Retinoblastoma in a child with tuberous sclerosis complex

Herpes zoster ophthalmicus (HZO) is a common ocular emergency caused by reactivation of the varicella zoster virus (VZV), leading to vesicular rash eruption in the ophthalmic division of the trigeminal nerve (V1). Clinical diagnosis is obtained with V1-distributed dermatomal rashes after a prodromal period of ocular pain, chemosis, visual impairment, diplopia, and ptosis.

Early recognition of this condition is important for timely medical management to prevent complications such as postherpetic neuralgia (PHN) and blindness. A less-documented, rare presentation of HZO is orbital myositis, which may be an early indicator of future vesicular rash eruption. We present a case of acute orbital myositis preceding vesicular rash eruption in HZO.

An 89-year-old female presented with a 4-day history of left periorbital edema, pain, and binocular diplopia. Her left eye (OS) demonstrated incomplete ophthalmoplegia, tonic pupil (fixed 5 mm), mild ptosis, proptosis, and conjunctival injection. The patient’s medical and surgical history was unremarkable except for 3+ nuclear sclerotic cataracts bilaterally. Retinal examination was unremarkable.

Two days after the initial presentation, the patient developed a vesicular rash in the left V1 distribution, with a positive Hutchinson sign. Slit-lamp examination demonstrated anterior chamber cells OS, and there was diffuse chemosis and complete ophthalmoplegia. Visual acuity OS declined from 20/200 to counting fingers, and her intraocular pressure increased from 19–22 mm Hg over these 2 days.

Axial computed tomography of the orbit (Fig. 1) and magnetic resonance imaging (MRI) brain (Fig. 2) demonstrated enlarged lateral, inferior, and medial recti muscles and proptosis OS. Immunologic and serologic analysis excluded autoimmune disorders and thyroid disease. The patient was started on intravenous acyclovir 450 mg TID and oral prednisone 60 mg. Repeat MRI done 2 weeks after initiation of treatment revealed improvement in the extraocular muscle (EOM) inflammation (Fig. 3). The patient reported localized ocular pain at initial presentation; however, this pain progressed to left facial discomfort in the V1 distribution over the following 2 months. PHN was diagnosed, and gabapentin 100 mg PO TID was started. By 4 months, her eye movements normalized in the left eye, coinciding with further improvement of the EOM thickening on MRI (Fig. 4). Visual acuity improved back to 20/200 and intraocular pressure normalized to 10 mm Hg. Symptoms of PHN resolved by the 11-month mark; MRI brain demonstrated resolution of proptosis and normal EOMs at this time (Fig. 5).

Ocular myositis is a rare inflammatory disorder of the EOMs. There are 2 major forms of ocular myositis, limited oligosymptomatic ocular myositis with conjunctival injection and severe exophthalmic ocular myositis with accompanying ptosis, diplopia, chemosis, and proptosis.

Our patient’s initial symptoms and imaging findings correlated well with severe exophthalmic ocular myositis. When the patient’s vesicular lesions erupted 2 days later, a diagnosis of HZO after reactivation of VZV was concluded. The reduction of visual acuity from 20/200 to counting fingers OS was most likely owing to uveitis secondary to HZO as demonstrated by the anterior chamber cells and the positive Hutchinson sign.

To our knowledge, only 7 previous cases of orbital myositis preceding vesicular rash eruption in patients with VZV reactivation have been published in literature. The first case published on this presentation by Volpe et al in 1991 described a 45-year-old male with unilateral periorbital edema, sharp pain, ptosis, chemosis, and diplopia owing to limited upgaze and adduction in his left eye.

Six other case reports with similar presentations of orbital myositis preceding vesicular rash eruption have since been noted in literature.

In all 6 previous cases, mean time to vesicular eruption after initial symptoms of orbital myositis was 4.8 days (range, 2–7 days); our patient presented with a V1 rash 6 days after initial symptoms. In concordance with our patient, all previous 6 cases demonstrated resolution of orbital symptoms after intravenous or oral antiviral and corticosteroid therapy. Our case further adds to the relative paucity of literature regarding the clinical course of orbital myositis preceding HZO rash presentation.

Of note, the case reported by Kim et al in 2012 was the only patient to develop PHN after initial presentation; this is a similar disease course as our patient, who experienced neurogenic left-sided facial pain.

PHN is a chronic, painful sequela of acute VZV reactivation that is the most common neurological complication of HZO and is associated with reduced quality of life.

Early and aggressive treatment of HZO with antiviral therapy could possibly reduce the risk for developing this neurological complication.

With over 90% of the world population currently hosting latent VZV, and with an estimated 25% recurrence of VZV infections, HZO is not an uncommon ocular emergency.

Common ocular involvement such as iritis, scleritis, and keratoconjunctivitis are seen in about 50% of patients with HZO,

and some of these patients may develop PHN, which can persist.

Acute orbital myositis as the initial presentation of HZO is very rare. Early recognition and prompt treatment of ocular myositis caused by HZO can possibly reduce the risk for blindness and PHN.

https://www.canadianjournalofophthalmology.ca/article/S0008-4182(19)30863-4/fulltext

Journal : CJO

Ref : HZO Orbit Orbital myositis

Primary intraocular mesenchymal chondrosarcoma: a histopathological surprise in an enucleated eye

7 Jun 2020

Ratnesh Ranjan, Parag K. Shah, Sarang Giratkar, Santhi Ramachandran, Narendran Venkatapathy

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.

https://www.canadianjournalofophthalmology.ca/article/S0008-4182(19)30546-0/fulltext

Journal : CJO

Ref : Mesenchymal chondrosarcoma Ocular Oncolgy RB Retinoblastoma

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