Publications by authors named "Paolo Galluzzi"

48 Publications

Retinoblastoma Is Characterized by a Cold, CD8+ Cell Poor, PD-L1- Microenvironment, Which Turns Into Hot, CD8+ Cell Rich, PD-L1+ After Chemotherapy.

Invest Ophthalmol Vis Sci 2021 Feb;62(2)

Department of Medicine, Surgery and Neuroscience, Ophthalmology Unit, University Hospital of Siena, Siena, Italy.

Purpose: To investigate the impact of chemotherapy (CHT) on human retinoblastoma (RB) tumor microenvironment (TME).

Cases And Methods: Ninety-four RBs were studied, including 44 primary RBs treated by upfront surgery (Group 1) and 50 primary RBs enucleated after CHT (CHT), either intra-arterial (IAC; Group 2, 33 cases) or systemic (S-CHT; Group 3, 17 cases). Conventional and multiplexed immunohistochemistry were performed to make quantitative comparisons among the three groups, for the following parameters: tumor-infiltrating inflammatory cells (TI-ICs); programmed cell death protein 1 (PD-1) positive TI-ICs; Ki67 proliferation index; gliosis; PD-1 ligand (PD-L1) protein expression; vessel number. We also correlated these TME factors with the presence of histological high-risk factors (HHRF+) and RB anaplasia grade (AG).

Results: After CHT, a decrease in both RB burden and Ki67 positivity was observed. In parallel, most subsets of TI-ICs, PD-1+ TI-ICs, gliosis, and PD-L1 protein expression significantly increased (P < 0.001, P = 0.02, P < 0.001, respectively). Vessel number did not significantly vary. Age, HHRFs+ and AG were significantly different between primary and chemoreduced RBs (P < 0.001, P = 0.006, P = 0.001, respectively) and were correlated with most TME factors.

Conclusions: CHT modulates host antitumor immunity by reorienting the RB TME from anergic into an active, CD8+, PD-L1+ hot state. Furthermore, some clinicopathological characteristics of RB correlate with several factors of TME. Our study adds data in favor of the possibility of a new therapeutic scenario in human RB.
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http://dx.doi.org/10.1167/iovs.62.2.6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7862737PMC
February 2021

Orbital Pseudocellulitis: A Retinoblastoma-Associated Masquerade Syndrome.

Ocul Oncol Pathol 2020 Dec 8;6(6):430-437. Epub 2020 Oct 8.

Unit of Ophthalmology, Department of Medicine, Surgery and Neuroscience, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Introduction: A masquerade syndrome is an atypical presentation of a neoplastic process that mimics an inflammatory condition. In this paper, we focus on orbital pseudocellulitis.

Case Series: Our case series includes 5 retinoblastoma patients with orbital pseudocellulitis at presentation. In 3 patients the disease was bilateral, in 1 trilateral, and in 1 unilateral. The eyes with pseudocellulitis were enucleated, while the fellow eyes were treated conservatively, when affected. Four patients responded well to the therapy and showed remission of the tumor. The patient with trilateral retinoblastoma did not respond to therapy and died of disease.

Discussion: Differential diagnosis with infectious orbital cellulitis is extremely important. Patients with orbital cellulitis present with fever, sinusitis, leukocytosis, and raised inflammatory markers, while ophthalmoscopic examination is negative and imaging studies show sinus involvement. On the contrary, patients with retinoblastoma do not show systemic inflammation, while ophthalmoscopic examination reveals leukocoria, buphthalmos, and an intraocular tumor mass associated with retinal detachment. Magnetic resonance imaging shows intralesional calcifications and soft tissue edema without sinus involvement. Histology confirms the diagnosis.

Conclusions: Medical history, physical examination, and imaging studies are crucial in the diagnosis of retinoblastoma-associated orbital pseudocellulitis. Retinoblastoma should be excluded in all patients with signs of pre-septal orbital cellulitis through fundoscopy and/or imaging studies.
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http://dx.doi.org/10.1159/000509810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772876PMC
December 2020

MR Imaging Features to Differentiate Retinoblastoma from Coats' Disease and Persistent Fetal Vasculature.

Cancers (Basel) 2020 Nov 30;12(12). Epub 2020 Nov 30.

Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Center Amsterdam, 1081HV Amsterdam, The Netherlands.

Retinoblastoma mimickers, or pseudoretinoblastoma, are conditions that show similarities with the pediatric cancer retinoblastoma. However, false-positive retinoblastoma diagnosis can cause mistreatment, while false-negative diagnosis can cause life-threatening treatment delay. The purpose of this study is to identify the MR imaging features that best differentiate between retinoblastoma and the most common pseudoretinoblastoma diagnoses: Coats' disease and persistent fetal vasculature (PFV). Here, six expert radiologists performed retrospective assessments (blinded for diagnosis) of MR images of patients with a final diagnosis based on histopathology or clinical follow-up. Associations between 20 predefined imaging features and diagnosis were assessed with exact tests corrected for multiple hypothesis testing. Sixty-six patients were included, of which 33 (50%) were retinoblastoma and 33 (50%) pseudoretinoblastoma patients. A larger eye size, vitreous seeding, and sharp-V-shaped retinal detachment were almost exclusively found in retinoblastoma ( < 0.001-0.022, specificity 93-97%). Features that were almost exclusively found in pseudoretinoblastoma included smaller eye size, ciliary/lens deformations, optic nerve atrophy, a central stalk between optic disc and lens, Y-shaped retinal detachment, and absence of calcifications ( < 0.001-0.022, specificity 91-100%). Additionally, three newly identified imaging features were exclusively present in pseudoretinoblastoma: intraretinal macrocysts ( < 0.001, 38% [9/24] in Coats' disease and 20% [2/10] in PFV), contrast enhancement outside the solid lesion ( < 0.001, 30% [7/23] in Coats' disease and 57% [4/7] in PFV), and enhancing subfoveal nodules (38% [9/24] in Coats' disease). An assessment strategy was proposed for MR imaging differentiation between retinoblastoma and pseudoretinoblastoma, including three newly identified differentiating MR imaging features.
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http://dx.doi.org/10.3390/cancers12123592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7760210PMC
November 2020

Rescue intra-arterial chemotherapy in unilateral multirelapsed peripapillary retinoblastoma: Decision making and the role of MRI.

Eur J Ophthalmol 2020 Sep 9:1120672120957586. Epub 2020 Sep 9.

Department of Ophthalmology, University of Siena, Siena, Italy.

Introduction: In this case report we report our experience with rescue intra-arterial chemotherapy in a case of multi-relapsed peripapillary Retinoblastoma (RB) and the importance of high resolution MRI in detecting possible optic disc infiltration.

