Malignant blue melanoma.

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

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.

Clinicopathologic description of a cutaneous melanocytic tumor in a 1-year-old cat.

A feline cutaneous melanocytic tumor in a 1-year-old cat is reported. The cytologic, histologic, and immunohistochemical characteristics of the pediatric feline cutaneous melanocytoma are included. A solitary, black-colored nodule on the head was histologically diagnosed as the epithelioid type of melanocytoma. Immunohistochemically, the neoplastic melanocytes demonstrated immunoreactivity to the S100 and MelanA antibodies but not to the PNL2 antibody. Despite high mitotic counts (17/10HPFs) and a Ki67 index (33%) suggesting malignant melanoma, the patient exhibited a favorable 5-month outcome. The mitotic activity of the neoplastic cells may not provide a reliable prediction for feline melanocytic tumors.

Clinical descriptive and long-term outcome of melanocytic uveal lesions in young dogs: 40 cases (45 eyes) including 13 cases of sector iridectomy.

PURPOSE: To describe the clinical features surgical technique, early and long-term outcome with or without surgery, and histopathological findings of melanocytic anterior uveal lesions in young dogs. METHODS: Medical records of dogs at a guide dog facility removed from training due to a pigmented iris lesion were reviewed from 2014 to 2021. Selected dogs had surgical iridectomies performed. RESULTS: Iridal melanocytic lesions were characterized as well-delineated, pigmented, and flat (nevus) or raised (mass) lesions of the iris. Forty dogs (18 Labrador retrievers, 18 German shepherd dogs, 1 Golden retriever, 3 Labrador/Golden mixes) ranging from 0.5 to 3.1 years of age were affected unilaterally (n = 35) or bilaterally (n = 5). Sector iridectomy was performed in 13 dogs with prominent and well-isolated mass lesion and enucleation was carried out in 2 dogs with extensive lesions, while all other cases were monitored without surgical intervention. Postoperative complications included dyscoria (13/13), focal posterior synechia (9/13) and focal nonprogressive cataract (8/13). All eyes remained visual and comfortable up to 6.2 years post-iridectomy with no clinically identifiable local recurrence. Histopathology was consistent with uveal melanocytoma in all samples obtained surgically. All cases that did not undergo surgery remained free of complications up to 4.5 year post diagnosis. CONCLUSION: Melanocytic anterior uveal lesions may be overrepresented in certain lineages of breeds and be present at a young age. While none of the eyes developed complications when monitored without surgery, early surgical excision of the mass by sector iridectomy yields noteworthy functional outcome and retention of a comfortable globe.

The elusive BAP1 mutation in pediatric melanocytic tumors.

Cutaneous BAP1-inactivated melanocytomas (BIM) are melanocytic proliferations defined histopathologically by an epithelioid, predominantly dermal melanocytic proliferation with loss of BAP1, and have been largely characterized in adult patients but less well-described in pediatric cohorts. BIM share overlapping histological features with those seen in Spitz nevi; however, unlike Spitz nevi, the majority of BIM carry both BAP1 and BRAFV600E mutations. This study investigated the potential overlap of BIMs with pediatric Spitz nevi by performing immunohistochemical staining of BAP1 and BRAFV600E on pediatric melanocytic tumors with banal Spitz and dermal features. None of the stained tumors in our study exhibited the concurrent BAP1 loss and BRAFV600E positivity that are characteristic of adult BIM, suggesting that this is a low-frequency mutation among banal tumors in the pediatric population.

Primary Meningeal Melanocytic Tumors of the Central Nervous System: A Review from the Ultra-Rare Brain Tumors Task Force of the European Network for Rare Cancers (EURACAN).

