A Rare Case : Unilateral Retinoblastoma in Adult Onset

Rani Yunita Patong, Suliati P.Amir, Halimah Pagarra

Departement of Ophthalmology, Faculty of Medicine, Hasanuddin University, Makassar

PURPOSETo report a rare case of Unilateral Retinoblastoma in Adult Onset

DESIGNA case report

METHOD This case was examined completely, underwent a history taking, ophthalmology examination, B-scan ultrasonography, computerized tomography scan, laboratory test, histopathology examination, and immunohistochemistry. Unilateral Retinoblastoma was found, partial tumor exenteration were done and continued by chemotherapy.

RESULTA 40 years old woman presented to us with a complain of decreasing visual acuity in the right eye of 2 years of duration. Ophthalmology examination revealed no light perception in right eye, conjungtival hyperemia, iris neovascularisation, fixed pupil, and leukocoria. B-scan ultrasonography examination revealed a solid mass lesion without calcification and computerized tomography scan revealed the right retrobulbar mass that infiltrated the right bulbus oculi. She underwent exenteration and the diagnosis was confirmed histopatologically.

CONCLUSIONThe diagnosis of retinoblastoma should be kept in mind in case presenting with proptotic or white mass lesion of unknown etiology, in the fundus of an adult. Due to the aggressive nature of the tumor and metastatic potential, prompt diagnosis and management is essential.

KEYWORD : Retinoblastoma, Adult, Exenteration, and Immunohistochemistry.

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INTRODUCTION

Retinoblastoma (Rb) is the most common

intraocular tumor in children. More than 90%

of cases are diagnosed before 5 years of age,

and presentation of retinoblastoma in adults is

rare. (Shields CL, et al; 1991) About 23 adult

cases of Rb have been published in literature

till 2013. (Singh SK, et al; 2011) Because of

the rarity of the disease the diagnosis

occasionally delayed. Our aim is to highlight

therarity of occurrence of Rb in adults along

with its features and to emphasize the need to

suspect Rb in adults, who present with a

intraocular and retrobulbar mass, to ensure its

early diagnosis. We report a case of adult

onset retinoblastoma in a 40-year-old woman

that appeared with intraocular and retrobulbar

mass on B-scan ultrasonography and

computerized tomography scan. She

underwent exenteration and the diagnosis was

confirmed histopathologically.

CASE REPORT

A 40 years old female presented to

DR.Wahidin Sudirohusodo Hospital with a

chief complain of decreasing visual acuity in

the right eye of 2 year duration, gradually.

Other complain of severe pain since one

month ago, with red eye, and lacrimation. She

had been treated earlier with topical and oral

anti-glacoma agent. At 2 years past, she had

been diagnosed with retinal detachment, but

untreated. No history of trauma, no family

history of the same illness, no history of

surgery, no history of prior systemic disease.

On General examination were found

moderate sickness, well nutrition, and

Glasgow Coma Scale (GCS) was 15 and vital

sign such as blood pressure, pulse rates,

respiratory rates and temperature are within

normal limits.

On ophthalmology examination was

found visual acuity in right eye was no light

perception and left eye was 20/20. Intraocular

pressure in right eye was > 40 mmHg, and in

left eye was 15 mmHg. Anterior segment of

right eye was looked proptotic, conjunctival

hyperemic, iris neovascularisation, fixed pupil,

and leukocoria. (Figure 1) Posterior segment

of the right eye was looked negative of fundus

reflex, other details was difficult to evaluated.

Examination of the left eye did not show any

abnormality in anterior and posterior segment.

Figure 1. Right eye. Proptotic, conjungtival hyperemic,

iris neovascularization, fixed pupil and leukocoria.

There were no enlargement of the lymph

node in preauricular, submandibular, jugular,

axial and inguinal. There was no

hepatospleenomegaly. The extremities were

within normal limit.

B-scan ultrasonography of her right eye

showed a hyperechoic endophytic mass with

no calcification in intraocular and retrobulbar.

(Figure 2)

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Figure 2. B-scan ultrasonography. Intraocular (red row)

and retrobulbar growth (black row) without any

calcification.

On radiologic examination were found a

picture thorax radiography of normal lungs.

