Demyelinating neuropathy due to primary IgM kappa B cell lymphoma of peripheral nerve

A 53-year-old man presented with a painful, demyelinating sensorimotor peripheral neuropathy with lymphomatous infiltration on sural nerve biopsy, but no evidence of systemic lymphoma. The neuropathy responded to cytotoxic therapy. Seven years later he developed generalized lymphadenopathy due to B cell lymphoplasmacytoid lymphoma, with a subpopulation of cells expressing a monoclonal pattern of IgM kappa. The lymphomatous infiltrate in the original nerve biopsy showed similar monoclonal IgM kappa reactivity. The mechanism of demyelination of the peripheral nerves may be similar to that described in patients with IgM kappa monoclonal gammopathies.     

Lymphoma and peripheral neuropathy: a clinical review

Lymphoma occasionally affects the peripheral nervous system. When it does, the diagnosis can be elusive since many patients present without known lymphoma. Most peripheral nerve complications are due to non-Hodgkin's lymphoma (NHL), which infiltrates nerves causing axonal damage. This disorder can affect nerve roots and cranial nerves, often associated with lymphomatous meningitis. NHL may also infiltrate peripheral nerves and cause plexopathy, mononeuropathy, or generalized neuropathy. These neuropathies may resemble an asymmetric mononeuropathy multiplex or a generalized disorder such as chronic inflammatory demyelinating polyradiculoneuropathy. When NHL infiltrates diffusely, the term neurolymphomatosis is used. Hodgkin's lymphoma (HL), by contrast, rarely infiltrates nerves. More often, HL causes immunological disorders of the peripheral nervous system such as inflammatory plexopathy or Guillain-Barré syndrome. Other rare lymphomas such as intravascular lymphoma and Waldenstrom's macroglobulinemia can also affect peripheral nerves in specific ways. In addition, other malignant and nonmalignant lymphoproliferative disorders enter into the differential diagnosis of lymphomatous neuropathy. This review discusses the multiple peripheral nerve presentations of lymphoma from the clinician's point of view and provides a guide to the evaluation and diagnosis of these uncommon, challenging disorders.     

Neurolymphomatosis associated with muscle and cerebral involvement caused by natural killer cell lymphoma: a case report and review of literature

We report a biopsy-proven case of neurolymphomatosis (NL) presenting with sensory motor axonal polyneuropathy, polymyositis, and cerebral involvement. Ours is the second reported case of NL caused by natural killer-cell lymphoma defined by morphology and immunophenotyping. For 3 months, the patient developed stocking-glove distribution of hypesthesia, subacute progressive weakness and mental deterioration. EMG showed severe sensorimotor mixed axonal-demyelinating polyradiculoneuropathy. Lumbar puncture revealed mildly high protein level with normal glucose and cell count. Sural nerve biopsy demonstrated lymphomatous axonal neuropathy and muscle biopsy was indicative of lymphomatous polymyositis. Brain MRI revealed multiple white matter lesions, consistent either with progressive multifocal leukoencephalopathy or cerebral lymphoma. Bone marrow biopsy showed neoplastic infiltrates. The patient died of multiple organ failure prior to initiation of chemotherapy.     

Craniocerebral involvement in lymphoma

Nine-hundred-eighty-nine patients with lymphoma were studied. Fifty-three cases (5.3%) had lymphomatous craniocerebral infiltration. The principal factors of risk for this complication were: advanced stage of the lymphoma (III or IV), diffuse histiocytic, diffuse poorly differentiated lymphocytic, or mixed cellularity lymphoma histological type, bone marrow involvement, and previous systemic chemotherapy. Thirty-two per cent of the cases of meningeal lymphomatous infiltration were asymptomatic and represented autopsy findings. CT-scan was an useful test to detect brain focal parenchymatous infiltration, as opposed to meningeal infiltration. Mean survival time in patients with lymphomatous meningeal infiltration was 4.3 months, following the combined use of systemic chemotherapy, radiation therapy and intrathecal methotrexate. Two cases had primary cerebral lymphoma, although without associated immunodeficiency. Twenty patients (2%) had intracranial hemorrhage, in clear relationship with platelet alterations. Fifteen patients (1.5%) had CNS infection, caused by common bacteria or opportunistic agents. In 7 cases, the diagnosis was made at autopsy. Thirty-six autopsies were performed. In 8 cases (22%), pathologic findings such as, demyelination, microcalcifications, coagulative necrosis, or gliosis, suggested complications from treatment.     

