Beyond nest size: the clinicopathological spectrum of large nested melanocytic tumours and the value of comparative genomic hybridisation and messenger RNA expression analysis.

Large nested melanomas (LNMs) are a rare subtype of naevoid melanoma consisting of large junctional melanocytic nests that are more common in older individuals and/or associated with sun damage. However, the presence of large melanocytic nests alone does not lead to a diagnosis of malignancy, â€‹as they can also be found in melanocytic naevi. LNMs are challenging because they lack most classic histological features of malignancy and require thorough clinicopathological evaluation. This ambiguity calls for a critical reassessment of the current diagnostic criteria for the subclassification of benign or malignant within the spectrum of large nested melanocytic tumours (LNMTs). Eighteen LNMTs and six special-site melanocytic naevi (SSMNs) â€‹were studied using different approaches: clinical features, dermoscopy, histopathology, immunohistochemistry, array comparative genomic hybridisation (aCGH) and messenger RNA (mRNA) sequencing analysis, with the aim of identifying novel and reproducible criteria for the recognition of LNMs.Careful clinicopathological evaluation of the 18 LNMTs led to the diagnosis of seven LNMs and 11 large nested melanocytic naevi (LNMNs). Lentiginous spread and nest bridging were significantly associated with LNMs after Holm-Bonferroni correction. Asymmetry, largest nest size, poor lateral demarcation, the number of colours and dermoscopic structures, and preferentially expressed antigen in melanoma (PRAME) immunostaining were more common in LNMs but did not reach statistical significance. Four of seven LNMs and nine of 11 LNMNs lacked the BRAF V600E mutation. Regarding aCGH, no LNMN or SSMN cases had ≥3 copy number variations (CNVs), in contrast to 50% of LNM cases. Importantly, LNM and LNMN could be distinguished by differential mRNA expression of nine genes. Our study demonstrates that there is a spectrum of LNMTs and that the clinicopathological diagnosis of LNM, for which we support the term 'late-onset nested naevoid melanomas', can be significantly strengthened by the presence of lentiginous pattern, nest bridging, gene CNV and differential mRNA expression.

More than one shade of pink as a marker of early amelanotic/hypomelanotic melanoma.

Amelanotic/hypomelanotic melanoma (AHM) may be difficult to diagnose because of a lack of pigmentation. To evaluate whether dermoscopy can be useful for the diagnosis of early AHM, 133 digital dermoscopic images of lesions histopathologically diagnosed as amelanotic/hypomelanotic superficial spreading melanoma with ≤1 mm thickness (AHSSMs) (n = 27), amelanotic/hypomelanotic non-melanocytic lesions (AHNMLs) (e.g., seborrhoeic keratosis and basal cell carcinoma) (n = 79), and amelanotic/hypomelanotic benign melanocytic lesions (AHBMLs) (e.g., compound and dermal nevi) (n = 27), were dermoscopically assessed by three blinded dermatologists. Using multivariate analysis, we found a significantly increased risk of diagnosing AHSSM versus AHNML and AHBML when the lesion was characterized by the presence of more than one shade of pink (odds ratio [OR] 37.11), irregular dots/globules (OR 23.73), asymmetric pigmentation (OR 8.85), and structureless pattern (OR 7.33). In conclusion, dermoscopy may improve early AHM detection, discriminating AHSSM from amelanotic/hypomelanotic non melanoma lesions.

Malignant Cutaneous Neurocristic Hamartoma With Features of Melanoma: A Rare Entity.

Neurocristic cutaneous hamartoma (NCH) is a rare, benign neoplastic skin lesion characterized by a combination of neuroectodermal and mesodermal components. Clinically, NCH typically presents as asymptomatic, well-circumscribed, and elevated cutaneous nodules. Histopathologically, it is characterized by nests of pigmented melanocytes and varying degrees of fibrosis and collagen deposition. The precise etiology of NCH remains undetermined; however, it is hypothesized to arise from the aberrant development of neuromesenchyme. Due to its potential to mimic other pigmented melanocytic disorders, accurate differential diagnosis is crucial to prevent mismanagement. Surgical excision is the preferred treatment modality, offering a generally favorable prognosis and low recurrence rate. Conversely, malignant cutaneous neurocristic hamartoma (MCNH), an exceedingly rare malignant variant of NCH, poses a significantly different clinical challenge. This review focuses on the diagnostic criteria, clinical presentation, and management strategies for MCNH, emphasizing the need for differentiation from other similar cutaneous lesions. We present a detailed case report of MCNH in a 56-year-old female, highlighting its histopathological and immunohistochemical features to provide insights into the diagnosis and therapeutic approach for this exceptionally rare malignancy.

