Nodulo-ulcerative squamous cell carcinoma of the conjunctiva mimicking necrotizing sclerokeratitis in a young patient.

Purpose: A delay in diagnosing and treating ocular surface squamous neoplasia (OSSN) with an atypical manifestation can lead to a progression to more advanced stages, resulting in a decrease in cure rates and treatment effectiveness. Observations: This case report describes a 21-year-old white male who presented to our Cornea Division with peripheral nasal corneal and scleral thinning with prolapse of uveal tissue in the right eye for over four months and who had received a sclerocorneal patch graft. The patient underwent systemic immunosuppressive therapy for presumed Mooren's ulcer after laboratory evaluation eliminated a collagen vascular disorder. Approximately three months after the procedure the patient returned with an inferior and superior sclerocorneal perforation. Six months after the first visit to our department, he returned to our ophthalmological emergency department with self-evisceration of the intraocular contents. He underwent an emergency evisceration procedure, and histopathological analysis of the intraocular contents revealed a poorly differentiated nodulo-ulcerative squamous cell carcinoma of the conjunctiva with intraocular invasion. A tomographic evaluation suggested orbital invasion. Subsequently, he underwent exenteration. Conclusions and Importance: OSSN should be considered in the differential diagnosis of corneal or scleral thinning, perforation, and inflammation of an unknown cause even in young patients, especially after systemic disorders have been excluded.

Conjunctival squamous cell carcinoma with massive apoptosis and immune cell infiltration: A case report.

This case reports a rare case of conjunctival squamous cell carcinoma in China. The elderly (86-year-old) female patient was diagnosed and treated effectively after three times of diagnosis. During this period, she was misdiagnosed and ineffective treatment for many times. Therefore, we propose to make an integrated diagnosis based on histopathological diagnosis, combined with a variety of diagnostic methods including MRI and CDFI, supplemented by updated multiple immunohistochemically techniques, so as to achieve the purpose of accurate diagnosis.

Identification of Metastatic Conjunctival Squamous Cell Carcinoma through Neck Palpation.

An 80-year-old male with a distant 10 pack-years smoking history and squamous cell carcinoma (SCCA) of the scalp diagnosed 15 years ago presented with a new right nasal bulbar conjunctival lesion found to be invasive SCCA. The patient was started on interferon alfa-2b for 5 months until there was no evidence of residual disease. During a follow-up visit 10 months after diagnosis and during routine ophthalmic follow-up, an enlarged right submandibular lymph node was found through neck palpation and revealed to be SCCA without extranodal extension. The lesion was likely to have metastasized from his right conjunctival squamous cell carcinoma (CSCCA). Regional lymph nodes are a commonplace of metastasis for CSCCA making neck palpation a reasonable and recommended part of clinical examination to monitor for metastasis. This is the first known case of identifying regional metastasis of CSCCA through neck palpation.

OVOL1 immunohistochemical expression is a useful tool to diagnose invasion in ocular surface squamous neoplasms.

BACKGROUND AND OBJECTIVES: OVOL1 is a gene that negatively regulates mesenchymal transformation, which allows epithelial cells to invade the stroma. On the other hand, it negatively regulates c-Myc, which has a positive effect on cell proliferation. The aim of this study is to evaluate the expression of OVOL1 and c-Myc in ocular surface squamous neoplasia (OSSN). PATIENTS AND METHODS: Cross-sectional cohort study of 36 samples including 6 squamous papillomas, 19 conjunctival intraepithelial neoplasms, 6 squamous carcinomas and 7 normal conjunctivae were evaluated using immunohistochemistry against OVOL1 and c-Myc. The expression of both markers was analysed using the H-score (intensity 1-3 multiplied by the percentage of positive cells). RESULTS: Percentages of 98 and 100 of the OSSN, and 57 and 71% of the normal conjunctivae expressed OVOL1 and c-Myc respectively, however, the mean H-score of OVOL1 and c-Myc was higher in the OSSN than in normal conjunctivae group (P=0.0001 in both). Within the OSSN, OVOL1 demonstrated a higher H-score in the conjunctival intraepithelial neoplasms and papilloma, compared to the squamous carcinoma (P<0.01) group. c-Myc did not show differences between the OSSN groups. An H-score lower than 35 differentiates a squamous cell carcinoma from other OSSN lesions with a sensitivity of 83.3% and a specificity of 100%. CONCLUSIONS: The expression of OVOL1 is a useful tool to differentiate between a squamous carcinoma of conjunctival intraepithelial neoplasms and papilloma. OVOL1 could play a role in the invasiveness of squamous neoplasms and places it as a potential therapeutic target.