Case Report: In 2007, a 14 month-old caucasian girl was referred to our ocular oncology unit for leukocoria. Only left eye was interested, with a single mass of the posterior pole. Patient underwent six cycles of systemic chemotherapy and focal laser consolidation. Several relapses occurred during follow-up. Selective intra-arterial chemotherapy (SIAC) with Melphalan was performed and type IV remission was achieved. A new relapse occurred next to the optic disc. MRI was performed and we decided to try to save the globe with a rescue cycle of SIAC.

Conclusion: MRI has demonstrated to be useful in decision making in RB, giving us a last chance to save the globe.
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http://dx.doi.org/10.1177/1120672120957586DOI Listing
September 2020

Focus on progressive myoclonic epilepsy in Berardinelli-Seip syndrome.

Neurol Sci 2020 Nov 21;41(11):3345-3348. Epub 2020 May 21.

Dipartimento di Medicina Molecolare e dello Sviluppo, Universita' degli Studi di Siena, viale Bracci 16, 53100, Siena, Italy.

Introduction: Berardinelli-Seip syndrome or congenital generalized lipodystrophy type 2 is a rare genetic disorder characterized by selective loss of subcutaneous adipose tissue associated with peripheral insulin resistance and its complications. Nonprogressive mental retardation, dystonia, ataxia, and pyramidal signs are commonly present, whereas epilepsy has only occasionally been observed.

Case Report: We report the case of two sisters, 11 and 18 years old respectively, with an overlapping clinical phenotype compatible with Berardinelli-Seip syndrome and progressive myoclonic epilepsy. Molecular analysis identified an autosomal recessive c.1048C > t;(p(Arg350*)) pathogenic mutation of exon 8 of the BSCL2 gene, which was present in a homozygous state in both patients.

Conclusions: Our paper contributes to further delineate a complex phenotype associated with BSCL2 mutation, underlining how seipin has a central and partially still unknown role that goes beyond adipose tissue metabolism, with a prominent involvement in central nervous system pathology.
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http://dx.doi.org/10.1007/s10072-020-04418-1DOI Listing
November 2020

Conventional, diffusion, and permeability MR findings in ocular medulloepithelioma.

Neuroradiology 2018 Nov 19;60(11):1213-1222. Epub 2018 Sep 19.

Department of Ophthalmology, Referral Center for Retinoblastoma, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Purpose: To describe the neuroradiological features of intraocular medulloepithelioma.

Methods: We retrospectively analyzed the clinical, histopathological, and MRI data of five children with medulloepithelioma. In addition to conventional images, DWI was performed in four patients and mean ADC was calculated; this was limited to the technique of this cohort of patients. DCE was performed in all patients. This is the first paper that presents diffusion and perfusion characteristics of medulloepithelioma.

Results: Four tumors were malignant teratoid variants, two non-teratoid variants. Tumors were hyperintense on T1-weighted images and hypointense on T2-weighted images. Calcifications were detectable in two out of five tumors. Cavities were detectable in three out of five tumors. All tumors showed some degree of enhancement. The mean ADC of all four patients was 1.156 ± 242.75 × 10 mm/s. Mean ktrans, Ve, Kep, TME, AUC, SER, and peak enhancement were 0.082 ± 0.054, 0.19 ± 0.076, 0.31 ± 0.084, 0.97 ± 0.0784, 1.22 ± 0.81, 67.34 ± 31.7, and 14.84 ± 7.34 respectively. TICs showed a very high ratio of slow increase, > 50% persistence and some degree of wash out. Teratoid variants showed higher K-trans, AUC, VE, TME, and persistent TIC pattern than non-teratoid ones, while plateau pattern ratio was lower.

Conclusion: Conventional MR findings were similar to previously reported cases. Mean ADCs were moderately high. TICs showed slow increase and presence of wash out. K-trans, AUC, VE, and TME were higher in teratoid variants. Permeability parameters in differential diagnosis with lesions mimicking medulloepithelioma need further investigations.
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http://dx.doi.org/10.1007/s00234-018-2094-1DOI Listing
November 2018

Stroke in Pregnancy and Review of Current Literature: Arterial Spin-Labeling MRI Can Identify the Presence and Intensity of Collateral Circle.

J Stroke Cerebrovasc Dis 2018 Dec 15;27(12):3575-3577. Epub 2018 Sep 15.

Unit of Neuroimaging and Neurointervention, Department of Neurological and Neurosensorial Sciences, University Hospital of Siena, "Santa Maria alle Scotte", Siena, Italy. Electronic address:

Diagnosis and treatment of acute ischemic stroke is challenging during pregnancy. We present a diagnostic strategy in a pregnant woman with suspect of acute stroke. We perform magnetic resonance with arterial spin labeling sequence, an X-ray and contrast medium safe perfusion technique. Arterial spin labeling can detects collateral vessels in patient with acute ischemic stroke. Demonstrating collateral vessels is relevant for better understanding prognosis and for improving the diagnostic assessment in pregnancy.
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http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2018.08.027DOI Listing
December 2018

MR Imaging Features of Retinoblastoma: Association with Gene Expression Profiles.

Radiology 2018 08 1;288(2):506-515. Epub 2018 May 1.

From the Departments of Radiology and Nuclear Medicine (R.W.J., M.C.d.J., J.A.C., P.d.G.), Clinical Genetics (I.E.K., J.C.D.), Ophthalmology (A.C.M.), Pathology (P.v.d.V.), Pediatric Oncology (J.C.), and Epidemiology and Biostatistics (I.E.), VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands; European Retinoblastoma Imaging Collaboration (ERIC) (R.W.J., M.C.d.J., S.S., S.G., H.J.B., P.M., P.G., J.A.C., P.d.G.); Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany (S.S., S.G.); Department of Radiology, Institut Curie, Paris, France and Paris Sciences et Lettres Research University, Paris, France (H.J.B.); Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland (P.M.); and Unit of Neuroimaging and Neurointervention, Department of Neurosciences, Siena University Hospital, Siena, Italy (P.G.).

