A 60-year-old woman underwent evaluation for a 6-year history of Parkinsonism. One year earlier, she had been diagnosed with malignant melanoma of the left palpebral conjunctiva, which recurred despite treatment. For the assessment of Parkinson disease, 123 I FP-CIT and Tc-99m ECD SPECT were performed. Unexpectedly, intense 123 I FP-CIT uptake was observed in the left eyelid lesion, whereas 99m Tc-ECD showed no uptake. CT and MRI demonstrated a corresponding mass consistent with recurrent malignant melanoma. This first report underscores the need to recognize extrastriatal tracer uptake.

Background: Conjunctival melanoma is a rare but potentially life-threatening ocular malignancy. It may masquerade for months or even years as a benign-appearing red lesion or focal conjunctivitis resistant to topical therapy, leading to delayed diagnosis. Case Presentation: We report a rare and misleading case of conjunctival melanoma presenting as a highly vascularized, friable, and bleeding conjunctival mass, clinically suggestive of a conjunctival hemangioma. Histopathological and immunohistochemical analyses confirmed the diagnosis of conjunctival melanoma. Conclusion: This case highlights the diagnostic challenge posed by atypical hemorrhagic presentations of conjunctival melanoma and underscores the importance of early biopsy in suspicious conjunctival lesions.

Interferon Alpha-2a as Treatment for Primary Acquired Melanosis With Atypia and for Primary Acquired Melanosis With Atypia Surrounding Conjunctival Melanoma.

ObjectiveThis study aimed to assess the demographic, clinical, histological classifications, and anterior segment optical coherence tomography (AS-OCT) features of conjunctival malignancies. The goal was to identify factors associated with tumor malignancy.Materials and MethodsThis retrospective analysis included 37 patients with conjunctival tumors. Data collected comprised age, gender, tumor coloration, histological type, location, corneal involvement, subepithelial reflectivity of the lesion on AS-OCT, lesion homogeneity on AS-OCT, and the presence of intralesional cysts on AS-OCT. Statistical analysis was performed using chi-square and t-tests, with a significance level of α<0.05. The study protocol was approved by the Erciyes University Health Sciences Research Ethics Committee (Approval Number: 2025/365, Date: 09.07.2025).ResultsMalignant tumors were identified in significantly older patients. No significant gender differences were found regarding malignancy. Amelanotic appearance was significantly more common in malignant tumors. The types of tumors identified included conjunctival nevus, conjunctival ocular surface squamous neoplasia (OSSN), conjunctival lymphoma, conjunctival melanoma, and conjunctival cyst. No significant relationship was found between tumor location and malignancy. Corneal involvement was significantly associated with malignancy. On AS-OCT, malignant tumors exhibited a hyporeflective subepithelial lesion with homogeneous internal reflectivity. Although benign tumors contained more intralesional cysts on AS-OCT, this finding was not statistically significant.ConclusionConjunctival tumors exhibit various characteristics. Advanced age, amelanotic pigmentation, corneal involvement, and a hyporeflective homogeneous lesion on AS-OCT are significant indicators of malignancy, highlighting the importance of detailed examination and increased vigilance.

Ocular surface tumors (OSTs) are rare but potentially life-threatening neoplasms encompassing entities such as ocular surface squamous neoplasia (OSSN), conjunctival melanoma, and lymphoma. Accurate diagnosis often requires expert ophthalmologists and pathologists, compounded by the reliance on advanced imaging modalities, with excisional biopsy being the gold standard. These limitations underscore the need for less invasive, accessible diagnostic approaches, where artificial intelligence (AI) holds significant promise. This review provides a comprehensive overview of AI advancements in OST management. It begins with definitions of AI and its key branches, followed by an examination of AI models applied to ophthalmic tumors using imaging data. Current developments in AI-related diagnostic tools for OSTs are discussed, highlighting their potential to enhance patient management, with classifications based on imaging modalities and specific OST types. Finally, the review addresses main challenges in AI implementation, including data limitations and ethical considerations, while outlining future directions to integrate AI into clinical ophthalmology practice. By bridging technological innovation with clinical needs, AI shows promise in OST diagnosis and management, ultimately improving outcomes in this challenging condition.

