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Retinoblastoma, the most common primary malignant intraocular tumor of childhood is a great success story in pediatric and ocular oncology. Pathology of retinoblastoma is important to guide the treatment modalities. Differentiated retinoblastoma is commonly seen in younger age group. Since a hundred years, we have been observing two typical true ro...
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... Bentuk roset atau yang disebut juga Flexner-Wintersteiner (FW) rosette merupakan salah satu bentuk histopatologi dari retinoblastoma. 18 Hal ini sesuai dengan kecurigaan diawal maka kasus ini dapat di diagnosis pasti sebagai retinoblastoma. ...
Background: Retinoblastoma is a primary malignant intraocular neoplasm derived from retinoblast beyond retinal development.Purpose: To report a case of Unilateral Retinoblastoma in secondary health care with limited facilities.Case report: We present a case of a 34-months old girl with unilateral retinoblastoma that transfer to the hospital with proptosis of the right eye, severe pain and drastic weight loss. Orbital exenteration was the treatment of choice due to poor prognosis of visual function and due to lack of facilities for further ancillary studies. After family members consented to right eye exenteration, then the ophthalmologist did the surgery. Later on, about one month post exenteration, histopatological report confirmed the diagnosis of retinoblastoma. Based on the need for chemotherapy, patient was referred to a more complete health care facilities.Conclusion: Retinoblastoma should be considered as an intraocular tumors especially in children until proven otherwise. Specifically in areas with limited facilities, it is very important to be able to detect early signs of retinoblastoma and avoid the development of disease to worse stage (extraocular retinoblastoma). Latar Belakang: Retinoblastoma merupakan neoplasma intraokular maligna primer yang berasal dari sel retina imatur (retinoblas) dalam perkembangan retina.Tujuan: Untuk melaporkan kasus Retinoblastoma Unilateral dalam perawatan kesehatan sekunder dengan fasilitas terbatas.Laporan kasus: Kami menghadirkan kasus seorang gadis berusia 34 bulan dengan retinoblastoma unilateral yang diperiksakan ke rumah sakit dengan proptosis mata kanan, nyeri parah, dan penurunan berat badan yang drastis. Orbital exenteration adalah pengobatan pilihan karena prognosis buruk dari fungsi visual dan karena kurangnya fasilitas untuk studi tambahan lebih lanjut. Setelah anggota keluarga menyetujui pembedahan mata kanan, maka dokter mata melakukan operasi. Kemudian, sekitar satu bulan pasca eksenterasi, laporan histopatologis mengkonfirmasi diagnosis retinoblastoma. Berdasarkan kebutuhan untuk kemoterapi, pasien dirujuk ke fasilitas perawatan kesehatan yang lebih lengkap.Kesimpulan: Retinoblastoma harus dianggap sebagai tumor intraokular terutama pada anak-anak sampai terbukti sebaliknya. Khususnya di daerah dengan fasilitas terbatas, sangat penting untuk dapat mendeteksi tanda-tanda awal retinoblastoma dan menghindari perkembangan penyakit ke tahap yang lebih buruk (retinoblastoma ekstraokular).
... The lumen corresponds to subretinal space whereas the cells surrounding the lumen are joined near the apices by intracellular connections (zonulae adherentes), akin to the external limiting membrane of the retina. Hence, the FW rosette is recognized as an early attempt for retinal differentiation (10,11). FW rosette formation is a characteristic finding in retinoblastoma, but they are not pathognomonic as they can also be encountered in other embryonal tumors, such as pineoblastoma and the old-termed medulloepitheliomas, ependymoblastoma, or embryonal tumor with abundant neuropil and true rosettes, now also known as ETMR (10,(12)(13)(14). ...
... They lack a central lumen and their constituent cells encompass a central tangle of neural filaments. Their presence indicates neuroblastic differentiation (11). ...
