---
title: "Probable CLIPPERS in a Patient with Cutaneous T‑Cell Lymphoma Remission: 5‑Year Follow‑Up (Report"
id: "frontiers-in-immunology-11-case-report-probable-clippers-in-a-patient-with-cutaneous-t-cell-lymphoma-in"
canonical_url: "https://medichelpline.com/clinical-feed/frontiers-in-immunology-11-case-report-probable-clippers-in-a-patient-with-cutaneous-t-cell-lymphoma-in"
content_type: "clinical_feed_article"
specialty: "Infectious Disease"
source_name: "Frontiers in Immunology"
source_url: "https://www.frontiersin.org/articles/10.3389/fimmu.2026.1892153"
published_at: "2026-08-05T00:00:00.000Z"
evidence_level: "Journal Feed"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Probable CLIPPERS in a Patient with Cutaneous T‑Cell Lymphoma Remission: 5‑Year Follow‑Up (Report
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/frontiers-in-immunology-11-case-report-probable-clippers-in-a-patient-with-cutaneous-t-cell-lymphoma-in
- **Specialty:** [Infectious Disease](https://medichelpline.com/clinical-feed/infectious-disease.md)
- **Primary Source:** Frontiers in Immunology
- **Source URL:** [Original Journal Publication](https://www.frontiersin.org/articles/10.3389/fimmu.2026.1892153)
- **Published At:** 2026-08-05T00:00:00.000Z
- **Evidence Rating:** Journal Feed
## Executive GIST (TL;DR)
- The source article title reports a case of probable **CLIPPERS** in a patient with **cutaneous T‑cell lymphoma** in remission, with a five‑year follow‑up. The available SOURCE JINA content contains only website navigation and no case details. - Key clinical data (presentation, imaging, cerebrospinal fluid findings, histopathology, treatment, response, relapse, and longitudinal follow‑up metrics) were not provided in the source text accessible to this task. - No authorship, institutional, diagnostic criteria, management decisions, or outcome measures were available in the supplied source content. - Because the source body lacked substantive article text, all specific clinical, imaging, laboratory, and therapeutic details are unavailable and must not be inferred or assumed. - The absence of the case details prevents extraction of evidence about the association between CLIPPERS and prior cutaneous T‑cell lymphoma, diagnostic challenges, response to immunotherapy, or long‑term prognosis in this patient. - For clinical readers, the missing information limits interpretation and clinical applicability; the full article at the publisher site should be consulted for complete data, methods, and conclusions. - The title alone suggests relevance to neuroimmunology and oncology overlap, long‑term follow‑up in a rare syndrome, and potential diagnostic considerations in patients with prior lymphoma, but supporting data were not reported in the provided source content.
## Clinical Analysis & Structured Key Points
Frontiers | Case Report: Probable CLIPPERS in a patient with cutaneous T-cell lymphoma in remission: 5-year follow-up CASE REPORT article Front. Immunol. , 05 August 2026 Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1892153 Published in Frontiers in Immunology Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders 7 impact factor 11.3 citescore Editor & Reviewers Edited by V F Vincenzo Fiorentino Reviewed by J A Juan Antonio Antonio Encarnacion G P Gianluca Prencipe Outline Figures and Tables Figure 1 View in article Figure 2 View in article Figure 3 View in article Figure 4 View in article CASE REPORT article Front. Immunol. , 05 August 2026 Sec. Autoimmune and Autoinflammatory Disorders : Autoimmune Disorders Volume 17 - 2026 | https://doi.org/10.3389/fimmu.2026.1892153 Case Report: Probable CLIPPERS in a patient with cutaneous T-cell lymphoma in remission: 5-year follow-up K H Kun Hong 1,2 † L L Lantao Liang 1,2 † R L Ruohao Li 1,2 Z S Zhijiao Song 1,2 M Z Meiling Zhang 1,2 H B Hui Bu 1,2 * Y Z Yu Zhang 1,2 * 1. Department of Neurology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, China 2. Neurological Laboratory of Hebei Province, Shijiazhuang, Hebei, China Article metrics View details Abstract Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) may be associated with lymphoma, although the underlying relationship between these entities remains unclear. While the diagnosis is centered on specific imaging characteristics and can be difficult to establish, CLIPPERS typically responds robustly to corticosteroid therapy. We report a 60-year-old woman who presented with memory and cognitive impairment 4 years after achieving complete remission from