Purpose To identify associations between magnetic resonance (MR) imaging features and gene expression in retinoblastoma. Materials and Methods A retinoblastoma MR imaging atlas was validated by using anonymized MR images from referral centers in Essen, Germany, and Paris, France. Images were from 39 patients with retinoblastoma (16 male and 18 female patients [the sex in five patients was unknown]; age range, 5-90 months; inclusion criterion: pretreatment MR imaging). This atlas was used to compare MR imaging features with genome-wide messenger RNA (mRNA) expression data from 60 consecutive patients obtained from 1995 to 2012 (35 male patients [58%]; age range, 2-69 months; inclusion criteria: pretreatment MR imaging, genome-wide mRNA expression data available). Imaging pathway associations were analyzed by means of gene enrichment. In addition, imaging features were compared with a predefined gene expression signature of photoreceptorness. Statistical analysis was performed with generalized linear modeling of radiology traits on normalized log2-transformed expression values. P values were corrected for multiple hypothesis testing. Results Radiogenomic analysis revealed 1336 differentially expressed genes for qualitative imaging features (threshold P = .05 after multiple hypothesis correction). Loss of photoreceptorness gene expression correlated with advanced stage imaging features, including multiple lesions (P = .03) and greater eye size (P < .001). The number of lesions on MR images was associated with expression of MYCN (P = .04). A newly defined radiophenotype of diffuse-growing, plaque-shaped, multifocal tumors displayed overexpression of SERTAD3 (P = .003, P = .049, and P = .06, respectively), a protein that stimulates cell growth by activating the E2F network. Conclusion Radiogenomic biomarkers can potentially help predict molecular features, such as photoreceptorness loss, that indicate tumor progression. Results imply a possible role for radiogenomics in future staging and treatment decision making in retinoblastoma.
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http://dx.doi.org/10.1148/radiol.2018172000DOI Listing
August 2018

The spectrum of magnetic resonance findings in cerebrotendinous xanthomatosis: redefinition and evidence of new markers of disease progression.

J Neurol 2017 May 21;264(5):862-874. Epub 2017 Mar 21.

Unit of Diagnostic and Therapeutic Neuroradiology, Azienda Ospedaliera Siena, Siena, Italy.

Cerebrotendinous xanthomatosis (CTX) is a metabolic disease characterized by systemic signs and neurological impairment, which can be prevented if chenodeoxycholic acid (CDCA) treatment is started early. Despite brain MRI represents an essential diagnostic tool, the spectrum of findings is worth to be reappraised, and follow-up data are needed. We performed clinical evaluation and brain MRI in 38 CTX patients. Sixteen of them who were untreated at baseline examination underwent clinical and MRI follow-up after long-term treatment with CDCA. Brain MRI abnormalities included cortical and cerebellar atrophy, and T2W/FLAIR hyperintensity involving subcortical, periventricular, and cerebellar white matter, the brainstem and the dentate nuclei. Regarding the dentate nuclei, we also observed T1W/FLAIR hypointensity consistent with cerebellar vacuolation and T1W/FLAIR/SW hypointense alterations compatibly with calcification in a subgroup of patients. Long-term follow-up showed that clinical and neuroradiological stability or progression were almost invariably associated. In patients with cerebellar vacuolation at baseline, a worsening over time was observed, while subjects lacking vacuoles were clinically and neuroradiologically stable at follow-up. The brains of CTX patients very often show both supratentorial and infratentorial abnormalities at MRI, the latter being related to clinical disability and including a wide spectrum of dentate nuclei alterations. The presence of cerebellar vacuolation may be regarded as a useful biomarker of disease progression and unsatisfactory response to therapy. On the other hand, the absence of dentate nuclei signal alteration should be considered an indicator of better prognosis.
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http://dx.doi.org/10.1007/s00415-017-8440-0DOI Listing
May 2017

Exome sequencing coupled with mRNA analysis identifies NDUFAF6 as a Leigh gene.

Mol Genet Metab 2016 11 3;119(3):214-222. Epub 2016 Sep 3.

Medical Genetics, University of Siena, Siena, Italy.

We report here the case of a young male who started to show verbal fluency disturbance, clumsiness and gait anomalies at the age of 3.5years and presented bilateral striatal necrosis. Clinically, the diagnosis was compatible with Leigh syndrome but the underlying molecular defect remained elusive even after exome analysis using autosomal/X-linked recessive or de novo models. Dosage of respiratory chain activity on fibroblasts, but not in muscle, underlined a deficit in complex I. Re-analysis of heterozygous probably pathogenic variants, inherited from one healthy parent, identified the p.Ala178Pro in NDUFAF6, a complex I assembly factor. RNA analysis showed an almost mono-allelic expression of the mutated allele in blood and fibroblasts and puromycin treatment on cultured fibroblasts did not lead to the rescue of the maternal allele expression, not supporting the involvement of nonsense-mediated RNA decay mechanism. Complementation assay underlined a recovery of complex I activity after transduction of the wild-type gene. Since the second mutation was not detected and promoter methylation analysis resulted normal, we hypothesized a non-exonic event in the maternal allele affecting a regulatory element that, in conjunction with the paternal mutation, leads to the autosomal recessive disorder and the different allele expression in various tissues. This paper confirms NDUFAF6 as a genuine morbid gene and proposes the coupling of exome sequencing with mRNA analysis as a method useful for enhancing the exome sequencing detection rate when the simple application of classical inheritance models fails.
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http://dx.doi.org/10.1016/j.ymgme.2016.09.001DOI Listing
November 2016

Combined ultrasound and exome sequencing approach recognizes Opitz G/BBB syndrome in two malformed fetuses.

Clin Dysmorphol 2017 Jan;26(1):18-25

aMedical Genetics, Department of Medical Biotechnologies bBioengineering Unit, Department of Medical Biotechnologies, University of Siena cMedical Genetics Unit, Department of Medical Biotechnologies dDepartment of Neurology NINT (Neuroimmagini e Neurointerventistica), Azienda Ospedaliera Universitaria Senese eDepartment of Obstetrics and Gynecology, Azienda, Siena, Italy.

Orofacial clefts are the most common congenital craniofacial anomalies and can occur as an isolated defect or be associated with other anomalies such as posterior fossa anomalies as a part of several genetic syndromes. We report two consecutive voluntary pregnancy interruptions in a nonconsanguineous couple following the fetal ultrasound finding of cleft lip and palate and posterior fossa anomalies confirmed by means of post-termination examination on the second fetus. The quantitative fluorescent PCR, the karyotype, and the comparative genomic hybridization-array analysis after amniocentesis were normal. Exome sequencing on abortive material from both fetuses detected a missense mutation in MID1, resulting in a clinical diagnosis of Opitz G/BBB syndrome. The same mutation was found in the mother and in her brother, who both revealed cerebellar anomalies at an MRI examination. Our study supports the efficacy of exome sequencing in the presence of both a family history suggestive of an inherited disorder and well-documented ultrasound findings. It reveals the importance of a synergistic effort between gynecologists and geneticists aimed at the integration of the most sophisticated ultrasound techniques with the next-generation sequencing tools to provide a definite diagnosis essential to orient the final decision and to estimate a proper recurrence risk.
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http://dx.doi.org/10.1097/MCD.0000000000000152DOI Listing
January 2017

MRI-based assessment of the pineal gland in a large population of children aged 0-5 years and comparison with pineoblastoma: part II, the cystic gland.

