SAINT LOUIS, MO — Diagnosing B-cell lymphoma-associated mononeuritis multiplex, a peripheral neuropathy, can be challenging because of its rarity and the potential co-existence of other causes of the symptoms.
A study team led by researchers from Saint Louis University and including participation from the John D. Dingell VAMC in Detroit recently reported a case of a 74-year-old male who initially presented with left cranial neuropathies followed by right-sided extremity weakness with hyporeflexia, right facial involvement, and subsequently asymmetric weakness and multifocal muscle wasting.
The article in the journal Cureus noted minor improvements with multiple rounds of steroid treatment. The diffuse large B-cell lymphoma diagnosis wasn’t established until six months later, however, after a repeat mediastinal lymph node biopsy and cerebrospinal fluid cytology. 1
“A nerve biopsy demonstrated severe axonal neuropathy with loss of axons in all fascicles without evidence of vasculitis,” the authors explained. “A muscle biopsy showed atrophy in both type 1 and type 2 fibers. A presentation of mononeuritis multiplex warrants concern for B-cell lymphoma, mainly when other mechanisms of peripheral neuropathy are less likely.”
Background information in the report pointed out that B-cell lymphoma is the most common non-Hodgkin lymphoma (NHL); patients sometimes present with diverse extranodal and extramedullary symptoms.
“One pattern of lymphoma-associated peripheral neuropathy is mononeuritis multiplex (MNM), a distinctive neuropathy type marked by painful, disproportional, and asymmetric motor and sensory symptoms involving two or more separate peripheral nerves spontaneously,” according to the report. “MNM is observed across a broad spectrum of conditions, including diabetes mellitus, amyloidosis, neurosarcoidosis, infections, rheumatological disorders, hematological disorders, and malignancies (lymphoma, B-cell leukemia, carcinoid tumors, and small-cell lung cancers).”
The authors explained that, in lymphoma, MNM can arise from neoplastic processes, such as neurolymphomatosis (NL), where lymphoma cells directly invade the peripheral nervous system (PNS), paraneoplastic effects, or autoimmune-mediated mechanisms. “Diagnosing B-cell lymphoma-associated MNM can be challenging,” they wrote. “Although its connection with malignancies is less common, MNM’s emergence should serve as an alarming indication for early workup of underlying neoplastic sources, facilitating early treatment and averting disease progression.”
In the recent article, the authors presented a rare case of B-cell lymphoma manifesting as mononeuritis multiplex. A 74-year-old man was initially discharged with oral prednisone for Bell’s palsy after he presented with an acute onset of left-sided facial weakness for two days and droopiness of the left eyelid for one day. He had a past medical history of atrial fibrillation. A month later, the man developed right arm and leg weakness and an abnormal gait.
Two months after his initial presentation, improvement occurred with his left facial symptoms. Brain magnetic resonance imaging (MRI) showed asymmetric enhancement of the left facial nerve, while an MRI of the cervical spine showed cervical spondylosis prominently at C5-C6, with no signal changes within the cord.
The patient displayed slightly reduced strength in the distal right upper extremity and proximal right lower extremity, diminished right patellar and Achilles reflexes, and decreased pinprick sensation in the right leg. Examining clinicians also detected elevated cerebrospinal fluid protein and lambda light chains were detected.
Even though computed tomography (CT) of the chest showed mediastinal lymphadenopathy, lymph node biopsy results were benign. The patient was treated with three days of 1g pulse intravenous methylprednisolone (IVMP) and showed minor improvement.
Four months after his initial presentation, he presented with right facial droop and right upper extremity weakness. Left internal auditory canal enhancement and a new enhancement of the right facial nerve was found with a repeat MRI.
The man again received 1g of IVMP with valacyclovir for Bell’s palsy. A CT of the abdomen/pelvis showed small, solid-appearing cysts at the upper pole of the right kidney. Ruled out by laboratory analysis were monoclonal gammopathy of undetermined significance and myeloma; a paraneoplastic panel was normal. The patient was discharged on a prednisone taper.
Six months after his initial presentation, the patient had muscle wasting in the intrinsic hand muscles on the right side and in the deltoid and biceps on the left side. Physical examination revealed decreased motor function in fingers and lower extremities on the right side, deltoid and biceps on the left side, and diminished reflexes in bilateral lower extremities.
The authors reported that electromyography/nerve conduction studies showed asymmetric, severe sensorimotor axonal peripheral polyneuropathy with severe active and chronic denervation and motor unit drop-out, consistent with a chronic MNM pattern.
The next day, the patient had a hypovolemic shock, worsening right upper and lower extremity weakness, and associated muscle atrophy. A nerve biopsy showed severe axonal neuropathy with 50%-60% axonal loss in all fascicles without evidence of vasculitis, while a muscle biopsy showed type 1 and type 2 fiber atrophy.
Diffuse large B-cell lymphoma (DLBCL) was revealed with repeat mediastinal lymph node biopsies and cerebrospinal fluid cytology. While rituximab plus cyclophosphamide-doxorubicin-vincristine-prednisone (R-CHOP) was initially recommended for treatment, it was recognized that the patient was taking amiodarone for atrial fibrillation. The combination of amiodarone and high-dose cyclophosphamide in R-CHOP put him at risk of lung toxicity. “Therefore, the patient received one treatment cycle of bendamustine and rituximab,” the authors wrote. “It was not intrathecal. However, after treatment, he developed sepsis secondary to community-acquired pneumonia and died in the intensive care unit from medical complications.”
The authors said their B-cell lymphoma-associated MNM case report sought to emphasize the significance of considering lymphoma as a potential cause of asymmetric cranial neuropathies and asymmetric, asynchronous, painful, sensorimotor axonal peripheral polyneuropathy.
“Although B-cell lymphoma-associated MNM is uncommon and its clinical presentation can mimic other commonly seen peripheral neuropathies, its prognosis and response to treatment are unique,” the authors concluded. “Timely workup of lymphoma is warranted when empiric treatment of neuropathies yields no improvement. Future investigations into B-cell lymphoma-associated MNM can help elucidate the mechanisms, diagnostic approaches, and therapeutic strategies for this rare condition.”
- Chen Y, Wang Y, Corrigan J, Memon AB. B-Cell Lymphoma Presenting With Seventh Cranial Nerve Palsy and Mononeuritis Multiplex: A Case Report and Comprehensive Literature Review. Cureus. 2023 Sep 10;15(9):e44983. doi: 10.7759/cureus.44983. PMID: 37822434; PMCID: PMC10564262.
