Sporadic Retinal Astrocytic Hamartoma Mimicking Retinoblastoma in a Child: A Case Report and Literature Review

ABSTRACT

Retinal astrocytichamartoma (RAH) is a rare benign glial neoplasm most commonly associated with tuberous sclerosis complex (TSC). Sporadic cases, occurring in the absence of systemic phakomatosis, are uncommon and may closely mimic retinoblastoma, particularly when presenting with a calcified intraocular mass, creating a diagnostic challenge with potentially irreversible therapeutic consequences. We report a 6‐year‐old boy with progressive exotropia and complete visual loss in the right eye. Multimodal imaging revealed a calcified posterior intraocular mass with diffusion restriction and contrast enhancement on MRI, features highly suspicious for retinoblastoma. Given the high radiologic suspicion of malignancy, the absence of residual visual potential, and the unavailability of optical coherence tomography, primary enucleation of the right eye with orbital implant placement was performed. Histopathological and immunohistochemical evaluation demonstrated astrocytic proliferation with focal glialfibrillary acidic protein (GFAP) positivity and synaptophysin negativity, favoring RAH; however, the unavailability of cone‐rod homeobox (CRX) and other neuronal markers precluded definitive exclusion of well‐differentiated retinoblastoma. The postoperative course was uneventful, and at one‐year follow‐up the patient remained clinically stable with no recurrence or intracranial pathology on MRI. This case illustrates the difficulty of differentiating sporadic RAH from retinoblastoma in young children when advanced diagnostics are limited, and underscores the need to weigh over treatment of a benign lesion against the risk of an unrecognizedintraocular malignancy. Expanding access to OCT and comprehensive immunohistochemistry is essential to reduce diagnostic uncertainty and unnecessary enucleation.

Key Clinical Message.

Sporadic retinal astrocytichamartoma (RAH) is rare and can closely mimic retinoblastoma when presenting as a calcified intraocular mass with visual loss. In resource‐limited settings, limited access to advanced imaging modalities such as optical coherence tomography (OCT) can hinder accurate preoperative differentiation and potentially lead to aggressive surgical intervention for an ultimately benign lesion. Integrated clinical and multimodal imaging evaluation is essential to minimize diagnostic uncertainty and balance the risks of overtreatment against those of missed malignancy.

Abbreviations

CRX

Cone‐rod homeobox transcription factor

FNAB

Fine‐needle aspiration biopsy

GFAP

Glial fibrillary acidic protein

H&E

Hematoxylin and eosin

MAP 2

Microtubule‐associated protein 2

MRI

Magnetic resonance imaging

NF1

Neurofibromatosis Type 1

NSE

Neuron‐specific enolase

OCT

Optical coherence tomography

RAH

Retinal astrocytic hamartoma

RB

Retinoblastoma

TSC

Tuberous sclerosis complex

1. Introduction

Retinal astrocytic hamartoma (RAH) is a benign glial tumor arising from astrocytes within the retinal nerve fiber layer or optic nerve head [1]. It is one of the most recognized ocular manifestations of tuberous sclerosis complex (TSC), occurring in approximately 30%–50% of affected individuals and typically presenting as bilateral, multifocal retinal lesions [2, 3]. Less commonly, RAH has been described in association with other neurocutaneous or inherited disorders, including neurofibromatosis Type 1, retinitis pigmentosa, Usher syndrome, and Stargardt disease [4]. Sporadic RAH, occurring in the absence of systemic disease, is rare and particularly uncommon in children [2, 5]. These isolated lesions tend to be unilateral and solitary, demonstrating a wide morphological spectrum ranging from flat, semitranslucent, noncalcified nodules to prominently elevated, calcified masses with intrinsic vascularity [6, 7]. Although most RAHs follow a stable, asymptomatic clinical course, lesions located in proximity to the macula or optic disc may cause significant visual impairment, strabismus, or other serious ocular complications [7, 8, 9].