cutaneous T-cell lymphoma. Brain MRI revealed atypical CLIPPERS features, including scattered enhancing lesions in both supratentorial and infratentorial regions. During a subsequent relapse, transient low-titer serum anti-myelin oligodendrocyte glycoprotein antibodies (titer 1:32) were detected, which later reverted to negative. Initial PET/CT demonstrated transient hypermetabolic splenic lesions suspicious for lymphoma involvement, which resolved on follow-up imaging. Subsequently, new skin lesions with T-cell atypia developed; however, skin biopsy findings, CSF T-cell receptor gene rearrangement studies, and clinical evaluations did not provide evidence supporting lymphoma recurrence or CNS involvement. After comprehensive evaluation and exclusion of alternative diagnoses, follow-up brain MRI revealed characteristic “pepper-like” pontocerebellar enhancing lesions. In combination with a favorable response to high-dose corticosteroids, these findings supported a diagnosis of probable CLIPPERS. This case highlights the complex interplay among CLIPPERS, potential neoplastic states, and transient autoantibodies during long-term follow-up, underscoring the need for prolonged clinical surveillance for possible lymphoma recurrence. It also underscores the diagnostic complexity of CLIPPERS in patients with prior lymphoma and suggests that transient low-titer MOG-IgG seropositivity should be interpreted cautiously in the absence of CSF positivity or a typical MOGAD phenotype. 1 Introduction Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) was initially reported by Pittock et al. in 2010, who summarized eight patients presenting with subacute gait ataxia and diplopia; neuroimaging revealed characteristic areas of punctate and curvilinear gadolinium enhancement with a “pepper-like” appearance, predominantly in the pons and cerebellum. Brain biopsy was performed in four, which showed perivascular lymphocytic infiltration within the white matter. All patients exhibited symptomatic improvement after corticosteroid treatment. Post-treatment neuroimaging demonstrated a reduction in the number as well as in the size of lesions. However, long-term maintenance immunosuppressive therapy was required. Six patients experienced relapse when steroid dose reduction or discontinuation was attempted ( 1 ). While the pathogenesis of CLIPPERS remains incompletely understood, it is classified as an autoimmune-mediated inflammatory disorder. Its characteristic of perivascular inflammation has led to the organ-specific autoantigen hypothesis. Other proposed disease mechanisms include virus-induced autoimmunity and a Th17 cell-mediated pathway ( 1 , 2 ). The etiology of CLIPPERS has not been elucidated. However, it frequently occurs after viral infections (chronic hepatitis B, Epstein-Barr, SARS-CoV-2, varicella-zoster) and influenza vaccination ( 3 – 6 ). Ortega et al. described a patient with multiple sclerosis who developed CLIPPERS following the withdrawal of natalizumab ( 7 ). In a study of 140 patients with CLIPPERS, the prevalence of malignancy was 16% ( 8 ). The most common associated malignancy is central nervous system (CNS) lymphoma, followed by renal cell carcinoma, thyroid cancer, malignant nerve sheath tumor, breast cancer, prostate cancer, and adrenal adenoma. In a retrospective analysis of 88 CLIPPERS patients, 10 had lymphoma ( 8 – 10 ). There appears to be no clear temporal relationship between the onset of CLIPPERS and lymphoma—in one case, CLIPPERS appeared 11 years after a cured Hodgkin lymphoma; in another, Hodgkin lymphoma was diagnosed 2 years after the onset of CLIPPERS ( 5 , 11 ). Additionally, T-cell lymphoma has been documented 5 to 10 years after CLIPPERS onset, and CNS B-cell lymphoma has been observed several years after a CLIPPERS diagnosis. Nonetheless, CLIPPERS is clearly closely associated with lymphoma ( 12 – 15 ). The question is whether it is a truly distinct new disease entity, or rather a syndrome encompassing different, potentially overlapping conditions and their prodromal stages. We report a case of CLIPPERS occurring 4 years after complete remission of cutaneous T-cell lymphoma (CTCL). The patient has been followed for 5 years since the onset of CLIPPERS. 