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.

Melanoma arising in a child with a medium-sized congenital melanocytic nevus.

Pediatric melanomas are rare and some of them may arise on giant congenital melanocytic nevi. The risk of developing melanoma on a medium-sized nevus is not clear but is thought to be very rare. Proliferative cellular nodules which mimic malignant melanoma may pose significant diagnostic challenges. We report the case of a 9-year-old patient who developed a melanoma on a medium-sized congenital melanocytic nevus on the tip of the nose, requiring a complex surgery with excellent aesthetic results.

Los melanomas en pediatría son raros y algunos de ellos pueden surgir sobre nevos melanocíticos congénitos gigantes. El riesgo de desarrollar melanoma en un nevo de tamaño mediano no está claro, pero se cree que es muy raro. Los nódulos proliferativos celulares, que imitan al melanoma, pueden plantear importantes desafíos diagnósticos. Presentamos el caso de una paciente de 9 años que desarrolló un melanoma sobre un nevo melanocítico congénito de tamaño mediano en la punta de la nariz, que requirió un procedimiento quirúrgico complejo con excelentes resultados estéticos.

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.

Agminated Eruptive Melanocytic Nevi and Nail Changes Following Toxic Epidermal Necrolysis in a Pediatric Patient: A Case Report and Systematic Review of the Literature.

Eruptive melanocytic nevi (EMN) have been reported in the setting of immunosuppression, chemotherapy, and bullous skin disease, including less commonly, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). This case report presents a 4-year-old girl who developed agminated EMN and nail changes after TEN. A systematic review of the literature supports clinically appropriate follow-up of EMN, as there is no reports of malignancy in EMN following SJS/TEN, nor reports of pediatric melanoma arising within EMN of any etiology. Further study of the possible correlation of nail changes with the development of EMN and better characterization of the dermoscopic features of EMN could improve monitoring and care of these patients.

Isolated melanoma metastasis in a patient with large congenital nevus without detectable primary melanoma: a case report and review of literature.

Giant congenital pigmented nevi constitute an extremely diverse group of skin lesions with varying morphologies. These nevi are often associated with many clinical implications, such as increased risk of melanoma and the presence of neurocutaneous melanosis, with melanoma being the primary concern. We present a rare case of a 62-year-old patient with a giant congenital birthmark who reported to the oncology department due to a tumor in the lower abdomen detected during an ultrasound examination. A biopsy of the lesion showed the presence of melanoma metastasis. Four independent dermatologists performed a dermoscopic examination of the patient's skin and mucous membranes. In the PET/CT examination, apart from the previously described change in the lower abdomen, no metabolically active foci with features of malignant growth were found. The patient underwent surgical removal of the lesion in the lower abdomen. The postoperative histopathological examination confirmed the presence of metastasis of melanoma in the subcutaneous tissue of the abdomen with no connection to the epidermis. The BRAFV600 mutation was not found in the molecular test. For stage IV R0 melanoma with distant metastasis, with stage T0N0M1a, the only adjuvant treatment option following radical resection is nivolumab. After a rheumatological consultation, the patient was qualified for adjuvant treatment with nivolumab.

["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.

Concurrent Eruptive Melanocytic Nevi and Multiple Keratoacanthomas Induced by Encorafenib.

Eruptive melanocytic nevi and multiple keratoacanthomas are rare cutaneous conditions, often linked to drug-related toxicities but rarely reported simultaneously, particularly in cancer patients undergoing BRAF-targeted therapies. We present a case of a 64-year-old male with metastatic colorectal cancer who developed severe pruritus and widespread new skin lesions following treatment with encorafenib, a v-Raf murine sarcoma viral oncogene homolog B (BRAF) inhibitor, and panitumumab, an anti-epidermal growth factor receptor (EGFR) monoclonal antibody. The dermatological assessment identified both pigmented and non-pigmented lesions, including benign nevi and keratoacanthomas. Despite close monitoring, larger keratoacanthomas persisted, prompting surgical excision, which confirmed lichenoid keratosis. The Naranjo scale indicated a definite association between encorafenib and cutaneous reactions, with a score of nine. The mitogen-activated protein kinase pathway's role in cutaneous adverse events was explored, suggesting a paradoxical activation mechanism. Discontinuation of encorafenib and panitumumab led to gradual resolution of most lesions, highlighting a possible etiopathogenic link. This study emphasizes the need for thorough dermatologic evaluation and follow-up in patients receiving BRAF inhibitors to optimize management and avoid unnecessary treatment cessation.

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.

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.

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.

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.

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.

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.

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.