Computerized tomography scan of the orbits

and brain without contrast showed intraocular

and retrobulbar growth with no calcification in

the right bulbus oculi. (Figure 3)

Figure 3.Right bulbus oculi CT Scan of the orbits and

brain. Intraocular and retrobulbar growth with no

calcification.(red row)

From laboratory test result were founded

WBC : 12.100 /mm3 , RBC : 4.780.000/mm3,

HGB : 13,7 g/dL , PLT : 390.000/mm3, HCT :

42,7 %, HBsAg /AntiHCV (rapid test) :

negative / negative, CT/BT : 8’00”/2’00”,

PT/APTT : 12,9 / 29,5 seconds, Blood

Glucose : 102 mg/dL, Ureum/Creatinin :

28/0,7mg/dl, SGOT/SGPT : 13/27U/L,

Electrolyte: Sodium : 135 mmol/L, Potassium

: 3,5 mmol/L, Chloride : 102 mmol/L.

Laboratory results showed leukocytosis.

From the examination above the patient

was suspected retinoblastoma, with differential

diagnosis was meningioma, malignant

lymphoma, than was performed partial

exenteration as a primary treatment in the right

eye. (Figure 4) The whole globe, tumor tissue

surround were removed except the palpebra

and also optic nerve to investigate the

involvement and fixed with 10% formalin

solution then sent for histopathology

examination.(Figure 5)

Figure 4. Partial exenteration. All tumor tissue removed

except palpebra.

Figure 5. Tumor tissue fixed with formaline 10%. Whole

globe with white yellow smooth mass intraocular (red

row), but irregular mass at the retrobulbar (black row)

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Histopathology examination revealed

the microscopic image showed tumor tissue

consist of round nuclei tumor cells, less

cytoplasm, arranged solid like layer, separated

by small amounts of loose connective tissue,

there is no rosset form, no datia cells, and

tumor cells grow by infiltrated to soft tissue

around. The conclusion is undifferentiated

retinoblastoma with malignant lymphoma as a

differential diagnosis. (Figure 5 and 6)

Figure 5. Histophatology with a magnification of 100x

Figure 6. Histophatology with a magnification of 400x.

Round nuclei tumor cells, less cytoplasm, arranged solid

like layer, separated by small amounts of loose

connective tissue, there is no rosset form, no datia cells,

and tumor cells grow by infiltrated to soft tissue around

Confirmed the diagnose, tumor tissue

went immunohistochemistry of CD45 antigen

or leukocyte common antigent (LCA)

examination. This examination revealed

lymphocyte cell was less in this tissue, and

conclusion was negative immunoreactivity for

malignant lymphoma. (Figure 7)

Figure 7. Immunohistochemistry CD45 (LCA). Less

lymphocyte that colored revealed negative

immunoreactivity result for malignant lymphoma.

By all of the result above found final

conclusion was this case is a undifferentiated

retinoblastoma. Patient was consultated to the

Departement of Hematology Oncology and

chemotherapy treatment were done.

DISSCUSION

Retinoblastoma is the most common primary

ocular malignancy (eye cancer) of childhood,

occurring in 1 in 14.000-20.000 live birth.

Retinoblastoma in an adult is extremely rare

entity and for this reason it is usually not

considered in the differential diagnosis of a

retinal or intraocular mass in an adult.(Rosa

RH, et al., 2013) In 1919, Maghy reported a

well-documented retinoblastoma in a 20-year-

old female. Since that report, an additional

twenty-two cases of retinoblastoma have

appeared in world literature in patients 20

years or older.(Singh SK, et al., 2011) Was

reported a rare case of unilateral

retinoblastoma with histopathology

confirmation, in a 40-year-old woman.

Retinoblastoma may occur in one or

both eyes in children (Ramasubramanian A, et

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al., 2012). But almost all retinoblastomas in

adults are sporadic and unilateral. Adult onset

Rb is very rare therefore it is usually missed in

the differential diagnosis of a retinal growth in

this age. Singh et al. gave a review of 24 cases

till 2011. (Singh SK, et al., 2011, Rosa RH,et

al., 2012) Khetan et al. and Zhang et al. also

described one case each in 2012. All were

sporadic and like our patient, unilateral.

It is not well established whether Rb

in an adult occurs de novo or is preceded by a

retinocytoma.(Biswas J, et al., 2000) Some

theorize that these lesions arise from a

previously existing retinocytoma that

underwent malignant transformation.(Singh

SK, et al., 2011; Biswas J, et al., 2000) There

is a possibility of the presence of

retinocytoma, which undergoes oncogenic

mutations, resulting in the malignant

transformation of the retinocytoma. Singh et

al. stated that the risk of malignant

transformation of a retinocytoma into a

retinoblastoma is 4%. Patients with

retinocytoma must be kept in follow-up for

several years due to the possibility of

malignant transformation.(Rosa RH, et al.,

2012)

In this case presented with decreasing

visual acuity in the right eye of 2 years

duration and from ophthalmology examination

showed increase intraocular pressure,

proptotic, conjungtival hyperemia, iris

neovacularization, fixed pupil and leukocoria.