Diagnosis and classification of poorly differentiated tumors with primitive features of the central nervous system heavily relies on molecular and genetic findings of the tumors. Although RB1 gene mutation underlies the development of retinoblastoma and many other systemic cancers, RB1 gene mutation in a brain tumor is mainly limited to infiltrating gliomas. We describe what we believe to be a hitherto unreported case of sellar/suprasellar embryonal tumor with distinctive Flexner-Wintersteiner rosette formation, and somatic RB1 gene mutation in a 5-month-old infant. There were no molecular features associated with the embryonal tumor with multi-layered rosettes, and there were no histological or genetic features of a germ cell tumor. A follow up of 14 months duration showed good clinical response to VETOPEC regimen and no development of retinal disease. Our case shows an interesting association between RB1 mutation and Flexner-Wintersteiner rosettes in an embryonal tumor of the central nervous system and underscores the utility of large scale next generation sequencing in helping to identify the genetic aberrations that may help in clinical pathologic correlations of unusual or out-of-place histologic findings.
... Here, we had seen differentiated RB with FW, HW and the new rosettes described by us. 4 The newer rosettes were evolving one and they were associated with histopathological high risk factors such as focal rubeosis and superficial RPE involvement. 10 These findings stressed that newer rosettes may be strong indication to mark the bad prognosis in RB. 4 Positive IHC for TGF-β is an important indicator of a hypoxic condition. ...
... Here, we had seen differentiated RB with FW, HW and the new rosettes described by us. 4 The newer rosettes were evolving one and they were associated with histopathological high risk factors such as focal rubeosis and superficial RPE involvement. 10 These findings stressed that newer rosettes may be strong indication to mark the bad prognosis in RB. 4 Positive IHC for TGF-β is an important indicator of a hypoxic condition. We wanted to co-relate for the hypoxic condition of the lens and its surrounding. ...
Retinoblastoma, the most common primary malignant intraocular tumor of childhood has been previously associated with neovascularisation of the iris and retina. New vessel formation in the crystalline lens is an extremely rare entity in association with retinoblastoma. In the present case, we describe such a case with new rosettes and histopathological high risk factors with detailed pathological and histological documentations.
... In intraocular tumours, IHC was done in 13 cases, of which six were in RB specimen and four in choroidal melanoma specimen. In RB, IHC was seen in the tumours with new rosettes, which were previously described by the authors 10 . Various markers (NSE, p53, p16) showed positivity in the tumour cells along with high-risk factors 10 . ...
... In RB, IHC was seen in the tumours with new rosettes, which were previously described by the authors 10 . Various markers (NSE, p53, p16) showed positivity in the tumour cells along with high-risk factors 10 . The utility of IHC in clinical conditions such as RB could be in demarcating the high-risk factor such as optic nerve invasion. ...
Background & objectives:
Ocular and adnexal tumours are important causes of morbidity in India and globally. Immunohistochemistry (IHC) is a vital molecular pathology tool, which helps to diagnose a tumour with more accuracy. The present study was undertaken to document the profile of ocular and adnexal tumour with IHC at a tertiary eye care center in Northeast India.
Methods:
This was a prospective and laboratory-based study. Histopathological and IHC study of the ocular and adnexal tumour was carried out from 2012 to 2014. Selection of pathological cases was made on the result of the histological diagnosis. All samples were subjected to IHC using kits for different antibodies as per indications.
Results:
In total, 645 tumours were included in our study, with 449 benign conditions and 196 were malignant tumours. Total IHCs were done in 87 tumours and 238 of antibodies were used. Non-Hodgkin's lymphomas (B-cell, low-to-intermediate type and mucosal-associated lymphoid tumours) were the most common tumor.
Interpretation & conclusions:
Clinical utility of the IHCs in different ophthalmic tumours can enable pathologists to make an accurate diagnosis and thus help in the overall management of the patient care. IHC may be carried out using various methods and some of the methods practiced are time consuming and tedious. In this study, kit methods were used which were found to be simpler and less time-consuming.
... [1][2][3][4] The present success story of RB is much better than what was seen 100 years ago. [1][2][3][4][5] However, the scenario is a bit different in underdeveloped countries where even today, the disease is diagnosed at late stages and thereby affects the survival of children. [1][2][3]5] In 2014, we described and published the third true rosette [5] in RB, which had a characteristic morphology distinct from two other true rosettes which had been described over a century earlier. ...
