Conjunctival Lesions Research Articles

Significance of the preferentially expressed antigen in melanoma in discriminating the conjunctival malignant melanoma and pigmented nevus

Objective: To investigate the significance of the preferentially expressed antigen in melanoma (PRAME) in the differential diagnosis of the conjunctival malignant melanoma and pigmented nevus. Methods: Specimens from 86 patients with conjunctival malignant melanoma (42 males and 44 females, aged 18 to 84 years) and 86 patients with conjunctival pigmented nevus (47 males and 39 females, aged 1 to 82 years) were collected at Zhongshan Ophthalmic Center, Sun Yat-sen University from January 2017 to July 2024. Immunohistology was performed to detect the PRAME expression. The difference of PRAME expression in the two kinds of conjunctival melanocyte hyperplasia lesions and the correlation of PRAME expression with clinical stages of the conjunctival malignant melanoma (T1 to T4) were analyzed. Results: Most patients with malignant melanoma had a positive PRAME expression (89.53%, 77/86), while only 1 patient with pigmented nevus showed a positive PRAME expression (1.16%, 1/86). The positive expression rate of the PRAME in conjunctival malignant melanoma tissues was significantly higher than that in conjunctival pigmented nevi (P<0.05). The PRAME had a sensitivity and specificity of 89.53% and 98.84%, respectively. The expression of the PRAME among patients with conjunctival malignant melanoma in different age groups (>50, 30 to 50, <30) was significantly different (P<0.05). However, the PRAME expression had no difference in different clinical stages of the conjunctival malignant melanoma (P>0.05). Conclusions: The PRAME has significance in discriminating the conjunctival malignant melanoma and pigmented nevus. It is a useful biomarker in the diagnosis of conjunctival malignant melanoma.

Two Decades of Insights: Comprehensive Histopathological and Epidemiological Analysis of Conjunctival Tumors

This study analyzed 2102 conjunctival lesions excised between 1981 and 2003 at a single tertiary center in Serbia, with the aim of evaluating their histopathological characteristics, anatomical localization, and demographic distribution. Of the total cases recorded, 55.1% were male, indicating a slight male predominance. The bulbar conjunctiva was the most commonly affected site (34.5%), with 39.3% of tumors extended to multiple regions of the conjunctiva, including areas such as the plica and caruncula. The most common benign lesion was compound conjunctival nevus (16.7%), while squamous cell carcinoma (SCC) (11.4%) and melanoma (11.3%) were the most prevalent malignant tumors. Tumor incidence peaked in the 61–70 and 51–60 year age groups, with malignant tumors such as SCC being more frequent in males. Comparisons with similar global studies reveal that our findings align with worldwide trends, such as the predominance of SCC, which has been linked to UV exposure, and the frequency of melanoma in fair-skinned populations. However, the lower prevalence of fibrodegenerative lesions like pterygia and pinguecula in our cohort likely reflects Serbia’s cooler climate compared to regions with higher UV exposure. These findings underscore the diverse nature of conjunctival tumors, the critical role of histopathological examination for diagnosis, and the influence of environmental factors. This study provides valuable insights into the epidemiology of conjunctival tumors, contributing to global understanding and guiding future diagnostic and therapeutic approaches.

Erosive Tarsal Conjunctival Lesions Following Immunogenic Events in Early Development of Ocular Graft-vs-Host Disease.

