Abstract

Neurolymphomatosis is a rare manifestation of non-Hodgkin's lymphoma (NHL) and is characterized by infiltration of the nerves by neoplastic lymphoid cells and is seen in up to 0.2% of all NHL cases. Diagnosing this syndrome is quite a challenge to the hematologists given the vague symptoms and signs and the low incidence. Newer imaging modalities such as positron emission tomography–computed tomography and magnetic resonance imaging have enabled early diagnosis with a sensitivity reaching up to 100%. Despite a variety of therapies reported in the literature for the treatment, the prognosis is very poor. We report a 46-year-old male diagnosed to have NHL–diffuse large B-cell lymphoma and treated with rituximab, cyclophosphamide, vincristine, and prednisolone (R-CHOP) therapy who presented with left brachial plexus neurolymphomatosis as the initial feature of disease relapse.

| Figure 1: Magnetic resonance imaging of the thorax shows diffuse thickening of the roots, trunks, cords, and divisions of the left brachial plexus (arrow mark), which is hyperintense on T2 and STIR sequence

| Figure 2: Positron emission tomography–computed tomography shows increase fluorodeoxyglucose avidity (maximum standardized uptake value of 15.67) of the left brachial plexus (arrow mark)

Discussion

NL is a unique condition that occurs due to direct infiltration of the endoneurium of the nerve by neoplastic lymphocytes.[1] It has more frequently been observed in patients with NHL. DLBCL is the most common histological subtype, followed by follicular lymphoma and very rarely T-cell lymphomas. NL may be the primary presentation of NHL or may present as disease progression or relapses.[2],[4]

The clinical manifestations of NL depend on the cranial and peripheral nerves involved. Baehring et al. [2] have described four patterns of clinical presentation: (i) painful involvement of nerves and roots, (ii) cranial neuropathy with or without pain, (iii) painless involvement of peripheral nerves, and (iv) painful or painless involvement of single peripheral nerve. Peripheral nervous system involvement is usually in the form of mononeuropathy and rarely polyneuropathy, isolated sciatic nerve, median nerve, and ulnar nerve involvements have also been reported.[4],[5],[6],[7],[8],[9],[10]

Brachial plexus involvement due to NL has been documented with clinical presentation ranging from focal distal mononeuropathy to multifocal brachial plexopathy.[6],[7],[8],[9],[10] Kamiya-Matsuoka et al., in a case series of six patients with NL, found that four of them had NHL-DLBCL. Brachial plexus involvement was seen in three patients, and they had presented with unilateral upper limb weakness and hyporeflexia.[8] The fourth patient had radiculopathy of the left T1 and right L5 spinal nerves. Choi et al. have reported two cases of NL of the brachial plexus and both were DLBCL histological subtype. One patient developed right arm weakness and pain during remission of the disease following eight cycles of R-CHOP chemotherapy. The second patient, a 50-year-old female, presented with right upper limb pain and weakness during the course of therapy for primary central nervous system (CNS) lymphoma.[9] Bourque et al. have also reported three cases with NL of the brachial plexus: one patient had cutaneous B-cell NHL and three patients had NHL-DLBCL [Table 1].[10] Systemic chemotherapy (CHOP/R-CHOP) with intrathecal methotrexate and local radiotherapy (35 to 40 Gy in 15 to 18 fractionated doses) have been the main modalities of treatment in these patients. Intravenous immunoglobulins and plasma exchange have also been used (8.10). NHL patients who achieved disease remission showed neurological improvement and have had better overall survival (OS) compared to those patients who had disease progression or relapse during therapy. These patients showed transient or no improvement in their neuropathy and had a poorer OS [Table 1].

Table 1 Clinical profile and treatment outcome of patients with neurolymphomatosis

NL can be diagnosed by radiologically MRI and PET-CT. A MRI study in NL thickening of the involved peripheral nerves or roots with isointensity to muscle on T1 sequence, hyperintensity on T2 or STIR signaling, and significant focal diffuse gadolinium enhancement.[4],[11] The sensitivity of MRI ranges between 70% and 80%[2],[3] PET-CT appears to be the single most sensitive imaging tool in identifying NL with a sensitivity reaching up to 100%. The affected nerve shows enhanced FDG uptake due to increased metabolic activity. PET-CT invariably confirms NL in previously diagnosed and treated cases of NHL.[4],[5] When both the imaging modalities have combined, the diagnosis of NL is more or less certain, and nerve biopsy may not be required. Treatment protocols for NL have not standardized because of the rarity of this condition.

In the majority of published articles, systemic chemotherapy R-CHOP with added HD-MTX has been the treatment of choice. The latter penetrates the blood–brain barrier and reduces the risk of the CNS disease relapse.[4],[12]z Radiotherapy has a role limited to reducing neuropathic pain and local disease control.[12] The prognosis of patients with NL is extremely poor with a 36-month survival of only 24% and median survival of 10 months.[4] The poor survival is probably due to the fact that NL is more frequently seen in more aggressive disease and chemotherapy resistance, both of which are associated with early relapses.[4]

Our patient presented with left brachial plexopathy 1 year after successful treatment of NHL with R-CHOP therapy as a sole manifestation of disease relapse. He had no evidence of systemic relapse. He has shown neurological improvement after two cycles of R-DHAP salvage chemotherapy and HD-MTX but died due to post-chemotherapy neutropenic septicemia after the third cycle. In conclusion, we would like to state that NL must be suspected in any NHL patients presenting with cranial nerve or peripheral nerve involvement as the diagnosis is often missed because it mimics nonneoplastic and paraneoplastic neuropathies. Integrating clinical, laboratory results and imaging findings helps in confirming the diagnosis and starting early treatment.

