High-risk invasive retinoblastoma masquerading as orbital cellulitis: a case report

¹Department of Ophthalmology, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria, ²Department of Ophthalmology, Lagos University Teaching Hospital, Idi-Araba, Lagos, Nigeria, ³Department of Pathology, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria, ⁴College of Medicine, University of Lagos, Lagos, Nigeria

^&Corresponding author
Gbenga Jonathan Babalola, College of Medicine, University of Lagos, Lagos, Nigeria

Introduction    

Retinoblastoma is the most common primary intraocular malignancy of childhood and accounts for about 2.5% to 4% of paediatric malignancies [1]. It is primarily associated with pathogenic alteration of the RB1 tumour suppressor gene and is estimated to occur in approximately 1 in 15,000 to 18,000 live births [2]. Most cases are unilateral and sporadic [3]. Leukocoria and strabismus are the commonest presenting features, whereas proptosis, orbital swelling, orbital cellulitis, red eye, iris discoloration and hyphema are less common presentations that may obscure the diagnosis [4].

Retinoblastoma usually occurs in early childhood. Hereditary bilateral disease commonly manifests during the first year of life, while most unilateral cases are diagnosed in the second year; late presentation beyond five years is uncommon and may reflect delayed presentation, delayed diagnosis or an atypical clinical course [5,6]. Diagnostic difficulty is more likely when inflammatory signs dominate or when a history of trauma directs attention away from an intraocular tumour. We report a case of high-risk invasive retinoblastoma in a 12-year-old Nigerian girl who presented with features mimicking orbital cellulitis with panophthalmitis.

Patient and observation     

Patient information: a 12-year-old Nigerian girl, the fourth and youngest child of non-consanguineous parents, presented with a two-year history of progressive visual loss in the right eye associated with recurrent swelling, pain, tearing and ocular discharge. The symptoms reportedly began after accidental blunt trauma to the right eye. According to her mother, she did not complain immediately after the injury but developed ocular pain about four days later, after which poor visual acuity was noted at a clinic. During the subsequent months, she had recurrent swelling, discharge and pain and was treated repeatedly with intravenous antibiotics, oral analgesics and anti-inflammatory medications, with only temporary improvement. Her family was of middle socioeconomic status, both parents had tertiary education, and there was no history of retinoblastoma, childhood malignancy, blindness, enucleation or inherited eye disease among first-degree or extended family members.

Timeline of current episode: two years before specialist presentation, the patient sustained blunt trauma to the right eye, followed by progressive visual loss. In the subsequent months, she developed recurrent right ocular swelling, pain, tearing and discharge and received repeated treatment for presumed infection and inflammation. At the specialist presentation, she had a painful, blind right eye with persistent orbital inflammatory signs. B-scan ultrasonography and orbital computed tomography redirected the diagnosis towards retinoblastoma. She subsequently underwent right enucleation with orbital implant placement. A custom ocular prosthesis was fitted six weeks after surgery, and systemic chemotherapy with vincristine, etoposide and carboplatin was commenced after histopathological confirmation.

Clinical findings: visual acuity in the right eye was no light perception. There was marked right periorbital oedema with ptosis, conjunctival injection, chemosis, shallow anterior chamber and fixed dilated pupil (Figure 1). Fundus examination showed anterior displacement of the retina with haemorrhagic choroidal detachment. The left eye was clinically normal, with visual acuity of 6/5, intraocular pressure of 14 mmHg, normal eyelids, quiet and clear conjunctiva, clear cornea, normal anterior chamber depth and clear crystalline lens.

Diagnostic assessment: B-scan ultrasonography demonstrated haemorrhagic choroidal detachment with abnormal intraocular echoes and no obvious retinal detachment (Figure 2). Orbital computed tomography showed replacement of the right vitreous cavity by a poorly enhancing heterogeneous soft-tissue density lesion with a focal calcific focus adjacent to the retina, intraocular lens displacement, and thickening of the superior rectus muscle, lacrimal gland and sclera; the left orbit and intracranial structures were preserved, with no evidence of intracranial extension (Figure 3). The enucleated globe showed sheets and nests of small, round blue tumour cells with scanty cytoplasm and high mitotic activity involving the retina (Figure 4), extensive necrosis, old and recent haemorrhages, and poorly formed Flexner-Wintersteiner rosettes (Figure 5). Tumour cells infiltrated the optic nerve up to the resected margin, representing a high-risk histopathological feature (Figure 6). Immunohistochemistry showed synaptophysin positivity with moderate staining and 20% distribution, p53 positivity with weak staining and 10% distribution, and Ki-67 positivity with moderate staining and 15% distribution, suggesting an intermediate proliferative index. CD45, S100, AE1/AE3, GFAP and desmin were negative, supporting retinoblastoma and helping to exclude lymphoma and epithelial, melanocytic, glial and myogenic neoplasms.

Diagnosis: the final diagnosis was unilateral invasive poorly differentiated retinoblastoma with high-risk histopathological features, including optic nerve infiltration reaching the resected margin. The main alternative diagnoses considered clinically were orbital cellulitis and panophthalmitis, while immunohistochemistry helped exclude lymphoma and other small round blue cell tumours.

Therapeutic interventions: right enucleation with orbital implant placement was performed because the affected eye had no visual potential and malignancy was suspected. After histopathological confirmation of high-risk invasive retinoblastoma, she was referred to the paediatric oncology team and commenced systemic chemotherapy with vincristine, etoposide and carboplatin. Six cycles were planned, and two cycles had been completed at the time of manuscript preparation.

