A 5-year-old boy initially presented with headache, right eye pain, and vomiting, to a rural district hospital in the State of Sabah, East Malaysia on Borneo island. The boy also experienced difficulty in walking, blurring of vision, and fluctuating consciousness 1 month before admission. There was a significant (but unquantified) loss of weight and anorexia. He completed his bacille Calmette-Guerin (BCG) vaccination but missed all scheduled shots after his first birthday because of poor family support. On examination, a Glasgow Coma Scale (GCS) of 9 was documented (E2V2M5) with left lateral strabismus. The pupils were unequal (4 mm/3 mm) and sluggish. Power in all four limbs was 4/5 (Medical Research Council scale) with normal reflexes. Babinski was downgoing, and Kernig's sign was not elicited.
The boy was transferred to our center for further evaluation and treatment. Non-contrast CT brain showed acute hydrocephalus with cerebral edema. Subsequently, an external ventricular drain was inserted. Intra-operatively, the opening pressure was high, and outflowing cerebrospinal fluid (CSF) was clear and colorless.
Magnetic resonance imaging of the brain revealed diffuse enhancing nodular leptomeningeal thickening, especially at the basal cisterns (Figure 1). No intra-axial lesion was present. Small non-enhancing cystic lesions were seen along the leptomeningeal surface (Figure 2B1), and no restricted diffusion was depicted. A diagnosis of tuberculous meningitis was considered, and an extensive TB workup was undertaken. The positive results from that battery of tests were a high erythrocyte sedimentation rate (ESR) of 90 mm/h and elevated CSF protein with normal CSF glucose levels. Otherwise, the Mantoux test was negative, and the blood, CSF, and CSF TB cultures showed no organism. The CSF for acid-fast bacilli as well as CSF GeneXpert were also negative. CSF latex agglutination was negative for streptococcus Group B, haemophilus influenzae, streptococcus pneumoniae, neisseria meningitidis, and escherichia coli. Both gastric lavage for acid fast bacilli stain and gastric lavage for GeneXpert were negative.
Smear-negative TB was considered after reviewing the biochemical and imaging findings. Using the Composite Reference Standard (CRS) criteria, this child was classified as probable TB. A standard anti-TB regimen was started consisting of isoniazid, rifampicin, pyrazinamide, and ethionamide. Intravenous dexamethasone was prescribed during the first 2 weeks of admission and was subsequently changed to oral administration.
The boy's condition improved considerably after 14 days, and he was well enough to undergo a comprehensive ophthalmology examination. He had a visual acuity of 1/60 in the right eye, and there was no light perception in the left eye. A positive right afferent pupillary defect was detected. Ophthalmoscopy showed normal macula bilaterally.
Both his parents were screened and found to be negative for TB. He was discharged well after a 4-week hospital stay.
One month later, he presented again with vomiting, unsteady gait, and anorexia. The follow-up MR brain study revealed exuberant nodular leptomeningeal enhancement that was more extensive than the initial study (Figure 1). Also, the previously seen cystic lesions have increased in size and number (Figures 2B2,C). MR spectroscopy (single voxel placed at the thickened tentorium cerebelli) showed a markedly elevated choline:creatine ratio of 4.34 and absence of a singlet peak at 3.8 ppm (Figure 3). A biopsy sample was obtained and sent for histopathological examination (HPE). Transcranial approach at the right Keen's point was used to obtain the biopsy sample. The patient incidentally needed a revision of his external ventricular shunt at that time, so dural tissue was obtained via the Burr hole just prior to the shunt revision.
Histopathological examination (HPE) revealed a moderately cellular neoplastic proliferation with background desmoplastic and myxoid changes seen from the hematoxylin and eosin (H&E) stain slides (Figure 4A). The cells were fairly monomorphic with mild nuclear pleomorphism displaying enlarged round to oval nuclei with fine chromatin and inconspicuous nucleoli (Figure 4B). Occasional mitosis was seen (Figure 4C). The Ki-67 proliferation rate was high, accounting for about 80% (Figure 4D). Immunohistochemical (IHC) studies showed that the tumor cells were positive for S100 and synaptophysin (Figures 4E,F). Given these findings, the boy was diagnosed with DL-GNT.
A family conference was held to counsel the parents on possible treatment options. The parents decided to opt for palliative treatment. The patient succumbed to the illness 3 months later, 22 weeks in total, after diagnosis.