Accessory Nerve Palsy as the Initial Manifestation of Chronic Lymphocytic Leukemia: A Case Report

Introduction

Chronic lymphocytic leukemia (CLL) is a hematological malignancy leading to a predominance of monoclonal B lymphocytes in peripheral blood. It is one of the most common types of leukemia in adults, with rising global incidence annually. In the United States, CLL makes up around one-third of all new leukemia cases, and around 1% of cancers overall. In 2025, an estimated 23 690 new cases and 4460 deaths from CLL are expected. CLL is slightly more common among men than women [1]. Patients with CLL have a median overall survival of 21 years [2].

Central and peripheral nervous system complications are rare in CLL [3]. The causes for such presentations are hypothesised to be from secondary infections, metastasis, growth of disease, or iatrogenic [4].

Central nervous and peripheral nervous system complications in CLL have both been studied. Lymphocyte infiltration of the central nervous system (CNS) causing neurological symptoms in CLL is rare [5]. Similarly, the connection between peripheral neurological manifestations and CLL is not yet fully understood, making it challenging to determine whether they result solely from neoplastic processes or are influenced by other factors [2].

To our knowledge, there are no literature records of accessory nerve palsy as the first presenting feature of CLL. We record the first case in this report, addressing that gap and adding to the limited understanding of neurological manifestations in CLL. A structured search was performed in PubMed and other databases, details of which are included in the Discussion section.

This case highlights the importance of including hematological malignancy in the differential diagnosis of cranial nerve palsies, especially when accompanied by lymphadenopathy. It also suggests that cranial neuropathies can be early signs of systemic hematological disease. Understanding these rare manifestations may prompt earlier diagnosis, reducing diagnostic delay in similar patients.

This case also demonstrates the importance of a multidisciplinary approach, as it involved input from Hematology, Ear, Nose, and Throat (ENT), and Orthopedic Surgery teams. Hence, this report offers valuable insights not only for hematologists but also for clinicians in ENT, orthopedic surgery, and possibly neurologists, who may all encounter similar presentations.

Case Report

We present the case of a woman in her 40s who presented to the ENT clinic on a fast-track pathway with a 4-week history of severe left-sided neck pain, difficulty moving her left shoulder, and a left-sided tender neck swelling. This constellation of symptoms raised concern for a cranial nerve palsy. She had no other symptoms on presentation. There was no relevant past medical history, which made pre-existing neurological or haematological conditions less likely. She denied smoking and had no previous radiation exposure or family history of leukemia or other cancers, reducing the likelihood of environmental or hereditary risk factors for malignancy. On examination, she had left-sided trapezius muscle weakness, weak left shoulder abduction and left scapula winging. A neck examination revealed multiple tender lymph nodes in the left posterior triangle, which were easily palpable. There was no other lymphadenopathy. A flexible nasendoscopy was performed and showed no abnormality in the upper areo-digestive tract.

The patient was referred to our local specialist ENT service and the multidisciplinary team (MDT) for further investigation. The ENT, Hematology, and Orthopedic Surgery teams all had early involvement in this case. At the initial ENT consult, considering the persistent neck swelling, a full blood count (FBC) and peripheral blood film were arranged alongside an ultrasound and fine-needle aspiration (FNA) for cytology. Furthermore, cross-sectional imaging was performed with a magnetic resonance imaging (MRI) neck and a whole-body staging computed tomography (CT) scan.

The FBC revealed a normal hemoglobin of 132, a lymphocytosis with a white cell count (WCC) of 49.5, lymphocytes of 44.8, platelets of 272, and neutrophils of 3.8. Flow cytometry of peripheral blood was diagnostic of a kappa restricted B-cell CLL. Molecular studies showed that the leukemia was associated with the CDKN2A mutation at 4% VAF and KMT2D at 58% VAF, and negative for TP53 mutations.