Follow-up and outcome of interventions: the postoperative period was satisfactory, and a custom ocular prosthesis fitted six weeks after surgery produced a good cosmetic outcome (Figure 7). During chemotherapy, she developed thrombocytopaenia and anaemia, which were managed with transfusion support using platelet concentrates and whole blood. She remained clinically stable and continued multidisciplinary follow-up with the ophthalmology, pathology and paediatric oncology teams.

Patient perspective: "I was very sad when I lost the vision in my right eye and kept having pain and swelling. I was scared when I was told that my eye had to be removed, but the doctors explained everything to me and my parents. After the surgery, I became much better, and I am happy with my artificial eye. I hope to get completely better, and I will continue my treatment and attend all my follow-up appointments."

Informed consent: the patient's parent provided written informed consent for publication of the case report and associated clinical images. Identifying facial areas in the clinical images were obscured to protect patient confidentiality.

Discussion     

This case is unusual because high-risk invasive retinoblastoma presented in a 12-year-old child with clinical features that mimicked orbital cellulitis with panophthalmitis. Retinoblastoma generally occurs early in childhood, and more than 95% of cases are diagnosed before five years of age [5]. Presentation after the first decade of life is rare and may be associated with atypical symptoms, delayed diagnosis, and more advanced disease at presentation [6]. Although this patient had no family history suggestive of heritable disease, absence of family history should not exclude retinoblastoma because many unilateral cases are sporadic [3].

The diagnostic challenge in this case was driven by recurrent orbital inflammation and a history of blunt trauma. Pain, swelling, discharge and tearing favoured an inflammatory diagnosis, while the trauma history may have reinforced the assumption that the visual loss and inflammation were post-traumatic. Similar diagnostic overlap has been described in advanced retinoblastoma, especially where ocular malignancy is not initially suspected [7]. In older children, persistent unilateral visual loss, painful blind eye, recurrent orbital inflammation, haemorrhagic choroidal detachment or poor response to antibiotics should prompt urgent ocular imaging and specialist referral.

Imaging and histopathology were central to diagnosis. Ultrasonography showed haemorrhagic choroidal detachment with abnormal intraocular echoes, while computed tomography demonstrated a heterogeneous intraocular lesion with focal calcification and no intracranial extension. Calcification is a useful imaging clue in retinoblastoma, although it may be less obvious in atypical or advanced cases. Magnetic resonance imaging is preferable when available because it avoids ionising radiation and better evaluates optic nerve and intracranial extension [6]. Definitive diagnosis in this case depended on histopathology, which showed small round blue tumour cells, high mitotic activity, necrosis, haemorrhage and poorly formed Flexner-Wintersteiner rosettes [1].

The most important prognostic feature in this patient was tumour infiltration of the optic nerve up to the resected margin. Optic nerve margin involvement is a high-risk histopathological feature because it increases concern for extraocular dissemination and supports the use of adjuvant systemic chemotherapy after enucleation. Enucleation remains appropriate for advanced unilateral retinoblastoma in an eye with no visual potential, while globe-sparing options are more applicable to selected less advanced cases [6]. The use of vincristine, etoposide and carboplatin was therefore consistent with the need for systemic treatment after high-risk histopathological confirmation.

A strength of this report is that it documents the full clinical pathway from misleading inflammatory presentation to imaging, histopathological confirmation, immunohistochemistry, enucleation, prosthetic rehabilitation and chemotherapy. Its main limitations are the absence of magnetic resonance imaging and the limited duration of follow-up at the time of manuscript preparation. The case reinforces global and regional concerns that delayed diagnosis contributes to advanced retinoblastoma and worse outcomes in low- and middle-income settings [8-10]. The practical lesson is that retinoblastoma should remain in the differential diagnosis of older children with chronic unilateral ocular disease, particularly when the eye is blind, painful, inflamed, or poorly responsive to antibiotics.

Conclusion     

This case describes high-risk invasive retinoblastoma in a 12-year-old Nigerian girl who presented with a chronic painful blind eye and recurrent orbital inflammatory features initially treated as orbital cellulitis with panophthalmitis. The main lesson is that retinoblastoma should be considered in older children with persistent unilateral visual loss, atypical post-traumatic ocular symptoms, haemorrhagic choroidal detachment, or recurrent orbital inflammation, because timely imaging, referral, histopathological confirmation, and multidisciplinary treatment can improve the patient's outcome.

Competing interests     

The authors declare no competing interests.

Authors' contributions     

Patient management: Rosemary Aleonasomi Ngwu, Olubanke Theodora Ilo, Bolanle Grace Balogun, and Maryam Bola Fashola; histopathological evaluation: Daniel Ayodele Sanni; data collection: Rosemary Aleonasomi Ngwu, Maryam Fashola, and Gbenga Jonathan Babalola; manuscript drafting: Gbenga Jonathan Babalola and Rosemary Aleonasomi Ngwu; manuscript revision: all the authors. All the authors read and approved the final version of this manuscript.

Acknowledgements     

The authors acknowledge the Ophthalmology, Pathology, Radiology and Paediatric Oncology teams involved in the care of this patient.

Figures     

Figure 1: clinical appearance at presentation showing marked upper eyelid oedema and ptosis

Figure 2: ultrasonography of the right eye showing abnormal intraocular echoes with haemorrhagic choroidal detachment

Figure 3: computed tomography image showing a heterogeneous intraocular lesion occupying the right globe, with features suspicious for retinoblastoma

Figure 4: histological sections showing sheets of small round blue tumour cells with scant cytoplasm (arrows)

Figure 5: histological section showing a poorly formed Flexner-Wintersteiner rosette (arrow)

Figure 6: histological section showing tumour cells infiltrating the optic nerve up to the resected end (arrows), representing a high-risk histopathological feature

Figure 7: appearance after ocular prosthesis fitting, showing a satisfactory cosmetic rehabilitation

References