A Case of Diffuse Large B-Cell Lymphoma Presenting As Transverse Myelopathy

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J Neurocrit Care 2008;1:177-180 ISSN 2005-0348

A Case of Diffuse Large B-Cell Lymphoma Presenting as Transverse Myelopathy

Hyun Sook Kim, MD, Kyoung-Keun Kim, MD and Ok Joon Kim, MD, PhD Department of Neurology, College of Medicine, Pochon CHA University, Seongnam, Korea

Background: In patients with lymphoma, transverse myelopathy can be induced by direct infiltration of tumor cells into spinal cord, ischemic cord change secondary to intravascular infiltration of tumor cells or immunogenic paraneoplastic syndrome. We report an unusual case of diffuse large B-cell lymphoma presenting as transverse myelopathy. Case Report: A 78-year-old woman was presented with paraparesis and hypoesthesia below T6 level. C-T-L-spine magnetic resonance image (MRI) showed multiple bulging discs without signal change on spinal cord. Brain MRI and CSF study showed no specific finding. After steroid pulse therapy, paraparesis was partially improved. Two months after the onset, papaparesis and hypoesthesia were aggravated. Spine MRI showed increased signal intensities on T2-4 level without contrast enhancement. Ultrasonography-guided lymph node biopsy confirmed diffuse large B-cell lymphoma. Conclusion: Our patient presented with only clinically suspected transverse myelopathy, which turned out to be paraneoplastic. Underlying lymphoma could be revealed byunusual clinical courses and careful physical examination. J Neurocrit Care 2008;1:177-180

KEY WORDS: Paraneoplastic·Diffuse large B-cell lymphoma·Transverse myelopathy.

Introduction myelopathy in whom lymphoma was discovered at lymph node biopsy after 2 months. Lymphoma may be associated with neurological symptoms in various ways such as direct metastasis to central nervous Case system (CNS), opportunistic infection or paraneoplastic syn- 1 drome. Paraneoplastic neurological diseases (PNDs) are a A 78-year-old woman presented with 18 days history of rare group of syndromes that occur in patients with cancer ascending sensory loss, progressive weakness of both legs and which are not due to the presence of metastases or direct and dysuria. She didn’t complain back pain, weight loss or infiltration of the tumor into the nervous system. Most of night sweating. Her medical history was unremarkable ex- PNDs are associated with lung cancer, lymphoma and gy- cept hypertension under control. On neurological examination, 2 necological tumors. The anatomical distributions of PNDs higher cortical function and cranial nerve functions were include muscle (polymyositis), neuromuscular junction normal. Motor power was MRC grade II at both legs and (Lambert-Eaton myasthenic syndrome, myasthenia gravis sensory level was present at T6 level. Deep tendon reflexes and neuromyotonia), peripheral nerves (neuropathies and were hyperactive at both knee and ankle joint, but Babinski’s polyradiculopathies) and CNS. PNDs involving CNS can cli- sign was absent. Magnetic resonance imaging (MRI) study nically present as subacute cerebellar degeneration, enceph- was performed on C-T-L spine areas. There were postero- alomyelitis (limbic encephalitis, brainstem encephalitis, my- central disc herniations and bulging discs at many cervical 3 elitis) or opsoclonus-myoclonus syndrome. But, there are and lumbar areas without cord compression, and there was few reports available on lymphoma primarily causing neu- no evidence of spinal cord lesion (Fig. 1A, B). Nerve con- rological signs, especially with paraneoplastic myelopathy. duction studies showed decreased amplitude but normal con- We report a 78-year-old woman presenting with transverse duction velocity on left sural nerve. Somatosensory-evoked Address for correspondence: Hyun Sook Kim, MD potentials of the median and posterior tibial nerves showed Department of Neurology, College of Medicine, Pochon CHA Univer- normal latencies and amplitudes. Studies of biochemical sity, 351 Yatap-dong, Bundang-gu, Seongnam 463-712, Korea Tel: +82-31-780-5483, Fax: +82-31-780-5198 profiles including thyroid function, urine analysis, antinuclear E-mail: [email protected] antibody, antiphospholipid antibodies, anti-SS-A/SS-B anti-

J Neurocrit Care ■ 2008;1:177-180 bodies were not remarkable. Vitamin levels including vitamin III) and sensory symptoms.

