Retinoblastoma in an Adult.

Retinoblastoma is a rare malignant tumor of the retina usually seen in children before 5 years of age. The tumor is extremely rare in adults. We report here an unusual case of retinoblastoma in a 55-year-old adult female who presented to us with an orbital mass at a late stage of the disease. Detailed laboratory investigations and imaging studies could not make a precise diagnosis. The treating ophthalmologist suspected primary intraocular tumor, metastatic carcinoma, malignant melanoma, or lymphoma and referred the patient for fine needle aspiration cytology (FNAC). Cytopathological examination of Giemsa-stained FNAC smear was consistent with that of retinoblastoma and established the diagnosis.

INTRODUCTION

Retinoblastoma is the most common ocular malignancy of childhood usually presenting in children before 5 years of age with an incidence rate of 1 in 15000 to 18000 live births.[1] This tumor is extremely rare in adults. Ever since the first case of retinoblastoma reported in an adult in 1929 by Verhoeff [2] there have been only 30 case reports of retinoblastoma in adults.[34] We report a rare case of unilateral retinoblastoma with cytopathological confirmation in a 55-year-old woman.

CASE REPORT

A 55-year-old female presented to the ophthalmology department of the hospital with complaints of a painful swelling in the left eye. The swelling had been gradually increasing in size over the last 8 months with dull continuous pain in the eye and periorbital area. There was progressive diminution of vision for the last 6 months in the affected eye, and at the time of presentation in the hospital, the affected eye was completely blind. The progressive increase in the size of the swelling and pain in and around the eye compelled the patient to avail hospital services. The treatment history was not significant. The patient was being treated by a local doctor with eye drops and certain oral medicines the records of which were not available with her. She did not have any history of significant ocular disease or any ophthalmic surgery. There was no history of similar disease in the family.

On examination, an intraorbital mass protruding from the left eye was visible. Axial proptosis with stretched out sclera along with dilated blood vessels covering the entire exposed part of the eye ball was seen. The underlying cornea was barely visible through the widened palpebral aperture with hyperemic keratinized conjunctiva tissue. The swelling was more prominent in the region superior to the upper eye lid. The skin appeared stretched along with dilated vessels in the superior part of the eye ball [Figure 1a]. On palpation, the mass was tender and soft in consistency. Fundus examination was not possible because of overlying vascularized keratinized tissue over cornea. The intraocular tension was also not recorded because of these reasons. The status of the pupil of the diseased eye could also not be commented upon, even though it appeared slightly dilated. The patient had no perception of light in the left eye. Ophthalmological examination of the right eye did not show any abnormality both in the anterior as well as in posterior chamber. The fundus examination of the right eye was normal. The intraocular tension of right eye was also normal.

Figure 1

(a) Clinical Picture showing orbital mass protruding from the left eye with axial proptosis and stretched out sclera along with dilated blood vessels, covering the entire exposed part of the eye with hyperemic keratinized conjunctiva tissue. (b) NCCT showing markedly expanded left ocular globe by a hyperdense mass and few cystic components with extension into left anterior cranial fossa with destruction of left orbital walls

Systemic examination of the patient was normal. Breast examination and gynecological examination were also normal. Clinically, at that stage, differential diagnoses of metastatic carcinoma, astrocytoma, and adult-onset retinoblastoma were considered by treating ophthalmologist and investigations were planned.

Blood examination was within normal limits. This included hemoglobin values, total leucocyte count, differential leucocyte count, and erythrocyte sedimentation rate. Peripheral blood smear was normal. The kidney function tests, liver functions tests, serum alkaline phosphatase, serum calcium, and serum phosphorus were normal. Urine examination was also normal. Electrocardiogram was also normal.

Noncontrast computed tomography (NCCT) scan off the orbit and Para Nasal Sinuses (PNS) revealed marked left proptosis with markedly expanded left ocular globe by a hyperdense mass, few cystic components with extension into left anterior cranial fossa, left anterior ethmoid, left frontal sinus, left frontal fossa soft tissues with destruction of left orbital walls, and great wing of sphenoid bone [Figure 1b]. A precise diagnosis was not possible based upon CT findings. The radiologist considered provisional diagnosis of primary intraocular tumor, metastatic carcinoma, malignant melanoma, or lymphoma and advised further investigations. Chest CT and abdomen ultrasonography were carried out and found to be normal. The patient was referred to us for fine needle aspiration cytology (FNAC) at this stage.

FNAC was done using a 22-gauze needle. Smears were prepared, air dried, and stained with Giemsa stain and Periodic Acid Schiff's stain (PAS stain). The microscopic examination of Giemsa-stained smears showed small, round cells in cluster and rosettes formation, suggestive of retinoblastoma [Figure 2a]. PAS positive granules in the cytoplasm of tumor cells were seen in PAS-stained smears, consistent with the diagnosis of retinoblastoma [Figure 2b].