The differential diagnosis of an intraocular mass in a child is broad, encompassing retinoblastoma, retinocytoma, acquired retinal astrocytoma, massive retinal gliosis, choroidal osteoma, and inflammatory chorioretinal lesions, among others. Among these, retinoblastoma remains the most critical and urgent diagnostic consideration, as it is the most common primary intraocular malignancy in children and frequently demonstrates intratumoral calcification on imaging [10, 11, 12, 13, 14]. Distinguishing RAH from retinoblastoma is particularly challenging when calcification, intrinsic vascularity, and overlapping ultrasonographic features are present; in such cases, diagnostic uncertainty has historically compelled clinicians to proceed with enucleation when malignancy could not be confidently excluded [11, 12, 13].

Advances in multimodal imaging, particularly OCT, and refined immunohistochemical panels have meaningfully improved the ability to differentiate these entities in well‐resourced settings; however, definitive preoperative diagnosis remains challenging where access to advanced modalities is limited. Reports of sporadic RAH in young children that closely simulate retinoblastoma remain exceedingly rare in the published literature [5, 15]. Herein, we present a diagnostically challenging case of unilateral sporadic RAH in a 6‐year‐old child that closely simulated retinoblastoma on clinical and radiologic evaluation, and we discuss the implications of this diagnostic overlap for clinical practice in resource‐limited settings.

2. Case Presentation

A 6‐year‐old boy from rural Ethiopia presented with a 10‐month history of progressively worsening outward deviation of the right eye and a 3‐month history of complete visual loss in the same eye. The ocular deviation developed insidiously and progressed gradually before becoming clinically prominent; this was followed by progressive visual deterioration culminating in complete loss of vision. He had been evaluated previously at multiple healthcare facilities and had received intermittent topical ophthalmic medications without improvement. He was born at term following an uncomplicated pregnancy and delivery, and his growth and developmental milestones were appropriate for his age. There was no family history of retinoblastoma, tuberous sclerosis complex, neurofibromatosis, or other hereditary disorders.

On general physical examination, the child appeared well, with normal vital signs and anthropometric parameters. Dermatologic assessment revealed no hypomelanotic macules, facial angiofibromas, shagreen patches, or other cutaneous stigmata of tuberous sclerosis complex, and neurologic and systemic examinations were unremarkable. Ophthalmologic examination demonstrated marked exotropia of the right eye with leukocoria. Visual acuity testing revealed a complete absence of light perception in the right eye (no light perception, NLP). In contrast, visual acuity in the left eye was 6/6, and the anterior segment was normal bilaterally. Funduscopic evaluation of the right eye revealed a well‐defined, elevated, yellow‐white chorioretinal mass involving the macular region, with focal surface hyperpigmentation and retinal vessels traversing the lesion surface, suggesting an intraretinal origin. The left fundus was normal. No Intraocular pressure elevation in both eyes.

3. Investigations, Differential Diagnosis, and Treatment

Baseline laboratory investigations, including complete blood count, serum electrolytes, renal function tests, and liver function tests, were within normal limits. Abdominal ultrasonography showed no visceral abnormalities, including no evidence of renal angiomyolipomas. B‐scan ultrasonography demonstrated a well‐defined, elevated, hyperechoic intraocular mass measuring approximately 10 × 6 mm, extending from the retina into the vitreous cavity. Doppler interrogation revealed internal tumor vascularity, and highly echogenic foci with posterior acoustic shadowing were identified, consistent with intralesional calcification. No retinal detachment was identified (Figure 1).

FIGURE 1.

B‐scan ultrasonography of the right eye demonstrating a well‐defined peripapillary echodense intraocular mass measuring 10 × 6 mm in basal diameter (white arrow), with high internal reflectivity and extension from the retina into the vitreous cavity.

Magnetic resonance imaging (MRI) of the brain and orbits revealed a 5 × 9 mm posterior intraocular lesion arising from the retina adjacent to the optic disc. The lesion was isointense on T1‐weighted imaging and hypointense on T2‐weighted imaging, with evidence of diffusion restriction on diffusion‐weighted imaging and mild, homogeneous gadolinium contrast enhancement. There was no evidence of optic nerve invasion, extraocular extension, or intracranial involvement, and no subependymal nodules or cortical/subcortical tubers suggestive of TSC were identified, although a dedicated neurocutaneous imaging protocol was not specifically performed (Figure 2).

