Objective: This study correlated the patterns of ocular B- and A-scans of intraocular retinoblastoma (RB) with corresponding histopathology sections. It aimed to establish a more objective basis for determining intraocular retinoblastoma by ultrasonography (UTZ) and to determine the degree of malignancy and viability of the tumor cells. Methods: New cases of retinoblastoma seen at the University of the Philippines-Philippine General Hospital (UP-PGH) from January 1994 to December 2003 were reviewed. Included were patients who underwent enucleation and whose eyeballs were processed at the UP Institute of Ophthalmology. Those with good quality ocular ultrasonographs (UTZ) and clear matching histopathologic sections were finally selected. Findings were correlated and analyzed.Results: Retinoblastoma (RB) showed multiplicity of lesions on UTZ corresponding to multiple lesions on histopathology. The following characteristic patterns were seen: Very malignant RB or pseudorosettes: fine, grainy densities on B-scan with short to medium broad spikes on A-scan ("V-W" pattern). Moderate differentiation with moderate necrosis and early calcific plaques: fine, dense grainy opacities on B-scan with multiple thin, high spikes admixed with tall, broad spikes of calcium deposits on A-scan. Well-differentiated RB with compact viable cells and no necrosis: large, white densities on B-scan with an initial high spike and high internal reflectivity, sometimes "plateauing," on A-scan with no calcific deposits. Complete tumor necrosis with calcific plaques: echolucent space with dense, white, plaque-like opacities on B-scan; flat or low spikes mixed with tall, broad spikes corresponding to calcium plaques on A-scan. Normal vitreous, serous subretinal fluid, or recent hemorrhage: echolucent area on B-scan with flat or low spikes on A-scan. Conclusion: The three most frequent findings in intraocular retinoblastoma were calcific plaques with liquefaction necrosis, multiplicity of lesions, and pseudorosettes. Ocular ultrasound of retinoblastoma showed good histopathologic correlation.
Human ; RETINOBLASTOMA ; ULTRASONOGRAPHY ; RETINAL NEOPLASMS ; RETINAL DISEASES ; EYE DISEASES ; PATHOLOGY

The variety of human cancers in which the retinoblastoma protein pRb is inactivated reflects both its broad importance for tumor suppression and its multitude of cellular functions. Accumulating evidence indicates that pRb contributes to a diversity of cellular functions, including cell proliferation, differentiation, cell death, and genome stability. pRb performs these diverse functions through the formation of large complexes that include E2F transcription factors and chromatin regulators. In this review we will discuss some of the recent advances made in understanding the structure and function of pRb as they relate to tumor suppression, and highlight research using Drosophila melanogaster that reveals important, evolutionarily conserved functions of the RB family.
Animals ; Humans ; Neoplasms ; etiology ; pathology ; prevention & control ; Retinoblastoma Protein ; metabolism

Retinoblastoma (RB) is the most common intraocular malignant tumor in infants and young children. The key causative factors in the progression of RB remain unclear. Therefore, identifying genes closely associated with RB progression may provide important clues for disease diagnosis and gene therapy. However, tumor tissues have strong cellular heterogeneity. There may be significant differences in cell function and gene expression among cells in different pathological states. In this study, we downloaded single-cell transcriptome sequencing data of RB tumors and adjacent tissues from the GEO public database. Subsequently, we analyzed RB tumor transcriptional profiles with different disease duration at the single-cell level and identified cell groups and gene sets potentially associated with RB progression. The results showed that the tumor tissue and the adjacent tissues had overall consistency in the single-cell transcriptional map, but there were obvious differences in the distribution proportions of G1 phase cells, G2 phase cells, and microglia cells of cone precursors in RB tumor and the adjacent tissues. Furthermore, the role of three cell populations in the progression of RB tumors was emphatically analyzed. We found that in the early stage of RB tumors, cone precursor cells proliferated abnormally in G1 phase. With the progression of RB tumors, the proportion of cone precursor cells in G2 phase increased significantly. Meanwhile, the results of differential analysis of microglial populations during RB progression showed that the key genes mainly involved in immune response include RPL23, B2M, and HLA superfamily genes. This study provides new perspectives and data resources for the research of RB pathogenesis and progress.
Child ; Infant ; Humans ; Child, Preschool ; Retinoblastoma/pathology* ; Transcriptome ; Retinal Neoplasms/pathology*

