Clinical profile of melanocytic lesions of the ocular surface in a Hispanic population.

PURPOSE: To determine the prevalence, clinical characteristics, and demographic factors of melanocytic lesions of the ocular surface, such as racial melanosis, primarily acquired melanosis, conjunctival nevus, and conjunctival melanoma in a Hispanic population. MATERIALS AND METHODS: A cross-sectional and observational study was undertaken in a tertiary referral ophthalmological center in northern Mexico from December 2020 to April 2021. All patients attending an ophthalmology specialty clinic were screened during their first visit in order to detect melanocytic lesions of the ocular surface. Demographic factors, clinical characteristics, and diagnosis and treatment were recorded. RESULTS: 227 patients were screened for melanocytic lesions. Melanocytic lesions were identified in 114 patients (50.2%). The prevalence of the different melanocytic lesions in the screened population was racial melanosis, 45.3%; primary acquired melanosis, 3.5%, and conjunctival nevus 1.3%. No conjunctival melanoma was identified in the screened population. Primary acquired melanosis was more common in the fifth to sixth decade of life and in females. Racial melanosis showed no gender predilection and was also more common in the fifth to sixth decade of life. Only 1 melanocytic lesion (a primary acquired melanosis) required medical treatment with excisional biopsy and cryotherapy. CONCLUSION: The prevalence of racial melanosis is remarkably high in the Hispanic population. While less prevalent, primary acquired melanosis is also present in a considerable percentage of Hispanic patients. Both melanocytic lesions exhibit demographic characteristics that match those previously reported in the medical literature.

A Case of Inflammatory Juvenile Conjunctival Nevus with a Rare Histopathological Type.

Introduction: Inflammatory juvenile conjunctival nevus (IJCN) is a rare condition affecting both children and adolescents. It has misleading clinical and histopathological features; therefore, careful assessment is necessary. We present a case of IJCN with a rare pathological type and misleading histopathological features. Case Presentation: A 13-year-old girl with IJCN in the right eye was treated with antiallergic and steroid eye drops but showed no response and was referred to our hospital for excisional biopsy. Slit-lamp examination revealed a nonpigmented juxtalimbal tumor in the right eye. Histopathologically, nevus cells with mild nuclear atypia proliferated within the conjunctival epithelium. Confluent growth of junctional nests, conjunctival cysts, and prominent inflammatory infiltration were also observed. Considering the young age of the patient and immunohistochemical characteristics (HMB-45, SOX10, p16 and Ki-67), the patient was finally diagnosed with IJCN. IJCN has three pathological subtypes - compound, subepithelial, and junctional - depending on the location of the nevus cells. This case was diagnosed as a rare junctional type, as most of the examined sections only showed lesions within the epithelium; no lesions were clearly identified extending beneath the epithelium. Conclusion: The pathological diagnosis of IJCN is difficult because some features of IJCN suggest malignancy. Detailed microscopic examination, immunohistochemical staining, and the patient's young age helped render a final diagnosis.

Pigmented Conjunctival Nevus: A Mystery Solved by Histopathology.

Inflammatory juvenile conjunctival nevi (IJCN) is a rare type of nevus and its clinical presentation overlaps with that of malignant conjunctival melanoma. It is a benign lesion that has been described to progress to melanoma in some cases. IJCN may clinically mimic melanoma due to its rapid growth features and atypical histology. Thus, its accurate diagnosis by histopathology is a prerequisite for proper management. Here, we present a case of conjunctival lesion mimicking melanoma clinically.

Infected Inclusion Cyst of a Conjunctival Nevus Treated with a Mini-Incision: A Case Report.

