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CASE REPORT
Year : 2023 | Volume
: 38
| Issue : 1 | Page : 44-49
A case series of neurolymphomatosis: role of fluorodeoxyglucose positron emission tomography-computed tomography scan reiterated
Manoj Gupta1, Sunil Pasricha2, Rayaz Ahmed3, Partha Sarathi Choudhury1
1 Department of Nuclear Medicine, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
2 Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
3 Department of Hemato-Oncology, Rajiv Gandhi Cancer Institute and Research Centre, New Delhi, India
Correspondence Address:
Dr. Manoj Gupta
Department of Nuclear Medicine, Rajiv Gandhi Cancer Institute and Research Centre, Rohini, New Delhi - 110 085
India
Source of Support: None, Conflict of Interest: None
CheckDOI: 10.4103/ijnm.ijnm_165_22
Abstract
Neurolymphomatosis is rarely encountered in high-grade lymphomas. In this case series, we retrospectively analyzed six neurolymphomatosis cases to look for possible risk factors, common and uncommon presentations, and the lessons learned. Neuropathic pain was the most common symptom with mono or polyradiculopathy in this series. However, all lymphomatous infiltrated nerves diagnosed on fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) were not symptomatic. The lumbar, brachial plexus, and trigeminal nerve were the most common sites and were depicted well on FDG PET/CT. Magnetic resonance imaging (MRI) of the brain better delineates cranial nerves and meningeal involvement. Cerebrospinal fluid flow cytometry was normal until meninges were involved. FDG PET/CT incrementally evaluated extra-neural disease sites, thus helping in deciding biopsy sites and further management. We concluded that a whole-body FDG PET/CT including limbs with MRI brain was the appropriate investigation for evaluating suspected neurolymphomatosis in advanced-stage diffuse large B-cell lymphoma.
Keywords: Cranial nerve, diffuse large B-cell lymphoma, fluorodeoxyglucose positron emission tomography-computed tomography, neurolymphomatosis, peripheral neuropathy
Introduction 
Neurolymphomatosis is rarely encountered in high-grade lymphomas.[1] It is nonspecific symptoms such as neuropathic pain, numbness, and paresthesia, warrant differentiation from postchemotherapy-induced neurotoxicities, radiation-induced plexopathy, inflammatory neuritis, benign or malignant compression neuropathy, autoimmune diseases, and paraneoplastic syndrome.[2],[3] Contrast-enhanced magnetic resonance imaging (MRI) is the preferred investigation for neuropathy, whereas fluorine-18 fluorodeoxyglucose positron emission tomography-computed tomography (FDG PET/CT) for high-grade lymphoma staging, response assessment, and suspected recurrence.[4],[5] In this case series, we reiterate the incremental value of FDG PET/CT in the investigation of suspected neurolymphomatosis.
Case Reports Case 1
A 78-year-old male stage IV diffuse large B-cell lymphoma (DLBCL) patient, involving supra and infra diaphragmatic lymph nodes, pulmonary nodules, and left adrenal gland, was treated with six cycles of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-mini-CHOP) chemotherapy. Fifteen days postchemotherapy, he presented with left leg radicular pain with no sensory-motor loss. An MRI lumbosacral spine revealed degenerative changes in the lumbar spine with disc desiccation, loss of disc height, and left L2-L3 foraminal narrowing indenting exiting nerve root. No enhancing vertebral/cord/meningeal lesion was noted. FDG PET/CT scan revealed avid left adrenal lesion and intense linear avidity in the left L5-S1 nerve root of the sciatic nerve, extending through greater sciatic foramina into the posterior compartment of the upper thigh [Figure 1]. Another focal avidity was noted in the right fifth cranial nerve (Vth CN) and V3 division, extending through the foramen oval to the infra-temporal fossa. Cerebrospinal fluid (CSF) flow cytometry was unremarkable. A left adrenal biopsy confirmed recurrence.
Figure 1: FDG PET/CT maximum intensity projection (a), axial (b and d), sagittal (c), and coronal (e) fused images. Metabolically active left L5-S1 sciatic nerve roots (block arrows, image a and e), right trigeminal nerve (arrows, image a-c), and left adrenal (curved arrow, image d) involvements. FDG PET/CT: Fluorodeoxyglucose positron emission tomography-computed tomographyCase 2
A 48-year-old male stage IV DLBCL patient, involving supra and infra diaphragmatic lymph nodes, spleen, and bone marrow, was treated with six cycles of R-CHOP chemotherapy with the normal end-of-treatment FDG PET/CT scan. Two months later, he presented with weakness and neurological pain in the right upper and lower limbs. A cervical spine MRI revealed no enhancing lesion in the cord, meninges, and bones. FDG PET/CT showed a linear avid lesion in the right ulnar nerve, left brachial plexus, and left obturator nerve [Figure 2]. An avid nodular thickening in the left 6th intercostal space and fusiform nodular thickening in the right sciatic nerve was also noted. Right sciatic nerve biopsy was positive [Figure 3].