BACKGROUND: Primary meningeal melanocytic tumors are ultra-rare entities with distinct histological and molecular features compared with other melanocytic or pigmented lesions, such as brain and leptomeningeal metastases from metastatic melanoma. METHODS: The European Network for Rare Cancers (EURACAN) Task Force on Ultra-Rare Brain Tumors (domain 10, subdomain 10) performed a literature review from January 1985 to December 2023 regarding the epidemiologic and clinical characteristics, histological and molecular features, radiological findings, and efficacy of local treatments (surgery and radiotherapy) and systemic treatments for these entities. RESULTS: Molecular analysis can detect specific mutations, including GNAQ, GNA11, SF3B1, EIF1AX, BAP1, that are typically found in circumscribed primary meningeal melanocytic tumors and not in other melanocytic lesions, whereas NRAS and BRAF mutations are typical for diffuse primary meningeal melanocytic tumors. The neuroimaging of the whole neuroaxis suggests a melanocytic nature of a lesion, depicts its circumscribed or diffuse nature, but cannot predict the tumor's aggressiveness. Gross-total resection is the first choice in the case of circumscribed meningeal melanocytoma and melanoma; conversely, meningeal biopsy may be reserved for patients with diffuse and multinodular leptomeningeal spread to achieve a definitive diagnosis. High-dose radiotherapy is rarely indicated in diffuse melanocytic tumors except as palliative treatment to alleviate symptoms. Last, a definitive advantage of a specific systemic treatment could not be concluded, as most of the data available derive from case reports or small cohorts. CONCLUSIONS: As primary meningeal melanocytic tumors are extremely rare, the correlations between the clinical characteristics, molecular profile, radiological findings at diagnosis and progression are weak, and poor evidence on the best therapeutic approach is available. There is a need to develop shared platforms and registries to capture more knowledge regarding these ultra-rare entities.

Unsatisfactory Neurological Outcome in an Intramedullary Thoracic Intermediate-Grade Melanocytoma-Systematic Review and Illustrative Case.

BACKGROUND: Intramedullary melanocytomas are exceedingly rare, with only twenty-four cases reported up to now. They present as local invasive tumors despite their benign biological behavior. Attempting a complete safe resection often results in severe post-operative neurological deficits, as in our case presented here. METHODS: A systematic review was conducted across the PubMed and Scopus databases including studies published till February 2024. RESULTS: A total of 19 studies were included, encompassing 24 cases. A similar distribution between sexes was noted (M:F 13:11), with ages ranging from 19 to 79 years. The thoracic segment was most affected, and intermediate-grade melanocytoma (19 cases) was the most common histotype. Radiographically, intramedullary melanocytomas usually appear as hyperintense hemorrhagic lesions peripheral to the central canal with focal nodular enhancement. Intraoperatively, they are black-reddish to tan and are tenaciously adherent lesions. In the sampled studies, IONM employment was uncommon, and post-operative new-onset neurological deficits were described in 16 cases. Adjuvant RT was used in four cases and its value is debatable. Recurrence is common (10 cases), and adjuvant therapies (RT or repeated surgery) seem to play a palliative role. CASE PRESENTATION: A 68-year-old woman presented with a three-year history of worsening spastic paraparesis and loss of independence in daily activities (McCormick grade 4). An MRI revealed an intramedullary tumor from Th5 to Th7, characterized by T1-weighted hyperintensity and signs of recent intralesional hemorrhage. Multimodal neuromonitoring, comprising the D-Wave, guided the resection of a black-tan-colored tumor with hyper-vascularization and strong adherence to the white matter. During final dissection of the lesion to obtain gross total resection (GTR), a steep decline in MEPs and D-Wave signals was recorded. Post-operatively, the patient had severe hypoesthesia with Th9 level and segmental motor deficits, with some improvement during neurorehabilitation. Histopathology revealed an intermediate-grade melanocytoma (CNS WHO 2021 classification). A four-month follow-up documented the absence of relapse. CONCLUSIONS: This literature review highlights that intramedullary T1 hyperintense hemorrhagic thoracic lesions in an adult patient should raise the suspicion of intramedullary melanocytoma. They present as locally aggressive tumors, due to local invasiveness, which often lead to post-operative neurological deficits, and frequent relapses, which overwhelm therapeutic strategies leading to palliative care after several years.