Figure 2

(a) FNAC smear (Giemsa stain x100) showing small, round cells in cluster and rosettes formation, suggestive of retinoblastoma. PAS (b) Showing positive granules in the cytoplasm of tumor cells, consistent with diagnosis of retinoblastoma (PAS stain x200)

DISCUSSION

Retinoblastoma is a rare malignant neoplasm originating from the photoreceptor precursor cells of the eye, presenting usually in early childhood with an incidence rate of 1 in every 15000 to 18000 live births. The tumor can be either heritable with a germline mutation of the RB1 gene or nonheritable. Heritable mutations typically present in the first year of life with bilateral disease. In comparison, the nonheritable form typically presents slightly later and is primarily unilateral.[5] The retinoblastoma gene was the first tumor suppressor gene discovered in the human genome.[6]

Retinoblastoma in adults is an extremely rare tumor. Only about 30 cases have been reported in the world literature till date.[34578] Almost all these adults were sporadic and unilateral cases aged between 20 and 74 years. Characteristic manifestation of adult retinoblastoma was whitish, elevated, vascularized retinal mass, and diminution or loss of vision. Our patient was an adult female who reported at a very late stage of the disease with a significant degree of proptosis and extra propulsion of the whole ocular globe with hyperemic keratinized conjunctiva over the entire exposed part of the sclera and cornea. The affected eye was blind and it was not possible to examine the posterior chamber and retina.

CT is considered to be the best imaging modality for detection of intraocular calcifications.[910] Arrigg et al.[11] in their retrospective study of 21 cases of retinoblastoma using high-resolution CT found intraocular calcification in 83% of the cases. The degree of calcification appeared to depend on tumor size and only small tumors were devoid of calcification. The amount and distribution of calcification was similar on both histological study and CT scan. In patients less than 3 years of age in whom a retinoblastoma is suspected, the presence of calcification on CT is virtually diagnostic of it. The calcification which is a characteristic of retinoblastoma in children is usually not found in adults. Among most of the case reports of adult retinoblastoma available in the literature, only a few patients showed calcification in imaging studies. Our patient also did not show any calcification on NCCT. In a majority of cases of adult retinoblastoma reported in the literature [Table 1], the diagnosis was made at a fairly advanced stage. Our patient also reported to us at a very late stage of the disease.

Table 1

Comparative analysis of some case reports of retinoblastoma in adults

Various case reports of adult retinoblastoma emphasize the role of clinical diagnosis and confirmation by biopsy to be the most important tool in final diagnosis. However, in the last three decades, the role of additional modalities such as CT scan, ultrasonography, magnetic resonance imaging (MRI) scan, FNAC, and immunohistochemistry (IHC) has become very important.[711] IHC can be performed on biopsy samples, cytological smears, and cell blocks prepared from FNA sample. To differentiate retinoblastoma from malignant melanoma and malignant lymphoma, IHC stains used are NSE (neuron-specific enolase), synaptophysin, GFAP (glial fibrillary acidic protein), S-100, LCA (leucocyte common antigen), and HMB45 (human melanoma black 45).[5] Retinoblastoma cells show positivity for NSE, synaptophysin, GFAP, and S-100 whereas malignant melanoma cells are positive for S-100 and HMB-45. The LCA is positive for lymphoma and is regarded as an excellent marker to distinguish lymphomas from poorly-differentiated tumors of epithelial, mesenchymal, or neural derivation. Char and Miller in 1984 studied the role of FNAC in retinoblastoma in 3 patients and established its role in the correct diagnosis of the disease.[12] Over the last three decades, especially with the advent of imaging studies, the role of FNAC in the diagnosis of retinoblastoma and other orbital malignancies has gained importance. It has a sensitivity of 86.6%, specificity 100%, and positive predictive value 100%, as reported by Nag et al.[13] They carried out FNAC under direct vision or under ultrasonography/CT guidance a using 22-gauze needle without anesthesia. The final diagnosis in our patient was also established after FNAC. FNAC was carried out transcutaneously on the palpable mass in the superior part of the swelling. The cytological examination was consistent with the diagnosis of retinoblastoma. In our patient, the CT scan findings established that the tumor had breached the orbital wall and had locally spread out of the orbit to the neighboring areas. Unlike our case, most other case reports did not have adequate sample on FNAC.[514] Diagnosis in most cases was based on the enucleated orbital mass on histopathology, which supplemented by IHC in many case reports.[5714] However, in our patient, surgery was not done due to extension of tumor into the anterior cranial fossa and other adjoining areas.

CONCLUSION

Retinoblastoma should be considered as one of the uncommon differential in the diagnosis of an intraocular mass in adults despite its low frequency compared to other tumors including metastasis, melanomas, lymphomas, astrocytomas, etc. Clinical diagnosis is often possible unless the patients reports very late, as was in our case. When the diagnosis is not established clinically and by other noninvasive techniques, FNAC is indicated. It is a cheap, cost-effective, and simple procedure and helps in establishing the diagnosis with a very high degree of accuracy.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.