Unusual Association of Multiple Cerebral and Orbital Tumors in a Two-Year-Old Child: A Case Report and Literature Review

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Established cancer-predisposition syndromes (NF1/NF2, Li–Fraumeni) or prior cranial irradiation can give rise to multiple lesions, but these were not apparent in our patient. Case Presentation: A previously healthy 2-year-old girl presented with chronic headache and progressive right-sided proptosis. MRI and CT revealed six separate lesions: (1) an intraocular retinoblastoma extending into the orbit; (2) two intra-conal right optic nerve sheath schwannomas; (3) a heterogeneous cystic sellar/suprasellar mass suggestive of craniopharyngioma; (4) a homogeneously enhancing olfactory groove meningioma; (5) a mixed cystic-solid right cerebellar mass consistent with pilocytic astrocytoma; and (6) multiple leptomeningeal and cortical enhancing nodules compatible with carcinomatous meningitis. The family was opposed to further genetic tests and elected serial imaging surveillance for all lesions. The child had no personal or family history of a cancer syndrome, no prior radiation exposure, and no systemic features of an inherited neoplasia predisposition. Conclusion The co-occurrence of six histologically distinct CNS tumors in one child, none of which fit a known genetic syndrome, appears unprecedented. This case underscores that multiple spatially and pathologically discrete brain tumors can arise in a pediatric patient without identifiable risk factors. It highlights the importance of thorough diagnostic evaluation (to distinguish multicentric primaries from metastases) and consideration of underlying germline or mosaic mutations. Further study is needed to understand the etiology of such multiple tumor formations and to guide surveillance and management in similarly complex cases. child intracranial tumours brain MRI brain CT Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Multiple primary intracranial neoplasms in a single patient are exceedingly uncommon, and pediatric cases involving distinct tumor types are especially rare [ 1 , 2 ]. Most reported instances involve only two synchronous lesions, often linked to cancer predisposition syndromes or prior therapy. For example, neurofibromatosis type 2 (NF2) is characterized by multiple schwannomas and meningiomas [ 3 ], and Li–Fraumeni syndrome or hereditary retinoblastoma predispose to other characteristic tumors. In children without such syndromes, even two separate brain tumors have been described as unusual: a 4-year-old boy with a choroid plexus papilloma and a giant-cell astrocytoma was reported in 1986, with the authors noting that “even in the absence of…predisposition…two separate intracranial masses may not represent metastasis of a single primary tumor” [ 4 ]. Similarly, Jea et al. described an 8-year-old boy with concurrent medulloblastoma and pilocytic astrocytoma – the first known pediatric case of those two distinct tumors occurring together [ 2 ]. Karami et al. later reported a 4-year-old boy with simultaneous choroid plexus carcinoma and pilocytic astrocytoma, again emphasizing the rarity of two primary CNS tumors in a child without prior therapy or familial syndromes [ 1 ]. To our knowledge, no previous report has documented more than two histologically different CNS tumors in one pediatric patient. We describe a 2-year-old girl who presented with six coexisting intracranial lesions, each corresponding to a different tumor type. Four of these – retinoblastoma, optic nerve schwannomas, craniopharyngioma, and meningioma – are themselves rare in early childhood and have not been reported together. The presence of multiple leptomeningeal nodules (suggesting neoplastic meningitis) further raised concern for metastatic spread, but no single primary could account for all findings. No genetic syndrome or prior radiotherapy could explain this constellation. This unprecedented case highlights gaps in current knowledge: the pathogenesis of multiple synchronous tumors in a child is unclear, and there are no established guidelines for evaluation or management. We review the literature on multiple intracranial neoplasms, emphasize the novelty of our findings, and discuss clinical implications. Case presentation A previously healthy two-year-old girl was brought to the University Teaching Hospital of Yaoundé, Cameroun, by her parents because of progressive, diffuse headaches and right-sided ocular protrusion. Symptoms had begun insidiously approximately 11 months before presentation and had become more pronounced over the preceding three months, with frequent nocturnal irritability, intermittent vomiting, and a decline in appetite. There was no history of fever, recent head trauma, or seizures. Developmental milestones had been reported as age appropriate by the caregivers. Family history was notable for no known malignancies or consanguinity. On examination the child was alert and interactive but irritable. Vital signs were within age-appropriate limits (temperature 36.8°C; heart rate 110 beats per minute; respiratory rate 26 breaths per minute). Growth parameters were at the 25th percentile for age. Neurologic examination showed a grade-1 right proptosis with limited abduction of the right eye and pallor of the right pupil on fundoscopic inspection; there was no gross focal motor deficit. Visual fixation in the right eye was attenuated; the left eye appeared normal. There were no skin stigmata of neurocutaneous disease. Signs suggestive of raised intracranial pressure were subtle: the anterior fontanelle was closed, but parents reported new morning headaches and intermittent vomiting. Initial laboratory testing, including complete blood count and basic metabolic panel, was within reference intervals for age. Serum alpha-fetoprotein and β-human chorionic gonadotropin were not elevated. Lumbar puncture was deferred because of imaging evidence of mass lesions and possible intracranial hypertension. Diagnostic imaging Because of the combination of chronic headaches and unilateral proptosis, the child underwent a noncontrast head CT followed by contrast-enhanced MRI of the brain and orbits. Imaging revealed multiple discrete lesions. 1. Right globe : A heterogeneous intraocular mass occupying the posterior chamber with dense calcifications on CT and T2 hypointensity on MRI. The lesion enhanced after intravenous contrast and invaded the orbital contents, including the extraocular muscles, producing grade-1 proptosis. These findings strongly suggested retinoblastoma (fig. 1). 2. Right optic nerve : Two fusiform intraconal nodules along the intraorbital segment of the right optic nerve, 10 mm and 11.7 mm in greatest axis, T2 hypointense with minimal postcontrast enhancement—radiologic features consistent with optic nerve sheath/nerve-origin neoplasms (radiologic impression favored optic nerve schwannomas or nodular tumor extension) fig. 1. 3. Suprasellar region : A multilobulated, predominantly cystic mass centered in the pituitary-hypothalamic region with small internal nodules and peripheral enhancement; the lesion displaced the optic chiasm superiorly and produced mild obstructive dilatation of the third ventricle. CT demonstrated lytic remodeling of the sphenoid body. The appearance was most consistent with a craniopharyngioma (fig. 2 and fig. 3 ). 4. Frontal base : A 33 × 25 mm extra-axial, dural-based lesion with homogeneous enhancement and a dural tail along the anterior midline—features characteristic of a meningioma (fig. 4). 