FIGURE 2.

Contrast‐enhanced magnetic resonance imaging (MRI) of the brain and orbits demonstrates a small round‐to‐ovoid intraocular lesion arising from the posterior‐superior retina of the right globe (red arrows). The lesion is hypointense on sagittal T2‐weighted imaging (A), hyperintense on coronal FLAIR imaging (B), and shows mild contrast enhancement on post‐contrast sagittal T1‐weighted imaging (C). Diffusion‐weighted imaging (D) shows restricted diffusion, with hyperintensity on DWI (D) and corresponding hypointensity on the ADC map (E).

Optical coherence tomography (OCT), the most diagnostically specific non‐invasive imaging modality for differentiating RAH from retinoblastoma, was not available at our institution at the time of presentation. Its absence substantially limited assessment of the lesion's retinal layer of origin and internal architecture, compounding diagnostic uncertainty. Fine‐needle aspiration biopsy (FNAB) was not pursued in this case for several compelling reasons. When retinoblastoma is the primary clinical and radiological consideration, FNAB is widely regarded as a relative to absolute contraindication due to the risk of extraocular seeding of the poorly cohesive, highly malignant retinoblastoma cells through the needle track, with potential for devastating orbital dissemination or distant metastasis [16]. Moreover, the institutional absence of an experienced ocular oncologist, appropriate fine‐gauge instrumentation, and safe vitreoretinal biopsy facilities rendered this option impracticable. Given the complete and irreversible loss of visual function in the affected eye, the risk‐benefit assessment strongly favoredenucleation over an invasive diagnostic procedure that itself carried life‐threatening oncological risk. Germline RB1 mutation testing, which can provide additional diagnostic clarification and inform contralateral‐eye and family surveillance in children with suspected retinoblastoma, represents a further diagnostic resource limitation in this setting.

Based on the integrated clinical, ultrasonographic, and MRI findings, the differential diagnosis included retinoblastoma, retinal astrocytic hamartoma (RAH), acquired retinal astrocytoma, massive retinal gliosis, choroidal osteoma, amelanotic choroidal melanoma, and ocular toxocariasis. Among these, retinoblastoma was considered the most likely diagnosis because of intralesional calcification, restricted diffusion on MRI, contrast enhancement, and a progressive clinical course in a young child. Given the strong radiologic suspicion for retinoblastoma, the complete and irreversible loss of vision in the affected eye, and the inability to confidently exclude malignancy with the available diagnostic resources, histopathologic confirmation was considered more appropriate than a period of observation. Accordingly, primary enucleation of the right eye was performed, followed by placement of an orbital implant for cosmetic rehabilitation. The family was counseled regarding the diagnostic uncertainty underlying this decision, and written informed consent for enucleation was obtained accordingly.

4. Histopathological and Immunohistochemical Findings

Gross examination of the enucleated specimen revealed a well‐circumscribed intraocular mass measuring approximately 0.5 × 0.5 cm. Histopathological evaluation demonstrated a retinal lesion composed of proliferating astrocytic cells with moderate pleomorphism: tumor cells showed eccentric nuclei with irregular nuclear membranes, vesicular chromatin, prominent nucleoli, abundant eosinophilic cytoplasm, and distinct cell borders. Focal, predominantly lymphocytic inflammatory infiltrates were also identified. The lesion was confined entirely to the retina, with no choroidal invasion, optic nerve involvement, scleral infiltration, or extraocular extension, and no mitotic activity, tumor necrosis, or vascular invasion was observed (Figure 3A). Immunohistochemistry demonstrated focal positivity for glial fibrillary acidic protein (GFAP), supporting glial differentiation, while synaptophysin staining was negative, arguing against the neuronal differentiation characteristic of retinoblastoma (Figure 3B). Collectively, these histopathological and immunohistochemical findings, together with the absence of mitotic activity and invasive growth, favored a diagnosis of retinal astrocytic hamartoma.