Non-Hodgkin's malignant lymphoma of the peripheral nervous system: clinicopathological correlations in ten patients

INTRODUCTION: Identifying tumor infiltration or compression in patients with non-Hodgkin's malignant lymphoma presenting peripheral neuropathy can be a difficult task. METHODS: We collected a series of patients with peripheral neuropathy with demonstrated lymphomatous infiltration or compression managed between October 1977 and October 2001 to search for clinico-pathological correlations. RESULTS: Ten cases were reviewed. Neurological manifestations were the inaugural symptom of the disease in 7 patients. Clinical presentations included 5 focal (3 cranial nerve palsies, 2 brachial radiculopathies) and 5 diffuse neuropathies (3 polyradiculoneuropathies, 1 polyneuropathy and 1 mononeuritis multiplex). The mechanisms of peripheral nerve involvement were classified into lymphomatous meningoradiculitis (5 cases), involvement of cranial nerves or spinal roots in their extraneuraxial course (3 cases) and infiltration of distal peripheral nerves (2 cases). Four long lasting survivals after treatment were observed. CONCLUSIONS: Prognosis depends much more on the haematological disease than on the neurological symptoms or tumor location.     

Clinical aspects and pathogenesis of neurological complications due to malignant lymphomas]

Malignant lymphomas cause various neurological complications by several ways. They include 1) infiltration and compression due to lymphoma itself, 2) ischemia due to intravascular proliferation of lymphoma cells, 3) paraneoplastic syndrome, 4) immunodeficiency due to lymphomas, 5) organ dysfunction due to lymphomatous infiltration, and 6) complication related to therapies against lymphomas. We presented 4 patients with neurological complications caused by B cell lymphomas as follows. Our first patient was a 67-year-old woman with primary intracranial lymphoma whose onset simulated that of a cerebral infarct. The second patient was a 52-year-old man with lymphoma, who developed myelopathy caused by an intradural extramedullary spinal cord tumor. He received chemotherapy and radiation therapy, followed by complete remission. The third was a 80-year-old man with left cavernous sinus syndrome, which did not respond to therapies against lymphoma. The fourth was a 55-year-old man who presented with numb chin syndrome on both sides, followed by multifocal lymphomatous involvement of the cranial nerves, spinal roots and leptomeninges. Malignant lymphomas may affect any regions of the central and peripheral nervous systems by various ways. Early diagnosis and treatment are essential for the better outcome of neurological complications due to lymphomas.     

Peripheral neuropathies and lymphoma without monoclonal gammopathy: a new classification

Summary Recent progress in immunopathological studies of peripheral nerve and lymph node fragments together with 16 personal cases and numerous clinicopathological reports have suggested a new classification of peripheral neuropathies (PN) and lymphomas. These are: (1) PN due to local infiltrations by a T-cell lymphoma; (2) acute polyradiculoneuritis due to active demyelination and associated with infiltrates of a T-cell lymphoma in the epineurium, resembling Marek's disease (which is a T-cell lymphoma); (3) B-cell lymphoma proliferation which may be restricted to or predominate in the peripheral nervous system, with a large clinicopathological heterogeneity ranging from localized forms to ascending polyradiculoneuropathies; (4) angiotropic lymphoma, which is a B-cell lymphoma and may present as an acute mononeuropathy; (5) patients with acquired immunodeficiency syndrome due to lymphomatous infiltrates in the endoneurium, of which 2 cases of PN have been reported; (6) PN associated with organomegaly, endocrinopathy, M-component and skin lesions, certain cases being associated with a plasmocytoma and sometimes Castleman's disease but without any monoclonal gammopathy; (7) classic Guillain-Barré syndrome, prone to develop in patients with extraneural lymphoma but without any lymphomatous infiltrates in the peripheral nervous system; (8) certain cases (4 out of 16 in our series) where there is no clear relationship between PN and lymphoma, and there are mainly features of axonal degeneration. Inflammatory perivascular infiltrates were sometimes present in the epineurium.     