Recurrent Conjunctival Squamous Cell Carcinoma and Intraocular Tumor Extension after Topical Erythropoietin: A Case Report.

Topical erythropoietin has been recently introduced for the treatment of avascular conjunctival and scleral lesions. Before this treatment can be routinely used, however, its safety profile and contraindications should be determined. Herein, we report a case of recurrent conjunctival squamous cell carcinoma (SCC) and intraocular tumor extension after treatment with topical erythropoietin for excisional biopsy-induced scleral necrosis. An 87-year-old man underwent excisional biopsy for a conjunctival leukoplakic mass. Histological examination showed a well-differentiated SCC on the postoperative day 10. All borders of the specimen were reported to be involved with tumoral cells. The patient did not receive further surgical intervention or topical mitomycin since he developed surgically induced scleral necrosis on the postoperative day 14. Topical erythropoietin 3,000 IU/mL was started every 6 h, and avascular scleral lesion healed over 21 days of treatment with topical erythropoietin. However, 4 months after complete improvement, the tumor recurred with extension into the anterior chamber. Ultrasound biomicroscopy showed the involvement of sclera, iris root, and ciliary body with blunting of the anterior chamber angle. Orbital extension was not detected in magnetic resonance imaging. Topical erythropoietin administered in eyes with a history of conjunctival SCC could be linked to tumor recurrence and intraocular invasion. We recommend avoiding topical erythropoietin in eyes with existing conjunctival SCC or a previous history of conjunctival SCC that was incompletely removed.

Demographic and clinical features of conjunctival tumours at a tertiary care centre.

CLINICAL RELEVANCE: This study investigates the demographic and clinical features of conjunctival tumours. BACKGROUND: Conjunctival tumours include a large spectrum of conditions ranging from benign lesions to aggressive, life-threatening malignancies. Knowing the distribution of conjunctival tumours by age and gender is important for reducing cancer morbidity. METHODS: The clinical records of 375 patients (410 eyes) diagnosed with a conjunctival mass at a tertiary referral centre between February 1999 and November 2020 were retrospectively evaluated. RESULTS: Two-hundred-seventeen (57.9%) patients were male and 158 (42.1%) were female. Of 410 conjunctival tumours, 159 (38.8%) were benign, 106 (25.9%) premalignant, and 145 (35.4%) malignant. Overall, the 3 most common diagnoses were squamous cell carcinoma (SCC, 19.5%), conjunctival intraepithelial neoplasia (CIN, 18.3%), and naevus (17.8%). The most common benign, premalignant, and malignant tumours were naevus (n = 73/159, 45.9%), CIN (n = 75/106, 70.8%), and SCC (n = 80/145, 55.2%) respectively. Naevus was the most common tumour in ≤20 years and > 20-40 years old patient groups (56.2% and 25.4% respectively). CIN was the most frequent tumour in patients aged > 40-60 years (25.7%). SCC was the most common tumour in > 60-80 years and > 80 years old patient groups (44.3% and 80.0% respectively). The median patient age was greater in patients with malignant tumours (64.5 years) compared to patients with premalignant (55.5 years, p = 0.011) and benign tumours (22.0 years, p < 0.001). Malignant tumours displayed larger base diameter, greater thickness, and intrinsic vessels compared to premalignant or benign lesions (p < 0.001 for each parameter). Malignant tumours also displayed more amelanotic vs melanotic appearance (p < 0.001) and limbal vs extralimbal bulbar location compared to benign lesions (p < 0.001). CONCLUSION: Premalignant and malignant tumours comprised 61.2% of all conjunctival tumours and were usually detected in patients > 40 years of age in this study.

Expression of thrombospondin-1 in conjunctival squamous cell carcinoma is correlated to the Ki67 index and associated with progression-free survival.

