Presence of crystalline inclusions in the peripheral nerve of a patient with IgA lambda monoclonal gammopathy of undetermined significance

Abstract

Association of a peripheral neuropathy with an IgA monoclonal gammopathy of undetermined significance (MGUS) is not commonly observed and is sometimes considered as coincidental. We present a case in which the nerve biopsy revealed the presence of crystalline inclusions in the endoneurium, a very unusual finding. A 75-year-old man complained of paresthesiae in both feet and unsteady gait for 6 months. He had no weakness, but deep tendon reflexes were absent and vibratory sensation distally diminished in both legs. An IgA lambda MGUS was evidenced in his serum at 10.2 g/L with 7% plasma cells in his bone marrow and no lytic lesion at skeletal examination. A superficial peroneal nerve biopsy was performed and showed numerous crystalline inclusions in the endoneurium. These were located in the cytoplasm of macrophagic histiocytes or free in the vicinity of nerve fibers. There was also a marked loss of myelinated nerve fibers and several "onion bulb" formations surrounding either isolated remyelinating fibers or small clusters of remyelinating fibers. Such crystalline inclusions have mainly been observed in the cytoplasm of plasma cells in cases of multiple myeloma, and correspond to non-secreted IgA or IgG immunoglobulins with a kappa or rarely lambda light chain. Such inclusions have also been reported in the cytoplasm of the epithelial cells from corneal fragments, in patients with multiple myeloma or IgG MGUS, and in the tubular cells from the kidney of patients with multiple myeloma and a nephrotic syndrome. In the literature, there is only one very briefly mentioned case of neuropathy associated with a myeloma and with crystalline inclusions present in the epineurium. Thus, in dysglobulinemic neuropathy, nerve fibers can be damaged by three kinds of interstitial deposits, easily identified by immunohistochemistry and at ultrastructural examination: the well known amyloid fibrils, granulo-fibrillar deposits and also crystalline inclusions.