Validation of the Newly Proposed World Health Organization Classification System for Conjunctival Melanocytic Intraepithelial Lesions: A Comparison with the C-MIN and PAM Classification Schemes.

PURPOSE: We sought to compare the sensitivity, specificity, accuracy, and interobserver agreement of the two most commonly used classification systems for conjunctival melanocytic intraepithelial lesions with the new World Health Organization (WHO) classification. DESIGN: Retrospective case series and evaluation of classification systems. METHODS: We reviewed the pathology and medical records of all patients who underwent a primary biopsy procedure for conjunctival primary acquired melanosis (PAM) at Wills Eye Hospital between 1974 and 2002 who had ≥36 months of follow-up. Data collected included age, sex, clinical findings, recurrence, and progression to melanoma. Twelve ophthalmic pathologists analyzed scanned hematoxylin and eosin-stained virtual microscopic slides using 3 classification systems: PAM, conjunctival melanocytic intraepithelial neoplasia, and the WHO 4th edition classification of conjunctival melanocytic intraepithelial lesions. Observer agreement, sensitivity, specificity, and diagnostic accuracy of each classification system were assessed. RESULTS: There were 64 patients who underwent 83 primary excisions with cryotherapy for conjunctival PAM who had adequate tissue for histopathologic evaluation. The interobserver agreement in distinction between the low- and high-grade lesions was 76% for PAM, 67% for conjunctival melanocytic intraepithelial neoplasia, and 81% for WHO classification system. Low-grade lesions provided the greatest interpretative challenge with all 3 classification systems. The 3 classification systems had comparable accuracy of 81%-83% in their ability to identify lesions with potential for recurrence. CONCLUSIONS: This study highlights the comparable strengths and limitations of the 3 classification systems for conjunctival melanocytic intraepithelial lesions and suggests that the simplified WHO classification scheme is appropriate for evaluation of these lesions.

Prognostic factors for relapse and survival among patients with ocular adnexal lymphoma: validation of the eighth edition of the American Joint Committee on Cancer (AJCC) TNM classification.

BACKGROUND/AIMS: To validate the prognostic performance of the American Joint Committee on Cancer (AJCC) eighth edition classification for ocular adnexal lymphoma (OAL). METHODS: We performed a retrospective review of 140 consecutive patients treated for primary OAL between March 2010 and September 2017. Associations between T/N/M categories at presentation and disease-related outcomes, including relapse, progression-free survival (PFS) and overall survival (OS) were evaluated. RESULTS: Seventy-nine women and 61 men (median age, 52 (range 20-84) years; median follow-up, 57 (range 7-131) months) were included. Histological subtypes included mucosa-associated lymphoid tissue lymphoma (92.1%, n=129), diffuse large B-cell lymphoma (5.0%, n=7), follicular lymphoma (1.4%, n=2) and mantle cell lymphoma (1.4%, n=2). Patients with ≥T2 disease had significantly higher risks of overall relapse (unadjusted HR)=4.32, p=0.016), decreased PFS (uHR=5.19, p=0.004) and decreased OS (uHR=9.21, p=0.047). Patients with ≥N1 disease had significantly higher risks of overall relapse (uHR=9.17, p<0.001) and decreased PFS (uHR=9.24, p<0.001). M1 disease was significantly associated with higher risks of overall relapse (uHR=3.62, p=0.036), decreased PFS (uHR=5.13, p=0.001) and decreased OS (uHR=9.24, p=0.013). On considering TNM categories as continuous data, the uHRs for per level increase in T, N and M categories were 1.77, 1.83 and 2.30 for overall relapse and 1.72, 1.87 and 2.78 for decreased PFS, respectively (p<0.05 for each comparison). CONCLUSION: The T, N and M categories of the AJCC eighth edition classification have prognostic value for relapse and survival among patients with primary OAL. Particularly, nodal/metastatic involvement at presentation indicated less favourable outcome.

MACE RNA sequencing analysis of conjunctival squamous cell carcinoma and papilloma using formalin-fixed paraffin-embedded tumor tissue.