PurposeTo describe the clinicopathological profile of conjunctival melanoma in a referral ophthalmology center in Peru.Patients and MethodsObservational, descriptive, and retrospective study including 29 patients with conjunctival melanoma confirmed by histopathological examination, attended between 2012 and 2023 at the Instituto Nacional de Oftalmología “Dr. Francisco Contreras Campos”, Lima, Peru. The main variable was the clinicopathological profile, which comprised clinical characteristics (clinical course, topography, symptoms, and signs) and pathological characteristics (macroscopic and microscopic).ResultsThe mean age of patients was 60.4 ± 17.5 years, and 69% were female. Right eye involvement was observed in 58.6% of cases, and in 93.1% the melanoma was located in the bulbar conjunctiva. In 67.9%, the disease extended to several quadrants of the ocular surface; moreover, 87% did not show additional foci of pigmented lesions. Conjunctival melanoma presented with an irregular shape in 62.1% of cases, firm consistency in 58.6%, was melanotic in 100%, and was of medium size in 41.7%. In addition, the lesion originated from primary acquired melanosis (PAM) in 66.7% of cases and from a nevus in 27.8%.ConclusionThe clinicopathological profile revealed predominant involvement of the right eye, bulbar conjunctiva, multiple quadrants and pigmented medium-sized lesions.

Objective: To investigate the clinical, pathological and molecular genetic characteristics of conjunctival melanoma (CoM). Methods: A retrospective case series study was conducted. The clinical, imaging and pathological data of patients diagnosed with CoM from January 2004 to June 2025 at Shaanxi Eye Hospital of Xi'an People's Hospital (Xi'an Fourth Hospital) and Xi'an First Hospital were analyzed. Some patients were detected for the BRAF V600E mutation. The χ2 test or the χ2 correction test was used for statistical analysis. Results: A total of 70 patients (70 eyes) with CoM were enrolled, aged (60.8±10.6) years, including 40 males (57.1%) and 30 females (42.9%). There were 33 cases (47.1%) in the left eye and 37 cases (52.9%) in the right eye. The tumor was located at the bulbar conjunctiva in 37 cases (52.9%), at the vault conjunctiva in 24 cases (34.2%), and at the palpebral conjunctiva in 9 cases (12.9%), involving the orbit in 13 cases (18.6%), the eyeball in 3 cases (4.3%), and the lacrimal sac in 6 cases (8.6%). Most patients presented with black nodules or cauliflower-like masses in the conjunctival area. Some tumors were accompanied by superficial vascular hyperplasia and pigmentation of adjacent tissues, while some invaded the cornea or orbit, resulting in clinical manifestations such as visual field defects, exophthalmos and limited movement. Imaging showed irregular soft tissue density shadows at the conjunctival site. According to the criteria of the American Joint Committee on Cancer, the tumor was at the T1 stage in 10 cases (14.3%), T2 stage in 41 cases (58.6%), and T3 stage in 19 cases (27.1%), with superficial ulcers in 6 cases (8.6%). Histopathology results disclosed that 67 cases (95.7%) were of the nodular type, 3 cases (4.3%) were of the superficially diffuse type, 47 cases (67.1%) were of the epithelial cell type, and 23 cases (32.9%) were of the mixed cell type. Sixty-three cases (90.0%) were accompanied by melanin, 32 cases (45.7%) were accompanied by primary acquired melanosis, including 23 cases (32.9%) with atypical primary acquired melanosis and 2 cases (2.9%) with conjunctival nevus, and 48 cases (68.6%) had tumor infiltrating lymphocytes. Immunohistochemistry demonstrated positive melanin markers such as human melanoma-associated antigen 45, melanocyte antigen A, S-100 protein and sex-determining region Y-frame protein 10. Thirty cases (42.9%) completed the detection of BRAF V600E mutations, of which 11 had BRAF V600E point mutations, with a positive rate of 36.7%. Sixty-two patients (88.6%) were followed up, with a recurrence rate of 27.4% (17/62), a metastasis rate of 19.4% (12/62), and a case fatality rate of 54.8% (34/62). The recurrence rate was 4/5 among patients with ulcers, versus 22.8% (13/57) among patients without ulcers (χ2=4.96, P=0.026); it was 8/13 among patients with orbital invasion, versus 18.3% (9/49) among patients without orbital invasion (χ2=9.62, P=0.002). Thirty-four patients (48.5%) underwent complete resection of the ocular mass, 16 (22.9%) underwent partial resection, and 20 (28.6%) underwent ocular or intraorbital enucleation. Ten patients (14.3%) received BRAF inhibitor-targeted therapy. Seven patients had a significant reduction of the residual mass and no tumor progression, and 3 patients did not respond to the treatment and died from the disease progression. Conclusions: CoM mostly occurs in the unilateral eye of middle-aged and elderly patients, more common at the bulbar conjunctiva and fornix conjunctiva, and histopathological epithelial cell types are the main types, with a high recurrence and metastasis rate.