Ocular graft-versus-host disease (oGVHD) affects more than half of the patients following allogeneic hematopoietic stem cell transplantation (HSCT). The disease onset and the pathogenesis of oGVHD are not well understood. We hope to identify the triggers and explore the clinical signs and symptoms of oGVHD development at the early stages. The records of post-HSCT patients seen consecutively in a 1-year span in a single provider's clinic were reviewed. The history, symptoms, and clinical findings of the patients with erosive tarsal conjunctival lesions (ETCLs) were analyzed. Out of the 228 patients screened, 19 had clinically witnessed ETCL in at least one eye during the period. Twelve (63%) patients had a never-before-described nodular erosion on the subtarsal conjunctiva; seven (37%) had previously described pseudomembranous erosions. The ocular symptom onset was within 1 month after immunosuppression (IS) taper, vaccination, or donor lymphocyte infusion (DLI) in 16 of the 19 patients. While 16 (84%) patients reported painless mucous discharge, only 9 (47%) reported dryness as the initial symptom. Within 6 months, only 4 (21%) had discharge but 15 (82%) patients endorsed dryness. Subepithelial conjunctival fibrosis followed ETCL immediately in situ. Corneal punctate staining increased with time, while aqueous tear production decreased. The ETCL described is likely one of the earliest detectable findings of oGVHD and triggered by certain immunogenic events. The ocular symptoms of wet mucous discharge should be considered a warning sign for oGVHD onset, particularly when it occurs shortly after prominently immunogenic events.

Probable IgG4-related Orbital Disease Masked by Exuberant Ocular Surface Pseudoepitheliomatous Hyperplasia

A 40-year-old woman presented with a mass in her OS for 2 years. Examination revealed a large conjunctival lesion on the nasal bulbar conjunctiva OS and a small upper tarsal conjunctival lesion in the OD. Biopsy OD revealed inflammatory granulation tissue, and OS revealed pseudoepitheliomatous hyperplasia with granulation tissue. The lesion responded well to steroids. She was lost to follow-up and returned with an enlarged lesion with orbital extension and corneal perforation. Orbital exenteration was performed. The entire conjunctiva showed extensive epithelial downgrowth and mononuclear round cell infiltrates, predominantly plasma cells admixed with neutrophils suggestive of aggressive pseudoepitheliomatous hyperplasia. Orbital tissue showed ill-defined granuloma formation with acute on chronic inflammation and plasma cells. The tissue IgG4/IgG ratio was 34%, suggestive of probable IgG4-related orbital disease. Based on this case, we conclude that IgG4-related orbital disease can rarely cause conjunctival and scleral inflammation with secondary pseudoepitheliomatous hyperplasia-like changes.

Primary Conjunctival Molluscum Contagiosum in a Patient With Ocular Graft-Versus-Host Disease.

Primary conjunctival molluscum contagiosum (MC) is rare and usually reported in patients with acquired immunodeficiency syndrome. In this study, we present a case of bilateral primary conjunctival MC in a patient with ocular graft-versus-host disease (oGVHD). This is a case report study. Clinical evaluation, in vivo confocal microscopy imaging, and histopathology were used to confirm the diagnosis. A 38-year-old woman with a history of allogeneic bone marrow transplant and secondary chronic oGVHD presented with ocular discomfort, redness, and dryness. On examination, clusters of white gelatinous nodular lesions, stained with fluorescein and Lissamine green, were observed on the bulbar conjunctiva, along with similar solitary nodular lesions in all quadrants of both eyes. In vivo confocal microscopy revealed nests of epithelial cells with bright inclusions measuring approximately 30-35 μm. Excisional biopsy confirmed the diagnosis of MC. A 6-month post-operative follow-up showed healed conjunctiva with no recurrence and improved ocular comfort. Molluscum contagiosum should be considered in the differential diagnosis of conjunctival lesions in patients with impaired immunity such as oGVHD. In diagnosing MC lesions, in vivo confocal microscopy proves to be valuable. In the absence of topical antiviral treatment, surgical excision is warranted.

Treatment of conjunctival palpebral lesions using ruthenium plaque brachytherapy "Sandwich Technique"

