Giant cerebral tuberculoma mimicking a high-grade tumour in a child

Abstract

We present an 11-year-old girl who manifested with unprovoked right-sided focal motor seizures. CT revealed a large lobulated hypodense mass in the left temporoparietal lobe, with perilesional oedema and postcontrast peripheral enhancement. Diagnostic uncertainty resulted in further neuroimaging, which included MRI with modalities including diffusion-weighted imaging, perfusion imaging, as well as spectroscopy. We discuss the radiological features of the lesion, which steered us in the direction of an infective cause. Definitive diagnosis was achieved by brain needle biopsy, which demonstrated necrotising granulomatous inflammation indicative of tuberculous infection on histology. In addition, GeneXpert yielded a positive result. We believe this unique case highlights the diagnostic dilemma clinicians face in differentiating ring-enhancing lesions on neuroimaging in tuberculosis-endemic regions. It also highlights the potential benefit of a brain needle biopsy (histology and GeneXpert) in cases of uncertainty.

Background

Urgent neuroimaging is indicated in any child presenting with focal seizures residing in a tuberculosis (TB)-endemic area. However, the differential diagnosis of a ring-enhancing cerebral lesions on CT is broad, and no single radiological feature is pathognomonic. Precise diagnosis is critical as it has important therapeutic and prognostic implications.

Case presentation

An 11-year-old girl presented to the ambulatory paediatrics department with a right-sided focal motor seizure involving the face and arm. Her family reported a 3-month history of intermittent headaches (without vomiting), decline in scholastic performance and loss of weight. There was no known contact with a household adult TB source case. On admission, her vitals were normal and the neurological examination proved unremarkable besides for a mild tremor of the right hand. Formal funduscopy (although indicated) was not performed.

Investigations

Haematological results indicated no abnormalities; serum leucocyte count and C reactive protein level were within normal limits. Chest radiography was normal. GeneXpert and TB cultures proved negative on gastric washing samples. Cerebral CT revealed a large lobulated hypodense mass (51 mm×46 mm×39 mm) in the left temporoparietal lobe, with an irregular border, perilesional oedema and postcontrast peripheral enhancement (figure 1A–C). No abnormal leptomeningeal or basal meningeal enhancement was observed. Tortuosity and enlargement of the optic nerves suggested raised intracranial pressure. MRI, magnetic resonance spectroscopy (MRS) and perfusion imaging were requested to further delineate the nature of the lesion. Subsequent axial MRI T2 Fluid Attenuated Inversion Recovery (FLAIR) (figure 2A) and T1-weighted postgadolinium images (figure 2B) showed a central inhomogeneous T2 and T1 hypointense left temporoparietal lesion with ring enhancement and marked perilesional oedema. Only peripheral restriction of diffusion was noted (figure 2C, D). MRS demonstrated diminished metabolite peaks and proved unhelpful. Perfusion MRI (figure 2E) showed low relative cerebral blood volume within the core of the lesion with the enhancing wall demonstrating a perfusion ratio of 2. The MRI T2 signal characteristics and perfusion parameters were deemed inconsistent with a high-grade glioma, and preferentially an infective cause (solitarily tuberculoma) was considered. Due to diagnostic uncertainty and the peripheral location of the lesion, a brain needle biopsy was performed; histological analysis revealed necrotising granulomatous inflammation indicative of tuberculous infection with no evidence of malignancy, fungal infection or parasitic organisms. GeneXpert of the biopsy sample proved positive for Mycobacterium tuberculosis with rifampicin sensitivity.

Figure 1.

(A–C) Axial, sagittal and coronal brain CT images, respectively, showing a large lobulated hypodense mass in the left temporoparietal lobe, with an irregular border, perilesional oedema and postcontrast peripheral enhancement.

Figure 2.

(A–E) Axial MRI T2 Fluid Attenuated Inversion Recovery (FLAIR) (A) and T1 postgadolinium (B) demonstrating a hypointense lesion with marked contrast enhancement and perilesional oedema. Diffusion-weighted imaging (C) and apparent diffusion coefficient (D) demonstrated peripheral restriction of diffusion. MRI perfusion imaging (E) demonstrated high relative cerebral blood volume within the enhancing wall of the lesion.

