Amelanotic melanoma involving the central nervous system (CNS) in association with congenital melanocytic naevi (CMN) is exceptionally rare and aggressive. Our literature review identified only two prior paediatric cases, reported in 1999 and 2021. To the best of our knowledge, this is the first reported paediatric case of CNS amelanotic melanoma with systemic metastases associated with CMN. We present a 2-year-old girl with CMN who developed an afebrile seizure, vomiting and neurological decline. Imaging revealed hydrocephalus, diffuse leptomeningeal enhancement, spinal cord compression and distant metastases. Histopathology confirmed metastatic amelanotic melanoma. She was treated with targeted therapy comprising trametinib and azacitidine, with a plan for immunotherapy (nivolumab and ipilimumab) after weaning off intravenous dexamethasone for cord compression. This case underscores the diagnostic challenge due to imaging similarities with other neoplastic, infectious and inflammatory pathologies. Given the aggressive nature and poor prognosis, a high index of suspicion should be raised for melanoma in patients with CMN and neurocutaneous melanosis who develop progressive neurological symptoms.

Aggressive Amelanotic Melanoma Masquerading as Squamous Cell Carcinoma.

Rationale:This case report presents an unusually rare instance of primary malignant melanoma of the esophagus (PMME) occurring concurrently with gastric cardia adenocarcinoma. It emphasizes diagnostic pitfalls in amelanotic melanoma and provides evidence supporting the role of adjuvant radiotherapy in achieving prolonged disease-free survival for this aggressive malignancy.Patient concerns:A 60-year-old male with chronic tobacco and alcohol use presented with a 2-week history of progressive dysphagia. Endoscopy identified an obstructive esophageal mass and a gastric cardia ulcer, initially misdiagnosed as poorly differentiated carcinomas due to the absence of melanin pigmentation.Diagnoses:The patient received a diagnosis of PMME in conjunction with gastric cardia adenocarcinoma.Interventions:Transthoracic esophagectomy with lymphadenectomy followed by adjuvant radiotherapy (5000 cGy/DT/25F) targeting the surgical bed and regional lymphatics.Outcomes:No recurrence or metastasis was observed over 7 years posttreatment, surpassing typical survival outcomes for PMME.Lessons:Amelanotic PMME poses significant diagnostic challenges due to its resemblance to poorly differentiated carcinoma, necessitating immunohistochemical confirmation (S-100, HMB-45, Melan-A). This case highlights the potential survival benefit of combining surgery with adjuvant radiotherapy in PMME, contrasting with historical outcomes in cases managed by surgery alone. Clinicians should maintain a high index of suspicion for synchronous malignancies in high-risk patients, particularly those with chronic carcinogen exposure. Emerging therapies, including immune checkpoint inhibitors targeting programmed cell death-1/CTLA-4 or NF-1 mutation-driven pathways, warrant exploration in PMME management. The unique lymph node metastasis pattern underscores the importance of comprehensive nodal sampling and tailored adjuvant strategies in dual-primary malignancies.

First report of oral amelanotic melanoma in a yellow-legged gull (Larus michahellis)

Mitotic count and proliferative index in 24 cases of canine oral amelanotic melanoma: Tissue microarray cores and whole-section tissue analysis

Case PresentationAn otherwise healthy, 30-year-old female was referred to the emergency department by a local optometrist after having flashers and blurry vision for two weeks. Point-of-care ultrasound revealed partial retinal detachment with underlying mass, and dilated fundoscopic examination suggested hyperpigmented lesions. Ophthalmology was consulted, and the diagnosis of amelanotic choroidal melanoma was confirmed.DiscussionChoroidal melanoma is the most common primary malignant tumor in the eye, but its diagnosis is often delayed due to non-specific symptoms. Early identification is crucial given relatively high rates of metastasis. This case highlights how a tentative diagnosis, made using point-of-care ultrasound and funduscopic examination, can drive timely referral to ophthalmology.