Neuroradiology 2016 Jul 29;58(7):713-21. Epub 2016 Apr 29.

Unit of Diagnostic and Therapeutic Neuroradiology, Department of Neurosciences, Azienda Ospedaliera Universitaria Senese, Siena, Italy.

Introduction: Pineal cysts are a common incidental finding on brain MRI with resulting difficulties in differentiation between normal glands and pineal pathologies. The aim of this study was to assess the size and morphology of the cystic pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases.

Methods: In this retrospective multicenter study, 257 MR examinations (232 children, 0-5 years) were evaluated regarding pineal gland size (width, height, planimetric area, maximal cyst(s) size) and morphology. We performed linear regression analysis with 99 % prediction intervals of gland size versus age for the size parameters. Results were compared with a recent meta-analysis of pineoblastoma by de Jong et al.

Results: Follow-up was available in 25 children showing stable cystic findings in 48 %, cyst size increase in 36 %, and decrease in 16 %. Linear regression analysis gave 99 % upper prediction bounds of 10.8 mm, 10.9 mm, 7.7 mm and 66.9 mm(2), respectively, for cyst size, width, height, and area. The slopes (size increase per month) of each parameter were 0.030, 0.046, 0.021, and 0.25, respectively. Most of the pineoblastomas showed a size larger than the 99 % upper prediction margin, but with considerable overlap between the groups.

Conclusion: We presented age-adapted normal values for size and morphology of the cystic pineal gland in children aged 0 to 5 years. Analysis of size is helpful in discriminating normal glands from cystic pineal pathologies such as pineoblastoma. We also presented guidelines for the approach of a solid or cystic pineal gland in hereditary retinoblastoma patients.
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http://dx.doi.org/10.1007/s00234-016-1683-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958131PMC
July 2016

MRI-based assessment of the pineal gland in a large population of children aged 0-5 years and comparison with pineoblastoma: part I, the solid gland.

Neuroradiology 2016 Jul 29;58(7):705-12. Epub 2016 Apr 29.

Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany.

Introduction: Differentiation between normal solid (non-cystic) pineal glands and pineal pathologies on brain MRI is difficult. The aim of this study was to assess the size of the solid pineal gland in children (0-5 years) and compare the findings with published pineoblastoma cases.

Methods: We retrospectively analyzed the size (width, height, planimetric area) of solid pineal glands in 184 non-retinoblastoma patients (73 female, 111 male) aged 0-5 years on MRI. The effect of age and gender on gland size was evaluated. Linear regression analysis was performed to analyze the relation between size and age. Ninety-nine percent prediction intervals around the mean were added to construct a normal size range per age, with the upper bound of the predictive interval as the parameter of interest as a cutoff for normalcy.

Results: There was no significant interaction of gender and age for all the three pineal gland parameters (width, height, and area). Linear regression analysis gave 99 % upper prediction bounds of 7.9, 4.8, and 25.4 mm(2), respectively, for width, height, and area. The slopes (size increase per month) of each parameter were 0.046, 0.023, and 0.202, respectively. Ninety-three percent (95 % CI 66-100 %) of asymptomatic solid pineoblastomas were larger in size than the 99 % upper bound.

Conclusion: This study establishes norms for solid pineal gland size in non-retinoblastoma children aged 0-5 years. Knowledge of the size of the normal pineal gland is helpful for detection of pineal gland abnormalities, particularly pineoblastoma.
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http://dx.doi.org/10.1007/s00234-016-1684-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4958126PMC
July 2016

Unusual case of traumatic neuroma of the orbit.

Orbit 2016 18;35(2):62-5. Epub 2016 Feb 18.

d Department of Medicine, Surgery and Neuroscience , University of Siena , Siena , Italy.

Traumatic or amputation neuromas are neoformations developing after damage to a peripheral nerve. They are not proper tumors but rather a reactive process or a frustrated attempt of nerve regeneration. Traumatic neuromas are potentially found in every sensory peripheral nerve and often at the site of past surgical intervention, including orbital surgery. A 29-year-old Northern African migrant presented progressive exophthalmos and progressive loss of acuity in left eye, which had started about 6 months before after a cranio-facial trauma caused by a violent assault. MRI of the orbits showed a massive intra-orbital, intra-conical lesion, clearly compressing and dislocating the optic nerve and extending posteriorly to the orbital apex. Surgery was performed through lateral approach of Kroenlein and led to complete excision of the lesion. Histology revealed fibrotic, adipose and striated muscle tissues, a disordered, non-neoplastic overgrowth of small and large fascicles of nerves, inflammatory infiltrates, and fibrosis with sparse calcifications were diffusely observed in a background of fat, scar and striated muscle tissued. Patient was discharged on the fifth day in good health condition, without deficit of eye motion but without recovery of visual acuity. In conclusion, this case demonstrates that traumatic neuromas may arise in the orbit in patients with minor direct trauma to nerves and without previous surgical treatment.
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http://dx.doi.org/10.3109/01676830.2015.1099703DOI Listing
December 2016

High-Resolution Magnetic Resonance Imaging Can Reliably Detect Orbital Tumor Recurrence after Enucleation in Children with Retinoblastoma.

Ophthalmology 2016 Mar 12;123(3):635-45. Epub 2015 Dec 12.

Department of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Essen, Germany.

Purpose: Orbital tumor recurrence is a rare but serious complication in children with retinoblastoma, leading to a high risk of metastasis and death. Therefore, we assume that these recurrences have to be detected and treated as early as possible. Preliminary studies used magnetic resonance imaging (MRI) to evaluate postsurgical findings in the orbit. In this study, we assessed the diagnostic accuracy of high-resolution MRI to detect orbital tumor recurrence in children with retinoblastoma in a large study cohort.

Design: Consecutive retrospective study (2007-2013) assessing MRI findings after enucleation.

Participants: A total of 103 MRI examinations of 55 orbits (50 children, 27 male/23 female, mean age 16.3±12.4 months) with a median time of 8 months (range, 0-93) after enucleation for retinoblastoma.

Methods: High-resolution MRI using orbital surface coils was performed on 1.5 Tesla MRI systems to assess abnormal orbital findings.

Main Outcome Measures: Five European experts in retinoblastoma imaging evaluated the MRI examinations regarding the presence of abnormal orbital gadolinium enhancement and judged them as "definitive tumor," "suspicious of tumor," "postsurgical condition/scar formation," or "without pathologic findings." The findings were correlated to histopathology (if available), MRI, and clinical follow-up.