2 Case presentation A 60-year-old woman had been diagnosed with CTCL in 2008 and achieved complete remission in 2016 after approximately 8 years of treatment with interferon, immunosuppressants, and ultraviolet phototherapy. Four years later, in 2020, she presented with fatigue, memory impairment, hypersomnia, reduced verbal output, and vomiting. Her memory impairment was so severe that she had forgotten to turn off the stove after boiling water and was unable to account for other recent activities. Positron emission tomography (PET)/computed tomography (CT) showed an enlarged spleen with slightly heterogeneous density focal nodular hypermetabolism, suggesting a high probability of lymphoma (Deauville score, 4); however, splenic biopsy was not performed, precluding histopathological confirmation. Neurological examination revealed severe impairments in calculation, memory, executive function, and orientation. Her cranial nerves were intact. Sensation and coordination were normal. She exhibited generalized weakness in all four limbs. Deep tendon reflexes were hyperactive throughout. Her modified Rankin scale score was 3. Rapidly progressive dementia was diagnosed. A broad serologic workup was negative for human immunodeficiency virus, rapid plasma reagin, antinuclear antibodies, and abnormalities in kidney and liver markers; levels of vitamin B12, folate, electrolytes, and thyroid-stimulating hormone were normal. Routine cerebrospinal fluid (CSF) analyses were also within normal limits. CSF protein was elevated (50 mg/dL). Serum and CSF aquaporin-4 (AQP4) and myelin oligodendrocyte glycoprotein (MOG) immunoglobulin G (IgG) antibodies were undetectable, as were serum and CSF autoimmune/paraneoplastic encephalitis panels. No oligoclonal bands were detected. Electroencephalography showed background slowing with diffuse polymorphic delta and theta waves. A low burden of spike-and-wave and sharp-wave complexes was seen maximally over the bilateral temporal regions, including the sphenoidal electrodes. Brain MRI showed multiple punctate and patchy T 2 -weighted (T 2 WI) and fluid-attenuated inversion recovery (FLAIR) hyperintensities involving both supratentorial and infratentorial regions, including the subcortical and deep white matter, brainstem, thalami, cerebellar hemispheres, and medulla oblongata, with prominent post-contrast enhancement ( Figures 1A, B, E, F ). On diffusion-weighted imaging (DWI), some lesions in the bilateral cerebral hemispheres were mildly hyperintense, with corresponding isointensity on apparent diffusion coefficient (ADC) maps. Brain magnetic resonance angiography (MRA) revealed no vascular abnormalities. Spinal MRI showed multiple small patchy T 2 -hyperintense lesions in the cervical spinal cord, with multiple punctate and linear areas of enhancement and no mass effect ( Figures 1C, D, G, H ). MR spectroscopy (MRS) of the right periventricular and insular regions was performed with an echo time (TE) of 144 ms, with the spectroscopy voxel centrally positioned within the enhancing component of the lesion. It demonstrated an elevated choline peak, a stable creatine peak, and a reduced N-acetylaspartate peak, yielding a choline/creatine (Cho/Cr) ratio of 0.68–1.45 and a choline/N-acetylaspartate (Cho/NAA) ratio of 1.03–1.18. No lipid or lactate peaks were observed. The patient received a course of high-dose intravenous methylprednisolone (500 mg/day for 5 days), which was tapered to oral prednisone (1 mg/kg/day). Her symptoms gradually improved, with notable recovery in recent memory and calculation abilities. Follow-up MRI of the brain showed a significant reduction in both the size and the enhancement of the previously noted lesions ( Figures 1I, J ). Upon follow-up at 3 months, repeat imaging showed complete resolution of the cervical cord lesions ( Figures 1K, L ); clinically, she had also improved (modified Rankin scale score 1). Figure 1 Brain and spinal cord MRI at disease onset (A–H) and post-treatment (I–L) . (A, B, E, F) Multiple slightly hyperintense FLAIR signals with enhancement are present in the brainstem, cerebellar gray and white matter (A, E) , the bilateral subcortical and deep cerebral white matter, thalami (B, F) . (C, D, G, H) Multiple small patchy slightly hyperintense T 2 WI signals with enhancement in the cervical spinal cord parenchyma. (I, J) Reduction in the number and size of lesions in the bilateral cerebral hemispheres, brainstem, and cerebellar hemispheres. (K, L) No abnormal signal or abnormally enhancing lesions are seen in the cervical spinal cord. MRI, magnetic resonance imaging; T 1 WI, T 1 -weighted imaging; T 2 WI, T 2 -weighted imaging; FLAIR, fluid-attenuated inversion recovery. Four years later, she presented with transient loss of consciousness, worsening recent memory loss, and