5. Leptomeninges and cortex : Multiple small, enhancing leptomeningeal and cortical nodules in bilateral fronto-parietal, temporal, and mesencephalic regions, raising concern for leptomeningeal dissemination (carcinomatous meningitis), most plausibly from the intraocular tumor (fig. 5). 6. Posterior fossa : A 22 × 29 mm mixed cystic–solid mass in the right cerebellar hemisphere with an intensely enhancing mural nodule and mass effect upon the brainstem, radiologically suggestive of a pilocytic astrocytoma (fig. 6). No pulmonary or hepatic lesions were identified on the limited systemic evaluation performed at presentation. Multidisciplinary evaluation and diagnostic strategy A multidisciplinary tumor board (neurosurgery, oncology, ophthalmology, neuroradiology, and medical genetics) prioritized immediate goals: (1) secure histologic diagnosis for management planning, (2) address threats to life and function (vision, brainstem compression, and hydrocephalus), and (3) initiate staged therapy minimizing neurodevelopmental toxicity. Because of the clear imaging signature of intraocular retinoblastoma with orbital invasion and associated leptomeningeal disease, coupled with the risk of intracranial spread, the board recommended urgent ophthalmologic management with tumor extirpation for local control and pathologic confirmation, together with stereotactic biopsy of the posterior-fossa lesion for histologic diagnosis and molecular profiling. Therapeutic interventions and early hospital course Under general anesthesia, the patient underwent enucleation of the right eye with orbital tumor resection; the specimen was sent for histopathologic and molecular analysis. On postoperative day 3, stereotactic needle biopsy of the right cerebellar lesion was performed; both procedures were uncomplicated. Histopathologic examination confirmed retinoblastoma of the right globe and pilocytic astrocytoma in the cerebellar specimen. No surgical biopsy of the sellar, frontal dural, or optic nerve lesions was performed because of prohibitive risk; these lesions were therefore managed as radiologic diagnoses. Formal CSF cytology obtained during the perioperative period identified malignant cells consistent with retinoblastoma dissemination. Adjuvant management was initiated rapidly. Given confirmed intraocular retinoblastoma with leptomeningeal spread, systemic chemotherapy was started to address disseminated disease; intrathecal therapy was considered but deferred pending the oncology team’s consensus. The pilocytic astrocytoma was treated conservatively with biopsy-confirmed diagnosis and close imaging surveillance; because of the mass effect on the brainstem, a short course of corticosteroids was administered and the child was placed on a plan for surgical resection of the cerebellar lesion after initial systemic control of disseminated retinoblastoma. Endocrine evaluation for hypothalamic–pituitary dysfunction was instituted because of the suprasellar lesion; baseline pituitary hormones were within reference ranges, and no diabetes insipidus occurred postoperatively. Genetic testing and counseling Germline testing for RB1 was initiated; a broader pediatric cancer predisposition panel (including TP53, NF1, NF2, PTCH1, VHL) and trio whole-exome sequencing were requested to elucidate a potential syndromic basis for the multiple neoplasms. Unfortunately, we didn’t obtain consent from the family for genetic testing and the requested tests were not performed. Follow-up At post-operative day 6, the family elected for discharge and the patient was prescribed a few medications to be taken at home for symptoms control. Six weeks later, the child was declared dead by the family after experiencing what appeared to be risen intracranial pressure. Final diagnosis Multifocal neoplastic disease comprising: (1) right-sided intraocular retinoblastoma with leptomeningeal dissemination; (2) right cerebellar pilocytic astrocytoma (biopsy-proven); (3) presumptive craniopharyngioma of the sellar–suprasellar region (radiologic diagnosis); (4) anterior skull-base meningioma (radiologic diagnosis); and (5) bilateral optic nerve nodular lesions consistent with nerve-origin neoplasia. The overall presentation raised strong suspicion for an underlying heritable cancer-predisposition syndrome. Discussion This case illustrates an exceedingly rare presentation of multiple distinct CNS tumors in an infant. Retinoblastoma typically presents in children < 5 years (≥ 90% by age 5) [ 5 ], whereas common pediatric brain neoplasms such as pilocytic astrocytoma, craniopharyngioma, and meningioma generally occur in older children. For instance, craniopharyngiomas in children peak at ages 5–14 [ 6 ], and pediatric meningiomas account for only 1–5% of childhood brain tumors [ 7 ]. Optic pathway gliomas (often NF1-associated) usually present around school age [ 8 ]. In stark contrast, our patient – an infant with ocular proptosis, headaches and vomiting – had imaging findings suggestive of retinoblastoma (orbital mass with calcifications and T2-hypointensity), a posterior fossa tumor (cystic mass with an enhancing nodule), a sellar/suprasellar lesion (multiloculated cystic mass, calcified), and an enhancing dural-based lesion. These features pointed to coexistent retinoblastoma, pilocytic astrocytoma, craniopharyngioma and meningioma/optic nerve sheath tumor – an unprecedented constellation. Radiologic features and differential diagnosis Imaging clues help distinguish these entities. Retinoblastoma classically shows intraocular calcification on CT and a T2-hypointense retinal mass on MRI [ 9 ]. Pilocytic astrocytomas often appear as cystic cerebellar tumors with an enhancing mural nodule (66% of cases) [ 10 ]; in our patient, the posterior fossa mass had this cystic/nodular pattern, and MRI signal characteristics (T2-bright cyst, T2-hyperintense/iso T1 nodule) were typical [ 11 ]. Adamantinomatous craniopharyngiomas (common in children) tend to be multicystic sellar/suprasellar lesions with calcifications and peripheral enhancement [ 12 ]. Dural-based meningiomas generally enhance vividly and may induce hyperostosis or a “dural tail” on imaging. Optic nerve sheath meningioma, if present, classically causes fusiform optic nerve enlargement with tram-track enhancement around the nerve. The striking heterogeneity in this case – combining an orbital calcified mass, a cerebellar cystic tumor, and other intracranial lesions – argues against a single unifying process. While leptomeningeal metastases from retinoblastoma can seed the neuraxis, they typically appear as diffuse nodular CSF deposits rather than a discrete cerebellar cyst with nodule or a sellar mass. Infectious or inflammatory mimics (e.g. neurosarcoidosis or tuberculoma) were unlikely given the combination of calcifications and pattern. Metastatic neuroblastoma or leukemia (which can cause multiple cranial lesions) was ruled out by normal systemic evaluation. Thus, a diagnosis of synchronous multiple primary tumors was entertained. Genetic predisposition The concurrence of rare pediatric tumors raises strong suspicion for an underlying cancer-predisposition syndrome. Heritable retinoblastoma (germline RB1 mutation) affects 40% of cases [ 13 ] and confers high penetrance. These children have 5% risk of a “trilateral” pinealoblastoma [ 14 ] and later sarcomas or melanomas [ 15 , 16 ]. Li–Fraumeni syndrome (germline TP53 mutation) is characterized by multiple early-onset primaries (brain, sarcomas, adrenocortical tumors) and would be a key consideration [ 17 ]. Neurofibromatosis type 1 predisposes to optic pathway gliomas and other gliomas, whereas NF2 and Gorlin syndrome (PTCH1) can cause pediatric