ABSTRACT
Neuroblastomas are the most common extracranial solid tumor in the pediatric age group (~8%–10% of childhood neoplasms). Most cases of intracranial neuroblastomas occur due to metastasis from some primary extracranial sites and are known as secondary neuroblastomas. However, the occurrence of primary central nervous system neuroblastomas (PCN-NB) is very rare, and only a few cases and case series have been reported in the literature. PCN-NB is mainly an intra-axial pathology, and extra-axial involvement is mainly due to metastasis from some extracranial primary site with involvement of the skull bone. Herein we report a case of a 23-year-old female having a large extra-axial space-occupying lesion in the right frontal region that was mimicking a meningioma, and surprisingly the histopathology was suggestive of a supratentorial neuroblastoma. A right frontal craniotomy was made, and Simpson’s grade 1 excision of the tumor was done. The excised tissue was sent for histopathological examination. PCN-NB located extra-axially are extremely rare to occur. Due to inconsistent radiological imaging, it becomes very difficult to diagnose these tumors preoperatively, and these should be kept in mind as one of the differential diagnoses of extra-axial intracranial space-occupying lesions. Histopathological examination is crucial in diagnosing the intracranial neuroblastomas.
KEY WORDS: Case report, extra-axial, neuroblastoma, primary, supratentorial
Introduction
Neuroblastomas are the most common extracranial solid tumor in the pediatric age group (~8%–10% of childhood neoplasms). These are basically embryonal tumors that originate from the migrating neuroectodermal cells and are derived from the neural crest.[1] Neuroblastomas are characteristically very aggressive with an early age of onset and tend to metastasize to other organs.[2] Most cases of intracranial neuroblastomas occur due to metastasis from some primary extracranial sites and are known as secondary neuroblastomas. However, the occurrence of primary central nervous system neuroblastomas (PCN-NB) is very rare, and only a few cases and case series have been reported in the literature.[3,4,5] PCN-NB occurs most commonly in childhood (children <5 years) and adults are involved very rarely. PCN-NB is mainly an intra-axial pathology, and extra-axial involvement is mainly due to metastasis from some extracranial primary site with involvement of the skull bone.[5] PCN-NB occurring extra-axially is even rarer, and only two or three cases have been reported in the literature.[6]
Herein we report a case of a 23-year-old female in her early 20s, having a large extra-axial space-occupying lesion in the right frontal region that mimicked a meningioma, and surprisingly the histopathology reported it to be a “supratentorial neuroblastoma.”
Case Report
A 23-year-old female presented with chief complaints of headache associated with nausea and vomiting for the last 15 days and decreased vision in both eyes for the past 1 week. On physical examination, she was fully conscious and oriented to time, place, and person, with a Glasgow Coma Scale (GCS) score of 15. She had no significant past medical or surgical history. On neurological examination, she had a visual acuity of 6/60 in both eyes, with grade 2 papilledema bilaterally on fundoscopy. The rest of the cranial nerves were within normal limits.
Computed tomography (CT) of the head revealed a well-defined extra-axial, iso-to-hyperdense lesion with calcific specs within, involving the right frontal region with evidence of significant mass effect in the form of compression of ipsilateral lateral ventricle with midline shift toward the contralateral side [Figure 1a]. Contrast magnetic resonance imaging (MRI) of the brain showed a large well-defined extra-axial altered signal intensity mass lesion in the right frontal convexity with broad-based at dura mater, measuring 6.4 cm × 5.2 cm × 5.3 cm in size and associated with significant mass effect in the form of midline shift. The lesion was iso-intense to grey matter on T1-weighted imaging and iso-intense to hyper-intense on T2 and T2 FLAIR imaging. The lesion showed homogenous post-contrast enhancement [Figure 1b–e].
Figure 1.
