Neurolymphomatosis Caused by Diffuse Large B-Cell Lymphoma Presenting as Isolated Brachial Plexopathy
Neurolymphomatosis (NL) is a rare clinical disorder characterized by peripheral neuropathy resulting from lymphomatous infiltration of the nerves. It is most commonly associated with intermediate or high-grade non-Hodgkin lymphoma (NHL), particularly diffuse large B-cell lymphoma (DLBCL). This case report highlights an unusual presentation of NL as an isolated brachial plexopathy, emphasizing the diagnostic challenges and therapeutic considerations in managing this condition.
Case Presentation
A 66-year-old female presented with a 16-month history of muscle weakness, numbness, and pain in her left shoulder and arm. Over time, she developed muscle atrophy and forearm swelling. Initially, she was diagnosed with brachial plexus neuritis and treated with intravenous methylprednisolone (500 mg for 3 days) followed by a tapering course of oral prednisolone. However, the treatment provided minimal relief. Her medical and family histories were unremarkable.
Initial Diagnostic Workup
Prior to admission, imaging studies, including chest computed tomography (CT) and magnetic resonance imaging (MRI) scans of the brain, cervical spinal cord, and brachial plexus, showed no significant abnormalities. Needle electromyography (EMG) revealed weakened motor unit recruitment and abnormal spontaneous activities, such as positive sharp waves and fibrillations, in muscles innervated by the left brachial plexus. Nerve conduction studies demonstrated a significant decrease in compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes, along with prolonged distal latency, particularly in regions innervated by the inferior trunk of the brachial plexus (e.g., ulnar nerve-innervated muscles). Nerve conduction velocities, however, were minimally affected.
Neurological Examination and Advanced Imaging
Upon admission, neurological examination revealed reduced muscle strength (Medical Research Council [MRC] grade 2/5) in both proximal and distal parts of the left arm. Atrophy was evident in the deltoid and interosseous muscles. Reflexes, including the biceps, triceps, and radial periosteal reflexes, were absent on the left side. Sensory perception of light touch, pinprick, and temperature was severely impaired throughout the left forearm.
Repeat MRI showed extensive enlargement of the brachial plexus trunk and enhancement in several swollen supraclavicular lymph nodes. Positron emission tomography (PET) scan revealed increased uptake of 2-deoxy-2-[fluorine-18] fluoro-D-glucose (18F-FDG) in the upper region corresponding to the MRI abnormalities. These findings raised suspicion of a neoplastic process involving the brachial plexus.
Pathological Confirmation
A lymph node biopsy from the left supraclavicular region was performed for pathological evaluation. Hematoxylin and eosin (H&E) staining demonstrated destruction of the normal lymph node architecture, replaced by cancerous cells. Immunohistochemical staining confirmed the diagnosis of DLBCL, with positive expression of CD20, Bcl-2, Bcl-6, and MUM1, and negative expression of CD10. The Ki-67 proliferation index was 80%, indicating a moderately aggressive tumor.
Treatment and Follow-Up
The patient was initiated on systemic chemotherapy with rituximab and doxorubicin hydrochloride liposome. After eight courses of treatment over 10 months, follow-up MRI and PET scans showed significant regression of the lesions. However, there was no notable improvement in her neurological symptoms, likely due to the prolonged duration of nerve injury before diagnosis.
Discussion
Brachial plexopathy can arise from various etiologies, including hereditary neuropathies, autoimmune disorders, neoplasms, and idiopathic causes such as thoracic outlet syndrome. A slowly progressive unilateral brachial plexopathy without remission strongly suggests a neoplastic origin, either primary (e.g., schwannomas, neurofibromas) or secondary (e.g., Pancoast tumor, breast cancer). NL involving the brachial plexus is exceedingly rare, with a reported prevalence of 18% in NL cases.
Diagnostic Challenges
The initial diagnostic workup in this case was inconclusive, as routine MRI did not reveal significant abnormalities until 16 months after symptom onset. This underscores the importance of advanced imaging techniques, such as contrast-enhanced MRI and PET-CT, in evaluating unexplained progressive brachial plexopathy. In this case, PET-CT demonstrated increased 18F-FDG uptake in the affected brachial plexus and supraclavicular lymph nodes, which was pivotal in guiding further diagnostic investigations.
Pathological and Immunohistochemical Findings
The pathological examination of the lymph node biopsy was crucial in establishing the diagnosis of DLBCL. The immunohistochemical profile, including the expression of CD20, Bcl-2, Bcl-6, and MUM1, and the absence of CD10, is consistent with DLBCL. The Ki-67 index of 80% indicated a moderately proliferative tumor, which may have contributed to the relatively indolent clinical course observed in this patient.
Therapeutic Considerations
The management of NL is challenging due to its rarity and the lack of standardized treatment protocols. Systemic chemotherapy, typically rituximab plus CHOP (cyclophosphamide, hydroxydaunorubicin, oncovin, prednisone), is the first-line regimen for DLBCL. High-dose intravenous methotrexate has been reported to be effective in NL due to its ability to penetrate the blood-nerve barrier. In this case, the patient received rituximab and doxorubicin hydrochloride liposome, which resulted in significant tumor regression but no improvement in neurological function, likely due to irreversible nerve damage from prolonged disease duration.
Prognosis and Clinical Implications
The median survival of patients with primary NL is approximately 20 months. Early diagnosis and prompt initiation of treatment are critical to improving outcomes. This case highlights the importance of considering NL in the differential diagnosis of progressive painful unilateral brachial plexopathy, particularly when conventional imaging studies are inconclusive. Advanced imaging techniques and biopsy of extra-neural involved tissues are essential for accurate diagnosis and treatment planning.
Conclusion
DLBCL is the most common type of NL and can present as an isolated brachial plexopathy. Clinicians should maintain a high index of suspicion for NL in patients with progressive unilateral brachial plexopathy, especially when routine imaging studies are unremarkable. Advanced imaging modalities, such as contrast-enhanced MRI and PET-CT, along with biopsy of involved tissues, are crucial for establishing a definitive diagnosis. Early and aggressive treatment is essential to prevent irreversible neurological damage and improve patient outcomes.
doi.org/10.1097/CM9.0000000000000514
Was this helpful?
0 / 0