Introduction: Conjunctival cysts are usually asymptomatic but they can cause foreign body sensation and contribute to dry eye disease. The purpose of this case report is to describe the presentation and treatment of an infected inclusion cyst of a conjunctival nevus in a healthy 36-year-old patient. Case Presentation: A healthy 36-year-old man presented to the emergency department for redness and pain in his left eye for 1 day. Slit-lamp examination revealed a conjunctival hyperemia and a conjunctival nevus with 4 inclusion cysts, one of which was filled with purulent material. Fluorescein staining of the conjunctival epithelium was negative. Α mini-incision of the white cyst was performed using a 30 G needle, followed by bimanual drainage and topical treatment with tobramycin and moxifloxacin drops every 3 h for a week. A swab of the purulent drainage was positive for gram-positive flora. One week after the drainage of the cyst, the patient was asymptomatic and on slit-lamp examination, the 4 inclusion cysts were filled with a transparent liquid, there was not any vessel dilation and fluorescein staining was negative. Conclusion: Conjunctival inclusion cysts, although considered benign, can become infected and form a conjunctival abscess. A mini-incision on the slit lamp combined with bimanual drainage and followed by topical antibiotic drops seems to be a safe and effective treatment.

Conjunctival Nevus.

Purpose of Review: To provide an up-to-date review of the epidemiology, presentation, diagnosis, and treatment options for conjunctival nevi (CN). Recent Findings: Around 17.2%-42% of all conjunctival tumors have been found to be CN, which most frequently present in White individuals between the first to early third decade of life, with equal distribution between males and females. CN commonly occur in the interpalpebral bulbar conjunctiva with pigmentation ranging from amelanotic to dark. Diagnosis is typically made through slit lamp examination, visualized by a well circumscribed, variably elevated, variably pigmented, solitary lesion with clear cysts distributed throughout the pigment. In ambiguous cases, anterior segment optical coherence tomography (AS-OCT) can highlight the presence of sub-clinical cysts, whose presence points to a diagnosis of nevus. However, excisional biopsy with histopathology examination is the gold standard for identifying CN. Summary: CN are benign, variably pigmented lesions. They are the most common of the conjunctival melanocytic tumors. Due to the extremely low risk of transformation to malignant melanoma (MM), CN are usually managed with routine observation and photo documentation.

Management of Inflamed Conjunctival Nevus with Topical Antiallergic Medications: Case Series.

PURPOSE: To report our findings in three cases of an inflamed conjunctival nevus whose size and degree of pigmentation were reduced by topical antiallergic and immunosuppressive ophthalmic solutions. METHODS: Observational case series. Three patients with inflamed conjunctival nevus were examined by slit-lamp biomicroscopy, and the findings before and after the treatments were compared. RESULTS: All three patients had a slightly pigmented and edematous conjunctival tumor at the corneal limbal area. The tumors were hyperemic, and papillae and follicles were present on the superior conjunctiva in all patients. All of the patients had an allergic predisposition. The antiallergic treatment not only resolved the hyperemia and edema of the palpebral conjunctiva, but also reduced the tumor size. In one case, the topical antiallergic agent alone led to a reduction of the tumor size. A combination of topical antiallergic agent and topical immunosuppressant was effective in reducing the tumor size and degree of pigmentation in the other two patients. CONCLUSION: The hyperemia and pigmentation in eyes with inflamed conjunctival nevus can be resolved by topical antiallergic agent and topical immunosuppressant without resection of the tumor.

Adopting low-shot deep learning for the detection of conjunctival melanoma using ocular surface images.

