Would you consider a patient with DLBCL to have CNS involvement if no brain lesion is seen on imaging, CSF flow cytometry is negative, but PCR is positive for MYD88 and KMT2D mutations?

Cerebrospinal fluid (CSF) is an ultrafiltrate of plasma contained within the ventricles of the brain and the subarachnoid spaces of the cranium and spine.

It is possible that cfDNA fragments containing MYD88 and KMT2D mutations may have found their way into the CSF and thereby detected by PCR technique. Alternatively, there is a possibility that the patient may have a subclinical disease in the brain, not detected by traditional methods of MRI imaging and CSF cytology.

The two possible explanations are inextricably intertwined and it may be impossible to differentiate. However, if the patient has controlled disease extracranially and the biomarker levels in the plasma are lower than the CSF level, then I would argue that there is a reservoir of lymphoma cells in the CNS (not yet detected by traditional techniques) and I would recommend that the patient receive IT chemotherapy (Methotrexate) and then re-check the CSF levels of MYD88 and KMT2D at the completion of IT- chemo. If the hypothesis is correct, the level of the CSF biomarkers should drop or completely disappear.