Malignant course of a rare case of cauda equina neurolymphomatosis

This is an unauthorised machine translation into English made using the DeepL Translate Pro translator. The editors do not guarantee that the content of the article corresponds fully to the original language version.

Dear Editor,

Malignant lymphoma cells can rarely be found in the spinal cord, or even less commonly in the cauda equina, in addition to their typical locations. The cauda equina consists of the spinal roots L2-S5 together with the coccygeal nerve and is located in the spinal canal distal to the conus medularis in the lumbar cistern of the spinal canal. Primary cauda equina lymphoma is a very rare neoplasm belonging to a group of diagnoses known as neurolymphomatoses. Neurolymphomatosis is characterized by infiltration of malignant lymphoma cells between the cranial nerves, nerve roots or plexus, and peripheral nerves [1,2]. Neurolymphomatosis can be further subdivided into primary and secondary according to the original site of diagnosis. The latter represents progression or recurrence of another systemic lymphoma or leukemia. Primary neurolymphomatosis accounts for about 20% of all neurolymphomatoses and only 0.2% of all non-Hodgkin's lymphomas [3]. Only a little over 20 cases of primary cauda equina lymphoma have been reported in the literature, with no comprehensive data set. In our case report, we would like to present a difficult diagnosis of this malignancy.

A 76-year-old female patient was admitted to a catchment neurology unit for the development of left-sided limb weakness (mild paresis with acral accentuation on the left upper limb, moderate paresis on the left lower limb) and a suspicious peripheral lesion of the n. VII on the left side for about a month. Due to the central type of paresis, MRI of the brain with contrast agent was performed after admission, which revealed only a small v.s. neurinoma of the internal auditory canal on the left (Fig. 1A, B).

In the next step, a lumbar puncture was performed, which showed a proteinocytological association (protein 2 837 mg/l, lactate 7.95 mmol/l, lymphocytic pleocytosis 15 284 segments, coefficient of energy balance [KEB] -57.4). Initially, treatment with intravenous ceftriaxone was started, which was replaced by meropenem after one week due to the patient's allergic reaction. Infections with Lyme disease, treponema pallidum, tick-borne meningoencephalitis virus, herpes viruses, enteroviruses and aspergillus were excluded. Neither onconeural antibodies nor antibodies associated with autoimmune encephalitides were found. The only abnormal findings detected were borderline significant demonstration of antiganglioside antibodies GM1 IgM and elevation of chemokine CXCL 13. On the basis of these results and the patient's clinical condition, which was not entirely typical of neuroinfection, a diagnostic workup was recommended in the context of a search for hematooncological disease. Additional CT of the trunk and ultrasound of the lymph nodes were performed, along with further laboratory diagnostics and sternal puncture. CT of the trunk expressed suspicion of cholangiocarcinoma in the left hepatic lobe, but subsequent punch biopsy showed only a benign biliary adenoma. Due to the suspected haemato-oncological pathology, it was intended to complement the lymphatic examination with flow cytometry, but repeated attempts at lumbar puncture (despite targeted navigated puncture under CT) were unsuccessful due to the inability to obtain cerebrospinal fluid ("dry spinal canal"). During hospitalisation, the left-sided facial paresis regressed, but a new development of flaccid paraparesis of the lower limbs began. Muscle strength was reduced in all segments without impairment of sensation. Because of the progression of the findings, MRI of the cervical, thoracic and lumbar spine with contrast agent was performed, which revealed diffuse intradural involvement of the cauda equina to the spinal cord and suspected metastatic involvement of the Th7 vertebra (Figure 1C-F).