ObjectiveTreatment of palpebral conjunctival lesions is problematic due to late diagnosis, difficult surgical approach, and the need to preserve eyelid integrity. We describe our treatment experience using plaque brachytherapy in the "sandwich technique.” DesignA retrospective study. ParticipantsWe reviewed the medical records of patients treated by plaque brachytherapy for conjunctival lesions at the Hadassah Medical Center between January 1, 2013, and January 1, 2024, and included in the analysis patients treated for palpebral conjunctival lesions. MethodsRuthenium plaque was sutured to the palpebral conjunctiva. The matching nonradioactive “dummy” plaque was sutured to the external eyelid to flip the tarsal's curvature. ResultsThe study cohort included 5 patients, 2 men (40%) and 3 women (60%) at a median age of 68.11 years (range: 47-79.7 years). Three patients had conjunctival melanoma (60%), 1 had sebaceous carcinoma (20%), and 1 had extensive carcinoma in situ (20%). All lesions were in the left upper eyelid. Median follow-up was 37.6 months (range: 18.7-110.6 months). Four patients demonstrated a complete response (80%), while one had a partial response (20%). There was local recurrence in 1 patient (20%), and 1 patient had new foci elsewhere (20%). All patients had full local control after adding local treatments. One patient developed metastatic disease and died (20%). All patients had manageable madarosis and conjunctival scars. ConclusionsTreatment of palpebral conjunctival lesions using “sandwich” plaque brachytherapy is safe and effective. To the best of our knowledge, this treatment was never described before, and we believe it should be added to our armamentarium.

Isolated conjunctival cavernous hemangioma: a rare case report

Vascular conjunctival tumors are uncommon, usually benign lesions. Here, we report a 65-year-old male who presented with a nasal interpalpebral bulbar firm, oval, and dark-brown and non-mobile conjunctival mass. The systemic and ocular examinations including fundoscopy and gonioscopy were within normal limits. With a diagnosis of conjunctival malignant melanoma (CMM), the patient underwent excisional biopsy, partial sclerectomy, and cryotherapy. Microscopic examination revealed dilated vascular channels filled by red blood cells, separated by fibrous interstitium and no sign of malignancy. Therefore, a diagnosis of conjunctival cavernous hemangioma was made. Our case demonstrates that the conjunctival cavernous hemangioma can mimic malignant conjunctival lesions as well as extrascleral extension of uveal melanoma or uveal prolapse due to scleral necrosis.

Solitary Langerhans Cell Histiocytosis of the Palpebral Conjunctiva Presenting as Leukoplakia: Case and Review of Literature.

A 69-year-old male presented with a superior palpebral conjunctival white leukoplakic lesion. Excisional biopsy showed Langerhans cell histiocytosis. Positron emission tomography scanning revealed no lesions beyond this site. Native Langerhans cells are known to exist in the conjunctiva, yet only a few cases in the literature have described Langerhans cell histiocytosis of the conjunctiva, mostly in children. Conjunctival Langerhans cell histiocytosis has rarely been reported in an adult as leukoplakia. The authors advocate excisional biopsy for palpebral conjunctival Langerhans cell histiocytosis in older patients if the morbidity of closure is minimal, in addition to surveillance for multifocal disease.

Role of Topical 5-Fluorouracil in Demodex -Associated Blepharitis.

The aim of this study was to report clinical observations suggesting the efficacy of topical 1% 5-fluorouracil (5-FU) in treating Demodex -associated blepharitis. An observational retrospective review of 13 eyes from 13 individuals with conjunctival neoplastic lesions and concomitant Demodex lash infestation that received topical 1% 5-FU eye drops. Patients underwent slit-lamp examination at each follow-up visit. Clinical photographs of the lash line were obtained after treatment initiation. In a subset of patients, lashes were epilated bilaterally and microscopically analyzed for presence of Demodex mites before and after treatment initiation. The mean age of the population was 68 ± 14 years (range: 30-84 years) and 92% were male. In all 13 patients, a marked reduction in cylindrical dandruff was noted in the treated eye by slit-lamp examination after 2 cycles of 5-FU. There was complete resolution of cylindrical dandruff in 10 of 13 treated eyes compared with 0 resolution of cylindrical dandruff in untreated eyes ( P = 0.0001). In the 6 patients who received epilation, the lashes from the treated eye showed no Demodex , whereas lashes from the fellow untreated eye revealed persistent Demodex . Topical 1% 5-FU shows efficacy in treating Demodex -associated blepharitis. Further studies are indicated to reproduce our findings and evaluate the potential use of 5-FU as a treatment ingredient.