Results: Abnormal orbital enhancement was a common finding after enucleation (100% in the first 3 months after enucleation, 64.3% >3 years after enucleation). All histopathologically confirmed tumor recurrences (3 of 55 orbits, 5.5%) were correctly judged as "definitive tumor" in MRI. Two orbits from 2 children rated as "suspicious of tumor" received intravenous chemotherapy without histopathologic confirmation; further follow-up (67 and 47 months) revealed no sign of tumor recurrence. In 90.2%, no tumor was suspected on MRI, which was clinically confirmed during follow-up (median follow-up after enucleation, 45 months; range, 8-126).

Conclusions: High-resolution MRI with orbital surface coils may reliably distinguish between common postsurgical contrast enhancement and orbital tumor recurrence, and therefore may be a useful tool to evaluate orbital tumor recurrence after enucleation in children with retinoblastoma. We recommend high-resolution MRI as a potential screening tool for the orbit in children with retinoblastoma to exclude tumor recurrence, especially in high-risk patients within the critical first 2 years after enucleation.
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http://dx.doi.org/10.1016/j.ophtha.2015.10.054DOI Listing
March 2016

Diagnostic Accuracy of Intraocular Tumor Size Measured with MR Imaging in the Prediction of Postlaminar Optic Nerve Invasion and Massive Choroidal Invasion of Retinoblastoma.

Radiology 2016 Jun 19;279(3):817-26. Epub 2015 Dec 19.

From the Departments of Radiology and Nuclear Medicine (M.C.d.J., F.J.S.v.d.M., D.P.N., J.A.C., P.d.G.), Pathology (P.v.d.V.), and Ophthalmology (A.C.M.), VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands; Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, Germany (S.L.G., S.S.); Departments of Radiology (H.J.B.) and Tumor Biology (X.S.G.), Institut Curie, Paris, France; Unit of Neuroimaging and Neurointervention, Department of Neurosciences, Siena University Hospital, Siena, Italy (P.G., A.C.); Department of Radiology, Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland (P.M.); Unit of Ophthalmology, University of Siena, Policlinico Santa Maria alle Scotte, Siena, Italy (S.D.F.); and Department of Pathology and Neuropathology, Institute of Pathology and Neuropathology, Faculty of Medicine, University Duisburg-Essen, Essen, Germany (K.A.M.).

Purpose To assess the correlation of intraocular retinoblastoma tumor size measured with magnetic resonance (MR) imaging in the prediction of histopathologically determined metastatic risk factors (postlaminar optic nerve invasion and massive choroidal invasion). Materials and Methods The ethics committee approved this retrospective multicenter study with a waiver of informed consent. The study population included 370 consecutive patients with retinoblastoma (375 eyes) who underwent baseline MR imaging, followed by primary enucleation from 1993 through 2014. Tumor sizes (maximum diameter and volume) were measured independently by two observers and correlated with histopathologic risk factors. Receiver operating characteristic curves were used to analyze the diagnostic accuracy of tumor size, and areas under the curve were calculated. Logistic regression analysis was performed to evaluate potential confounders. Results Receiver operating characteristic analysis of volume and diameter, respectively, yielded areas under the curve of 0.77 (95% confidence interval [CI]: 0.70, 0.85; P < .0001) and 0.78 (95% CI: 0.71, 0.85; P < .0001) for postlaminar optic nerve invasion (n = 375) and 0.67 (95% CI: 0.57, 0.77; P = .0020) and 0.70 (95% CI: 0.59, 0.80; P = .0004) for massive choroidal tumor invasion (n = 219). For the detection of co-occurring massive choroidal invasion and postlaminar optic nerve invasion (n = 219), volume and diameter showed areas under the curve of 0.81 (95% CI: 0.70, 0.91; P = .0032) and 0.83 (95% CI: 0.73, 0.93; P = .0016), respectively. Conclusion Intraocular tumor size shows a strong association with postlaminar optic nerve invasion and a moderate association with massive choroidal invasion. These findings provide diagnostic accuracy measures at different size cutoff levels, which could potentially be useful in a clinical setting, especially within the scope of the increasing use of eye-salvage treatment strategies. (©) RSNA, 2015 Online supplemental material is available for this article.
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http://dx.doi.org/10.1148/radiol.2015151213DOI Listing
June 2016

Alternated intra-arterial and intravitreal chemotherapy for advanced intraocular retinoblastoma: preliminary successful results without systemic chemotherapy.

Int Ophthalmol 2015 Dec 28;35(6):887-95. Epub 2015 Sep 28.

Unit of Ophthalmology, Referral Center for Retinoblastoma, Department of Surgery, Policlinico "Santa Maria alle Scotte", Siena, Italy.

To describe the efficacy of intravitreal chemotherapy (IViC) preceded by intra-arterial chemotherapy (IAC) for the treatment of advanced stage retinoblastoma. This non-comparative interventional case series retrospectively reviewed the medical records of six patients who presented within months of each other with unilateral retinoblastoma, Reese-Ellsworth stage Vb/D of ABC classification in the affected eye. After clinical and ophthalmoscopic evaluation, they underwent MRI to exclude local and CNS dissemination. The IAC was given to treat retinal masses and intravitreal injections to treat vitreous seeding. Patients had received two cycles (six infusions) of IAC, and from six up to ten melphalan injections into the vitreous, with an interval of 7-10 days between them. From one to four intravitreal injections were performed for partial remission or consolidation. No permanent complications of procedures have been reported. All patients underwent to bimonthly MRI examination, during treatment and every 3 months for 1 year after last injection, to exclude orbital dissemination. Successful control (100 %) of tumor masses and vitreous seeds was achieved in all cases at 12 months follow-up. Complications were posterior lens opacity, acute ischemic papillitis, partial CVR thrombosis, hypotonia (case 1), partial vitreous hemorrhage (case 4). No complications appeared in cases 2, 3, 5, and 6. No intraocular or orbital tumor recurrence or retinoblastoma metastases (follow-up range, 12-33 months) were observed. Sequential IAC and intravitreal melphalan for advanced retinoblastoma allowed to provide retinal and vitreous seed control.
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http://dx.doi.org/10.1007/s10792-015-0129-8DOI Listing
December 2015

Identification of Intraorbital Arteries in Pediatric Age by High Resolution Superselective Angiography.

Orbit 2015 8;34(5):237-47. Epub 2015 Jul 8.

f Department of Life Sciences , University of Siena , Siena , Italy.

Purpose: Angiography is a powerful tool to identify intraorbital arteries. However, the incidence by which these vessels can be identified is unknown. Our purpose was to determine such incidence and which angiographic approach is best for the identification of each artery.

Methods: A retrospective study of 353 angiographic procedures (via ophthalmic artery and/or external carotid artery) carried out on 79 children affected by intraocular retinoblastoma was made to investigate the arterial anatomy in 87 orbits. For each intraorbital artery two parameters were calculated: the angiographic incidence, as the percentage of times a given artery was identified, and the visibility index, as the ratio between the angiographic incidence and the true anatomic incidence.