generalized limb weakness. She denied seizures. Brain MRI revealed multiple enhancing lesions in both cerebral hemispheres and the brainstem and cerebellum, with DWI demonstrating punctate hyperintensities in the pons and left temporal lobe, corresponding to isointensity on ADC maps ( Figures 2A–D ). CSF analysis was notable for an elevated protein level (87 mg/dL). Serum MOG-IgG was positive (1:32) on two separate tests by live cell-based assay (live CBA), performed at V-Medical Laboratory Co., Ltd., whereas CSF testing was consistently negative. Testing for paraneoplastic, glial fibrillary acidic protein (GFAP), and AQP4 antibody panels was negative in both the serum and CSF. Intravenous methylprednisolone (500 mg daily for 3 days) followed by rituximab (400 mg; infusion discontinued because of infusion-related chills and fever) was initiated for recurrent neurological symptoms, which resulted in symptom resolution. Two months later, follow-up MRI demonstrated significant reduction or complete resolution of the brain lesions ( Figures 2E–H ). Figure 2 Brain MRI images at first relapse (A–D) and during remission (E–H) . (A–D) Multiple areas of mild FLAIR hyperintensity in the bilateral cerebral hemispheres, brainstem, and cerebellum, with enhancement. (E–H) Reduced extent or disappearance of multiple enhancing lesions in the cerebral hemispheres, brainstem, and cerebellum. MRI, magnetic resonance imaging; T 1 WI, T 1 -weighted imaging; FLAIR, fluid-attenuated inversion recovery. Ten months later, the patient developed bilateral lower extremity weakness and an unsteady gait, accompanied by depressed mood, anhedonia, and irritability. She was then hospitalized, during which, her family members reported significant recent memory decline, agitation, reduced nighttime sleep, and visual hallucinations. MRI revealed an increase in scattered punctate and linear enhancing lesions within the pons and bilateral cerebellar hemispheres, with no abnormal signal detected in the cervical spinal cord. DWI demonstrated no abnormal hyperintense signal in the brain parenchyma. ( Figures 3A–D ). These findings were consistent with CLIPPERS. CSF analysis showed 18 nucleated cells/µL and an elevated protein level (84 mg/dL). Serum MOG IgG was negative. Her physical examination revealed new skin lesions consisting of scattered, dark red, patchy macules on both lower limbs and two slightly infiltrated erythematous plaques on the left lower leg ( Figures 4A , a, b). A biopsy from the left lower leg demonstrated atypical T-lymphoid hyperplasia with a subcutaneous, irregular nested proliferation of T-lymphocytes. The immunophenotype was CD3(+), CD5(+), CD7(+), and CD43(+), with partial expression of CD4 and CD8; GrB was scattered positive, and Ki-67 was approximately 20%. Cells were negative for ALK, CD2, CD20, CD30, CD56, and EBER ( Figures 4A , c). T-cell receptor (TCR) gene rearrangement analyses of both skin biopsy and cerebrospinal fluid samples were negative. Regrettably, the original raw data from the skin TCR gene rearrangement assay were not available, as the test was performed at an external institution. A repeat whole-body PET/CT, performed approximately 4.75 years after the initial examination, demonstrated complete resolution of the previously noted splenic hypermetabolic nodules ( Supplementary Table 1 ) and identified only a small focus of mildly increased metabolic activity in the posterior aspect of the right lower leg. Figure 3 Brain MRI images at second relapse (A–D) and during remission (E–H) . (A–D) Increased number of scattered punctate and linear enhancing foci in the pons and cerebellar hemispheres. (E–H) Decreased number of scattered small punctate and linear enhancing foci in the brainstem and cerebellar hemispheres. MRI, magnetic resonance imaging; T 1 WI, T 1 -weighted imaging; FLAIR, fluid-attenuated inversion recovery. Figure 4 (A) Gross image and histopathology of the patient’s skin: (a, b) Scattered dark red macules on both lower limbs and two indurated erythematous plaques on the left lower leg. (c) Subcutaneous irregular nested proliferation of atypical T-lymphocytes (left lower leg biopsy). (B) The timeline of relevant results and interventions during the diagnosis and treatment of the patient. After a 3-day pulse of intravenous methylprednisolone (500 mg/day), the patient’s symptoms improved. To prevent relapse, oral prednisone was initiated on discharge at 1 mg/kg/day, and then tapered. At the most recent follow-up, brain MRI demonstrated reduction of multiple scattered small dot-like and linear enhancing lesions in the brainstem and bilateral cerebellar hemispheres relative to prior imaging, and the patient was independent in basic routine activities (modified Rankin scale score 1), with recovered memory and no further relapses ( Figures 3E–H ). The relevant diagnosis and treatment results of the patient are shown in Figure 4B . 