Paraneoplastic Cerebellar Degeneration: How a Rare Neurological Syndrome Revealed MALT Lymphoma and Undiagnosed Sjögren’s Syndrome
Imagine a 29-year-old woman struggling with months of dizziness and unsteady walking—symptoms that seemed unrelated until tests uncovered a hidden link to cancer and an autoimmune disease she didn’t even know she had. This is the story of how paraneoplastic cerebellar degeneration (PCD)—a rare neurological condition tied to cancer—became the first sign of mucosa-associated lymphoid tissue (MALT) lymphoma in a patient with undiagnosed primary Sjögren’s syndrome (pSS).
The Patient’s Journey: From Dizziness to a Hidden Diagnosis
In 2016, a 29-year-old Chinese woman arrived at West China Hospital (Sichuan University) with 5 months of recurring dizziness and 2 months of trouble walking. Doctors found she had a wide-based gait (unsteady, feet-apart stance), horizontal nystagmus (involuntary eye movement), and a positive heel-knee-shin test (difficulty coordinating leg movements)—classic signs of cerebellar dysfunction.
Initial tests were confusing: blood work, hormone levels, and tumor markers were normal. Her brain and cervical spine MRI looked fine, but her cerebrospinal fluid (CSF) showed oligoclonal bands—abnormal proteins that signal immune activity in the nervous system. A chest CT finally revealed a clue: an anterior mediastinal mass (in the middle of her chest).
Surgery to remove the mass confirmed it was MALT lymphoma—a slow-growing B-cell lymphoma linked to chronic inflammation (like autoimmune diseases or infections). But more surprises followed: rheumatology tests showed she had antinuclear antibodies, Sjögren’s-related antigen A (SS-A) antibodies, and low C3 (a sign of immune activation)—all pointing to primary Sjögren’s syndrome (pSS), an autoimmune disease that attacks salivary and tear glands (causing dry eyes/mouth).
Even more telling? A 2012 parotid gland mass (originally called an “adenoma”) was re-examined—and found to be MALT lymphoma too. The patient had no dryness symptoms at the time, so pSS stayed hidden until her neurological and lymphoma diagnosis.
The Link Between pSS, MALT Lymphoma, and PCD
pSS is a systemic autoimmune disease where immune cells attack exocrine glands (like salivary glands), leading to dryness (“sicca symptoms”). But up to 40% of patients have extraglandular involvement—symptoms outside the glands—before dryness appears. Crucially, pSS patients have a 15-fold higher risk of B-cell lymphomas, most often MALT lymphoma, which typically grows in organs where pSS is active (like salivary glands).
In this case, “silent” autoimmunity (no dryness) likely drove chronic B-cell activation—fueling MALT lymphoma in both her parotid gland and mediastinum. The parotid lymphoma was misdiagnosed initially, but the 2016 mediastinal mass finally uncovered the pattern.
Her neurological symptoms? Paraneoplastic cerebellar degeneration (PCD), a classic paraneoplastic neurological syndrome (PNS). PNS occurs when the immune system’s response to cancer mistakenly attacks the nervous system—even if the tumor is small. While many PNS cases involve onconeural antibodies (proteins that target both cancer and nerve cells), less than 50% of patients have detectable antibodies. Here, the diagnosis was clear: subacute cerebellar dysfunction (her initial symptoms), later cerebellar atrophy on MRI, and the underlying lymphoma.
Treatment and Outcome
Removing the mediastinal mass didn’t improve her neurological symptoms—so she received R-CHOP chemotherapy (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), a standard treatment for B-cell lymphomas. But her ataxia worsened: she developed slurred speech (dysarthria) and movement problems (dyskinesia) and needed a wheelchair.
Ten months later, dry eyes and mouth appeared—confirming pSS with a positive Schirmer’s test (low tear production) and lymphocytic sialadenitis (inflammation of salivary glands). Treatment shifted to immunosuppressants (hydroxychloroquine, prednisone, mycophenolate mofetil) and rehabilitation.
After two years, her ataxia stabilized: she could stand and walk slowly on her own. Her dryness improved with tear substitutes. Repeat scans showed no lymphoma recurrence, and her cerebellar atrophy didn’t progress.
What This Case Teaches Us
This story highlights three key lessons:
- MALT lymphoma and pSS are closely linked: If you or someone you know has MALT lymphoma—especially in the salivary glands—ask about pSS testing. Most salivary MALT lymphomas are tied to pSS.
- PCD can present without onconeural antibodies: Neurological symptoms like unsteady walking or dizziness in cancer patients should raise suspicion for PNS, even if antibody tests are negative.
- “Silent” autoimmunity is real: pSS can hide for years without dryness. Chronic immune activation can drive serious complications (like lymphoma) before classic symptoms appear.
About the Research
This case was reported by Dr. Xia Cao and Prof. Cai-Gang Xu from the Department of Hematology, West China Hospital, Sichuan University (Chengdu, China) in the Chinese Medical Journal (2020). The study underscores the importance of connecting rare neurological syndromes to underlying cancer and autoimmune diseases—even when symptoms seem unrelated.
doi.org/10.1097/CM9.0000000000000736
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