Results: All collaterals of the ophthalmic artery could be spotted. Most of them were identified with a high angiographic incidence; some of them were less easily identified because too thin or because frequently shielded. The visibility index paralleled the angiographic incidence of most arteries. However, the lacrimal and meningolacrimal arteries had a higher visibility index suggesting that their identification was more frequent than the angiographic incidence alone could suggest. Statistical analysis demonstrated that the lacrimal artery and some muscular branches had higher chances to be identified if the angiography of the ophthalmic artery was accompanied by the study of the external carotid system.

Conclusion: This work provides an objective measure of how powerful angiography is to identify intraorbital arteries as well as useful references for professionals who need to operate in the orbit.
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http://dx.doi.org/10.3109/01676830.2015.1049368DOI Listing
April 2016

MRI helps depict clinically undetectable risk factors in advanced stage retinoblastomas.

Neuroradiol J 2015 Feb;28(1):53-61

Neuroimaging and Neurointerventional (NINT) Unit.

This study compared high-resolution MRI with histology in advanced stage retinoblastomas in which ophthalmoscopy and ultrasonography did not give an exhaustive depiction of the tumour and/or its extension. MRI of orbits and head in 28 retinoblastoma patients (28 eyes) treated with primary enucleation were evaluated. Iris neoangiogenesis, infiltrations of optic nerve, choroid, anterior segment and sclera suspected at MR and histology were compared. Abnormal anterior segment enhancement (AASE) was also correlated with histologically proven infiltrations. Brain images were also evaluated. Significant values were obtained for: prelaminar optic nerve (ON) sensitivity (0.88), positive predictive value (PPV) (0.75) and negative predictive value (NPV) (0.71); post-laminar ON sensitivity (0.50), specificity (0.83), PPV (0.50) and NPV (0.83); overall choroid sensitivity (0.82), and massive choroid NPV (0.69); scleral specificity (1), and NPV (1). AASE correlated with iris neoangiogenesis in 14 out of 19 eyes, and showed significant values for: overall ON PPV (0.65), prelaminar ON sensitivity (0.65), and PPV (0.61), post-laminar ON NPV (0.64); overall choroid sensitivity (0.77), PPV (0.59) and NPV (0.73); scleral NPV (0.83); anterior segment sensitivity (1), and NPV (1). Odds ratios (OR) and accuracy were significant in scleral and prelaminar optic nerve infiltration. Brain examination was unremarkable in all cases. High-resolution MRI may add important findings to clinical evaluation of advanced stage retinoblastomas.
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http://dx.doi.org/10.15274/NRJ-2014-10103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4757124PMC
February 2015

The potential of 3T high-resolution magnetic resonance imaging for diagnosis, staging, and follow-up of retinoblastoma.

Surv Ophthalmol 2015 Jul-Aug;60(4):346-55. Epub 2015 Jan 28.

Department of Radiology, University Hospital, Lausanne, Switzerland.

We demonstrate the value of high-resolution magnetic resonance imaging (MRI) in diagnosing, staging, and follow-up of retinoblastoma during eye-saving treatment. We have included informative retinoblastoma cases scanned on a 3T MRI system from a retrospective retinoblastoma cohort from 2009 through 2013. We show that high-resolution MRI has the potential to detect small intraocular seeds, hemorrhage, and metastatic risk factors not visible with fundoscopy (e.g., optic nerve invasion and choroidal invasion), and treatment response. Unfortunately, however, the diagnostic accuracy of high-resolution MRI is not perfect, especially for subtle intraocular seeds or minimal postlaminar optic nerve invasion. The most important application of MRI is the detection of metastatic risk factors, as these cannot be found by fundoscopy and ultrasound.
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http://dx.doi.org/10.1016/j.survophthal.2015.01.002DOI Listing
December 2015

Cerebral circulation time is prolonged and not correlated with EDSS in multiple sclerosis patients: a study using digital subtracted angiography.

PLoS One 2015 13;10(2):e0116681. Epub 2015 Feb 13.

Dept. of Medicine, Surgery & Neuroscience, University of Siena, Siena, Italy.

Literature has suggested that changes in brain flow circulation occur in patients with multiple sclerosis. In this study, digital subtraction angiography (DSA) was used to measure the absolute CCT value in MS patients and to correlate its value to age at disease onset and duration, and to expand disability status scale (EDSS). DSA assessment was performed on eighty MS patients and on a control group of forty-four age-matched patients. CCT in MS and control groups was calculated by analyzing the angiographic images. Lesion and brain volumes were calculated in a representative group of MS patients. Statistical correlations among CCT and disease duration, age at disease onset, lesion load, brain volumes and EDSS were considered. A significant difference between CCT in MS patients (mean = 4.9s; sd = 1.27 s) and control group (mean = 2.8s; sd = 0.51 s) was demonstrated. No significant statistical correlation was found between CCT and the other parameters in all MS patients. Significantly increased CCT value in MS patients suggests the presence of microvascular dysfunctions, which do not depend on clinical and MRI findings. Hemodynamic changes may not be exclusively the result of a late chronic inflammatory process.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0116681PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4334558PMC
January 2016

Assessment of early-stage optic nerve invasion in retinoblastoma using high-resolution 1.5 Tesla MRI with surface coils: a multicentre, prospective accuracy study with histopathological correlation.

Eur Radiol 2015 May 30;25(5):1443-52. Epub 2014 Nov 30.

Department of Radiology, Institut Curie, Paris, France,

Objectives: To assess the accuracy of high-resolution (HR) magnetic resonance imaging (MRI) in diagnosing early-stage optic nerve (ON) invasion in a retinoblastoma cohort.

Methods: This IRB-approved, prospective multicenter study included 95 patients (55 boys, 40 girls; mean age, 29 months). 1.5-T MRI was performed using surface coils before enucleation, including spin-echo unenhanced and contrast-enhanced (CE) T1-weighted sequences (slice thickness, 2 mm; pixel size <0.3 × 0.3 mm(2)). Images were read by five neuroradiologists blinded to histopathologic findings. ROC curves were constructed with AUC assessment using a bootstrap method.

Results: Histopathology identified 41 eyes without ON invasion and 25 with prelaminar, 18 with intralaminar and 12 with postlaminar invasion. All but one were postoperatively classified as stage I by the International Retinoblastoma Staging System. The accuracy of CE-T1 sequences in identifying ON invasion was limited (AUC = 0.64; 95 % CI, 0.55 - 0.72) and not confirmed for postlaminar invasion diagnosis (AUC = 0.64; 95 % CI, 0.47 - 0.82); high specificities (range, 0.64 - 1) and negative predictive values (range, 0.81 - 0.97) were confirmed.