Background: The diagnostic process in dermatology often hinges on visual recognition and clinical pattern matching, making it an attractive field for the application of artificial intelligence (AI). Large language models (LLMs) like ChatGPT-4o, Claude 3.7 Sonnet, and Gemini 2.0 Flash offer new possibilities for augmenting diagnostic reasoning, particularly in rare or diagnostically challenging cases. This study evaluates and compares the diagnostic capabilities of these LLMs based solely on clinical presentations extracted from rare dermatological case reports.Methodology: Fifteen published case reports of rare dermatological conditions were retrospectively selected. Key clinical features, excluding laboratory or histopathological findings, were input into each of the three LLMs using standardized prompts. Each model produced a most probable diagnosis and a list of differential diagnoses. The outputs were evaluated for top-match accuracy and whether the correct diagnosis was included in the differential list. Performance was analyzed descriptively, with visual aids (heatmaps, bar charts) illustrating comparative outcomes.Results: ChatGPT-4o and Claude 3.7 Sonnet each correctly identified the top diagnosis in 10 (66.7%) out of 15 cases, compared to 8 (53.3%) out of 15 for Gemini 2.0 Flash. When differential-only matches were included, both ChatGPT-4o and Claude 3.7 achieved a total coverage of 86.7%, while Gemini 2.0 reached 60.0%. Notably, all models failed to identify certain diagnoses, including blastic plasmacytoid dendritic cell neoplasm and amelanotic melanoma, underscoring the potential risks associated with plausible but incorrect outputs.Conclusions: This study demonstrates that ChatGPT-4o and Claude 3.7 Sonnet show promising diagnostic potential in rare dermatologic cases, outperforming Gemini 2.0 Flash in both accuracy and diagnostic breadth. While LLMs may assist in clinical reasoning, particularly in settings with limited dermatology expertise, they should be used as adjunctive tools, not substitutes, for clinician judgment. Further refinement, validation, and integration into clinical workflows are warranted.

Background and purpose:Jatropha podagrica Hook, belongs to the Euphorbiaceae family, which possesses anticancer activities and is traditionally applied to treat skin diseases. No reports of J. podagrica anti-neoplastic activity on an amelanotic melanoma and associated inflammatory mediators exist.Experimental approach:The biological activities, including cytotoxic and anti-inflammatory effects of J. podagrica extracts, were evaluated. Key compounds in the extracts were identified using LC-MS/MS analysis.Findings/Results:The hexane extract of the root (RMH) demonstrated the highest inhibition of NO production with an IC50 of 4.94 ± 0.25 μg/mL, followed by the ethanolic extracts of the root (RME) and stem (SME) with IC50 values of 24.90 ± 1.06 and 25.20 ± 0.10 μg/mL, respectively. However, RMH showed cellular toxicity at 50 pg/mL, while other extracts were non-toxic up to 100 μg/mL. None of the extracts affected the concentrations of inflammatory mediators PGE2 or TNF-α. The cytotoxic activity of SME showed an IC50 of 5.62 ± 0.58 μg/mL, comparable to that of the anticancer drug 5-fluorouracil, with an IC50 of 0.59 ± 0.01 μg/mL. The selectivity index of SME was >17.79, significantly higher than that of 5-fluorouracil, which was 0.08. LC-MS/MS analysis identified two main compounds from the coumarin group: fraxetin at 5.357 min and its positional isomer tomentin at 5.943 min.Conclusion and implications:The study indicates that SME exhibits good cytotoxic activity and inhibits key cancer hallmarks such as NO production. The presence of coumarins, identified through LC-MS/MS, suggests that these compounds may play a crucial role in the extract's anticancer effects, highlighting the potential for future development as cancer therapeutics.

The high incidence of melanoma leading to a poor prognosis rate endorses the development of alternative and innovative approaches in the treatment of melanoma. Therefore, the present study aims to develop and characterize, in terms of physicochemical features and biological impact, an aqueous suspension of magnetite (Fe3O4) coated with β-cyclodextrin (Fe3O4@β-CD) as a potential innovative alternative nanosystem for melanoma therapy. The nanosystem exhibited physicochemical characteristics suitable for biological applications, revealing a successful complexation of Fe3O4 NPs with β-CD and an average size of 18.1 ± 2.1 nm. In addition, the in vitro evaluations revealed that the newly developed nanosystem presented high biocompatibility on a human keratinocyte (HaCaT) monolayer and selective antiproliferative activity on amelanotic human melanoma (A375) cells, inducing early apoptosis features when concentrations of 10, 15, and 20 μg/mL were employed for 48 h and 72 h. Collectively, the Fe3O4@β-CD nanosystem reveals promising features for an adjuvant approach in melanoma treatment, mainly due to its β-cyclodextrin coating, thus endorsing a potential co-loading of therapeutic drugs. Furthermore, the intrinsic magnetic core of Fe3O4 NPs supports the magnetically based cancer treatment strategies.

