Extraocular Extension Research Articles

Uveal Melanoma Tumor Size Correlated with Gene Expression Profiling: the Md Anderson Experience

ABSTRACT Aim: Uveal melanoma is the most common eye cancer in adults affecting approximately 6,000 patients worldwide each year. Classically, prognostication for this disease involved histopathologic parameters such as tumor size, thickness, histologic cell type, mitoses, or extraocular extension. Recently, gene expression profiling (GEP) has armed clinicians with a powerful tool for risk assessment that more accurately stratifies patients according to metastatic risk than previous histopathologic categories. This test, commercially available in the U.S. as DecisionDx-UM, stratifies patients into low-risk for distant metastasis (DM), Class 1A and 1B, and high-risk for DM, Class 2. The relationship between tumor size and GEP remains unclear. Here we aim to analyze and clarify that relationship. Methods: Between December 2009 and April 2014, consecutive uveal melanoma patients at MD Anderson Cancer Center who received prognostication with DecisionDx-UM were captured. Data regarding original tumor size was obtained from echography measurements or pathology specimens, where available. We correlated tumor size and GEP in this dataset. Results: A total of 115 uveal melanoma patients with GEP and size measurements were included for analysis. A Kruskal-Wallis test and ordinal logistic regression were conducted to assess the relationship between largest tumor dimension (basal and apical) and GEP. Largest tumor dimension was not significantly different by GEP class, nor was it a significant predictor of GEP class (p = 0.6390). Class 1 tumors had similar sizes compared to Class 2 tumors. GEP and Largest Tumor Dimension GEP Largest dimension (mm) p-value n Median Minimum Maximum Class 1A 31 13.00 5.90 25.00 0.6390 Class 1B 29 12.00 5.50 22.00 Class 2 55 13.00 5.20 22.00 Conclusions: In our single institution case series, uveal melanoma tumor size did not significantly correlate with GEP. Therefore size alone does not predict a patient's more powerful prognosticator, GEP. Clinicians should not rely on tumor size to counsel patients regarding metastatic risk. Disclosure: All authors have declared no conflicts of interest.

Reasons for secondary enucleation after eye preventing treatment of uveal melanoma

AbstractPurpose To determine the reasons for secondary enucleation after eye preventing treatment of uveal melanoma (UM).Methods A retrospective analysis of cases of enucleation after previously treated UM. During 2007 65 patients underwent secondary enucleation ‐ 39 (60%) women and 26 (40%) men, mean age before enucleation was 54 years (range, 25‐75). The period of time between UM local treatment and enucleation planning composed 32 ± 26,7 months (range, 2‐108).Results Tumor thickness prior the enucleation was 4,36±3,5 mm and base diameter ‐ 9,8 ± 5,6 mm, before local therapy‐5,2±2,7 mm and 11,7 ± 4,3 mm, respectively. UM was localized in the choroid (43 patients, 66.1%), ciliochoroidal localization was observed in 12 (18.5%), in the iris ‐ 1 (1.5%), iridociliary ‐ 5 (7,8%), iridociliochoroidal ‐ 4 (6.1%) patients. In most cases, the patients had previously been undergone brachytherapy (45 patients, 69.2%), much less ‐ other methods: combined treatment ‐ 6 (9.2%), laser treatment ‐ 4 (6.2%), local excision ‐ 8 (12.3%), proton irradiation ‐2 (3.1%) patients. The reasons for enucleation were: continued growth ‐ 41 patients (63.1%), secondary incurable hypertension ‐ 23 (35.4%), vitreos body hemorrhage ‐ 13 (20%), extraocular extension ‐ 19 (29.2%), sclera necrosis ‐ 8 (12.3%), the residual tumor ‐ 23 (35.4%). Histologically, spindle cell tumor type was confirmed in 17 patients (26.1%), epitelioid cell UM ‐ 15 (23.1%), mixed cell UM ‐ 19 (29.2%) patients and total tumor necrosis‐ 14 (21.6%).Conclusion The most frequent causes of enucleation after previously local treatment were tumor continued growth and the presence of incompletely tumor tissue resorption. UM any location and with different cell types can be the cause of secondary enucleation.