CT AND MRI images of the patient, (a) Preoperative plain CT head showing a well-defined extra-axial iso-to-hyperdense lesion with calcific specs within (marked with white arrow); (b) T1-weighted axial MRI image showing a well-defined extra-axial iso-intense lesion in right frontal region (marked with white arrow); (c) Contrast MRI axial image showing a well-defined homogenously enhancing lesion in right frontal region (marked with white arrow); (d) T2-weighted coronal image showing a iso-to-hyperintense lesion (marked with white arrow); (e) T2-weighted sagittal image showing the iso-to-hyperintense lesion (marked with white arrow); (f) Postoperative plain CT head showing the complete excision of the tumor
The radiology of the patient was more in favor of a meningioma; hence, we planned for the surgery accordingly. A right frontal craniotomy was made, and Simpson’s grade 1 excision of the tumor was done. Intraoperatively, the tumor had varied consistency; the part attached to the sagittal sinus was firm and moderately vascular, whereas the deeper part was soft in consistency and highly vascular. The tumor was closely abutting the superior sagittal sinus, but there was no invasion of the sinus. The excised tissue was sent for histopathological examination. The postoperative CT scan showed complete excision of the tumor, and the patient was neurologically intact with GCS 15/15 [Figure 1f]. On histopathological examination, the tumor was disposed of in sheets with intervening blood vessels. The tumor cells were small to medium-sized, having salt and pepper chromatin, elongated in shape with a scanty amount of cytoplasm. On immunohistochemistry, tumor cells showed positive expression for synaptophysin and negative expression for chromogranin and glial fibrillary acidic protein (GFAP) [Figure 2a–f]. The final histopathology reported the tumor tissue as “supratentorial neuroblastoma,” which was very unexpected.
Figure 2.
(a) H and E section shows tumor disposed in sheets with intervening blood vessels (b) tumor cells are small to medium sized, salt and pepper chromatin, elongated shape, scant amount of cytoplasm; (c) Tumor cells show positive expression for synaptophysin and negative expression for (d) chromogranin, (e and f) GFAP and Ki-67 proliferation index of 30%
The patient was discharged on postoperative day 10 with a GCS of 15/15 and no added neurological deficit. As the histopathology of the excised tumor reported it to be “supratentorial neuroblastoma,” we advised PET-CT scan to look for any extracranial “primary” site of the tumor. However, the PET-CT scan showed no other sites of involvement; hence, we made a diagnosis of PCN-NB. We referred this patient for postoperative chemo-radiation. The patient received radiotherapy and is symptom-free with no signs of recurrence on radiology at 2 months follow-up.
Discussion
PCN-NB is an extremely rare and aggressive tumor originating from neural crest cells. Neuroblastomas are primary tumors of the peripheral nervous system having unique features and biological properties such as spontaneous regression, aggressive progression, and maturation.[2] Intracranial neuroblastomas are very rare and are mostly reported as secondary metastatic lesions from some extracranial primary sites. PCN-NB is even rarer, and very few cases and case series have been reported in the literature.[3,4,5,7] These are mostly reported in the pediatric age group, and involvement in adults is very rare. Horten and Rubinstein reported that the incidence of primary CNS-NB is approximately one case every decade.[4,5] Lu et al.[8] conducted a surveillance, epidemiology, and end results program from 1973 to 2013 to understand the epidemiology and natural history of PCN-NB along with the accompanying histopathological changes. They reported that the annual prevalence of PCN-NB decreased from 0.28 to 0.12 cases per 1,00,000 from 1973 to 2013, and the mean age of patients of PCN-NB is around 5 years. In 2016, Era’s Medical College in Lucknow, India, reported a case of a 6-year-old female with large extra-axial lesion in the right frontal region, which was confirmed by histopathology as PCN-NB.[9]
PCN-NB was previously categorized under the group of primitive neuroectodermal tumors (PNET), which included entities such as medulloblastomas, ependymoblastoma, pineoblastoma, and cerebral neuroblastoma. However, Horten and Rubinstein in 1976 suggested that primary cerebral neuroblastoma is a separate entity and is characterized by (a) a cellular tumor of neuronal origin without glial differentiation; (b) occasional differentiation into mature ganglion cells; (c) the presence of a fine fibrillary matrix of axonal material; and (d) the frequent exhibition of well-formed Homer-Wright rosettes.[4,5] Due to the accumulation of several pieces of evidence over the years concluding that neuroblastomas are a separate entity from PNET, in the 2016 WHO classification of tumors, the term “PNET” was discontinued, and the cerebral neuroblastomas were classified separately under “neuronal and paraneuronal tumors.”[10] In the recent 2021 WHO classification of CNS tumors, the PCN-NB is further classified under the category of “other CNS embryonal tumors.”[11] The PCN-NB in the 2021 WHO classification of tumors is labelled as “CNS neuroblastoma with FOXR2 activation (CNS-NB FOXR2)” due to the presence of characteristic histology and FOXR2 gene activation.[12] Histologically, the two common subtypes of PCN-NB are neuroblastoma and ganglioneuroblastoma.