BACKGROUND AND OBJECTIVE: The purpose of the present study was to investigate low-shot deep learning models applied to conjunctival melanoma detection using a small dataset with ocular surface images. METHODS: A dataset was composed of anonymized images of four classes; conjunctival melanoma (136), nevus or melanosis (93), pterygium (75), and normal conjunctiva (94). Before training involving conventional deep learning models, two generative adversarial networks (GANs) were constructed to augment the training dataset for low-shot learning. The collected data were randomly divided into training (70%), validation (10%), and test (20%) datasets. Moreover, 3D melanoma phantoms were designed to build an external validation set using a smartphone. The GoogleNet, InceptionV3, NASNet, ResNet50, and MobileNetV2 architectures were trained through transfer learning and validated using the test and external validation datasets. RESULTS: The deep learning model demonstrated a significant improvement in the classification accuracy of conjunctival lesions using synthetic images generated by the GAN models. MobileNetV2 with GAN-based augmentation displayed the highest accuracy of 87.5% in the four-class classification and 97.2% in the binary classification for the detection of conjunctival melanoma. It showed an accuracy of 94.0% using 3D melanoma phantom images captured using a smartphone camera. CONCLUSIONS: The present study described a low-shot deep learning model that can detect conjunctival melanomas using ocular surface images. To the best of our knowledge, this study is the first to develop a deep learning model to detect conjunctival melanoma using a digital imaging device such as smartphone camera.

Genomic analysis of adult case of ocular surface giant congenital melanocytic nevus and associated clinicopathological findings.

INTRODUCTION: Conjunctival nevi are the most common tumor of the ocular surface. There are some rare reports of so-called 'giant' conjunctival nevi. We report a case of a 47-year-old female with a cutaneous and ocular surface giant congenital melanocytic nevus and describe her clinical course. CASE DESCRIPTION: This is a retrospective case report of a single patient. A 47-year-old female with a history of biopsy-proven periorbital congenital melanocytic nevus, with an associated giant conjunctival nevus presented for structural and functional rehabilitation. Serial surgeries were performed and excised tissue was sent for histopathological and genetic examination. The conjunctival nevus had a low tumor mutation burden, and of the 647 somatic mutations, only one occurred within a protein coding region, namely NRAS p.Gln61Arg. CONCLUSION: This is the first reported adult case including genomic analysis of an ocular surface giant congenital melanocytic nevus. The case shows a possible association between periorbital congenital melanocytic nevi and giant conjunctival nevi, and underscores the possible role that targeted drug therapies may have in malignant transformation of these conditions.

Conjunctival nevi and melanoma: multiparametric immunohistochemical analysis, including p16, SOX10, HMB45, and Ki-67.

The role of p16 in the diagnosis and prognosis of conjunctival melanocytic lesions in the context of other clinical and immunohistochemical parameters has not been systematically explored. This study was conducted to determine whether p16 is a useful parameter in the diagnosis and prognosis of conjunctival melanocytic nevi and melanoma, either independently or as a component of immunohistochemical panels. Sixty-one patients underwent 61 biopsies for conjunctival melanocytic lesions between 2014 and 2018. Pathologic diagnoses were melanoma (n = 25, 41%), nevus (n = 21, 34%), and conjunctival melanocytic lesion of uncertain malignant potential (n = 15, 25%). The biopsies were assessed for expression of p16, SOX10, HMB45, and Ki-67. In a multivariable model, the parameters most predictive of melanoma versus nevus were diffuse HMB45 staining (odds ratio [OR] = 45, confidence interval [CI] = 4.4-457, P = .02] and p16 nuclear H-score≤115 (OR = 9.5, CI = 1.2-77; P = .04). There was no association of p16 expression with melanoma thickness. Next-generation sequencing identified no CDKN2A mutations or copy number alterations in 12 conjunctival melanomas, including the tumors with absent p16 expression. This study demonstrates that p16 immunohistochemical stain is useful in distinguishing conjunctival melanocytic nevi from melanoma, particularly in combination with HMB45. P16 expression does not appear to correlate with CDKN2A status and melanoma thickness.

Search for histopathological characteristics of inflammatory juvenile conjunctival nevus in conjunctival nevi related to age: Analysis of 33 cases.