Guillain-Barre syndrome in patient with Burkitt's lymphoma and type 2 diabetes mellitus

Although peripheral neuropathies are commonly observed in patients with non-Hodgkin's malignant lymphomas (NHML), Guillain-Barre syndrome (GBS) belongs to the occasional complications of lymphoproliferative disorders. It appears in less than 0.3 per cent of NHML. It is worthy of note that in the reported case there occurred three independent risk factors of peripheral neuropathy: Burkitt's lymphoma, chemotherapy and type 2 diabetes mellitus. Based on clinical course, EMG finding and neuropathological examination, in spite of normal cerebrospinal fluid protein content, GBS as a paraneoplastic disorder was diagnosed. It was assumed that chemotherapy and diabetes mellitus conduced to severe neuropathy.     

Optic neuropathy and central retinal artery occlusion in non-Hodgkin lymphoma.

We report a patient with systemic large cell non-Hodgkin lymphoma in remission who presented with the rare combination of optic neuropathy and central retinal artery occlusion. Another unusual feature of this case is the lack of enhancement in the affected region on magnetic resonance imaging only hours after the first dose of steroids. Despite prompt treatment with steroids and radiotherapy, lymphomatous infiltration of the meninges developed 2 months later and was ultimately fatal.     

Primary leptomeningeal lymphoma: report of 9 cases, diagnosis with immunocytochemical analysis, and review of the literature

We describe 9 patients who presented with a neoplastic meningitis of lymphomatous origin. No evidence of parenchymal central nervous system or systemic tumor was identified either at the time of presentation or throughout the course of their disease. We have chosen to call this entity "primary leptomeningeal lymphoma" (PLML). This unusual form of neurologic lymphoma must be differentiated from the more common clinical situations of primary parenchymal lymphoma with meningeal involvement and systemic lymphoma complicated by lymphomatous meningitis.     

Fatal peripheral neurolymphomatosis after remission of histiocytic lymphoma

A 32-year-old woman with histiocytic lymphoma was in complete clinical remission after two courses of chemotherapy, when peripheral neuropathy developed fulminantly. Abnormalities included facial nerve paralysis, dysphagia, quadriparesis, myalgia, and incontinence. She died 10 days after onset of these symptoms. Postmortem examination revealed infiltration of peripheral nerves by lymphomatous cells with no involvement of meninges, brain, lymph nodes, or other organs. Differences in the blood-brain barrier of peripheral and central nervous system are suggested: The peripheral barrier may be more penetrable by malignant histiocytes or less permeable to cytotoxic drugs. Intrathecal chemotherapeutic drug instillation and irradiation may be beneficial.     

Subacute demyelinating polyradiculoneuropathy complicating Epstein–Barr virus infection in GATA2 haploinsufficiency

Introduction: Autosomal dominant haploinsufficiency of GATA2 causes monocytopenia and natural killer cell lymphopenia, resulting in predisposition to mycobacterial, fungal, and viral infections. Methods: Herein we report on the clinical, serologic, electrophysiologic, and pathologic evaluations of a 29‐year‐old woman with GATA2 haploinsufficiency and active Epstein–Barr virus (EBV) infection complicated by subacute painful neuropathy. Results: Nerve conduction and electromyography studies showed predominantly demyelinating sensorimotor polyradiculoneuropathy. Lumbar spine MRI showed thickening and enhancement of the cauda equina nerve roots. Serum and cerebrospinal fluid anti‐IgG and IgM EBV capsid and nucleic acid antibodies were positive. Sural nerve biopsy showed microvasculitis and an increased frequency of fibers with segmental demyelination. Intravenous immunoglobulin and steroids improved the patient's neuropathy. Conclusion: GATA2 mutation–related immunodeficiency may predispose to EBV‐associated subacute demyelinating polyradiculoneuropathy by both viral susceptibility and immune dysregulation. In patients who present in this manner, immunodeficiency syndromes should be considered when lymphomatous infiltration is excluded. Immunotherapy can be helpful. Muscle Nerve 57 : 150–156, 2018     

