Prenatal versus Postnatal Screening for Familial Retinoblastoma.

Purpose: To compare overall outcomes of conventional postnatal screening of familial retinoblastoma and prenatal RB1 mutation identification followed by planned early-term delivery.

Design: Retrospective, observational study.

Participants: Twenty children with familial retinoblastoma born between 1996 and 2014 and examined within 1 week of birth.

Molecular analysis distinguishes metastatic disease from second cancers in patients with retinoblastoma.

The pediatric ocular tumor retinoblastoma readily metastasizes, but these lesions can masquerade as histologically similar pediatric small round blue cell tumors. Since 98% of retinoblastomas have RB1 mutations and a characteristic genomic copy number "signature", genetic analysis is an appealing adjunct to histopathology to distinguish retinoblastoma metastasis from second primary cancer in retinoblastoma patients. Here, we describe such an approach in two retinoblastoma cases.

Intra-arterial Chemotherapy for Retinoblastoma: A Systematic Review.

Importance: Intra-arterial chemotherapy has emerged as a treatment for intraocular retinoblastoma and has been quickly adopted by centers worldwide.

Objective: To conduct a systematic review and attempt a meta-analysis to summarize the reported outcomes of intra-arterial chemotherapy.

Evidence Review: In January 2015, we performed comprehensive searches in Medline, Embase, Cochrane, and Web of Science from inception through January 2015, including any peer-reviewed English-language publication that described outcomes related to toxicity or efficacy in at least 4 patients.

Hypersensitivity to sub-Tenon's topotecan in fibrin adhesive in patients with retinoblastoma.

Sub-Tenon's space delivery of topotecan in a fibrin sealant was used as an adjunct to laser therapy for small retinoblastoma tumors in 25 children (77 injections). We report serious hypersensitivity reactions in 2 children on their third sub-Tenon's injection of topotecan in fibrin sealant. One child subsequently had topotecan in an autologous blood clot with no allergic reaction.

Late-diagnosis retinoblastoma with germline mosaicism in an 8-year-old.

We describe bilateral retinoblastoma in an 8-year-old girl presenting with macular tumor in one eye and a small peripheral tumor in the other but no detected RB1 gene mutation. Despite chemotherapy, multiple focal laser, cryotherapy, and periocular chemotherapy, tumor activity persisted and enucleation was performed. Two RB1 mutations were found in the tumor; one RB1 mutation was present in 10% of blood cells, identifying mosaicsm.

No ocular motility complications after subtenon topotecan with fibrin sealant for retinoblastoma.

Objective: To report our long-term experience with the local toxicity profile and ocular motility changes after treatment of intraocular retinoblastoma with subtenon topotecan chemotherapy.

Design: Cross-sectional study.

Participants: Ten eyes in 8 patients with retinoblastoma treated with subtenon topotecan.

Molecular testing prognostic of low risk in epithelioid uveal melanoma in a child.

Aims: To characterise a histologically unusual paediatric uveal melanoma by gene expression and karyotypic profiling and assess prognosis.

Methods: The tumour was studied by histopathology, karyotype analysis, single nucleotide polymorphism and gene expression profile analysis for correlation with clinical outcome.

Results: The tumour had predominantly epithelioid histology.

Hand-held high-resolution spectral domain optical coherence tomography in retinoblastoma: clinical and morphologic considerations.

Purpose: Hand-held spectral domain optical coherence tomography (HHSD OCT) has greatly expanded the imaging/diagnostic capacity for clinicians managing children with intraocular retinoblastoma. We present our early experience with HHSD OCT and conventional spectral domain OCT imaging in these patients.

Methods: In this retrospective cross-sectional observational study, infants were imaged during examination under anaesthesia with HHSD OCT in the supine position.

Retinoblastoma.

Retinoblastoma is an aggressive eye cancer of infancy and childhood. Survival and the chance of saving vision depend on severity of disease at presentation. Retinoblastoma was the first tumour to draw attention to the genetic aetiology of cancer.

Oncologic surveillance for subjects with biallelic mismatch repair gene mutations: 10 year follow-up of a kindred.

Background: Heterozygous germline mutations in DNA mismatch repair (MMR) genes cause Lynch syndrome. Biallelic MMR mutations cause a distinct syndrome characterized by brain tumors, lymphoid malignancies, and gastrointestinal cancers during childhood. These children usually succumb to multiple cancers before adulthood.

Periocular topotecan for intraocular retinoblastoma.

Objective: To review the effectiveness and toxicity of periocular topotecan hydrochloride in fibrin sealant (Tisseel) for the control of intraocular retinoblastoma.

Methods: Retrospective medical record review of visually threatening or recurrent intraocular retinoblastoma treated with periocular topotecan.

Results: Eight children (10 eyes) received 1 to 4 injections of periocular topotecan in fibrin sealant, without or with concomitant laser and/or single freeze-thaw prechemotherapy cryotherapy.

Pre-enucleation chemotherapy for eyes severely affected by retinoblastoma masks risk of tumor extension and increases death from metastasis.