Those clinical sign can be found in neo-

vascular glaucoma. In 2013, Saemah NZ, et al.

also reported retinoblastoma in adult that

presented neo-vaskular glaucoma. There are

many causes of secondary angle-closure

glaucoma. Contraction of various types of

pathologic membranes that form over surface

of the iris over the trabecular meshwork,

occluding aqueous outflow. For example,

chronic retinal ischemia is associated with the

up-regulation of VEGF and other pro-

angiogenic factors. The appearance of VEGF

in the aqueous humor is thought to induce the

development of thin, clinically transparent

fibrovascular membranes over the surface of

the iris. Contraction of myofibroblastic

elements in these membranes leads to

occlusion of the trabecular meshwork by the

iris: neovascular glaucoma. Necrotic tumors,

especially retinoblastomas, can also induce iris

neovascularization and glaucoma. (Kumar V,

et al., 2010)

The clinical findings in all the stages of

retinoblastoma are numerous and varied.

Leukocoria (white pupillary reflex or cat's eye

reflex) is the most common presenting sign,

accounting for about 56.1% of cases. Other

clinical finding is strabismus, glaucoma,

retinal detachment, proptosis, and secondary

inflammation to tumor necrosis.(Zhang Z, et

al., 2012) In this cases showed retinal

detachment in early and neovascular

glaucoma, proptosis and leukocoria in latest.

A diagnostic dilemma often exists, as we

do not expect retinoblastoma in adults. When

the appearance of the tumor is quite classical,

as in this case, the diagnosis can be made by

B-scan ultrasonography and CT scan. B-scan

ultrasonography and CT scan may show

calcification and characteristic imaging

patterns. In certain cases, however, even with

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both investigations, the diagnosis may not be

clear. B-scan ultrasonography and a

computerized tomography scan may or may

not reveal calcification, which is characteristic

of retinoblastoma in children. Calcification is

not an important finding in adult-onset

retinoblastoma. (Odashiro AN, et al; 2005) In

our patient, calcification was not present, but

intraocular and retrobulbar mass founded by

B-scan ultrasonography and CT scan

examination.

By those clinical sign, symptom and

additional examination, this case underwent

partial exenteration and exenteration tumor

tissue showed retrobulbar and intraocular mass

as picture in B-scan ultrasonography and CT

scan and suggested that the tumor had

endophytic and exophytic growth. Endophytic

growth occurs when the tumor breaks through

the internal limiting membrane and has an

ophthalmic appearance of a white-to-cream

mass showing either no surface vessels or

small irregular tumor vessels. Exophytic

growth occurs in the subretinal space. This

growth pattern is often associated with

subretinal fluid accumulation and retinal

detachment. The tumor cells may infiltrate

through the Bruch membrane into the choroid

and then invade either blood vessels or ciliary

nerves or vessels. Retinal vessels are noted to

increase in caliber and tortuosity as they

overlie the mass. (Zhang Z, et al.; 2012, Nork

TM, et al.; 1996)

Based on clinical sign, ophthalmology

examination and radiologic examination, we

suspected in some diagnose such as

retinoblastoma, meningioma, and malignant

lymphoma. To confirm that and identified the

differentiation of tumor, exenteration tissue

underwent histopathology examination. The

result is undifferentiated retinoblastoma with

malignant lymphoma as a differential

diagnosis.

Histopathology of the exenteration globe

confirmed the diagnosis and identifies the

differentiation of the tumor. Tumors devoid of

Flexner-Wintersteiner rosettes and fleurettes

are classified as undifferentiated

retinoblastomas. Such tumors may contain

Homer-Wright rosettes. These rosettes contain

fewer differentiated neoplastic cells and have

no central lumen (Figure 8).(Bishop JO, et al.,

1975)

Figure 8. Retinoblatoma. Note the viable tumor cells (asterisk) surrounding a blood vessel (arrow) and the

alternating zones of necrosis (N). This histologic arrangement is referred to as a pseudorosette. (Kumar V,

et al., 2010)

Immunohistochemical techniques

involve staining tumor cells with a specific

monoclonal antibodies to tissue antigens.

Retinoblastoma is detected with

immunohistochemistry neuron-specific

enolase antigent. (Bishop JO, et al., 1975, Kim

JW, et al., 2007) In this case, CD45 antigent or

leukocyte common antigent (LCA) was used.

Leukocyte common antigent is a antigent

specific for malignant lymphoma. By

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distinguished the diagnose identification had

continued identification by

immunohistochemistry LCA showed negative

result of LCA immunohistochemistry wich is

revealed by less lymphocyte cell, and

malignant lymphoma was removed and final

diagnose was undifferentiated retinoblastoma.

