Objective:

We sought to characterize reported cases of paraneoplastic Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids (CLIPPERS). 

Background:

CLIPPERS is a rare neuroimmunological disorder marked by inflammation classically affecting the pons and cerebellum. While consensus diagnostic criteria exist, several conditions can mimic CLIPPERS, making definitive diagnosis challenging. Association with underlying cancer or paraneoplastic CLIPPERS is less understood, with reports of malignancy at time of diagnosis as well as after onset of the disorder. 

Design/Methods:

A PubMed literature search was conducted using the following terms: “Chronic Lymphocytic Inflammation with Pontine Perivascular Enhancement Responsive to Steroids,” “CLIPPERS,” and “cancer.” Of the 21 results, 16 publications were identified as CLIPPERS with a concurrent cancer diagnosis, including individual case reports and one retrospective cohort study. 

Results:

We identified 13 cases in the literature of patients with CLIPPERS who had a cancer diagnosis within five years of CLIPPERS diagnosis. Three cases were analyzed separately due to presentations of CLIPPERS outside of this time frame. Men comprised 76.9% of cases, with an average age of 54.2 years. Non-Hodgkin lymphoma was the most common cancer type (76.9%), diagnosed on average at 7.14 [range 4-48] months post-CLIPPERS. Of this subset, 4 were classified as primary central nervous system B-cell lymphoma. CSF analysis from 9/13 cases reported elevated protein and 5/13 noted pleocytosis. Positive Epstein-Barr Virus (EBV) PCR was found in 3/13 CSF samples alongside EBV-infected cells on neuropathology. Post-treatment, 12/13 cases reported some level of clinical improvement, but only 5/13 noted radiological improvement. 

Conclusions:

Our review revealed a majority of paraneoplastic associations with non-Hodgkin lymphoma, contributing to the ongoing discussion of CLIPPERS presenting as a potential pre-lymphoma state or paraneoplastic phenomenon. It is important to screen patients with CLIPPERS for malignancy and monitor them prospectively.