1461 Correlation of PRAME Expression by Immunohistochemistry with Genomic Profiling: A comprehensive clinicopathologic study of 51 conjunctival melanomas

To determine the prevalence and clinicopathological features of malignant melanocytic lesions in specimens clinically diagnosed as pterygia. This retrospective study analysed all conjunctival specimens submitted with the clinical diagnosis 'pterygium' to the ophthalmic pathology laboratory of the Eye Center, University of Freiburg, Germany, between August 1999 and August 2024. Specimens that unexpectedly revealed a histopathological diagnosis of malignant melanocytic lesions were further reviewed for their clinical and pathological characteristics. Among 2298 clinically presumed pterygia, seven specimens (0.30%) harboured a malignant melanocytic lesion: four (0.17%) were invasive conjunctival melanomas and three (0.13%) were high-grade conjunctival melanocytic intraepithelial lesions (C-MIL). Three of four melanomas were amelanotic or hypomelanotic (75%) or exhibited atypical temporal localisation (75%). Malignant melanocytic lesions, though rare, may arise within or mimic pterygia. Their often amelanotic presentation can complicate clinical recognition. Routine histopathological evaluation of all excised pterygia is therefore essential to detect unexpected malignancies as conjunctival melanoma C-MIL.

Artificial intelligence (AI) has been explored as a promising diagnostic aid for ocular surface diseases (OSDs). The spectrum of OSD ranges from highly prevalent benign conditions such as dry eye disease (DED) to rare but potentially dangerous disorders, including ocular surface squamous neoplasia (OSSN) and conjunctival melanoma. This review provides an overview of current applications of AI across the major categories of ocular surface pathology and specifically highlights anterior segment imaging modalities, including slit-lamp examination, optical coherence tomography (OCT), and in vivo confocal microscopy (IVCM). Meibography, tear film dynamics, biochemical profiling, and other DED-related measures are also examined. Across these domains, reported AI model performance matches or exceeds that of ophthalmologists, offering consistent, reproducible, and accurate approaches for guiding diagnosis. However, studies with limited external or prospective validation, variable labeling strategies, and small, device-specific datasets predominate in the current literature, thereby limiting generalizability. Large multicenter datasets, standardized diagnostic frameworks, multimodal integration, and prospective trials that assess human-AI cooperation in practical settings should be an emphasis in future research. By filling these gaps, AI systems could advance from experimental tools to clinically reliable applications that improve access and diagnostic accuracy in the care of ocular surface disease and tumors.

Ocular surface lesions encompass a wide spectrum of entities ranging from benign degenerative lesions to non-invasive and invasive malignant tumours. Accurate clinical differentiation is essential to ensure timely management. In this manuscript, we describe a series of benign and malignant ocular surface lesions and their clinical and specific imaging findings on anterior segment optical coherence tomography (AS-OCT), highlighting the diagnostic utility of this non-invasive imaging modality. We characterise ocular surface squamous neoplasia, pterygia, Salzmann's nodular degeneration, conjunctival melanoma, primary acquired melanosis, conjunctival nevus, conjunctival lymphoma, benign reactive lymphoid hyperplasia and conjunctival amyloidosis. This series underscores the growing role of AS-OCT in supporting clinical assessment, guiding biopsy decisions and monitoring response to therapy in patients with ocular surface lesions. Its integration into routine practice offers a valuable, non-invasive supplement to slit-lamp biomicroscopy and histopathology.