Recent advances in the field of biomedical research allow for elucidation of the transcriptional signature of rare tumors such as conjunctival squamous cell carcinoma (SCC). In this study we compare its expression profile to conjunctival papilloma (Pap) and healthy conjunctival tissue (Ctrl) and develop a classification tool to differentiate these entities. Seven conjunctival SCC, seven Pap and ten Ctrl were formalin-fixed and paraffin-embedded (FFPE) and analyzed using Massive Analysis of cDNA Ends (MACE) RNA sequencing. Differentially expressed genes (DEG) and gene ontology (GO) clusters were explored and the abundance of involved cell types was quantified by xCell. Finally, a classification model was developed to distinguish SCC from Pap and Ctrl. Among the most prominent DEG in SCC a plethora of keratins were upregulated when compared to Pap and Ctrl. xCell analysis revealed an enrichment of immune cells, including activated dendritic cells and T-helper type 1 cells (Th1), in SCC when compared to Ctrl. The generated classification model could reliably discriminate between the three entities according to the expression pattern of 30 factors. This study provides a transcriptome-wide gene expression profile of rare conjunctival SCC. The analysis identifies distinct keratins, as well as dendritic and Th1 cells as important mediators in SCC. Finally, the provided gene expression classifier may become an aid to the conventional histological classification of conjunctival tumors in uncertain cases.

Conjunctival 'mucoepidermoid carcinoma' revisited: a revision of terminology, based on morphologic, immunohistochemical and molecular findings of 14 cases, and the 2018 WHO Classification of Tumours of the Eye.

In 2018, the consensus meeting for the WHO Classification of Tumours of the Eye decided that conjunctival mucoepidermoid carcinoma should be reclassified as adenosquamous carcinoma, as this represented a better morphological fit. To examine the applicability of this terminology, we studied the clinical, histopathological, immunohistochemical and molecular pathology of 14 cases that were originally diagnosed as conjunctival mucoepidermoid carcinoma. There were 7 (50%) females and 7 (50%) males. The median age was 64 years. The left eye was affected in 8 and the right eye in 6 patients. In-situ carcinoma was present in 11/14 (79%) cases and comprised in-situ squamous cell carcinoma (SCC) and conjunctival intraepithelial neoplasia with mucinous differentiation (CIN-Muc). Invasive carcinoma was present in 11/14 (79%) cases. Group 1 (1/11 cases, 9%) comprised invasive SCC only. Group 2 (6/11 cases, 55%) comprised SCC with mucinous differentiation, manifesting as scattered intracellular mucin, occasionally together with intercellular mucin, with no evidence of true glandular differentiation. Group 3 (3/11 cases. 27%) comprised true adenosquamous carcinoma. Group 4 (1/11 cases, 9%) comprised pure adenocarcinoma. Thirteen of 14 cases (93%) underwent FISH for MAML2 translocation and none were rearranged. Two cases harboured high-risk HPV (type 16 and 18). The combined findings confirm that all lesions in our study were not mucoepidermoid carcinoma, but represented predominantly SCC with mucinous differentiation and adenosquamous carcinoma. We, therefore, recommend future revision of the WHO classification to include SCC with mucinous differentiation alongside adenosquamous carcinoma.

Analysis of HSP90 Expression Is Valuable in the Differential Diagnosis of Ocular Surface Squamous Lesions.

OBJECTIVES: The aim of this study was to evaluate heat shock protein 90 (HSP90) expression in squamous lesions (SLs) and to assess its diagnostic value for different lesions within the SL spectrum. METHODS: A total of 70 conjunctival SLs, including 19 papillomas, 22 cases of conjunctival intraepithelial neoplasia (ConINs) I, 11 cases of ConIN II, six cases of ConIN III, and 12 squamous carcinomas (sqCAs), were evaluated using the German immunoreactive score against HSP90. RESULTS: Cytoplasmic HSP90 expression differed between low- and high-grade lesions (P < .001). Among high-grade lesions, the nuclear HSP90 score was higher in the ConIN III-sqCA group than in the ConIN II group (P = .0162). A percentage of total thickness staining of less than 73% differentiated between ConIN III and sqCA. CONCLUSIONS: The expression of HSP90 is particularly useful to differentiate low-grade from high-grade lesions of the conjunctiva. HSP90 may play an important role in the malignant transformation of SLs and could be a new target for therapy.

Conjunctival Primary Acquired Melanosis: Is It Time for a New Terminology?