The renal, liver, bone, and thyroid function tests were normal and viral screen, including Hepatitis C virus, Hepatitis B virus, and HIV virus, were negative.

The beta-2 micro-globulin was 2.14, paraprotein was absent, and she had normal immunoglobulins levels. Her International Prognostic Index for Chronic Lymphocytic Leukemia was low risk [6].

The Hematology team arranged a CT scan of the thorax, abdomen, and pelvis, which found enlarged lymph nodes bilaterally in the neck and axilla up to 1.1 cm in the short axis, and further lymphadenopathy in the retroperitoneum, particularly in the para-aortic region, approximately 0.7 cm in the short axis, and further lymphadenopathy bilaterally in the inguinal regions up to 0.9 cm. Hepatosplenomegaly was absent.

The orthopedic surgeons reviewed the case and confirmed an accessary nerve palsy with otherwise normal shoulder anatomy. Electrophysiological and nerve conduction studies were performed and confirmed the reported findings as an accessory nerve palsy. Separately, an MRI shoulder was performed and did not reveal any other pertinent findings.

A FNA of the lymph node in the left posterior triangle was performed because of suspicion of a Richter’s syndrome by Hematology. She underwent a positron emission tomography-CT (PET-CT) scan due to the concerns raised that her newly diagnosed CLL may have transformed to a high-grade lymphoma as suggested by the development of a unilateral left accessory nerve palsy. The PET-CT scan confirmed the clinical findings of small-volume disease, with all the lymph nodes measuring less than 1 cm in diameter. The lymph nodes had very low maximum metabolic activity and there was no evidence of a high-grade lymphoma.

The case was managed by an MDT from the perspective of her CLL and accessory nerve palsy. The Hematology team actively monitored the patient’s CLL, and she underwent routine vaccinations for COVID-19, influenza, and pneumococcus. The Orthopedics team arranged follow-up with nerve conduction studies after 8 weeks, and this confirmed complete resolution of the accessory nerve palsy from the electrophysiological perspective. After 2 months, the accessory nerve palsy had clinically mostly spontaneously recovered, with the patient able to lift her left arm almost normally.

Discussion

This case report details an unusual first presentation of CLL as an accessory nerve palsy. Three specialities were involved using an MDT approach that utilized multiple investigations to arrive at the diagnosis of CLL. The patient currently is following up with the Hematology team.

The MDT approach was central to this patient’s diagnostic journey. The ENT team was initially involved to evaluate the neck mass and cranial nerve dysfunction. Given the suspicion of a structural lesion compressing the accessory nerve, MRI of the neck and shoulder was performed. Orthopedic Surgery was consulted to assess for musculoskeletal causes of scapular winging, and nerve conduction studies were arranged to characterize the deficit. As lymphadenopathy was evident on examination and imaging, Hematology was consulted early, leading to further blood tests and flow cytometry, which confirmed a diagnosis of CLL. Due to the isolated neurological involvement and the possibility of Richter’s transformation, a PET-CT scan was performed. Although no evidence of high-grade transformation was found, this step was essential to exclude aggressive pathology and guide subsequent follow-up. This case illustrates how collaborative, stepwise clinical reasoning involving multiple specialties was key to establishing a rare diagnosis.

CLL most commonly presents with painless lymphadenopathy. It can also be detected on routine FBC with incidental lymphocytosis. Treatment options are diverse, ranging from conservative approaches to immunotherapy [7].

Strati et al conducted a study that investigated the prevalence of CNS complications in CLL patients [8]. The study investigated 4174 patients with known CLL between the years 1999 and 2014; 172 out of this cohort developed neurological complications. This subset of patients then underwent lumbar puncture and/or MRI of the CNS. The study revealed that CLL infiltration of CNS was found in only 18 of the cases (10%). They concluded that direct CNS infiltration only accounts for a minority of the causes of neurological complications in CLL.