Differential diagnostic possibilities such as lymphocytic leukemic meningitis, neurolymphomatosis, metastatic leptomeningitis or myeloid sarcoma were considered. To complete the diagnosis, a PET/CT scan was ordered, which confirmed a highly ¹⁸F FDG-avid infiltrate in the spinal canal from Th12 to the sacrum with protruding infiltrates following the course of the neural structures, together with an osteolytic lesion in the Th7 vertebra (Fig. The intracanalicular picture suggested the possibility of leptomeningitis, but due to the finding of a lesion in Th7, a suspicion of a tumor infiltrate of the cauda equina was expressed. On examination, the neurological findings in the lower limbs progressed rapidly over 7 days and practical paraplegia occurred, while perianogenital sensation and limb hemiplegia were preserved. The patient was consulted at an interdisciplinary neurosurgical referral seminar, where biopsy of the cauda equina lesion was indicated. The patient was subsequently transferred to the Neurosurgical Clinic of the Hradec Kralove University Hospital, where surgery was performed. L3 laminectomy with durotomy was performed under general anaesthesia. Intraoperatively, no solid mass was found, the intradural space was filled with edematous nerve roots of the cauda equina, which were "glued" with thickened arachnoid (Figure 2B).

Several small samples of root sheaths were collected for histopathological examination. The postoperative course was uncomplicated, there was no deterioration but no improvement of neurological functions. Histological examination was severely limited by the small sample of material collected, but the presence of atypical leukocytes around the roots led to the suspicion of a rare cauda equina lymphoma. The patient was transferred to the oncology and radiotherapy clinic, but unfortunately died before treatment could be started. An anatomic-pathologic autopsy confirmed extensive infiltration of the entire 130 mm length of the cauda equina by malignant non-Hodgkin's lymphoma (diffuse large B-cell lymphoma from the germinal center [GC-like type]; DLBCL GC), including infiltration of the bone marrow of the Th7 vertebra (Figure 2C-F).

Neurolymphomatosis cauda equina is a very rare disease that presents both diagnostic and therapeutic challenges. Just over 20 cases of primary cauda equina lymphoma have been documented in the literature. The average age of patients is around 55 years, with the youngest reported patient being 11 years of age [3,4]. Clinically, patients usually present with initial paresthesias, dysesthesias, pain and varying degrees of lower limb mobility impairment. In the subsequent course, progressive paraparesis to paraplegia of the lower limbs usually occurs [5]. Non-invasive diagnosis consists mainly of imaging examinations. MRI of the lumbar spine shows opacification of the root sheaths, edematous changes or nodular nerve extensions. However, the aforementioned changes are also present in other diagnostic entities, such as chronic inflammatory demyelinating polyradiculitis, neurofibromatosis, malignant peripheral nerve sheath tumor, or metastatic involvement of the cauda equina by epithelial tumors [6]. ¹⁸FDG-PET/CT demonstrates increased uptake of radiopharmaceutical in the course of the affected parts of the cauda equina. Invasive investigations include lumbar puncture, which may contain lymphoma cells detectable by cytology or positive biomarkers such as IL-2, IL-10 and CXCL13 [7]. Flow cytometry can then increase the sensitivity of cytological examination [8]. Very often, however, the changes in the lysate are only non-specific -⁠ usually the detection of an increased leukocyte count (82.4% of cases), protein elevation (88.2% of cases) or decreased glucose levels (41.2% of cases) [3]. Most often, the diagnosis is confirmed by a biopsy of the lesion, which is performed from a laminectomy of the lumbar spine. Nerve root infiltration gives the appearance of a filled dural sac with swollen nerve roots. Nerve root biopsy is recommended in patients with preserved motor function of the lower extremities with perioperative monitoring of motor evoked potentials and bulbocavernous reflex [9,10]. Chemotherapy, radiotherapy or combined chemoradiotherapy is usually indicated in the treatment of primary cauda equina lymphoma [9]. High-dose methotrexate, rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) are used in systemic chemotherapy [5]. The overall prognosis of patients depends on the degree of infiltrative involvement, the rate of diagnosis, age and comorbidities.

This deliverable was produced within the Cooperatio programme, SURG.

Conflict of interest

The authors declare that they have no conflict of interest in relation to the subject of the study.