3 Discussion and conclusions This report describes a complex case of probable CLIPPERS that developed following complete remission of CTCL, with a longitudinal follow-up of five years. Several features made the diagnostic evaluation particularly challenging, including cognitive impairment as the initial presenting manifestation, extensive supratentorial and infratentorial lesions on MRI, transient low-titer serum MOG-IgG positivity during the disease course, and the subsequent development of cutaneous lesions with atypical T-cell hyperplasia. The coexistence of these findings posed diagnostic challenges regarding CLIPPERS, occult lymphoma, and the clinical significance of dynamic autoantibody positivity. This case highlights the importance of comprehensive differential diagnosis and long-term multidisciplinary surveillance in patients with atypical manifestations of CLIPPERS. According to the revised diagnostic criteria proposed by Tobin et al. (2017), this patient met the criteria for probable CLIPPERS ( 9 ), as detailed in Supplementary Table 2 . Notably, the diagnostic criteria were not fulfilled until the first relapse, when the characteristic clinical manifestations and pontocerebellar MRI features became evident. Therefore, the diagnosis was established retrospectively rather than at the index presentation. The diagnosis was supported by characteristic clinical and radiological features, including brainstem, cerebellar, and cognitive involvement with a relapsing–remitting course, punctate and curvilinear pontocerebellar enhancement with a typical “pepper-like” appearance, a robust response to corticosteroids, and evaluation of major mimics including CNS lymphoma. Brain biopsy was considered at the initial presentation but was ultimately not performed because the patient declined the procedure. Therefore, the diagnosis remained classified as probable CLIPPERS, and the absence of histopathological confirmation remains an important limitation of this case. This case exhibited several atypical clinical and radiological features that merit further discussion. Firstly, the patient presented predominantly with cognitive impairment, including memory, calculation, and executive dysfunction, rather than the classic brainstem and cerebellar manifestations of CLIPPERS, such as dysarthria, ataxia, and diplopia. Previous studies have suggested that cognitive dysfunction is an easily overlooked manifestation of CLIPPERS, particularly in patients with prominent supratentorial involvement ( 16 , 17 ). Secondly, the patient’s initial brain MRI demonstrated extensive infratentorial and supratentorial involvement, including the bilateral subcortical and deep cerebral white matter as well as the thalami, rather than the typical pontocerebellar distribution. This “supratentorial-predominant” presentation is sometimes termed “supratentorial lymphocytic inflammation with parenchymal perivascular enhancement responsive to steroids (SLIPPERS)” ( 18 – 20 ). Notably, characteristic pontocerebellar punctate enhancement emerged only during subsequent relapses in our patient, suggesting that the radiological phenotype may evolve over time, and early atypical imaging should not exclude CLIPPERS. Thirdly, MRI revealed multiple small enhancing lesions in the cervical cord. While spinal cord involvement is uncommon in CLIPPERS, prior reports ( 21 , 22 ) present diagnostic challenges regarding MOGAD, multiple sclerosis, and lymphoma. Importantly, lesion resolution following corticosteroid therapy supports the reversible, inflammatory process to some extent, although this finding does not completely exclude an underlying neoplastic process. Distinguishing CLIPPERS from lymphoma represents the primary diagnostic challenge in this case, particularly in the absence of brain biopsy. Primary or systemic lymphoma can mimic CLIPPERS, often responding transiently to steroids ( 12 , 23 ) and showing potential evolution over time ( 24 ). Although the patient presented with risk factors predictive of underlying lymphoma, including a history of CTCL, spl
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