Purpose: Initial response of intraocular retinoblastoma to chemotherapy has encouraged primary chemotherapy instead of primary enucleation for eyes with clinical features suggesting high risk of extraocular extension or metastasis. Upfront enucleation of such high-risk eyes allows pathologic evaluation of extraocular extension, key to management with appropriate surveillance and adjuvant therapy. Does chemotherapy before enucleation mask histologic features of extraocular extension, potentially endangering the child's life by subsequent undertreatment?

Methods: We performed retrospective analysis of 100 eyes with advanced retinoblastoma enucleated with, or without, primary chemotherapy, in Beijing Tongren Hospital, retrospectively, from October 31, 2008.

Medical radiation exposure and risk of retinoblastoma resulting from new germline RB1 mutation.

Although ionizing radiation induces germline mutations in animals, human studies of radiation-exposed populations have not detected an effect. We conducted a case-control study of sporadic bilateral retinoblastoma, which results from a new germline RB1 mutation, to investigate gonadal radiation exposure of parents from medical sources before their child's conception. Parents of 206 cases from nine North American institutions and 269 controls participated; fathers of 184 cases and 223 friend and relative controls and mothers of 204 cases and 260 controls provided information in telephone interviews on their medical radiation exposure.

Using RB1 mutations to assess minimal residual disease in metastatic retinoblastoma.

To assess complete remission before subjecting nongermline metastatic retinoblastoma patients to an autologous peripheral stem cell transplant, we tested for patient-specific retinoblastoma tumor suppressor gene (RB1) mutant alleles in cerebrospinal fluid (CSF) and bone marrow. In 1 child with CSF and 1 with bone marrow metastases, allele-specific polymerase chain reaction (AS-PCR) detected the biallelic RB1 mutations specific to their tumors. The tumor of Child A was homozygous for R251X, and in Child B, it was homozygous for R358X.

High-dose chemotherapy with autologous hematopoietic stem cell rescue for stage 4B retinoblastoma.

Background: Stage 4b retinoblastoma (central nervous system metastatic disease) has been lethal in virtually all cases reported. Here we describe a series of eight patients treated with intensive chemotherapy, defined as the intention to include high-dose chemotherapy with autologous hematopoietic stem cell rescue.

Procedure: Induction chemotherapy included cyclophosphamide and/or carboplatin with a topoisomerase inhibitor.

Retinoblastoma CSF metastasis cured by multimodality chemotherapy without radiation.

Objective: Cerebrospinal fluid (CSF) metastasis is the most difficult type of retinoblastoma metastasis to cure, even with bone marrow transplant. Most metastatic retinoblastoma cells express P-glycoprotein causing multidrug resistance (MDR). P-glycoprotein-rich blood vessels form blood-brain and blood-eye barriers, inhibit drug entry into central nervous system (CNS) and eyes.

Toxocariasis mimicking liver, lung, and spinal cord metastases from retinoblastoma.

A boy with bilateral retinoblastoma underwent metastatic surveillance for increased risk of systemic and central nervous system metastasis because of the extensive choroid and optic nerve invasion in his enucleated eye. Two years after finishing chemotherapy, surveillance MRI showed multiple new liver, lung and spinal cord lesions. High Toxocara antibody titers, eosinophilia, and elevated IgE levels supported a diagnosis of toxocariasis, rather than retinoblastoma metastasis.

Trilateral retinoblastoma with pituitary-hypothalamic dysfunction.

Trilateral retinoblastoma is characterized by retinal tumors in one or both eyes, as well as tumors of the pineal gland or parasellar region of the brain. Here we describe a 4-month-old girl, presenting with pituitary dysfunction, hypothalamic overgrowth syndrome and central blindness, in addition to suprasellar and bilateral retinal tumors. Biopsy of the suprasellar tumor confirmed the diagnosis of trilateral retinoblastoma.

A visual approach to providing prognostic information to parents of children with retinoblastoma.

Objective: Parents must rapidly assimilate complex information when a child is diagnosed with cancer. Education correlates with the ability to process and use medical information. Graphic tools aid reasoning and communicate complex ideas with precision and efficiency.

Global issues and opportunities for optimized retinoblastoma care.

The RB1 gene is important in all human cancers. Studies of human retinoblastoma point to a rare retinal cell with extreme dependency on RB1 for initiation but not progression to full malignancy. In developed countries, genetic testing within affected families can predict children at high risk of retinoblastoma before birth; chemotherapy with local therapy often saves eyes and vision; and mortality is 4%.

Extranodal Rosai-Dorfman disease with multifocal bone and epidural involvement causing recurrent spinal cord compression.

Sinus histocytosis with massive lymphadenopathy, or Rosai-Dorfman disease, is a rare histiocytic disorder that typically presents with chronic, self-limiting, cervical lymphadenopathy. We present a case, a diagnostic dilemma for multiple consultation services, of an otherwise well 17-year-old boy without lymphadenopathy who, 8 months after excision of a T9 lytic vertebral lesion and epidural mass that caused cord compression, again presented with cord compression from progressive vertebral disease, recurrent epidural mass, and development of a paraspinal mass and tibial lesion. The excised vertebral and epidural lesions, 2 paraspinal biopsies, and tibial biopsy were interpreted as chronic inflammation until large histiocytes were noted, which were positive for CD68, S100 protein, fascin, and MAC387, and demonstrated characteristic emperipolesis (lymphophagocytosis) that was diagnostic of Rosai-Dorfman disease.