The pathology of ocular cancer

Eagle, Ralph C.

doi:10.1038/eye.2012.237

Cited by 51 publications

(70 citation statements)

References 55 publications

(34 reference statements)

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“…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). Our results are consistent with Eagle et al, their harbor mutations in both copies of the RB1 gene and associated with uveal invasion and retrolaminar optic nerve invasion [5,16,17]. Laurie et al proved this association at molecular basis, and their "detailed analysis of these cells as they were propagated in culture from the primary tumor shows that changes in cadherin-mediated cell adhesion are associated with retinoblastoma invasion of the optic nerve prior to metastasis.…”

Section: Discussionsupporting

confidence: 81%

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

Khan¹,

Mehboob²,

Bukhari³

2013

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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.

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Section: Discussionsupporting

confidence: 81%

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

Khan¹,

Mehboob²,

Bukhari³

2013

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“…In tumors affecting young children, rosettes are classified into three types based on the degree of retinal differentiation. 27 Homer Wright (HW) rosettes, common in neuroblastoma, contain primitive neuroblastic cells encircling a solid 30-50 μm-diameter central tangle of neural filaments, rather than a lumen. 27 Flexner-Wintersteiner (FW) rosettes, common in retinoblastoma, contain early differentiated photoreceptors surrounding a central lumen 40-60 μm in diameter.…”

Section: Discussionmentioning

confidence: 99%

“…27 Homer Wright (HW) rosettes, common in neuroblastoma, contain primitive neuroblastic cells encircling a solid 30-50 μm-diameter central tangle of neural filaments, rather than a lumen. 27 Flexner-Wintersteiner (FW) rosettes, common in retinoblastoma, contain early differentiated photoreceptors surrounding a central lumen 40-60 μm in diameter. Fleurettes are advanced differentiated photoreceptors with IS pointing centrally and lacking a lumen.…”

Section: Discussionmentioning

confidence: 99%

Outer Retinal Tubulation in Advanced Age-Related Macular Degeneration

Schaal

Freund

Litts

et al. 2015

Retina

110

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Purpose To compare optical coherence tomography (OCT) and histology of outer retinal tubulation (ORT) secondary to advanced age-related macular degeneration (AMD) in patients and in post-mortem specimens, with particular attention to the basis of the hyper-reflective border of ORT. Method A private referral practice (imaging) and an academic research laboratory (histology) collaborated on two retrospective case series. High-resolution OCT raster scans of 43 eyes (34 patients) manifesting ORT secondary to advanced AMD were compared to high-resolution histological sections through the fovea and superior perifovea of donor eyes (13 atrophic AMD and 40 neovascular AMD) preserved ≤4 hours after death. Results ORT seen on OCT corresponded to histologic findings of tubular structures comprised largely of cones lacking outer segments (OS) and lacking inner segments (IS). Four phases of cone degeneration were histologically distinguishable in ORT lumenal walls, nascent, mature, degenerate, and end-stage (IS and OS; IS only; no IS; no photoreceptors and only Müller cells forming external limiting membrane, ELM, respectively). Mitochondria, which are normally long and bundled within IS ellipsoids, were small and scattered within shrunken IS and cell bodies of surviving cones. A lumenal border was delimited by an ELM. ORT observed in closed and open configurations were distinguishable from cysts and photoreceptor islands on both OCT and histology. Hyper-reflective lumenal material seen on OCT represents trapped retinal pigment epithelium (RPE) and non-RPE cells. Conclusions The defining OCT features of ORT are location in the outer nuclear layer (ONL), a hyper-reflective band differentiating it from cysts, and RPE that is either dysmorphic or absent. ORT histologic and OCT findings corresponded in regard to composition, location, shape, and stages of formation. The reflectivity of ORT lumenal walls on OCT apparently does not require an OS or an IS/OS junction, indicating an independent reflectivity source, possibly mitochondria, in the IS.

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“…When the tumor outgrows its vascular supply 90-110μm away from the central vascular channel, it undergoes ischemic necrosis and may contain areas of dystrophic calcification, thus yielding a grossly visible chalky or cottage cheese appearance. 40;41 The tumor may also grow diffusely within the retina and derive its nutrition from the retinal vasculature. Vitreous and subretinal seeds of retinoblastoma are avascular and contain areas of necrosis in the center of the seed away from the vitreous or subretinal fluid.…”

Section: Pathologymentioning

confidence: 99%

Retinoblastoma. Fifty Years of Progress. The LXXI Edward Jackson Memorial Lecture

Grossniklaus¹

2014

American Journal of Ophthalmology

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Purpose To review the progress made in understanding the genetic basis, molecular pathology, and treatment of retinoblastoma since the previous Jackson lecture on the topic was published 50 years ago. Design Perspective based on personal experience and the literature. Methods The literature regarding retinoblastoma was reviewed since 1963. Advances in understanding the biology and treatment of retinoblastoma provided context through the author’s clinical, pathological and research experiences. Results Retinoblastoma was first identified in the 1500s and defined as a unique clinicopathologic entity in 1809. Until the mid-1900s, knowledge advanced sporadically, with technological developments of ophthalmoscopy and light microscopy, and with the introduction of surgical enucleation, chemotherapy and radiation therapy. During the last 50 years, research and treatment have progressed at an unprecedented rate due to innovations in molecular biology and the development of targeted therapies. During this time period, the retinoblastoma gene was discovered; techniques for genetic testing for retinoblastoma were developed; and plaque brachytherapy, chemoreduction, intraarterial chemotherapy, and intraocular injections of chemotherapeutic agents were successfully introduced. Conclusions Nearly all patients with retinoblastoma in developed countries can now be cured of their primary cancer- a remarkable achievement for a childhood cancer that once was uniformly fatal. Much of this success is owed to deciphering the role of the Rb gene, and the benefits of targeted therapies, such as chemoreduction with consolidation as well as intra-arterial and intravitreal chemotherapies. Going forward, the main challenge will be ensuring that access to care is available for all children, particularly those in developing countries.

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The pathology of ocular cancer

Cited by 51 publications

References 55 publications

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

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

Outer Retinal Tubulation in Advanced Age-Related Macular Degeneration

Retinoblastoma. Fifty Years of Progress. The LXXI Edward Jackson Memorial Lecture

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