Mycobacterium abscessus Corneal Ulcer with Conjunctival Toxicity due to Topical Amikacin

Purpose: This report presents a case of repeated toxic conjunctival necrosis caused by amikacin eye drops in a patient with a corneal ulcer induced by Mycobacterium abscessus (M. abscessus).Case summary: During treatment for herpetic keratitis with complaints of conjunctival hyperemia and eye pain in the right eye for 1 month. Slit-lamp microscopy revealed a circular corneal epithelial defect and stromal infiltration of her right eye. Gram staining and culture were performed, and eye drops were prescribed for empirical treatment. The bacterial culture grew M. abscessus. Antibiotic susceptibility tests showed resistance to quinolone. The patient was prescribed amikacin eye drops and the corneal epithelial defects improved. Two weeks later, circular conjunctival epithelial defects and hyperemia were observed on the inferior conjunctiva. Conjunctival necrosis caused by amikacin was suspected. The amikacin eye drops were discontinued and the conjunctival lesion improved. However, the patient’s corneal ulcer recurred. The amikacin eye drops were restarted, but conjunctival toxicity recurred, so she was treated with topical clarithromycin and moxifloxacin. The eye drops were gradually reduced and the lesion healed leaving mild corneal opacity.Conclusions: M. abscessus-induced keratitis resistant to quinolone antibiotics requires long-term combined therapy with multiple drugs. Amikacin eye drops should be used carefully as conjunctival toxicity may occur.

Histological Outcome of Conjunctival Lesions at a Tertiary Hospital in North East Nigeria

Objective: The objective of this study was to determine the relative frequency of histologically diagnosed conjunctival lesions at a tertiary hospital over a 12-month period. Methods: It was a prospective study in which all patients who presented to the ophthalmology clinic with suspicious conjunctival lesions between January and December 2022 were recruited. Data recorded were age, sex, duration of the growth and the affected eye. All the patients underwent basic ocular examination and an examination of the growth to document its site and size. Lesions were excised in the operating theatre under anaesthesia. The excised tissue was preserved in a formalin bottle and sent for histology. Data were entered into Excel and analysed using SPSS version 20.0. Results: A total of 73 eyes were recruited during the period of study. There were 41 males (56.2%) with M:F ratio of 1.3:1. Mean age was 38.44 ± 19.07 years with a range of 2–77 years. Forty patients (54.8%) presented with lesions in the right eye and 33 (45.2%) in the left eye. Fifteen types of conjunctival lesions were diagnosed, including pterygium 37%, conjunctival intraepithelial neoplasia 2.7%, melanoma 2.7%, ocular surface squamous neoplasia 4.1% and squamous cell carcinoma 4.1%, respectively. Conclusion: Pterygium was the most common benign lesion in this study. When conjunctival lesions appear suspicious, it is of utmost importance for the surgeons to differentiate between benign, premalignant and malignant lesions as this may aid in prompt patient management as well as better outcomes.

Dermoscopy can be safely and reliably used in ophthalmology

ObjectiveTo determine if dermoscopy, a technique widely utilized in dermatology for improved diagnosis of skin lesions, can be used comfortably for evaluating periorbital, eyelid, and conjunctival lesions. DesignProof-of-concept study in which a technique for performing dermoscopy near the eye was developed, related educational material was prepared, and a protocol for dermoscopic image capture was created. MethodsTechnicians used the developed materials to learn to take high-quality pictures with a 10x dermoscope attached to a standard cell phone camera. The images were assessed for diagnostic utility by an oculoplastic surgeon and two dermatologists. Participants115 patients recruited from ophthalmology clinics from July 2021 to April 2023 were photographed, yielding 129 lesions with high-quality dermoscopic images as assessed by an oculoplastic surgeon and two dermatologists. ResultsTechnicians reported a significant increase in confidence (measured on a 1–10 scale) with dermoscopy after training (pre-instruction mean = 1.72, median = 1, mode = 1, IQR = 1.25 vs mean = 7.69, median = 7.75, mode = 7 and 8, IQR = 1.5 post-instruction. Wilcoxon rank sum test with continuity correction, W = 0, p < 0.001, paired t = 13.95, p < 0.0001). Incorporating a contact plate with a 4 × 4mm reticule on the dermoscope aided in photographing ocular and periocular lesions. ConclusionMedical support staff in eye-care offices can be taught to use dermoscopes to capture high-quality images of periorbital, eyelid, and conjunctival lesions. Dermoscopy illuminates diagnostic features of lesions and thus offers a new avenue to improve decision-making in ophthalmology. Dermoscopy can be incorporated into telemedicine evaluations by ophthalmologists, oculoplastic surgeons, or affiliated dermatologists for triage of or rendering advice to patients and for planning of surgery if needed.