PURPOSE: Conjunctival nevi in young individuals can correspond to the entity named Inflammatory Juvenile Conjunctival Nevus (IJCN), presenting clinically as a rapid growth lesion, and showing at the histopathological study an inflammatory infiltrate surrounding the lesion. All these findings can suggest a diagnosis of malignancy. Due to a case of IJCN diagnosed in our Pathology department, we realized that this entity is rarely reported in the literature and histopathological diagnostic criteria are not well defined. The aim of our study is to compare the histopathological characteristics of conjunctival nevi in patients aged thirty years or less to those in patients above 30 years, looking for the findings described in IJCN. METHODS: All the excisional specimens of resected conjunctival nevus in a tertiary hospital from 2000 to 2018 were retrieved from the Pathology department archives. Demographic data were recorded, and histopathological variables (histological type of nevus, lymphocytic infiltration, eosinophilic infiltration, presence of lymphoid follicles, stromal nevomelanocytic component, intraepithelial nevomelanocytic component, epithelial inclusions, quantity of goblet cells in epithelial inclusions, cellular atypia, mitoses and maturation of the lesion) were evaluated by three independent observers. Statistical analysis was performed comparing the two age groups. RESULTS: The study determined a significant predominance of the lymphocytic and eosinophilic infiltration in the group of patients aged thirty years or less respect to the elderly group. The percentage of stromal component of the lesion is larger in patients over thirty years compared to the younger group. There was no correlation between epithelial inclusions, maturation or cytological atypia and age groups. CONCLUSION: We found some histopathological differences in conjunctival nevi related to young age, some of them coincident with the ones described in IJCN, which histopathologically could lead to a misleading diagnosis. However, we did not find significant differences related to age in many of the described histopathological findings described in IJCN. Larger series with a greater number of cases would be of interest to characterize more precisely this lesion.

Analysis of Melanin Structure and Biochemical Composition in Conjunctival Melanocytic Lesions Using Pump-Probe Microscopy.

PURPOSE: We analyze melanin structure and biochemical composition in conjunctival melanocytic lesions using pump-probe microscopy to assess the potential for this method to assist in melanoma diagnosis. METHODS: Pump-probe microscopy interrogates transient excited-state photodynamic properties of absorbing molecules, which yields highly specific molecular information with subcellular spatial resolution. This method is applied to analyze melanin in 39 unstained, thin biopsy specimens of melanocytic conjunctival lesions. Quantitative features of the biochemical composition and structure of melanin in histopathologic specimens are assessed using a geometric representation of principal component analysis (PCA) and principles of mathematical morphology. Diagnostic power is determined using a feature selection algorithm combined with cross validation. RESULTS: Conjunctival melanomas show higher biochemical heterogeneity and different overall biochemical composition than primary acquired melanosis of the conjunctiva (PAM) without severe atypia. The molecular signatures of PAMs with severe atypia more closely resemble melanomas than other types of PAMs. Pigment organization in the tissue becomes more disorganized as diagnosis of the lesions worsen, but nevi are more inconsistent biochemically and structurally than other lesions. Relatively high sensitivity (SE) and specificity (SP) is achieved for differentiating between various melanocytic lesions, particularly PAMs without severe atypia and melanomas (SE = 89%; SP = 87%). CONCLUSIONS: Pump-probe microscopy is a powerful tool that can identify quantitative, phenotypic differences between various types of conjunctival melanocytic lesions. TRANSLATIONAL RELEVANCE: This study further validates the use of pump-probe microscopy as a potential diagnostic aid for histopathologic evaluation of conjunctival melanocytic lesions.

Surgical management of a conjunctival nevus with amniotic membrane transplantation.

PURPOSE: Nevi of the conjunctiva are usually benign pigmented tumorous lesions located in the bulbar conjunctiva. In most conjunctival nevus cases, the patient wants the lesion to be removed for cosmetic reasons, but excisional biopsies are best for lesions suspicious for malignancy. This case report illustrates the intraoperative surgical management, histological findings, and the course of healing in a conjunctival nevus patient. CASE REPORT: A 26-year-old man was referred to our eye hospital with a large bulbar conjunctival nevus of the right eye. Upon examination, there was a large pigmented lesion with numerous small cysts present on the superior bulbar conjunctiva. The conjunctival tumor was resected, and an amniotic membrane transplantation was performed for the bulbar conjunctival reconstruction. The histopathological diagnosis suggested a conjunctival nevus. After the resection, a reduction in the inflammation and healing of the conjunctival lesion could be seen. The epithelialization of the bulbar conjunctiva over the amniotic membrane was complete 4 weeks after the resection. At the 6-month follow-up, there was no sign of recurrence or any postoperative complications. CONCLUSION: A surgical excision combined with reconstruction via amniotic membrane transplantation is effective and economical for the treatment of large conjunctival lesions.