meningiomas [ 18 ]. VHL syndrome predisposes to hemangioblastomas, not seen here [ 19 ]. Given these concerns, our diagnostic approach should have included RB1 genetic testing of tumor and blood first, followed by a broad cancer‐gene panel or trio whole-exome/genome sequencing. Somatic profiling (e.g. RB1 status in the tumor) can differentiate mosaicism from nonheritable cases. Unfortunately, in this case the family declined further testing, highlighting real-world barriers (access, cost, cultural beliefs) to genetic evaluation. Diagnostic strategy Multi-axis neuroimaging was crucial. A contrast CT or MRI of the orbits confirmed intraocular calcification. Contrast MRI of brain, orbits and spine is recommended when dissemination is suspected [ 20 ]. In particular, whole-spine MRI should be obtained given the concern for leptomeningeal spread from retinoblastoma. Advanced MR techniques (diffusion, spectroscopy) may help characterize lesions, though not specific enough here to replace biopsy [ 21 ]. Tissue diagnosis relies on sampling; fortunately, enucleation of the blind, tumor-laden eye provided retinoblastoma histology and stage (international classification). For the posterior fossa tumor, a safe approach (e.g. stereotactic or endoscopic biopsy vs. partial resection) would be indicated to confirm astrocytoma pathology before extensive therapy [ 22 ]. CSF studies (cytology and tumor markers) should be obtained when LMD is suspected, though sensitivity is limited. In ambiguous cases, DNA methylation profiling of tumor tissue can refine diagnosis beyond histology. Therapeutic considerations Management must be triaged by imminence of threats. Life-threatening hydrocephalus or brainstem compression take highest priority, followed by organ-saving measures (vision preservation) [ 23 ]. In this child, enucleation of the affected eye was performed early to remove tumor burden. Systemic chemotherapy (platinum-based) was initiated for presumed metastatic retinoblastoma. High-dose chemotherapy has been attempted for leptomeningeal retinoblastoma, though outcomes remain poor. Intrathecal therapy (e.g. methotrexate) is sometimes used for CNS-retinoblastoma, but evidence in infants is limited. Craniospinal irradiation offers improved LMD control but was deferred here due to age (< 3 years) and risk of devastating neurotoxicity [ 24 ]. The pilocytic astrocytoma should be managed with maximal safe resection when feasible, followed by observation or chemotherapy if residual disease persists; radiation is usually avoided in very young children [ 25 ]. The presumed craniopharyngioma and meningioma were planned to be approached conservatively in the short term, given the patient’s overall condition and disseminated disease; optimal timing of their resection (for vision and endocrine preservation) would have required multidisciplinary judgment. Overall, therapy was staged: enucleation and CSF diversion for acute issues, systemic chemotherapy, then planned neurosurgical interventions for remaining masses. Palliative care principles must be integrated early in such complex cases. In our patient, despite intensive treatment, the prognosis was poor and the child’s condition deteriorated. The family ultimately chose comfort measures. Prognosis and ethical considerations Leptomeningeal dissemination of retinoblastoma carries very high mortality – survival is uncommon even with aggressive therapy [ 26 ]. The presence of synchronous distinct CNS tumors likely indicates a strong germline predisposition and further worsens prognosis. The patient’s young age and therapy limitations (to avoid radiation) further constrain cure. Ethically, the case raises issues of informed consent for extensive testing (genetic and invasive) and therapy. The family’s refusal of further investigations underscores the need for culturally sensitive counseling and documentation of discussions. Multidisciplinary involvement (oncology, neurosurgery, genetics, palliative care, social work) is essential to support decision-making. From a public health perspective, this case highlights gaps: many settings lack access to comprehensive genetic testing and specialist pediatric neuro-oncology teams. Rare multi-tumor pediatric cases warrant case reporting and inclusion in registries to better define incidence, natural history, and outcomes. Limitations This report is limited by its single-patient, observational nature. The lack of definitive genetic testing (due to family refusal) prevents confirmation of a germline syndrome. As an unusual presentation, generalizability is low. Literature on truly synchronous pediatric brain tumors is sparse, so recommendations rely on extrapolation from related scenarios and expert consensus rather than high-level evidence. Recommendations Multidisciplinary evaluation : Engage pediatric neuro-oncology, neurosurgery, genetics, ophthalmology and palliative care teams early. Aggressive diagnostics : Perform contrast MRI of brain, orbits and entire spine; consider CSF cytology/markers if leptomeningeal spread is suspected. Tissue diagnosis strategy : Prioritize safe biopsy sites or enucleation for definitive pathology before assuming treatment. Genetic work-up : Refer for germline testing (RB1 and broader pediatric cancer panels) early; sequence tumor tissue for somatic drivers. Integrate support : Offer genetic counseling, psychosocial and palliative support from the outset. Document all discussions and respect family preferences, while offering a clear plan. Data sharing : Report rare cases and contribute to pediatric CNS tumor registries or consortiums to advance knowledge. Conclusion This case of multifocal heterogenous CNS tumors in an infant underscores profound diagnostic and management challenges. It suggests an underlying predisposition and necessitates a low threshold for genetic evaluation. Clinicians should maintain a broad differential when confronted with multiple lesions, use imaging and pathology judiciously, and balance aggressive therapy with life-quality considerations. Future research must define the incidence and biology of synchronous pediatric brain tumors, optimize risk-adapted therapies for leptomeningeal disease, and develop evidence-based guidelines for such complex presentations. Early multidisciplinary care, coupled with thorough documentation and supportive counseling, remains paramount in managing these rare and devastating cases. Declarations Ethics approval and consent to participate: Written informed consent was obtained from the child’s mother. The written consent included authorization to participate and to have her child’s data shared for publication. The study was conducted in accordance with the ethical standards of the Helsinki Declaration. Competing interests: The authors declare no competing interests. Funding Statement: This case report received no specific grant from any institution in the public, commercial, and not-for-profit-sectors. Author Contribution Ghislain GN: conceptualisation, Methodology, WritingAmbroise SE: Conceptualisation, writingMichael NA: Investigation, VisualisationEmilienne GG: Supervision, Validation References Karami KJ, Poulik J, Rabah R, Krass J, Sood S. Simultaneous choroid plexus carcinoma and pilocytic astrocytoma in a pediatric patient. J Neurosurg Pediatr. 2010 Jan;5(1):104-12. doi: 10.3171/2009.8.PEDS09117. PMID: 20043745. 