An overlooked cause of longitudinally extensive spinal cord lesions: Primary central nervous system lymphoma

Background: Primary central nervous system lymphoma (PCNSL ) is a rare and aggressive malignant tumor. It is easy to be misdiagnosed due to its low incidence and unspecic presentations in clinical practice. PCNSL mainly occurs intracranially in the brain while spinal cord is rarely involved. Case presentation: Here we report a 76-year-old woman who had a suspicious tumor history and presented retardant paralysis, bladder dysfunction and sensory loss of the lower limbs. Magnetic resonance imaging (MRI) of the thoracic spine disclosed longitudinally extensive lesions extending from thoracic 4 (T4) to lumbar 1 (L1) vertebral level with an enhanced nodular lesion noting at levels of T10 and T11 . In order to further identify the cause, the whole body 18 F-uorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT) was performed and showed a hypermetabolic nodule corresponded to MRI enhancing lesions, which further suggesting the possibility of a tumor. The patient then underwent a surgical resection and spinal cord biopsy conrmed the diagnosis of non-Hodgkin's lymphoma (diffuse large B-cell type). The patient then received a high-dose chemotherapy based on methotrexate combined with Rituximab. Unfortunately, the symptoms of this patient have not been improved signicantly after three rounds of chemotherapy. Conclusion: Our case indicates that PCNSL may also serve as a possible cause for longitudinally extensive spinal cord lesions, especially the patients who had a suspicious tumor history, MRI enhancing lesion s in the spinal cord corresponded to hypermetabolic nodules on 18 F-FDG- PET/CT at the same level.

presented retardant paralysis, bladder dysfunction and sensory loss of the lower limbs. Magnetic resonance imaging (MRI) of the thoracic spine disclosed longitudinally extensive lesions extending from thoracic 4 (T4) to lumbar 1 (L1) vertebral level with an enhanced nodular lesion noting at levels of T10 and T11 . In order to further identify the cause, the whole body 18 F-uorodeoxyglucose  positron emission tomography (PET)/computed tomography (CT) was performed and showed a hypermetabolic nodule corresponded to MRI enhancing lesions, which further suggesting the possibility of a tumor. The patient then underwent a surgical resection and spinal cord biopsy con rmed the diagnosis of non-Hodgkin's lymphoma (diffuse large B-cell type). The patient then received a high-dose chemotherapy based on methotrexate combined with Rituximab. Unfortunately, the symptoms of this patient have not been improved signi cantly after three rounds of chemotherapy.
Conclusion: Our case indicates that PCNSL may also serve as a possible cause for longitudinally extensive spinal cord lesions, especially the patients who had a suspicious tumor history, MRI enhancing lesion s in the spinal cord corresponded to hypermetabolic nodules on 18 F-FDG-PET/CT at the same level.

Background
Longitudinally extensive transverse myelitis (LETM) is usually de ned as spinal cord lesions that extended vertically through three or more vertebral segments (1). LETM can be usually noted in in ammatory demyelinating diseases in the central nervous system (CNS), such as neuromyelitis optica spectrum disorders (NMOSD), myelin oligodendrocyte glycoprotein (MOG)-antibody disease, multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), systemic in ammatory diseases and spinal malignancies (2). LETM caused by PCNSL is rare in clinical practice. The magnetic resonance imaging (MRI) ndings are important to distinguish between PCNSL and other myelopathic etiologies. Researchers have showed that the speci city and sensitivity of 18 F-FDG-PET/CT in the diagnosis of PCNSL are 0.86 and 0.88 respectively (3). Here we report a patient with pathologically con rmed spinal cord PCNSL. Our case highlights that PCNSL in the spinal cord may also serve as a possible cause for longitudinally extensive spinal cord lesions.