PURPOSE: To review the diagnostic categories of a group of conditions referred to as "primary acquired melanosis." DESIGN: Literature review on the subject and proposal of an alternative diagnostic schema with histopathologic and immunohistochemical illustrations. METHODS: Standard hematoxylin-eosin-stained sections and immunohistochemical stains for MART-1, HMB-45, microphthalmia-associated transcription factor (MiTF), and Ki-67 for calculating the proliferation index are illustrated. RESULTS: "Melanosis" is an inadequate and misleading term because it does not distinguish between conjunctival intraepithelial melanin overproduction ("hyperpigmentation") and intraepithelial melanocytic proliferation. It is recommended that "intraepithelial melanocytic proliferation" be adopted for histopathologic diagnosis. Atypical proliferations are characterized either by bloated dendritic melanocytes with enlarged cell components (dendrites, cell bodies, and nuclei) or by epithelioid melanocytes without dendrites. Atypical polygonal or epithelioid pagetoid cells may reach higher levels of the epithelium beyond the basal layer. Immunohistochemistry defines the degree of melanocytic proliferation or the cellular shape (dendritic or nondendritic) (MART-1, HMB-45) or identifies the melanocytic nuclei (MiTF). Intraepithelial melanocytic proliferation without atypia represents increased numbers of normal-appearing dendritic melanocytes (hyperplasia or early neoplasia) that generally remain confined to the basal/basement membrane region. Intraepithelial nonproliferative melanocytic pigmentation signifies the usually small number of conjunctival basal dendritic melanocytes that synthesize increased amounts of melanin that is transferred to surrounding keratinocytes. CONCLUSION: All pre- and postoperative biopsies of flat conjunctival melanocytic disorders should be evaluated immunohistochemically if there is any question regarding atypicality. This should lead to a clearer microscopic descriptive diagnosis that is predicated on an analysis of the participating cell types and their architectural patterns. This approach is conducive to a better appreciation of features indicating when to intervene therapeutically. An accurate early diagnosis should forestall unnecessary later surgery.

Comparison of American Joint Committee on Cancer TNM-based staging system (7th edition) and Ann Arbor classification for predicting outcome in ocular adnexal lymphoma.

OBJECTIVE: To compare the TNM and Ann Arbor staging systems in predicting outcome in ocular adnexal lymphoma (OAL). METHODS: Retrospective review of the clinical, imaging and histopathologic records of OALs between 1986 and 2009. Outcome measures included local recurrence and progression. RESULTS: One hundred and sixty patients of OAL were included. Mean age was 65 ± 15 years (range 20-97) and 68 (43%) were male. The median follow-up of all OAL patients was 65 months (range 2.5-238). Histopathology identified low-grade, indolent B-cell lymphomas in 140 patients (87.5%) and rest had aggressive grades. Of 134 indolent OAL patients, those with unilateral disease had a 10-year progression free survival of 72% versus 48% in their bilateral counterparts (p = 0.001). Amongst unilateral OAL patients staged within the T1-2 group, a significantly better outcome was noted for patients without nodal or metastatic involvement compared to those with such involvement (p = 0.0001). The above observations helped to formulate a simple scoring system to prognosticate OALs based on their laterality and node/metastatic status. Amongst the 3 groups identified, group 1 with a score of 0 (unilateral OALs with no nodes or metastasis) had a 10-year progression free survival of 75%; group 2 with score 1 (either bilateral or positive nodes/metastasis) 50% and group 3 with score 2 (both bilateral OAL with positive nodes/metastasis) zero at 10 years (p < 0.00001). CONCLUSIONS: The TNM-based staging system better predicts outcome in OAL than the Ann Arbor system primarily by delineation of bilateral disease and nodal/metastatic involvement at presentation.

Interferon for ocular surface squamous neoplasia in 81 cases: outcomes based on the American Joint Committee on Cancer classification.

PURPOSE: To assess the efficacy of interferon alpha-2b (IFNα2b) in the management of ocular surface squamous neoplasia (OSSN). METHODS: This is a retrospective, nonrandomized interventional case series study of 80 patients with 81 tumors treated with IFNα2b eye drops and/or injection combined with surgical excision when necessary. The main outcome measure was complete response or partial response based on the American Joint Committee on Cancer classification. RESULTS: The OSSN was classified as Tis (n = 10, 12%), T1 (n = 13, 16%), T2 (n = 6, 7%), T3 (n = 51, 63%), and T4 (n = 1, 1%). IFNα2b was used as immunotherapy alone (n = 22, 27%) or combined with surgery (n = 59, 73%). Overall (n = 81), complete response was achieved in 90% Tis, in 100% T1, in 100% T2, in 94% T3, and in 100% T4. Specifically for immunotherapy (n = 22), IFNα2b alone achieved complete response in 75% (3/4) Tis, in 100% (8/8) T1, and in 70% (7/10) T3. Planned IFNα2b plus surgery (n = 59) achieved control in 100% (6/6) Tis, in 100% (5/5) T1, in 100% (6/6) T2, in 100% (41/41) T3, and in 100% (1/1) T4. Tumor recurrence was noted in 5% (4/81) of cases over a median follow-up of 1 year. Ocular side effects included conjunctival hyperemia (n = 4, 5%), ocular irritation (n = 3, 4%), superficial punctate keratitis (n = 3, 4%), and conjunctival follicles (n = 1, 1%). Systemic side effects included postinjection flu-like syndrome for 1 day (n = 7, 9%). CONCLUSIONS: IFNα2b, when appropriately combined with surgical excision for OSSN, provides complete control in 95% of cases overall, specifically in 90% Tis, in 100% T1, in 100% T2, in 94% T3, and in 100% T4.