Trilateral retinoblastoma is a rare, but well recognized syndrome. These tumors usually occur in the pineal, parasellar, or suprasellar regions several years after successful management of ocular retinoblastomas without evidence of direct extension or distant metastasis. Here we report a case of trilateral retinoblastoma presenting initially with a sellar tumor and with concurrent unilateral retinoblastoma. The patient was a 5-month-old baby girl showing poor eye contact and nystagmus for several days. She had no family history of retinoblastoma. Brain MRI revealed a midline suprasellar tumor without evidence of cerebrospinal fluid seeding or extracranial metastasis. A pathologic diagnosis of retinoblastoma was made for her brain tumor, and a small, intraocular retinoblastoma was detected in the left eye by thorough examination of the fundus. If a retinoblastoma occurs in the midline of the brain, including the pineal and sellar regions, a careful screening to detect any additional retinal tumors should be performed. Moreover, since these tumors are often hereditary and harbor a worse prognosis, the diagnosis has implications for genetic counseling. This is the first report on a case of trilateral retinoblastoma in Korea presented with a sellar mass.
Brain/*pathology/radiography ; Brain Neoplasms/pathology/radiography/*secondary/surgery ; Female ; Humans ; Infant ; Retinal Neoplasms/*pathology/radiography/surgery ; Retinoblastoma/pathology/radiography/*secondary/surgery

It has been well known that the survivors of retinoblastoma are prone to have osteosarcoma. But the secondary tumor usually occurs in bilateral, hereditary type of retinoblastoma. We report one case of osteosarcoma in a survivor of unilateral, sporadic retinoblastoma. A fourteen year old male presented with a painfully swollen distal forearm of 2 month duration. He had enucleated his left eye 10 years ago due to retinoblastoma with no other adjuvant therapy. We managed him with our conventional protocol and identified deletion of Rb gene from his pathological specimen by using the PCR-RFLP method. This result is unusual for unilateral nonhereditable retinoblastoma and may suggest gene level change even in sporadic cases. And Rb gene study may be helpful for unilateral, sporadic retinoblastoma patient in detecting the possibility of late osteosarcoma.
Adolescent ; Base Sequence ; Case Report ; DNA Primers ; *Gene Deletion ; *Genes, Retinoblastoma ; Human ; Magnetic Resonance Imaging ; Male ; Molecular Sequence Data ; Osteosarcoma/complications/*genetics/pathology ; Retinoblastoma/complications/*genetics/pathology ; Support, Non-U.S. Gov't ; Survivors

A blastoma is a type of cancer, which is common in children; it is caused by malignancies derived from in the precursor cells, often called blasts. Examples are nephroblastomas, retinoblastomas, pleuropulmonary blastomas, and pancreatoblastomas. Pancreatoblastomas are extremely rarely in adults. It is difficult preoperatively to distinguish this tumor from other pancreatic tumors including solid and papillary epithelial neoplasm of the pancreas (SPEN), acinar cell carcinoma, islet cell tumor, and ductal adenocarcinoma with cystic degeneration. To our knowledge, this case may be the second report of a pancreatoblastoma occurring in an adult in Korea. We report a case of a pancreatoblastoma that was confirmed by pathology, despite the radiologic finding that assumed it was a SPEN.
Adenocarcinoma ; Adenoma, Islet Cell ; Adult* ; Carcinoma, Acinar Cell ; Child ; Humans ; Korea ; Neoplasms, Glandular and Epithelial ; Pancreas ; Pathology ; Retinoblastoma ; Wilms Tumor

BACKGROUNDThe use of post-enucleation adjuvant therapy to decrease the extraocular relapse rate is frequently considered, but there is much controversy about the indications for adjuvant therapy. The aim of this retrospective study was to observe the treatment and prognosis for different degrees of invasion of eye tissue in retinoblastoma (RB) and identify the indications for post-enucleation adjuvant therapy.