Intraocular lymphomas may arise in

different parts of the eye, expressing various

clinical manifestations. Primary intraocular

lymphoma (PIOL) (also known as large cell

lymphoma, vitreoretinal lymphoma, or retinal

lymphoma), is the most common and most

aggressive type of lymphoma involving the

eye and is usually associated with primary

central nervous system lymphoma (PCNSL).

Ocular signs and symptoms may occur before

central nervous system findings. Clinically,

PIOL presents most commonly as a vitritis.

Some patients have sub-RPE infiltrates. In

such cases, the disease may masquerade as a

nonspecific uveitis.(Rosa RH, et al., 2012) In

these case, there is retinal detachment in early,

and neovascular glaucoma, no sign of vitritis

and uveitis.

Histophatology examination in

lymphoma maligna consist of oval shape with

small cleaved, amount of chromatine, and

sometime there are macrophage. (Kumar V, et

al., 2010) Characteristic of lymphoma

malignant mimicking with undifferentiated

retinoblastoma that had no characteristirized

with Flexner-Wintersteiner rosettes or Homer-

Wright rosette. In this case was found round

nuclei tumor cells, less cytoplasm, arranged

solid like layer, that separated by small

amounts of loose connective tissue. Because of

the mimicking and to confirmed the diagnosis,

inmmunohistochemistry leucocyte common

antigen (LCA) were done and the result was

negative.

Figure 9. Lymphoma cell in histophatology examination.

oval shape cell with small cleaved, amount of cromatine,

and sometime there are macrophage.

Figure 10. Malignant lymphoma immunohistochemistry.

Large amount of lymphocyte that colored revealed

positive immunoreactivity result.

Treatment for retinoblastoma is usually

individualized to the specific patient, consist

of radiation theraphy, chemotheraphy, laser

photocoagulation, cryotheraphy, enucleation

and exenteration. Treatment should be directed

toward complete control of the tumor and the

preservation of as much useful vision as

possible. (Ramasubramanian A, et al.;2012,

Bishop JO, et al.; 1975, Kim JW, et al.; 2007)

Radiation therapy, chemotherapy, laser

photocoagulation, and cryotherapy is

conservative treatment based on Reese-

Ellworth or International Classification and

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enucleation and exenteration for the advanced

tumor. Indication for the use of enucleation

with retinoblastoma include failure of all

known effective conservative therapies, the

presence of glaucoma as the result of

neovascularization of the iris or tumor

invasion into the anterior chamber, long

standing retinal detachment, pars plana tumor

seeding, optic nerve or orbital tumor

extension, no expectation for useful vison, and

poor visualization of an active tumor.

(Ramasubramanian A, et al., 2012)

Exenteration was choosen as primary therapy,

because there is retrobulbar invasion from the

intraocular. The patient got chemotherapy with

Etiposide 170 mg perday and Carboplatin 275

mg perday in every their circle of theraphy.

Retinoblastoma have poorly prognosis

with mortality ratio 25-100%, but the

prognosis is good where prompt medical care

is available. The cure rate is almost 90% if the

optic nerve is not involved and enucleation is

performed before the tumor passes through the

lamina cribrosa. Some author have reported

improved survival when surgery was

combined with chemotheraphy or

radiotherapy.(Ramasubramanian A, et al.,

2012; Singh SK, et al., 2011; Odashiro AN, et

al., 2005) In this case showed good prognosis

with therapy was given, surgery combined

with chemotherapy. The patient looked the

healthier with vital signs are normal limit.

CONCLUSION

Unilateral retinoblastoma in an adult is a rare

case. The diagnosis of retinoblastoma should

be kept in mind in case presenting with

proptotic or white mass lesion of unknown

etiology, in the fundus of an adult. Due to the

aggressive nature of the tumor and metastatic

potential, prompt diagnosis and management

is essential.

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Biswas J, Mani B, Shanmugam MP, et al.

Retinoblastoma in adults: Report of three

cases and review of the literature. Surv

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Khetan V, Mathur G, et al. Late recurrence of

tumor necessitating enucleation in an adult

onset retinoblastoma. Ophthalmic Genet.

2013;6(1–2):87–89.

Kim JW, Abramson DH, Dunkel IJ: Current

management strategies for intraocular

retinoblastoma. Drugs. 2007,67(15):2173–

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Kumar V, Abbas AK, et al. Robbin and Cotran

Pathologic Basis of Disease 8th Edition.

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Shields CL, Shields JA, Shah P, et al:

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