It arises from the retina and most frequently presents within the first
two years of life, and sometimes even at birth.
The presenting signs include a white pupil
(leukocoria), squint (strabismus), poor vision, spontaneous hyphema or a
red, painful eye, often with secondary glaucoma.
While most retinoblastomas are unilateral,
up to 25% of the sporadic cases and most inherited retinoblastomas are
bilateral.
Most retinoblastomas (about 95%) occur
sporadically, but some (6 to 8%) are inherited and recent evidence
suggests that the retinoblastoma (Rb) susceptibility gene, located on the
long arm of chromosome 13 (13q14), is actually recessive, and not dominant
as one thought.
The Rbgene, which has been
sequenced, is located on chromosome 13 in close proximity to the gene for
esterase D.
The oncogene N-mycis
amplified 10 to 200 fold in some retinoblastomas and may play a cardinal
role in the tumorigenesis of retinoblasoma.
A recent hypothesis suggests that the Rbgene normally regulates a set of proto-oncogenes, and that when both
alleles of this gene are lost or inactivated, the structural transforming
gene (which may be an oncogene) is expressed.
Even survivors of sporadic retinoblastoma
sometimes transmit the tumour to their offspring in an apparent 'autosomal
dominant' manner. These offspring are especially prone to bilateral
tumours.
There is a high incidence of retinoblastoma
in individuals with a deletion of chromosome 13.
Some
retinoblastomas grow towards the vitreous humor and can be seen clinically
with an opthalmoscope (endophytic retinoblastoma).
Others grow between the sensory retina and the retinal pigment epithelium,
thereby detaching the retina (exophytic retinoblastoma).
Other retinoblastomas are both endophytic and exophytic.
The
retina often contains several distinct foci of tumour in the same eye,
some of which represent distinct points of origin, while others reflect
tumor implantations from intravitreal dissemination.
This cream-colored tumour usually contains
scattered, chalky white, calcified flecks within yellow necrotic zones.
The amount of calcification within
retinoblastomas is often sufficient to be detected radiologically.
Retinoblastomas are intensely cellular and
display several morphologic patterns. In some instances, densely packed,
round neoplastic cells with hyperchromatic nuclei, scanty cytoplasm, and
abundant mitoses are randomly distributed.
In other tumors the cells are commonly
arranged radially around a central cavity (Flexner-Wintersteiner
rosettes), as they differentiate towards photoreceptors.
In some retinoblastomas the cellular
arrangement resembles the fleur-de-lis (fleurette).
Viable tumor cells align themselves around
blood vessels, while necrotic areas with calcification are seen a short
distance from the vascularized regions.
Retinoblastomas
disseminate by several routes.
They commonly extend
into the optic nerve, from where they spread intracranially.
They also invade
blood vessels, especially in the highly vascular choroids, before
metastasizing hematogenously throughout the body.
The bone marrow is a
common site of blood-borne metastases, but surprisingly the lung is rarely
involved.
Retinoblastomas are
almost always fatal if left untreated.
However, the
early diagnosis and modern therapy, survival is high (about 90%).
On rare occasions,
spontaneous regression occurs for reasons that remain unknown.
Individuals
with retinoblastomas have an increased susceptibility to other potentially
fatal neoplasms including osteogenic sarcoma,
Ewing’s sarcoma and pinealoblastoma.
Expression of immature
and mature retinal cell markers in retinoblastoma. Eye.2007 Feb
2;
Aim To clarify
the expression of immature and mature retinal cell makers in
retinoblastoma cells and to give insights into the cell origin of the
retinoblastoma.Materials and methodsFive samples from five eyes
diagnosed with retinoblastomas were analysed by a standard
immunohistochemistry using antibodies against Nestin and the hairy and
enhancer of split mammalian homologue-1 (HES-1), both as markers for
undifferentiated cells, and against Chx10, as a marker for both
undifferentiated retinal cells and mature bipolar cells.
Photoreceptor-specific nuclear receptor (PNR) was used as a
postmitotic rod photoreceptor cell-specific marker, glial fibrillary
acidic protein (GFAP) as a mature glia cell marker, and
microtubule-associated protein (MAP) 2 as a mature neuronal cell
marker.ResultsNestin was detected in what were possibly Muller cells,
but not in the tumour stroma. HES-1 was not detected in the
retinoblastoma tissue. Chx10 was detected in one of the five samples.
In this one sample, Chx10 expression was confined in a minor portion
of the retinoblastoma cells. PNR was not detected in the
retinoblastoma tissue. Expression of GFAP was detected only in the
stromal cells of the tumour, which presumably represents reactive
stromal astrocytes. In contrast, in all the samples, MAP2 was
expressed in most of the retinoblastoma cells.ConclusionsThe results
of the current study support that retinoblastomas are derived from
mature neural cells but do not originate from tumour stem cell(s).Eye
advance online publication, 2 February 2007;
doi:10.1038/sj.eye.6702715.
