunohistochemistry, enhances the diagnostic accuracy of challenging STs by identifying the genetic alterations linked to malignancy risk. This aids in the detection of high-risk lesions that need a more detailed work-up and more stringent follow-up, and those that will follow a benign course. Larger studies are needed to validate the clinical utility and broader applicability. Full article

Introduction: Diagnostic uncertainty for ambiguous lesions that fall on the spectrum between nevi and melanoma remains a significant challenge and can have consequences for patient management. Methods: This study aimed to compare the diagnostic utility of preferentially expressed antigen in melanoma (PRAME) immunohistochemistry to molecular testing (FISH and SNP array) in 34 diagnostically challenging melanocytic lesions and 9 non-diagnostically challenging melanomas. Results: We conclude that while PRAME immunohistochemistry demonstrates high specificity (96.2%) in diagnostically challenging melanocytic lesions, its low sensitivity (12.5%) suggests that it should not replace histopathological evaluation in rendering the final diagnosis. Conclusions: These findings suggest that PRAME may serve as a useful adjunct in the diagnostic workup, particularly due to its high negative predictive value, but should be used in conjunction with other established diagnostic modalities. Full article

Background/Objectives: Genetics and epigenetics play an important role in the pathogenesis of cutaneous melanoma. The majority of cases harbor mutations in genes associated with the MAPK signaling pathway, i.e., BRAF, NRAS, or NF1. The remaining neoplasms, often located on acral sites, are condensed as the triple-wildtype subtype and are characterized by other molecular drivers. This study aimed to elucidate genetic and epigenetic differences within cutaneous melanoma and to compare it with melanocytic nevi. Methods: DNA was extracted from archived tissue samples of cutaneous melanoma (n = 19), melanocytic nevi (n = 11), and skin controls (n = 11) and subsequently analyzed by massive parallel (next generation) gene panel sequencing and genome-wide DNA methylation array analysis. The sample size was increased by including repository data from an external study. Results: There were major differences in the genomic landscape of MAPK-altered and triple-wildtype cutaneous melanoma, the latter presenting with a lower number of mutations, a different pattern of copy number variants, and a low frequency of TERT promoter mutations. Dimensional reduction of DNA methylation array analysis clearly separated cutaneous melanoma from melanocytic nevi but revealed no major differences between classical cutaneous melanoma and the triple-wildtype cases. However, it identified a possible biological subgroup characterized by intermediately methylated CpGs. Conclusions: Dimensional reduction of methylation array data is a useful tool for the analysis of melanocytic tumors to differentiate between malignant and benign lesions and may be able to identify biologically distinct subtypes of cutaneous melanoma. Full article

Mucosal melanomas (MMs) are under-researched tumors with a poor prognosis that arise from melanocytes found in the mucous membranes at different anatomical locations throughout the body. MMs are an uncommon yet highly aggressive tumor that typically develops on mucosal surfaces, predominantly in the head and neck region. MM of the head and neck occurs in 8–10% of all head and neck melanomas. It most commonly affects the mucosa of the nasal cavity and paranasal sinuses (75%), followed by the oral cavity mucosa (25%). A family history and the presence of mucosal nevi are associated with the occurrence of MM. Inhaled and dietary carcinogens are also linked to the development of sinonasal melanoma, much like other malignancies of the nasal cavity. Overexpression of the C-KIT gene is found in more than 80% of all primary mucosal melanomas, with somatic mutations in 10–30% of cases. The presence of these genetic alterations is also reflected in recent clinical studies of specific gene inhibitors that have proven efficiency in the systemic therapy of melanoma. There are various treatment modalities for MM. Surgical therapy involves en bloc surgical resection with a macroscopically visible and palpable mucosal margin of 1.5–2 cm. Partial resection of the maxilla may be considered if it ensures adequate tumor-free margine. Because of its rarity, outcome data for locally advanced head and neck MM is limited and primarily derived from retrospective studies with small case numbers. This review aims to update and summarize findings from clinical trials, prospective observational studies, and retrospective studies, while also exploring future directions for multimodal treatment approaches in this area. Full article

Background: Cutaneous melanoma (CM) is a malignant tumor originating from melanocytes. Despite improvements in prevention, Central and Eastern European countries continue to report higher rates of advanced-stage melanoma and lower survival rates. This study aims to characterize CM and the associated risk factors in Northwestern Romania. Methods: This cross-sectional cohort study was conducted in Cluj and Bihor counties. Between January 2023 and May 2024, 172 patients with histopathologically confirmed melanoma completed a standardized questionnaire addressing demographics, sun exposure history, nevi count, and melanoma-specific characteristics. Results: The median age at diagnosis of participants was 44 years. The median Breslow index (BI) was 1.5 mm, and 39% of cases presented with a BI > 2 mm. Superficial spreading melanoma (SSM) was the most common subtype, predominantly affecting women, while nodular melanoma (NM) was more frequent in men. Higher BI was associated with NM and acral lentiginous melanoma (ALM). Limbs were women’s most frequent tumor site, whereas the trunk was predominant in men. Significant associations were observed between younger age at diagnosis and factors such as high nevus count, indoor activity, and smoking status. Rural residents reported a higher history of sunburns compared to urban residents. Conclusions: Our findings underscore the importance of targeted public health interventions to promote early detection and primary prevention of melanoma. Establishing a national melanoma registry is crucial to improving epidemiological surveillance and reducing the burden of melanoma in Romania. Full article