Strati et al reported that cranial nerve deficits made up 14% of the neurological complications (24 patients) [8]. However, the report did not specify if accessory nerve palsy was among the neurological complications. Interestingly, all the neurological complications reported were in patients with an established CLL diagnosis. The study did not report any cases of accessory nerve palsy as the presenting concern that led to the diagnosis of CLL.

A retrospective study conducted by Bower et al assessed 962 patients with CLL to examine development of neurological complications [3]; 109 patients (11.3%) of this cohort developed neurological complications. Herpes zoster infection accounted for 69 cases of this subset (63%). Direct CLL infiltration of CNS was rare; only found in 8 cases (7.3%). Again, none of the reported complications included an accessory nerve palsy.

Both studies provide insight into the prevalence of neurological complications in CLL. However, their retrospective design limited their ability to establish causal relationships. Additionally, rare neurological manifestations (such as accessory nerve palsies) may be underrepresented due to potential selection bias or underreporting in medical records. Importantly, in both studies, all the reported neurological complications were in patients with an already established CLL diagnosis, and there is no mention of accessory nerve palsy as the initial presenting feature.

We identified 2 cases illustrating cranial nerve involvement in CLL, albeit with important differences from our case. Maleita et al described a patient with untreated but previously diagnosed CLL who developed optic neuropathy as the first neurological complication [9]. Also, Timmers et al reported a case of an elderly woman with known CLL who presented with oculomotor nerve palsy nearly 2 years after her initial diagnosis [5].

The similarities between these cases and our case is that they all involved focal cranial nerve palsy and required multidisciplinary evaluation. The most notable difference from our case is that our patient had no known diagnosis of CLL at presentation, and the accessory nerve palsy directly triggered the diagnostic process. Additionally, our case involved a concurrent cervical lymphadenopathy, which, while not uncommon in CLL, was key in guiding further investigation.

Together, these cases show that cranial nerve palsies can appear at different stages of CLL, either in the context of established disease or, as in our report, as the first clinical sign. This demonstrates the importance of considering hematological malignancies in the differential diagnosis of unexplained cranial neuropathies, especially when accompanied by regional lymphadenopathy.

We considered various causes for the accessory nerve palsy in our patient, who had no history of trauma, surgery, or procedures involving the posterior triangle of the neck, making iatrogenic injury unlikely. An infectious etiology was considered, but the patient had no history of recent infection and showed no systemic signs. Autoimmune causes, such as vasculitis and sarcoidosis, were considered but were not supported by systemic symptoms or laboratory findings. The possibility of idiopathic presentation was considered, but given the presence of pathological lymph nodes and the blood film confirming CLL, this was accepted as the final diagnosis.

PubMed, BMJ Case Reports, and the American Journal of Case Reports were searched using the terms “chronic lymphocytic leukemia”/”chronic lymphocytic leukemia” AND “accessory nerve”. “Case Reports” filter was applied. There were no relevant articles found. To our knowledge, there are currently no reported cases of accessory nerve palsy as a presenting sign of CLL. Therefore, this highlights a gap in the current literature and shows why further research is needed to determine whether such presentations can be the signal for diagnosis of CLL.

This case report does have several limitations. Given it is a single patient observation, it cannot establish a causal relationship between CLL and accessory nerve palsy, only an association. Secondly, although the diagnosis of CLL and accessory nerve palsy was well established, the underlying mechanism linking the 2 remains unclear, as no histological confirmation of nerve infiltration or direct involvement was available. Finally, the follow-up was short, and long-term neurological outcomes beyond initial recovery remain unknown.

Conclusions

RECOMMENDATIONS:

Clinicians should include hematological causes in the differential diagnosis when faced with cranial nerve palsies of unclear origin, especially when accompanied by lymphadenopathy. Early involvement of haematology can expedite diagnosis and avoid unnecessary investigations or delays.

Further research is needed to better understand the neuro-oncological spectrum of CLL and whether certain neurological signs can be early markers of disease.