Survival in uveal melanoma spanish patients: 1992‐2012

AbstractPurpose To analize the specific survival of spanish patients diagnosed and treated of uveal melanoma in a national referral unit and compare the results with the previously published in other populationMethods Patients diagnosed of choroidal and ciliary body melanoma between 1992 and 2012 were included. Epidemiologic and general data, clinical and tumor characteristics, histopathologic features, survival status and cause of death were collected prospectively in a database. Statistical analysis was descriptive for baseline clinical features; survival was analysed by Kaplan‐Meier curves and multivariate Cox's regression model.Results 480 patients were included. Mean follow up of 58.6 months; mean age of 61.7 in males (48.5%) and 62.6 in females, arising in choroid 95.6%. Iris color was grey in 19%, and brown in 43.8%. Most of the tumors were medium size (40.4%) without neither extraocular (94.6%) nor systemic(98.7%) extension.Brachytherapy was performed in 43.4%, observation in 36.4% and enucleation in 18.2%. Predominant histologic types were mixed (39.1%) and fusiform (34.3%). Thirty nine patients died during the follow up time due to metastatic melanoma. Survival rate at 5 and 10 years was 87.7% and 85.5%. Patients with grey/blue iris presented worse survival at 5 years (75.6%) than hazel (91.4%). No deaths were registered in patients with small size; for medium and large survival was 91.2% and 64%. Factors with prognostic significance were: ciliary body location, extraocular extension, epithelioid type and grey/blue iris color.Conclusion The present study show a better survival than previously published series. Lighter iris color as showed prognostic value.These results may be due to epidemiologic differences.

An aggressive small choroidal melanoma

AbstractPurpose To describe a small non diffuse choroidal melanoma with extraocular extension.Methods Case‐reportResults We describe the case of a 50year‐old patient presenting with visual loss and metamorphopsia. Fundus examination revealed a suprapapillary trilobular choroidal mass with inhomogenous pigmentation and lipofuscin. The optic nerve was slightly oedematous. On fluorescein angiography, the lesion revealed pin‐points and exsudation. Ultrasound sonography (20Mhz) showed a peripapillary lesion of 3mm thickness. MRI was performed and confirmed the diagnosis of choroidal melanoma. No extraocular extension was seen on MRI or ultrasound imaging. Because of optic nerve oedema we decided to perform an enucleation. On pathology, the lesion measured 9mm diameter and 3mm thickness. It was mostly composed of epithelioïd cells and it showed scleral, perineural , optic nerve and periocular soft tissue invasion. Complementary orbital radiotherapy was performed. Until now, after one year follow‐up, the patient has shown no metastasis or local recurrence.Conclusion Extraocular invasion in a small thickness non diffuse choroidal melanoma is rare. In times of eye‐sparing choroidal melanoma treatment, the ophthalmologist should not forget the possibility of extra‐ocular involvement, even in small tumors.

Congenital uveal malignant melanoma

We report the clinical and pathological findings of a rare case of congenital uveal melanoma. A 7-week-old girl presented with history of a black area at the inner corner of her left eye since birth. Examination revealed an enlarged globe with an area of visible uveal pigment nasal to the cornea, an iris mass, and shallow anterior chamber in the left eye. Magnetic resonance imaging revealed an intraocular mass. Enucleation was performed when the girl was 2 months of age. Pathologic examination confirmed a malignant melanoma epithelioid cell type with extraocular extension. She was treated with chemotherapy and subtotal exenteration.