Fluorescence in situ hybridisation (FISH) in histologically challenging conjunctival melanocytic lesions.

BACKGROUND: Even in experienced hands, the classification of some melanocytic lesions of the conjunctiva remains challenging. In skin pathology, the recent application of fluorescence in situ hybridisation (FISH) has been demonstrated to be of use for the analysis and diagnosis of ambiguous melanocytic neoplasms of the skin. This study set out to evaluate this method on seven prospective conjunctival cases that were histologically equivocal. METHODS: 18 unequivocal retrospective melanocytic controls were exposed to FISH. Commercially available probes assessing copy numbers of RREB1 (6p25), MYB (6q23) and CCND1 (11q13) genes compared with CEP6 (a chromosome six centromeric reference point) were used. After control verification, seven prospective, equivocal cases were identified and exposed to FISH. RESULTS: There was complete correlation between FISH result and the control section histopathology report. Control cases of melanoma cases were all positive for FISH and control benign lesions were negative. Of the seven equivocal cases, five were positive and classed as invasive melanoma or melanoma-in situ, one was negative and one tetraploid, classed as negative (these last two cases were classed as naevi with careful clinical observation). CONCLUSIONS: FISH is very useful in classifying equivocal conjunctival melanocytic lesions, especially those with atypical junctional activity and naevoid melanocytic proliferations of the conjunctiva.

Conjunctival melanoma and melanocytic intra-epithelial neoplasia.

The rarity of conjunctival melanoma has impeded progress in the management of patients with this cancer; however, much progress has occurred in recent years. Primary acquired melanosis is now differentiated histologically into hypermelanosis and conjunctival melanocytic intra-epithelial neoplasia, for which an objective reproducible scoring system has been developed. Mapping and clinical staging of conjunctival disease has improved. Adjunctive radiotherapy and topical chemotherapy have made tumour control more successful, with reduced morbidity. Genetic analyses have identified BRAF and other mutations, which may predict responsiveness to new chemotherapeutic agents, for example Vemurafenib, should metastatic disease develop. Multicentre studies are under way to enhance survival prediction by integrating clinical stage of disease with histological grade of malignancy and genetic abnormalities. Such improved prognostication would not only be more relevant to individual patients, but would also provide greater opportunities for basic science research.

Pattern of conjunctival masses seen at Guinness Eye Centre Luth Idi-Araba.

BACKGROUND: Conjunctival masses are growth on the surface of the outer eye; which may represent benign or malignant transformations. OBJECTIVE: To determine the pattern of presentation of conjunctival masses at the Guinness Eye Centre (GEC), Lagos University Teaching Hospital (LUTH) Idi-Araba over a 13 year period (Jan 1995-Dec 2007). METHOD: A retrospective review of the clinical notes of all patients that presented to GEC with conjunctival masses during the study period was carried out. The bio-data, clinical features, stage, laterality and associated features of the masses were noted. The diagnosis, treatment and complications of treatment were also recorded. RESULTS: Case notes of 612 eyes of 393 patients were included in the study. There were 219 (55.7%) males, 174 (44.3%) females with ages ranging from 4-85 years with a male to female ratio of 1.26: 1. Three hundred and eighty-eight patients (98.7%) presented as elective cases to the outpatient department while 5 (1.3%) presented as emergencies on account of associated ocular inflammation. There were 220 (56%) bilateral masses while 44% were uniocular. Pterygium was the leading conjunctival mass affecting 548 eyes (89.5%) of 329 patients. Pingueculae occurred in 53 eyes (8.7%), conjunctival cysts in 5 (0.8%) eyes, neoplastic growths in 3 (0.5%) eyes, conjunctival granulomas in 2 (0.3%) eyes and limbal teratoma in 1 (0.2%) eye. Most of these patients defaulted from surgery as only 141 eyes (23%) of 121 patients had surgery. Post-operative complications occurred in 33 eyes (5.4%) of 30 patients. The commonest postoperative complication was pterygium recurrence which occurred in 18 eyes of 15 patients. CONCLUSION: Pterygium was the commonest conjunctival mass and preventive strategies need to be advocated. Prevention of recurrence remains a challenge in the management of pterygium as recurrence after surgical excision occurred in 13.2% of eyes. Our study however did not confirm outdoor occupations as a risk factor for pterygium.

