Congenital melanocytic nevus syndrome: An association between congenital melanocytic nevi and neurological abnormalities.

Congenital melanocytic nevus syndrome describes congenital melanocytic nevi (CMN) associated with extracutaneous abnormalities, most often involving the nervous system. CMN syndrome is usually caused by postzygotic mutations in the neuroblastoma RAS viral oncogene homolog (NRAS) gene. CMN, collections of melanocytes within the skin, are typically multiple in number and serve as a visible, cutaneous marker of this syndrome. CMN can be classified by predicted maximum diameter in adulthood as well as other clinical features such as anatomic location, color heterogeneity, hypertrichosis, number of satellite nevi, nodules, and surface rugosity. Common neurological abnormalities in CMN syndrome include melanin with the central nervous system (CNS), seizures, and neurodevelopmental delays. Early screening magnetic resonance imaging (MRI) of the CNS during the initial months of life is crucial for predicting the risk of neurodevelopmental abnormalities, seizures, and the need for neurosurgical intervention. Children with a normal screening CNS MRI or intraparenchymal melanosis alone tend to have favorable outcomes. Prognosis otherwise varies widely given the breadth of neurological abnormalities that can occur in CMN syndrome, however if primary melanoma develops in the skin or CNS then outcomes are typically poor.

Treatment Options in Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP): Case Presentation and Review of the Literature.

PURPOSE: To outline the therapeutic approach for a rare case of Bilateral Diffuse Uveal Melanocytic Proliferation (BDUMP) and examine the current management recommendations of this uncommon condition. METHODS-RESULTS: Literature review on the current treatment options in BDUMP cases. An 82-year-old woman was referred to our clinic due to bilateral visual loss. She was treated elsewhere with anti-vascular endothelial growth factors (anti-VEGF) in both eyes for presumed choroidal neovascularization (CNV) without improvement. Her past medical history (PMH) entailed colon cancer, treated with surgical resection and adjuvant chemotherapy 15 years ago. The patient presented with low visual acuity in both eyes, multiple oval orange patches in the fundus with striking hyperfluorescent pattern in fluorescein angiography (FA), giraffe pattern in fundus autofluorescence (FAF) and rapidly progressive cataracts. Intravitreal dexamethasone implants were administered with mild improvement and subretinal fluid absorption. CONCLUSIONS: The management strategy in BDUMP should focus on the systemic, often occult malignancy. There is no standard treatment protocol for BDUMP; however, plasmapheresis in combination with primary malignancy treatment seems to yield promising results in current literature reports. Anti-VEGF injections failed to control BDUMP sequelae, however intravitreal dexamethasone implants may offer temporary relief.

["Red flags" during pregnancy-skin symptoms and their causes during pregnancy]. / "Red flags" in der Schwangerschaft ­ Hautsymptome und ihre Ursachen in der Schwangerschaft.

Pregnancy is a special state for the expectant mother. Not only is a human being growing, but the pregnant woman's body is also constantly changing during the 40-week pregnancy. One organ that is frequently affected by these changes is the skin. As diagnosis and treatment during pregnancy can present treating physicians with particular challenges, it is important to know the relevant pregnancy dermatoses, to recognize and diagnose them reliably, and to observe red flags in order to protect the pregnant women and the unborn child. In this article, the most important changes in the skin of pregnant patients are explained and potential warning signs are presented. In addition to aspects of altered pigmentation, the influence of pregnancy on pre-existing inflammatory dermatoses and their improvement or worsening is also described. The occurrence of so-called specific pregnancy dermatoses over the course of pregnancy is also explained. Finally, the extent to which autoimmune diseases of the mother can also affect the unborn child and to what extent skin changes in the newborn can indicate a disease of the mother are described. The respective "red flags" are presented as leading symptoms and their relevance is discussed.

Concomitant melanoma and keratoma affecting the equine digit: clinical, pathological, and long-term follow-up findings.

