John Vekinis, Ana M Susana Morley
Background/Aims To describe the results of all ocular surface biopsies performed on patients with xeroderma pigmentosum (XP) under the care of the UK Nationally Commissioned XP Service as well as the treatment of any subsequent ocular surface conditions diagnosed.
Methods Retrospective analysis of medical records. All patients with XP seen by the service from 2010 to 2019 were included and those with ocular surface biopsies were identified. Data was collected on demographics, complementation subgroup (A–G and V), biopsy details, histopathological analysis and subsequent management.
Results Of 108 patients seen in our service, 17 underwent at least one ocular surface biopsy. 45 biopsy samples were available from 13 patients of which 65% were performed on patients from complementation subgroup C (XP-C). Biopsies were categorised as either non-mapping (clinically abnormal ocular surface tissue) or mapping (multiple sites including clinically normal tissue). 67 percent of non-mapping biopsies had a mass as their indication and 46% showed ocular surface squamous neoplasia. General non-dysplastic damage was seen in 67% of non-mapping biopsies and melanocytic changes were seen in 25% of non-mapping and 81% of mapping biopsies. 47 percent of biopsy outcomes required no additional treatment but, of those that did, 50% received mitomycin C.
Conclusions This is the largest reported series of ocular surface biopsies in patients with XP. It identifies a background of ocular surface melanocytic, degenerative and inflammatory changes, with patients with XP-C showing the most severe effects. We highlight challenges faced in interpreting their histopathology and in planning subsequent treatments.
Beatrice Gallo, Caroline Thaung, Gordon Hay, Amit K Arora, Victoria ML Cohen, Bertil Damato, Mandeep S Sagoo
Background Conjunctival melanoma is the second most common conjunctival malignant tumour after squamous cell carcinoma, usually arising from primary acquired melanosis and less commonly from a conjunctival naevus or de novo. We report four cases of conjunctival melanoma masquerading as ocular surface squamous neoplasia.
Methods Four patients (2 females and 2 males; mean age 60.7 years; range 41–72 years) were referred for suspicious conjunctival lesions. In all cases, the lesions had a perilimbal location, were non-pigmented (cases 1 and 3) or mildly pigmented (cases 2 and 4), had a fleshy (cases 1, 2 and 4) or papillomatous (case 3) appearance and involved the corneal surface. In each case, our main clinical differential diagnosis included conjunctival intraepithelial neoplasia and squamous cell carcinoma. All four patients underwent an excisional biopsy with double freeze-thaw cryotherapy and alcohol keratoepitheliectomy.
Results In all four cases, the histopathological diagnosis was of invasive conjunctival melanoma with extension to the deep surgical margins. Adjuvant therapy consisting of strontium-90 β radiotherapy (all 4 patients) and topical Mitomicyn C (patient 2) was administered.
Conclusion Conjunctival melanoma can clinically resemble ocular surface squamous neoplasia. Clinical impressions therefore need to be confirmed histopathologically.
Roland Hӧllhumer, Susan Williams, Pamela Michelow
Ocular surface squamous neoplasia (OSSN) is the most common ocular tumour with an incidence ranging from 0.03 to 1.9 per 100,000 persons/year. The diagnosis is made on clinical suspicion and confirmed with anterior-segment optical coherence tomography (AS-OCT), cytology, or histology. The purpose of this review is to provide an overview of the management options available for OSSN and review their success and recurrence rates. Surgery is the gold standard for the management of small OSSN lesions. With the increased use of less invasive diagnostic modalities such as AS-OCT and cytology, there has been a move to use topical therapies for the management of OSSN. The most commonly used agents are interferon-α2b (IFN), mitomycin-C (MMC) and 5-fluorouracil (5FU). They have been shown to have similar resolution and recurrence rates but differ in cost and side effect profile. IFN has the lowest side effect profile, but is also the most expensive, whereas MMC has the greatest surface toxicity and is priced midway between the three. 5FU is the cheapest of the three topical agents with less surface toxicity than MMC. Radiotherapy is mostly employed as adjuvant therapy. Newer novel therapies are available but have not been widely adopted as mainstream therapy due to cost and lack of clinical evidence. OSSN has the benefit of many management options. No single modality has been shown to superior and some patients will need the use of combination therapy to achieve an optimal clinical outcome.
Ágnes Füst, Jeannette Tóth, László Imre & Zoltán Zsolt Nagy
To observe and describe the anterior segment optical coherence tomography features of limbally localised non-malignant epithelial mass lesions
Thirteen patients (age: 66.9 ± 16.3 years) with conjunctival mass suggesting ocular surface squamous neoplasia with biomicroscopic examination were imaged using anterior segment ocular coherence tomography (anterior segment optical coherence tomography)/Cirrus HD-OCT, Model 4000, Carl Zeiss Meditec, Inc., Dublin, CA, and Spectralis HRA + OCT system, Heidelberg Engineering, Vista, CA/. Cases with ocular surface squamous neoplasia-like anterior segment optical coherence tomography (hyperreflective, thickened epithelium and an abrupt transition from normal to abnormal) were included in the study. Maximal thickness of the epithelium was measured. Histological diagnosis was gained from an excisional or incisional biopsy or impression cytology specimens.
