Treatment of ocular surface squamous neoplasia in an Indian rural facility: a study of 38 eyes.

PURPOSE: To report the demographic profile, clinical presentation, and management outcomes of ocular surface squamous neoplasia (OSSN) treated with primary topical chemotherapy in a limited resource secondary eye care facility in rural parts of South India. METHODS: Retrospective interventional study of 38 eyes of 37 patients with OSSN treated with topical 1% 5-Fluorouracil (5FU), over a period of two years. RESULTS: The median age at presentation with OSSN was 44 years (mean, 46 years; range 13 to 74 years). Majority (76%) were males. The most common morphological variant was placoid OSSN (18, 47%). Limbus was the most common epicenter (31, 82%). Corneal OSSN was the most initially misdiagnosed variant (n = 3). Of the 38 eyes receiving one week on and 3-weeks off cycles of 5FU regimen, complete tumor resolution was achieved in 36 (95%) eyes. The median number of topical 5FU cycles for tumor resolution was 2 (mean, 2; range, 1 to 4). Over a median follow-up period of 5 months (mean, 6 months; range, 1 to 27 months), tumor recurrence was noted in 3 eyes (8%), of which one case had xeroderma pigmentosum with bilateral multifocal recurrence. Complication rate was 5% (n = 2), which included transient conjunctival hyperemia (n = 1), and bacterial keratitis (n = 1) which resolved with fortified antibiotics. CONCLUSION: Primary chemotherapy with topical 1% 5FU is a safe and effective management modality for OSSN at limited resource settings in rural India.

Prognostic Impact of Notch1 Intracellular Domain, P63, and c-MYC in Lacrimal Gland Adenoid Cystic Carcinoma.

Purpose: We assessed whether NICD1 expression, c-MYC expression, and P63 expression by immunohistochemistry (IHC) correlate with prognosis and high-risk clinicopathological features in lacrimal gland adenoid cystic carcinoma (ACC). Methods: Records of patients with lacrimal gland ACC who underwent surgery between 1998 to 2018 were reviewed. Clinicopathologic and treatment data were collected. Tumor tissues were subjected to light microscopy and IHC. Results: Of 43 patients treated during the study period, 21 had archived tumor tissue available and were included. The median age at diagnosis was 47 years, and 13 patients (62%) were male. Thirteen patients (62%) had T2 disease, and none had nodal or distant metastasis at diagnosis. Tumors were positive for NICD1 expression in eight cases (38%), c-MYC expression in eight (38%), and P63 expression in 11 (52%). Positive NICD1 expression was associated with predominantly solid (vs. cribriform/tubular) pattern (P < 0.001), treatment with orbital exenteration (vs. eye-sparing surgery) (P = 0.008), local recurrence (P = 0.047), and death (P = 0.012). Negative P63 expression was associated with predominantly solid pattern (P = 0.001), local recurrence (P = 0.012), distant metastasis (P = 0.001), and death (P = 0.035). A higher percentage of tumor cells staining for c-MYC was associated with presence of perineural invasion (P = 0.036). Positive NICD1 expression was associated with worse disease-free survival (hazard ratio, 6.27; 95% CI, 1.29-30.46), whereas positive P63 expression was associated with better disease-free survival (hazard ratio, 0.03; 95% CI, 0.0002-0.26). Conclusions: IHC for NICD1 and P63 should be considered in lacrimal gland ACC because of their prognostic value and potential as treatment targets.

Bilateral development of biclonal ocular adnexal marginal zone lymphoma at a 2-year interval.