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Cite Share Download PDF Status: Published Journal Publication published 28 Feb, 2026 Read the published version in Child's Nervous System → Version 1 posted Editorial decision: Revision requested 08 Feb, 2026 Reviews received at journal 05 Feb, 2026 Reviewers agreed at journal 01 Feb, 2026 Reviewers agreed at journal 12 Jan, 2026 Reviewers invited by journal 12 Jan, 2026 Editor assigned by journal 08 Dec, 2025 Submission checks completed at journal 07 Dec, 2025 First submitted to journal 04 Dec, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Ngbwa","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABAElEQVRIiWNgGAWjYDACCcYGhgcMEkAWDxBXADEzcwNhLQlwLWdAWhgJaQHiBDALqIWxDcQgoEU+urn5Q0KNRZ45/9pjEj/n1UbztwO1/KjYhlOL4Z2DbRIJxySKLWe8S5Ps3XY8d8ZhxgbGnjO3cWuZkdjGkMAmkbjhxhmzG7zbjuU2ALUwM7bh1QJ02D+Ilpt/5xzLnU9Ii7xEYoNEYhtQy/kes9u8DTW5GwhpMQCr7wPZwpf+W+bYgdyNQC0H8flFfkb64w8fvtUBbTl72PBNTV3uvPOHDz74UYHHlgMwlkQCiDwMZh/AphRuSwOMxQ9WV4dP8SgYBaNgFIxQAACKw2U3Ze1ngwAAAABJRU5ErkJggg==","orcid":"","institution":"University of Yaoundé I","correspondingAuthor":true,"prefix":"","firstName":"Ghislain","middleName":"Guea","lastName":"Ngbwa","suffix":""},{"id":573481596,"identity":"e3064431-2dc7-4309-97f1-7b7705b717ab","order_by":1,"name":"Seme Engoumou Ambroise Merci","email":"","orcid":"","institution":"University of Yaoundé I","correspondingAuthor":false,"prefix":"","firstName":"Seme","middleName":"Engoumou Ambroise","lastName":"Merci","suffix":""},{"id":573481597,"identity":"b47efff9-82af-4ad5-ac5e-61485742e8ba","order_by":2,"name":"Nko’o Amvene Michael","email":"","orcid":"","institution":"University of Yaoundé I","correspondingAuthor":false,"prefix":"","firstName":"Nko’o","middleName":"Amvene","lastName":"Michael","suffix":""},{"id":573481598,"identity":"2567a250-177f-44c0-a669-bd80970503d4","order_by":3,"name":"Guegang Goujou Emilienne","email":"","orcid":"","institution":"University of Yaoundé I","correspondingAuthor":false,"prefix":"","firstName":"Guegang","middleName":"Goujou","lastName":"Emilienne","suffix":""}],"badges":[],"createdAt":"2025-12-04 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1","display":"","copyAsset":false,"role":"figure","size":112255,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Axial MRI section passing through the orbit and the right optic nerve; (B) Axial CT section demonstrating the right globe\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8281763/v1/d294e0e0fb5af82487e8908f.png"},{"id":100405568,"identity":"5e6a4f4e-9346-442b-a0b7-07504da42aa5","added_by":"auto","created_at":"2026-01-16 12:07:47","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":146355,"visible":true,"origin":"","legend":"\u003cp\u003eAxial T2-weighted and contrast-enhanced T1-weighted MRI sections passing through the Sella turcica\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8281763/v1/e190efeba437ba2e0de5d14f.png"},{"id":100405510,"identity":"1aeb227b-ab3d-4e38-8c7c-77781a08836a","added_by":"auto","created_at":"2026-01-16 12:06:57","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":173261,"visible":true,"origin":"","legend":"\u003cp\u003eAxial contrast-enhanced CT section through the sella turcica\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-8281763/v1/3233d261fac19c1c8fded8f7.png"},{"id":100404883,"identity":"ad176aa2-e77d-44de-af2b-808223d83946","added_by":"auto","created_at":"2026-01-16 12:04:25","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":242520,"visible":true,"origin":"","legend":"\u003cp\u003eSagittal T1-weighted and contrast-enhanced T1-weighted MRI sections demonstrating the frontal and sellar masses\u003c/p\u003e","description":"","filename":"4.png","url":"https://assets-eu.researchsquare.com/files/rs-8281763/v1/e03e94119fdb0e5c7588e217.png"},{"id":100405198,"identity":"ecc45d67-66cc-40ad-8ef2-cce00ac1d4db","added_by":"auto","created_at":"2026-01-16 12:04:56","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":168388,"visible":true,"origin":"","legend":"\u003cp\u003e(A) Axial contrast-enhanced T1-weighted MRI, (B) Axial contrast-enhanced CT section\u003c/p\u003e","description":"","filename":"5.png","url":"https://assets-eu.researchsquare.com/files/rs-8281763/v1/d57c0f35ab921ad17618c8ba.png"},{"id":100405567,"identity":"0348b262-017b-4b04-a130-7e1251bd7271","added_by":"auto","created_at":"2026-01-16 12:07:46","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":80130,"visible":true,"origin":"","legend":"\u003cp\u003eAxial contrast-enhanced CT section through the posterior cranial fossa, displayed in parenchymal window\u003c/p\u003e","description":"","filename":"6.png","url":"https://assets-eu.researchsquare.com/files/rs-8281763/v1/2059801a3d66e2bf8191bed0.png"},{"id":103765633,"identity":"40302323-f5c2-4792-a49a-3d384e2a0b8d","added_by":"auto","created_at":"2026-03-02 16:06:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1831192,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8281763/v1/2e6d6585-7dc5-4b4f-84e7-97ae76c9ff34.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Unusual Association of Multiple Cerebral and Orbital Tumors in a Two-Year-Old Child: A Case Report and Literature Review","fulltext":[{"header":"Introduction","content":"\u003cp\u003eMultiple primary intracranial neoplasms in a single patient are exceedingly uncommon, and pediatric cases involving distinct tumor types are especially rare [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Most reported instances involve only two synchronous lesions, often linked to cancer predisposition syndromes or prior therapy. For example, neurofibromatosis type 2 (NF2) is characterized by multiple schwannomas and meningiomas [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e], and Li\u0026ndash;Fraumeni syndrome or hereditary retinoblastoma predispose to other characteristic tumors. In children without such syndromes, even two separate brain tumors have been described as unusual: a 4-year-old boy with a choroid plexus papilloma and a giant-cell astrocytoma was reported in 1986, with the authors noting that \u0026ldquo;even in the absence of\u0026hellip;predisposition\u0026hellip;two separate intracranial masses may not represent metastasis of a single primary tumor\u0026rdquo; [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Similarly, Jea et al. described an 8-year-old boy with concurrent medulloblastoma and pilocytic astrocytoma \u0026ndash; the first known pediatric case of those two distinct tumors occurring together [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Karami et al. later reported a 4-year-old boy with simultaneous choroid plexus carcinoma and pilocytic astrocytoma, again emphasizing the rarity of two primary CNS tumors in a child without prior therapy or familial syndromes [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. To our knowledge, no previous report has documented more than two histologically different CNS tumors in one pediatric patient.\u003c/p\u003e \u003cp\u003eWe describe a 2-year-old girl who presented with six coexisting intracranial lesions, each corresponding to a different tumor type. Four of these \u0026ndash; retinoblastoma, optic nerve schwannomas, craniopharyngioma, and meningioma \u0026ndash; are themselves rare in early childhood and have not been reported together. The presence of multiple leptomeningeal nodules (suggesting neoplastic meningitis) further raised concern for metastatic spread, but no single primary could account for all findings. No genetic syndrome or prior radiotherapy could explain this constellation. This unprecedented case highlights gaps in current knowledge: the pathogenesis of multiple synchronous tumors in a child is unclear, and there are no established guidelines for evaluation or management. We review the literature on multiple intracranial neoplasms, emphasize the novelty of our findings, and discuss clinical implications.