B6 (53.6 nmol/L, normal range: 21.6-104.1 nmol/L), B12 Two months after the onset, paraparesis was aggravated (1,912 pg/mL, normal range: 211-911 pg/mL), E (0.99 and she had to be hospitalized again. Neurological examina- mg/dL, normal range: 0.75-1.41 mg/dL) and folate (14.75 tion showed MRC grade 0 on both legs and sensory level at ng/mL, normal range: 3.45-13.77 ng/dL) were within nor- T4. Physical examination revealed 1.5 cm sized palpable mal ranges. The patient was seronegative for syphilis sero- mass on right lower abdomen and right axillary region. Re- logy, human T-cell lymphotrophic virus-I, human immunode- peated spinal MRI scans revealed poorly delineated increas- ficiency virus (HIV), IgM for HSV and CMV, and paraneo- ed signal intensity in spinal cord of T2-T4 level on T2WI. plastic antibodies including anti-VGCC (voltage-gated cal- There was neither enhancement nor mass effect in that lesion cium channels), antiHu, anti-Ri and anti-Yo. Serum lactate (Fig. 1C, D). Ultrasound assisted needle biopsy was perform- dehydrogenase was 1,028 U/L (normal range: 200-470 U/L). ed on a 1.5×1.4×0.9 cm sized mixed echoic nodule within Cerebrospinal fluid (CSF) examination showed normal pro- the subcutaneous fat layer of the abdominal wall. Biopsy tein level (38 mg/dL) without pleocytosis. No malignant cell specimens of the lymph nodule revealed that the infiltration was found on cytological examination. Myelin basic protein was composed of large lymphoid cells. Immunohistochemical was elevated by 7.20 ng/mL (normal range; 0-2.0 ng/mL). investigations demonstrated that the majority of large lym- IgG index was within normal range (0.47) and no oligoclo- phoid cells strongly expressed the L26 and CD79a antigen, nal band was detected from CSF. She was treated with a five- and partial composition of them expressed the CD43 and day course of intravenous steroid therapy of 1.0 gram/day CD5 antigen (Fig. 2). The patient did not consent to chemo- and there were partial improvement of motor (MRC grade therapy and she died four months after the symptom onset.

A B C D

FIGURE 1. Spinal cord MRIs at first presentation and 2-months later. A, B: There is no abnormal signal intensity on cervico-thoracic spinal cord at initial MRI (A: T2WI, B: T1WI). C, D: After two months later, there is increased SI without enhancement in the spinal cord of T2-T4 level (C: T2WI, D: Enhancement study).

A B C

FIGURE 2. Ultrasonography on abdominal wall and pathological findings. A: About 1.5×1.4×0.9 cm sized mixed echoic nodule exists within the subcutaneous fat layer of the abdominal wall on RLQ area. B, C: Pathological study of abdominal lymph node shows diffuse large B-cell lymphoma (A: H-E stain, B: CD20 immunohistochemical stain).

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A Case of Diffuse Large B-Cell Lymphoma Presenting as Transverse Myelopathy ■ HS Kim, et al.

A postmortem examination was not performed. contrast medium enhancement. The absence of epidural mass or discrete intramedullary enhancement rules out metastatic Discussion myelopathy, which is more common. It is suggested that PNDs including myelopathy come from the disturbance of Current WHO modification of the REAL classification re- immunologic reaction, and antigen-derived oligoclonal cyto- cognized three major categories of the lymphoid malignancies toxic T-cell response may be involved.14 It may also be based on morphology and cell lineage: B-cell neoplasms, T- caused by the overproduction of cytokines and ectopic hor- cell/natural killer-cell neoplasms, and Hodgkin’s lymphoma.4 mone production in patients with lymphoma.15 Treatment is Among B-cell neoplasms, diffuse large B-cell lymphoma usually unsuccessful; however, there are some reports to have (DLBC) is the most common type. It is also the most com- responded to steroid or underlying malignancy therapy.12,13 mon type of the aggressive lymphoma. The international We assume that the response to treatment is inconsistent be- prognostic index for aggressive non-Hodgkin’s lymphoma cause of these variable pathogenesis and pathologic findings identifies five significant prognostic factors of overall sur- in paraneoplasstic myelopathy. vival: age, serum lactate dehydrogenase (LDH), performance In general, investigation of a patient suspected of having status, stage, and extranodal site involvement. This patient paraneoplastic syndrome might fail to reveal the tumor until had all of the risk factors (age over 60 years, high serum it becomes symptomatic, typically 3-13 months later.1 Our LDH level, completely disabled performance status, advanc- patient showed myelopathy as presenting symptom of DLBC, ed stage and extranodal site involvement) to show poor prog- which finally diagnosed after two months. We could not con- nosis. firm the pathology of the spinal cord and find a paraneoplastic In lymphoma, neurological symptoms of myelopathy can antibody in our case. However, because this patient had be caused by two ways of direct involvement of the spinal steroid responsiveness, normal serum and CSF findings, init- cord. One mechanism is tumor cell invasion of spinal cord ially normal spinal cord images, and progressive clinical def- proper. Epidural, intradural-extramedullary, and intramedul- icit, immune-mediated paraneoplastic process is probable lary spinal cord metastasis of lymphoma was previously do- pathophysiology in this patient. cumented.5 Primary intramedullary lymphoma of the spinal cord is an uncommon neoplasia, and hyperintensities on T2WI REFERENCES and enhancement would be expected at initial spinal MRI 1. Ellison DW, Wilkins BS. Lymphoma and the nervous system. Curr examination.6 The other mechanism is spinal cord ischemia Top Pathol 2001;95:239-65. 2. 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