Clinical/Scientific Notes Diagnosis of neurolymphomatosis with FDG PET

Neurolymphomatosis (NL) is a rare condition caused by intraneural infiltration of malignant lymphocytes in peripheral nerves. Clinically, NL is characterized by a progressive and painful axonal polyneuropathy. It may develop in patients with widespread nonHodgkin lymphoma (NHL) but may also be the first manifestation or sole relapse site of NHL. In 50% of cases, it is associated with leptomeningeal involvement. The diagnosis has to be confirmed by biopsy of an affected nerve showing lymphomatous infiltration; however, this may not be feasible or nondiagnostic. We present a case that shows the value of [F]fluorodeoxyglucose (FDG) PET in such cases.1 Case report. In March 2001, a 57-year-old woman presented with progressive paresis of the left and right arm, with radicular pain radiating to the left thumb. Her medical history revealed a swelling of the left orbit in 1998, diagnosed elsewhere as a possible low-grade NHL, which had been treated with radiotherapy. At neurologic examination, there was atrophy of the left trapezius and deltoid muscles, with a paralysis and areflexia of the left arm and a mild paresis of the right deltoid muscle. Sensibility was diffusely impaired in the left arm. MRI showed enhancing roots C3 to C6 on the left and C4 and C5 on the right side (figure, A). CSF revealed a slightly increased monocytic cell count with 11% B-lymphocytes, 9% of which were of monoclonal origin, and the diagnosis of B-cell NHL was made. Further staging, including immunologic examination of peripheral blood and bone marrow and CT of neck, thorax, and abdomen did not reveal other localizations of the NHL. Electromyography (EMG) showed widespread denervation signs in the left arm but intact sensory nerve potentials, consistent with a polyradiculopathy and without evidence of peripheral nerve involvement. At this stage, the patient developed progressive motor disturbances of the tongue, right arm, and left leg. She was treated with radiotherapy of the neuraxis followed by intrathecal Ara-C. Initially, the symptoms improved dramatically, and strength improved to a paresis of Medical Research Council (MRC) grade 3 to 4. However, in July 2001, the pain in the left arm returned, and the function of the left arm deteriorated to a paresis MRC grade 2 to 3 despite ongoing intrathecal treatment. T1-weighted subtraction MR images showed gadolinium-enhanced signal of root C8, continuing outside the dural sac (figure, B). Also, a dubious gadolinium-enhanced signal of the cervicobrachial plexus on the left side was seen (figure, C). Repeat EMG showed a decreased amplitude of sensory potentials of the left arm. CSF showed a persistent mild monocytic pleiocytosis, without a monoclonal cell proliferation. Renewed staging showed no evidence of systemic NHL. An FDG PET was performed, which showed two regions of increased metabolism: one in the left cervicobrachial region consistent with plexus involvement and another in the right submandibular region (figure, D). Ultrasound identified an enlarged submandibular lymph node, which was biopsied; microscopy showed a large B-cell NHL. The patient was treated with six cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) chemotherapy with intrathecal methotrexate and Ara-C. The function of the left arm improved during the treatment up to a global MRC scale score of 4, and the pain decreased. Currently, 4 years after treatment, there is no evidence of tumor activity. Discussion. Our patient with leptomeningeal lymphoma without evidence of systemic disease was initially treated with radiotherapy of the neuraxis. After an initial dramatic improvement, clinical signs and symptoms quickly recurred. Based on the clinical findings and suggestive but uncertain MRI findings, we suspected intraneural lymphoma localization within the cervicobrachial plexus. This suspicion was substantiated by the FDG PET scan, which also suggested asystemic lymphoma localization in a submandibular gland. Apart from nerve biopsy, MRI may also give evidence of NL by revealing enhancing and thickened peripheral nerves.1-3 FDG PET is increasingly recognized as a novel technique useful in staging and monitoring treatment responses in patients with cancer, including lymphoma.4,5 As shown in the current case, FDG PET may have clinical value when the diagnosis of NL is considered, especially when lymphomatous infiltration in large peripheral nerves or plexus is suspected and histologic findings of the biopsy is negative or not possible.6,7 The treatment of choice for NL is systemic chemotherapy. Although in some patients, the outcome is poor, the durable response in our patient shows that intraneural lymphoma localizations can be susceptible to chemotherapy with agents that do not readily penetrate an intact blood–brain barrier, although penetration in peripheral nerves may be different.