The Prognostic Value of Extraocular Extension in Relation to Monosomy 3 and Gain of Chromosome 8q in Uveal Melanoma

To identify the prognostic value of extraocular extension in enucleated uveal melanoma (UM) patients and to correlate extraocular extension to chromosomal aberrations, metastasis-free survival (MFS), and clinico-histopathological risk factors. Retrospective study of patients with UM treated with enucleation between 1987 and 2011. Melanoma-related metastasis and death were recorded. Statistical analysis (log-rank test or Cox regression analysis) was performed to correlate MFS with tumor characteristics, extraocular extension, episcleral diameter of the extraocular extension, cell type, extracellular matrix patterns, inflammation, loss of chromosome 3, and gain of chromosome 8q. In 43 (12%) of 357 patients, extraocular extension was observed. In this subset of patients, we noted a reduced survival of 70 months (105.5 months, P = 0.010) compared with patients without extraocular extension (175.8 months). Patients with gain of chromosomal region 8q in UM with extraocular extension had an increased risk of metastatic disease (P < 0.001). In multivariate Cox proportional hazard analysis, largest basal tumor diameter (P = 0.001), extracellular matrix patterns (P = 0.009), episcleral diameter of the extraocular extension (P = 0.016), loss of chromosome 3 (P < 0.001), and gain of 8q (P < 0.001) were independent predictors for MFS. Larger episcleral diameter of the extraocular extension and additional gain of chromosome 8q in extraocular extension UM correlates to a worse prognosis. MFS is significantly reduced in UM with a large basal tumor diameter, extracellular matrix patterns, loss of chromosome 3, and gain of chromosome 8q.

Intravitreal Melphalan for Persistent or Recurrent Retinoblastoma Vitreous Seeds

Recurrent or persistent vitreous seeds following treatment of retinoblastoma poses difficult management and often leads to enucleation. To describe the technique and evaluate the efficacy and complications of intravitreal melphalan for vitreous seeding from retinoblastoma. This retrospective noncomparative analysis was conducted at a tertiary referral center. The study included 11 consecutive eyes of 11 patients with viable persistent or recurrent vitreous seeds following treatment of retinoblastoma. All eyes received intravitreal melphalan injection (20-30 µg) by transconjunctival pars plana route with concomitant triple-freeze cryotherapy at the injection site during needle withdrawal for prevention of extraocular seeding. Each patient was offered planned 6 monthly cycles. Vitreous seed control and complications of therapy. The mean patient age at vitreous injection was 37 months (median, 27 months; range, 16-82 months). Viable vitreous seeds involved 2 (n = 1), 3 (n = 4), or 4 (n = 6) quadrants. The solid intraretinal retinoblastoma and subretinal seeds showed regression in all eyes following intravenous chemotherapy (n = 6) or intra-arterial chemotherapy (n = 5). There were a total of 55 injections, with a mean number per patient of 5 (median, 6; range, 2-6). Fewer than 6 injections (n = 5) were delivered owing to complete vitreous seed control and parental desire to avoid more injections. By a mean of 9 months' follow-up (median, 9 months; range, 6-16 months), therapeutic success with complete vitreous seed regression was achieved in all 11 cases (100%). Globe salvage was attained in all cases (100%). Further vitreous seed development did not occur in any case. Complications included focal retinal pigment epithelial mottling near the site of chemotherapy injection (2 eyes) and nonaxial posterior lens opacity (2 eyes). There was no case of extraocular tumor extension, hypotony, or phthisis bulbi. These preliminary short-term results suggest that intravitreal melphalan injection for persistent or recurrent vitreous retinoblastoma seeding can provide tumor control with minimal toxicity and complications.

下顎骨に転移が認められた網膜芽細胞腫の1例

Retinoblastoma is a malignant tumor originally derived from the immature retina in infancy and childhood. It usually occurs in patients younger than 2 years. Although the prognosis after treatment is relatively good, the prognosis becomes poor if extraocular extension, distant metastases, or both occur. A 1 and a half-year-old male had been given a diagnosis of a retinoblastoma of the left eye and received conservative treatment. A recurrent tumor was later found, and metastatic tumors were detected in the bone marrow, femur, and mandible 6 months later. Chemotherapy was performed at that time. Thereafter, enucleation of the left eye and peripheral blood stem-cell transplantation with ultra-high-dose chemotherapy were performed. Consequently, cerebrospinal irradiation was also performed. The patient has been in remission for 6 years. The mandible has no findings of recurrence and no dysgenesis. The permanent teeth have nearly all erupted with short roots and provide good occlusion.

