Case Report/Case Series |

Fatal B-cell Lymphoma Following Chronic Lymphocytic Inflammation With Pontine Perivascular Enhancement Responsive to Steroids

Hjalmar J. De Graaff, BSc1; Mike P. Wattjes, MD, PhD2; Annemieke J. Rozemuller-Kwakkel, MD, PhD3; Axel Petzold, MD, PhD4; Joep Killestein, MD, PhD5
[+] Author Affiliations
1Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands
2Department of Radiology, VU University Medical Center, Amsterdam, the Netherlands
3MS Center Amsterdam and Department of Pathology, VU University Medical Center, Amsterdam, the Netherlands
4Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands
5Department of Neurology, VU University Medical Center, Amsterdam, the Netherlands
JAMA Neurol. 2013;70(7):915-918. doi:10.1001/jamaneurol.2013.2016.
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Importance  Recent reports on chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) suggest that patients who have a relapse respond very well and that disease progression can be avoided if timely corticosteroid therapy is started. We report on a well-documented patient who presented with clinical, radiological, and pathological characteristics of CLIPPERS and who had an unfavorable outcome.

Observations  We present the clinical, imaging, laboratory, brain biopsy, and autopsy findings of a 57-year-old male patient with CLIPPERS who repeatedly responded well to high-dose corticosteroids. During follow-up, however, treatment failed, and he had a biopsy-confirmed diagnosis of lymphomatoid granulomatosis that evolved into fatal B-cell lymphoma of the central nervous system.

Conclusions and Relevance  The clinical and imaging features of CLIPPERS include an abundance of differential diagnoses, and the follow-up periods of the described cases classified as CLIPPERS have been limited. Therefore, the question remains whether CLIPPERS is an actual new disease entity or represents a syndrome that includes different overlapping diseases and their prestages. Our case report shows that a typical presentation of CLIPPERS does not uniformly imply a favorable outcome, even when timely treatment regimens have been given.

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Figure 1.
Axial Contrast–Enhanced T1-Weighted Sequences of the Posterior Fossa

Axial contrast–enhanced T1-weighted sequences of the posterior fossa (top row) and the corresponding axial T2-weighted images (bottom row) of the posterior fossa, which demonstrate the magnetic resonance imaging (MRI) findings during the disease course. The initial MRI scan performed on July 21, 2008, showed punctuate-enhancing lesions in the pons, the left middle cerebellar peduncle, and the right cerebellar hemisphere (arrows) with a perivascular enhancement pattern fulfilling the imaging criteria of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) (A). On the follow-up MRI performed on September 29, 2008, the progression of these changes was observed (B). After the initiation of steroid treatment, a substantial regression of the changes was visible on the MRI scan from January 15, 2009 (C). However, during the later disease course, a mass lesion with an inhomogeneous contrast-enhancement pattern (arrow) was detected in the pons; this lesion was no longer consistent with MRI criteria of CLIPPERS (MRI of May 15, 2009 [D]).

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Figure 2.
Initial Frontal Brain Biopsy

The image shows findings negative for Epstein-Barr virus–encoded RNA using in situ hybridization (hematoxylin-eosin, original magnification ×400) (A). The results of in situ hybridization to test for Epstein-Barr virus–encoded RNA in the second brain biopsy show cell nuclei in the lymphoid infiltrate at the transition of the medulla oblongata and the pons (hematoxylin-eosin, original magnification ×100) (B).

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