PURPOSE: Conjunctival squamous cell carcinoma (SCC) is primarily treated with surgical resection. SCC has various stages, and local recurrence is common. The purpose of this study was to investigate thrombospondin-1 expression and its association with prognosis. METHODS: In this retrospective study, a gene expression array along with immunohistochemistry were performed for the evaluation of thrombospondin-1 expression, localization, as well as Ki67 labeling cell indices in carcinoma in situ (Tis) and advanced conjunctival SCC (Tadv). The presence or absence and intensity of cytoplasmic and nuclear staining in tumor cells were also divided into groups with a score of 0-3 and semi-quantitatively analyzed to investigate intracellular staining patterns. The association between thrombospondin-1 expression and tumor progression in a series of 31 conjunctival SCCs was further investigated. RESULTS: All 31 patients in the cohort (100%) were East Asian. A simple comparison between Tis and Tadv demonstrated significant differences in expressions of 45 genes, including thrombospondin-1 (p < 0.01). In this cohort, 30/31 tumors were positive (96%) for thrombospondin-1. Furthermore, thrombospondin-1 intracellular staining pattern analysis scores were 2.12 and 0.96 for nuclear and cytoplasmic staining, respectively, with a significant difference observed between Tis and Tadv (p < 0.01). Alteration of the Ki67 labeling index was significantly correlated with that of the thrombospondin-1 cytoplasmic score (p = 0.030). Furthermore, univariate Cox regression analysis showed a significant correlation between thrombospondin-1 staining and progression-free survival (p = 0.026) and final orbital exenteration (p = 0.019). CONCLUSIONS: The present results demonstrated that thrombospondin-1 is a potential molecular target in the pathology of conjunctival SCC, in addition to serving as a prognostic factor.

Intraocular Invasion of Ocular Surface Squamous Neoplasia Through a Corneal Wound.

PURPOSE: We report a case of intraocular invasion of ocular surface squamous neoplasia (OSSN) through a cataract surgery wound that manifested as an anterior chamber membrane, and perform a review of the literature. METHODS: An 87-year-old woman with history of an incompletely excised OSSN 10 days prior presented with decreased vision due to an anterior chamber membranous film that seemed connected to an old cataract wound. The membrane was biopsied, and histopathology revealed dysplastic squamous epithelial cells of conjunctival origin. Ten days later the tumor expanded to cover the entire iris surface, and a modified enucleation was performed. RESULTS: Histopathology revealed invasive OSSN extending deep to the ciliary body and laterally into the anterior chamber. The patient developed a submandibular node metastasis 7 months later. Literature review revealed six cases of invasive OSSN resulting from extension through a corneal wound, with varied presentations and outcomes. CONCLUSION: Our case is the first to report invasive OSSN presenting as an anterior chamber membrane as a result of incomplete excision of an ocular surface malignancy adjacent to a corneal wound poses a risk for intraocular tumor extension and distant metastasis.

Conjunctival Adenosquamous Carcinoma Lacks MAML2 Translocation: A Variant of Squamous Cell Carcinoma With Mucoepidermoid Differentiation and Aggressive Behavior?

Conjunctival adenosquamous carcinoma, also known as mucoepidermoid carcinoma (MEC), is a rare tumor that preferentially affects the perilimbal area of the conjunctiva with aggressive local invasion. Consisting of infiltrative proliferation of squamous cells and mucous cells, its morphologic features are reminiscent of the salivary gland-type MEC except for the absence of intermediate cells and frequent keratin production. We reported 2 cases of conjunctival adenosquamous carcinoma and, for the first time, studied the MAML2 translocation status of this rare entity. The 2 patients were women, aged 45 and 42 years, presenting with an erythematous lesion in the left lower palpebral conjunctiva and a pigmented nodule over the left nasal conjunctiva, respectively. One tumor recurred 6 months after the initial biopsy. Excision with lid reconstruction and postoperative radiotherapy was performed for margin involvement and perineural invasion. This patient was disease free at 3-year follow-up. The other patient was lost to follow-up after tumor excision. Fluorescence in situ hybridization and reverse transcription polymerase chain reaction failed to demonstrate MAML2 translocation and CRCT1-MAML2 transcripts in both tumors. The absence of this characteristic translocation and reappraisal of the cellular composition, morphologic features, and precursor lesion suggest that conjunctival MEC may represent a variant of conjunctival squamous cell carcinoma but not related to the salivary gland-type MEC.

