Martina C Herwig-Carl, Hans E Grossniklaus, Philipp L Müller, Lisa Atzrodt, Karin U Loeffler, Claudia Auw-Haedrich
Aims To systematically describe the clinical and histopathological features of a case series of conjunctival carcinomatous lesions underlying as—and also masquerading—pyogenic granuloma.
Methods Nine cases of conjunctival carcinomatous lesions underlying a pyogenic granuloma (which were clinically predominant) were retrospectively identified. Patients’ records were analysed for demographic data, clinical appearance and the postoperative course. Formalin-fixed paraffin-embedded specimens were routinely processed and stained with H&E and periodic acid-Schiff. Immunohistochemical stains for cytokeratin were performed in selected cases.
Results All nine tumours were located in the conjunctiva (bulbar, tarsal, limbal conjunctiva) of patients between 44 and 80 years. The lesions exhibited clinical features of pyogenic granuloma which dominated the clinical appearance. Additional features comprised a papillomatous appearance of the adjacent conjunctiva, a more whitish aspect of the lesion and a history of squamous cell carcinoma (SCC) respectively surgery for other entities. Histopathological analysis revealed a carcinomatous lesion (conjunctival intraepithelial neoplasia or SCC) at the base of a classic pyogenic granuloma in all nine cases. Surgical removal (R0 resection) was performed. Three cases received adjuvant mitomycin C or interferon α2b treatment. Two lesions locally recurred within 2 years after initial presentation.
Conclusion Carcinomatous lesions may be accompanied by a pyogenic granuloma which may dominate the clinical pictures. As the tumour is usually located at the base of the lesion, a complete surgical excision followed by histopathological analysis is mandatory for each lesion appearing as conjunctival pyogenic granuloma.
Lily Zhang BS, Carolina Mercado MD, Anat Galor MD, MSPH, Edward J. Holland MD, Gaofeng Wang PhD & Carol L. Karp MD
Purpose: Few studies have described ocular surface squamous neoplasia (OSSN) and its association with atopic diseases and there is no consensus on the course of OSSN in atopic patients. We thereby report three patients with atopy and OSSN.
Methods: Retrospective case series.
Results: Three male patients with mean age of 73 presented with OSSN and history of atopy treated with immunosuppressant therapy. Their histories included atopic dermatitis and keratoconjunctivitis. All patients had treatment complicated by multiple surgeries, recurrences, or advanced disease. The patients initially received medical treatment with topical interferon-alpha-2b (IFNα2b). However, all the patients had recurrences and required modification of treatment including topical 5-fluorouracil (5-FU).
Conclusion: We report on three patients with a history of atopy whose OSSN presentation and course was challenging. Overall, our cases responded better to topical 5-fluorouracil compared to topical interferon-alpha-2b, but recurrences were common. These patients may benefit from more aggressive and long-term treatment.
Nandini Venkateswaran, Carolina Mercado, Anat Galor, Carol L. Karp
To compare the efficacy of topical 5-fluorouracil 1% (5FU) and interferon alfa-2b 1 MIU/mL (IFN) eye drops as primary treatment modalities for ocular surface squamous neoplasia (OSSN).
Retrospective, comparative, interventional case series.
Fifty-four patients who received 5FU and 48 patients who received IFN as primary therapy for OSSN were included. Primary outcome measures were the frequency of clinical resolution and time to OSSN recurrence by treatment modality. Secondary outcome was the frequency of side effects with each therapy.
The mean age of patients was 68 years. More Hispanics were treated with 5FU. In a univariable analysis, frequency of OSSN resolution was higher with 5FU (96.3%, n = 52) than with IFN (81.3%, n = 39), P = .01. In a multivariable analysis, treatment modality did not remain a significant predictor of resolution. In patients whose OSSN resolved, time to resolution was similar with both agents, (5FU mean 6.6 months, standard deviation (SD) 4.5 vs IFN mean 5.5 months, SD 2.9, P = .17). Of the 52 eyes whose OSSN resolved with 5FU, 11.5% of lesions (n = 6) recurred, whereas of the 39 eyes whose OSSN resolved with IFN, 5.1% of lesions (n = 2) recurred, P = .46. Kaplan-Meier survival curves of OSSN recurrence were similar between groups (log-rank = 0.16). One-year recurrence rates were 11.4% with 5FU and 4.5% with IFN. Eyelid edema (P = .04) and tearing (P = .02) were more significant with 5FU.
