Metastatic melanoma presenting with subacute sensory neuronopathy

Abstract

Subacute sensory neuronopathy (SSN) is characterized by loss of sensory nerve fibers due to destruction of dorsal root ganglion neurons and may be related to a malignancy, Sjögren s syndrome, HIV, chemotherapy, and pyridoxine. Small-cell lung carcinoma is the most common malignancy associated with SSN, but it has also been described with breast, ovarian, and prostate cancers; sarcoma; and Hodgkin lymphoma. SSN has not been associated with malignant melanoma. A 52-year-old man was referred for evaluation of a presumed neuropathy. Five years earlier a malignant melanoma had been removed from the skin over the right scapula. Axillary lymph nodes were removed at that time as well, due to one positive sentinel node. On clinical follow-up the patient showed no signs of recurrence and received no further treatment. Twelve months before referral, he experienced sudden onset of numbness in the feet and hands, difficulty with fine motor skills, and unsteady gait, all of which progressed over 5 months and then stabilized. The patient was otherwise healthy, had not received chemotherapy or pyridoxine, did not have diabetes, and had no history of alcohol abuse. Neurological examination revealed normal muscle strength, hypoactive deep tendon reflexes, impaired pinprick, temperature, and light touch sensations from the wrist and ankles distally, reduced distal position and vibration sensations, and a broad-based unsteady gait with a positive Romberg test. Nerve conduction studies (NCS) showed reduced sensory amplitudes (asymmetric in the sural nerves) with normal sensory conduction velocities (Table 1). Motor nerve studies were normal. Blood tests revealed normal or negative erythrocyte sedimentation rate, C-reactive protein, anti-nuclear antibodies, anti-neutrophil cytoplasmic antibodies, anti-SSA, anti-SSB (anti-La), HIV, and hepatitis studies. A monoclonal immunoglobulin G level of 2 g/L was found and a diagnosis of monoclonal gammopathy of undetermined significance was established. Paraneoplastic antibody screening showed no antiHu antibodies (Ab), whereas anti-SOX1 and anti-Zic4 Ab were slightly positive but did not bind via indirect immunofluorescence to primate cerebellar slices and were considered clinically insignificant findings. Cerebrospinal fluid (CSF) was acellular without malignant cells. CSF protein level was normal, and there were oligoclonal bands with a normal IgG index. Whole-body computed tomographic fluorodeoxyglucose positron emission tomography scan revealed two hypermetabolic enlarged lymph nodes in the mediastinum (Figure 1). Lymph node biopsy contained metastatic melanoma cells that stained positive with S100, MelanA, and SOX10. Analysis of the BRAF gene from biopsied cells revealed a mutation (c.1799 T > A, p.V600E). Three months after initiation of pembrolizumab treatment of metastases, the patient reported improved hand function although sensory disturbances in legs and gait instability were unchanged. Neurological examination was unaltered except that Achilles reflexes were now absent. NCS 8 months after treatment showed that the sensory nerve action potential in the right sural nerve was no longer absent and there was a slight increase in amplitude in six nerves (Table 1).