A diagnosis dilemma of back pain in non‐Hodgkin lymphoma

To the Editor: CNSmetastasis is relatively rare in NHL that is limited to the mediastinum. When CNS involvement occurs, it is often fatal, as our experience with an affected adolescent demonstrates. Accurate diagnosis and prompt treatment of this condition are essential for providing symptomatic relief, preserving neurologic function, and improving survival. A 19-year-old female with diffuse, large B-cell lymphoma of the mediastinum presented with a 10 day history of progressively worsening lower back pain after completing four cycles of CHOP chemotherapy 2 weeks ago. The back pain was associated with bilateral lower extremity weakness and paresthesia in addition to constipation and urinary retention. Physical examination revealed marked tenderness along the L4 to S1 vertebrae. Furthermore, shewas noted to have symmetric decrease in strength, sensation to pinprick, and reflexes in her lower limbs. There was no meningismus and digital rectal examination demonstrated normal anal tone. Part of the different diagnosis was the possibility of secondary CNS lymphoma in this young patient. ACT scan of the chest showed a reduction in size of the mediastinal lymphoma following chemotherapy, while a CT scan of the abdomen was benign. Findings on initial CT and gadolinium-enhanced MRI of the brain and spine were unremarkable. The lumbar puncture performed on admission showed elevated protein (2.38 g/L) and low glucose (0.3 mmol/L) levels in the CSF, but was also otherwise normal. Additional tests of the CSF, including cultures and serology for viral, fungal, and mycobacterial disease as well as cytology for malignant cells, were negative. Over the next 72 hr, attempts to repeat the lumbar puncture to obtain CSF for further analyses was unsuccessful. The patient reported excruciating pain that radiated down her legs as the lumbar puncture needle was advanced into her back. When this occurred, the lumbar puncture was aborted. Attempts under general anesthesia and fluoroscopic guidance were likewise unsuccessful, leaving clinicians with a diagnostic dilemma. Without a conclusive diagnosis, the patient meanwhile experienced progressive paresthesia and weakness in both feet and worsening back pain. Given the patient’s neurologic deterioration, she was offered empiric therapy with high-dose dexamethasone, methotrexate, intrathecal cytarabine, and local spinal irradiation for presumptive leptomeningeal disease. An Omaya reservoir was ultimately placed to gain access to CSF; results of all cytologic examination, both preceding and following empiric treatment, remained remarkably normal and consistently negative for malignant cells. Following initiation of therapy and 12 days after initial presentation, a repeat gadolinium MRI study showed substantial enhancement from T8 to L5 consistent with a diagnosis of extensive lymphomatous involvement of the spine. Despite transient clinical improvement shortly after therapy, the patient subsequently developed progressive neurologic impairment involving the upper limbs and cranial nerves. The patient ultimately expired secondary to complications of NHL. Autopsy revealed B-cell NHL involving the cerebellar leptomeninges with extensive spinal nerve root destruction. The lower spinal cord was marked by substantial fibrosis and collagen deposition which may be consistent with either malignant CNS invasion or necrosis induced by radiotherapy or chemotherapy. Secondary lymphomatous involvement of the CNS was first documented by Murchison in the early 19th century [1]. With the advent of more effective therapy against primary lymphoma in the past several decades, the natural history of lymphoma has been prolonged and the incidence of secondary CNS lymphomas has subsequently risen [2]. The standard for diagnosis of leptomeningeal disease continues to be the detection of malignant cells in the cerebrospinal fluid [3]. A MEDLINE review of published world literature between 1966 and 2004 did not reveal any reports rivaling the magnitude of diagnostic challenges encountered in our patient. Glantz et al. [4] previously found that false-negative results from cerebrospinal fluid cytology could be minimized by performing another lumbar puncture. Olson et al. [5] supported this finding, and reported the sensitivity of a single spinal tap and after multiple taps as 45 and 80%, respectively. Although