Retinoblastoma: A Major Review.

Retinoblastoma is the most common primary intraocular tumor with an incidence of 1: 16,000 to 18,000 live birth and represents 11% of cancer that develop in the first year of life. Retinoblastoma may be unilateral (60%) or bilateral (40%). Bilateral cases always heritable and median age of diagnosis is 1 year. Unilateral cases are mostly non heritable but 15% can be heritable and median age of presentation is 2 years. All children with heritable form carry mutation in RB1 gene. Though most frequent symptoms during diagnosis are leucocoria and strabismus, can present as most severe form in under developed countries. Diagnosis is made by fundus examination. Ultrasonography and imaging (CT, MRI) contribute both in diagnosis and assessment of extension of diseases. The aim of treatment is to save the child first, followed by globe and vision salvage. Treatment depends on laterality, size, location and extent of tumor. The main prognosis depends on early detection of tumor and treating the child by multidisciplinary team approach. Due to advancement in treatment modalities for the last two decade the survival rate of retinoblastoma has increased. But long term follow up is mandatory for retinoblastoma survivor as there is risk for development of second cancers in later life. Proper genetic screening and genetic counseling can help parents and patients in their adulthood to understand the disease properly.

Primary orbital Ewing sarcoma family of tumors: a study of 12 cases.

PurposeThe purpose of this study is to discuss the clinical presentation, management, and outcomes of patients with primary orbital Ewing sarcoma family of tumors (ESFTs).Patients and methodsRetrospective study of 12 patients with biopsy-proven primary orbital ESFT.ResultsThe mean age at presentation of primary orbital ESFT was 12 years (median, 8 years; range, 5 months to 28 years). There were seven (58%) females and five (42%) males. The presenting complaints included proptosis (n=10; 83%) and swelling in the upper eyelid (n=2; 17%). The mean duration of symptoms was 9 weeks (median, 5 weeks; range, 2-24 weeks). Tumor epicenter was located in the superior orbit (n=6; 50%), lateral orbit (n=3; 25%), inferior orbit (n=2; 17%), and medial orbit (n=1; 8%). Computed tomography of the orbits revealed predominant bony lesion (n=10; 83%) or isolated soft tissue/extraosseous lesion (n=2, 17%). At presentation, extraorbital extension was noticed in 10 patients including intra cranial extension (n=7; 58%), extension into temporal fossa (n=4; 33%), nasal cavity (n=2; 17%), maxillary sinus (n=2; 17%), and ethmoid sinus (n=1, 8%). Systemic metastases at presentation was detected in five (42%) patients involving the bone marrow (n=4; 33%), kidney (n=1; 8%), and retroperitoneal lymphnode (n=1; 8%). Multi-modal treatment including a combination of neoadjuvant chemotherapy, excision biopsy/debulking, and/or radiotherapy was given. Over a mean follow-up period of 21 months (median, 7 months; range, 1-152 months), disease-related death occurred in 11 (92%) cases.ConclusionPrimary orbital ESFT is aggressive at presentation and is associated with poor prognosis.

Uveal melanoma: relatively rare but deadly cancer.

Although it is a relatively rare disease, primarily found in the Caucasian population, uveal melanoma is the most common primary intraocular tumor in adults with a mean age-adjusted incidence of 5.1 cases per million per year. Tumors are located either in iris (4%), ciliary body (6%), or choroid (90%). The host susceptibility factors for uveal melanoma include fair skin, light eye color, inability to tan, ocular or oculodermal melanocytosis, cutaneous or iris or choroidal nevus, and BRCA1-associated protein 1 mutation. Currently, the most widely used first-line treatment options for this malignancy are resection, radiation therapy, and enucleation. There are two main types of radiation therapy: plaque brachytherapy (iodine-125, ruthenium-106, or palladium-103, or cobalt-60) and teletherapy (proton beam, helium ion, or stereotactic radiosurgery using cyber knife, gamma knife, or linear accelerator). The alternative to radiation is enucleation. Although these therapies achieve satisfactory local disease control, long-term survival rate for patients with uveal melanoma remains guarded, with risk for liver metastasis. There have been advances in early diagnosis over the past few years, and with the hope survival rates could improve as smaller tumors are treated. As in many other cancer indications, both early detection and early treatment could be critical for a positive long-term survival outcome in uveal melanoma. These observations call attention to an unmet medical need for the early treatment of small melanocytic lesions or small melanomas in the eye to achieve local disease control and vision preservation with the possibility to prevent metastases and improve overall patient survival.

Prognosis of uveal melanoma based on race in 8100 patients: The 2015 Doyne Lecture.