... [1][2][3][4][5] However, the scenario is a bit different in underdeveloped countries where even today, the disease is diagnosed at late stages and thereby affects the survival of children. [1][2][3]5] In 2014, we described and published the third true rosette [5] in RB, which had a characteristic morphology distinct from two other true rosettes which had been described over a century earlier. The aim is to study new RB rosettes by molecular pathology interpretation with immunohistochemistry (IHC). ...
... [1][2][3][4][5] However, the scenario is a bit different in underdeveloped countries where even today, the disease is diagnosed at late stages and thereby affects the survival of children. [1][2][3]5] In 2014, we described and published the third true rosette [5] in RB, which had a characteristic morphology distinct from two other true rosettes which had been described over a century earlier. The aim is to study new RB rosettes by molecular pathology interpretation with immunohistochemistry (IHC). ...
Newly described retinoblastoma (RB) rosettes have various kinds of pathological significance. Some of their characteristics have been revealed in this immunohistochemistry study. Five paraffin-embedded eyeballs with RB and new rosettes were studied for neuron-specific enolase (NSE), p53, p16, BAX, c-Myc, glial fibrillary acidic protein, synaptophysin, and chromogranin. They were compared and interpreted using control specimens. NSE, P53, and P16 were significantly expressed in the cells of the new rosettes. The presence of new RB rosettes that mostly have histopathological high-risk factors and p53 positivity may be a strong marker of poor prognosis of RB.
... Retinoblastoma tumors exhibit varying degrees of differentiation with heterogenous distribution of rosettes, including Homer Wright and Flexner-Wintersteiner rosettes [4,5]. Retinoblastoma cells which constitute Flexner-Wintersteiner rosettes retain features of primordial photoreceptor cells [4][5][6][7]. ...
... Retinoblastoma tumors exhibit varying degrees of differentiation with heterogenous distribution of rosettes, including Homer Wright and Flexner-Wintersteiner rosettes [4,5]. Retinoblastoma cells which constitute Flexner-Wintersteiner rosettes retain features of primordial photoreceptor cells [4][5][6][7]. However, as in other cancers, with the progression of retinoblastoma, retinoblastoma cells lose their ability to differentiate [8,9] and there was a significant inverse relationship between age at enucleation and the degree of tumor differentiation, demonstrated by the presence of rosettes [6]. ...
... Retinoblastoma tumors from patients who underwent enucleation at older age demonstrate fewer Flexner-Wintersteiner rosettes which represent differentiated retinoblastoma tumors [6]. Electron microscopy studies demonstrate that retinoblastoma cells in Flexner-Wintersteiner rosettes possess cilia, which are thought to be the precursor of photoreceptor outer segments [4,7]. Although the cell of origin of retinoblastoma is yet to be established [48][49][50], these features indicate that retinoblastoma cells retain the characteristics of differentiated retinal constituent cells. ...
Retinoblastoma is the most common intraocular cancer in children, affecting 1/20,000 live births. Currently, children with retinoblastoma were treated with chemotherapy using drugs such as carboplatin, vincristine, and etoposide. Unfortunately, if conventional treatment fails, the affected eyes should be removed to prevent extension into adjacent tissues and metastasis. This study is to investigate the roles of L1 in adhesion-mediated proliferation and chemoresistance of retinoblastoma. L1 was differentially expressed in 30 retinoblastoma tissues and 2 retinoblastoma cell lines. Furthermore, the proportions of L1-positive cells in retinoblastoma tumors were negatively linked with the number of Flexner-Wintersteiner rosettes, a characteristic of differentiated retinoblastoma tumors, in each tumor sample. Following in vitro experiments using L1-deleted and -overexpressing cells showed that L1 increased adhesion-mediated proliferation of retinoblastoma cells via regulation of cell cycle-associated proteins with modulation of Akt, extracellular signal-regulated kinase, and p38 pathways. In addition, L1 increased resistance against carboplatin, vincristine, and esoposide through up-regulation of apoptosis- and multidrug resistance-related genes. In vivo tumor formation and chemoresistance were also positively linked with the levels of L1 in an orthotopic transplantation model in mice. In this manner, L1 increases adhesion-mediated proliferation and chemoresistance of retinoblastoma. Targeted therapy to L1 might be effective in the treatment of retinoblastoma tumors, especially which rapidly proliferate and demonstrate resistance to conventional chemotherapeutic drugs.