The radiological imaging features of PCN-NB are non-specific, and it is very difficult to differentiate it from other CNS tumors. PCN-NB are generally large intracranial, multilobulated tumors with little or no peri-focal edema. There may be the presence of calcifications, cystic degeneration, and areas of hemorrhage and necrosis. They occur most commonly in supratentorial space and predominantly involve the frontal and parietal lobes. These may be purely solid or solid-cystic in appearance. Purely solid tumors appear isointense to hypointense on both T1- and T2-weighted MRI imaging. They appear heterogeneous on contrast-enhanced MRI imaging due to the presence of areas of hemorrhage and necrosis. As reported in the literature, PCN-NB are usually intra-axial masses, whereas secondary intracranial neuroblastomas are mainly extra-axial in location with involvement of the skull bone. Meningiomas are typical extra-axial tumors with or without broad-based dural attachments and appear isointense to hypointense on both T1- and T2-weighted MRI sequences with homogenous post-contrast enhancement.[11,12,13]
In our case, the tumor was extra-axially located and was iso-intense in both T1 and T2 sequences, with homogenous post-contrast enhancement. We were not considering neuroblastoma as a differential diagnosis in our case based on the imaging features; rather our working diagnosis was a meningioma based on the radiology, but surprisingly, the histopathology revealed it to be a neuroblastoma.
Due to the presence of inconsistent imaging features, the diagnosis of PCN-NB is mostly done by histopathological examination. There are two important criteria to label a CNS tumor as PCN-NB: first, the histopathological findings, and second, the exclusion of any other systemic neuroblastomas.[8] Histologically, the neuroblastomas are highly cellular, showing round to oval cells with hyperchromatic nuclei. Homer-Wright rosette formation can also be seen in 25%–30% of cases, along with areas of necrosis or hemorrhage. On immunohistochemistry, they show positivity for vimentin, neuron-specific enolase, and synaptophysin, and negativity for GFAP, cytokeratin, and chromogranin.[6,13] In our case also, the histopathology showed similar findings and reported the tumor as supratentorial neuroblastoma. After getting the diagnosis of neuroblastoma on histopathology, we did a PET-CT scan of the patient to look for any other common sites of involvement. However, the PET-CT scan was reported to be normal; hence, a diagnosis of PCN-NB was made.
Surgical excision of the tumor as much as possible is considered the first-line treatment in the management of PCN-NB.[13] There are no standard adjuvant treatment guidelines for PCN-NB. However, chemotherapy with or without radiotherapy can be advised to the patient on the basis of their age of presentation. Bennett and Rubinstein concluded that prophylactic whole brain and spinal irradiation is justified due to the high incidence of local recurrence and cerebrospinal metastasis.[5] Lu et al.[8] also advocated supportive radiotherapy as adjuvant treatment in PCN-NB and reported favorable outcomes. Despite the favorable outcomes, radiotherapy has a very limited role in cases of neuroblastomas as these tumors tend to have higher incidences in pediatric patients. Due to the rarity of the PCN-NB cases and the paucity of treatment options, no standard management protocol exists, and many aspects of this rare pathology are yet to be discovered.