Case Presentation
A 76-year-old Chinese woman was admitted to the Department of Neurology and Neuroscience Center in the First Hospital of Jilin University, Changchun, China. She had been healthy until ve months earlier when progressive weakness of her left lower limb was noticed. She reported no signi cant changes of her body weight recently. Brain MRI demonstrated lesions in the right temporal and occipital lobes. The lesions showed hypointense signal on T1-weighted images, hyperintense signal on T2-weighted images and uid attenuated inversion recovery (FLAIR) sequence ( Fig. 1: ABC). A clinical diagnosis of tumor was originally considered by the local hospital and the patient was therefore received radiotherapy. One week after treatment, her strength of lower limbs started to improve. Two months later after radiotherapy, repeated brain MRI revealed the lesions were ameliorated compared with the initial scans ( Fig. 1: DEF).
She was admitted to our hospital due to acute onset of lower limbs weakness and bladder dysfunction that quickly culminated within 2 days. Physical examinations re ected the features of the spinal cord shock stage, concretely showing retardant paralysis and anesthesia below T10. Deep tendon re exes were disappeared in both lower limbs, while normal in the upper extremities. Bilateral Babinski signs were negative. Urinary catheter was used due to urinary retention. Other physical examination results were unremarkable.
Routine laboratory investigations such as C-reactive protein, complete blood count, blood biochemical analysis, Vitamin B12 level, human immunode ciency virus (HIV), syphilis and circulating tumor markers were normal. Serological assays for autoimmune diseases and connective tissue diseases such as thyroid status, antinuclear antibodies were also negative. Aquaporin-4 (AQP4) antibody, MOG-antibody and paraneoplastic antibodies including CV2/collapsin response mediator protein5 (CRMP5), Ma2, RI, Yo, Hu and Amphiphys in both serum and CSF were negative. CSF analysis showed 36 × 10 6 /L of cell number, 0.67 g/L of protein and no oligoclonal bands. Brain MRI showed lesions in the right parietal lobe (Fig. 2: ABC). The lesions were nodular enhancement on T1-weighted contrast enhanced images (Fig. 2:   D). MRI of the spinal cord showed a longitudinally extensive hypointensive lesion from thoracic 4 (T4) to lumbar 1 (L1) vertebral level on T1-weighted images, hyperintensive signal on T2-weighted images and T2 fat-suppressed images, respectively ( Fig. 3: ABC). Axial thoracic MRI images showed a mass lesion located in the ventral part of the cord (Fig. 3: E). Post contrast-enhanced MRI revealed an enhanced nodular lesion (Fig. 3: DF). In support of MRI results, 18 F-FDG-PET/CT demonstrated hypermetabolism lesions ( Fig. 3: GH). Then, the patient received a tumor resection 8 days after admission. Spinal cord biopsy was performed at around T10-T11 level, con rming the diagnosis of diffuse large B cell lymphoma. Hematoxylin and eosin-staining staining showed diffuse proliferation of large atypical lymphocytes. Immunohistochemical studies demonstrated that neoplastic lymphocytes are positive for B-cell lymphoma-2 (Bcl-2), CD20 and c-Myc (Fig. 4). Thus, the patient received high-dose methotrexate (HD-MTX) combined with Rituximab chemotherapy. The patient discharged from the hospital after the rst chemotherapy. The patient was followed up by phone. Unfortunately, the patient could not tolerate high-dose chemotherapy drugs after receiving three rounds of chemotherapy, therefore she decided to forgo her fourth chemotherapy. Until now, the symptoms of accid paralysis, sensory disorder and persistent bladder dysfunction did not alleviate signi cantly during four months follow-up period. Discussion PCNSL represents 0.8-6.6% of all CNS neoplasms and only 1% of all lymphoma diagnoses (4). Intramedullary lymphoma with spinal cord involvement is rare, accounting for 1% of PCNSL (5). The average age of the disease was 50 years, with a higher prevalence being observed in men and 50-60 years being the peak period of incidence (6). The clinical symptoms of primary intramedullary spinal cord lymphoma are usually non-speci c and related to the levels of the spinal cord involvement (7).
Clinically, the onset symptoms were subacute or insidious and then became progressive in nature. In this case, the patient was an old woman who presented with acute onset sensory and motor impairments that quickly culminated within 2 days, which was similar to clinical features of in ammatory demyelinating disease.
More than half of PCNSL cases were involved the conus medullaris and/or cauda equina (8). The expansile spinal cord is often presented in MRI with isointense to hypointense on T1-weighted images and signal intensity on T2-weighted images, meanwhile they are usually solitary lesions (9)(10). In most cases, the lesions were enhanced homogeneously (11). The application of 18  with active myelopathy was much more common than in ammatory myelopathies (12). PCNSL has a strong uptake of 18 F-FDG, while the 18 F-FDG uptake is not obvious in non-enhancing lesions on MRI (13).
Some researchers demonstrated that higher 18 F-FDG-PET/CT hypermetabolism and maximum standardized uptake value in PCNSL than other tumors and in ammatory diseases (14)(15). Furthermore, the CSF and serum tests are usually inconclusive. In our case, the patient presented with a LETM extending from T4 to L1 level. The lesions displayed hypointensity in T1-weighted images and hyperintensity in T2-weighted images which consistent with other studies (16). Our patient had one enhancing lesion with homogeneous enhancement on imagings with 18 F-FDG-PET/CT showing a hypermetabolic nodule at the level of T10 to T11.
PCNSL is sensitive to chemotherapy and radiotherapy (17). The most effective treatment for newly diagnosed PCNSL is HD-MTX based combination chemotherapy (18). The role of surgery in PCNSL is limited given the characteristic of diffusely in ltrating growth of PCNSL (19). In our case, the risk of radiation therapy-related neurotoxicity is higher in order patients than other young patients.
In conclusion, the reason of LETM is broad. Our case highlights that PCNSL may also serve as a possible  Figure 1 Initial brain MRI before radiotherapy showed lesions in the right temporal and occipital lobes. The lesions showed hypointense signal on T1-weighted images (A), hyperintense signal on T2-weighted (B) and FLAIR images (C). Repeat MRI showed the brain lesions have almost been disappeared (DEF). Brain MRI showed lesions in the right parietal lobe. The lesions were hypointense on T1-weighted images (A), hyperintense on T2-weighted (B) and FLAIR images (C) (white arrows). (D) T1-weighted contrast enhanced images reveled enhancing nodular lesions in the right parietal lobe (white arrows).