American Joint Committee on Cancer (AJCC) clinical classification predicts conjunctival melanoma outcomes.

PURPOSE: The aim of this study was to evaluate conjunctival melanoma outcomes based on American Joint Committee on Cancer classification. The study design constituted a nonrandomized interventional case series. METHODS: This was a retrospective chart review comprising 343 participants, and the main outcome measures were melanoma local recurrence, lymph node metastasis, distant metastasis, and death. RESULTS: On the basis of the American Joint Committee on Cancer classification (seventh edition), conjunctival melanoma was classified as T1 (196 [57%]), T2 (110 [32%]), T3 (37 [11%]), and T4 (0). The mean tumor basal diameter increased with tumor staging with 8.5 mm for T1, 12.7 mm for T2 (p = 0.0003), and 16 mm for T3 (p < 0.0001). The melanoma arose from primary acquired melanosis (T1 = 71%; T2 = 84%; T3 = 81%), preexisting nevus (T1 = 8%; T2 = 5%; T3 = 3%), or de novo (T1 = 21%; T2 = 12%; T3 = 16%). Outcomes at 5 years (Kaplan-Meier) revealed melanoma local recurrence/new tumor in 44% T1, 78% T2 (p < 0.0001), and 76% T3 (P=0.0044); regional lymph node metastasis in 17% T1, 52% T2 (p < 0.0001), and 49% T3 (p = 0.0092); melanoma-related distant metastasis in 11% T1, 35% T2 (p < 0.0001), and 42% T3 (p = 0.0018); and melanoma-related death in 5% T1, 20% T2 (p = 0.0655), and 23% T3 (p = 0.0526). Based on American Joint Committee on Cancer classification, factors predictive of melanoma recurrence included T2 stage (p < 0.0001), and T3 stage (p = 0.0061). After adjusting for tumor origin, factors predictive of regional lymph node metastasis, melanoma-related distant metastasis, and melanoma-related death included melanoma arising de novo (p < 0.0001; p < 0.0001; p < 0.0001), T2 stage (p < 0.0001; p < 0.0001; p = 0.007), and T3 stage (p = 0.005; p = 0.0014; p = 0.0342). CONCLUSION: The American Joint Committee on Cancer staging predicts prognosis of conjunctival melanoma. Melanoma classified as T2 and T3 (compared with T1) showed significantly higher rates of local recurrence, regional lymph node metastasis, distant metastasis, and death.

Clinicopathologic correlation of ocular surface squamous neoplasms at Bascom Palmer Eye Institute: 2001 to 2010.

PURPOSE: To describe the clinical and histologic characteristics of ocular surface squamous neoplasia (OSSN) lesions and provide clinicopathologic correlation to determine clinical features that may indicate higher-grade lesions. DESIGN: Retrospective case series. PARTICIPANTS: A total of 612 consecutive OSSN lesions sent to the Bascom Palmer ocular pathology laboratory from January 1, 2001 to September 20, 2010. METHODS: Pathologic examination of lesions by a single experienced ocular pathologist (S.R.D.). Review of pathology records and patient charts. MAIN OUTCOME MEASURES: Correlation of clinical factors and histology of higher-grade OSSN. RESULTS: Over the studied period, 33% of submitted specimens were characterized as mild, moderate, or severe dysplasia; 52% were classified as carcinoma in situ; and 11% were graded as squamous cell carcinoma. Characteristics associated with higher-grade OSSN lesions included male gender, biopsy at Bascom Palmer Eye Institute, temporal and superior locations, lack of corneal involvement, papillomatous and nodular appearance, microscopic multifocality, and positive margins on biopsy. CONCLUSIONS: Certain clinical factors are associated with higher-grade histologic lesions. These findings may help clinicians more accurately evaluate and anticipate the pathologic grade of conjunctival and corneal lesions suspected to be OSSN.

Predictive value of the seventh edition American Joint Committee on Cancer staging system for conjunctival melanoma.