AS-OCT Guided Treatment Of Diffuse Conjunctival Squamous Cell Carcinoma With Resection, Amniotic Membrane Graft And Topical Mitomycin C.

PURPOSE: To evaluate the efficacy of combined limited surgical resection, amniotic membrane graft and topical mitomycin C in treatment of diffuse conjunctival squamous cell carcinoma (CSCC) diagnosed and followed up by anterior segment optical coherence tomography (AS-OCT). SUBJECTS AND METHODS: A prospective study was performed on 24 eyes with diffuse CSCC. Fifteen eyes underwent lesion limited resection followed by postoperative topical mitomycin C 0.04% eye drop (MMC group) while nine eyes underwent complete excision and cryotherapy (no MMC group). Amniotic membrane graft was applied in all cases. The diagnosis was based on clinical and AS-OCT specific criteria of CSCC and was confirmed by histopathological results. RESULTS: The study population was similar between the two groups. Mean postoperative follow-up was 27.1±4.1 months. The mean extent of the limbal involvement was 7.0±0.7 and 7.25±0.6 clock hours in MMC and no MMC groups, respectively. The mean size of conjunctival defect after tumor excision in MMC group (60.8±9.2 mm2) was significantly lower than in no MMC group (92.4±17.3 mm2). Histopathological diagnosis revealed invasive SCC in all specimens. The mean preoperative conjunctival epithelial thickness decreased significantly in both groups at 2-year follow-up. It decreased from 267±24.2 and 256±19.1 µm preoperatively to 56.7±11.6 and 60.4±9.6 µm at 2-year follow-up in MMC and no MMC groups, respectively. The mean number of MMC treatment cycles was 2.1±0.85 cycles. Recurrence was recorded in zero (0%) and 1 (11%) patients at 2-year follow-up in MMC and no MMC groups, respectively. Histopathological diagnosis revealed invasive SCC in all specimens. The mean preoperative conjunctival epithelial thickness decreased significantly in both groups at 2-year follow-up. It decreased from 267±24.2 and 256±19.1 µm preoperatively to 56.7±11.6 and 60.4±9.6 µm at 2-year follow-up in MMC and no MMC groups, respectively. The mean number of MMC treatment cycles was 2.1±0.85 cycles. Recurrence was recorded in zero (0%) and 1 (11%) patients at 2-year follow-up in MMC and no MMC groups, respectively. CONCLUSION: The treatment of diffuse CSCC with AS-OCT guided combined therapy includes limited surgical resection, AMG, and postoperative topical MMC, achieves a complete tumor resolution and good functional and cosmetic outcomes minimizing the burden of surgery, and improves postoperative patient comfort in our study cohort.

Malignant transformation of a conjunctival keratoacanthoma requiring enucleation.

PURPOSE: We report a rare case of rapid transformation of a conjunctival keratoacanthoma (KA) into a highly aggressive squamous cell carcinoma requiring enucleation. To our knowledge, this is the second such case reported in the literature. METHODS: Case report. RESULTS: A 73-year-old man presented with a recurrent conjunctival lesion in the right eye. A slit lamp examination revealed a hyperkeratotic lesion in the limbar conjunctiva adhered to deep planes but with no ocular involvement. An incisional biopsy was performed because an area of scleromalacia was observed underlying the lesion. Histological findings were consistent with conjunctival KA. One week later, a raised lesion was observed invading the anterior chamber. Histological examination of another excisional biopsy specimen indicated conjunctival squamous cell carcinoma. The right eye was enucleated. Histological analysis confirmed intraocular tumor invasion. Complete clinical remission was observed over one year of follow up. CONCLUSIONS: Although conjunctival keratoacanthoma is normally benign, it is important to correctly differentiate between KA and squamous cell carcinoma, and closely monitor the eye after surgery because of the rare possibility of recurrence or conversion to squamous cell carcinoma. Immunohistochemistry could help in the diagnosis and management of dubious cases.

Predictors of Ocular Surface Squamous Neoplasia and Conjunctival Squamous Cell Carcinoma among Ugandan Patients: A Hospital-based Study.