Melanocytoma of the eyelid: Case report and introduction of new nomenclature.

Purpose: The term melanocytoma was recently proposed for intermediate-stage melanocytic lesions with specific histopathologic and molecular genetic features. Prior studies have demonstrated a heightened potential for these intermediate lesions to spread to regional lymph nodes, with decreased likelihood for distant spread, when compared to melanomas. Observations: Herein we present a case of a 28-year-old male who presented with a recurrent right lower eyelid margin combined cutaneous and palpebral conjunctival pigmented lesion, ultimately classified as a melanocytoma, to highlight this new nomenclature, characteristic histopathologic and genetic findings, and prognostic implications. Conclusions: Ophthalmologists should be aware of this new cutaneous histopathologic classification system and apply to the periorbital region to improve melanocytic lesion management and surveillance.

The Role of Radiotherapy for Meningeal Melanocytomas - A 20 Year Update.

BACKGROUND/AIM: Meningeal melanocytomas are rare tumors of the central nervous system and optimal treatment needs further clarification. This study compared subtotal resection (STR), STR plus radiation therapy (RT), gross total resection (GTR), and GTR+RT to better define the role of postoperative RT. PATIENTS AND METHODS: All cases reported in the literature were reviewed. Patients (n=184) with complete data were analyzed for local control (LC) and overall survival (OS). RESULTS: On univariate analysis, GTR (vs. STR) was associated with improved LC (p=0.016). When comparing the treatment regimens, best and worst results were found after GTR+RT and STR alone, respectively (p<0.001). On univariate analysis, GTR resulted in better OS than STR (p=0.041). Moreover, the treatment regimen had a significant impact on OS (p=0.049). On multivariate analyses of LC and OS, extent of resection and treatment regimen were found to be significant factors. After STR, RT significantly improved LC but not OS. After GTR, RT did not significantly improve LC or OS. CONCLUSION: GTR was significantly superior to STR regarding LC and OS. STR+RT resulted in significantly better LC when compared to STR alone.

A rare case of multifocal craniospinal leptomeningeal melanocytoma: A case report and scoping review.

Introduction: Leptomeningeal melanocytomas are rare tumours originating from neural crest derived melanocytes. They are usually solitary and presentation with multifocal meningeal melanocytoma is very rare and indicative of potentially more aggressive behaviour. This case report and scoping review sought to evaluate the presentation, and key radiological features that can help differentiate multifocal meningeal melanocytoma from other differentials and provide a discussion of the key management and prognostic points once these tumours are diagnosed. Case presentation: A 26 year old male presented with neck pain radiating to both shoulders and subjective weakness in left shoulder movement. MRI demonstrated a large enhancing C2-C3 intradural-extramedullary lesion with further lesions at the T7/T8 level, left cerebellopontine angle and midline suprachiasmatic region. Whilst the imaging appearances were initially thought be indicative of a phacomatosis such as NF2-related schwannomatosis, surgical excision of the cervical tumour confirmed a melanocytic tumour of leptomeningeal origin, consistent with multifocal meningeal melanocytoma. Patient made a good post-operative recovery and remains under half yearly radiological surveillance, with repeat MRI 6 months after surgery demonstrating subtle growth of the untreated intracranial and spinal lesions. Literature review and conclusions: This is the first description, to our knowledge, of a multifocal meningeal melanocytoma associated with both cerebellopontine angle and suprasellar lesions. This case and included scoping review highlight the need to consider this rare diagnosis whenever multifocal craniospinal lesions are encountered, and the need to consider aggressive management through surgical resection and adjuvant craniospinal radiotherapy once these tumours are diagnosed.

Melan-A immunolabeling in canine extramedullary plasmacytomas.