Ocular adnexal marginal zone B-cell lymphoma (OAMZL) of the mucosa-associated lymphoid tissue is a distinct subtype of B-cell lymphoma. OAMZL occasionally occurs on both sides with a varied sequence in the time course. However, few case reports have described clonal analysis of bilateral OAMZ. Here we present a case of biclonal OAMZL, that developed bilaterally at a 2-year interval. A 38-year-old woman was diagnosed with OAMZL in the right lower eyelid conjunctiva and received local radiation therapy, resulting in the disappearance of the tumor. Two years later, she developed another tumor in the left lower eyelid and was diagnosed with relapse of OAMZL. She was re-treated successfully with radiation therapy. Analysis of immunoglobulin (Ig) gene rearrangement in the bilateral tumor samples showed different clonotypic VDJ recombination within the Ig heavy chain gene and different patterns of rearrangement of the Ig light chain genes. The results indicated that independent B-cell clones causing the specific subtype of lymphoma had generated in both eyes. The biclonal nature of the lymphoma that developed sequentially in the same anatomic site in this case suggests that underlying inherent or environmental factors may lead to ongoing emergence of new tumor clones.

Bilateral Lacrimal Gland Lymphoma - Case Presentation.

Lacrimal gland lymphomas are rare orbital tumors, constituting a minor fraction of all orbital and ocular adnexal malignancies. This case study presents an 83-year-old male with bilateral lacrimal gland tumors, more prominent in the left orbit, causing decreased visual acuity, red eye, excessive tearing, and diplopia. Initial ophthalmological evaluations and imaging suggested bilateral lacrimal gland lymphoma, confirmed by histopathology as diffuse large B-cell non-Hodgkin lymphoma of the MALT type. Due to the significant tumor size and risk of visual function loss, surgical intervention was performed, followed by corticosteroid therapy. Postoperatively, a marked improvement in symptoms and a reduction in tumor size were observed. This case underscores the importance of comprehensive diagnostic approaches, including clinical, imaging, and histopathological evaluations, highlighting the need for a multidisciplinary approach in managing rare orbital tumors like lacrimal gland lymphoma. The patient's postoperative and follow-up care included oncological management to monitor and ensure long-term disease control and patient well-being. Abbreviations: RE = right eye, LE = left eye, CT = Computer tomography, MRI = Magnetic Resonance Imaging, TOD = intraocular pressure of right eye, TOS = intraocular pressure of left eye, US = ultrasound.

Utility of PD-1, PD-L1, and IDO-1 Stains in Ocular Extranodal Marginal Zone Lymphoma (MZL) and Diffuse Large B-cell Lymphoma (DLBCL).

Extranodal marginal zone lymphoma (EMZL) is the most common subtype of ocular lymphomas. Diffuse large B-cell lymphoma (DLBCL) and EMZL with large-cell transformation present diagnostic challenges. Radiotherapy is the standard treatment for ocular lymphomas, but complications and relapse are common. Diagnostic utility in challenging cases, as well as treatment options using immune checkpoint inhibitors, are unclear in ocular lymphomas. We herein investigated the PD-1, PD-L1, and IDO1 staining patterns in 20 cases of ocular lymphomas, including EMZL (n=14), EMZL with increased large cells (n=2), and DLBCL (n=4). PD-1, PD-L1, and IDO1 staining was not detected in lymphoma cells in any cases but was observed within the tumor microenvironment in all cases. Positivity for PD-1, PD-L1, and IDO1 in inflammatory cells was seen either intratumorally or peritumorally. In all 6 cases with significantly more large B cells, the density of PD-1, PD-L1, and IDO1 expression in the tumor microenvironment was higher than that of the remaining 14 cases without large B cells ( P -value<0.0001), whereas other clinicopathologic features showed no statistical correlation. Increased expression of PD-1, PD-L1, and IDO1 in the inflammatory milieu in cases with large cells may provide diagnostic utility in small biopsies as well as therapeutic potential.

Efficacy of topical 5-Fluorouracil in the management of ocular surface squamous neoplasia: a study of 101 eyes.