Figure 2: FDG PET/CT maximum intensity projection (a), coronal (b), and axial (c) fused images. Metabolically active linear tracer uptake in right ulnar (arrows, image a and b), right sciatic (block arrows, image a and c), and left obturator (curve arrow, image c) nerves. FDG PET/CT: Fluorodeoxyglucose positron emission tomography-computed tomography
Figure 3: (a) CT-guided biopsy from the right sciatic nerve lesion showed diffuse infiltration by the neoplastic lymphoid population of cells (H and E, ×40). (b) The neoplastic lymphoid cells were predominantly large with vesicular nuclei and conspicuous nucleoli exhibiting brisk mitosis (arrows) (H and E, ×400). (c) Neoplastic large lymphoid cells were diffusely positive for CD20, confirming the recurrence of DLBCL Diaminobenzidine (DAB, ×100). (d) CD3 highlights background nonneoplastic reactive T-lymphoid cells (DAB, ×100). (e) MUM-1 showed diffuse nuclear immunoexpression with strong intensity (DAB, ×100). (f) BCL6 showed diffuse nuclear immunoexpression with moderate intensity (DAB, ×100). CT: Computed tomography, DLBCL: Diffuse large B-cell lymphomaCase 3
A 36-year-old male stage IV DLBCL with liver lesions, supraclavicular lymph node, and left paravertebral lesion, was treated with six cycles of R-CHOP chemotherapy. Two months post-chemotherapy, he presented with pain lower back and thighs. MRI showed diffuse enhancing thickening of the bilateral Vth CN, V2-V3 divisions, bilateral hypoglossal nerves, and olfactory fossa. Diffuse enhancing thickening of exiting nerve roots of C7-D2, lower dorsal and lumbosacral region and altered signal intensity in multiple dorsal and lumbosacral vertebral bodies and posterior elements were noted. FDG PET/CT scan revealed corroborative to MRI [Figure 4]. L3 vertebra and nerve root dural layer biopsy confirmed recurrence [Figure 5].
Figure 4: FDG PET/CT maximum intensity projection (a), axial (b and c), and sagittal (d) fused images. Metabolically active multiple focal tracer uptake in bilateral neural forminas in the cervical and dorsal spine (Black block arrow, image a). Focal tracer uptake was seen in bilateral trigeminal (white block arrows, images b and c), right hypoglossal (white curve arrow, image c) nerves, and intense tracer uptake in multiple lumbar vertebrae (white arrow, image d). FDG PET/CT: Fluorodeoxyglucose positron emission tomography-computed tomography
Figure 5: (a) CT-guided L3 vertebra and nerve root dural layer core biopsy showed fibro-adipose tissue infiltrated by the atypical lymphoid population of cells. Foci of ischemic necrosis were also seen (arrow) (H and E, ×40). (b) Neoplastic lymphoid cells were predominantly large and were admixed with reactive lymphoid infiltrate. Significant mitosis noted (arrow) (H and E, ×400). (c) Neoplastic large lymphoid cells were positive for CD79a, confirming the recurrence in a known case of DLBCL. The admixed reactive lymphoid cells were negative (DAB, ×200). (d) Neoplastic large lymphoid cells were however negative for CD20 (as the patient had received rituximab) (DAB, ×100). (e) Neoplastic large lymphoid cells showed nuclear strong immunoexpression for BCL6 (DAB, ×200). (f) Mindbomb E3 ubiquitin protein ligase 1 (MIB)-1 (ki-67) index was 60%, and immunoexpression was seen in large neoplastic lymphoid cells (DAB, ×200). CT: Computed tomography, DLBCL: Diffuse large B-cell lymphomaCase 4
A 38-year-old male was diagnosed with stage IV DLBCL involving bilateral Vth CN, leptomeninges, and bone marrow. CSF flow cytology was positive for atypical cells. He was treated with five cycles of R-CHOP and one cycle of cyclophosphamide, vincristine, doxorubicin, and methotrexate. He developed central nervous system relapse within 3 months and was treated with high-dose methotrexate as per DeAngelis protocol, followed by R-ibrutinib-based chemotherapy. Follow-up MRI showed progressive enhancing thickening of bilateral Vth CN extending along Meckel's cave and foramen ovale. MRI lumbosacral spine showed bilateral sacral nerve root-enhancing thickening at L5-S1-2 levels. FDG PET/CT scan showed avid bilateral Vth CN thickening extending into the foramen ovale, with focal meningeal thickening along the left temporal lobe [Figure 6]. Diffuse linear avidity was seen in the bilateral brachial plexus, its branches, and the left 7th dorsal neural foramen, which extended into the respective intercostal space. Bilateral lumbosacral plexus also showed avid liner thickening involving L5-S1-S2 nerve roots and sciatic nerves extending into lower limbs. A focal lytic lesion with a soft-tissue component was also seen in the left femur mid-shaft and biopsy from which was positive.