Histologic diagnosis of less well-differentiated cases of canine extramedullary plasmacytomas (CEMPs) may require immunohistochemical confirmation to discriminate these tumors from other round cells tumors including lymphoma, cutaneous histiocytoma, and amelanotic melanomas. CEMPs are characterized by widespread immunoreactivity for multiple myeloma 1 (MUM1) antigen and λ light chains, while the melanocytic marker melan-A has been reported to yield negative results. Here, 33 randomly selected CEMPs, 20 melanocytomas, and 20 malignant melanomas were immunohistochemically tested for MUM1, melan-A, and PNL2. In addition, CEMPs were examined for PAX5, E-cadherin, CD3, CD18, CD20, S100, as well as λ and κ light chain immunoreactivity. All CEMPs were characterized by labeling for MUM1 and λ light chain, as well as variable immunopositivity for the remaining antibodies. Notably, 13 cases of CEMPs (39.4%) exhibited immunolabeling for melan-A. Melanocytic tumors immunolabeled for melan-A (40/40; 100%) and PNL2 (34/40; 85%). An unexpected cytoplasmic immunoreactivity for MUM1 was observed in 2 melanocytic tumors. Summarized, MUM1 or melan-A immunomarkers alone are not sufficient to differentiate between CEMPs and amelanotic melanomas and should be part of a larger immunopanel including λ light chain, CD20, and PNL2.

A case of choroidal melanocytoma treated by transscleral resection: A clinicopathological study.

Purpose: Choroidal melanocytoma is a rare benign melanocytic tumor. We report a case of choroidal melanocytoma that was definitively diagnosed by histopathological findings after local resection. Observation: A 71-year-old female complained of blurred vision in her left eye. Her best-corrected visual acuity (BCVA) was 1.0. A dark-brown elevated lesion, measuring 5 papilla-diameter was found in the periphery of the fundus in her left eye. The mass showed hyperfluorescence on fluorescein angiography, early hypofluorescence and late hyperfluorescence on indocyanine green angiography. B-mode echography indicated the mass was originated from the choroid. Orbital magnetic resonance imaging showed isointense signal intensity on T1-weighted images (WI) and hypointense signal intensity on T2-WI, and poor Gadolinium enhancement on T1WI. The tumor was suspected to be melanocytoma, but it was difficult to differentiate from malignant melanoma. Transscleral tumor resection combined with 25-gauge vitrectomy was performed. Histopathological examinations led to the diagnosis of choroidal melanocytoma. Two years after local resection, her BCVA was 1.0 with no tumor recurrence. Conclusions/importance: Local resection was useful as a diagnostic treatment for choroidal tumors confined to the periphery of the fundus that were difficult to clinically differentiate from malignant melanoma.

Amplification of Mutant NRAS in Melanocytic Tumors With Features of Spitz Tumors.

NRAS activating mutations are prevalent in melanocytic neoplasia, occurring in a subset of common acquired melanocytic nevi and ∼30% of cutaneous melanomas. In this study, we described a cohort of 7 distinctive melanocytic tumors characterized by activating point mutations in codon 61 of NRAS with amplification of the mutant NRAS allele and shared clinicopathologic features. These tumors occurred predominantly in younger patients, with a median age of 20 years (range, 6-56 years). They presented as papules on the helix of the ear (4 cases) or extremities (3 cases). Microscopically, the tumors were cellular, relatively well-circumscribed, compound, or intradermal proliferations. The tumor cells often extended into the deep reticular dermis and involved the superficial subcutaneous fat in some cases. The melanocytes were epithelioid to spindled with moderate amounts of cytoplasm and conspicuous nucleoli. They were arranged in short plexiform fascicles, nests, and cords. Some cases had occasional pleomorphic and multinucleated melanocytes. Rare dermal mitotic figures were present in all cases. The dermis contained thick collagen bundles and minimal solar elastosis. Follow-up data were available for 5 patients, with a median period of 4.2 years (range, 1-9 years), during which no recurrences or metastases were reported. Our series highlights a clinicopathologically and molecularly distinctive subset of NRAS-mutated tumors with amplification of the mutant NRAS allele.