MicroRNA expression analysis and Multiplex ligation‐dependent probe amplification in metastatic and non‐metastatic uveal melanoma

To determine the association of microRNA expression and chromosomal changes with metastasis and survival in uveal melanoma (UM). Thirty-six patients with UM were selected based on the metastatic status, and clinicopathological data were collected. Multiplex ligation-dependent probe amplification (MLPA) was used to identify chromosomal changes. Chromosomal changes and clinicopathological data were correlated with survival and metastasis. The microRNA expression was analysed in 26 of the 36 archived UM samples. Unsupervised analysis, differential expression analysis and Cox regression analysis were performed to determine the association with metastasis and survival. Metastasis and metastatic death occurred in 20 patients, two patients died of other causes and one patient of unknown causes. A significant association between increasing size category (p=0.002, log-rank), extraocular extension (p=0.001), chromosome 3 loss (p=0.033) and 1p loss (p=0.030) and development of metastases was observed. Tumour, node, metastasis (TNM) staging showed a significant association with survival (p<0.0001, log-rank). Adjusting for gender and age TNM size category T4 (p=0.016, Cox regression analysis), mixed (p=0.029) and epithelioid (p=0.0058) cell types, chromosome 3 loss (p=0.014) and 8q gain (p=0.010) were significant prognosticators for a poor survival. Hierarchical clustering divided the UM into three groups based on microRNA expression. The clusters showed no association with clinical or histopathological features, TNM staging, metastasis or survival. Differential expression analysis did not reveal microRNAs related to metastasis or survival. The prognostic significance of chromosome 3 loss and 8q gain identified by MLPA analysis was confirmed in archived UM samples. The value of microRNA expression as a predictor of metastasis and survival in UM could not be confirmed.

Extraocular Extension of Uveal Melanoma After Fine-Needle Aspiration, Vitrectomy, and Open Biopsy

The most potentially devastating complication of fine-needle aspiration biopsy (FNAB) or open biopsy is extraocular extension of the tumor. In this collaborative case series, we report 4 cases of orbital recurrence of malignant melanoma as a late complication of biopsy and/or vitrectomy performed at referring institutions and then sent to us for evaluation. Four cases of extraocular extension of melanoma are documented following multiple procedures including FNAB, vitrectomy, and open biopsies. Three of the patients in this series underwent more than 1 FNAB, biopsy, and/or vitrectomy. One underwent FNAB only but did not undergo brachytherapy afterward. Most of the FNABs, open biopsies, and vitrectomies reported in these cases were not performed by us, so details of the technique are not available. From these cases, we are not able to determine whether the FNAB or additional invasive procedures caused the subsequent extraocular disease or if growth of the tumor into the extraocular space occurred independent of or prior to the procedures. Large series of FNAB for uveal melanoma with no extraocular recurrence have been reported by multiple experienced centers, and the vast majority of these procedures are performed without effect on the patient's prognosis. However, the patients described in this series demonstrate that this complication is rarely possible.

Imaging features of medulloepithelioma: report of four cases and review of the literature