Background/Objectives: Facial lesions, including lentigo maligna and lentigo maligna melanoma (LM/LMM), both malignant, present significant diagnostic challenges due to their clinical similarity to benign conditions. Although standard dermoscopy is a well-established tool for diagnosis, its inability to reveal cellular-level details highlights the necessity of new magnified techniques. This study aimed to assess the role of standard dermoscopy, high-magnification dermoscopy, and fluorescence-advanced videodermatoscopy (FAV) in diagnosing LM/LMM and differentiating them from benign facial lesions. Methods: This retrospective, observational, multicenter study evaluated 85 patients with facial skin lesions (including LM, LMM, basal-cell carcinoma, solar lentigo, seborrheic keratosis, actinic keratosis, and nevi) who underwent dermatological examination for skin tumor screening. Standard dermoscopy at 30× magnification (D30), high-magnification dermoscopy at 150× magnification (D150), and FAV examination were performed. Dermoscopic images were retrospectively evaluated for the presence of fifteen 30× and twenty-one 150× dermoscopic features, and their frequency was calculated. To compare D30 with D150 and D150 with FAV, the Gwet AC1 concordance index and the correct classification rate (CCR) were estimated. Results: Among 85 facial lesions analyzed, LM/LMM exhibited distinctive dermoscopic features at D30, including a blue–white veil (38.9% vs. 1.7%, p < 0.001), regression structures (55.6% vs. 21.7%, p = 0.013), irregular dots or globules (50.0% vs. 10%, p = 0.001), angulated lines (72.2% vs. 6.7%, p < 0.001), an annular granular pattern (61.1% vs. 20%, p = 0.002), asymmetrical pigmented follicular openings (100.0% vs. 21.7%; p < 0.001), and follicular obliteration (27.8% vs. 3.3%). At D150, roundish melanocytes (87.5% vs. 18.2%, p < 0.001) and melanophages (43.8% vs. 14.5%, p = 0.019) were predominant. FAV examination identified large dendritic cells, isolated melanocytes, and free melanin in LM/LMM (all p < 0.001) with high concordance to D150. Conclusions: Integrating D30, D150, and FAV into clinical practice may enhance diagnostic precision for facial lesions by combining macroscopic and cellular insights, thereby reducing unnecessary biopsies. However, future studies are essential to confirm these results. Full article

The diagnosis, interpretation, and classification of melanocytic tumors is a very complex topic in the pathology and dermatopathology field that lacks standardization and is still subject to discordance and debate. Here, we review the definitions of dysplastic nevus and superficial atypical melanocytic proliferations and provide an overview of some areas still subject to debate and some attempts of standardization. Furthermore, we describe an algorithmic classification, and provide some examples of clinico-pathological correlation. This step-by-step algorithm has an educational purpose and may automatize the work of dermatopathologists. We hope that through further molecular studies, this fine-grained scheme will prove to be related to the biological behavior of these atypical melanocytic lesions. Full article

Background/Objectives: Melanoma, an aggressive form of skin cancer, accounts for a significant proportion of skin-cancer-related deaths worldwide. Early and accurate differentiation between melanoma and benign melanocytic nevi is critical for improving survival rates but remains challenging because of diagnostic variability. Convolutional neural networks (CNNs) have shown promise in automating melanoma detection with accuracy comparable to expert dermatologists. This study evaluates and compares the performance of four CNN architectures—DenseNet121, ResNet50V2, NASNetMobile, and MobileNetV2—for the binary classification of dermoscopic images. Methods: A dataset of 8825 dermoscopic images from DermNet was standardized and divided into training (80%), validation (10%), and testing (10%) subsets. Image augmentation techniques were applied to enhance model generalizability. The CNN architectures were pre-trained on ImageNet and customized for binary classification. Models were trained using the Adam optimizer and evaluated based on accuracy, area under the receiver operating characteristic curve (AUC-ROC), inference time, and model size. The statistical significance of the differences was assessed using McNemar’s test. Results: DenseNet121 achieved the highest accuracy (92.30%) and an AUC of 0.951, while ResNet50V2 recorded the highest AUC (0.957). MobileNetV2 combined efficiency with competitive performance, achieving a 92.19% accuracy, the smallest model size (9.89 MB), and the fastest inference time (23.46 ms). NASNetMobile, despite its compact size, had a slower inference time (108.67 ms), and slightly lower accuracy (90.94%). Performance differences among the models were statistically significant (p < 0.0001). Conclusions: DenseNet121 demonstrated a superior diagnostic performance, while MobileNetV2 provided the most efficient solution for deployment in resource-constrained settings. The CNNs show substantial potential for improving melanoma detection in clinical and mobile applications. Full article