Identification of novel RB1 genetic variants in Retinoblastoma patients and their impact on clinical outcome.

BACKGROUND: Retinoblastoma (RB) is an intraocular childhood cancer develops due to inactivation of RB1 gene. Identification of RB1 genetic variants, correlating and confirming genetic test results with clinical outcomes are crucial for effective RB management. METHODS: Retrospective study of 62 RB patients and 14 family members who underwent genetic testing either by next generation sequencing (NGS) or multiplex ligation-dependent probe amplification (MLPA) or by both for screening RB1 germline mutations present in peripheral blood. Mutational outcomes were correlated with clinical outcomes evaluated over a follow-up period of 12 months. RESULTS: Of the 62 patients, 35 (56%) had bilateral RB and 27 (44%) had unilateral RB. Out of 24 (52%) variants detected by NGS, 9 (37.5%) were novel and 15 (62.5%) were known in 46 probands. Six (18%) gross deletions were detected by MLPA in 34 probands. The mutation detection rate by NGS and MLPA in unilateral cases was 15% (n = 4) and 74% (n = 26) in bilateral cases. In patients with RB1 genetic mutations versus those without, the rate of primary enucleation (7 (12%) vs 18 (44%) eyes; p = .0008) was inversely proportional to tumor recurrence (25 (45%) vs 6 (15%) eyes; p = .002). There was no difference in the rate of globe salvage and metastasis, over a mean follow-up period of 12 months. CONCLUSION: The mutations screening is important for risk assessment in future siblings and offspring of RB patients and most important in unilateral RB for determining if hereditary or not hereditary RB. Its role in predicting clinical outcomes is yet to be determined.

High-risk retinoblastoma based on age at primary enucleation: a study of 616 eyes.

PURPOSE: To study the high-risk histopathology features of retinoblastoma based on age at primary enucleation. METHODS: Retrospective study of 616 patients. RESULTS: The mean age at presentation and primary enucleation for retinoblastoma was 34 months (median, 28 months; range, <1-455 months). Of these cases, 128 (21%) were aged ≤1 year, 149 (24%) were in the age group of 1-2 years, 117 (19%) in 2-3 years, 104 (17%) in 3-4 years, and 118 (19%) were >4 years of age at the time of enucleation. Bilateral retinoblastoma (34%; p < 0.0001) and buphthalmos (20%; p < 0.0001) were more common in children ≤1 year of age. Anterior chamber pseudohypopyon (15%; p < 0.0001) and vitreous seeds (53%; p < 0.0001) were more common in children aged >4 years. Based on 8th edition American Joint Committee on Cancer staging system, pT3 was less common in children ≤1 year of age (13%; p < 0.001). Based on histopathology, 38% patients had high-risk features including 24% children aged ≤1 year, 42% in the age group of 1-2 years, 34% in 2-3 years age group, 45% in 3-4 years age group, and 48% patients were >4 years of age. Post-laminar optic nerve infiltration (6%; p = 0.02) and massive choroidal infiltration (9%; p = 0.04) was least common in children ≤1 year of age. Over a mean follow-up period of 52 months (median, 36 months; range, <1-218 months), systemic metastasis and death occurred in 9% patients despite adjuvant systemic chemotherapy. CONCLUSION: The predominant high-risk histopathology feature of retinoblastoma varies with age at primary enucleation.

Malignant Eyelid Tumors in India: A Study of 536 Asian Indian Patients.