Intraocular medulloepithelioma is a childhood tumor arising from the nonpigmented primitive ciliary neuroepithelium. Although rarer than retinoblastoma, it remains the second most common primary intraocular neoplasm in children. The rarity of intraocular medulloepithelioma creates the challenge in establishing a clinical diagnosis, and radiologically the tumor is often confused with other intraocular masses. To describe the clinical, imaging and pathological features of intraocular medulloepithelioma with emphasis on the role of imaging to enable its differentiation from more common intraocular pathology. We retrospectively analyzed the clinical, histopathological and imaging data of four children with intraocular medulloepithelioma. All four children had medulloepithelioma arising from the ciliary body. The children were imaged with US (n = 3), MRI (n = 4), whole-body (99m)Tc-MDP scintigraphy (n = 2) and CT (n = 1). All four children had enucleation of the involved eye. One tumor was a malignant teratoid variant, two tumors were malignant nonteratoid variants and one was a nonteratoid variant of uncertain malignant potential. None of the tumors had extraocular extension on histopathology or imaging. Two children had associated retinal detachment on US and MRI examinations. All tumors were iso/hyperintense to vitreous on T1-weighted and hypointense on T2-weighted MRI and showed marked contrast enhancement of the solid components. No calcifications were identified on US or CT examinations. Our findings are consistent with previously reported cases of medulloepithelioma. This series emphasizes the roles of various imaging modalities, with pathological correlation, in differentiating the tumor from other ciliary body masses, in detecting tumor extension and in identifying associated ocular complications. In this series we also describe the results of postsurgical follow-up for tumor recurrence.

Intraocular malignant melanoma of the choroid presenting as orbital cellulitis

We report a case of choroidal melanoma with features suggestive of orbital cellulitis. A 24-year-old Asian Indian male presented with a 20-day history of sudden loss of vision in the right eye. Edematous eyelids with complete mechanical ptosis, complete ophthalmoplegia, gross proptosis accompanied by massive chemosis, and prolapse of the inferior forniceal conjunctiva were noted. He denied perception of light in the right eye. The left eye was unremarkable. B-scan ultrasonography of the right eye showed a large dome-shaped mass filling the posterior segment suggestive of choroidal melanoma. Computed tomography confirmed those findings and showed no extraocular tumor extension. The patient was conservatively treated with systemic steroids following which the inflammation subsided. He underwent enucleation of the right eye and a diagnosis of spindle A cell choroidal melanoma was confirmed by histopathological examination. Although rare, orbital cellulitis is one of the presenting features of choroidal melanoma. Uveal melanoma-associated orbital cellulitis can be well controlled with systemic steroids, does not always indicate extraocular tumor extension, and can occur in spindle A cell melanomas.

Malignant Teratoid Ciliary Body Medulloepithelioma in a Neonate

Ciliary body medulloepithelioma is an intraocular tumor manifesting in early childhood, rarely at birth. A unique case of intraocular malignant teratoid ciliary body medulloepithelioma in a neonate presenting as buphthalmos at birth is reported. There was rapid progression with extraocular extension within 2 months and developed regional lymph node metastasis despite enucleation. The child underwent lymph node dissection and local radiotherapy with complete remission.

Staging of Ciliary Body and Choroidal Melanomas Based on Anatomic Extent

To refine the anatomic classification and staging of ciliary body and choroidal melanomas in the TNM classification. Tumor largest basal diameter and thickness of 7,369 patients were analyzed based on registry data from five ocular oncology centers. T categories were derived empirically by dividing data into blocks representing 3- × 3-mm fractions. Blocks with similar survival were grouped together so that no T category comprised a large majority of tumors, and each was uniform in survival, using randomly drawn 60% building and 40% validation data sets. Presence of ciliary body involvement (CBI) and extraocular extension (EXE) was analyzed among 5,403 patients to define T subcategories. Stages were generated by iteratively combining subcategories with similar survival. Of the 7,369 tumors analyzed, 24% were classified as T1, 33% as T2, 31% as T3, and 12% as T4. Ten-year Kaplan-Meier survival estimates for the T categories were 89%, 77%, 58%, and 39%, respectively (P < .001). Survival of patients in four subcategories based on presence or absence of CBI and EXE differed significantly within each T category (P = .018 for T1; P < .001 for T2 to T4). EXE exceeding 5 mm in largest diameter carried a worse prognosis than smaller extensions (P < .001) and was assigned a separate subcategory. Ten-year Kaplan-Meier survival estimates for stages I, IIA to IIB, and IIIA to IIIC were 88%, 80%, 67%, 45%, 27%, 10%, respectively (P < .001). This evidence-based anatomic classification provides a basis for staging ciliary body and choroidal melanomas in the seventh edition of the Cancer Staging Manual of the American Joint Committee on Cancer.