BACKGROUND: This case report details a long-term follow-up of a hoof melanoma with dermo-epidermal activity (resembling Spreading Superficial Melanoma (SSM)) in a bay horse with a history of a right front hoof keratoma. Melanomas involving the horse's foot are seldom reported and usually diagnosed as anaplastic melanomas based on signalment and post-mortem examination. The clinical-pathological characteristics of the foot melanoma in this bay horse are consistent with SSM-like described in humans, which is considered an intermediate malignant tumour attending their biological behaviour. However, a definitive diagnosis is limited by the single case and the lack of references in horses. CASE PRESENTATION: A 12-year-old bay Andalusian gelding underwent keratoma removal on the lateral aspect of the hoof wall. A partial resection of the hoof wall was performed for this purpose. Additionally, a plaque-like, hyperkeratotic pigmented lesion, 2 × 2X0,4 cm in size, was observed at the lateral aspect of the coronary band and was also resected for histopathological examination. Microscopically, a melanocytic tumour, characterised by small nests of large polygonal or epithelioid cells infiltrating the basal and suprabasal epidermis, the dermo - epidermal junction, and the superficial dermis, was observed. The neoplastic cells exhibited large euchromatic nuclei, prominent nucleoli, moderate pleomorphism and 4 mitotic figures per 2,37mm2; variable amounts of dark granules (melanin) were present in the cytoplasm, as well as in numerous peritumoral macrophages. The immunophenotype of the tumour cells was PNL2 + + + , S100 + + , AE1/AE3-. A diagnosis of melanoma with dermo-epidermal junction and marked intraepidermal activity (consistent with superficial spreading melanoma) was made. A magnetic resonance imaging (MRI) performed, revealed no further invasion into surrounding structures. Treatment was based on surgical resection and multiple local chemotherapy sessions with cisplatin were applied. The biopsies obtained after treatment showed partial regression of the tumour and different stages of healing. After 26 months of follow-up, there was no signs of malignant spreading into surrounding structures including the pedal bone and distal metastasis but a dark - coloured area persists over the lateral aspect of the coronary band. CONCLUSIONS: This case presents a concomitant keratoma and melanoma with dermo - epidermal activity, resembling a spreading superficial melanoma. After a follow - up of 26 months the horse remains healthy and sound providing new information for clinicians and pathologists. Despite the poor prognosis associated with foot malignant melanocytic tumours, it is important that an early and accurate diagnosis is reached through different diagnostic modalities such as advanced imaging techniques and histopathology. Additionally, these findings demonstrate that the current classification and prognosis for equine foot melanomas are insufficient.

Update on cutaneous mesenchymal tumors in the 5th edition of WHO classification of skin tumors with an emphasis on new fusion-associated neoplasms.

The section on mesenchymal tumors in the 5th edition of WHO classification of skin tumors has undergone several changes, the most important of which is the inclusion of newly identified tumor entities, which will be the main focus of this review article. These specifically include three novel cutaneous mesenchymal tumors with melanocytic differentiation, and rearrangements of the CRTC1::TRIM11, ACTIN::MITF, and MITF::CREM genes as well as EWSR1::SMAD3-rearranged fibroblastic tumors, superficial CD34-positive fibroblastic tumors, and NTRK-rearranged spindle cell neoplasms. Some of the other most important changes will be briefly mentioned as well.

Computerizing the first step of the two-step algorithm in dermoscopy: A convolutional neural network for differentiating melanocytic from non-melanocytic skin lesions.

IMPORTANCE: Convolutional neural networks (CNN) have shown performance equal to trained dermatologists in differentiating benign from malignant skin lesions. To improve clinicians' management decisions, additional classifications into diagnostic categories might be helpful. METHODS: A convenience sample of 100 pigmented/non-pigmented skin lesions was used for a cross-sectional two-level reader study including 96 dermatologists (level I: dermoscopy only; level II: clinical close-up images, dermoscopy, and textual information). Dermoscopic images were classified by a binary CNN trained to differentiate melanocytic from non-melanocytic lesions (FotoFinder Systems, Bad Birnbach, Germany). Primary endpoint was the accuracy of the CNN's classification in comparison with dermatologists reviewing level-II information. Secondary endpoints included dermatologists' accuracies according to their level of experience and the CNN's area under the curve (AUC) of receiver operating characteristics (ROC). RESULTS: The CNN revealed an accuracy and ROC AUC with corresponding 95 % confidence intervals (CI) of 91.0 % (83.8 % to 95.2 %) and 0.981 (0.962 to 1). In level I, dermatologists showed a mean accuracy of 83.7 % (82.5 % to 84.8 %). With level II information, the accuracy improved to 87.8 % (86.7 % to 88.9 %; p < 0.001). When comparing accuracies of CNN and dermatologists in level II, the CNN's accuracy was higher (91.0 % versus 87.8 %, p < 0.001). For experts with level II information results were on par with the CNN (91.0 % versus 90.4 %, p = 0.368). CONCLUSIONS: The tested CNN accurately differentiated melanocytic from non-melanocytic skin lesions and outperformed dermatologists. The CNN may support clinicians and could be used in an ensemble approach combined with other CNN models.

