High-grade B-cell lymphoma relapse presenting as neurolymphomatosis of the median nerve

Abstract

Neurolymphomatosis (NL) is the infiltration of lymphocytes into the peripheral nervous system in a haematological malignancy. We describe the imaging features of NL in a patient with relapsed Burkitt-like non-Hodgkin’s lymphoma on positron emission tomography (PET) and ultrasound. Imaging features on ultrasound are infrequently described and provide useful information in helping to establish an imaging diagnosis of NL. Features of NL in our patient included intense linear fluorodeoxyglucose-18 (¹⁸FDG) uptake on PET along the affected median nerve. B-mode ultrasound demonstrated concentric tubular thickening and loss of fascicular architecture. Perineural and intraneural vascularity was present on colour Doppler ultrasound. It is important to be able to correlate ultrasound findings to features observed on ¹⁸FDG-PET as this aids in diagnosis and in guiding potential surgical biopsy.

Background

Neurolymphomatosis (NL) is the infiltration of lymphocytes into the peripheral nervous system in the setting of a known or unknown haematological malignancy.¹ NL is a rare neurological manifestation of a haematological malignancy, most commonly found in patients with diffuse large B-cell lymphoma.² NL can affect peripheral or cranial nerves, nerve roots or nerve plexuses.¹ The pathophysiology of NL is unclear, and it can present at any time during the course of a haematological malignancy, as a first presentation or during disease relapse.² Currently, the diagnosis of NL requires histopathological confirmation.³ Imaging features of NL include intense fluorodeoxyglucose-18 (¹⁸FDG) uptake in the affected nerve on positron emission tomography (PET).^{1 4} On MRI, nerves affected by NL appear enlarged with nodular thickening.¹

We describe the imaging features of a biopsy proven case of NL of the median nerve in a patient with Burkitt-like Non-Hodgkin’s lymphoma (NHL). In addition, we demonstrate B-mode and colour Doppler ultrasound findings and emphasise the importance of the sensitivity of ¹⁸FDG-PET in the diagnosis of NL.

Case presentation

A 68-year-old woman with a history of Burkitt-like NHL presented with a 2-month history of progressive neuropathic pain involving the first to fourth digits of her left hand. The patient had undergone two cycles of CODOX-M (cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate) and IVAC (ifosfamide, etoposide, high-dose cytarabine) chemotherapy for high-grade stage IVb Burkitt-like NHL diagnosed 1 year prior and was in complete remission. Her medical history was unremarkable apart from hypertension. The patient was reviewed in clinic for neuropathic pain refractory to medical management. On examination, there was slight distal non-pitting oedema in the left forearm, reduced sensation in the median nerve distribution and a positive Tinnel’s sign.

Investigations

Whole body ¹⁸FDG-PET demonstrated an unusual pattern of spinal cord uptake raising the possibility of neuroinflammation. ¹⁸FDG uptake was demonstrated within the left forearm however was initially presumed and reported to be secondary to radiotracer extravasation at the site of injection (figure 1). Subsequent post-contrast MRI brain, neck and cervical spine did not demonstrate features of cerebral or cervical cord NHL disease or relapse. No central cause of the neuropathic left arm pain was identified and in particular, there was no evidence of cervical nerve root impingement.

Figure 1.

Fluorodeoxyglucose-18 uptake within the left forearm was initially assumed to be consistent with radiotracer extravasation. This area correlated with the ultrasound findings demonstrated in figures 2 and 3. Subsequent histological analysis demonstrated neurolymphomatosis with a high-grade diffuse lymphoid infiltrate in keeping with high-grade B-cell lymphoma. The unusual pattern of spinal cord uptake is marked with an arrow.

Due to the lack of imaging findings and the patient’s persistent symptoms, the possibility of a deep vein thrombosis of the left upper limb was entertained. Subsequent duplex Doppler ultrasound of the left upper arm was performed revealing an abnormal lobulated soft tissue mass measuring 2.4×2.9×10.4 cm along the length of the median nerve in the forearm (figure 2A). Internal vascularity was demonstrated on colour Doppler assessment (figure 2B). In addition, a separate 1.3×1.5×2.5 cm hypoechoic nodule with internal vascularity within the left cubital fossa was also noted. These findings corresponded to the ¹⁸FDG avid areas on the previous ¹⁸FDG-PET examinations. In combination, these findings were highly suspicious for Burkitt-like NHL recurrence of the median nerve.

Figure 2.

(A) Longitudinal and transverse B-mode ultrasound images demonstrating a grossly abnormal lobulated segment of the median nerve measuring 2.4×2.1×10.4 cm with loss of the normal fascicular architecture. (B) Colour Doppler imaging demonstrates perineural and intraneural vascularity within the abnormal lobulated segment of the median nerve proximally.