Conclusion
PCN-NB located extra-axially are extremely rare to occur. Due to the inconsistent radiological imaging, it becomes very difficult to diagnose these tumors preoperatively, and these should be kept in mind as one of the differential diagnoses of extra-axial intracranial space-occupying lesions. The rarity of primary CNS neuroblastoma and its unusual presentation necessitate a high index of suspicion and thorough pathological evaluation.
Key message
Primary central nervous system neuroblastoma should be considered a different entity and should kept in mind as a differential diagnosis while dealing with an intracranial lesion.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References
- 1.Schmalisch K, Psaras T, Beschorner R, Honegger J. Sellar neuroblastoma mimicking a pituitary tumour: Case report and review of the literature. Clin Neurol Neurosurg. 2009;111:774–8. doi: 10.1016/j.clineuro.2009.06.011. [DOI] [PubMed] [Google Scholar]
- 2.Maris JM. Recent advances in neuroblastoma. N Engl J Med. 2010;362:2202–11. doi: 10.1056/NEJMra0804577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Davis PC, Wichman RD, Takei Y, Hoffman JC., Jr Primary cerebral neuroblastoma: CT and MR findings in 12 cases. AJNR. 1990;11:115–20. [PMC free article] [PubMed] [Google Scholar]
- 4.Horten BC, Rubinstein LJ. Primary cerebral neuroblastoma. A clinicopathological study of 35 cases. Brain. 1976;99:735–56. doi: 10.1093/brain/99.4.735. [DOI] [PubMed] [Google Scholar]
- 5.Bennett JP, Jr, Rubinstein LJ. The biological behavior of primary cerebral neuroblastoma: A reappraisal of the clinical course in a series of 70 cases. Ann Neurol. 1984;16:21–7. doi: 10.1002/ana.410160106. [DOI] [PubMed] [Google Scholar]
- 6.Huynh BQ, Hung ND, Khuong NH, Anh NN, Duc NM. A rare case of a primary central nervous system neuroblastoma mimicking a trigeminal schwannoma in an adult. Radiol Case Rep. 2023;18:2697–703. doi: 10.1016/j.radcr.2023.05.028. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Becker LE, Hinton D. Primitive neuroectodermal tumors of the central nervous system. Hum Pathol. 1983;14:538–50. doi: 10.1016/s0046-8177(83)80006-9. [DOI] [PubMed] [Google Scholar]
- 8.Lu X, Zhang X, Deng X, Yang Z, Shen X, Sheng H, et al. Incidence, treatment, and survival in primary central nervous system neuroblastoma. World Neurosurg. 2020;140:e61–72. doi: 10.1016/j.wneu.2020.04.145. [DOI] [PubMed] [Google Scholar]
- 9.Gupta P, Mehrotra S, Kumar A, Srivastara AN. Primary cerebral neuroblastoma: An unusual intracranial PNET with neuronal differentiation. IJAR. 2016;4:230–8. [Google Scholar]
- 10.Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol. 2016;131:803–20. doi: 10.1007/s00401-016-1545-1. [DOI] [PubMed] [Google Scholar]
- 11.Osborn AG, Louis DN, Poussaint TY, Linscott LL, Salzman KL. The 2021 World Health Organization classification of tumors of the central nervous system: What neuroradiologists need to know. AJNR Am J Neuroradiol. 2022;43:928–37. doi: 10.3174/ajnr.A7462. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Mishra R, Agrawal A, Mishra R, Agrawal A. London, England: IntechOpen; 2021. Primary Central Nervous System Neuroblastoma: An Enigmatic Entity. [Google Scholar]
- 13.Bianchi F, Tamburrini G, Gessi M, Frassanito P, Massimi L, Caldarelli M. Central nervous system (CNS) neuroblastoma. A case-based update. Childs Nervous Syst. 2018;34:817–23. doi: 10.1007/s00381-018-3764-3. [DOI] [PubMed] [Google Scholar]