Long-Term Stability of Melanocytomas With Persistent Vascular Activity Without Malignant Transformation.

Purpose: To present 2 cases of large atypical melanocytomas that simulate melanoma. Methods: The largest risk factors for malignant transformation from melanocytoma into malignant melanoma are a combination of lesions with a thickness greater than 2 mm, visual symptoms, and tumor margin at the disc. The patients in this report were chosen because they both presented these factors with their lesions. Results: Because the lesions were properly identified as melanocytomas of the optic disc, the decision was made to monitor them closely and treat the associated vascular activity. Ultrasounds and close observations are key in differentiating these benign lesions from malignant melanomas. Conclusions: Both patients experienced long-term stability with intravitreal injections when needed for vascular activity.

[Clinical, histological and genetic correlations in melanocytic tumours with chromosomal rearrangements]. / Corrélations cliniques, morphologiques et génétiques dans les tumeurs mélanocytaires avec translocations chromosomiques.

In some tumoral subtypes chromosomal translocations lead to an oncogenic chimeric protein acting as a tumorigenesis driver event. The main fusion model combines the promoter swapping of an inactivated tumor suppressor gene and a functional kinase that evades its regulatory system. The range of described fusions keeps growing in the 2023 WHO classification of melanocytic tumours. It is not limited to the group of Spitz tumours as previously but now extends to blue tumours and dermal tumours with a melanocytic phenotype. Molecular pathology helps detect these anomalies using clinical and morphological features. This analysis is essential as this strongly conditions the adapted local treatment of such tumours who are often overtreated.

Case Report: Optic Disc Melanocytoma with PHOMS-Minimum Intensity Projection Image.

Introduction: Optic disc melanocytoma (ODMC) with peripapillary hyperreflective ovoid mass-like structures (PHOMS) is rare. This study reports a case of the characteristics of multimodal imaging and Minimum intensity projection (Min-IP) images. Methods: A 25-year-old male patient was referred to our hospital due to the presence of a dark pigmented tumor located in the optic disc area of his left eye. The patient exhibited normal pupillary reactions and had a best corrected visual acuity of 1.0 (decimal) in both eyes. This patient underwent multimodal retinal imaging examination including color fundus photograph (CFP), B-scan ultrasonography, Fundus autofluorescence (FAF), SD-OCT (spectral-domain optical coherence tomography), OCTA (optical coherence tomography angiography), en-face Min-IP image and fluorescein angiography (FA). Results: CFP revealed a slightly elevated mass lesion in the inferior quadrant of the left optic disc, the lesion appeared black to dark brown in color. B-scan ultrasonography of the left eye confirmed the presence of a hyperechoic small dome-shaped lesion. Fundus autofluorescence (FAF) analysis revealed complete hypofluorescence in this area. SD-OCT (spectral-domain optical coherence tomography) and OCTA (optical coherence tomography angiography) with Min-IP were performed over the tumor and its surrounding areas. SD-OCT showed an elevated tumor mass arising from the optic disc with increased reflectivity. PHOMS appeared ovoid in shape on B-scan OCT image. PHOMS appeared peripapillary hyperreflective bright areas on en-face Min-IP image corresponding to PHOMS on B-scan OCT image. The fluorescein angiography (FA) showed the staining of PHOMS. A diagnosis of optic disc melanocytoma with PHOMS was established prompting the patient to be advised for regular follow-up. Conclusion: The optic disc melanocytoma with PHOMS is a rare benign ocular lesion that requires minimal active intervention, but demands a lifetime follow-up. The multimodal imaging and Min-IP images have clinical diagnostic value.

Clinicopathologic profiles of canine ocular melanosis: A comparative study between cairn terriers and non-cairn terriers.