PHOTO ESSAY: “New” Red Eye - A Case of Conjunctival Intraepithelial Neoplasia

Ocular surface squamous neoplasia (OSSN) covers a wide range of ocular diseases that affect the squamous epithelial cells on the surface of the eye. This includes conjunctival intraepithelial neoplasia, corneal epithelial dysplasia, squamous cell carcinoma, and mucoepidermoid carcinoma. Anterior segment OCT can be used to differentiate between CIN and other benign conjunctival lesions, by evaluating for epithelial activity, stromal invasion, and corneal involvement.

Epibulbar Choristoma, Dermolipoma

Introduction : Choriostoma is a tissue anomalie distinguished by distinct cell types that are not typically present at the affected region. Dermolipoma is one type of choriostoma.&#x0D; Case Illustration : A twenty three year old woman is presented with epibulbar mass in the left eye since birth. She wished to remove the mass for cosmetic purposes. She denied any underlying medical condition and ocular history. Her visual acuity was 6/6 in both eyes and intraocular pressure was normal. Slit lamp examination revealed a yellowish white lesion of the external canthus of the left eye, no redness, and no discharge. The mass was 5 x 10 mm. Fundus examination was unremarkable. Patient underwent mass excision with cosmetic indication and has a satisfactory result.&#x0D; Discussion : A dermolipoma is an epibulbar choriostoma made of thick connective tissue and adipose tissue. The benign tumor is rare and makes up 4.2% of all conjunctival lesions. Dermolipoma can be very large, involving the extraocular muscle, lacriminal gland, and orbital tissue. Dermolipoma may be connected to epidermal nevus syndromes, Goldenhar syndrome, or coloboma. The majority of the time, these tumors don't need to be treated unless they are larger or have an unfavorable appearance.&#x0D; Conclusion : Dermolipoma is not cosmetically acceptable may be treated with excision of the mass.

Stromal area differences with epithelial-mesenchymal transition gene changes in conjunctival and orbital mucosa-associated lymphoid tissue lymphoma.

To examine the molecular biological differences between conjunctival mucosa-associated lymphoid tissue (MALT) lymphoma and orbital MALT lymphoma in ocular adnexa lymphoma. Observational case series. A total of 129 consecutive, randomized cases of ocular adnexa MALT lymphoma diagnosed histopathologically between 2008 and 2020.Total RNA was extracted from formalin-fixed paraffin-embedded tissue from ocular adnexa MALT lymphoma, and RNA-sequencing was performed. Orbital MALT lymphoma gene expression was compared with that of conjunctival MALT lymphoma. Gene set (GS) analysis detecting for gene set cluster was performed in RNA-sequence. Related proteins were further examined by immunohistochemical staining. In addition, artificial segmentation image used to count stromal area in HE images. GS analysis showed differences in expression in 29 GS types in primary orbital MALT lymphoma (N=5,5, FDR q-value <0.25). The GS with the greatest difference in expression was the GS of epithelial-mesenchymal transition (EMT). Based on this GS change, immunohistochemical staining was added using E-cadherin as an epithelial marker and vimentin as a mesenchymal marker for EMT. There was significant staining of vimentin in orbital lymphoma (P<0.01, N=129) and of E-cadherin in conjunctival lesions (P=0.023, N=129). Vimentin staining correlated with Ann Arbor staging (1 versus >1) independent of age and sex on multivariate analysis (P=0.004). Stroma area in tumor were significant difference(P<0.01). GS changes including EMT and stromal area in tumor were used to demonstrate the molecular biological differences between conjunctival MALT lymphoma and orbital MALT lymphoma in ocular adnexa lymphomas.

