The incidence of clinical and histopathological discordance in eyes enucleated for retinoblastoma, though not rare, has reduced significantly over a period of years.
Benign ocular lesions such as coats’ disease and persistent hyperplastic primary vitreous in end-stage conditions simulate retinoblastoma.
Nonmalignant ocular tumours such as ocular teratoma, astrocytic hamartoma, and retinal astrocytoma can also mimic retinoblastoma, clinically as well as on imaging, resulting in potentially avoidable enucleation.
Mesenchymal chondrosarcoma (MCS), a rare cartilage-forming tumour with potential aggressive course, is usually found in the skeleton. However, about one-third of the cases are also found in extra-skeletal sites, including orbit.
Although primary intraocular chondrosarcomas have been reported in fish and other mammals such as cats and dogs, there is no report of intraocular MCS in human eye. We are reporting the first case of presumed primary intraocular MCS confirmed on histopathological examination in an eye enucleated for retinoblastoma.
A 9-year-old girl was brought to our outpatient department with complaints of redness and pain in the right eye (RE) of 3 days’ duration. There was history of squinting and white reflex in the same eye for the past 3 years, but no prior ophthalmic consultation was taken. On examination, there was no perception of light in RE, and the best-corrected visual acuity in the left eye (LE) was 6/6. Anterior segment examination of RE revealed circumcorneal congestion, microcystic corneal oedema, shallow anterior chamber depth with 3+ cells, mid-dilated pupil, neovascularisation iris, and clear lens with retrolental white reflex (Fig. 1A). Findings of anterior segment and fundus examinations of LE were within normal limits. During examination under anaesthesia, same findings were noted in anterior segment of RE. Fundus examination showed exudative retinal detachment with white intraocular mass lesion. Intraocular pressure measured was 50 mm Hg in RE and 15 mm Hg in LE. Ultrasound B-scan showed well-defined mass lesion with intralesional calcification in the vitreous cavity with exudative retinal detachment suggestive of endophytic retinoblastoma (Fig. 1B). Magnetic resonance imaging (MRI) showed well-defined endophytic lesion in the temporal half of the right globe having features suggestive of retinoblastoma with scleral involvement in RE as detailed in Figure 2.
A diagnosis of stage 0 group E retinoblastoma was made, and the patient underwent enucleation with implant in RE. Enucleated globe was sent for histopathological analysis. Gross appearance of the cut open eye globe showed an intraocular multilobular greyish white well-defined tumour, measuring 1.2 cm × 1.4 cm, with interspersed tiny hemorrhagic foci arising from the posterior pole and extending anteriorly. The tumour appeared to be originating from choroid pushing retinal pigment epithelium, and causing retinal detachment (Fig. 3). Anterior chamber, sclera, and optic nerve were found uninvolved. Microscopic analysis of hematoxylin and eosin–stained sections from the eye ball showed intraocular tumour tissue involving choroid and vitreous, and closely intricated with retina. Tumour tissue showed sheets of undifferentiated round, oval, and spindle cells with abrupt transition. Small well-defined nodules of well-differentiated hyaline cartilage with central calcification and ossification were also seen. Areas of cartilaginous foci blending in hemangiopericytomatous pattern with undifferentiated cell tumour, haemorrhage, and necrosis were present. Immunohistochemical analysis confirmed the presence of cartilage by positive staining for S100 (Fig. 4). The histopathological features were suggestive of intraocular MCS.
Postenucleation computed tomography (CT) scan of the right orbit showed no residual lesion, whereas CT scan of the left orbit was normal. The child was referred to paediatric oncologist for systemic evaluation, but no other tumours or skeletal lesions were identified, ruling out the possibility of ocular metastasis.
Extraskeletal MCS is a very rare tumour, with orbit being the third most common site following meninges and lower extremities.
Since the first case reported by Cardenas-Ramirez et al in 1971, approximately 40 cases of primary orbital MCS are reported in literature till now, highlighting the rarity of primary intraocular MCS.
No case of intraocular MCS, primary or metastatic, in human being has been previously reported in literature.
Naturally occurring cartilage in fish eyes could be the source of origin for primary intraocular MCS in fish.
Mammals do not have cartilage or bone within their globes, and hence the source of origin of intraocular MCS is not clear in mammals. In mammals, the multipotent mesenchymal stem cells derived from the trabecular meshwork or from pericytes of bovine retina are found to have potential to differentiate into osteoblasts and chondrocytes, and hence could be the possible origin for the tumour in our case.
Extraskeletal MCS is usually seen in younger age group compared with conventional chondrosarcoma. Although orbital MCS commonly presents in second or third decades of life, paediatric cases, including congenital orbital MCS, are also reported.
Orbital MCS tends to present like benign orbital tumours with globe compression resulting in progressive proptosis, diplopia, reduction in visual acuity, and pain of variable severity.
In our case, due to its highly unusual location and late presentation, tumour mimicked as end-stage retinoblastoma and presented with pain and redness.
Imaging features of orbital MCS on CT and MRI scan are well described. CT scan shows well-defined, heterogeneously enhancing mass with calcification seen as high-intensity signal.
It usually causes widening of bony orbit without bone erosion.
MRI shows hypo- or isointense signal in T1-weighted scans, isointense signal in T2-weighted scans, and moderate to marked heterogenous enhancement of the soft-tissue component. Intralesional calcifications are seen as low-signal-intensity spots.
As an orbital tumour, ultrasonographic feature of MCS is very rarely reported in literature appearing as well-demarcated hypoechoic mass lesion with heterogenous echogenicity.
In our case, intraocular MCS appeared as large, well-defined, moderately echoic mass lesion with intralesional calcification causing high echogenicity and back-shadowing.
Macroscopic and microscopic features of tumour in our case were consistent with histological features of orbital MCS. Macroscopically, MCS appears as lobulated, soft-to-firm, grey-white mass with focal calcification or cartilaginous component
Microscopically, bimorphic appearance is the pathognomonic feature of MCS characterized by the presence of undifferentiated, round, or spindle-shaped mesenchymal cells arranged in sheets or small clusters, and islands of mature hyaline cartilaginous tissue. This cartilaginous differentiation is crucial for diagnostic confirmation, which often shows central calcification and even ossification.
Some tumours may show arrangement of mesenchymal cell surrounding vascular space resembling hemangiopericytoma.
Immunohistochemical analysis often reveals strong positivity for the S-100 protein by the cartilaginous component, whereas the cellular component shows positivity for CD99, vimentin, and Leu7. For diagnostic confirmation, however, immunohistostaining is used only in case of doubt when tumours such as malignant lymphoma, hemangiopericytoma, Ewing sarcoma, and soft-tissue chondroma mimic MCS.
Radical surgical excision with negative margins is the most effective treatment modality for MCS. Vision and globe salvaging resection is possible in cases of extraskeletal orbital MCS.
In our case, MCS being intraocular, enucleation was the only option for complete surgical removal, though it was done for a suspected diagnosis of retinoblastoma. Role of radiotherapy or chemotherapy in the management of MCS is limited for cases with incomplete removal or histologically aggressive tumour.
To the best of our knowledge, this is the first case to report intraocular MCS in the human eye. The presentation of intraocular MCS can mimic retinoblastoma. Imaging studies are of little use in differentiating intraocular MCS from retinoblastoma due to common imaging features. Being a malignant tumour with risk of distant metastasis, enucleation is the best treatment modality for intraocular MCS. Diagnostic confirmation is possible only after histopathological study of enucleated specimen.