Melanocytic Nevus of the Tarsal Conjunctiva.

BACKGROUND: Melanocytic nevus is a rare occurrence in the tarsal conjunctiva and only 7 well-described cases have been reported previously in the English literature. CASE REPORT: The medical records of 4 patients with tarsal conjunctival melanocytic nevus were reviewed, together with the relevant literature. All patients (3 women and 1 man; age range: 17 - 40 years) had been referred with a suspicion of melanoma. There was one tarsal nevus in the lower eyelid in 3 patients and 2 nevi in the upper eyelid in 1 patient. All lesions were darkly pigmented with irregular borders and were associated with a history of a recent growth in size. An intralesional cyst was present in 1 nevus only. After surgical excision, no recurrence or complication occurred during the follow-up period (range: 7 - 48 months). CONCLUSION: Tarsal melanocytic nevus has been described in detail in 11 cases, including these 4 cases, in the English literature. The lesion arose from the lower eyelid in all cases except one. Tarsal melanocytic nevi may frequently display clinical features suggesting melanoma, such as advanced patient age, recent growth, dark and irregular pigmentation, nodularity, hypervascularity, and the absence of an intralesional cyst. After total excision, nevus recurrence or malignant transformation has not been reported.

Pterygium concomitant with other ocular surface lesions: Clinical implications and pathogenetic links.

In the present study, we aimed to evaluate the co-existence of ophthalmic pterygium with other ocular surface lesions in a cohort of patients from the Cretan population. This is a retrospective evaluation of all pterygia in patients examined and treated at the Department of Ophthalmology of the University Hospital of Heraklion, Greece during an 8-year period (from June 2006 to June 2014). A total of 158 cases was examined. Ocular surface images and medical history were evaluated in order to detect concomitant ocular surface pathological conditions. Concomitant lesions included conjunctival nevi (5 cases, 3.16%), iris nevi (4 cases, 2.53%), conjunctival papillomas (8 cases, 5.06%), conjunctival intraepithelial neoplasia (CIN; 4 cases, 2.53%) and 6 cases of hypertophy of the plica semilunaris (3.79%). Of note, pterygium was overlying the iris which was occupied by the iris nevus in 2 out of the 4 cases of iris nevus. Overall, our data indicate that ophthalmic pterygium may often co-exist with other clinically significant ocular surface lesions. The association of ophthalmic pterygium with conjunctival papillomas or CIN stresses the potential involvement of human papilloma virus in the pathogenesis of ophthalmic pterygium, whereas the topographical association of pterygium with iris nevus may offer support to the transcameral light pathway pathogenetic mechanism.

Imaging microscopic pigment chemistry in conjunctival melanocytic lesions using pump-probe laser microscopy.