Subsequent open biopsy of the median nerve revealed a high-grade diffuse lymphoid infiltrate with morphological features consistent with relapse of a high-grade B-cell lymphoma.

Treatment

The patient was treated with radiotherapy to the left forearm.

Outcome and follow-up

Repeat ¹⁸FDG-PET demonstrated an excellent local response to targeted radiotherapy, however disease recurrence was demonstrated within the left axilla, adrenals, kidneys and mediastinum and the patient subsequently died 4 months later (figure 3).

Figure 3.

Repeat fluorodeoxyglucose-18 (¹⁸FDG)- positron emission tomography demonstrated resolution of the abnormal ¹⁸FDG uptake within the left forearm reflecting a good response to radiotherapy. Unfortunately, disease relapse was evident in the left axilla, adrenals, kidneys and mediastinum.

Discussion

NL is a rare, poorly understood entity, involving the infiltration of lymphocytes into a peripheral nerve in the setting of a haematological malignancy. It may present in the context of disease recurrence or as a first presentation. Of the cases reported, 90% of NL cases have been described in subtypes of NHL and 10% in acute leukaemia’s.¹ The exact pathogenesis of NL is poorly understood but involvement of the brachial plexus, lumbar plexus and cranial nerves, in addition to major peripheral nerves has been observed.^{4 5} The clinical presentation is that of painful peripheral neuropathy or radiculopathy, cranial nerve neuropathy, painless mononeuropathy or polyneuropathy.^{1 6}

There is currently no consensus for the imaging diagnosis of NL. Definitive diagnosis relies on nerve biopsy with histopathological confirmation; however, this carries the risk of permanent neurological deficit and is therefore not routinely performed on all patients with suspected NL.⁷ Imaging, in addition to clinical, biochemical and electrophysiological studies, thus play an important role in these patients.²

Unfortunately, despite linear tracer uptake within the affected left limb, the possibility of NL was overlooked in our patient with initial ¹⁸FDG-PET findings attributed to radiotracer extravasation. It is important for radiologists and nuclear medicine physicians to understand the imaging characteristics, utility and limitations of ¹⁸FDG-PET and MRI.

¹⁸FDG-PET is a sensitive method in the detection of NL. Ninety-one to 100% of patients with NL demonstrate ¹⁸FDG uptake within the peripheral nervous system.^{2 4 5} NL on ¹⁸FDG-PET typically shows patchy linear intense ¹⁸FDG uptake along the affected nerve.⁸ Nerve thickening and skip lesions have also been described.^{4 9}

The limitations of MRI were highlighted in our case. Good clinical examination and history are of great importance in the diagnostic process and in directing the radiologist to a body region of interest. Unfortunately, a negative MRI does not exclude NL as the patchy distribution and small size of many lesions in NL reduces the sensitivity for lesion detection.⁵ Reported MRI imaging features include thickened or nodular nerves and contrast enhancement, however these findings are not specific.⁹

Ultrasound, while not routinely performed, may add important diagnostic and prognostic information. Our case demonstrates ultrasound features of NL in a histologically confirmed case. Transverse and longitudinal B-mode ultrasound demonstrated concentric tubular thickening of the median nerve with loss of the fascicular architecture. The lesion’s contours were smooth with no features to suggest invasion of surrounding soft tissues, findings consistent with lymphocyte infiltration into a peripheral nerve. Colour Doppler ultrasound demonstrated perineural and intraneural vascularity. Our findings correlate with those of Vijayan et al,¹⁰ who demonstrated similar findings in three patients with histologically confirmed lymphoma subtypes. Perineural and intraneural vascularity has been hypothesised to relate to tumour angiogenesis and correlate with aggressive lymphoma subtypes.¹¹ Ultrasound may therefore provide prognostic information as well as allowing for assessment of an appropriate biopsy target. In our case, subsequent skin marking at the time of ultrasound, guided open surgical biopsy.

Learning points.

• While fluorodeoxyglucose-18 positron emission tomography (¹⁸FDG-PET) is the most sensitive imaging modality when diagnosing neurolymphomatosis (NL), ultrasound provides useful diagnostic and potential prognostic information.

• While lymphoma relapse in the central nervous system is more common, peripheral nerve involvement is also possible and should not be overlooked, especially in patients presenting with neuropathy or radiculopathy.

• It is important for radiologists, nuclear medicine physicians and clinicians to understand the expected findings of NL on ¹⁸FDG-PET, MRI and ultrasound.