Amelanotic melanoma: Diagnostic challenges, treatment innovations, and the emerging role of in early detection

Atypical fibroxanthoma (AFX) is a rare skin tumour related to the group of fibrohistiocytic tumours. The tumour is most often occurs in elderly people against the background of photodamage of the skin. As a rule, it is located in the area of the head, shoulders, upper third of the back. It is typical of local destructive growth and extremely rare metastasis. However, in patients, against the background of immunosuppression, aggressive behaviour of this tumor is possible. The similarity of atypical fibroxanthoma with such aggressive tumours as amelanotic melanoma and Merkel's carcinoma poses a problem for the clinician. The diagnosis can be reliably made based solely on characteristic histological and immunohistochemical findings. We present a case of this tumour in a 72-year-old patient with photodamaged skin in combination with other skin tumours.

Ten dogs with oral malignant melanoma were evaluated and treated with surgery, of which four dogs were diagnosed with melanotic melanoma and six were diagnosed with amelanotic melanoma. Serum samples from oral malignant melanoma (OMM) were collected at baseline, the day of the surgery, and every 3-4 months, during which time a clinical examination and chest X-rays were performed. Concentrations of GM-CSF, IFN-γ, IL-2, IL-6, IL-7, IL-8, IL-10, IL-15, IL-18, IP-10, KC-like, MCP-1, and TNFα were quantified. Follow-up samples indicated that after the removal of malignant melanoma, the serum levels of GM-CSF, IFN-γ, MCP-1, IL-18, and IL-2 increased significantly. In contrast, when comparing samples from dogs with OMM to those of patients in remission, the concentrations of IL-7 and MCP-1 were significantly higher in the remission samples than in the OMM samples. Furthermore, when comparing the serum concentrations between the OMM-metastasis samples and those patients in remission, elevated levels of MCP-1 were associated with poorer overall survival due to the development of OMM metastasis. Finally, a comparison of cytokines in the melanotic OMM and amelanotic OMM samples revealed that the amelanotic OMM samples exhibited higher concentrations of IL-6, IL-10, and IL-15 compared to the melanotic OMM samples.

The differential diagnosis of early nail unit melanoma can be challenging. This retrospective cross-sectional study aimed to characterize the clinical and dermoscopic changes in a series of cases of longitudinal melanonychia that underwent clinical and dermoscopic sequential digital monitoring. All patients were adults presenting with a single acquired pigmented nail band and were monitored over time. Histologic diagnosis served as the gold standard for cases where excision was performed. For non-excised cases, inclusion in the study required a minimum of 1 year of documented clinical and dermoscopic stability. Clinical and dermoscopic features were assessed at baseline and during the final follow-up visit. After a median follow-up of 17 months, 27 out of 62 lesions were excised. Among these, six cases (9.7%) were diagnosed as insitu melanomas, nine (14.5%) as nevi and 12 (19.4%) as lentigo or melanocytic hyperplasia. At baseline clinical evaluation, most of the bands, both benign and malignant, occupied less than one-third of the nail plate (62.5% and 50%, respectively). Comparing dermoscopic features between baseline and follow-up, granular pigmentation emerged in 33.3% of malignant nail bands but only in 3.6% of benign bands (p = 0.04). An increase in the number of colours was observed in 50% of insitu melanomas, compared with 8.9% of benign lesions (p = 0.02). Additionally, 83.3% of melanomas showed an increased intensity of pigmentation, a feature seen in only 14.3% of benign bands (p = 0.001). Limitations include the relatively small number of melanoma cases (n = 6), all cases were from pigment lesion clinics in Europe and involved only Caucasian patients. Lastly, only pigmented lesions were included, so no conclusions can be drawn regarding amelanotic subungual melanoma. In conclusion, digital dermoscopy follow-up of longitudinal melanonychia is a valuable management strategy in uncertain cases. The emergence of new colours, granular pigmentation or increased intensity of pigmentation during follow-up should prompt a biopsy to rule out malignancy.