Figure 6: FDG PET/CT maximum intensity projection (a), axial (b-e) fused images and T1W contrast-enhanced images (f-i). Focal tracer uptake was seen in bilateral trigeminal (black arrows, image a, b, f and g), bilateral brachial plexus (curved up arrows, image a), left 7th intercostal nerve (white curve arrow, image c), diffuse meningeal thickening (image h), with thickening of the exiting nerve roots in the bilateral lower dorsal and lumbosacral nerve roots (image a, d and i), and lytic lesion with soft tissue along the posterior aspect of left femur midshaft region (white elbow arrow, image e). FDG PET/CT: Fluorodeoxyglucose positron emission tomography-computed tomographyCase 5
A 76-year-old male patient with stage III DLBCL involving supra- and infra-diaphragmatic lymph nodes, and spleen was treated with six cycles of R-CHOP chemotherapy. Seven months end of chemotherapy, he presented with pain in the left scrotal and perianal regions. MRI pelvis revealed enhancing thickening of left S1 to S3 nerve roots. FDG PET/CT also showed linear avid thickening in the left S1 to S3 nerve root region [Figure 7]. However, the rest of the body showed no avid lesions. Left S2 nerve root biopsy confirmed recurrence.
Figure 7: FDG PET-CT maximum intensity projection (a), fused sagittal (b), coronal (c) axial (d), and TIW post contrast fat saturated sagittal (e) and coronal (f) images. Metabolically active enhancing linear thickening in sacral canal extending in S1-S3 left sacral foramina (Block arrows). FDG PET/CT: Fluorodeoxyglucose positron emission tomography-computed tomographyCase 6
A 49-year-old male patient was diagnosed with stage IV DLBCL involving supra and infra diaphragmatic lymph nodes, liver, and right pleural thickening. Post six cycles of R2-CHOP chemotherapy, FDG PET/CT scans showed a complete response. Three months later, he presented with pain with paraesthesia in both forearms and the distal half of both soles. Bilateral neck region swelling and hardness were also reported. FDG PET/CT showed multiple FDG-avid supra- and infra-diaphragmatic lymph nodes with multiple fusiform and focal linear thickening in the left brachial plexus, bilateral ulnar nerve, right sciatic nerve, and bilateral tibial nerves [Figure 8]. Right axillary lymph node biopsy revealed DLBCL infiltration.
Figure 8: FDG PET-CT maximum intensity projection (a), coronal (b-d) fused images. Scan showed metabolically active lymph nodes with fusiform and linear thickening in the left brachial plexus, bilateral ulnar nerve (in arm and forearm, arrows, image a and c), right sciatic nerve and bilateral tibial nerves (block arrows, image a and d). FDG PET/CT: Fluorodeoxyglucose positron emission tomography-computed tomography Discussion Neoplastic plexopathy may develop in high-grade lymphomas, prostate, breast, and head-and-neck cancers.[6] Perineural invasion is a more common pathology in other cancer types, while in lymphoma, it is due to direct infiltration of endoneurium.[7] DLBCL is the most reported subtype (75%) with neurolymphomatosis, as also seen in our case series.[8] It may manifest during diagnosis (26%) or, more commonly, during the recurrence or progression of the disease.[9] We had five cases during recurrence or progression, while one patient had cranial neurolymphomatosis at the time of diagnosis. Neurolymphoma commonly involves peripheral nerves, with the lumbosacral plexus, brachial plexus, and trigeminal nerves being the preferred sites.[10] Neuropathic pain is the most common symptom with single or multiple dermatomes distributions and different degrees of involvement. CSF examination is usually unremarkable until meninges involve, as in our series, only case 4 had positive CSF.[11] Nerve conduction studies mostly show nonspecific changes.[12] Nerve biopsy is the gold standard but may be a false-negative due to patchy involvement.[13] MRI shows T2 hyperintensity with diffusion restriction and mild-to-moderate post-contrast enhancement.[14] Length of nerve involvement is difficult to assess on MRI as reactive neuritis may show similar changes. Nonetheless, mri is indispensable due to superb soft-tissue contrast for intracranial disease, and better delineation of neural foramina, disc, and dural pathology. An international collaborative group reported mri positivity in 77% of neurolymphoma while 84% for FDG PET/CT.[10] FDG PET/CT neurography better illustrates peripheral neuropathy and its extent.[15],[16],[17],[18],[19],[20] Identifying extra-neural disease sites was another incremental value of FDG PET/CT scan.
Conclusions We concluded that a whole-body FDG PET/CT including limbs with MRI brain was the appropriate investigation for evaluating suspected neurolymphomatosis in advanced-stage DLBCL.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
References 
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