FIGURE 3.

(A) Hematoxylin and eosin–stained section (×400) showing a tumor composed of moderately pleomorphic astrocytic cells with eccentric nuclei, irregular nuclear membranes, vesicular chromatin, and abundant eosinophilic cytoplasm, with a focal mild lymphocytic infiltrate. (B) Glial fibrillary acidic protein (GFAP) immunohistochemistry (×200) demonstrating focal cytoplasmic immunoreactivity in tumor cells.

Several important diagnostic limitations must, however, be explicitly acknowledged. Additional neuronal markers, cone‐rod homeobox transcription factor (CRX), neuron‐specific enolase (NSE), and microtubule‐associated protein 2 (MAP2) were unavailable at our institution. CRX is a transcription factor of exceptional diagnostic value in this context; it is highly sensitive and specific for photoreceptor differentiation and is characteristically expressed in retinoblastoma while being absent in glial tumors [17]. Its absence from the immunohistochemical panel constitutes a fundamental diagnostic limitation and prevents definitive exclusion of well‐differentiated retinoblastoma. Furthermore, fleurette‐like structures were identified on H&E staining, structures that may be seen in well‐differentiated retinoblastoma as well as in reactive glial lesions, further complicating definitive histopathologic classification [18, 19]. Accordingly, the diagnosis of RAH in this case must be considered probable rather than definitive, and the complete exclusion of well‐differentiated retinoblastoma or retinocytoma cannot be established with certainty on the basis of the available histopathological and immunohistochemical data.

5. Outcome and Follow‐Up

The postoperative course was uneventful. The patient recovered well from enucleation and orbital implant placement, with a satisfactory cosmetic outcome and no immediate surgical complications. At one‐year follow‐up, the patient remained clinically stable with no systemic or neurological complaints. Follow‐up MRI of the brain and orbits demonstrated no evidence of residual tumor, local recurrence, orbital relapse, or new intracranial pathology, including no new subependymal nodules or cortical tubers. No adjuvant systemic chemotherapy, radiation therapy, or local ocular therapy was administered, given the histopathological and immunohistochemical findings collectively supporting a benign astrocytic lesion. The patient continues to undergo regular clinical follow‐up. Given the diagnostic uncertainty at the time of histopathological evaluation, longer‐term follow‐up will be required to further substantiate the benign biological behavior of this lesion.

6. Discussion

Retinal astrocytic hamartoma is a rare benign glial neoplasm that typically arises in the setting of tuberous sclerosis complex but may uncommonly occur as a sporadic lesion, particularly in the pediatric age group [20]. Most sporadic cases have been reported in young adults; a large multicenter retrospective study by Prabha et al. confirmed a mean age at diagnosis of approximately 26 years with a modest male predominance [4], while the seminal pathological series by Ulbright et al. demonstrated that approximately 29% of histologically confirmed intraocular astrocytic tumors were sporadic in origin [15]. The present case is notable for its occurrence in a 6‐year‐old child with no clinical, familial, neuroimaging, or dermatologic evidence of TSC or any neurocutaneous syndrome, extending the recognized age spectrum of sporadic RAH and reinforcing the importance of considering this diagnosis in very young children presenting with a calcified intraocular mass [5].

RAH has been morphologically classified into three types: Type 1 lesions are small, flat, semitranslucent, and noncalcified; Type 2 lesions are nodular, elevated, and prominently calcified; and Type 3 lesions exhibit features of both [18, 21]. Based on the nodular configuration, marked intralesional calcification, and retinal elevation documented in this case, the lesion is most consistent with Type 2 RAH. Tumor location carries independent clinical significance, as peripapillary lesions tend toward earlier progression and visual compromise, whereas peripheral lesions typically remain stable [9, 22]. The combined peripapillary and macular location of the tumor in this case likely contributed to the early onset of severe visual impairment and progressive exotropia.