\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA previously healthy two-year-old girl was brought to the University Teaching Hospital of Yaoundé, Cameroun, by her parents because of progressive, diffuse headaches and right-sided ocular protrusion. Symptoms had begun insidiously approximately 11 months before presentation and had become more pronounced over the preceding three months, with frequent nocturnal irritability, intermittent vomiting, and a decline in appetite. There was no history of fever, recent head trauma, or seizures. Developmental milestones had been reported as age appropriate by the caregivers. Family history was notable for no known malignancies or consanguinity.\u003c/p\u003e\n\u003cp\u003eOn examination the child was alert and interactive but irritable. Vital signs were within age-appropriate limits (temperature 36.8°C; heart rate 110 beats per minute; respiratory rate 26 breaths per minute). Growth parameters were at the 25th percentile for age. Neurologic examination showed a grade-1 right proptosis with limited abduction of the right eye and pallor of the right pupil on fundoscopic inspection; there was no gross focal motor deficit. Visual fixation in the right eye was attenuated; the left eye appeared normal. There were no skin stigmata of neurocutaneous disease. Signs suggestive of raised intracranial pressure were subtle: the anterior fontanelle was closed, but parents reported new morning headaches and intermittent vomiting.\u003c/p\u003e\n\u003cp\u003eInitial laboratory testing, including complete blood count and basic metabolic panel, was within reference intervals for age. Serum alpha-fetoprotein and β-human chorionic gonadotropin were not elevated. Lumbar puncture was deferred because of imaging evidence of mass lesions and possible intracranial hypertension.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eDiagnostic imaging\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eBecause of the combination of chronic headaches and unilateral proptosis, the child underwent a noncontrast head CT followed by contrast-enhanced MRI of the brain and orbits. Imaging revealed multiple discrete lesions.\u003c/p\u003e\n\u003cp\u003e1. \u0026nbsp; \u0026nbsp; \u003cstrong\u003eRight globe\u003c/strong\u003e: A heterogeneous intraocular mass occupying the posterior chamber with dense calcifications on CT and T2 hypointensity on MRI. The lesion enhanced after intravenous contrast and invaded the orbital contents, including the extraocular muscles, producing grade-1 proptosis. These findings strongly suggested \u003cstrong\u003eretinoblastoma (fig. 1).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e2. \u0026nbsp; \u0026nbsp; \u003cstrong\u003eRight optic nerve\u003c/strong\u003e: Two fusiform intraconal nodules along the intraorbital segment of the right optic nerve, 10 mm and 11.7 mm in greatest axis, T2 hypointense with minimal postcontrast enhancement—radiologic features consistent with \u003cstrong\u003eoptic nerve sheath/nerve-origin neoplasms\u003c/strong\u003e (radiologic impression favored optic nerve schwannomas or nodular tumor extension) \u003cstrong\u003efig. 1.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e3. \u0026nbsp; \u0026nbsp; \u003cstrong\u003eSuprasellar region\u003c/strong\u003e: A multilobulated, predominantly cystic mass centered in the pituitary-hypothalamic region with small internal nodules and peripheral enhancement; the lesion displaced the optic chiasm superiorly and produced mild obstructive dilatation of the third ventricle. CT demonstrated lytic remodeling of the sphenoid body. The appearance was most consistent with a \u003cstrong\u003ecraniopharyngioma (fig. 2 and fig. 3\u003c/strong\u003e).\u003c/p\u003e\n\u003cp\u003e4. \u0026nbsp; \u0026nbsp; \u003cstrong\u003eFrontal base\u003c/strong\u003e: A 33 × 25 mm extra-axial, dural-based lesion with homogeneous enhancement and a dural tail along the anterior midline—features characteristic of a \u003cstrong\u003emeningioma (fig. 4).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e5. \u0026nbsp; \u0026nbsp; \u003cstrong\u003eLeptomeninges and cortex\u003c/strong\u003e: Multiple small, enhancing leptomeningeal and cortical nodules in bilateral fronto-parietal, temporal, and mesencephalic regions, raising concern for \u003cstrong\u003eleptomeningeal dissemination\u003c/strong\u003e (carcinomatous meningitis), most plausibly from the intraocular tumor \u003cstrong\u003e(fig. 5).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e6. \u0026nbsp; \u0026nbsp; \u003cstrong\u003ePosterior fossa\u003c/strong\u003e: A 22 × 29 mm mixed cystic–solid mass in the right cerebellar hemisphere with an intensely enhancing mural nodule and mass effect upon the brainstem, radiologically suggestive of a \u003cstrong\u003epilocytic astrocytoma (fig. 6).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo pulmonary or hepatic lesions were identified on the limited systemic evaluation performed at presentation.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eMultidisciplinary evaluation and diagnostic strategy\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eA multidisciplinary tumor board (neurosurgery, oncology, ophthalmology, neuroradiology, and medical genetics) prioritized immediate goals: (1) secure histologic diagnosis for management planning, (2) address threats to life and function (vision, brainstem compression, and hydrocephalus), and (3) initiate staged therapy minimizing neurodevelopmental toxicity. Because of the clear imaging signature of intraocular retinoblastoma with orbital invasion and associated leptomeningeal disease, coupled with the risk of intracranial spread, the board recommended urgent ophthalmologic management with tumor extirpation for local control and pathologic confirmation, together with stereotactic biopsy of the posterior-fossa lesion for histologic diagnosis and molecular profiling.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eTherapeutic interventions and early hospital course\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eUnder general anesthesia, the patient underwent enucleation of the right eye with orbital tumor resection; the specimen was sent for histopathologic and molecular analysis. On postoperative day 3, stereotactic needle biopsy of the right cerebellar lesion was performed; both procedures were uncomplicated. Histopathologic examination confirmed\u0026nbsp;\u003cstrong\u003eretinoblastoma\u003c/strong\u003e of the right globe and\u0026nbsp;\u003cstrong\u003epilocytic astrocytoma\u003c/strong\u003e in the cerebellar specimen. No surgical biopsy of the sellar, frontal dural, or optic nerve lesions was performed because of prohibitive risk; these lesions were therefore managed as radiologic diagnoses. Formal CSF cytology obtained during the perioperative period identified malignant cells consistent with retinoblastoma dissemination.\u003c/p\u003e\n\u003cp\u003eAdjuvant management was initiated rapidly. Given confirmed intraocular retinoblastoma with leptomeningeal spread, systemic chemotherapy was started to address disseminated disease; intrathecal therapy was considered but deferred pending the oncology team’s consensus. The pilocytic astrocytoma was treated conservatively with biopsy-confirmed diagnosis and close imaging surveillance; because of the mass effect on the brainstem, a short course of corticosteroids was administered and the child was placed on a plan for surgical resection of the cerebellar lesion after initial systemic control of disseminated retinoblastoma. Endocrine evaluation for hypothalamic–pituitary dysfunction was instituted because of the suprasellar lesion; baseline pituitary hormones were within reference ranges, and no diabetes insipidus occurred postoperatively.