METHODSWe recruited 537 children who had been diagnosed with unilateral RB and had received enucleation from January 2006 to December 2012 in our hospital, and divided them into three groups according to their number of histopathologic risk factors: 0 factor, 1 factor, or ≥2 factors. Histopathologic high-risk factors included invasion of the optic nerve posterior to the ethmoid plate (including optic nerve stumps) and extensive invasions of the choroid, sclera, anterior chamber, iris, and ciliary body. Treatment was delivered accordingly, and the prognosis of different degrees of histopathologic invasion was observed. The subjects were followed up for 6 months to 7 years (average follow-up time: 35 months). Statistical analysis was analyzed using χ(2) test. P < 0.05 was considered significant.

RESULTSOf the 537 RB patients who received enucleation, 25 died (overall survival: 95.3%). Of the 369 (68.7%) with no histopathologic risk factors, 1 died of recurrence, with a mortality rate of 0.3%, whereas of the 168 (31.3%) with histopathologic risk factors, 26 had recurrences and 24 died (mortality rate: 14.3%; P = 0.000). Of the 93 patients (17.3%), each of whom had a single risk factor, nine had recurrences, 16 died (8.6%). Of the 75 patients (14%) with two or more high-risk factors, 16 died (21.3%). These differences were statistically significant between the three (P = 0.000).

CONCLUSIONChemotherapy is recommended for patients with histopathologic risk factors, especially those with two or more histopathologic risk factors.

Antineoplastic Agents ; therapeutic use ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Prognosis ; Retinoblastoma ; drug therapy ; pathology ; Risk Factors

Antineoplastic Agents, Alkylating ; administration & dosage ; Child ; Humans ; Intravitreal Injections ; Male ; Melphalan ; administration & dosage ; Neoplasm Seeding ; Retinal Neoplasms ; drug therapy ; pathology ; Retinoblastoma ; drug therapy ; pathology ; Vitreous Body ; pathology

Aged ; Anthracosis ; complications ; metabolism ; pathology ; Cyclin-Dependent Kinase Inhibitor p16 ; metabolism ; Humans ; Lung ; metabolism ; pathology ; Lung Neoplasms ; complications ; metabolism ; pathology ; Male ; Middle Aged ; Retinoblastoma Protein ; metabolism

The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were investigated using MTT assay against two human retinoblastoma cell lines, Y79 and WERI-Rb-1. Y79 and WERI-Rb-1 were totally resistant to doses up to 5.0 micrograms/ml of verapamil. Cyclosporin A inhibited the survival of Y79 and WERI-Rb-1 dose-dependently, however, the maximum inhibition at the highest concentration tested (5.0 micrograms/ml) was less than 50% (% survival at 5.0 micrograms/ml of cyclosporin A: 65.6% and 66.9% in Y79 and WERI-Rb-1, respectively). Combination of cyclosporin A and verapamil did not further inhibit the survival of Y79 and WERI-Rb-1 compared with cyclosporin A alone. Adramycin inhibited the survival of Y79 and WERI-Rb-1 dose-dependently. The chemosensitizing effects of cyclosporin A and verapamil on the cytotoxicity of adriamycin were evaluated in terms of sensitizing index (SI: the ratio of IC50 to adriamycin alone to IC50 to adriamycin in the presence of cyclosporin A and/or verapamil). Cyclosporin A significantly enhanced SI and the addition of verapamil enhanced SI further: SI values at 5.0 micrograms/ml of cyclosporin A, 5.0 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of cyclosporin A plus 1.5 micrograms/ml of verapamil, 5.0 micrograms/ml of cyclosporin A plus 3.0 micrograms/ml of verapamil were 2.0, 2.6 and 2.8 in Y79 and 2.6, 5.8 and 9.7 in WERI-Rb-1, respectively. These results suggest that cyclosporin A and verapamil are promising chemosensitizers to adriamycin in the treatment of retinoblastoma.
Cell Survival/drug effects ; Cyclosporine/*pharmacology ; Doxorubicin/*pharmacology ; Eye Neoplasms/drug therapy/*pathology ; Humans ; Retinoblastoma/drug therapy/*pathology ; Tumor Cells, Cultured ; Verapamil/*pharmacology