Paraneoplastic Cerebellar Degeneration: Initial Presentation of Mucosa-Associated Lymphoid Tissue Lymphoma in a Patient with Primary Sjögren’s Syndrome
This case report describes a 29-year-old Chinese woman with a unique presentation of paraneoplastic cerebellar degeneration (PCD) as the initial manifestation of mucosa-associated lymphoid tissue (MALT) lymphoma, occurring in the context of undiagnosed primary Sjögren’s syndrome (pSS). The case highlights the diagnostic challenges in identifying autoimmune disorders and their paraneoplastic complications, particularly when atypical or delayed clinical features obscure the underlying pathology.
Clinical Presentation and Diagnostic Journey
The patient initially presented with a 5-month history of recurrent dizziness and a 2-month progression of gait disturbance. Neurological examination revealed horizontal nystagmus, a wide-based gait, and a positive heel-knee-shin test. Initial laboratory evaluations, including hematological, biochemical, microbiological, hormonal, and tumor marker assessments, were unremarkable. Cerebrospinal fluid (CSF) analysis detected oligoclonal bands, suggesting intrathecal immunoglobulin synthesis, but no other abnormalities. Magnetic resonance imaging (MRI) of the brain and cervical spine showed no structural lesions at disease onset. However, computed tomography (CT) of the thorax identified an irregular anterior mediastinal mass [Figure 1A], prompting further investigation for malignancy.
Despite the absence of classic paraneoplastic antibodies—including anti-Hu, anti-Ri, anti-Yo, anti-CV2, anti-Ma, anti-Amphiphysin, anti-Tr, and anti-glutamic acid decarboxylase (GAD)—in both serum and CSF, the subacute cerebellar syndrome strongly suggested a paraneoplastic neurological syndrome (PNS). The mediastinal mass was surgically resected and pathologically confirmed as extranodal MALT lymphoma. Histopathological analysis revealed lympho-epithelial lesions, and immunohistochemistry demonstrated CD20 and BCL2 positivity, with light chain restriction, consistent with a clonal B-cell proliferation. Notably, neoplastic cells were negative for CD3, CD5, CD10, CD23, Cyclin D1, SOX-11, BCL6, and CD117, excluding other lymphoma subtypes.
Linking MALT Lymphoma to Primary Sjögren’s Syndrome
The patient’s rheumatological workup revealed antinuclear antibodies (ANA), anti-Sjögren’s syndrome-related antigen A (anti-SSA/Ro) antibodies, and rheumatoid factor (RF), alongside mildly reduced complement C3 levels. Although she lacked sicca symptoms (dry eyes and mouth) at initial presentation, these findings supported a diagnosis of pSS. A retrospective review of her medical history uncovered a prior left parotid mass excised in 2012, originally diagnosed as “reactive lymphoid hyperplasia.” Re-evaluation of the parotid tissue using archival paraffin sections confirmed it was, in fact, MALT lymphoma. This critical reassessment established a timeline of two distinct MALT lymphomas (parotid and mediastinal) preceding the formal diagnosis of pSS, underscoring the indolent progression of both autoimmune and neoplastic processes.
Evolution of Sjögren’s Syndrome and Neurological Decline
Following resection of the mediastinal mass, the patient received R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone). Despite treatment, her neurological symptoms worsened, progressing to dysarthria, dyskinesia, and wheelchair dependence. Ten months post-diagnosis, she developed sicca symptoms, including dry eyes and mouth. Subsequent evaluations confirmed pSS through abnormal Schirmer’s test results, labial gland biopsy showing lymphocytic sialadenitis, and persistent serological markers. Repeat brain MRI demonstrated cerebellar atrophy [Figure 1B], consistent with advanced PCD. Hereditary ataxia was excluded through genetic testing.
Pathophysiological Insights and Management Challenges
The case illustrates several key mechanisms:
- Paraneoplastic Cerebellar Degeneration: PCD, a classical PNS, is characterized by immune-mediated cerebellar injury, often irreversible due to Purkinje cell loss. While onconeural antibodies aid diagnosis, their absence—as seen here—does not exclude PNS. The subacute onset and cerebellar atrophy on imaging were pivotal for diagnosis.
- MALT Lymphoma and Autoimmunity: Chronic inflammation in pSS drives B-cell hyperactivity, increasing lymphoma risk. MALT lymphomas frequently arise in organs affected by pSS, such as salivary glands. In this patient, the parotid MALT lymphoma predated sicca symptoms, suggesting “silent” autoimmunity with compensatory gland function masking early disease.
- Diagnostic Pitfalls: The initial misclassification of the parotid MALT lymphoma as benign reactive hyperplasia delayed pSS diagnosis. This underscores the importance of rigorous histopathological review in patients with autoimmune predispositions.
Therapeutic Outcomes and Long-Term Follow-Up
Neurological stabilization was achieved through immunomodulation (hydroxychloroquine, prednisone, mycophenolate mofetil) and rehabilitation, though cerebellar dysfunction persisted. Repeat PET-CT showed no lymphoma recurrence, and the patient regained limited mobility after two years. The stable imaging findings and clinical course suggest that early tumor resection and immunosuppression halted further neurodegeneration.
Clinical Implications
This case emphasizes:
- Screening for Autoimmunity in MALT Lymphoma: Patients with MALT lymphoma, particularly in salivary glands, should undergo evaluation for pSS, even without sicca symptoms.
- PNS Recognition in Lymphoproliferative Disorders: Neurological deficits in lymphoma patients warrant consideration of PNS, even without paraneoplastic antibodies.
- Multidisciplinary Management: Coordinated care between hematologists, neurologists, and rheumatologists is essential to address overlapping pathologies.
doi.org/10.1097/CM9.0000000000000736
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