Conclusion: HR-MRI with surface coils is recommended to appropriately select retinoblastoma patients eligible for primary enucleation without the risk of IRSS stage II but cannot substitute for pathology in differentiating the first degrees of ON invasion.

Key Points: • HR-MRI excludes advanced optic nerve invasion with high negative predictive value. • HR-MRI accurately selects patients eligible for primary enucleation. • Diagnosis of early stages of optic nerve invasion still relies on pathology. • Several physiological MR patterns may mimic optic nerve invasion.
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http://dx.doi.org/10.1007/s00330-014-3514-1DOI Listing
May 2015

First report of spondylodiscitis due to vancomycin heteroresistant Staphylococcus capitis in immunocompetent host.

J Infect Chemother 2014 Oct 12;20(10):639-42. Epub 2014 Aug 12.

Department of Medical Biotechnologies, University of Siena, Siena, Italy; University Division of Infectious Diseases, Hospital Department of Specialized and Internal Medicine, Siena, Italy. Electronic address:

We report a successfully treated case of spondylodiscitis and bloodstream infection due to vancomycin heteroresistant Staphylococcus capitis, in an adult immunocompetent patient with multiple antibiotics intolerance. S. capitis is rarely involved in osteomyelitis and, to our knowledge, this is the first report of vancomycin heteroresistance phenomenon in an S. capitis strain causing spondylodiscitis.
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http://dx.doi.org/10.1016/j.jiac.2014.04.004DOI Listing
October 2014

Epithelial cyst of the superior oblique muscle trochlea.

Orbit 2014 Oct 12;33(5):392-4. Epub 2014 Jun 12.

Department of Neurosurgery, Policlinico "Santa Maria alle Scotte" , Siena , Italy .

Most of the congenital orbital cysts are choristomas such as dermoid or epidermoid and only in a few cases they are epithelial. Clinically, they manifest as cystic movable formations mostly localized in the upper temporal quadrant of the orbit. We describe here the case of a 49-year-old man with an orbital cyst localized in the upper-nasal quadrant of the orbit and which was showing signs of a gradual enlargement and progression over the past weeks. Computed tomography revealed a cyst of 1.9 × 1.6 cm in size and located within the trochlea of the upper oblique muscle. The cyst was completely extirpated after orbitotomy performed by superciliary approach. Histopathology revealed a cyst with nonkeratinized cuboidal epithelium. Postoperative course was uneventful, without inflammation signs, and after 5 weeks excellent functional and aesthetic effects were achieved with no iatrogenic alteration of the ocular motility.
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http://dx.doi.org/10.3109/01676830.2014.902476DOI Listing
October 2014

Diagnostic performance of magnetic resonance imaging and computed tomography for advanced retinoblastoma: a systematic review and meta-analysis.

Ophthalmology 2014 May 1;121(5):1109-18. Epub 2014 Mar 1.

Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands.

Purpose: To determine and compare the diagnostic performance of magnetic resonance imaging (MRI) and computed tomography (CT) for the diagnosis of tumor extent in advanced retinoblastoma, using histopathologic analysis as the reference standard.

Design: Systematic review and meta-analysis.

Participants: Patients with advanced retinoblastoma who underwent MRI, CT, or both for the detection of tumor extent from published diagnostic accuracy studies.

Methods: Medline and Embase were searched for literature published through April 2013 assessing the diagnostic performance of MRI, CT, or both in detecting intraorbital and extraorbital tumor extension of retinoblastoma. Diagnostic accuracy data were extracted from included studies. Summary estimates were based on a random effects model. Intrastudy and interstudy heterogeneity were analyzed.

Main Outcome Measures: Sensitivity and specificity of MRI and CT in detecting tumor extent.

Results: Data of the following tumor-extent parameters were extracted: anterior eye segment involvement and ciliary body, optic nerve, choroidal, and (extra)scleral invasion. Articles on MRI reported results of 591 eyes from 14 studies, and articles on CT yielded 257 eyes from 4 studies. The summary estimates with their 95% confidence intervals (CIs) of the diagnostic accuracy of conventional MRI at detecting postlaminar optic nerve, choroidal, and scleral invasion showed sensitivities of 59% (95% CI, 37%-78%), 74% (95% CI, 52%-88%), and 88% (95% CI, 20%-100%), respectively, and specificities of 94% (95% CI, 84%-98%), 72% (95% CI, 31%-94%), and 99% (95% CI, 86%-100%), respectively. Magnetic resonance imaging with a high (versus a low) image quality showed higher diagnostic accuracies for detection of prelaminar optic nerve and choroidal invasion, but these differences were not statistically significant. Studies reporting the diagnostic accuracy of CT did not provide enough data to perform any meta-analyses.

Conclusions: Magnetic resonance imaging is an important diagnostic tool for the detection of local tumor extent in advanced retinoblastoma, although its diagnostic accuracy shows room for improvement, especially with regard to sensitivity. With only a few-mostly old-studies, there is very little evidence on the diagnostic accuracy of CT, and generally these studies show low diagnostic accuracy. Future studies assessing the role of MRI in clinical decision making in terms of prognostic value for advanced retinoblastoma are needed.
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http://dx.doi.org/10.1016/j.ophtha.2013.11.021DOI Listing
May 2014

Second cranio-facial malignancies in hereditary retinoblastoma survivors previously treated with radiation therapy: clinic and radiologic characteristics and survival outcomes.

Eur J Cancer 2013 May 14;49(8):1939-47. Epub 2013 Feb 14.

Department of Radiology, VU University Medical Center, Amsterdam, The Netherlands.

Introduction: Hereditary retinoblastoma survivors have an increased risk for cranio-facial second primary tumours (SPT), especially after treatment with external beam radiotherapy (EBRT). This multicentre study evaluates the clinical and imaging characteristics and outcomes of cranio-facial SPTs in irradiated retinoblastoma survivors.

Patients And Methods: Clinical and radiological data of 42 hereditary retinoblastoma patients with 44 second and third malignancies were reviewed. Radiological data included anatomic location and computed tomography (CT) and magnetic resonance (MR) characteristics. Cox regression and likelihood ratio chi-square test were used to evaluate differences in patients' survival rates.

Results: Cranio-facial SPTs were diagnosed at a median age of 13 years. Histological types included osteosarcomas (43%), rhabdomyosarcomas (20%) (57% embryonal, 43% alveolar) and a variety of other types of SPT (37%). Predilection sites were: temporal fossa (39%), ethmoid sinus (23%), orbit (18%), maxillary sinus (16%) and intracranial dura mater (4%). Most of the osteosarcomas (78%) and rhabdomyosarcomas (80%) occurred in patients treated with EBRT in the first year-of-life. Treatment of SPTs with a microscopically complete surgical resection led to a significantly better 5-year overall survival (OS) (P=0.017) and event-free survival (EFS) (P=0.012) compared to patients treated without surgery or incomplete resection (OS: 83% versus 52%; EFS: 80% versus 47%).

