Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) associated with or without lymphoma: Comparison of clinical features and risk factors suggestive of underlying lymphomas

Abstract

Background: We studied patients with chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) associated with or without lymphoma and measured risk factors suggestive of an underlying lymphoma and follow-up outcomes. Methods: CLIPPERS patients associated with or without lymphoma were included into this study. Clinical presentations were documented, risk factors suggestive of an underlying lymphoma were tested, and prognostic differences in terms of death were compared. Results: Ten patients had a diagnosis of CLIPPERS associated with lymphoma, with 6 B-cell non-Hodgkin lymphoma, 2 T-cell non-Hodgkin lymphoma and 2 Hodgkin lymphoma. Using multivariate logistic analysis, the following 3 independent risk factors were found to be related to a final diagnosis of lymphoma: hyperreflexia (HR 16.56; 95% CI 1.03-265.29; p = 0.032), elevated protein in CSF (HR 11.59; 95% CI 1.24-108.39; p = 0.047), and recurrences between 2 months and 1 year after treatment (HR 29.27; 95% CI 2.09-409.58; p = 0.012). The model calibration was satisfactory (p = 0.392 with the Hosmer-Lemeshow test), and the discrimination power was good (area under the receiver operating characteristic curve 0.921; p < 0.001, 95% CI 0.826-1.000). Patients with CLIPPERS associated with lymphoma had higher mortality rate and lymphoma was a significant predictor of total mortality (HR 0.040; 95% CI 0.006-0.262; p = 0.001). Conclusions: Hyperreflexia, elevated protein in CSF and recurrences between 2 months and 1 year after treatment are risk factors suggesting an underlying lymphoma. Relapses during high-dose steroids maintenance therapy can be indicative of lymphoma, too. Patients having CLIPPERS associated with lymphoma have a worse prognosis than those without lymphoma.

Hemophagocytic Lymphohistiocytosis Gene Mutations in Adult Patients Presenting With CLIPPERS-Like Syndrome

“…25 Other possible triggers associated with CLIPPERS were also described as triggers of HLH such as Epstein-Barr virus, systemic lymphomas, and more recently histiocytic sarcoma. 26–28…”

“…25 Other possible triggers associated with CLIPPERS were also described as triggers of HLH such as Epstein-Barr virus, systemic lymphomas, and more recently histiocytic sarcoma. [26][27][28] Given the small number of patients genetically tested in our cohort, additional studies are needed to better evaluate the prevalence of mutations in genes related to primary HLH in the patients presenting with CLIPPERS. In addition, because signs of HLH were not systematically searched in the untested patients of our cohort, we cannot totally rule out a selection bias.…”

<p>The Expression of IgG and IgG4 in Orbital MALT Lymphoma: The Similarities and Differences of IgG4-Related Diseases</p>

“…32 IgG4 may even promote tumor-related immune surveillance escape and its effect on cancer immunotherapy through some mechanisms, while it has also been reported that lymphoid cells may produce monoclonal IgG-kappa. 33 At the same time, the relationship between inflammation and tumors has been confirmed, 34 including lymphoma. 35 Among them, MATL lymphoma is considered to be a tumor model mediated by chronic inflammation.…”

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids triggered by Hodgkin's lymphoma: A case report and brief literature review

“…Different hypotheses have been proposed regarding the relationship between lymphoma and CLIPPERS, which need further validation: (a) Lymphoma may be misdiagnosed as CLIPPERS at the onset or recurrence of symptoms. Studies reporting these cases highlight the role of biopsy and red flags such as inadequate response to corticosteroids in differentiating CLIPPERS from lymphoma 6–8,16 19 after a variable time in response to EBV reactivation, 11,20 chronic stimulation of perivascular antigens, 12 blood brain barrier dysregulation, 21 or compromised immune system resulting from treatment of CLIPPERS 9,10,12 ; (c) CLIPPERS may be a lymphocytic response through immune reconstitution or autoimmune reaction to various triggers such as HBV infection, influenza vaccination, or natalizumab withdrawal that may resolve or progress to more severe diseases such as lymphoma depending on management and other unknown prognostic factors 22,23 ; (d) CLIPPERS may be a spectrum rather than a disease caused by heterogeneous mechanisms.…”

“…3,5 To find previous lymphoma-associated cases up to November 2023, PubMed and Scopus online databases were searched using the keywords "CLIPPER" and "Lymphoma". To the best of our knowledge, 20 patients with lymphoma-associated CLIPPERS have been reported [6][7][8][9][10][11][12][13][14][15][16] since the first introduction of CLIPPERS. 2 A review of 10 patients by Zhang et al showed that patients with lymphoma-associated CLIPPERS had worse clinical outcomes and higher risk of mortality compared to those without lymphoma.…”