Multimodal imaging is indispensable in the preoperative evaluation of intraocular tumors. B‐scan ultrasonography is sensitive for detecting calcification but lacks specificity for distinguishing benign from malignant lesions [14], and the posterior acoustic shadowing observed in this case was consistent with either RAH or retinoblastoma. MRI demonstrated diffusion restriction and mild contrast enhancement, features characteristic of retinoblastoma due to high cellularity and disruption of the blood‐retinal barrier, yet these findings are neither pathognomonic nor exclusive to retinoblastoma and may occur in other calcified intraocular tumors, including RAH [10, 14]. By contrast, in the confirmed isolated RAH reported by Wojcik‐Niklewska et al. orbital MRI showed a low‐signal area with calcification and no contrast enhancement, findings that, in retrospect, distinguished it from retinoblastoma [23].

Optical coherence tomography (OCT) represents the most diagnostically specific non‐invasive modality for differentiating RAH from retinoblastoma and was the single most consequential missing diagnostic tool in this case. Shields et al. demonstrated in a systematic series of RAH cases that the lesion characteristically arises from the retinal nerve fiber layer in 100% of cases and exhibits distinctive “moth‐eaten” optically empty spaces in 91%, findings that are fundamentally distinct from the full‐thickness retinal disorganization and “retinal draping” appearance observed with retinoblastoma on OCT [24, 25]. Enhanced‐depth OCT reliably distinguishes these entities based on their different architectural signatures [15]. Batu Oto et al. demonstrated this capability in a 3‐month‐old infant in whom OCT findings of intraretinal cystic spaces confined to the nerve fiber layer established the correct diagnosis of RAH without requiring enucleation, a lesion subsequently confirmed as stable over six years of follow‐up [5]. The absence of OCT at our institution, therefore, likely contributed directly to the decision to proceed with enucleation in a case that, in a well‐resourced setting, might have been managed conservatively.

Histopathologic and immunohistochemical evaluation remains the gold standard when clinical and imaging findings are inconclusive or unavailable. RAH characteristically demonstrates GFAP immunoreactivity, reflecting its glial origin, while lacking neuronal markers such as synaptophysin [7, 14]. As illustrated by Pusateri and Margo in a case of coexisting RAH and retinoblastoma within the same eye, GFAP positivity and synaptophysin negativity constitute the core immunohistochemical distinction between the two entities [14]. Retinoblastoma, composed of primitive neuroectodermal cells forming Flexner‐Wintersteiner and Homer‐Wright rosettes, typically shows strong immunoreactivity for synaptophysin, NSE, and CRX [7, 9]. In the present case, focal GFAP positivity combined with synaptophysin negativity and the absence of invasive growth supported a diagnosis of RAH; however, the unavailability of CRX, a transcription factor that is highly sensitive and specific for photoreceptor differentiation and is characteristically expressed in retinoblastoma, represented a fundamental immunohistochemical limitation [17]. Together with the absence of NSE and MAP2, this incomplete panel precluded definitive exclusion of well‐differentiated retinoblastoma. Fleurette‐like structures identified on H&E staining, which are pathognomonic for retinoblastoma when confirmed, require complete immunohistochemical characterization, including CRX, to distinguish them from reactive glial elements [18, 19]. In well‐resourced settings, these additional markers would routinely be applied to resolve such diagnostic ambiguity; their absence in resource‐limited pathology laboratories represents a critical, actionable gap.