OBJECTIVES: To identify canine breeds at risk for ocular melanosis and to compare the clinical and histologic features between affected Cairn Terriers (CTs) and non-Cairn Terriers (NCTs). DESIGN: Relative risk (RR) analysis and retrospective cohort study of dogs histologically diagnosed with ocular melanosis. PROCEDURES: The COPLOW archive was searched for globe submissions diagnosed with ocular melanosis. Six hundred fifty globes were included, and RR analysis was performed to identify at-risk NCT breeds. A cohort of 360 CT and NCT globes diagnosed from 2013 to 2023 were included in the retrospective cohort study. Clinical data were collected from submission forms, medical records, and follow-up surveys. One hundred fifty-seven submissions underwent masked histologic review. Immunohistochemical staining for CD204 was performed to determine the predominance of melanophages in affected uvea from five NCTs. RESULTS: At-risk NCT breeds included the Boxer, Labrador Retriever, and French Bulldog. Glaucoma was the reported reason for enucleation in 79.4% of submissions. At enucleation, clinical features less prevalent in NCTs than CTs included pigmentary abnormalities in the contralateral eye (33.7% vs. 63.1%, p = .0008) and abnormal episcleral/scleral pigmentation in the enucleated globe (25.4% vs. 53.6%, p = .0008). Histologic involvement of the episclera was also less frequent in NCTs than in CTs (39.7% vs. 76.9%, p = .008). Concurrent melanocytic neoplasms arising in melanosis were more common in NCTs (24.4%) than CTs (3.9%). Melanophages were not predominant in any samples evaluated immunohistochemically. CONCLUSIONS: Several popular NCT breeds carry risk for ocular melanosis, and some clinicopathologic disease features may differ from those described in CTs.

Intraoperative View of a Multinodal, Paralysis-Inducing Spinal Melanocytoma: Case Report and Literature Review.

Melanocytomas arising from the leptomeningeal melanocytes within the central nervous system are a rare occurrence, accounting for 0.06%-0.1% of brain tumors and having an incidence of 1/10 million people per year.1-14 Here, we describe the case of 68-year-old male presenting with bilateral lower extremity weakness progressing to paralysis and urinary incontinence (Video 1). Upon examination, this gentleman had no sensation below T11. Magnetic resonance imaging showed multiple contrast-enhancing lesions with a major intradural lesion at level T11 arising from the ventrolateral surface and causing severe spinal cord compression. The multifocal nature of this tumor further adds to its rarity. Interdisciplinary indication for surgical resection of the intradural lesion was made. This was accomplished through a T11 laminectomy and concomitant T11-12 stabilization with neuromonitoring. Pathologic analysis of the resected tumor identified an S100+, HMB45+, pigmented melanocytoma. No complications occurred during the procedure. The patient was discharged to rehabilitation with persistent neurologic deficits. Routine follow-up is indicated given the high rates of recurrence and the multiple remaining tumor nodules.14.

Pigmented epithelioid melanocytoma arising from a teratoma of a Carney complex patient.

A 25-year-old female Carney complex patient with a PRKAR1A mutation who had undergone surgery to remove teratomas visited our dermatology department. She was suspected of having a malignant melanoma in a teratoma. On clinical examination, a black nodule was found within the cyst. On histopathological examination, the black lesion was composed of heavily pigmented round cells with vesicular nuclei and single prominent nucleoli. Additionally, there were large cells with irregularly shaped nuclei. Upon immunohistochemical examination, the large, irregularly shaped cells were positively stained with Melan A, HMB45, S-100 protein, SOX10, CD10 (focally), and BRAFV600E , but negatively stained with PRAME. Based on the histopathological features, we diagnosed the patient with pigmented epithelioid melanocytoma (PEM) in a teratoma of a Carney complex patient. This is the first case of PEM developing from a teratoma. Since PEM lesions may spread to regional lymph nodes, careful follow-up is necessary.