PURPOSE: To study the proportion of eyelid malignant tumors in an Asian Indian population and to review their clinical features and outcomes. METHODS: This is a retrospective study of 536 patients. RESULTS: The mean age at presentation with eyelid malignancy was 58 years. Histopathology-proven diagnoses of these patients included sebaceous gland carcinoma (SGC) (n = 285, 53%), basal cell carcinoma (BCC) (n = 128, 24%), squamous cell carcinoma (SCC) (n = 99, 18%), and miscellaneous tumors (n = 24, 4%). The statistically significant differences between eyelid malignant tumors included age at presentation, tumor location, and tumor extent. The clinicopathological correlation of SGC, BCC, SCC, and miscellaneous tumors was 91, 86, 46, and 38% (p = 0.001), respectively. Comparing SGC with BCC, SCC, and miscellaneous tumors, SGC was more commonly associated with tumor recurrence (21 vs. 3, 8, and 13%; p = 0.001), systemic metastasis (13 vs. 0, 4, and 13%; p = 0.001), and death (9 vs. 0, 4, and 0%; p = 0.004). Compared to SGC, BCC, and SCC, locoregional lymph node metastasis was more common with miscellaneous tumors (26 vs. 16, < 1, and 8%; p = 0.001) over a mean follow-up period of 19 months. CONCLUSION: In Asian Indians, SGC is twice as common as BCC and 3 times more common than SCC. SGC is associated with poorer prognosis compared to other eyelid malignant tumors.

RETINOBLASTOMA IN INDIA: Clinical Presentation and Outcome in 1,457 Patients (2,074 Eyes).

PURPOSE: To study the clinical presentation, treatment, and outcome of patients with retinoblastoma (RB) in India. METHODS: Retrospective study of 1,457 patients with RB (2,074 eyes). RESULTS: The mean age at presentation of RB was 29 months (median, 24 months; range, <1-370 months). There were 812 (56%) men and 645 (44%) women with unilateral presentation of RB in 57% (n = 834) and bilateral in 43% (n = 623). Familial RB was present in 4% (n = 55). The most common presenting complaints included leukocoria (n = 1,100; 75%), proptosis (n = 91; 6%), strabismus (n = 77; 5%), and red eye (n = 68; 5%). Most (n = 1,889; 91%) tumors were intraocular in location, and 185 (n = 185; 9%) had extraocular tumor extension at presentation. The most common modalities of primary treatment-included systemic chemotherapy (n = 1,171; 60%) and enucleation (n = 674; 35%). At a mean follow-up period of 44 months (median, 30 months; range, 3-234 months), 92% (n = 1,206) were alive, and 108 (8%) patients died because of RB. Based on Kaplan-Meier analysis, the survival at 1, 3, 5, and 10 years was 94%, 91%, 90%, and 89%, respectively. CONCLUSION: The most common presenting signs of RB in Asian Indian population are leukocoria and proptosis. With appropriate treatment, the survival rate is favorable at 92%.

Enucleation in Asian Indian patients: a histopathological review of 2009 cases.

OBJECTIVE: To review the indications of enucleation in Asian Indian patients and study the trend over the 22-year period. METHODS: Retrospective study of 2009 patients who underwent enucleation. RESULTS: The mean age at presentation of patients who underwent enucleation was 155 months The histopathology diagnosis included a benign tumor (n = 22, 1%), malignant tumor (n = 1472, 73%), acute trauma (n = 93, 5%), retinal vascular disease (n = 50, 3%), inflammatory/infective pathology (n = 33, 2%), or other miscellaneous/non-specific diagnosis (n = 460, 23%). There was a good correlation between the clinical and histopathology diagnoses at 96%. The most common indication for enucleation in young patients ( ≤ 20 years) was retinoblastoma (n = 1257, 82%; p < 0.001), atrophic bulbi or phthisis bulbi (n = 163, 39%; p < 0.001) in middle-age adults, and uveal melanoma (n = 25, 42%; p < 0.001) in older adults. Over the years, there was a decreasing trend of enucleations for atrophic bulbi/phthisis bulbi/painful blind eye (33% from the years 1996 through 2000 to 7% from 2010 to 2018; p < 0.001) and acute trauma (3% from the years 1996 through 2000 to < 1% from 2010 to 2018; p < 0.001) and an increasing trend for intraocular tumors including retinoblastoma (56% from the years 1996 through 2000 to 73% from 2010 to 2018; p = 0.01) and uveal melanoma (3% from the years 1996 through 2000 to 11% from 2010 to 2018; p < 0.006). CONCLUSION: In Asian Indian population, malignant tumors remain the most common indication for enucleation in young and older patients, while desire for better cosmesis with customized ocular prosthesis is the main indication for enucleation in middle-age adults.