Ciliary Body Medulloepithelioma: Analysis of 41 Cases

To describe the clinical features, histopathology, treatment, and outcomes of ciliary body medulloepithelioma. Retrospective study. Forty-one patients with medulloepithelioma. Cryotherapy, plaque radiotherapy, external beam radiotherapy, tumor removal by partial lamellar sclerouvectomy (PLSU), or enucleation. Metastasis and death. Of 41 patients with ciliary body medulloepithelioma, the median age at diagnosis was 5 years. The mean tumor basal diameter was 11 mm, and the mean tumor thickness was 7 mm. Related features included secondary glaucoma (n = 18, 44%), iris neovascularization (n = 21, 51%), cataract (n = 19, 46%), lens subluxation (n = 11, 27%), lens coloboma (n = 8, 20%), retrolental neoplastic cyclitic membrane (n = 21, 51%), intratumoral cysts (n = 25, 61%), and extraocular extension (n = 4, 10%). There was systemic association with pleuropulmonary blastoma in 2 cases (5%). Primary tumor treatment included enucleation (n = 21, 60%), tumor removal by PLSU (n = 8, 23%), plaque radiotherapy (n = 3, 9%), external beam radiotherapy (n = 1, 3%), cryotherapy (n = 1, 3%), or palliative chemotherapy (n = 1, 3%). In 1 case, medulloepithelioma was diagnosed histopathologically after inadvertent evisceration for blind painful eye. Subsequent treatment for residual or recurrent tumor in cases treated conservatively/inappropriately (n = 15) was necessary in 7 cases (47%). Histopathology disclosed benign features in 6 cases (20%), malignant features in 24 cases (80%), teratoid features in 11 cases (37%), and nonteratoid features in 19 cases (63%). In the 26 enucleated eyes, other features included retrolental neoplastic cyclitic membrane (n = 18, 69%), neoplastic epiretinal membrane (n = 6, 23%), and persistent hyaloid artery (n = 6, 23%). Systemic metastasis occurred in 3 cases (8%) over a mean follow-up of 49 months, all of whom presented with extrascleral extension of tumor due to mean delay in diagnosis by 39 months. Medulloepithelioma most commonly occurs in children. Systemic association with pleuropulmonary blastoma rarely is found. Patients with extrascleral medulloepithelioma are at risk for metastasis.

American Joint Committee on Cancer Classification of Posterior Uveal Melanoma (Tumor Size Category) Predicts Prognosis in 7731 Patients

To evaluate the clinical features and prognosis of posterior uveal (ciliary body and choroid) melanoma based on the American Joint Committee on Cancer (AJCC) classification (7th edition) of primary tumor(T). Retrospective, interventional case series. Seven thousand seven hundred thirty-one patients. Ocular management including plaque radiotherapy, enucleation, local resection, or laser therapy. Melanoma-related metastasis and death. Of 7731 patients with posterior uveal melanoma, the AJCC classification based on T was category T1 in 3557 (46%), T2 in 2082 (27%), T3 in 1599 (21%), and T4 in 493 (6%). Based on tumor categories T1, T2, T3, and T4, respectively, features that showed significant increase with tumor category included patient age at presentation (57, 58, 58, and 61 years; P<0.001), tumor base (8, 12, 15, and 20 mm; P<0.001), tumor thickness (3.5, 5.2, 8.9, and 11.4 mm; P<0.001), mushroom configuration (8%, 20%, 38%, and 39%; P<0.001), associated subretinal fluid (64%, 80%, 82%, and 83%; P<0.001), intraocular hemorrhage (5%, 12%, 17%, and 18%; P<0.001), rupture of Bruch's membrane (9%, 24%, 40%, and 40%; P<0.001), and extraocular extension (1%, <1%, 4%, and 12%; P<0.001). After therapy, Kaplan-Meier estimates of metastasis at 5, 10, and 20 years were 8%, 15%, and 25% for category T1, 14%, 25%, and 40% for category T2, 31%, 49%, and 62% for category T3, and 51%, 63%, and 69% for category T4, respectively (P<0.001). Kaplan-Meier estimates of death at 5, 10, and 20 years were 4%, 8%, and 11% for category T1, 8%, 13%, and 24% for category T2, 19%, 27%, and 36% for category T3, and 30%, 43%, and 51% for category T4, respectively (P<0.001). Compared with category T1, the hazard ratio for metastasis and death for T2 was 1.8 and 1.9, respectively, that for T3 was 4.5 and 4.7, respectively, and that for T4 was 8.2 and 8.8, respectively. Based on the AJCC classification, increasing tumor category was associated with older age, larger tumor, and greater incidence of subretinal fluid, hemorrhage, and extraocular extension. Compared with uveal melanoma classified as T1, the rate of metastasis and death was 2 times greater for T2, 4 times greater for T3, and 8 times greater for T4. The risk for metastasis and death increased 2-fold with each increasing melanoma category. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Le rétinoblastome : état des lieux au Mali et programme d’aide au diagnostic précoce, aux traitements et à la réhabilitation