Rare case of amelanotic nodular melanoma of the nipple in an elderly male

Abstract Amelanotic melanoma (AM) is a subtype of melanoma that lacks pigmentation, and often mimics various benign and malignant pathology, leading to delays in referral and diagnosis. AM is diagnosed through clinical evaluation, biopsy and immunohistochemical staining. We conducted a retrospective study over a 20-year period to identify the relative prevalence of amelanotic melanoma in our population and the clinicopathological features. Cases of AM were identified through a free-text search of the pathology database from 2005 to 2024 for ‘amelanotic melanoma’. A separate search for ‘melanoma’ was completed to establish the total number of cases diagnosed. The case notes and pathology reports were reviewed. In total there were 153 cases of melanoma within the study period, of which four cases were amelanotic melanoma (2.6%). In total 32 cases were identified in which amelanotic melanoma was part of the clinical differential diagnosis, including all four cases of AM. AM subtypes were nodular amelanotic melanoma (NAM; n = 3) and subungual spindle cell AM (SSAM; n = 1). All four cases were in male patients with Fitzpatrick skin types I–II, and the age at diagnosis ranged from 33 to 90 years. The cases of NAM were located on the lower back, ear and sole of the foot. The SSAM was on the hallux. Time from referral to definitive excision ranged from 20 to 68 days. Breslow thickness ranged from 2.0 to 6.4 mm. Ulceration was present in two cases. Clinical stage at presentation was stage 2A (n = 2), 2B (n = 1) and 2C (n = 1). Immunohistochemically all four cases were positive for S100 and Sox-10, while melan-A was positive only in the cases of NAM. Disease-specific survival at 2 years was 75%, with one patient dying from brain metastasis. Comparing the data from this study with existing literature we found that the 2.6% relative prevalence of AM falls within the reported range of 1–8% of all cases of melanoma. All cases were patients with Fitzpatrick skin types I–II, which is a well-established risk factor for amelanotic melanoma in addition to old age. Despite 32 clinically suspected cases over 20 years, only four were pathologically confirmed, reflecting the heterogeneity of amelanotic melanoma and its more common clinical mimics such as pyogenic granuloma and nonmelanoma skin cancer. The time from referral to definitive excision was within the national target range, so in this series there was no significant delay to treatment due to misdiagnosis. To minimize diagnostic delays clinicians should maintain a high suspicion for AM in nonpigmented lesions with atypical features, particularly in Fitzpatrick skin types I–II and older patients with chronic photodamage.

Pyridine derivatives are widely distributed in nature and have valuable pharmacological properties. The pyridine core can be found in drugs such as sorafenib, zapiclone or prothipendyl. Dipyridothiazines are derivatives of phenothiazines that exhibit valuable anticancer, antioxidant and immunomodulatory activities. In this study, we present the synthesis and preliminary in vitro analysis of anticancer activity towards melanotic (COLO829, G361) and amelanotic (A375, C32) melanoma cells and normal human fibroblasts (HDF) of a series of new tricyclic diazaphenothiazines containing a pyridine scaffold in their structure. The structures of these new molecules was confirmed using spectral techniques, including 1H NMR, 13C NMR, 2D NMR and HRMS. An in vitro panel of experiments was assessed using the WST-1 assay and cytometric techniques. The two most promising compounds were analyzed for their effect on intracellular GSH levels, mitochondrial membrane potential and their ability to initiate DNA fragmentation to determine the potential mechanism of both cytotoxic and proapoptotic activity. The conducted studies confirmed the ability of the new 3-methyl-1,6-diazaphenothiazines to induce apoptosis in cancer cells, especially in terms of inducing initial as well as late-phase apoptosis. Moreover, the studied compounds were found to induce redox imbalance (evidenced by GSH depletion) in the analyzed melanoma cells, which may be an important factor that directs melanoma cells towards cell death signaling pathways.

Amelanotic melanomas are aggressive neoplasms that are exceedingly rare in the oral cavity. We report the case of a 74-year-old woman who presented with a large, ulcerated, exophytic mass on the edentulous lower alveolar ridge. Histological examination revealed two distinct cell populations: epithelioid cells arranged in an alveolar pattern and spindle-shaped cells arranged in fascicles, both exhibiting prominent nucleoli. Immunohistochemical staining was performed using S-100, SOX10, Melan-A, HMB-45, PRAME, and Ki-67. S-100 and SOX10 showed strong positivity, PRAME was focally positive, and the Ki-67 index was high. Melan-A and HMB-45 were negative. Due to the absence of clinical and histological pigmentation, amelanotic melanoma can be easily overlooked. Therefore, any rapidly growing, ulcerated mass in the oral cavity should raise suspicion for this diagnosis.