OBJECTIVE: To evaluate the predictive value of the seventh edition American Joint Committee on Cancer (AJCC) staging system for conjunctival melanoma. METHODS: Retrospective, observational case series of 42 eyes of 42 patients with conjunctival melanoma studied by reviewing medical records, pathology reports, and color photographs. The main evaluated outcomes were demographic information, laterality, tumor size, thickness, pathologic diagnosis, seventh edition AJCC stage (clinical and pathologic), recurrence, metastasis, and duration of follow-up. RESULTS: There was no sex preference, and the median age was 61 years. Recurrent disease was noted in 33% of patients (n = 14 of 42), with 64% occurring at a median of 2.5 years (range, 1-5 years) after primary treatment. Metastasis was noted in 19% of patients. The significant predictive factors for high risk of tumor recurrence were tumors involving more than 1 quadrant (P = .02), tumors thicker than 0.5 mm (P = .04), and tumor multifocality (P = .04). The significant predictive factors for high risk of tumor metastasis were tumors thicker than 0.5 mm (P = .005), tumor invasiveness (P = .04), pathologic diagnosis of conjunctival melanoma rather than melanoma in situ (P = .04), and tumor recurrence (P < .001). Similarly, increasing AJCC T stages (clinical and pathologic) were associated with unfavorable outcomes. For example, clinical stage-related recurrence rates were 19% (Tis), 27% (T1), 33% (T2), and 75% (T3). Clinical stage-related lymphatic and distant metastasis rates were 0% (Tis), 20% (T1), 0% (T2), and 63% (T3). CONCLUSIONS: Advanced AJCC T-stage (clinical and pathologic) tumors were at higher risk for recurrence and metastasis. In this study, the seventh edition AJCC staging system was predictive of local control and systemic spread of conjunctival melanoma.

Topical interferon alfa-2b for management of ocular surface squamous neoplasia in 23 cases: outcomes based on American Joint Committee on Cancer classification.

OBJECTIVE: To evaluate the efficacy of topical interferon alfa-2b in the management of ocular surface squamous neoplasia (OSSN). METHODS: Clinically visible OSSN in 20 patients (23 tumors) was managed with topical interferon alfa-2b, 1 million IU/mL, 4 times daily. Tumor control and complications were evaluated according to American Joint Committee on Cancer classification. RESULTS: Complete tumor resolution was achieved in 19 tumors (83%) following topical interferon alfa-2b treatment for a median period of 6 months (mean, 7 months; range, 1-12 months) and maintained for up to 24 months of follow-up. Of the 4 tumors with partial resolution (17%), tumor surface area was reduced 44% (median) during 4 months (median) without further response and alternative therapy was used. Based on American Joint Committee on Cancer classification, complete control was achieved in 2 of 3 Tis (67%), 17 of 20 T3 (85%), 19 of 23 N0 (83%), and 19 of 23 M0 (83%) category tumors. Tumors involving the cornea responded earlier compared with those without corneal involvement (P = .01). Initial tumor size did not correlate with time to response (P = .27). Recurrence was noted in 1 case (Tis, 4%) at 3 months. Adverse effects included conjunctival hyperemia (2 [10%]), follicular hypertrophy (2 [10%]), giant papillary conjunctivitis (1 [5%]), irritation (1 [5%]), corneal epithelial defect (1 [5%]), and flulike symptoms (1 [5%]); all resolved within 1 month of medication discontinuation. CONCLUSION: According to American Joint Committee on Cancer classification, complete control with topical interferon alfa-2b can be achieved in 67% of Tis, 85% of T3, and 83% of all OSSN.

Current appraisal of conjunctival melanocytic tumors: classification and treatment.

Conjunctival melanocytic tumors represent a spectrum of pigmented tumors that include benign, premalignant and malignant tumors. Conjunctival nevi are the most common pigmented tumors and are typically found in the interpalpebral bulbar conjunctiva. These lesions usually contain fine clear cysts on slit lamp biomicroscopy. Primary acquired melanosis includes lesions from increased melanin pigmentation without proliferation of melanocytes to melanoma in situ. In the new classification system, the idea is to use the term 'primary acquired melanosis' only as a clinical description, highlighting the fact that the biologic behavior of acquired melanotic lesions cannot be predicted solely based upon clinical grounds without histopathologic examination. Conjunctival melanoma represents only 5% of all melanomas arising in the ocular region and is associated with a high mortality rate. The management of primary acquired melanosis, nevi and conjunctival melanomas involves various modalities used either alone or concomitantly depending on the size and extent of the lesion.