The Role of IL-6, IL-10, and TNF-α in Ocular GVHD Following Allogeneic Transplantation

ABSTRACT Purpose To figure out the roles of tear inflammatory cytokines in Ocular graft-versus-host disease (oGVHD) symptoms by analyzing tear cytokine levels and related factors. Methods This prospective study involved 27 post-HSCT patients and 19 controls with dry eye disease. Analyses included tear cytokine (IL-6, IL-10, and TNF-α), ocular surface evaluation, and conjunctival impression cell examination. Tear cytokine levels were evaluated in three grades of corneal epithelial lesions. The study also analyzed the correlation between tear cytokine levels and ocular surface parameters. Tear cytokine levels were then used in a Receiver Operating Characteristic (ROC) curve and linear regression model to predict oGVHD related factors. Results IL-6 has good diagnostic efficacy in oGVHD related dry eye. Elevated levels of tear IL-6 and TNF-α were observed in the group with severe corneal epithelial lesions. IL-6 levels were positively correlated with corneal fluorescein staining (CFS), eyelid margin hyperemia, conjunctival lesions, and meibum secretion. IL-6 showed excellent predictive ability with Area Under the Curve (AUC) values all greater than 0.70 (p < 0.05). IL-10 and TNF-α were negatively correlated with the meibomian gland proportion and conjunctival goblet cell (GC) density, while TNF-α was positively correlated with CFS and eyelid margin hyperemia. Conclusion Dry eye symptoms related to ocular GVHD, can be partly diagnosed and assessed using various tear cytokine level detection methods.

Spontaneous regression and rare relapse after excisional biopsy in long-term observation of 31 patients with primary conjunctival lymphoma.

To elucidate long-term outcome in primary conjunctival lymphoma, a review was conducted of 31 consecutive patients: 21 men and 10 women with an age range of 28 to 85 (median, 61) years at presentation and follow-up periods ranging from 1 to 19 (median, 7) years. Conjunctival lymphoma was on the right side in 10 patients, on the left side in 12, and on both sides in 9. Upper, lower, or both fornix lesions in 28 patients were all diagnosed as extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma), while thick nasal bulbar conjunctival lesions in 3 patients were differently diagnosed as MALT lymphoma, diffuse large B-cell lymphoma, and follicular lymphoma, respectively. Seven patients underwent local radiation (30 Gy): as initial treatment in 5 patients and treatment for relapse in 2 patients. The remaining 24 patients were observed without additional treatment after excisional biopsy: 5 of these 24 patients showed relapse 0.5 to 6 years later and underwent excisional biopsy again that revealed MALT lymphoma. Of the 5 patients with relapse, only one with second-time relapse underwent radiation. Fluorodeoxyglucose positron emission tomography was performed in 18 patients and showed no systemic lesions: high uptake was noted in the residual conjunctival lesions of 4 patients and in the relapsed conjunctival lesions of 3 patients. One patient died of rectal cancer while no patients died of lymphoma. Observation is an option in patients with primary conjunctival lymphoma after excisional biopsy. Radiation is a treatment option in the case of relapse.

Strigid herpesvirus-1 as a differential for chronic keratitis in owls

An adult free-ranging great horned owl was referred for evaluation of chronic ulcerative keratitis in the left eye that had been treated for several months. In vivo confocal microscopy confirmed that the corneal lesion was an inactive scar, and histopathology and molecular testing of a proliferative palpebral conjunctival lesion in the same eye confirmed infection with strigid herpesvirus- 1. Resolution of the conjunctivitis occurred following the biopsy and the owl was released. Four months later the owl re-presented with presumed rodenticide poisoning, and there was no evidence of recurrence of ocular disease.