Histopathologic findings in retinoblastoma. Arq Bras
Oftalmol.2005 May-Jun;68(3):327-31. Epub 2005 Jul 26
OBJECTIVE: To
study histopathological findings of enucleated eyes with
retinoblastoma. METHODS: Twenty-eight cases of retinoblastoma treated
by enucleation at the Federal University of Sao Paulo from December
2000 to October 2002 were histopathologically reviewed. Clinical data
included age, gender, race, unilateral or bilateral involvement and
previous treatment. The histopathological review evaluated the
presence of iris and/or angle neovascularization, tumor
differentiation and optic nerve and choroidal invasion according to
Khelfaoui's classification. RESULTS: Of 27 patients, 13 (48.5%) were
boys and 14 (59.3%) were girls, 16 were white, 6 were black and 5 were
asiatic, age ranging from 2 to 96 months (mean, 22.7 months). 13 cases
were bilateral and 14 cases were unilateral. All tumors were
histologically characterized by a proliferation of small cells with
high nuclear-to-cytoplasmic ratios and 20 (71.4%) of them were well
differentiated. Choroidal involvement was observed in 18 (64.2%) cases
(degree II, III) and optic nerve invasion in 8 (28.5%) cases (degree
III, IV, V). CONCLUSION: Neovascularization, necrosis and
calcification were the most commonly observed feature. The invasion
into the optic nerve and choroid, which are the two most important
predictors of patient outcome were found in 28.5% and 64.2% of the
cases, respectively.
Histopathologic analysis of 232 eyes with retinoblastoma conducted in
an Indian tertiary-care ophthalmic center. J Pediatr
Opthalmol Strabismus. 2003 Sep-Oct;40(5):265-7
PURPOSE: To study
the histopathologic features of 232 enucleated eyes with
retinoblastoma. MATERIALS AND METHODS: Two hundred thirty-two
enucleated eyes with retinoblastoma in a tertiary-care institute from
1982 to 2001 were reviewed. Data were collected and analyzed about the
type of growth and the presence or absence of vitreous or subretinal
seeding, rosettes and fleurettes, necrosis, calcification, iris
neovascularization, and invasion of the anterior chamber, iris,
choroid, optic nerve, and sclera. Choroidal invasion was graded using
a new system. Results were analyzed for statistical significance.
RESULTS: The endophytic growth pattern was common in 118 (51%) of the
eyes. Vitreous seeds were present in 109 (47%) of the tumors, 23 (10%)
of the tumors had subretinal seeds, and 14 (6%) of the tumors had
both. Poorly differentiated tumors were present in 134 (58%) of the
eyes. Iris neovascularization was noted in 71 (31%) of the eyes and
choroidal invasion was observed in 78 (34%) of the eyes. Of these 78
eyes, full-thickness (stage 4) choroidal invasion was present in 51
(65%). Optic nerve invasion was observed in 75 (32%) of the eyes, of
which prelaminar involvement occurred in 40 (53%) and postlaminar
involvement occurred in 22 (29%). CONCLUSION: A higher incidence of
choroidal and optic nerve infiltration was noted among Asian Indian
children than among children from the West. This could be due to
delayed diagnosis or to a difference in the biological behavior of
tumors occurring in the Asian Indian population.
Clinicopathologic study
of retinoblastoma including MIB-1, p53, and CD99
immunohistochemistry.Ann Diagn Pathol.2001 Jun;5(3):148-54
Retinoblastoma is
the most common intraocular tumor of childhood and has served as a
model for the understanding or tumorigenesis. This study
retrospectively examines the clinicopathologic features of 19
retinoblastomas and defines the MIB-1 (cell proliferation marker), p53
(tumor suppression gene), and CD99 (HBA71 or MIC2 antibody)
immunoreactivity in 10 selected cases. Nineteen patients (11 boys),
ranging in age from 6 to 47 months (mean, 20 months), were included
for study. Clinical presentations included: leukocoria (n = 12),
strabismus (n = 6), apparent decreased visual acuity (n = 5), and
proptosis (n = 1). Five patients had bilateral tumors and one neoplasm
arose in a patient with a known family history of retinoblastoma. All
tumors were histologically characterized by a proliferation of small
cells with high nuclear-to-cytoplasmic ratios. Commonly encountered
histologic features included necrosis (n = 17, 89%), calcification (n
= 16, 84%), fleurettes (n = 14, 74%), and Flexner-Wintersteiner
rosettes (n = 11, 58%). Retinal involvement was noted in 18 tumors
(95%) and optic nerve invasion in six cases (32%). The surgical optic
nerve margin was positive in one case. Mitosis counts were evaluable
in 18 cases and ranged from 1 to 42 mitotic figures/10 high power
field (mean, 13 mitotic figures/10 high power field). Ten tumors were
evaluated with MIB-1, p53, and CD99 antibodies by paraffin
immunohistochemistry. MIB-1 labeling indices ranged from 31.4 to 77.1
(mean, 49.4). p53 immunostaining was observed in six tumors; less than
10% of tumor cells were noted to be p53 positive in each case. CD99
positivity was demonstrable focally in three tumors. Adjuvant
chemotherapy and/or radiation therapy was administered in six
patients. Tumor recurrence was not observed in any of the patients
with a mean follow-up of 8.9 years. Only one patient died (20 years
after enucleation) because of metastatic osteosarcoma. In conclusion:
(1) Fleurettes and Flexner-Wintersteiner rosettes are variable
findings in retinoblastoma. (2) Retinoblastomas are characterized by
marked cell proliferation as evidenced by generally high mitosis
counts and extremely high MIB-1 labeling indices, but this does not
appear to adversely impact on prognosis. (3) Unlike peripheral
primitive neuroectodermal tumors, most retinoblastomas do not stain
positively with antibody to CD99. (4) Limited p53 immunostaining was
present in 60% of tumors studied. (5) Enucleation with negative optic
nerve margin is potentially curative in patients with retinoblastoma.