In six patients (age: 68.5 ± 15.4 years) with ocular surface squamous neoplasia-like anterior segment optical coherence tomography features, the histological diagnosis was other than ocular surface squamous neoplasia (papilloma, parakeratosis and a keratotic plaque with mild dysplasia), and ocular surface squamous neoplasia in seven cases (age: 65.6 ± 18.0 years). The maximal epithelial thickness was between 250 and 859 µm in non-ocular surface squamous neoplasia cases and between 252 and 596 µm in ocular surface squamous neoplasia cases.
Non-malignant epithelial lesions can mimic ocular surface squamous neoplasia on anterior segment optical coherence tomography
Vijitha S. Vempuluru, Anasua Ganguly Kapoor, Swathi Kaliki, Sai Divya Jajapuram, Ashik Mohamed & Dilip K. Mishra
To identify morphological parameters aiding clinical differentiation of conjunctival intraepithelial neoplasia (CIN) and invasive squamous cell carcinoma (iSCC) and to demonstrate the utility of image processing software to objectively assess ocular surface squamous neoplasia (OSSN).
This retrospective case series included all biopsy-proven cases of OSSN presenting as an ocular surface nodule. Based on histopathology, lesions were classified as CIN and iSCC. Clinical image analysis utilized ‘Contour’ and ‘ImageJ’ software. The effect of predictors demography, seropositivity, lesion dimensions, keratin, pigmentation, corneal involvement, vascularity and feeder vessels on the final histopathologic grade were assessed.
A total of 108 OSSN lesions (74 CIN and 33 iSCC) were included. Mean age was 46.1 ± 17.2 years in CIN and 47.2 ± 13.9 years in iSCC. By univariate logistic regression analysis, significant predictors of iSCC were HIV seropositivity (p < 0.0001), maximum diameter (p = 0.003), perpendicular to maximum diameter (p = 0.003), height (p = 0.003), nodular morphology (p = 0.006) and feeder vessels (p = 0.03), whereas gelatinous morphology (p = 0.02) was predictor of CIN. By multiple logistic regression, seropositivity was the predictor of iSCC (p < 0.0001, OR 13.33 ± 8.35, 95% CI 3.90–45.53).
HIV seropositivity is an important predictor of iSCC. Large, thick, nodular lesions with feeder vessels may favor the diagnosis of iSCC, whereas gelatinous, small, flatter lesions without feeder vessels may favor CIN. In a first of its kind study, simple and objective analysis of OSSN with image processing software was demonstrated.
Carol L Shields, Alexandru B Constantinescu, Sefy A Paulose, Antonio Yaghy, Lauren A Dalvin, Jerry A Shields, Sara E Lally
Purpose: The aim of this study was to evaluate tumor control of OSSN with topical IFNα2b alone based on tumor configuration (flat versus (vs.) dome-shaped). Methods: Retrospective, nonrandomized, interventional cohort study on 64 consecutive tumors in 63 patients with OSSN treated with topical IFNα2b. Topical IFNα2b (1 million international units/cc) was compounded and provided by the Thomas Jefferson University Hospital Pharmacy to be refrigerated and applied 4 times daily until biomicroscopic evidence of tumor resolution was observed. Results: The tumor configuration was flat (n = 15, 23%) or dome-shaped (n = 49, 77%). A comparison (flat vs. dome-shaped) revealed dome-shaped with older mean patient age at presentation (62 vs. 70 years, P = 0.04), greater patient history of smoking (13% vs. 42%, P = 0.04), greater corneal involvement (7% vs. 82%, P < 0.001), larger mean basal diameter (5.5 vs. 12.4 mm, P = 0.001) and mean thickness (1.9 vs. 4.3, P = 0.002), and longer mean duration IFNα2b therapy (3.7 vs. 6.3 months, P = 0.002). There was no difference in mean follow-up time (22.2 vs 23.1 months) or time to complete response (5.0 vs. 6.1 months). There was no difference in achievement of complete tumor control with IFNα2b alone (93% vs. 96%). There were no cases with metastasis or death. Conclusion: Topical IFNα2b alone shows excellent overall tumor control of 95% with no difference in efficacy based on tumor configuration.
