Case Presentation: 42-year-old female with lung adenocarcinoma (with metastases to T-spine s/p corpectomy and XRT to T-spine and lung) presented with four weeks of constant pressure-like headaches and oral intolerance due to nausea and vomiting. She denied fevers, chills, night sweats or hemoptysis. Home medication included osimertinib for her lung cancer. She had no significant family history and denied substance use.Patient was afebrile with stable vitals and unremarkable CBC and CMP. Lumbar puncture (LP) showed elevated lymphocytes/monocytes with decreased glucose, elevated opening pressure, and negative cytology. She was started on empiric antibiotics and dexamethasone. Three repeat LPs showed a similar profile with negative TTF-1. MRI brain showed hyperintense signal without evidence of metastasis. She was then started on HRZE therapy for empiric TB treatment and continued on dexamethasone. Given improvement on steroids and HRZE therapy (communicable TB ruled out), she was discharged on steroid taper and HRZE therapy. Shortly after discharge, Coccidioides IgM (immunodiffusion) returned positive, so she was also started on fluconazole.One month later, she presented with two weeks of nausea and vomiting and occipital headache and neck pain, again without fevers or chills. Repeat LP now showed abnormal TTF1+ cells compatible with malignancy. Repeat MRI Brain showed multifocal leptomeningeal metastases and intraparenchymal enhancing lesions. PET showed hypermetabolic cervical lymph nodes and osseous lesions, consolidation within the right lung, and leptomeningeal and intraparenchymal brain metastases. Fluconazole was discontinued given negative serum and CSF cocci antibody complement fixation (comp fix). HRZE therapy was discontinued, and patient was started on two weeks of WBRT and switched from osimertinib to carboplatin/pemetrexed.Unfortunately, 6 months later patient presented with concern for cord compression from progression of disease, shortness of breath from significant pleural effusion, and progressive dysphagia. Given worsening clinical status and complications from advanced lung adenocarcinoma with poor prognostication despite treatment, patient ultimately pursued SNF hospice.
Discussion: Carcinomatous meningitis (or leptomeningeal metastases) is characterized by persistent mild lymphocytic pleocytosis, elevated protein, hypoglycorrhachia, and elevated opening pressure, all present in this patient’s CSF studies. TB and Coccidioides meningitis typically cause CSF counts in the hundreds to low thousands and can result in an extremely high protein count, neither of which were present in the patient. Furthermore, a positive serum cocci IgM is not specific and is known to have false positives; the serum and CSF cocci antibody comp fix are both more specific, and it is unusual to have cocci meningitis with a negative comp fix. Having an earlier suspicion of carcinomatous meningitis during the first inpatient hospitalization may have led to earlier treatment for the metastases, though unfortunately carcinomatous meningitis already has a poor prognosis, with a median survival time of 2-4 months despite treatment.
Conclusions: Even if initial repeat LP cytologies do not reveal malignancy, the constellation of lymphocytic pleocytosis, elevated protein, hypoglycorrhachia, and elevated opening pressure on LPs should raise suspicion for carcinomatous meningitis, especially in the background of any prior oncologic history.