A Rare and Unusual Case of Ataxia Telangiectasia with Cervical Dystonia from India

We reported a rare and unusual case ATM gene variant responsible of familial Ataxia-Telangiectasia (A-T) with cervical dystonia rather than ataxia as hall mark clinical manifestations in 18-year-old male patient from India. Patient was presented with clinical indications of neck rotatory movements in the last 2 years. Initially intermittent, slowly become constant with more backwards turning and painful movements with severe disability. Examination findings revealed no conjunctival telangiectasia and neurological examination findings suggestive of cervical dystonia with severe retro collis. The patient has a family history of dystonia, his sister started noticing involuntary neck movement in the last 1.5 years with gradual progression. Her physical examination revealed no evidence of conjunctival lesions and neurological examination suggestive of cervical dystonia with lateral collis. MRI findings of patient were normal. Both the patient and her sister are siblings of a consanguineous product. Patient has been referred for whole exome sequencing. The exome data analysis identified a novel homozygous missense variant c.5751A&gt;T, p.Arg1917Ser (chr11:108307973A&gt;T) in ATM gene responsible for familial A-T with cervical dystonia without chorea as hall mark clinical manifestations. In conclusion, to the best of our literature knowledge this is the rare and unusual case from India wherein we are reporting a novel homozygous missense variant c.5751A&gt;T, p.Arg1917Ser (chr11:108307973A&gt;T) in ATM gene responsible for familial A-T with cervical dystonia rather than ataxia as hall mark clinical manifestations affecting both brother and sister in the same family. Thus, early onset of cervical dystonia should be taken into account as a key characteristic of variant A-T, which can manifest without general ataxia and may cause adults with primary dystonia to receive an incorrect diagnosis.

A Multicenter Study Validates the WHO 2022 Classification for Conjunctival Melanocytic Intraepithelial Lesions With Clinical and Prognostic Relevance

Several nomenclature and grading systems have been proposed for conjunctival melanocytic intraepithelial lesions (C-MIL). The fourth “WHO Classification of Eye Tumors” (WHO-EYE04) proposed a C-MIL classification, capturing the progression of noninvasive neoplastic melanocytes from low- to high-grade lesions, onto melanoma in situ (MIS), and then to invasive melanoma. This proposal was revised to the WHO-EYE05 C-MIL system, which simplified the high-grade C-MIL, whereby MIS was subsumed into high-grade C-MIL. Our aim was to validate the WHO-EYE05 C-MIL system using digitized images of C-MIL, stained with hematoxylin and eosin and immunohistochemistry. However, C-MIL cases were retrieved from 3 supraregional ocular pathology centers. Adequate conjunctival biopsies were stained with hematoxylin and eosin, Melan-A, SOX10, and PReferentially expressed Antigen in Melanoma. Digitized slides were uploaded on the SmartZoom platform and independently scored by 4 ocular pathologists to obtain a consensus score, before circulating to 14 expert eye pathologists for independent scoring. In total, 105 cases from 97 patients were evaluated. The initial consensus diagnoses using the WHO-EYE04 C-MIL system were as follows: 28 benign conjunctival melanoses, 13 low-grade C-MIL, 37 high-grade C-MIL, and 27 conjunctival MIS. Using this system resulted in 93% of the pathologists showing only fair-to-moderate agreement (kappa statistic) with the consensus score. The WHO-EYE05 C-MIL system (with high-grade C-MIL and MIS combined) improved consistency between pathologists, with the greatest level of agreement being seen with benign melanosis (74.5%) and high-grade C-MIL (85.4%). Lowest agreements remained between pathologists for low-grade C-MIL (38.7%). Regarding WHO-EYE05 C-MIL scoring and clinical outcomes, local recurrences of noninvasive lesions developed in 8% and 34% of the low- and high-grade cases. Invasive melanoma only occurred in 47% of the cases that were assessed as high-grade C-MIL. This extensive international collaborative study is the first to undertake a comprehensive review of the WHO-EYE05 C-MIL scoring system, which showed good interobserver agreement and reproducibility.