Retinoblastoma (RB) is a rare embryonic tumour that represents 1/16,000 births in France. In Mali, a study showed the characteristics of a hospital series of cases seen in Bamako in the Pediatric Oncology Unit of Gabriel Touré Teaching Hospital and in the Tropical Ophthalmology Institute of Africa (IOTA) between January 2005 and June 2007. Median age was 4 years versus 2 years in France for unilateral disease. Near two third of children with RB had extra-ocular extension at diagnosis, which is now exceptional in France. Only 11% were bilateral versus 35% in France. Cure rate was around 50%, but it is estimated only on the cases arriving in Bamako and with at least 20% lost of follow-up. Cure rate is over 95% in France within an exhaustive register. RB appears as an exemplary tumor and rapid improvements could be obtained in low-income countries with relatively limited means. This is why, the Alliance mondiale contre le cancer (AMCC), the Institut Curie in Paris, which is the reference center in France for RB, and teams in Bamako were proposing a program to help the development of early diagnosis, treatments, including eye preservation, and rehabilitation of children with RB in sub-Saharan Africa in collaboration with the Groupe franco-africain d’oncologie pédiatrique (GFAOP). The official launching of this program was held in Bamako November 4th, 2011 for Mali and the surrounding regions. After this first experience, this program is now implemented in other countries.

Elevated blood β-2 microglobulin is associated with tumor monosomy-3 in patients with primary uveal melanoma

Prognostic blood biomarkers for patients with uveal melanoma have not been identified. Tumor monosomy-3 is strongly associated with the development of metastatic disease. Tumor expression of human leukocyte antigen class I molecules and insulin-like growth factor (IGF)-1 receptor has also been associated with the development of metastatic disease. The relationship of blood levels of the human leukocyte antigen-class-I-associated β-2 microglobulin (β2M), IGF-1, and its binding protein, IGFBP-3, with tumor monosomy-3 was evaluated. Blood was drawn from patients with a clinical diagnosis of primary uveal melanoma without metastatic disease before fine-needle aspiration biopsy at the time of brachytherapy or enucleation. Tumor chromosome 3 status was determined by fluorescence in-situ hybridization. β2M, IGF-1, and IGFBP-3 levels were determined using enzyme-linked immunosorbent assays. A total of 76 patients were studied; 47 (62%) underwent brachytherapy and 29 (38%) underwent enucleation. Thirty-three (43%) of the tumors manifested monosomy-3. Most tumors were large, located in the choroid, mixed cell type, and nuclear grade 2. Most tumors did not manifest extraocular extension. Blood levels of IGF-1 and IGFBP-3 were not associated with tumor monosomy-3. In contrast, increases in blood β2M (P≤0.02) were associated with tumor monosomy-3. The independent association of increased blood level of β2M and tumor monosomy-3 status was confirmed in multivariable analysis. In conclusion, measurement of blood levels of β2M in patients with primary uveal melanoma may have prognostic value and may help guide surveillance and adjuvant therapy recommendations.