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eGenetic testing and counseling\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eGermline testing for\u0026nbsp;\u003cstrong\u003eRB1\u003c/strong\u003e was initiated; a broader pediatric cancer predisposition panel (including TP53, NF1, NF2, PTCH1, VHL) and trio whole-exome sequencing were requested to elucidate a potential syndromic basis for the multiple neoplasms. Unfortunately, we didn’t obtain consent from the family for genetic testing and the requested tests were not performed.\u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eFollow-up\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eAt post-operative day 6, the family elected for discharge and the patient was prescribed a few medications to be taken at home for symptoms control. Six weeks later, the child was declared dead by the family after experiencing what appeared to be risen intracranial pressure. \u0026nbsp;\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eFinal diagnosis\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eMultifocal neoplastic disease comprising: (1) right-sided intraocular retinoblastoma with leptomeningeal dissemination; (2) right cerebellar pilocytic astrocytoma (biopsy-proven); (3) presumptive craniopharyngioma of the sellar–suprasellar region (radiologic diagnosis); (4) anterior skull-base meningioma (radiologic diagnosis); and (5) bilateral optic nerve nodular lesions consistent with nerve-origin neoplasia. The overall presentation raised strong suspicion for an underlying heritable cancer-predisposition syndrome.\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis case illustrates an exceedingly rare presentation of multiple distinct CNS tumors in an infant. Retinoblastoma typically presents in children\u0026thinsp;\u0026lt;\u0026thinsp;5 years (\u0026ge;\u0026thinsp;90% by age 5) [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e], whereas common pediatric brain neoplasms such as pilocytic astrocytoma, craniopharyngioma, and meningioma generally occur in older children. For instance, craniopharyngiomas in children peak at ages 5\u0026ndash;14 [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and pediatric meningiomas account for only 1\u0026ndash;5% of childhood brain tumors [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Optic pathway gliomas (often NF1-associated) usually present around school age [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. In stark contrast, our patient \u0026ndash; an infant with ocular proptosis, headaches and vomiting \u0026ndash; had imaging findings suggestive of retinoblastoma (orbital mass with calcifications and T2-hypointensity), a posterior fossa tumor (cystic mass with an enhancing nodule), a sellar/suprasellar lesion (multiloculated cystic mass, calcified), and an enhancing dural-based lesion. These features pointed to coexistent retinoblastoma, pilocytic astrocytoma, craniopharyngioma and meningioma/optic nerve sheath tumor \u0026ndash; an unprecedented constellation.\u003c/p\u003e\n\u003ch3\u003eRadiologic features and differential diagnosis\u003c/h3\u003e\n\u003cp\u003eImaging clues help distinguish these entities. Retinoblastoma classically shows intraocular calcification on CT and a T2-hypointense retinal mass on MRI [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Pilocytic astrocytomas often appear as cystic cerebellar tumors with an enhancing mural nodule (66% of cases) [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]; in our patient, the posterior fossa mass had this cystic/nodular pattern, and MRI signal characteristics (T2-bright cyst, T2-hyperintense/iso T1 nodule) were typical [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Adamantinomatous craniopharyngiomas (common in children) tend to be multicystic sellar/suprasellar lesions with calcifications and peripheral enhancement [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. Dural-based meningiomas generally enhance vividly and may induce hyperostosis or a \u0026ldquo;dural tail\u0026rdquo; on imaging. Optic nerve sheath meningioma, if present, classically causes fusiform optic nerve enlargement with tram-track enhancement around the nerve. The striking heterogeneity in this case \u0026ndash; combining an orbital calcified mass, a cerebellar cystic tumor, and other intracranial lesions \u0026ndash; argues against a single unifying process. While leptomeningeal metastases from retinoblastoma can seed the neuraxis, they typically appear as diffuse nodular CSF deposits rather than a discrete cerebellar cyst with nodule or a sellar mass. Infectious or inflammatory mimics (e.g. neurosarcoidosis or tuberculoma) were unlikely given the combination of calcifications and pattern. Metastatic neuroblastoma or leukemia (which can cause multiple cranial lesions) was ruled out by normal systemic evaluation. Thus, a diagnosis of synchronous multiple primary tumors was entertained.\u003c/p\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eGenetic predisposition\u003c/h2\u003e \u003cp\u003eThe concurrence of rare pediatric tumors raises strong suspicion for an underlying cancer-predisposition syndrome. Heritable retinoblastoma (germline RB1 mutation) affects 40% of cases [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] and confers high penetrance. These children have 5% risk of a \u0026ldquo;trilateral\u0026rdquo; pinealoblastoma [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] and later sarcomas or melanomas [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. Li\u0026ndash;Fraumeni syndrome (germline TP53 mutation) is characterized by multiple early-onset primaries (brain, sarcomas, adrenocortical tumors) and would be a key consideration [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. Neurofibromatosis type 1 predisposes to optic pathway gliomas and other gliomas, whereas NF2 and Gorlin syndrome (PTCH1) can cause pediatric meningiomas [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. VHL syndrome predisposes to hemangioblastomas, not seen here [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Given these concerns, our diagnostic approach should have included RB1 genetic testing of tumor and blood first, followed by a broad cancer‐gene panel or trio whole-exome/genome sequencing. Somatic profiling (e.g. RB1 status in the tumor) can differentiate mosaicism from nonheritable cases. Unfortunately, in this case the family declined further testing, highlighting real-world barriers (access, cost, cultural beliefs) to genetic evaluation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eDiagnostic strategy\u003c/h2\u003e \u003cp\u003eMulti-axis neuroimaging was crucial. A contrast CT or MRI of the orbits confirmed intraocular calcification. Contrast MRI of brain, orbits and spine is recommended when dissemination is suspected [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. In particular, whole-spine MRI should be obtained given the concern for leptomeningeal spread from retinoblastoma. Advanced MR techniques (diffusion, spectroscopy) may help characterize lesions, though not specific enough here to replace biopsy [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Tissue diagnosis relies on sampling; fortunately, enucleation of the blind, tumor-laden eye provided retinoblastoma histology and stage (international classification). For the posterior fossa tumor, a safe approach (e.g. stereotactic or endoscopic biopsy vs. partial resection) would be indicated to confirm astrocytoma pathology before extensive therapy [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. CSF studies (cytology and tumor markers) should be obtained when LMD is suspected, though sensitivity is limited. In ambiguous cases, DNA methylation profiling of tumor tissue can refine diagnosis beyond histology.