Conclusions: Osteosarcomas and rhabdomyosarcomas are the most common cranio-facial SPTs in irradiated hereditary retinoblastoma survivors, which develop in specific locations and occur predominantly in patients irradiated in their first year-of-life. Microscopically complete surgical resection of SPTs is a major prognostic factor, suggesting the potential benefit of early detection by imaging.
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http://dx.doi.org/10.1016/j.ejca.2013.01.010DOI Listing
May 2013

Trilateral retinoblastoma: neuroimaging characteristics and value of routine brain screening on admission.

J Neurooncol 2012 Sep 18;109(3):535-44. Epub 2012 Jul 18.

Department of Radiology, VU University Medical Center, Postbox 7057, 1007 MB, Amsterdam, The Netherlands.

Trilateral retinoblastoma (TRb) is a rare disease associating intraocular retinoblastoma with intracranial primitive neuroectodermal tumor. Treatment is difficult and prognosis is poor. This multicenter study evaluates clinical findings and MR imaging characteristics of associated intracranial tumors in Rb patients. Clinical data of 17 patients (16 TRb and 1 quadrilateral Rb patients) included time intervals between Rb and TRb diagnosis and presence of baseline brain-imaging (BBI). Two reviewers reviewed all images individually and one reviewer per center evaluated their images. Consensus was reached during a joint scoring session. Studies were reviewed for tumor location, size and imaging characteristics (signal intensity (SI) on T1- and T2-weighted images, enhancement pattern and cystic appearance). Of 18 intracranial tumors, 78 % were located in the pineal gland and 22 % suprasellar. All tumors showed well-defined borders with mostly heterogenous enhancement (72 %) and isointense SI on T1- (78 %) and T2-weighted images (72 %) compared to gray matter. The majority of pineal TRbs showed a cystic component (57 %). TRb detected synchronously with the intraocular tumors on BBI (n = 7) were significantly smaller (P = 0.02), and mainly asymptomatic than TRb detected later on (n = 10). Overall, 5-year-survival of TRb patients detected on BBI was 67 % (95 % CI 29-100 %) compared to 11 % (95 % CI 0-32 %) for the group with delayed diagnosis. TRb mainly develops in the pineal gland and frequently presents with a cystic appearance that could be misinterpreted as benign pineal cysts. Routine BBI in all newly diagnosed Rb patients can detect TRb at a subclinical stage.
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http://dx.doi.org/10.1007/s11060-012-0922-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3434888PMC
September 2012

13q deletion syndrome and retinoblastoma in identical dichorionic diamniotic monozygotic twins.

Eur J Ophthalmol 2012 Sep-Oct;22(5):857-60

Retinoblastoma Referral Center, University of Siena, Siena, Italy.

Purpose: To report the case of identical dichorionic diamniotic female twins with unilateral retinoblastoma in 13q deletion syndrome.

Methods: Clinical and ophthalmoscopic evaluation, combination of multiple ligation-dependent probe amplification, array-comparative genomic hybridization analyses, and magnetic resonance imaging were performed.

Results: Peculiar facial features, marked hypotonia, gastroesophageal reflux, interatrial septal defect with left to right shunt and light dilatation of right chambers, 5th finger hypoplasia, 3rd-5th toes clinodactyly, 2nd toe overlapped to 3rd toe, and cutis marmorata were found. Ophthalmoscopic evaluation revealed unilateral retinoblastoma in both girls. Magnetic resonance imaging detected corpus callosum hypoplasia in both twins. A 34.4-Mb deletion involving bands 13q13.2-q21.33 and including the RB1 gene was identified in both twins. The deletion was not present in the DNA of their parents and older brother.

Conclusions: Dysmorphic features in children must be always suspicious of 13q deletion syndrome and a short ophthalmoscopic follow-up is necessary to detect the presence of a retinoblastoma.
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http://dx.doi.org/10.5301/ejo.5000151DOI Listing
December 2012

Superselective ophthalmic artery infusion of melphalan for intraocular retinoblastoma: preliminary results from 140 treatments.

Acta Ophthalmol 2013 Jun 23;91(4):335-42. Epub 2012 Jan 23.

Unit NINT Neuroimaging and Neurointervention, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Policlinico Santa Maria alle Scotte, Siena, Italy.

Purpose: To report our experience in superselective ophthalmic artery infusion of melphalan (SOAIM) for intraocular retinoblastoma.

Methods:   From June 2008 to October 2010, 38 patients (18 women, 20 men; age range at first treatment, 7 months to 22 years) with 41 eyes with retinoblastoma were scheduled for SOAIM, for 17 newly diagnosed retinoblastomas Tumour, Node and Metastasis (TNM) 7th Edition 1a (n = 1), 1b (n = 1), 2a (n = 7), 2b (n = 4) and 3a (n = 4) and 24 retinoblastomas with partial remission/relapse TNM 7th Edition 1b (n = 13), 2a (n = 1) and 2b (n = 10). Eight patients (ten eyes) have been treated by SOAIM alone. Follow-up was 6-27 months in 28 patients (30 eyes).

Results: Ophthalmic artery cannulation failed in two patients. Thirty-six patients underwent 140 treatments by internal (n = 112) or external (n = 28) carotid arteries. No major procedural complications occurred. Two patients have been lost to follow-up. Remaining 34 patients (37 eyes) had no metastatic disease. Four patients suffered permanent ocular complications: chorioretinal dystrophy (n = 2), ptosis (n = 1) and strabismus/exotropia (n = 1). Eight (22%) eyes in eight (24%) patients underwent enucleation: 7/16 (43%) newly diagnosed retinoblastomas and 1/22 (4.5%) retinoblastomas undergoing partial remission/relapse. For all treated eyes, Kaplan-Meier eye enucleation-free rates (K-M) were 85.4% (95% CI, 73.3-97.5%), 74.4% (95% CI, 57-91.8%) and still stable at 6, 12 months and 2 years, respectively. For eyes with partial remission/relapse, and eyes at presentation, K-M at 2 years were 95.5% (95% CI, 86.9-100%) and 45.6% (95% CI, 16.6-74.6%), respectively.

Conclusion: Superselective ophthalmic artery infusion of melphalan was safe and powerful, especially following other therapies. Superselective ophthalmic artery infusion of melphalan should be added to focal therapies spectrum. In selected cases, melphalan should be combined with other chemotherapeutic agents.
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http://dx.doi.org/10.1111/j.1755-3768.2011.02296.xDOI Listing
June 2013