Fine‐needle aspiration biopsy (FNAB) represents a potential means of resolving diagnostic uncertainty while avoiding enucleation. However, its role is limited when retinoblastoma cannot be confidently excluded because of the risk of extraocular tumor dissemination. Consequently, FNAB of an intraocular lesion suspicious for retinoblastoma is generally considered a relative contraindication and is reserved for carefully selected cases managed by experienced ocular oncology teams [16]. Shields et al. demonstrated the diagnostic utility of this approach in a 7‐week‐old infant with a minimally calcified macular mass associated with secondary retinal detachment. In that case, transvitreal FNAB revealed benign glial cells that stained positively for GFAP, establishing the diagnosis of retinal astrocytic hamartoma (RAH) and avoiding enucleation [19]. However, unlike the present case, the affected eye retained visual potential, and the clinical and radiologic findings were less suggestive of malignancy, making tissue diagnosis a more justifiable option. In contrast, in the present case, complete and irreversible vision loss, imaging findings highly suggestive of retinoblastoma, and the lack of an ocular oncology service experienced in intraocular biopsy favored primary enucleation. Although FNAB might theoretically have preserved the eye if the lesion had been benign, the risk of delaying treatment for a potential retinoblastoma outweighed its potential benefit.

The differential diagnosis of a calcified intraocular mass in a child also includes massive retinal gliosis, acquired retinal astrocytoma, choroidal osteoma, amelanotic choroidal melanoma, choroidal metastases, and ocular toxocariasis. Massive retinal gliosis presents as diffuse retinal thickening associated with chronic injury rather than a discrete mass [14]. Acquired retinal astrocytoma may show progressive growth and exudative features, distinguishing it from the typically stable course of RAH [26]. Amelanotic choroidal melanoma is exceedingly rare in children and typically demonstrates acoustic hollowness and choroidal excavation on ultrasonography [23, 27]. Choroidal osteoma, although calcified, arises from the choroid rather than the retina and is more commonly observed in young adult females [28]. Choroidal metastases occur almost exclusively in adults with known systemic malignancy [29], while ocular toxocariasis may simulate an intraocular mass but is typically associated with significant vitreous inflammation and tractional membranes [30]. Despite these distinguishing features, considerable diagnostic overlap persists, and misdiagnosis has historically led to unnecessary enucleation in cases presumed to represent retinoblastoma [11, 13, 15]. Table 1 summarizes the clinical, imaging, histopathological, and immunohistochemical features of the present case alongside previously published sporadic RAH cases and contrasts these findings with the corresponding features of retinoblastoma.

TABLE 1.

Comparative clinical, imaging, histopathological, and immunohistochemical features of the index case, previously published sporadic RAH cases, and retinoblastoma.