OBJECTIVE: To study the efficacy and side-effect profile of topical 5-Fluorouracil (5-FU) in the treatment of ocular surface squamous neoplasia (OSSN). METHODS: Retrospective study of 101 eyes of 100 patients treated with 5-FU with one week on and 3 weeks off regimen. RESULTS: Of the 100 patients (101 eyes), the mean age at diagnosis of OSSN was 49 (median, 52 years; range, 11-87 years). History of prior intervention was noted in 6 (6%) eyes. Tumor epicenter included bulbar conjunctiva (n = 54; 53%), limbus (n = 27; 27%), and cornea (n = 20;20%). Mean number of cycles of topical 5-FU administered was 3 (median, 3; range, 1-8). Complete tumor regression was achieved with topical 5-FU in 89 (88%) eyes with a mean number of 2 cycles (median, 2; range, 1-6) of 5-FU. The remaining 12 (12%) lesions underwent additional treatment including excisional biopsy (n = 7), extended enucleation (n = 3), and topical Interferon alpha 2b (n = 2) for complete tumor control. Over a mean follow-up period of 6 months (median, 5 months; range, 1-36 months) following treatment, tumor recurrence was noted in 2 (2%) patients, and side-effects were noted in 7 (7%) eyes including conjunctival hyperemia (n = 1), punctal stenosis (n = 1), sterile keratitis (n = 4), and limbal stem cell deficiency (n = 1). CONCLUSION: Topical 5-FU is an effective non-invasive therapy for OSSN with a minimal side-effect profile.

Unusual presentation of ocular surface squamous neoplasia in a young healthy patient: A case report.

PURPOSE: To report an unusual case of ocular surface squamous neoplasia (OSSN) associated with human papilloma virus (HPV)-16 infection with an atypical morphology in a young otherwise healthy patient. CASE DESCRIPTION: A 17 year-old healthy male was referred to our department for evaluation of a corneal infiltrate with anterior stromal neovascularization in the right eye. One year before, the patient underwent an excision of a corneo-conjunctival lesion that was located inferiorly in the same eye. Histopathological analysis had shown moderate and severe dysplasia of the conjunctival epithelium and resulted positive for HPV-16. We performed a diagnostic incisional biopsy of the limbal conjunctiva and of the corneal epithelium for histological examination and molecular testing for HPV and Chlamydia by using polymerase chain reaction (PCR). Histopathologic evaluation demonstrated low-grade dysplasia of conjunctiva. PCR testing of the corneal epithelium was positive for HPV-16, similarly to the first biopsy performed by another centre. The patient was successfully treated with topical interferon alfa-2b (1,000,000 IU/ml) for a total of six months. After the treatment, the corneal infiltrate improved dramatically with regression of neovascularization and improvement of corneal transparency and vision. DISCUSSION: The present report described an atypical presentation of HPV-related OSSN due to its unusual morphology, young age of onset and absence of associated comorbidity. CONCLUSION: Conservative treatment with topical interferon-alpha 2b could be used to treat successfully HPV-16 positive OSSN, with no corneal irregularity or potential loss of vision compared to surgical excision.

A six-year comprehensive review of eye cytology cases received at a tertiary level hospital.

BACKGROUND: Ocular cytology is an effective method of diagnosing infective, benign, and malignant ocular disease processes due to easy accessibility and rapid turnaround time. However, these specimens pose significant diagnostic challenges due to rarity of the specimen type, sparse diagnostic material available for ancillary workup, and unfamiliarity of the diagnostic entities by the cytopathologist. METHODS: This study conducted a 6-year comprehensive review of 65 eye cytology cases received at a tertiary level hospital. Cytopathologic diagnoses of "negative for malignancy" and "atypical" were categorized as negative findings (70.8%, n = 46) and diagnoses of "suspicious for malignancy" and "positive for malignancy" were categorized as positive findings (23.1%, n = 15). A 44.6% (n = 29) of cases had subsequent histopathology and/or flow cytometry diagnoses. Premalignant and malignant lesions detected on histopathology were considered as significant findings. Statistical analysis was performed to evaluate the concordance of ocular cytology with associated histopathology and/or flow cytometry diagnoses. RESULTS: The accuracy of final cytology-histopathology and/or cytology-flow cytometry diagnoses in this cohort of cases is 86.2%. The sensitivity and specificity of ocular diagnosis by cytology are 66.6% and 100%, respectively. The positive and negative predictive values of ocular diagnosis by cytology are 100% and 80.9%, respectively. CONCLUSION: Ocular cytology is a fast, effective, and sensitive method for diagnosing ocular pathology specimens. Familiarity with these specimen types by cytopathologists can help in diagnosing ocular diseases effectively on small, challenging cytologic preparations.