A retrospective, nonrandomized, interventional case series of 8100 patients with uveal melanoma were evaluated for melanoma-related metastasis based on patient race. The patient race was Caucasian (n=7918, 98%), Hispanic (n=105, 1%), Asian (n=44, <1%), or African American (n=33, <1%). On the basis of race (Caucasian, Hispanic, Asian, and African American), significant differences were noted in mean age at presentation (58, 48, 44, and 52 years; P<0.001), distance of posterior tumor margin to foveola (5, 5, 6, and 4 mm; P<0.001), distance of posterior tumor margin to optic disc (5, 5, 6, and 4 mm) (P<0.001), tumor base (11, 12, 12, and 13 mm; P<0.001), tumor thickness (5.4, 7.1, 6.5, and 7.5 mm; P<0.001), intraocular hemorrhage (10, 14, 11, and 24%; P=0.02), and rupture of Bruch's membrane (20, 27, 39, and 36%; P=0.001). On the basis of multivariate analysis, the rate of metastasis increased with increasing age (P<0.001), ciliary body location (P<0.001), increasing tumor base (P<0.001), increasing tumor thickness (P<0.001), pigmented tumor (P=0.001), subretinal fluid (P=0.001), intraocular hemorrhage (P=0.045), and extraocular extension (P=0.036). Kaplan-Meier estimates of metastasis at 3, 5, and 10 were 8, 15, and 25% in Caucasians; 13, 13, and 13% in Hispanics; 4, 4, and 36% in Asians; and 8, 8, and 8% in African Americans. Compared with Caucasians, despite relative risk for metastasis of 0.31 for African Americans, 0.73 for Hispanics, and 1.42 for Asians, there was no statistical difference in metastasis, or death from uveal melanoma based on race. In summary, uveal melanoma showed similar prognosis for all races.

Sebaceous gland carcinoma of the eyelid: clinicopathological features and outcome in Asian Indians.

PURPOSE: To study the clinical and histopathological features of eyelid sebaceous gland carcinoma (SGC) and to evaluate the prognosis in the Asian-Indian population. METHODS: This is a retrospective study of 191 patients with SGC. RESULTS: The mean age at presentation of eyelid SGC was 57 years (median, 56 years). The tumor epicenter was most commonly located in the upper eyelid (n=125, 65%). The mean tumor basal diameter was 15 mm (median, 10 mm). There was evidence of tumor extension into the orbit (n=30, 16%), paranasal sinuses (n=3, 2%), and brain (n=1, 1%). Wide excision biopsy (n=146, 78%) was the most common treatment modality. Tumor recurrence was noted in 42 (24%) patients over a mean follow-up period of 29 months (median, 20 months). On the basis of the Kaplan-Meier estimate, lymph node metastasis occurred in 18%, systemic metastasis was detected in 10%, and death occurred in 2% of patients at 10 years. On multivariate analysis, the factors predicting locoregional lymph node and systemic metastasis were medial canthal involvement (P=0.004; P=0.013), lateral canthal involvement (P=0.013; P=0.025), tumor basal diameter >10 mm (P=0.002; P=0.002), and perivascular invasion (P=0.043; P<0.001), respectively. The factors predicting death due to metastasis on multivariate analysis were medial canthal involvement (P=0.012) and tumor basal diameter >10 mm (P=0.001). CONCLUSION: Advanced eyelid SGC is a tumor associated with poor prognosis. In this study, canthal involvement, larger tumor diameter, and perivascular invasion were poor prognostic factors.

Retinoblastoma frontiers with intravenous, intra-arterial, periocular, and intravitreal chemotherapy.

In this report, we explore retinoblastoma diagnostic accuracy and review chemotherapy alternatives for retinoblastoma using intravenous, intra-arterial, periocular, and intravitreal routes. A review of 2775 patients referred for management of retinoblastoma, disclosed 78% with confirmed retinoblastoma and 22% with simulating lesions, termed pseudoretinoblastomas. Children ≤2 years old showed leading pseudoretinoblastomas of persistent fetal vasculature, Coats disease, and vitreous haemorrhage, whereas those >5 years showed simulators of Coats, toxocariasis, and familial exudative vitreoretinopathy. The diagnosis of retinoblastoma should be established before planning therapeutic strategy. Chemotherapy strategy depends on tumour laterality and stage of disease. If bilateral retinoblastoma, intravenous chemotherapy (IVC) is important as first-line therapy for control of intraocular disease, prevention of metastasis, and reduction in prevalence of pinealoblastoma and long-term second malignant neoplasms. Bilateral groups D and E retinoblastoma receive additional subtenon's carboplatin boost for improved local control. If unilateral disease is present, then intra-arterial chemotherapy (IAC) is often considered. IAC can be salvage therapy following chemoreduction failure. Unilateral retinoblastoma of groups D and E are managed with enucleation or globe-conserving IVC and/or IAC. Intravitreal chemotherapy is cautiously reserved for recurrent vitreous seeds following other therapies. In conclusion, the strategy for retinoblastoma management with chemotherapy depends on tumour laterality and stage of disease. Bilateral retinoblastoma is most often managed with IVC and unilateral retinoblastoma with IAC, but if advanced stage, combination IVC plus IAC or enucleation.