Association of retinoblastoma with clinical and histopathological risk factors

A study was conducted to see the association of retinoblastoma with age, bilaterism, Tumor size, site, grades, involvement of anterior chamber, iris, ciliary body, choroid, sclera and optic nerve, and extraocular extension. This was a retrospective descriptive analytical study. The records of the Institute of Ophthalmology, King Edward Medical University/Mayo hospital, Lahore: Pakistan January 2006-Dec 2011 was analyzed. Five years biopsies (June 2006 to June 2012) of the retinoblastoma, from the Pathology department, was retrieved to see optic nerve involvement in all the retrieved specimens. The mean age was 3.54 ± 1.686 years. There were 15 cases of bilateral retinoblastoma and 37 cases with unilateral neoplasms. The age range of bilateral tumors was 2 - 6 years while the range in unilateral tumor was 1 - 10 years male to female ratio was 1:1.5. Among 52 cases, 37 (71.2%) patients were unilateral retinoblastoma and 15 (28.28%) patients were with bilateral disease. On radiological examination of patients suffering from retinoblastoma by B-Scan (Ultrasound), there were 33 (63.5%) cases with exophytic presentation while 18 (34.6%) cases showed endophytic morphology. On clinical examinations, 28 patients presented with proptosis of (it was the most common presenting sign in our patients, accounting for about 53.8% of cases), 20 cases presented with leucocoria eye with strabismus. 29/52 patients showed involvement with optic nerve, 17 were from 1 - 3 years age and 12 were from 4 - 6 years. Statistically there was no difference in the involvement of optic nerve, disc involvement and extra ocular extension with the age of patients (p = 0.217). There was also no statistical difference seen in age and gender for but a strong association was seen with patient’s presentation, symptoms and size of the tumors and anterior chamber, iris, ciliary body, choroid, sclera and optic nerve, and extra ocular extension. We concluded that a positive association was seen with tumor size and tumor extension (optic nerve, and extraocular extension). No Association was seen with age, gender and laterality of the tumors.

Prognostic significance of retinoblastoma gene mutation in retinoblastoma eye with respect to pathological risk factors

Retinoblastoma (Rb) was reported firstly by Benedict is the commonest pediatric intraocular malignant tumor in children younger than 5 years of age. The study was conducted to detect the RB-1 gene for prognostic evaluation in retinoblastoma and to see the frequency of RB-1 gene in our population. This was a retrospective descriptive analytical study. Five years biopsies (January, 2006 to December 2011) of the retinoblastoma, from the Pathology department, was retrieved to see optic nerve involvement in all the retrieved specimens. The study was taken to see the mutation of RB1 gene by immunohistochemistry and PCR. The study plan was approved from Institutional Review Board (IRB) of the University. All the cases showed positivity of abnormal Rb-1 gene proteins expression by Immunohistochemistry staining. On PCR, 51/52 (98%) tumors expressed gene mutation as compared to 100% expression shown by IHC. Out of these, 28/51 (55%) cases showed ONI and ODI with positivity for mutated RB gene. A positive association was seen among RB gene mutation with ONI and ODI (p = 0.05). There were 33/51 (65%) cases who did not show any EOE but showed PCR positivity for RB gene mutation. While there were 18/51 (35%) cases who showed EOE and positivity of PCR for Rb-1 gene mutation and a positive association was seen with EOE and gene mutation (p = 0.005). The most common sequence of mutation was on 13 with 33 cases for double mutation, 12 cases for single and 6 patients for triple pattern of mutation. Most of the double and triple sequences of mutations were associated with ONI, ODI and EOE. We concluded that mutation of RB-1 gene is responsible in causation of the tumors with a positive association with tumor size and tumor extension (optic nerve, and extraocular extension), and mutation affects patients with all ages, both gender and unilateral and bilateral tumors.