Diagnosis and
current management of retinoblastoma.Oncogene.
2006 Aug 28;25(38):5341-9.
Retinoblastoma
represents the prototypic model for inherited cancers. The RB1 gene
was the first tumor suppressor gene to be identified. It represents
the most frequent primary eye cancer in children under 15 years old,
habitually occurring in infancy, even in utero, but can be observed in
older children or young adults. Many other retinal lesions may also
simulate retinoblastoma. The two major presenting signs are leukocoria
and strabismus, but other ocular or general signs may be observed. A
highly malignant tumor, retinoblastoma can nowadays be cured. The
heritable form, however, carries a high risk of second nonocular
tumors. Treatment in the early stages of disease holds a good
prognosis for survival and salvage of visual function. In very late
stages, however, the prognosis for ocular function and even survival
is jeopardized.
Retinoblastoma--a histologic and
immunohistologic study. Indian J Pathol Microbiol.1997
Jan;40(1):37-46
Histopathology
and various immunohistochemical markers were studied in 40 cases of
human retinoblastoma. In histopathology, tumour type, extent and
invasion were studied. In immunohistochemistry, both glial and neural
markers were used to know the histogenesis of this tumour. The glial
markers, glial fibrillary acidic protein and vimentin, were detected
in retinal astrocytes and Muller's cells in normal retina and
perivascular glia in retinoblastoma. The neural marker, neurone-specific
enolase stained neurones in outer and inner nuclear layers in normal
retina, Flexner-Wintersteiner rosettes in retinoblastoma and tumour
cells is differentiated retinoblastoma. Another neural marker,
neurofilament triplet polypeptide stained neurones in inner nuclear
layer of normal retina and Flexner-Wintersteiner rosettes in
well-differentiated retinoblastoma. These results support the view
that retinoblastoma has predominantly neuronal origin.
Extensively necrotic
retinoblastoma is associated with high-risk prognostic factors. Arch
Pathol Lab Med. 2006 ;130(11):1669-72.
CONTEXT: Retinoblastoma is the most common
malignant intraocular tumor in children. It has been shown that
adjuvant therapy following enucleation in patients with high-risk
histopathologic features significantly decreases the mortality. We
describe the association of extensive necrosis of tumor and
intraocular structures with 2 of the major risk factors: optic nerve
invasion and choroidal invasion. This may alert the pathologist who
makes the observation of extensive necrosis to carefully search for
histologic features associated with adverse outcome. OBJECTIVE: To
determine whether extensively necrotic retinoblastoma is associated
with high-risk histologic prognostic factors for metastatic disease
and patient survival. DESIGN: Retrospective case series. Forty-three
eyes of 43 patients with retinoblastoma who underwent enucleation
between 1990 and 2001 were evaluated. Medical records, histopathology
specimens, pathology reports, and clinical photographs were reviewed.
Tumors were designated as exhibiting extensive necrosis if more than
95% of tumor cells and intraocular tissues were necrotic. The main
outcome measure was the association of extensive tumor necrosis with 3
high-risk histopathologic features: extraocular extension, optic nerve
invasion, or choroidal invasion. Metastatic disease, patient survival,
and associations with pathologic findings were also analyzed. RESULTS:
Optic nerve head invasion (P < .001), post-lamina-cribrosal invasion
(P < .001), and choroidal invasion by tumor (P = .004) were observed
more frequently in eyes with extensive necrosis compared with eyes
without extensive necrosis. Two of the 11 patients with extensively
necrotic intraocular retinoblastoma died from metastatic disease (P =
.06). None of the 32 patients without extensive necrosis developed
metastatic disease or died. CONCLUSIONS: Extensive ocular tissue and
tumor necrosis is associated with histologic high-risk prognostic
factors for tumor metastasis and mortality.