Exploring the Epidemiology of Melanocytic Tumors in Canine and Feline Populations: A Comprehensive Analysis of Diagnostic Records from a Single Pathology Institution in Italy.

MTs are prevalent in dogs, representing the most frequent oral malignancy, compared to cats, in which ocular melanomas predominate. This study investigates the canine and feline MT epidemiology (2005-2024) of cases submitted to the Veterinary Pathology Service (University of Perugia). Among the canine neoplasms, 845 (4%) were melanocytic: 329 (39%) melanocytomas; 512 (61%) melanomas. Of these, 485 (57%) were cutaneous (4% of canine cutaneous neoplasms), 193 (23%) were oral (50% of oral canine neoplasms), and 104 (12%) were mucocutaneous. The average age of affected dogs was 10 years. Older dogs were more likely to have melanomas compared to melanocytomas (p < 0.001). There were 60 (1%) feline MTs: 6 (10%) melanocytomas; 53 (88%) melanomas. Of these, 29 (48%) were cutaneous (1% of feline cutaneous tumors), 18 (30%) were ocular, and 9 (15%) were oral (22% of feline oral tumors). The average age of affected cats was 11 years. In dogs, mucocutaneous melanomas were more common compared to cutaneous ones (p < 0.05); oral melanomas were more common compared to all other sites (p < 0.001). In cats, ocular melanomas were more common compared to cutaneous ones (p < 0.05). Our study provides the MT prevalence in a selected canine and feline population, revealing MT epidemiological patterns, highlighting species-specific differences in the tumor prevalence, localization, and age distribution.

Unusual Appearance of Meyerson Phenomenon Arising From a Congenital Melanocytic Nevus: Case Report and Literature Review.

Although melanocytic nevi have a relatively uneventful course throughout their existence, some may develop an inflammatory reaction known as the Meyerson phenomenon. Initially, the Meyerson phenomenon has been exclusively described in melanocytic nevi. However, it has since been observed in both pigmented and non-pigmented lesions, thus expanding the description from Meyerson nevus to the phenomenon. We report a case of an unusual Meyerson phenomenon arising from a congenital melanocytic nevus characterized by a weeping eczematous response.

Conjunctival Melanoma: A Clinical Review and Update.

Conjunctival melanoma (Co-M) is an aggressive, invasive eye and eyelid cancer. Its global incidence of ~1 in a million is increasing at a rate ratio of ~1.4, but this rises sharply in over 65-year-olds. Although rare, Co-M has a devastating impact on the lives of those who develop it. Co-M is often misdiagnosed or overlooked, leading to vision loss either from the destructive effects of the tumour or side effects of therapy, facial disfigurement from radical surgery, and death from metastases. Due to its rarity, there is limited evidence for diagnosis and management; hence, there is no standardised treatment and not all cases are referred to a specialised ocular oncology centre. Recent progress in cancer immunology and genetics have revolutionised the treatment of cutaneous melanomas, which share some similarities to Co-M. Importantly, a better understanding of Co-M and its precursor lesions is urgently needed to lead to the development of novel targeted and immunotherapies both for local tumour control and disseminated disease. This review aims to provide a comprehensive clinical overview of the current knowledge regarding Co-M, its epidemiology, pathogenesis, presentation, diagnosis and recent changes in the classification of its precursor lesions, management, and recent advances in novel biological therapies for personalised treatment of this disease.

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.

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.

Melanocytic cutaneous lesions in Sus ibericus, are these a cause for meat condemnation?