ObjectiveTo analyse the data of a cohort of patients with conjunctival melanoma in order to analyse risk and guarding factors and to investigate the impact on metastatic disease with and without adjuvant therapy.Methods and analysisWe have retrospectively analysed the impact of clinical aspects and adjuvant therapies after tumour excision or biopsy in 167 patients cared for at the University Hospital Essen and the University Hospital Tübingen, Germany. Clinical as well as histopathological data and therapeutic approaches were analysed with regard to regional (lymphatic) and/or distant (haematogenous) spread during follow-up. The Kaplan-Meier estimate method was used to analyse survival and the Cox regression hazard model to define the probability of metastases depending on different factors. P value of <0.05 was considered statistically significant.Results167 cases of malignant conjunctival melanoma were retrospectively analysed. The patients received treatment and were followed up for 78.3±67.5 months. Local tumour recurrence occurred in n=79 patients (47.3%) after a mean of 41.5±70.33 months. 30 patients (37.9%) with a recurrence had not received adjuvant therapy. The overall rate of metastasis was 24.5% (n=41). In n=31 cases, regional lymphatic metastases were found after a follow-up of 48.9±63.5 months; in n=24 cases, distant metastases were found, occurring after 55.5±67.4 months. In n=14, the metastatic disease took both pathways. Ruthenium-106 brachytherapy performed in localised melanoma of the bulbar conjunctiva showed a relevant effect of decreasing the risk for haematogenous metastases by 74% (HR=0.256, p=0.003). 4 out of 54 patients developed distant metastases.ConclusionIn conjunctival melanoma, it is important to perform an adjuvant therapy after excision. This reduces not only local recurrences but also significantly the risk for haematopoietic spread.

Loss of cyclin-dependent kinase inhibitors p16INK4a, p27, and p21 has been linked to melanoma progression. We evaluated their expression in conjunctival melanocytic proliferations and explored correlations among genomic, RNA, and protein levels of p16INK4a. Expression of p16INK4a, p27, and p21 was analyzed by immunohistochemistry in 51 conjunctival nevi, 38 conjunctival melanocytic intraepithelial neoplasia (C-MIN), and 49 conjunctival melanomas (CJMs). Whole-genome/exome sequencing and RNA sequencing were available for 14 and 11 CJMs, respectively. Three CJM cell lines were treated with a DNA methyltransferase inhibitor. p16INK4a was expressed in 92% of nevi, 23.7% of C-MIN, and 42.3% of CJMs; p27 in 98%, 13.5%, and 26.5%, respectively; and p21 in 33.3%, 2.8%, and 28.6%, respectively. Downregulation of p16INK4A and p27 in CJMs versus nevi was significant. No CDKN2A mutations were identified. One CJM showed homozygous CDKN2A loss and two had heterozygous loss, all lacking p16INK4a expression. Among 11 cases with normal ploidy, p16 mRNA was detected in eight (72.3%), but protein in only four (36.4%), suggesting post-transcriptional and post-translational regulation. Treatment with 5-aza-2'-deoxycytidine upregulated p16INK4a and reduced proliferation in two CJM cell lines. p16INK4a and p27 are significantly downregulated in CJM and may help in the histopathological differential diagnosis between melanoma and conjunctival nevus. p16INK4a loss involves genomic, epigenetic, and post-translational mechanisms. Restoring p16 function may reduce CJM aggressiveness.