... Januari 2016 penderita menjalani enukleasi, pada saat penderita menjalani enukleasi, dilakukan pemeriksaan histopatologi dengan hasil yang menunjukkan sel-sel hiperkromatosis dan formasi rossete (Gambar 6). 1,9 Tanggal 20 April 2016 penderita datang untuk kontrol paska-enukleasi dan kemoterapi (Gambar 7). Pada CT menunjukkan massa pada mata kanan dengan kalsifikasi tanpa disertai perluasan ekstra-okuler. ...
... The rosettes include Homer Wright and Flexner-Wintersteiner (FW) rosettes, dependent on the stages of retinal differentiation, and these two rosettes are exclusively found in retinoblastoma. 53 The lumen corresponds to subretinal space and stains with alcian blue (HR-AMP) that contains cytoplasmic extensions from the tumor cells. The cells surrounding the lumen are joined near the apices by intracellular connections (zonulae adherent), which are analogous to the external limiting membrane of retina. ...
... FW rosettes are not pathognomonic because they also occur in malignant medulloepitheliomas and some pineal tumors. 53,54 Taking into account all reported cases, Homer Wright rosettes were present in two cases whereas FW rosettes were present in two other cases. 37,38,41,42 On electron microscopy, tumor cells have a high nuclearto-cytoplasmic ratio, rare nucleoli, glycogen granules, intercellular junctions, sparse intracytoplasmic filaments, chromatin clumping, and cilia in the 9+0 configuration (cilia-like structures with a ring of nine doublet microtubular structures but no central component) that is characteristic of retinoblastoma and retinal photoreceptors. ...
Diffuse anterior retinoblastoma is a rare variant of retinoblastoma seeding in the area of the vitreous base and anterior chamber. Patients with diffuse anterior retinoblastoma are older than those with the classical types, with the mean age being 6.1 years. The original cells of diffuse anterior retinoblastoma are supposed to be cone precursor. Patients most commonly present with pseudouveitis, pseudohypopyon, and increased intraocular pressure. The retina under fundus examination is likely to be normal, and the clinical features mimic the inflammation progress, which can often lead to misdiagnosis. The published diffuse anterior retinoblastoma cases were diagnosed after fine-needle aspiration biopsy running the potential risk of inducing metastasis. The most common treatment for diffuse anterior retinoblastoma is enucleation followed by systematic chemotherapy according to the patient's presentation and clinical course. This review summarizes the recent advances in etiology (including tumorigenesis and cell origin), pathology, diagnosis, differential diagnosis, and new treatment. The challenges of early diagnosis and prospects are also discussed.
Purpose: To study the pathology of retinoblastoma (RB) seeds with supportive evidence
by field emission scanning electron microscopy and Raman spectroscopy.
Methods: Laboratory-based observational study. Enucleated eyeball received in the
ocular pathology department of a tertiary eye care center in northeast India were included
in the cohort after obtaining written informed consent during the surgery. The study was
carried out for six years (2015-2020). Most of the eyeballs were Group-E RBs. Standard
eyeballs sectioning were done by bread loaf techniques. Gross documentations included
RB seeds seen in the smallest calotte done with utmost care. Seeds were documented also in permanent sections. Scanning electron microscopy and Raman spectroscopy was
carried out in an index case.
Results: 35 RB cases had different seedings out of total 59 cases. Mean age at enucleation was 2.9 years. RB seeds were seen in vitreous (n=19), sub-retinal plus vitreous (n=7), anterior chamber (n=1), over crystalline lens (n=3), retinal surface (n=1), RPE (n=2), sub-retinal (n=1), calcified seeds (n=2). Other characteristics were dusts (n=7), clouds (n=11), spheres (n=4) and unspecified type (n=13). Histopathological high risk factors showed significant choroidal (n=22) and optic nerve (n=15) involvement. Few cases had extra-ocular spread. Undifferentiated tumor (n=24) was seen with higher evidence of necrosis (n=23). Raman spectra differentiated the seeds from normal tissue on the basis of lipid and protein content.
Conclusion: This study highlights different types of RB seeds with high risk factors. The
morphology of those seeds showed difference between vitreous and sub-retinal seeds
under advanced microscopic observations.