Clinicopathological and molecular biological studies in a patient with neurolymphomatosis

We describe a patient with a clinical disorder that resembled vasculitic neuropathy in which peripheral nerves were successively affected over several months, but without systemic involvement. An initial muscle biopsy near the involved nerves showed signs of nonspecific inflammation around the muscle and nerve fibers. Immunosuppressive treatment resulted in a dramatic reduction in pain, but relapses of the disease eventually occurred, and the patient died 22 months after onset of the first symptoms. Pathologically, a malignant non-Hodgkin's B-cell lymphoma, restricted to the intra- and extradural peripheral nervous system, was found. The demonstration by Southern blotting of immunoglobulin heavy chain gene rearrangement confirmed the monoclonal nature of the lymphomatous cells. In situ hybridization tests for Epstein-Barr and herpes virus subtypes were negative. Our case underlines i) how difficult diagnosis can be despite extensive investigations, ii) the usefulness of immunosuppressive treatment in the early stage of the disease, iii) the importance of immunostaining and genome analysis for distinguishing between different types of human neurolymphomatosis, and iv) the fact that the initial inflammatory process in the muscle biopsy may be interpreted either as a paraneoplastic effect of the lymphoma or as a viral inflammatory neuromyopathy that triggers the development of the malignant lymphoma.     

B-cell neurolymphomatosis confined to the peripheral nervous system

Patients with neurolymphomatosis show lymphoma cells within the peripheral nerves, nerve root/plexus, or cranial nerves. However, most neurolymphomatosis patients show lymphomatous infiltration not only in the peripheral nervous system (PNS), but also in the meninges, Virchow–Robin space, and brain parenchyma. Here, we report a 74-year-old woman with diffuse large B-cell lymphoma presenting with motor–sensory–autonomic polyneuropathy and multiple cranial neuropathies. A diagnosis of neurolymphomatosis was made by sural nerve biopsy. Postmortem examination indicated that lymphoma cell infiltration in the nervous system was confined to the PNS with no involvement of the central nervous system, including the meninges. This was a very rare case of B-cell neurolymphomatosis with lymphomatous infiltration confined to the PNS, suggesting specific affinity of the lymphoma cells for the PNS in this patient.     

Multiple radiculopathy as the presenting manifestation of primary spinal leptomeningeal B cell lymphoma detected by flow cytometry of cerebrospinal fluid

Primary leptomeningeal lymphoma is a rare syndrome characterized by lymphomatous meningeal infiltration without identification of systemic lymphoma or parenchymal central nervous system lymphoma. We report a case of a 62-year-old immunocompetent woman with primary spinal leptomeningeal lymphoma presenting as cervical and lumbar radiculopathy who is rare because of particularly unusual onset site of B cell lymphoma. Interestingly, the diagnosis was possible only by cerebrospinal fluid flow cytometry.     

Varicella-zoster virus encephalitis in acquired immunodeficiency syndrome: Report of four cases