Ocular melanomas, comprising uveal melanoma (UM) and conjunctival melanoma (CoM), represent the most common primary intraocular and ocular surface malignancies in adults. Although rare compared with cutaneous melanoma, they exhibit unique molecular landscapes that provide critical opportunities for biomarker-driven precision medicine. In UM, recurrent mutations in GNAQ and GNA11, together with alterations in BAP1, SF3B1, and EIF1AX, have emerged as key prognostic biomarkers that stratify metastatic risk and guide surveillance strategies. Conversely, in CoM, the mutational spectrum overlaps with cutaneous melanoma, with frequent alterations in BRAF, NRAS, NF1, and KIT, offering actionable targets for personalised treatment. Beyond genomics, epigenetic signatures, microRNAs, and protein-based markers provide further insights into tumour progression, microenvironmental remodelling, and immune evasion. In parallel, liquid biopsy has emerged as a minimally invasive approach for real-time disease monitoring. Analyses of circulating tumour DNA (ctDNA), circulating tumour cells (CTCs), and exosome-derived microRNAs demonstrate increasing potential for early detection of minimal residual disease, prognostic assessment, and evaluation of treatment response. However, the clinical integration of these biomarkers remains limited by tumour heterogeneity, technical variability, and the lack of unified translational frameworks. This review synthesises current knowledge of molecular and liquid biopsy biomarkers in ocular melanoma, highlighting their relevance for diagnosis, prognosis, and treatment personalisation. The integration of established tissue-based molecular markers with novel liquid biopsy technologies will enable a unique framework for biomarker-guided precision oncology and risk-adapted surveillance in uveal and conjunctival melanoma, offering insight into strategies for early detection, therapeutic monitoring, and personalised clinical management.

Melanoma of conjunctiva is arare but aggressive malignancy that has a high probability of recurrence. Topical Mitomycin C (MMC) is being used more commonly as an adjuvant. Our report presents a female patient with a temporal, bulbar conjunctival pigmented mass. Malignant melanoma was confirmed by excision with amniotic membrane transplantation and adjunctive cryotherapy. Although there was initial recovery, recurrence occurred within three months. Adjuvant MMC 0.04% was started in four intermittent cycles and each cycle was four days with a weekly pause. The regimen was also tolerated and only mild ocular irritation was present. Six months follow-up showed that the lesion was partially regressed with visual acuity remaining normal. The present case demonstrates that adjuvant MMC using another cycle regimen is a possible and effective alternative to recurrent conjunctival melanoma.

BRAFV600E and NRASQ61R Antibodies Are Sensitive and Specific Diagnostic Biomarkers for BRAF and NRAS Mutations in Conjunctival Melanomas.

There are limited effective treatment options for diffuse conjunctival melanoma in situ (MIS), diffuse conjunctival intraepithelial neoplasia, and squamous cell carcinoma. There is a need for a more effective treatment with less ocular adverse effects than mitomycin C for MIS and 5-fluorouracil for ocular surface squamous neoplasia (OSSN). To evaluate the outcomes of compounded imiquimod 5% in ophthalmic petrolatum-based ointment for diffuse conjunctival MIS or OSSN. This was an interventional case series study at a tertiary referral center conducted from June 2024 to March 2025. Patients with a histological diagnosis of either conjunctival intraepithelial neoplasia (CIN), conjunctival squamous cell carcinoma, conjunctival MIS, or conjunctival melanoma with adjacent clinical primary acquired melanosis (PAM) were included in the study. Compounded imiquimod 5% ointment applied to the conjunctival surface 5 days per week for 12 weeks at a minimum (range, 12-15 weeks) along with a topical antibiotic. Histological resolution of MIS or OSSN. This case series included 5 patients (mean [SD] age, 77.4 [6] years; 4 female [80%]). At 12 weeks of treatment, there was complete clinical and histological response of CIN with moderate dysplasia, partial histological response (downgrade from squamous cell carcinoma to CIN with moderate dysplasia), and no histological recurrence of positive margins of squamous cell carcinoma excision. At 12 weeks of treatment, there was partial clinical response of diffuse MIS with mild persistence of epithelial pigmentation at the corneal limbus at the 7-o'clock position; however, there was complete histological response in the areas of initial map biopsy. At 15 weeks of treatment, there was complete clinical and histological response of PAM. Of the 5 patients, all experienced ophthalmic adverse events only affecting the ocular surface and eyelids. All ocular surface adverse events resolved within 1 to 2 weeks of drug holiday or completing treatment. Study results suggest that, although definitive safety and efficacy cannot be determined across only 5 cases, compounded imiquimod 5% ointment may be a safe and effective approach to manage diffuse conjunctival MIS or OSSN. Longer-term follow-up with larger number of cases is warranted.