Parameter	Index case findings	Literature evidence and comparative analysis	References
Demographics	6‐year‐old male; no family history of ocular or systemic disease.	Sporadic RAH spans neonatal/infant onset (a 7‐week‐old boy in Shields et al., 1996; a 3‐month‐old infant in Batu Oto et al.) through adulthood (mean age ~26 years, slight male predominance, in the 38‐patient multicenter cohort of Prabha et al.). Pediatric sporadic presentation, as in the index case, remains distinctly uncommon. Retinoblastoma presents earlier still, with a mean age of ~24 months (unilateral) and ~15 months (bilateral) at diagnosis.	[4, 5, 19, 31]
Systemic associations	None; no cutaneous, neurologic, or neuroimaging stigmata of TSC or NF1	RAH is classically TSC‐associated (30%–50% of TSC patients), with bilateral, multifocal lesions. Sporadic, unifocal, unilateral lesions, as in the index case and in Batu Oto et al. and Wojcik‐Niklewska et al. occur without any systemic disease. Retinoblastoma is an isolated ocular (or, rarely, trilateral CNS) disease driven by an RB1 mutation, without cutaneous stigmata.	[3, 5, 18, 23, 31]
Clinical presentation	Progressive exotropia (10 months); complete, painless visual loss (3 months); no leukocoria	Sporadic RAH is usually an incidental, asymptomatic finding unless juxtapapillary or macular, where strabismus and visual decline may occur, as illustrated by the adolescent of Wojcik‐Niklewska et al. Retinoblastoma classically presents with leukocoria (the most common sign) and strabismus, typically before 3 years of age.	[6, 9, 23, 31]
Fundus findings	Elevated yellow‐white chorioretinal macular mass with surface hyperpigmentation; traversing retinal vessels	Calcified (Type 2) RAH typically shows a nodular, mulberry‐like, or yellow‐white elevated mass, as in Wojcik‐Niklewska et al. Retinoblastoma more often appears as a chalky‐white, friable mass, occasionally with vitreous or subretinal seeding.	[18, 21, 23, 24]
Ultrasonography (B‐scan)	Elevated hyperechoic mass, 10 × 6 mm; internal vascularity; posterior acoustic shadowing (calcification); no detachment	B‐scan reliably detects calcification but cannot reliably distinguish RAH from retinoblastoma, since both produce hyperechoic, shadowing lesions; this overlap directly underlay the historical misdiagnoses reported by Drewe et al. and Kothari and Lam.	[11, 13, 14]
MRI	5 × 9 mm posterior lesion; T1 isointense, T2 hypointense; restricted diffusion on DWI; mild contrast enhancement	Diffusion restriction and contrast enhancement are typical of the high cellularity and disrupted blood‐retinal barrier of retinoblastoma, but are not pathognomonic, as illustrated by the index case. The confirmed RAH of Wojcik‐Niklewska et al. instead showed a low‐signal, non‐enhancing calcified focus, an imaging pattern that favors RAH over retinoblastoma when present.	[10, 14, 23]
OCT	Not available at the treating institution	OCT is the single most specific noninvasive discriminator: RAH characteristically arises from the retinal nerve fiber layer with “moth‐eaten” optically empty spaces in up to 91% of cases, confirmed in the infant of Batu Oto et al. and the case of Kothari and Lam; retinoblastoma instead produces abrupt, full‐thickness retinal disorganization with a “retinal draping” pattern. Absence of OCT was the principal diagnostic limitation in the index case.	[5, 13, 24, 25]
Histopathology (H&E)	Astrocytic proliferation with eosinophilic cytoplasm; fleurette‐like structures identified	Classic RAH consists of bland spindle and stellate astrocytes (Shields et al.); a giant‐astrocyte morphology with eosinophilic cytoplasm, as in the index case, is also recognized (Ulbright et al.). Fleurette‐like structures are characteristic of well‐differentiated retinoblastoma but may rarely occur in reactive glial lesions, mandating immunohistochemical confirmation.	[15, 17, 19]
IHC	GFAP positive (+); synaptophysin negative (−); CRX, NSE, and MAP2 unavailable	GFAP positivity with synaptophysin negativity is the immunohistochemical signature of RAH, as also demonstrated by Shields et al. retinoblastoma instead shows strong synaptophysin, NSE, and CRX positivity. Absence of CRX from the index case panel precluded definitive exclusion of retinoblastoma.	[7, 14, 17, 19]
Management	Primary enucleation with orbital implant; no adjuvant therapy	Most sporadic RAH cases are managed by observation alone, as in Batu Oto et al. (6‐year stability) and Wojcik‐Niklewska et al. (7‐year stability); Shields et al. used fine‐needle aspiration biopsy to avoid enucleation altogether. Intervention (laser photocoagulation, photodynamic therapy, anti‐VEGF therapy) is reserved for exudative complications. Enucleation in the index case, as in the historical misdiagnoses of Drewe et al. and Kothari and Lam, was driven by irreversible visual loss and the inability to exclude malignancy without OCT or a complete immunohistochemical panel.	[5, 11, 13, 19, 23, 32]
Clinical outcome	Uneventful recovery; stable at 1‐year follow‐up; no recurrence or intracranial pathology	The natural history of RAH is benign and nonprogressive, with no documented malignant transformation; long‐term stability is similarly reported by Batu Oto et al. and Wojcik‐Niklewska et al. Untreated or misdiagnosed retinoblastoma, in contrast, carries a risk of metastasis and death.	[5, 23, 31, 33]

Abbreviations: CRX, cone‐rod homeobox transcription factor; DWI, diffusion‐weighted imaging; GFAP, glial fibrillary acidic protein; H&E, hematoxylin and eosin; IHC, immunohistochemistry; MAP2, microtubule‐associated protein 2; MRI, magnetic resonance imaging; NF1, neurofibromatosis Type 1; NSE, neuron‐specific enolase; OCT, optical coherence tomography; RAH, retinal astrocytic hamartoma; RB, retinoblastoma; T1, T1‐weighted sequence; T2, T2‐weighted sequence; TSC, tuberous sclerosis complex; TSC, tuberous sclerosis complex.

