A 71-year-old woman was admitted to our hospital for recurrent episodes of high fever (39.6 ℃) associated with headache, vomiting and a worsening of her aphasia, over the last two weeks. Her past medical history was significant for a left temporal glioblastoma, diagnosed 14 months before as a stage IV, Ki67 60%, p53 positive, ATRX positive, MGMT negative tumor. The patient underwent subtotal surgical ablation (> 90%), followed by adjuvant radiotherapy (RT) (58 Gy, 29 fractions) and chemotherapy with temozolomide (TMZ). Nine months later, a cerebral MRI showed local tumoral progression and TMZ was switched with irinotecan/bevacizumab and a second surgical intervention was planned, with no immediate complications. After discharge, the patient complained of the aformentioned symptoms and she was hospitalised in our department. The chronic treatment included levetiracetam 500 mg twice daily, fluoxetine 10 mg daily and eltrombopag 50 mg daily. On admission, the patients was alert, partially oriented, normal vital signs; the post craniotomy temporal scar was clean, with mild edema of surrounding tissues; no signs of meningeal irritation and no neurological deficits were recorded; the rest of the clinical examination was unremarkable.
The laboratory investigations revealed mild lymphopenia (1100/mm3 with a CD4 + count of 424/mm3), a mild anemia (hemoglobin of 11 g/dL) and a platelet count of 117,000/mm3. The inflammatory markers and chemistry findings were also within the normal ranges. SARS-CoV-2 and influenza tests were negative.
The lumbar puncture (LP) at admission showed a hypertensive xanthochromic CSF, with 283 cells/mm3, 85% mononuclears, low CSF glucose of 22 mg/dL (128 serum glucose) and hyperproteinorachia (193 mg/dL).
Extensive CSF/CNS and peripheral etiological workups were done. A Ziehl-Neelsen smear for acid-fast bacilli (AFB) and PCR (GeneXpert MTB/RIF) were negative for Mycobacterium tuberculosis (MTB). Gram stain, India ink and the repeated CSF cultures were all negative for bacterial and fungal growth. A multiplex CSF PCR (BioFire FilmArray Meningitis/Encephalitis Panel, Biomerieux) was performed especially for Listeria monocytogenes and Cryptococcus neoformans, with negative results also for all the other pathogens (bacteria, viruses and fungi). PCR for Aspergillus spp., JC virus and EBV from CSF were also negative.
The urinalysis and urine culture were negative. The repeated blood cultures were all negative for bacterial and fungal growth. Several viral studies, including antibody tests for HIV, hepatitis B and C, CMV (serology and quantitative blood DNA), EBV and Coxiella burnetii, were all negative. Echocardiography was not suggestive of infective endocarditis. Chest, abdomen and pelvic CT scans could not detect any inflammatory focus. Brain CT scan found a 35/18 mm heterogenous lesion in the left parietal lobe, with important surrounding edema and mass effect on the left lateral ventricle, suggestive of GBM recurrence, without signs of mastoiditis or sinusitis.
We started a therapeutic trial of standard antituberculous treatment considering the following: fever and no other identified cause, subacute onset of meningitis with no other etiology, xanthocromic lymphocytic CSF with hypoglycorrachia, immunosuppression, high local endemicity for MTB and the low sensitivity of MTB PCR and AFB from CSF. Corticosteroid therapy was not initiated in order to avoid the influence on CSF parameters. After two weeks of treatment, a follow-up LP was performed and we found no significant changes, with persistent xanthochromia, hypoglicorrahia (CSF/serum glucose ratio of 0.3) and hyperproteinorachia (246 mg/dL). The repetead AFB smear and GeneXpert MTB/RIF were negative. The CT scan found an increase in the edema surrounding the left parietal lesion and the cytopathological examination of the CSF revealed frequent large, polygonal cells with voluminous, inhomogeneous nuclei with infrequent inclusions, consistent with malignancy, with a cytopathological category C4. We established the diagnosis of GBM associated carcinomatous meningitis and referred the patient to oncology for further treatment.