The Alentejano pig (Sus ibericus) is an autochthonous breed of swine from Portugal phylogenetically close to the Iberian breed that is known to develop melanocytic lesions. In this study, 34 melanocytic skin lesions were identified and collected from Alentejano pigs slaughtered for human consumption for further routine histologic assessment. The samples were classified into 4 age ranges: 1 (1 to 6 months), 2 (7 to 12 months) 3 (13 to 24 months), and 4 (more than 25 months). All the lesions were considered benign after the histopathological assessment, of which 52.9% and 47.1%, were classified as melanosis and melanocytomas, respectively. Regarding the age ranges, a statistical difference between the groups was observed, indicating that the probability of melanosis presentation was higher at the age range 4 and for melanocytomas at the age range 3. While no malignant lesions were observed in this study, it was concluded that benign melanocytic lesions are commonly found in Alentejano pig carcasses. Further research is necessary to accurately distinguish between malignant and benign lesions, which is crucial for official veterinarians to make decisions regarding meat approval or condemnation.

Conjunctival melanoma with pronounced central corneal invasion: One-year relapse free follow-up.

Purpose: Conjunctival melanoma with large corneal involvement is a rarity. We here present a case of conjunctival melanoma with pronounced central corneal involvement. Observation: A 69-year-old fair white male presented with a visual axis impeding corneal nodular lesion with associated conjunctival melanosis. Tumor excision with intraoperative mitomycin c (0.02 %) application for 180 seconds and amniotic membrane transplantation for defect coverage was performed in retrobulbar anesthesia. Histopathological evaluation revealed the nodular lesion to be a conjunctival melanoma (pT1a) with associated conjunctival melanocytic intraepithelial lesion (C-MIL). Conclusion and importance: Most conjunctival melanomas with corneal affection reach a radial corneal involvement of 1 mm. The here reported case accounted for 4 mm, which is seldom and therefore an important report. Surgical excision followed by intraoperative and postoperative mitomycin c exposure was a successful primary treatment. Currently there are no signs of tumor relapse in any part of the eye or the organism 12 months after excision. However, the long-term follow-up needs to be awaited.

BRCA1-associated-protein-1 inactivated melanocytic tumours: characterisation of the clinicopathological spectrum and immunohistochemical expression pattern of preferentially expressed antigen in melanoma.

AIMS: BRCA1-associaed protein-1 (BAP1) inactivated tumours (BIMT) are rare melanocytic tumours that may be mistaken for Spitz tumours or melanoma. They occur sporadically or in association with the BAP1 tumour predisposition syndrome (BAP1-TPDS), which may be complicated by uveal or cutaneous melanoma, mesothelioma, basal cell carcinoma and renal cell carcinoma. The aim of this study was to characterise the clinicopathological features and the immunohistochemical expression pattern of preferentially expressed antigen in melanoma (PRAME) of BIMT in a large patient cohort. METHODS AND RESULTS: Ethical approval was obtained, haematoxylin and eosin-stained slides were reviewed, PRAME immunohistochemistry was performed and clinical follow-up was obtained from patient records. Sixty-five BIMT from 38 patients (F:M = 4.4:1) were identified. BIMT were typically located on the trunk and head and neck (median size = 0.5 cm). Seven patients with BAP1-TPDS (range = 16-66 years, median = 25) had multiple BIMT (median = 5), while sporadic BIMT were solitary (median patient age = 39 years). One of seven patients with BAP1-TPDS developed additional malignancies (mesothelioma and cutaneous spindle cell melanoma) and died of complications of mesothelioma. All other patients are alive without recurrence of BIMT (median follow-up = 42 months). BIMT presented as intradermal, nodular aggregates of epithelioid melanocytes with low mitotic activity and moderate to severe cytological atypia in 63% of cases. A background conventional naevus was present in 64%. PRAME immunohistochemistry showed negative or weakly patchy positive staining in all BIMT. CONCLUSIONS: BIMT are more common in a sporadic setting and behave indolently, despite worrying cytological atypia. PRAME immunohistochemistry is a reassuring tool in distinguishing BIMT from melanoma.

Evaluation of SOX-10 immunohistochemical expression in canine melanoma and non-melanocytic tumors by tissue microarray.