Presumed Lacrimal Gland Pleomorphic Adenoma With Extensive Ossification and Necrosis.

Calcification within pleomorphic adenomas of the lacrimal gland is well recognized but uncommon, being seen more readily in lacrimal gland carcinomas. Bony formation, ossification, in pleomorphic adenomas of the lacrimal glands is even rarer. Together with extensive sclerosis, or "coagulative necrosis," ossification and necrosis should alert the clinician to the risk of malignant transformation. However, both can mimic carcinomatous change, leading to misinterpretation of malignancy in an otherwise benign lacrimal gland neoplasm. We present 2 case reports of patients with clinically presumed pleomorphic adenomas of the lacrimal gland whose histopathology demonstrated lacrimal gland ossification and necrosis without features of malignancy or invasive disease.

[Isolated primary vitreoretinal lymphoma (case report)]. / Izolirovannaya pervichnaya vitreoretinal'naya limfoma (klinicheskoe nablyudenie).

This case report presents the diagnostic features of isolated primary intraocular lymphoma, which was initially misdiagnosed as neovascular age-related macular degeneration. A comprehensive examination using ultrasound, optical coherence tomography, and fundus autofluorescence revealed changes characteristic of vitreoretinal lymphoma. Molecular genetic analysis of the vitreous body showed the presence of a MYD88 gene mutation and B-cell clonality by immunoglobulin heavy chain (IGH) gene rearrangement tests, which confirmed the diagnosis.

DICER1 Syndrome Discovered Through an Eye Tumor.

This case report describes a patient with medulloepithelioma of the ciliary body that was subsequently diagnosed as DICER1 syndrome.

Mucosa-associated lymphoid tissue lymphoma of the lacrimal gland: A case report and literature review.

RATIONALE: The most common subtype of primary lymphoma of the ocular adnexa is the mucosa-associated lymphoid tissue (MALT) subtype. MALT lymphoma of the lacrimal gland is relatively rare among the lacrimal gland tumors, and the early clinical symptoms are atypical, which can easily lead to misdiagnosis and missed diagnosis. Here, we report a case of MALT lymphoma of the lacrimal gland and explore its clinical manifestations, pathological characteristics, management, and pathogenesis, with the aim of helping clinicians gain an in-depth understanding of ocular adnexal MALT lymphoma. PATIENT CONCERNS: A 60-year-old man presented to our hospital with proptosis and diplopia. The right eye deviated and shifted toward the lower part of the nose. DIAGNOSIS: Orbital enhanced magnetic resonance imaging suggested a mass with a maximum cross-section of 3.2 × 2.1 cm. T1 weighted image was isointense, and the enhancement was more uniform and obvious. INTERVENTIONS: The right orbital mass was treated surgically, and the final pathology report was MALT lymphoma. After the pathological report was released, the patient was transferred to the hematology department for further diagnosis and no further treatment was given eventually. OUTCOMES: Seven months later, the patient did not complain of discomfort. Whole-body positron emission tomography-computed tomography, superficial lymph node examination and orbital magnetic resonance imaging revealed no abnormal changes. LESSONS: The clinical manifestations of MALT lymphoma are heterogeneous. Imaging examination is important for assessing the size of the tumor and its relationship with adjacent tissues. Postoperative pathological examination may provide further evidence for the evaluation of the patient's surgical efficacy and prognosis. Management of MALT lymphoma of the lacrimal gland requires a multidisciplinary approach involving ophthalmologists, hematologists, and radiotherapists.

Efficacy and safety of topical 0.5% 5-Fluorouracil as primary treatment of ocular surface squamous neoplasia.