AIM: The aim of the study was to assess the predictors of ocular surface squamous neoplasia (OSSN) and conjunctival squamous cell carcinoma (SCC) among Ugandan patients. MATERIALS AND METHODS: Patients presenting for removal of ocular surface lesions received human immunodeficiency virus (HIV) testing, completed questionnaires about demographic, behavioral, and historical potential risk factors for conjunctival neoplasia, and had lesions examined for interpalpebral versus other locations, rough versus smooth texture, and number of feeder vessels. Biopsies were classified pathologically using standard definitions classified OSSN and SCC. HIV rates were calculated for patients: with OSSN, SCC, and benign lesions. Potential risk factors and gross findings were tested for abilities to predict OSSN and SCC. RESULTS: One hundred and ninety-five patients presented with 212 lesions in 203 eyes. Nearly 34% of the patients were more than 60 years old, 67% were peasants, 88% spent more than 20 h/week outdoors, and only 10% wore sun protection. No potential risk factors predicted neoplasia. HIV prevalence was 17.1% among patients with OSSN compared to 11.1% among those without OSSN; 42.9% among SCC patients compared to 12.0% among those without SCC. Rough tumor surface (adjusted odds ratio [aOR] = 4.4 and 95% confidence interval [CI]: 2.2-9.1), six or more feeder vessels (aOR = 2.6, 95% CI: 1.3-5.2), and interpalpebral tumor location (aOR = 3.3, 95% CI: 1.5-7.1) predicted OSSN. Only a rough tumor surface (aOR = 34.6, 95% CI: 7.8-153.4) predicted SCC. CONCLUSION: HIV infection remained a risk factor for OSSN and particularly, SCC, but less so than in the past. Lesions' rough surface, six or more feeder vessels, and interpalpebral location increased OSSN risk. Only a rough tumor surface increased risk for SCC.

Infiltrative Intraocular Conjunctival Squamous Cell Carcinoma after Local Resection and Brachytherapy: Clinical and Pathological Findings.

A pseudophakic 70-year-old man presented to the clinic with a slow-growing conjunctival mass in the left eye. He was diagnosed with a conjunctival exophytic lesion suspicious of invasive conjunctival squamous cell carcinoma (CSCC). Excisional biopsy showed a well-differentiated CSCC with positive margins and the patient underwent adjuvant brachytherapy. Six weeks later, examination of the anterior segment revealed cells in the anterior chamber and a neurotrophic corneal ulcer with corneal perforation. Considering the high suspicion of intraocular invasion of CSCC, the left eye was enucleated. Histopathologic findings showed scarring of the ciliary body with fibrosis temporally. Nasally, the sclera showed a lobular infiltration of well-differentiated squamous carcinoma. The central cornea exhibited a large ulcer with perforation and infiltrating squamous cells adhering to the posterior surface. To our knowledge, this is the first documented case of an intraocular diffuse recurrence of CSCC after resection and adjuvant brachytherapy, with clinicopathologic correlation of radiation effects on the ocular tissues.

Interferon alpha-2a as alternative treatment for conjunctival squamous cell carcinoma. / Interferón alfa-2a como tratamiento alternativo para el carcinoma conjuntival de células escamosas.

CASE REPORT: A 35 year-old male patient with a history of HIV infection characterized by progressive tumour growth in bulbar conjunctiva of the left eye, corresponding to conjunctival squamous cell carcinoma that responded to treatment with interferon alpha-2a. DISCUSSION: Interferon alpha-2b has been used at conjunctival level as a topical immunomodulator treatment, with complete remission of epithelial neoplasms being observed. However, there have not been any previous publications on the use of interferon alpha-2a, which differs from interferon alpha-2b in a single amino acid, for the treatment of conjunctival squamous cell carcinoma.

Epidemiology of ocular surface squamous neoplasia in Africa.

