A 60-year-old previously healthy female presented to her local health care providers with cognitive difficulties, memory loss, and social withdrawal, associated with unintentional 40-pound weight loss, and new night sweats. Brain MRI demonstrated multifocal mass lesions (Fig. 1). Stereotactic needle biopsy showed nonspecific perivascular lymphohistiocytic infiltrates. PCNSL could not be confirmed, and no microbiologic studies were performed on the brain tissue. Of note, she was a long-term Oklahoma resident with unremarkable social and personal history.
HIV, syphilis, Histoplasma serum and urinary antigen, cryptococcal serum antigen, Aspergillus antigen, Blastomyces antibodies, Coccidioides antibodies, Tropheryma whipplei serum PCR, and tuberculosis interferon gamma release assay (TB-IGRA) were negative. Blood cultures were negative. CSF analysis showed a white blood cell count of four lymphocytes, with no malignant cells identified, and CSF cultures for bacteria and mycobacteria were also negative. CT-scan of chest, abdomen, and pelvis was unremarkable.
The patient was initiated by her local doctor on empiric course of corticosteroid therapy. An updated MRI at two weeks demonstrated interval decrease in brain lesions. She came to our institution for a second opinion and underwent repeat lumbar puncture. Total nucleated cells in CSF were 13, 98 % lymphocytes, total protein 42 mg/dL, and glucose 59 mg/dL. Additional infectious work-up was negative, including CSF bacterial, mycobacterial, and fungal cultures, meningitis-encephalitis multiplex PCR, Epstein Barr Virus (EBV) PCR, and free-living amebae PCR were negative. Autoimmune encephalopathy panel, oligoclonal bands, and IgG index were also negative. Outside histopathology underwent direct review by our pathology team, who concurred with the result. TB-IGRA was positive twice this time and she had not been exposed to TB in the interim. A repeat CT chest and PET-CT demonstrated several scattered FDG-avid sub-centimeter mediastinal lymph nodes (Fig. 2), which underwent subsequent mediastinoscopic biopsy, ultimately revealing necrotizing granulomas. Tissue cultures grew pan-susceptible Mycobacterium tuberculosis (MTB). Three serial induced sputum cultures were negative.
Given the presumed diagnosis of disseminated TB with tuberculoma, the patient was initiated on standard-of-care quadruple therapy with isoniazid, rifampin, pyrazinamide, and ethambutol together with a tapered course of corticosteroids. Due to high degree of suspicion for PCNSL, repeat brain MRI at 8 weeks following initiation of anti-TB treatment was done, demonstrating recurrent multifocal, bifrontal enhancing mass lesions (Fig. 3). Repeat brain biopsy confirmed PCNSL, diffuse large B-cell type. Tissue cultures and PCR were negative for MTB or any other infectious etiology. The patient was referred to hematology and completed eight cycles of methotrexate, rituximab, and temozolomide. She is planned for autologous stem-cell transplantation.