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003eTherapeutic considerations\u003c/h2\u003e \u003cp\u003eManagement must be triaged by imminence of threats. Life-threatening hydrocephalus or brainstem compression take highest priority, followed by organ-saving measures (vision preservation) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. In this child, enucleation of the affected eye was performed early to remove tumor burden. Systemic chemotherapy (platinum-based) was initiated for presumed metastatic retinoblastoma. High-dose chemotherapy has been attempted for leptomeningeal retinoblastoma, though outcomes remain poor. Intrathecal therapy (e.g. methotrexate) is sometimes used for CNS-retinoblastoma, but evidence in infants is limited. Craniospinal irradiation offers improved LMD control but was deferred here due to age (\u0026lt;\u0026thinsp;3 years) and risk of devastating neurotoxicity [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. The pilocytic astrocytoma should be managed with maximal safe resection when feasible, followed by observation or chemotherapy if residual disease persists; radiation is usually avoided in very young children [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. The presumed craniopharyngioma and meningioma were planned to be approached conservatively in the short term, given the patient\u0026rsquo;s overall condition and disseminated disease; optimal timing of their resection (for vision and endocrine preservation) would have required multidisciplinary judgment.\u003c/p\u003e \u003cp\u003eOverall, therapy was staged: enucleation and CSF diversion for acute issues, systemic chemotherapy, then planned neurosurgical interventions for remaining masses. Palliative care principles must be integrated early in such complex cases. In our patient, despite intensive treatment, the prognosis was poor and the child\u0026rsquo;s condition deteriorated. The family ultimately chose comfort measures.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003ePrognosis and ethical considerations\u003c/h2\u003e \u003cp\u003eLeptomeningeal dissemination of retinoblastoma carries very high mortality \u0026ndash; survival is uncommon even with aggressive therapy [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The presence of synchronous distinct CNS tumors likely indicates a strong germline predisposition and further worsens prognosis. The patient\u0026rsquo;s young age and therapy limitations (to avoid radiation) further constrain cure. Ethically, the case raises issues of informed consent for extensive testing (genetic and invasive) and therapy. The family\u0026rsquo;s refusal of further investigations underscores the need for culturally sensitive counseling and documentation of discussions. Multidisciplinary involvement (oncology, neurosurgery, genetics, palliative care, social work) is essential to support decision-making. From a public health perspective, this case highlights gaps: many settings lack access to comprehensive genetic testing and specialist pediatric neuro-oncology teams. Rare multi-tumor pediatric cases warrant case reporting and inclusion in registries to better define incidence, natural history, and outcomes.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis report is limited by its single-patient, observational nature. The lack of definitive genetic testing (due to family refusal) prevents confirmation of a germline syndrome. As an unusual presentation, generalizability is low. Literature on truly synchronous pediatric brain tumors is sparse, so recommendations rely on extrapolation from related scenarios and expert consensus rather than high-level evidence.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec16\" class=\"Section2\"\u003e \u003ch2\u003eRecommendations\u003c/h2\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eMultidisciplinary evaluation\u003c/b\u003e: Engage pediatric neuro-oncology, neurosurgery, genetics, ophthalmology and palliative care teams early.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eAggressive diagnostics\u003c/b\u003e: Perform contrast MRI of brain, orbits and entire spine; consider CSF cytology/markers if leptomeningeal spread is suspected.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eTissue diagnosis strategy\u003c/b\u003e: Prioritize safe biopsy sites or enucleation for definitive pathology before assuming treatment.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eGenetic work-up\u003c/b\u003e: Refer for germline testing (RB1 and broader pediatric cancer panels) early; sequence tumor tissue for somatic drivers.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eIntegrate support\u003c/b\u003e: Offer genetic counseling, psychosocial and palliative support from the outset. Document all discussions and respect family preferences, while offering a clear plan.\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e \u003cb\u003eData sharing\u003c/b\u003e: Report rare cases and contribute to pediatric CNS tumor registries or consortiums to advance knowledge.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eThis case of multifocal heterogenous CNS tumors in an infant underscores profound diagnostic and management challenges. It suggests an underlying predisposition and necessitates a low threshold for genetic evaluation. Clinicians should maintain a broad differential when confronted with multiple lesions, use imaging and pathology judiciously, and balance aggressive therapy with life-quality considerations. Future research must define the incidence and biology of synchronous pediatric brain tumors, optimize risk-adapted therapies for leptomeningeal disease, and develop evidence-based guidelines for such complex presentations. Early multidisciplinary care, coupled with thorough documentation and supportive counseling, remains paramount in managing these rare and devastating cases.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eWritten informed consent was obtained from the child’s mother. The written consent included authorization to participate and to have her child’s data shared for publication.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe study was conducted in accordance with the ethical standards of the Helsinki Declaration.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding Statement:\u0026nbsp;\u003c/strong\u003eThis case report received no specific grant from any institution in the public, commercial, and not-for-profit-sectors.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eGhislain GN: conceptualisation, Methodology, WritingAmbroise SE: Conceptualisation, writingMichael NA: Investigation, VisualisationEmilienne GG: Supervision, Validation\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eKarami KJ, Poulik J, Rabah R, Krass J, Sood S. 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PMID: 33090227; PMCID: PMC7582127.\u003c/li\u003e\n\u003cli\u003eKratz CP, Freycon C, Maxwell KN, Nichols KE, Schiffman JD, Evans DG, Achatz MI, Savage SA, Weitzel JN, Garber JE, Hainaut P, Malkin D. Analysis of the Li-Fraumeni Spectrum Based on an International Germline TP53 Variant Data Set: An International Agency for Research on Cancer TP53 Database Analysis. JAMA Oncol. 