OBJECTIVE: To assess the efficacy and safety of topical 0.5% 5-Fluorouracil (5-FU) as a primary therapy of ocular surface squamous neoplasia (OSSN). DESIGN: Retrospective study. PARTICIPANTS: Patients with clinically suspected OSSN referred to a Brazilian tertiary health center between October 2015 and December 2022. METHODS: After diagnostic confirmation of OSSN with exfoliative cytology, 0.5% 5-FU was administered topically 4 times daily for 2 weeks followed by a pause of 2 weeks. RESULTS: A total of 54 patients were included in this study, 32 males (59.3%), mean age of 62.9 years old. Complete resolution of OSSN was achieved in 70.4%. The median number of cycles was 2 (range 1-5). Side effects were reported in 35.2%, which included eyelid erythema, conjunctival hyperemia, and punctal stenosis. None of the patients stopped treatment due to adverse effects. Patients who had partial response to 0.5% 5-FU had complementary treatment with surgery, Mitomycin-C and/or Interferon ⍺2b. Overall recurrence was 14.8%. Median follow-up was 14 months (range 2-92 months). In a multivariate Cox regression analysis, the risk of relapse was 84% lower in patients who had complete response to 0.5% 5-FU (p = 0.018). CONCLUSION: Topical 0.5% 5-FU may be considered a safe and effective primary therapy for OSSN, with a low rate of side effects.

[Clinical approach for solid intraocular metastases]. / Klinisches Vorgehen bei soliden intraokulären Metastasen.

BACKGROUND: Intraocular metastases arising from solid tumors are found in approximately 2% of patients with metastatic tumor diseases and are therefore more frequent than originally assumed. They often affect the uvea and are associated with a poor prognosis. Due to the difficult diagnosis and an inconsistent treatment regimen, ophthalmologists have a special responsibility here. OBJECTIVE: This article gives a summary of the various types of intraocular metastases with respect to clinical features, diagnostics, treatment and prognosis as well as recommendations for follow-up care. METHODS: A selective literature search was carried out on the topic of intraocular metastases using PubMed and Google Scholar. RESULTS: Intraocular metastases most frequently affect the uvea, specifically the choroid. In most cases the underlying disease is breast or lung cancer, but other rarer primary tumors have also been reported in the literature. Metastatic lesions can show very different morphological manifestations but can be distinguished based on the corresponding structure of manifestation in the eye and with the aid of targeted staging, thus providing valid information on the type of primary tumor. The treatment is partly experimental and usually depends on the primary tumor and leading symptoms of the patient. A differentiation between a curative or palliative treatment situation must always be made. CONCLUSION: Intraocular metastases are the most frequent intraocular tumor and are usually associated with a poor prognosis. Accurate diagnostics for finding the treatment as well as interdisciplinary collaboration and the presentation of the patient on the tumor board are essential.

H-VISTA Immunohistochemistry Score Is Associated with Advanced Stages in Cutaneous and Ocular Melanoma.

Melanoma represents a public health issue. One of the biggest goals of current research is to develop new therapeutic options for patients affected by this aggressive tumor. We conducted a retrospective study including 105 patients diagnosed with cutaneous and ocular melanoma, with stages varying from pT1a to pT4b and pT4e, respectively, and we performed immunohistochemistry reactions with the new potential prognostic marker, VISTA (V-domain Ig suppressor of T cell activation). We quantified the expression by applying the H-score adapted for VISTA and divided the patients, based on the median value, into groups that presented high, low, and negative expression. Therefore, we obtained 65 cases with positive expression for cutaneous melanoma and 8 cases with positive expression for ocular melanoma. Forty-one cases presented high expression in cutaneous melanoma and three cases presented high expression in ocular melanoma. In cutaneous melanoma, analytic statistics showed that VISTA expression was associated with a high Breslow index, high mitotic count, high Ki67 expression, and advanced clinicopathological stage. The majority of ocular melanoma cases demonstrating a positive reaction were classified as stage pT3, whereas earlier stages showed a negative reaction. Our findings underscore a significant correlation between VISTA expression and key prognostic factors in melanoma. Looking ahead, the prospect of future randomized studies holds promise in corroborating the clinical relevance of our findings. By further elucidating the intricate relationship between VISTA expression and melanoma progression, new treatment strategies could be found, improving patient outcomes in this challenging neoplasm.