This is the first direct comparison study between 5FU and IFN eye drops as primary treatment modalities for OSSN. Both modalities resulted in a high frequency of tumor resolution and low recurrence rates and are effective treatment options for OSSN.
Mohammad Javed Ali, Swati Singh, Anasua Ganguly, Milind N. Naik
Canalicular papillomatosis is a rare disorder characterized by a mass lesion arising from the epithelium as a stalk from one of the canalicular walls. Traditionally, they have been treated with an open canaliculotomy and excision biopsy with or without additional cryotherapy. A patient with upper canalicular squamous papillomas treated with dacryoendoscopy-guided transcanalicular intralesional and topical interferon alpha 2b is presented, and the ineffectiveness of interferons in this case is discussed.
Patel H. · Jeang L.J. · Shah A. · Espana E.M. · Margo C.E.
Purpose: To emphasize the importance of staging ocular surface squamous neoplasia when contemplating use of topical interferon alpha-2b alone. Cases: Two patients with 360 degrees of limbal involvement. Results: Two patients with in situ squamous cell carcinoma of the conjunctiva and clinical involvement of the entire limbus were treated with topical interferon alpha-2b. Thorough examination and multiple biopsies excluded invasive disease. The patients had complete response to therapy. Conclusion: Widespread intraepithelial squamous neoplasia involving the entire limbus can be successfully treated with topical therapies. Biopsy plays a role in excluding invasive disease. Interferon alpha-2b is a preferable agent to start with because it is well tolerated. Since long-term risks of recurrence are unknown, appropriate monitoring is essential.
Sonal S Chaugule, Jennifer Park, Paul T Finger
Purpose: The purpose of this study is to report on the efficacy and safety of topical chemotherapy alone for giant ocular surface squamous neoplasia (OSSN). Methods: In this retrospective, interventional series, 10 eyes with giant OSSN underwent exfoliative biopsy to confirm the diagnosis followed by application of interferon alpha 2b (IFN α2b) and/or 5 fluorouracil, 1% (5FU). Reported outcome measures were tumor response, visual acuity, recurrence, systemic metastasis, and treatment complications. Results: Ten patients (3 female, 7 male) had a mean age of 73 (median, 69; range 40–89) years. Mean tumor diameter was 13.1 (median, 12.3; range 8.2–19.4) mm. Five (50%) eyes were treated with IFN-α2b alone; 1 (10%) with 5-FU alone and 4 (40%) required both IFN-α2b and 5-FU. The mean duration of treatment was 3, 0.5, and 6.4 months for IFN-α2b alone, 5-FU alone, and both IFN-α2b and 5-FU respectively. Complete tumor response was observed in all 10 cases at mean follow-up of 12.8 (median, 11.5; range, 3–25) months. Complications noted were transient irritation and burning (n = 4), dry eyes (n = 2), and transient flu-like symptoms (n = 2). There was no evidence of chemotherapy-related symblepharon, stem cell deficiency, scleral thinning, or corneal opacity. There were no tumor recurrences, and no patient required surgical excision or cryotherapy. Conclusion: Topical chemotherapy was a safe and effective treatment, inducing complete regression in all cases of giant OSSN in this series. There were no sight-limiting complications.
Singh, Swati; Mittal, Ruchi; Rath, Suryasnata
A 64-year-old healthy female presented with a papillomatous limbal lesion involving 6 clock hours of superior limbus and diffuse involvement of upper tarsal conjunctiva of left eye of 6 months duration. Excision of superior limbal lesion on histopathology showed carcinoma in situ with focal breach in basement membrane and moderate degree of differentiation. The surgical base and margins were uninvolved. The tarsal lesion was initially treated with subconjunctival interferon alpha 2b (IFN alpha 2b) (3 cycles of IFN alpha 2b) with poor response. Subsequently treatment with topical mitomycin C 0.04% showed a dramatic response in the upper eyelid tarsal lesion. A small residual lesion needed excision. One year after treatment, she was completely tumor-free. In multifocal ocular surface squamous neoplasia, multimodal treatment with excision and topical mitomycin C may be effective in cases refractory to immunotherapy.