BACKGROUND: Malignant skin tumors occupy the second place among all oncological diseases worldwide. The most aggressive among them is skin melanoma, and of particular interest is its subspecies — pigmentless melanoma, which occurs from 2 to 8% among all skin malignancies. The atypical dermatoscopic picture, the frequent detection of pigmented melanoma in advanced stages, and its aggressive course, which worsens long-term treatment results, require a closer study of the issue and improvement of methods for early detection of the disease. AIM: Analysis of clinical cases of pigmented skin melanoma with assessment of pathognomonic clinical and dermatoscopic picture. METHODS: A retrospective analysis of the data of patients with pigmentless melanoma of the skin provided from the cancer registry of the Tyumen region for 2018-2023 was performed. RESULTS: During the study, it was revealed that at the initial request for medical help, most of the patients were not bothered by the existing pigmentation-free formation, and complaints of rapid growth of the lesion and contact bleeding were less common. When assessing the localization of tumors, it was found that pigmented melanoma was most common on the skin of the trunk (in 38.4%), less often on the skin of the head and neck (26.9%) and only in isolated cases on the skin of the upper and lower extremities. The primary lesion more often had the appearance of a node or papule, less often — spots or plaques. When assessing the dermatoscopic picture, vascular polymorphism became the most common feature (43.18%), regression zones were slightly less common. In exceptional cases, it was impossible to assess the dermatoscopic picture due to tumor disintegration. CONCLUSION: The rare occurrence of pigmented skin melanoma in clinical practice, the atypical dermatoscopic picture of the primary focus and the asymptomatic course are predictors of late diagnosis of the disease, which exacerbates the further course of the oncological process and long-term treatment results. This indicates to us the need to increase cancer awareness regarding pigmented melanoma of the skin, and the study and identification of typical clinical and dermatoscopic signs is an essential step towards early diagnosis of the malignant pathology in question and timely treatment of patients.

Meloxicam (MLX), a member of the non-steroidal anti-inflammatory drugs (NSAIDs), is a preferential inhibitor of cyclooxygenase-2 (COX-2) responsible for the synthesis of pro-inflammatory prostaglandins. MLX, due to its inhibition of the COX-2 enzyme, which is overexpressed in many cancers, including melanoma, leading to rapid growth, angiogenesis, and metastasis, represents a potentially important compound with anticancer activity. This study aimed to investigate the potential anticancer activity of meloxicam against amelanotic C32 and melanotic COLO 829 melanoma cell lines. The objective was achieved by assessing cell metabolic activity using the WST-1 assay and analyzing mitochondrial potential, levels of reduced thiols, annexin, and caspases 3/7, 8, and 9 by imaging cytometry, as well as assessing reactive oxygen species (ROS) levels using the H2DCFDA probe. The amelanotic melanoma C32 was more sensitive to MLX exposure, thus exhibiting antiproliferative effects, a disruption of redox homeostasis, a reduction in mitochondrial potential, and an induction of apoptosis. The results provide robust molecular evidence supporting the pharmacological effects of MLX, highlighting its potential as a valuable agent for in vivo melanoma treatment.

Abstract Amelanotic mucosal malignant melanoma of the penis is extremely rare. To our knowledge, this is the first case from India. In the present case report, we have discussed the diagnostic challenges, treatment, and prognosis related with this rare condition. A 55-year-old male presented with a 2-month history of a nonhealing penile ulcer. This duration reflects delayed presentation, as the diagnosis was only confirmed following comprehensive diagnostic workup, including imaging and immunohistochemistry. Partial penectomy with 2 cm margin with sentinel lymph node biopsy was performed. The postoperative period was uneventful. Currently, the patient is on close follow-up. In exceptionally rare cases like this, lack of melanin pigmented lesions may delay the diagnosis and management process. In such scenarios, knowledge related to this rare condition will promptly help the clinicians in early diagnosis, which will be a key for effective treatment and better prognosis of the patient.