PURPOSE: To report the application of a novel imaging technique, pump-probe microscopy, to analyze patterns of pigment chemistry of conjunctival melanocytic lesion biopsies. METHODS: Histopathologic specimens of eight previously excised conjunctival melanocytic lesions were analyzed with pump-probe microscopy. The technique uses a laser scanning microscope with a two-color pulsed laser source to distinguish hemoglobin, eumelanin, and pheomelanin pigment based on differences in transient excited state and ground state photodynamics. The pump-probe signatures of conjunctival melanins were compared with cutaneous melanins. The distributions of hemoglobin, eumelanin, and pheomelanin were analyzed, and pump-probe images were correlated with adjacent hematoxylin and eosin (H&E)-stained sections. RESULTS: The pump-probe signatures of conjunctival melanins are similar, but not identical to cutaneous melanins. In addition, there are qualitative and quantitative differences in the structure and pigment chemistry of conjunctival benign nevi, primary acquired melanosis of the conjunctiva (PAM), and conjunctival melanomas. The pump-probe images correlated well with histopathologic features observed in the adjacent H&E-stained sections, and provided a label-free means of discerning conjunctival anatomic features and pathologic benign or malignant tissue. CONCLUSIONS: Pump-probe laser microscopy shows promise as an adjuvant diagnostic tool in evaluation of ocular melanocytic lesions based on morphologic correlation with the histopathology results and pigment chemistry. This initial study suggests systematic differences in pigmentation patterns among conjunctival benign nevi, primary acquired melanosis, and melanomas. In addition, pump-probe microscopy has the potential for use as a noninvasive "in vivo" optical biopsy technique to aid clinical and surgical management of conjunctival melanocytic lesions.

Concordancia de la citología de impresión y la patología con nevus conjuntivales en la Clínica Oftalmológica de Cartagena / Concordance between impression cytology and pathology evaluation in patients with conjunctival nevus at Clínica Oftalmológica de Cartagena

Objetivos: evaluar la concordancia entre la citología de impresión y el estudio de anatomía patológica en pacientes con nevus conjuntivales que consultaron al Departamento de Córnea de la Clínica Oftalmológica de Cartagena. Diseño del estudio: estudio de concordancia. Métodos: se tomaron 48 ojos de 44 pacientes con hiper o hipopigmentación conjuntival a los que se le realizó citología de impresión y estudio histopatológico comparándose los resultados. Resultados: durante Junio 2011 a Junio 2012 se incluyeron 48 pacientes con sospecha de nevus conjuntivales a los cuales se les realizó citología de impresión y estudio histopatológico. Tuvo más prevalencia el sexo femenino con 68.75%. La edad promedio fué de 34.5 años. Las lesiones encontradas en OD fueron el 52.08%. El 60.42% presentaron pigmento leve o moderado seguido de un 35.42% de pacientes con abundante pigmentación. La localización más común de la lesión fue la conjuntiva bulbar con 93.75%. La citología de impresión resultó positiva para nevus en el 89.58% mientras que la patología arrojó resultados de nevus sub-epitelial en un 35.42%, seguido de nevus compuesto y de unión en el 33.33 y 20.83% respectivamente, y ausencia de nevus en el 10.42%. La sensibilidad de la citología de impresión fue de 93.02% con una especificidad del 40%. Conclusiones: la citología de impresión es un método altamente sensible para la detección de nevus conjuntivales y puede ser utilizado como prueba de tamizaje.

Objectives: to evaluate the concordancebetween impression cytology and pathology evaluation in patients with conjunctival nevus attending Cornea Clinic at Clinica Oftalmológica de Cartagena. Study Design: concordance study Methods: We evaluated 48 eyes from 44 patients with conjunctival hyper or hypopigmentation whom underwent impression cytology and histopathology assessment to find concordance between two methods. Results: during June 2011 to June 2012, we included 48 patients with suspected conjunctival nevus whom underwent impression cytology and histopathology study. Female prevalence was 68.75%. Average age was 34.5 years. Lesions were found in right eye in 52.08% of patients. 60.42% had moderate or mild pigment followed by 35.42% with abundant pigment. The most common location of injury was the bulbar conjunctiva with 93.75%. Impression cytology was positive for nevus in 89.58%, while pathology studies showed subepithelial nevus in 35.42% of cases, followed by compound nevus and union nevus with 33.33% and 20.83% respectively. 10.42% of patients showed absence of nevus. Sensitivity of impression cytology was 93.02% while specificity of the test achieved 40%. Conclusions: impression cytology is a highly sensitive method to detect conjunctival nevi and can be used as a screening test.