Rachna Meel, Rebika Dhiman, Murugesan Vanathi, Neelam Pushker, Radhika Tandon, Saranya Devi
Purpose: The aim is to study the clinicodemographic profile and treatment outcome of ocular surface squamous neoplasia (OSSN). Methods: This was a retrospective observational study of 57 eyes (56 cases) with clinically diagnosed OSSN, presenting in our center over the past year. Results: The median age of presentation was 55 years with male:female ratio being 4.5:1. Systemic predisposing conditions were xeroderma pigmentosa (1) postkidney transplant immunosuppression (1), and human immunodeficiency virus infection (1). Patients with predisposing conditions had a younger median age of onset (33 years). The majority of tumors were nodular (61.4%), gelatinous (61.4%), and had limbal involvement (96%). On ultrasound biomicroscopy (UBM), mean tumor height was 2.93 ± 1.02 mm, and intraocular extension was evident in seven eyes. OSSN with intraocular extension had a mean tumor height of 4.3 ± 1.32 mm. Nodal metastasis was seen in one case at presentation. As per American Joint Committee for Cancer Classification seventh edition staging-two cases were T1, one was T2, 46 were T3 and eight were T4. Treatment advised included conservative therapy for 39; wide local excision (4 mm margin clearance) with cryotherapy for seven; enucleation in four; and exenteration in four eyes. Overall, complete regression was achieved in 88% of cases during a mean follow-up of 13.5 ± 4.6 months. Recurrence was seen in three cases, which were treated with exenteration, radical neck dissection, and palliative chemo-radiotherapy, respectively. Conclusion: Although associated with old age, earlier onset of OSSN is seen in patients with systemic predisposing conditions. Thicker tumors in the setting of a previous surgery or immunocompromised status should be considered high-risk features for intraocular extension and should be evaluated on UBM.
Santosh G Honavar
Proposed by Lee and Hirst, the phrase ocular surface squamous neoplasia (OSSN) includes the clinical continuum of mild, moderate, and severe dysplasia, carcinoma in situ, and invasive squamous cell carcinoma (SCC). It is important to understand that dysplasia and carcinoma in situ, together constituting conjunctival intraepithelial neoplasia (CIN), are premalignant by definition, and SCC is malignant. Despite OSSN being one of the most common premalignant and malignant lesions of the ocular surface, confusion prevails regarding its basic nomenclature……
Iku Kikuchi, Satoru Kase, Kan Ishijima, Susumu Ishida
The purpose of this study was to report the clinical outcomes of patients with conjunctival melanoma treated with interferon (IFN) α-2b eye drops following local tumor resection.
Five eyes of five patients were enrolled in this study. All patients underwent the local resection of tumors, and topical IFNα-2b eye drops were subsequently administered 4 times/day until the complete disappearance of the pigmented lesions determined by slit-lamp examination. Ophthalmological findings, histopathological findings, and imaging modalities were retrospectively analyzed.
The age of the patients ranged from 65 to 84 years (mean: 75.4 years). Locations of the tumor were the bulbar conjunctiva in three eyes, multiple palpebral conjunctivas in one eye, and palpebral conjunctiva and caruncle in one eye. All patients received topical IFNα-2b eye drop treatment for 6–10 months. Follow-up periods after resection ranged from 18 to 78 months. Histologically, all excised conjunctival tumors were diagnosed with malignant melanoma, where the surgical margins were completely negative in one patient. No patients had suffered from severe adverse effects related to IFNα-2b. Four out of five patients consequently achieved complete remission. Since one eye in one case showed resistance to the local chemotherapy containing IFNα-2b eye drops and the subconjunctival injection of IFN-β, orbital exenteration was eventually required 12 months after local resection.
Topical IFNα-2b eye drops may be safe and one of the useful adjunctive treatments following surgical resection for patients with conjunctival melanoma.