Four patients with acquired immunodeficiency syndrome, a 27-year-old female intravenous drug abuser and three males (two drug addicts aged 27 and 33 years and a 40-year-old homosexual) presented with a rapidly progressive encephalopathy. Two had generalized varicella-zoster virus skin infection, one had had a regressive thoracic zoster rash 7 months previously and one had no history of cutaneous eruption. Neuropathological examination revealed, in each case, multifocal necrotic changes with numerous, intranuclear Cowdry type A inclusion bodies in glial cells, endothelial cells, macrophages and neurons, within and around the lesions. These inclusion bodies were stained positively for varicella-zoster virus by immunocytochemistry and contained herpes virus nucleocapsids by electron microscopy. Molecular biology using the polymerase-chain-reaction method demonstrated viral genome. In one case, zoster-induced non-inflammatory vasculopathy involved medium sized leptomeningeal vessels and was associated with circumscribed areas of cortico-subcortical infarction. In another case, varicella-zoster virus encephalitis was associated with human immunodeficiency virus encephalitis and a secondary cerebral lymphoma. Multinucleated giant cells expressing human immunodeficiency virus proteins in their cytoplasm, were found in the lymphomatous deposits and in the varicella-zoster virus necrotic lesions. In these latter lesions, Cowdry type A inclusion bodies could be seen in the nuclei of some multinucleated giant cells confirming previous observations of MGCs co-infected by HIV and CMV, and supporting the hypothesis that DNA viruses interact with HIV, thus increasing its effect.     

The epidemiology of human immunodeficiency virus-associated neurological disease in the era of highly active antiretroviral therapy

Highly active antiretroviral therapy (HAART) is effective in suppressing systemic human immunodeficiency virus (HIV) viral load and has decreased mortality rates and the incidence of systemic opportunistic infections in patients with acquired immunodeficiency syndrome (AIDS). Multiple studies now suggest that the incidence rates of HIV-associated neurological disease and central nervous system (CNS) opportunistic infections also are decreasing. Since the introduction of HAART in 1996, the incidence of HIV dementia has decreased by approximately 50%. The mean CD4 cell count for new cases of HIV dementia is increasing, but it remains as a complication of moderate-advanced immunosuppression. The incidence of HIV-associated distal sensory polyneuropathy has decreased, although the incidence of antiretroviral drug-induced toxic neuropathy has increased. However, as patients with AIDS live longer as a result of HAART, the prevalence of peripheral neuropathy in HIV-seropositive patients may be increasing. The incidence rates of CNS opportunistic infections (cryptococcal meningitis, toxoplasmosis, progressive multifocal leukoencephalopathy) and primary CNS lymphoma have decreased since the introduction of HAART. As patients develop increasing resistance mutations to antiretroviral drugs and with subsequent decline in CD4 cell counts, in the near future, the incidence of HIV-associated neurological disease may begin to rise.     

Burkitt's lymphoma: an unusual cause of childhood paraplegia

In this paper we present two paraspinal Burkitt's lymphomas, with paraplegia. This entity is very rare in our country. In the evaluation of a paraplegic child, we believe that Burkitt's lymphoma should always be kept in mind.     

Polyradiculopathy revealing an enteropathy associated T-cell lymphoma in a patient with celiac disease

INTRODUCTION: Celiac disease (CD) may be complicated by an enteropathy associated T-cell lymphoma (EATL), but lymphomatous dissemination outside the gastrointestinal tract is uncommon especially to the peripheral nervous sytem. OBSERVATION: We report a 54-year-old CD patient with EATL revealed by subacute polyradiculopathy. DISCUSSION: Peripheral neuropathies associated with CD are generally not polyradiculopathies, but sensorimotor neuropathies. Peripheral neurological complications of non-Hodgkin lymphoma are more frequent with B-lymphoma and a neurological presentation of EATL is very rare. CONCLUSION: This case illustrates the usefulness of searching for EATL in CD patients with polyradiculopathy.     

Unusual presentation of a primary spinal Burkitt's lymphoma

Primary CNS lymphomas are detected with increasing frequency in immunocompetent and immunodeficient persons. Primary involvement of the spinal roots has only rarely been reported. The unusual history is described of a patient with a primary spinal Burkitt's lymphoma initially presenting as an S1 syndrome showing lymphocytic pleocytosis in the CSF, leading to the misdiagnosis of meningoradiculitis. Repeated spinal MRI disclosed a spinal mass lesion and histological and immunohistological examination of the tumour confirmed the diagnosis of spinal Burkitt's lymphoma.