Stéphanie Lemaître, MD, PhD; Gordon Hay, BSc(Hons), MBBS; Amit Arora, MBBS
A 76-year old woman presented with an increasingly gelatinous lesion located on the nasal conjunctiva of the left eye (Figure, A), which had originally been discovered 6 months before as a white spot. She had no relevant ocular or medical history. A clinical diagnosis of ocular surface squamous neoplasia was made, and she was listed for an excisional biopsy with cryotherapy. No topical or systemic medication was commenced. The patient returned to the clinic before the planned surgery (35 days after the first visit), and it was noted then that the lesion had disappeared spontaneously (Figure, B), before histopathologic confirmation of the clinical diagnosis of ocular surface squamous neoplasia was made.
Yadav S. · Gupta N. · Singh R. · Patil M. · Meel R. · Vanathi M. · Kashyap S. · Tandon R.
Objective: To evaluate the adjunctive role of conjunctival autofluorescence in the management of ocular surface squamous neoplasia (OSSN). Materials and Methods: Seventeen patients with clinically diagnosed OSSN were included. Morphological characteristics, type of OSSN, and autofluorescence photographs of the lesion were captured. Presence and area of conjunctival ultraviolet autofluorescence (CUVAF) were the main outcome measures. Results: Overall, 17 patients with 15 (88%) primary and 2 (12%) recurrent OSSN were included. Common locations were temporal (n = 10), nasal (n = 5), and diffuse variety (n = 2). Morphologically, there were 4 (22.2%) nodular, 4 (22.2%) leucoplakic, 3 (16.7%) gelatinous, and 1 (5.5%) each of papillary, nodulo-ulcerative, and diffuse variety. Mixed morphology was present in 4 eyes (22.2%). Sixteen of 18 eyes (88.9%) with OSSN displayed autofluorescence on CUVAF images. The mean area of CUVAF was 15.82 mm2 (10.77–19.59 mm2). Autofluorescence was reported in 8 eyes (44.4%) which had negative reports on impression cytology. Conclusions: Conjunctival autofluorescence was seen in the majority of cases with OSSN, in spite of negative cytology reports. Our study demonstrates that CUVAF may serve as an effective ancillary, non-invasive, and resource-friendly tool for supplementing the clinical diagnosis of OSSN, especially in diffuse and recurrent lesions that are not amenable to surgical intervention.
Swathi Kaliki, Anthony V Das
PURPOSE: To describe the epidemiology of ocular and periocular tumors in patients presenting to a multi-tier ophthalmology hospital network in India using the electronic medical records (EMRs) system. METHODS: A retrospective, observational, referral, hospital-based study of 1,142,098 patients. The data were collected using the in-house developed EyeSmart EMR system. RESULTS: During a 6-year study period, 9633 (0.8%) new patients were diagnosed with eye tumors. Of the 9633 patients, 5209 (54%) were male and 4424 (46%) were female. Of all tumors, 6372 (65%) were benign, 282 (3%) were pre-malignant, and 3089 (32%) were malignant in nature, respectively. Overall, the three most common tumors included retinoblastoma (n = 1167, 12%), ocular surface squamous neoplasia (n = 957, 10%), and conjunctival nevus (n = 903, 9%). The three most common benign tumors included conjunctival nevus (n = 903, 9%), eyelid nevus (n = 358, 4%), and orbital dermoid cyst (n = 344, 4%). The three most common malignant tumors included retinoblastoma (n = 1167, 12%), ocular surface squamous neoplasia (n = 957, 10%), and sebaceous gland carcinoma (n = 202, 2%). The most common tumor in 0–10 years’ age group was retinoblastoma (n = 1163, 42%), 11–30 years was conjunctival nevus (n = 408, 16%), and > 30 years was ocular surface squamous neoplasia (n = 801, 17%), respectively. CONCLUSIONS: The present study results indicate the incidence and distribution of ocular and periocular tumors in a large cohort in India. Retinoblastoma is the most common tumor encountered in a referral-based comprehensive ophthalmic oncology practice in India. The use of EMRs enables to capture the structured information and big data analysis of the same.
Akshay Gopinathan Nair, Indumati Gopinathan, Vandana Jain
Ocular surface squamous neoplasia (OSSN) encompasses a variety of conjunctival and corneal epithelial tumors including dysplasia, carcinoma in situ, and invasive carcinoma. OSSN commonly affects the interpalpebral conjunctiva and typically arises from the nasal limbus as a solitary growth. It is generally believed that these tumor cells originate from dysfunctional limbal stem cells that have been altered by various mutagenic agents, such as UV radiation; however, these lesions can also be seen to extend across the limbus to involve the cornea. Rarely, OSSN may be seen to arise from atypical locations such as the palpebral conjunctiva.,, In addition, there have been documented cases of squamous cell carcinoma of the lacrimal sac and canaliculus presenting as punctal masses and canaliculitis as well.,, To the best of our knowledge, there has been no previous documented case of conjunctival squamous cell carcinoma presenting as an isolated peri-punctal mass with no involvement of the lacrimal sac. This study was adherent with the tenets of the Declaration of Helsinki.