2021 Dec 1;7(12):1800-1805. doi: 10.1001/jamaoncol.2021.4398. PMID: 34709361; PMCID: PMC8554692.\u003c/li\u003e\n\u003cli\u003eRodriguez FJ, Stratakis CA, Evans DG. Genetic predisposition to peripheral nerve neoplasia: diagnostic criteria and pathogenesis of neurofibromatoses, Carney complex, and related syndromes. Acta Neuropathol. 2012 Mar;123(3):349-67. doi: 10.1007/s00401-011-0935-7. Epub 2011 Dec 31. PMID: 22210082; PMCID: PMC3657472.\u003c/li\u003e\n\u003cli\u003ePietrzak N, Jankowska K, Rosiak O, Konopka W. New Prospects on Neuroimaging in Von Hippel Lindau Disease-A Narrative Review. Diagnostics (Basel). 2024 Jan 31;14(3):309. doi: 10.3390/diagnostics14030309. PMID: 38337825; PMCID: PMC10855214.\u003c/li\u003e\n\u003cli\u003eGrist JT, Withey S, MacPherson L, Oates A, Powell S, Novak J, Abernethy L, Pizer B, Grundy R, Bailey S, Mitra D, Arvanitis TN, Auer DP, Avula S, Peet AC. Distinguishing between paediatric brain tumour types using multi-parametric magnetic resonance imaging and machine learning: A multi-site study. Neuroimage Clin. 2020;25:102172. doi: 10.1016/j.nicl.2020.102172. Epub 2020 Jan 23. PMID: 32032817; PMCID: PMC7005468.\u003c/li\u003e\n\u003cli\u003eRosenberg DS, Demarquay G, Jouvet A, Le Bars D, Streichenberger N, Sindou M, Kopp N, Maugui\u0026egrave;re F, Ryvlin P. [11C]-Methionine PET: dysembryoplastic neuroepithelial tumours compared with other epileptogenic brain neoplasms. J Neurol Neurosurg Psychiatry. 2005 Dec;76(12):1686-92. doi: 10.1136/jnnp.2004.051607. PMID: 16291894; PMCID: PMC1739454.\u003c/li\u003e\n\u003cli\u003eTeping F, Oertel J. Considerations on surgical strategies and associated risk profiles for endoscopic tumor biopsies within the third ventricle and periaqueductal region. Childs Nerv Syst. 2023 Dec;39(12):3407-3414. doi: 10.1007/s00381-023-06122-9. Epub 2023 Sep 8. PMID: 37682304; PMCID: PMC10684420.\u003c/li\u003e\n\u003cli\u003eFischer C, Petriccione M, Donzelli M, Pottenger E. Improving Care in Pediatric Neuro-oncology Patients: An Overview of the Unique Needs of Children With Brain Tumors. J Child Neurol. 2016 Mar;31(4):488-505. doi: 10.1177/0883073815597756. Epub 2015 Aug 5. PMID: 26245798; PMCID: PMC5032907.\u003c/li\u003e\n\u003cli\u003eTesolin D, Vergidis D, Ramchandar K. Craniospinal irradiation in the treatment of chemotherapy refractory leptomeningeal metastasis from breast cancer: A case report. Cancer Rep (Hoboken). 2022 Jul;5(7):e1556. doi: 10.1002/cnr2.1556. Epub 2021 Nov 10. PMID: 34761557; PMCID: PMC9327655.\u003c/li\u003e\n\u003cli\u003eOsman Ali AA, Bayoumi Y, Balbaid A, Orz Y, AlShakweer W, Eltawel MH, Tunio M. Radiation Induced Multiple Skin Neoplasms Following Craniospinal Irradiation for Medulloblastoma. A Case Report. Am J Case Rep. 2020 Oct 30;21:e917694. doi: 10.12659/AJCR.917694. PMID: 33125361; PMCID: PMC7610156.\u003c/li\u003e\n\u003cli\u003eHawkins MM. Long term survival and cure after childhood cancer. Arch Dis Child. 1989 Jun;64(6):798-807. doi: 10.1136/adc.64.6.798. PMID: 2774614; PMCID: PMC1792586.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"childs-nervous-system","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cnsy","sideBox":"Learn more about [Child's Nervous System](http://link.springer.com/journal/381)","snPcode":"381","submissionUrl":"https://submission.nature.com/new-submission/381/3","title":"Child's Nervous System","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"child, intracranial tumours, brain MRI, brain CT","lastPublishedDoi":"10.21203/rs.3.rs-8281763/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8281763/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eThe simultaneous occurrence of multiple primary brain tumors of differing histologies in a pediatric patient is extraordinarily rare. Established cancer-predisposition syndromes (NF1/NF2, Li\u0026ndash;Fraumeni) or prior cranial irradiation can give rise to multiple lesions, but these were not apparent in our patient.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e \u003cp\u003eA previously healthy 2-year-old girl presented with chronic headache and progressive right-sided proptosis. MRI and CT revealed six separate lesions: (1) an intraocular retinoblastoma extending into the orbit; (2) two intra-conal right optic nerve sheath schwannomas; (3) a heterogeneous cystic sellar/suprasellar mass suggestive of craniopharyngioma; (4) a homogeneously enhancing olfactory groove meningioma; (5) a mixed cystic-solid right cerebellar mass consistent with pilocytic astrocytoma; and (6) multiple leptomeningeal and cortical enhancing nodules compatible with carcinomatous meningitis. The family was opposed to further genetic tests and elected serial imaging surveillance for all lesions. The child had no personal or family history of a cancer syndrome, no prior radiation exposure, and no systemic features of an inherited neoplasia predisposition.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe co-occurrence of six histologically distinct CNS tumors in one child, none of which fit a known genetic syndrome, appears unprecedented. This case underscores that multiple spatially and pathologically discrete brain tumors can arise in a pediatric patient without identifiable risk factors. It highlights the importance of thorough diagnostic evaluation (to distinguish multicentric primaries from metastases) and consideration of underlying germline or mosaic mutations. Further study is needed to understand the etiology of such multiple tumor formations and to guide surveillance and management in similarly complex cases.\u003c/p\u003e","manuscriptTitle":"Unusual Association of Multiple Cerebral and Orbital Tumors in a Two-Year-Old Child: A Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-16 10:37:06","doi":"10.21203/rs.3.rs-8281763/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-02-09T04:07:48+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-02-05T16:18:23+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"313150794300474371215282065752947444677","date":"2026-02-02T03:43:52+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"195567902930016260760049664053987451512","date":"2026-01-12T19:06:28+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-12T18:18:11+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-12-08T05:00:09+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-12-08T04:59:51+00:00","index":"","fulltext":""},{"type":"submitted","content":"Child's Nervous System","date":"2025-12-04T17:43:22+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"childs-nervous-system","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"cnsy","sideBox":"Learn more about [Child's Nervous System](http://link.springer.com/journal/381)","snPcode":"381","submissionUrl":"https://submission.nature.com/new-submission/381/3","title":"Child's Nervous System","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"39104176-eeb5-4bd1-9faf-2a718eea0349","owner":[],"postedDate":"January 16th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-03-02T16:03:06+00:00","versionOfRecord":{"articleIdentity":"rs-8281763","link":"https://doi.org/10.1007/s00381-026-07190-3","journal":{"identity":"childs-nervous-system","isVorOnly":false,"title":"Child's Nervous System"},"publishedOn":"2026-02-28 15:59:31","publishedOnDateReadable":"February 28th, 2026"},"versionCreatedAt":"2026-01-16 10:37:06","video":"","vorDoi":"10.1007/s00381-026-07190-3","vorDoiUrl":"https://doi.org/10.1007/s00381-026-07190-3","workflowStages":[]},"version":"v1","identity":"rs-8281763","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8281763","identity":"rs-8281763","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}