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.

Conflict of Interest

There are no conflicts of interest.

References

1. Hughes RA, Britton T, Richards M. Effects of lymphoma on the peripheral nervous system. J R Soc Med 1994; 87: 526-30
2. Baehring JM, Damek D, Martin EC, Betensky RA, Hochberg FH. Neurolymphomatosis. Neuro Oncol 2003; 5: 104-15
3. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E. et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano classification. J Clin Oncol 2014; 32: 3059-68
4. Grisariu S, Avni B, Batchelor TT, van den Bent MJ, Bokstein F, Schiff D. et al. Neurolymphomatosis: An International Primary CNS Lymphoma Collaborative Group report. Blood 2010; 115: 5005-11
5. Sideras PA, Matthews J, Sakib SM, Ofikwu F, Spektor V. Neurolymphomatosis of the peripheral nervous system: A case report and review of the literature. Clin Imaging 2016; 40: 1253-6
6. Swarnkar A, Fukui MB, Fink DJ, Rao GR. MR imaging of brachial plexopathy in neurolymphomatosis. AJR Am J Roentgenol 1997; 169: 1189-90
7. Liang R, Kay R, Maisey MN. Brachial plexus infiltration by non-Hodgkin's lymphoma. Br J Radiol 1985; 58: 1125-7
8. Kamiya-Matsuoka C, Shroff S, Gildersleeve K, Hormozdi B, Manning JT, Woodman KH. Neurolymphomatosis: A case series of clinical manifestations, treatments, and outcomes. J Neurol Sci 2014; 343: 144-8
9. Choi YJ, Shin JA, Kim YH, Cha SJ, Cho JY, Kang SH. et al. Neurolymphomatosis of brachial plexus in a patient with non-Hodgkin's Lymphoma. Case Rep Oncol Med 2013; 2013: 492329 DOI: 10.1155/2013/492329.
10. Bourque PR, Warman Chardon J, Bryanton M, Toupin M, Burns BF, Torres C. Neurolymphomatosis of the brachial plexus and its branches: Case series and literature review. Can J Neurol Sci 2018; 45: 137-43
11. Thawait SK, Chaudhry V, Thawait GK, Wang KC, Belzberg A, Carrino JA. et al. High-resolution MR neurography of diffuse peripheral nerve lesions. AJNR Am J Neuroradiol 2011; 32: 1365-72
12. Lagarde S, Tabouret E, Matta M, Franques J, Attarian S, Pouget J. et al. Primary neurolymphomatosis diagnosis and treatment: A retrospective study. J Neurol Sci 2014; 342: 178-81

Address for correspondence

Publication History

Received: 08 October 2019
Accepted: 03 January 2020
Article published online:
17 May 2021

© 2020. Indian Society of Medical and Paediatric Oncology. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/.)

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| Figure 1: Magnetic resonance imaging of the thorax shows diffuse thickening of the roots, trunks, cords, and divisions of the left brachial plexus (arrow mark), which is hyperintense on T2 and STIR sequence

| Figure 2: Positron emission tomography–computed tomography shows increase fluorodeoxyglucose avidity (maximum standardized uptake value of 15.67) of the left brachial plexus (arrow mark)

References

1. Hughes RA, Britton T, Richards M. Effects of lymphoma on the peripheral nervous system. J R Soc Med 1994; 87: 526-30
2. Baehring JM, Damek D, Martin EC, Betensky RA, Hochberg FH. Neurolymphomatosis. Neuro Oncol 2003; 5: 104-15
3. Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E. et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: The Lugano classification. J Clin Oncol 2014; 32: 3059-68
4. Grisariu S, Avni B, Batchelor TT, van den Bent MJ, Bokstein F, Schiff D. et al. Neurolymphomatosis: An International Primary CNS Lymphoma Collaborative Group report. Blood 2010; 115: 5005-11
5. Sideras PA, Matthews J, Sakib SM, Ofikwu F, Spektor V. Neurolymphomatosis of the peripheral nervous system: A case report and review of the literature. Clin Imaging 2016; 40: 1253-6
6. Swarnkar A, Fukui MB, Fink DJ, Rao GR. MR imaging of brachial plexopathy in neurolymphomatosis. AJR Am J Roentgenol 1997; 169: 1189-90
7. Liang R, Kay R, Maisey MN. Brachial plexus infiltration by non-Hodgkin's lymphoma. Br J Radiol 1985; 58: 1125-7
8. Kamiya-Matsuoka C, Shroff S, Gildersleeve K, Hormozdi B, Manning JT, Woodman KH. Neurolymphomatosis: A case series of clinical manifestations, treatments, and outcomes. J Neurol Sci 2014; 343: 144-8
9. Choi YJ, Shin JA, Kim YH, Cha SJ, Cho JY, Kang SH. et al. Neurolymphomatosis of brachial plexus in a patient with non-Hodgkin's Lymphoma. Case Rep Oncol Med 2013; 2013: 492329 DOI: 10.1155/2013/492329.
10. Bourque PR, Warman Chardon J, Bryanton M, Toupin M, Burns BF, Torres C. Neurolymphomatosis of the brachial plexus and its branches: Case series and literature review. Can J Neurol Sci 2018; 45: 137-43
11. Thawait SK, Chaudhry V, Thawait GK, Wang KC, Belzberg A, Carrino JA. et al. High-resolution MR neurography of diffuse peripheral nerve lesions. AJNR Am J Neuroradiol 2011; 32: 1365-72
12. Lagarde S, Tabouret E, Matta M, Franques J, Attarian S, Pouget J. et al. Primary neurolymphomatosis diagnosis and treatment: A retrospective study. J Neurol Sci 2014; 342: 178-81