Treatment, outcome and follow-up

The patient was started on antituberculous medication, which included rifampicin (20 mg/kg/day), isoniazid (20 mg/kg/day), ethionamide (20 mg/kg/day) and pyrazinamide (40 mg/kg/day), as well as prednisone (2 mg/kg/day). She has had no further seizures since commencement of therapy with complete resolution of the tremor. Repeat MRI is planned after 6 months of therapy.

Discussion

The differential diagnosis of peripheral or ring-enhancing cerebral lesions on CT includes infectious lesions (cerebral abscess, tuberculoma, neurocysticercosis, toxoplasmosis and cryptococcoma), malignant tumours (lymphoma, glioblastoma or metastasis), demyelination, subacute infarct/haemorrhage/contusion and vascular malformation. Precise diagnosis is extremely important as it has therapeutic and prognostic implications. Radiological features (enhancing wall characteristics, degree of surrounding oedema, number and size of the lesions and vascularity), as well as clinical presentation and patient demographics (immune status), need to be considered to help narrow the differential diagnosis.

No single radiological feature is deemed pathognomonic, although a cystic lesion that markedly restricts centrally (the fluid component) on MRI diffusion-weighted imaging should be considered an abscess until proven otherwise. In this particular case, the absence of central diffusion restriction argued against a pyogenic brain abscess or cryptococcoma. Cerebral neurocysticercosis is characterised by multiple small (less than 2 cm) lesions with thin walls and calcific foci. This was not evident in our patient. Neoplastic lesions are more likely to exhibit homogenous hyperperfusion in both the core and periphery. The decreased perfusion evident on the MRI perfusion scan was therefore not supportive of malignant tumours, metastasis and vascular malformations. An MRS signature characterised by a dominant lipid peak and near absence of other metabolites has been reported to have high sensitivity and specificity in differentiating tuberculomas from other non-neoplastic and neoplastic lesions.¹ Although the presence of lipids is non-specific and can be present in high-grade gliomas and lymphomas, the absence thereof makes the diagnosis of tuberculoma less likely. No lipid peak was detected in our patient. The complete ring enhancement of the lesion argued against the possibility of tumefactive demyelination. The latter is characterised by incomplete ring enhancement towards the cortex. In immunocompromised children, MRI is an important diagnostic modality to differentiate toxoplasmosis from tuberculoma and primary central nervous system lymphoma. Two imaging patterns described in cerebral toxoplasmosis include the MRI T2-weighted ‘concentric target sign’ (concentric alternating zones of hypointensity and hyperintensity) and the postcontrast CT/MRI ‘eccentric target sign’ (eccentrically located enhancing mural nodule). Neither were evident in this patient.

Neuroimaging findings that proved valuable in our case included the MRI T2 hypointensity (T2 black) in the centre of the lesion, which has been shown to represent necrosis of inflammatory granulation tissue, that is, gummatous necrosis.² Central T2 brightness in high-grade gliomas is the usual expectation. An additional supportive radiological feature was the higher perfusion value in the wall of the tuberculoma compared with the central core.³ This can be attributed to angiogenesis secondary to increased expression of vascular endothelial growth factor by inflammatory cells.⁴ The key to definitive diagnosis in the present case was the brain needle biopsy findings. Limited data suggest that the use of GeneXpert on brain tissue samples has high sensitivity and specificity in detecting M. tuberculosis.⁵

Learning points.

• The differential diagnosis of ring-enhancing cerebral lesions is broad, and no single radiological feature is pathognomonic.

• Tuberculomas usually exhibit centrally located MRI T2 hypointensity (T2 black).

• Perfusion MRI is a useful tool for differentiating cerebral tuberculomas from neoplasms.

• GeneXpert on brain biopsy samples may prove informative in cases of diagnostic uncertainty.

Ethics statements

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