OBJECTIVES: To describe the epidemiology and an aetiological model of ocular surface squamous neoplasia (OSSN) in Africa. METHODS: Systematic and non-systematic review methods were used. Incidence was obtained from the International Agency for Research on Cancer. We searched PubMed, EMBASE, Web of Science and the reference lists of articles retrieved. Meta-analyses were conducted using a fixed-effects model for HIV and cigarette smoking and random effects for human papilloma virus (HPV). RESULTS: The incidence of OSSN is highest in the Southern Hemisphere (16° South), with the highest age-standardised rate (ASR) reported from Zimbabwe (3.4 and 3.0 cases/year/100 000 population for males and females, respectively). The mean ASR worldwide is 0.18 and 0.08 cases/year/100 000 among males and females, respectively. The risk increases with exposure to direct daylight (2-4 h, OR = 1.7, 95% CI: 1.2-2.4 and ≥5 h OR = 1.8, 95% CI: 1.1-3.1) and outdoor occupations (OR = 1.7, 95% CI: 1.1-2.6). Meta-analysis also shows a strong association with HIV (6 studies: OR = 6.17, 95% CI: 4.83-7.89) and HPV (7 studies: OR = 2.64, 95% CI: 1.27-5.49) but not cigarette smoking (2 studies: OR = 1.40, 95% CI: 0.94-2.09). The effect of atopy, xeroderma pigmentosa and vitamin A deficiency is unclear. CONCLUSIONS: Africa has the highest incidence of OSSN in the world, where males and females are equally affected, unlike other continents where male disease predominates. African women probably have increased risk due to their higher prevalence of HIV and HPV infections. As the survival of HIV-infected people increases, and given no evidence that anti-retroviral therapy (ART) reduces the risk of OSSN, the incidence of OSSN may increase in coming years.

In situ carcinoma of the conjunctiva: surgical excision associated with cryotherapy.

BACKGROUND: Although frequently underdiagnosed, squamous cell carcinoma is the most commonly observed malignancy of the conjunctiva. Multiple different treatments have been proposed to date. The purpose of this paper is to report our experience in the treatment of In situ carcinoma of the conjunctiva by surgical excision associated with cryotherapy. METHODS: Four eyes in four consecutive patients (two men and two women) of average age 53.2 (range 39-71) years at the time of diagnosis of ocular surface squamous neoplasia were treated by simple surgical excision and cryotherapy of the resulting surgical bed margins. In all cases, the diagnosis of in situ carcinoma was confirmed histopathologically. RESULTS: On histopathology, the edges of the surgical specimens were free of malignant cells in three of four patients. All patients showed excellent evolution without recurrence. Mean follow-up was 6.5 (range 2-14) years. CONCLUSION: In situ carcinoma of the conjunctiva may be simply and successfully treated with surgical excision and cryotherapy.

Expression of αB-crystallin and vascular endothelial growth factor in conjunctival squamous cell carcinoma.

AIM: To examine the expression of αB-crystallin and vascular endothelial growth factor (VEGF) in conjunctival squamous cell carcinoma (CSCC). MATERIALS AND METHODS: Seven CSCCs and three normal conjunctivas that were surgically excised were studied. Paraformaldehyde-fixed, paraffin-embedded tissue sections were processed for immunohistochemistry with antibodies against αB-crystallin, its phosphorylated forms, and VEGF. In vitro experiments were conducted to investigate the effects of mitomycin C (MMC) treatment on the expression of αB-crystallin and VEGF secretion. RESULTS: αB-Crystallin and VEGF were strongly expressed in CSCCs compared to normal conjunctivas. αB-Crystallin immunoreactivity was co-localized with that for VEGF in CSCCs, whereas these signals were reduced in CSCC tissues treated with MMC before excision. MMC treatment suppressed the αB-crystallin expression and VEGF secretion in cultured conjunctival cells in a dose-dependent manner. CONCLUSION: This study demonstrated αB-crystallin and VEGF expressions in human CSCCs, which may play a role in the pathogenesis. αB-Crystallin expression, and VEGF secretion were reduced by MMC, indicating a novel therapeutic mechanism in MMC treatment for human CSCC.

Conjunctival squamous cell carcinoma in a reindeer (Rangifer tarandus tarandus).

An 8-year-old female adult reindeer (Rangifer tarandus tarandus) was referred to the Veterinary Hospital of Madrid for evaluation of a conjunctival mass on the left eye which had been present for about 2 months. A surgical excision was performed and biopsy material submitted for light microscopic evaluation which confirmed the diagnosis of conjuctival squamous cell carcinoma. Nuclear p53 immunolabeling was found in 52% of the neoplastic cells. Follow-up examination at 12 months postsurgery did not reveal recurrence of this neoplasm. Conjunctival squamous cell carcinoma has not been reported previously in reindeer and seems to have similar characteristics to the one existing in bovine species.