Innov Clin Neurosci. 2021;18(10–12):8.

Dear Editor:

Primary central nervous system (CNS) lymphoma (pCNL) is a rare neoplasia predominantly of the brain. Histologically, most of these neoplasias are diffuse large B-cell lymphomas.1 Although the exact diagnosis requires pathological confirmation, magnetic resonance imaging (MRI) often shows characteristic results, such as enhancement.2 However, nonenhancing pCNL have been described in individual cases.3 The analysis of specific chemokines in the cerebrospinal fluid (CSF), like CXCL13, as well as the usage of fluorodeoxyglucose-positron emission tomography (FDG-PET), can be useful in the diagnostic process.4,5

We present a case of a 60-year-old Caucasian, immunocompetent woman who was admitted to our hospital with a progressive atactic gait disorder. She further reported vertigo and vomiting for several weeks. The physical exam revealed a complex eye motility disorder. In addition, the patient presented incomplete right-sided hemiataxia. Within six months she lost her ability to walk and developed right-sided facial palsy and severe dysarthria and dysphagia. With an initial cerebral MRI scan of the brain, an aneurysm of the right middle cerebral artery and meningioma of the left os sphenoidale were diagnosed. No other signal disturbances or enhancing lesions of the brain were evident. CSF showed a slight elevation in protein level, but no pleocytosis, atypical cells, or intrathecal immunglobuline synthesis. Due to the medical history and clinical findings, we suspected incipient aseptic brainstem encephalitis. A whole-body 18-FDG-PET-computed tomography (CT) showed a diffuse impaired glucose uptake from the cervical myelon up to the posterior cranial fossa. Follow-up MRI investigations, up to 18 weeks after the clinical onset, showed diffuse white matter change with involvement of the brainstem in T2 fluid attenuated inversion recovery sequence, but no enhancement. 

Repeated samples of CSF showed a sustained moderate protein elevation, and at one point a slight pleocytosis of 30 cells/µL. Microbiological analyses were negative, as were onconeural and ganglioside antibodies. However, CSF levels of CXCL13 were slightly elevated in the late course of the disease (424pg/mL).

According to our primarily suspected diagnosis, the patient was initially treated with a high-dose of methylprednisolone, followed by intravenous immunoglobulin, cyclophosphamide, and tocilizumab as an ultima ratio therapy. Seven months after the onset of symptoms, our patient died. Postmortem histopathology revealed diffuse B-cell lymphoma that originated in the brainstem.  

Diagnosis of pCNL can be challenging, especially when typical MR features are absent. Typically, pCNL shows a good response to corticosteroid application.6 Interestingly, our patient developed progressive neurological deficits during therapy with methylprednisolone. Yet, it is possible that the administered steroids affected radiologic results, especially leading to nonenhancement in the affected areas. Another notable finding in our case was the elevated level of CXCL13. CXCL13 is a chemokine involved in the homing of B cells.4,7 In several studies, CXCL13 levels in CSF were elevated in pCNL; the cut-off values in these studies were not consistent but were relatively lower than in our case. Nevertheless, to the best of our knowledge, the distinct analysis and elevation of CXCL13 in a case of confirmed nonenhancing pCNL with an atypical presentation had not yet been reported. 

The FDG-PET showed a subtle uptake of the upper cervical myelon and the caudal brainstem. Increased uptake is a common finding in pCNL,5 but conflicting results in patients with atypical MRI findings were reported.8 In our particular case, it is remarkable that the pathologic findings in the FDG-PET preceded the changes in MRI. 

Advanced diagnostics with analysis of CXLC13 in CSF and the application of PET-CT can be useful in the diagnostic workup of suspected inflammatory processes or cerebral mass lesions, especially in cases when a biopsy is not realizable. 

Acknowledgment

The study was conducted in accordance with the Declaration of Helsinki.

References

  1. Grommes C, DeAngelis LM. Primary CNS lymphoma. J Clin Oncol. 2017;35(21):2410–2418. 
  2. Yap KK, Sutherland T, Liew E, et al. Magnetic resonance features of primary central nervous system lymphoma in the immunocompetent patient: a pictorial essay. J Med Imaging Radiat Oncol. 2012;56(2):179–186. 
  3. Lachenmayer ML, Blasius E, Niehusmann P, et al. Non-enhancing primary CNS lymphoma. J Neurooncol. 2011;101(2):343–344. 
  4. Gupta M, Gupta T, Purandare N, et al. Utility of flouro-deoxy-glucose positron emission tomography/computed tomography in the diagnostic and staging evaluation of patients with primary CNS lymphoma. CNS Oncol. 2019;8(4):CNS46.
  5. van Westrhenen A, Smidt LCA, Seute T, et al. Diagnostic markers for CNS lymphoma in blood and cerebrospinal fluid: a systematic review. Br J Haematol. 2018;182(3): 384–403. 
  6. Weller M. Glucocorticoid treatment of primary CNS lymphoma. J Neurooncol. 1999;43(3):237–239.  
  7. Ansel KM, Harris RBS, Cyster JG. CXCL13 is required for B1 cell homing, natural antibody production, and body cavity immunity. Immunity. 2002;16(1):67–76.
  8. Kawai N, Okubo S, Miyake K, et al. Use of PET in the diagnosis of primary CNS lymphoma in patients with atypical MR findings. Ann Nucl Med. 2010;24:(5)335–343. 

With regards,

Dietrich Sturm, MD; Marco Tosch, MD; Jörg Felsberg, MD; Cornel Haupt, MD; and Martin Kitzrow, MD

Drs. Sturm and Kitzrow are with the Department of Neurology, Agaplesion Bethesda Krankenhaus in Wuppertal, Germany. Dr. Tosch is with the Department of Nuclear Medicine, Helios Klinikum Wuppertal, University Hospital, University Witten/Herdecke in Wuppertal, Germany. Dr. Felsberg is with the Department of Neuropathology, Heinrich Heine University in Düsseldorf, Germany. Dr. Haupt is with the Department of Radiology, Agaplesion Bethesda Krankenhaus, in Wuppertal, Germany.

Funding/financial disclosures. The authors have no conflict of interest relevant to the content of this letter. No funding was received for the preparation of this letter.