Melanoma is the most common malignant oral tumor in dogs. It frequently presents a diagnostic challenge as many melanomas lack or contain scant melanin and may have a variable microscopic phenotype. Previous studies evaluating immunohistochemical markers for diagnosing melanoma have shown limited sensitivity and/or specificity for S-100, PNL2, melan A, TRP-1, TRP-2, and HMB-45. Sry-related HMG-box gene 10 (SOX-10) is a transcription factor associated with melanocytic, peripheral neural crest, and peripheral nervous system development. In humans, SOX-10 expression has been demonstrated in melanoma, breast carcinoma, glioma, and schwannoma, but has only recently been explored in veterinary species. In this study, 198 tumors comprised of 147 melanocytic neoplasms and 51 non-melanocytic neoplasms were evaluated by immunohistochemistry using a tissue microarray for SOX-10, PNL2, melan A, TRP-1, and TRP-2 expressions. The SOX-10 had the highest diagnostic sensitivity (96.7%) in melanomas. In addition, SOX-10 had the highest percentage (91.5%; 130/142) of melanomas label at least 75% of neoplastic cells. Of the 51 selected non-melanocytic tumors examined, SOX-10 labeling was observed in mammary carcinomas (6/6), gliomas (4/4), and oral soft tissue sarcomas (4/18). Of the 41 non-melanocytic oral neoplasms evaluated, SOX-10 had a specificity of 92.7%. Therefore, SOX-10 represents a useful immunohistochemical screening marker for the diagnosis of canine melanoma given its extremely high sensitivity and robust labeling intensity. The SOX-10 may have utility in diagnosing some non-melanocytic neoplasms in the dog, although this requires further investigation.

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.

Histopathologic, genomic, transcriptomic, and functional characteristics of eight melanocytic tumors with BRAF fusions showing stronger MAPK pathway activation compared to BRAF V600E tumors.

BACKGROUND: Activating BRAF gene alterations are central to melanocytic tumor pathogenesis. A small, emerging subset of melanocytic tumors driven by BRAF fusions has distinct therapeutic implications and has been described to have Spitzoid morphology patterns. However, such morphological patterns do not encompass all cases, and little is known about the functional molecular events. MATERIALS AND METHODS: We conducted a retrospective search through our molecular archives to identify melanocytic tumors with BRAF fusions. We reviewed clinical, histopathological, and genomic features. We further explored transcriptomic and protein-level findings. RESULTS: Histopathologic patterns varied, with many cases without a distinctive pattern. We identified novel and diverse BRAF gene fusion partners. Differential transcriptomic analysis between low-risk BRAF fusion tumors and reference BRAF V600E tumors showed no differentially expressed genes. However, quantitatively stronger MAPK pathway activation of BRAF fusion tumors over BRAF V600E tumors was demonstrated by statistically significant stronger staining of p-ERK immunohistochemistry. Gene-specific RNA analysis shows comparable BRAF transcript levels between the two groups. DISCUSSION AND CONCLUSION: The quantitatively stronger activation of the MAPK pathway of BRAF fusion tumors, instead of qualitatively different transcriptomes, may account for the morphology difference from conventional BRAF V600E tumors. BRAF fusions likely act through dysregulated protein function rather than RNA upregulation related to the characteristics of the fusion partners.

Parent experiences during delivery, postpartum, and adoption of children with congenital melanocytic nevi.

BACKGROUND/AIMS: Congenital melanocytic nevi (CMN) are often unexpected discoveries at time of childbirth or adoption. Understanding how parents/guardians cope with these visible birthmarks can help clinicians better care for children and their families. Using qualitative methods, we sought to categorize early family responses to CMN and identify approaches to better engage with parents early in their child's life. METHODS: Semi-structured interviews were conducted within a broader study on shared decision making for families with children with CMN. Discussions included information on birth and early life experiences. Data was dual-coded, inductively and deductively, and analyzed with the Parker and Endler framework exploring emotion-, task-, and avoidance-oriented coping. RESULTS: Fifteen parents of 13 children were interviewed. Parents described all three categories of coping. Emotions ranged from guilt, to neutrality, to positive responses seeing their child's CMN. Stress was lower in families with prior knowledge of CMN. Dermatology referral provided an opportunity for learning, but also triggered worry for some families. CONCLUSIONS: Parents process and react to the diagnosis of CMN with a range of emotions and coping styles. Dermatologists can utilize open-ended questions to understand family emotions and provide families with tailored knowledge and resources. Early discussion of the diagnosis and family education are important support tools.