The natural history of RAH is benign and generally nonprogressive, with malignant transformation undocumented in the literature [33]. Zimmer‐Galler and Robertson and Shields et al. both reported a greater tendency toward progression in peripapillary lesions [9, 22], directly relevant to the present case. Management is therefore conservative in most cases, with intervention, including laser photocoagulation, photodynamic therapy, and anti‐vascular endothelial growth factor therapy, reserved for lesions complicated by exudative retinal detachment, neovascular glaucoma, or vision‐threatening growth [7, 26, 32]. In the present case, primary enucleation was clinically justifiable given the strong radiologic suspicion for retinoblastoma, the complete and irreversible loss of visual function, and the absence of advanced diagnostic resources necessary to confidently exclude malignancy. Nevertheless, this case raises the possibility that, in a better‐resourced setting, alternatives, including serial OCT imaging, expanded immunohistochemical analysis with CRX and additional neuronal markers, fine‐needle aspiration biopsy by an experienced ocular oncology team, referral to a tertiary ocular oncology center, or close surveillance, might have been pursued before enucleation. In resource‐limited settings, such options are frequently unavailable, compelling clinicians to make consequential decisions under diagnostic uncertainty. This experience underscores the urgent need to strengthen access to advanced ophthalmic diagnostic tools in low‐ and middle‐income countries and to develop evidence‐based referral pathways aimed at minimizing unnecessary enucleation in similar clinical scenarios.

7. Conclusion

Sporadic RAH in young children is an exceptionally rare benign retinal neoplasm that can closely simulate retinoblastoma on clinical and radiological grounds, creating a diagnostic dilemma with potentially irreversible therapeutic consequences. In resource‐limited settings, where OCT and comprehensive immunohistochemical panels including CRX are often unavailable, a definitive preoperative diagnosis may not be achievable, and clinicians must carefully balance the risks of overtreatment (unnecessary enucleation of a benign eye) against the potentially fatal consequences of undertreating an intraocular malignancy. This case further underscores the need for greater clinical awareness of sporadic RAH presentations in the pediatric population, the expansion of advanced ophthalmic diagnostic capacity in resource‐limited settings, and the development of formalized referral pathways to specialized ocular oncology centers, with the shared goal of enhancing diagnostic precision and safeguarding both life and vision for affected children.

Author Contributions

Mesfin Wubishet Gurmu: conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, resources, software, supervision, validation, visualization, writing – original draft, writing – review and editing. Samuel Negash: conceptualization, data curation, formal analysis, methodology, validation, visualization, writing – original draft, writing – review and editing. Aneso Mohammed: conceptualization, data curation, formal analysis, funding acquisition, methodology, validation, writing – original draft, writing – review and editing. Hailu Alemu: conceptualization, data curation, formal analysis, methodology, resources, validation, visualization, writing – original draft, writing – review and editing. Diriba Fufa Hordofa: conceptualization, formal analysis, investigation, methodology, validation, visualization, writing – original draft, writing – review and editing. Melese Abere: conceptualization, data curation, funding acquisition, methodology, resources, validation, visualization, writing – original draft, writing – review and editing. Lensa Million: conceptualization, data curation, formal analysis, methodology, resources, validation, writing – original draft, writing – review and editing. Esubalew Mezgebu: conceptualization, data curation, formal analysis, methodology, project administration, resources, supervision, validation, visualization, writing – original draft, writing – review and editing.

Funding

The authors have nothing to report.

Ethics Statement

Institutional ethics approval was not required for the publication of this single case report, in accordance with the institutional policy.

Consent

Written informed consent was obtained from the patient's parent/legal guardian for the publication of this case report and any accompanying images.

Conflicts of Interest

The authors declare no conflicts of interest.

Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author.