Conjunctival melanoma (CJM) is a rare and aggressive malignancy. Mainly attributed to its rarity, the genomic features of CJM have not been well characterized. In the present study, we sequenced the exomes of primary and metastatic CJM tumors with the aim to unravel their genomic landscape. The results of the study suggest that CJM is a molecularly distinct melanoma subtype with mixed genotype and targetable mutations. Notably, there were features overlapping with both mucosal, and mainly cutaneous melanoma. Of note, some genetic alterations were found in association with specific subsets of CJM, such as bulbar anatomical localization. CJM tumors had intermediate tumor mutational burden, which was significantly higher compared to most cancers included in the cancer genome atlas (TCGA) project and suggest a role for immune checkpoint inhibitor treatment in patients with locally advanced or metastatic disease. These data allow for a better evaluation of the therapeutic options for CJM.

Primary Acquired Melanosis (PAM) with atypia is a rare but clinically significant precursor to conjunctival melanoma. We report a case of a 58-year-old female with multiple comorbidities who presented with persistent ocular redness and dryness, initially managed conservatively in primary care. Ophthalmologic evaluation revealed a vascularized temporal limbal conjunctival lesion with superficial corneal pigmentation. Ultrasound biomicroscopy demonstrated episcleral thickening (0.3–0.4 mm) over a 2.5 mm area, and MRI of the orbits and brain showed no intra orbital or intracranial extension. The lesion was excised using a “no-touch” technique with alcohol-assisted corneal epithelial removal and cauterization of the surgical bed. Histopathological analysis confirmed extensive PAM with high-grade atypia, with areas approaching melanoma in situ; superficial invasive melanoma could not be fully excluded. The patient remains under close ophthalmologic surveillance, with no evidence of recurrence to date. This case underscores the diagnostic challenges of PAM, especially in patients with non-specific ocular symptoms and prior eyelid surgery, where early malignant changes may be overlooked. Prompt recognition and surgical management are essential to prevent malignant transformation. The report highlights the importance of multidisciplinary coordination, appropriate imaging, and regular follow-up in managing high-risk conjunctival pigmented lesions to improve visual and oncologic outcomes.

PurposeUveal and conjunctival melanomas are rare ocular malignancies that present significant diagnostic and therapeutic challenges. This study investigates the efficacy of combining hyperthermic treatments with chemotherapeutics, such as cisplatin, docetaxel, and mitoxantrone, to develop more effective therapies for specific melanoma subtypes, aiming to overcome the limitations of traditional approaches.MethodsThe study used hyperthermia by exposing melanoma cell lines to temperatures of 42°C, 45°C, and 47°C for 1 hour. Alongside hyperthermia, cytotoxic drugs were applied at different concentrations to assess their combined effects on cell proliferation and viability. Expression of heat shock proteins was evaluated by immunocytochemistry stainings and Western blots.ResultsFindings reveal that certain melanoma cell lines exhibited increased proliferation at 42°C without a significant decrease in cell confluence. Conversely, temperatures of 45°C and above significantly impaired cell viability. Comparative statistical analysis suggests synergistic effects when combining mild to elevated hyperthermia with cisplatin and mitoxantrone, and to some extent with docetaxel.ConclusionsThis study serves as preliminary work for the inclusion of superparamagnetic iron oxide nanoparticles functionalized with cytotoxic drugs, which may present a promising therapeutic strategy for treating ocular melanomas. Although further research is necessary, this approach has the potential to significantly advance the treatment landscape for these ocular malignancies, offering a targeted, effective, and minimally invasive option for patients.