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A 35-year-old man had prolonged occupational exposure to lead carboxylate, triethylbenzene, xylene, and dichloromethane, when he developed a subacute predominantly sensory neuropathy. Ultrastructural examination of a peripheral nerve biopsy showed axonal degeneration and unusual lesions of the myelin, with Schwann cell sequestration of vesicular and lamellar debris. Biochemical analysis of lead in a frozen peripheral nerve specimen revealed no significant difference between the propositus and a control. The authors were unable to find any similar peripheral nerve lesions in the literature dealing with neurotoxic chemicals. Any of the several organic solvents could have equally caused the neuropathy and may have been potentialized by the other chemicals.

In 1969, Fardeau and Engel described polygonal organelles containing crystalline-like structures located in the Schwann cell cytoplasm of unmyelinated fibers. Such inclusions were reported in various conditions, mainly with axonal lesions. They were also reported in a few cases of peripheral neuropathy associated with primary mitochondriopathy. Although they are surrounded by a double membrane, their mitochondrial origin is not definitely proven. Their significance remains obscure but they deserve to be better known as Fardeau-Engel bodies, so as not to be mistaken with mitochondrial crystalline inclusions, which are frequently observed in patients with ragged-red fibers in muscle.

The authors recently reexamined the peripheral nerve biopsies from 42 patients with chronic inflammatory demyelinating polyneuropathy (CIDP). There were 27 males and 15 females, aged from 9 to 84 years, and 13 had relapses. No patient had vasculitis, monoclonal gammopathy, tumor, diabetes mellitus, Lyme disease, familial neuropathy, HIV, or any other immune deficiency. In the endoneurium, perivascular inflammatory cell infiltrates were present in only one case, but scattered histiocytes marked by KP1 on paraffin-embedded fragments were present in every case and there were no T-lymphocytes. At ultrastructural examination macrophage-associated demyelination was observed in 17 cases, of which 6 had relapses separated by intervals of several months or years. Axonal lesions without associated primary demyelination were observed in 4 cases and 3 of these had relapses. Thirty-two patients had mixed lesions of demyelination and axonal involvement. This study confirms other recent data indicating that in all cases of CIDP, macrophages are present in the endoneurium. Macrophage-associated demyelination is the characteristic feature of demyelinating forms. On the other hand, isolated primary axonal forms, which have been known since 1989, are relatively frequent and prone to relapses.

Inflammatory polyneuropathies are mainly known by their acute form, Guillain-Barré syndrome, but there are also chronic cases and all are considered as having an autoimmune mechanism. In each form, peripheral nerve biopsies show scattered macrophages in the endoneurium and in certain cases macrophages invade the Schwann cell cytoplasm and destroy the myelin sheath. In rarer cases there is a primary axonal degeneration. The authors studied two chronic cases, which both exhibited mixed primitive axonal and demyelinating lesions, with peculiar histiocytes in the endoneurium. These rounded cells were characteristically well marked by KP1 but showed well-developed rough endoplasmic reticulum cysternae at ultrastructural examination. Such plasmacytoid histiocytes have mainly been studied in subacute lymphadenopathies and have been only briefly illustrated in a few cases of peripheral neuropathies due to Lyme disease or HIV infection. The two cases reported here had no associated diseases and probably correspond to a peculiar subacute autoimmune reaction.

Characteristic myelin modifications in patients with IgM monoclonal gammopathy and anti-MAG activity have mainly been studied in cases of undetermined significance, but also exist in cases with indolent Waldenström's macroglobulinemia, i.e., when lymphoplasmocytic infiltration in bone marrow is 15% or more, without any visceral involvement. Since 1983, the authors have examined nerve biopsies from 8 cases with Waldenström's macroglobulinelia by direct immunofluorescence examination on frozen sections and ultrastructural examination. At direct immunofluorescence, fixation of anti-IgM serum on myelinated fibers was present in 7 cases. At ultrastructural examination, a widening of some myelin lamellae at the periphery of a few fibers was visible in 8 cases. A few fibers with hypermyelination were present in 5 cases. In 2 of these 5 cases widening of some myelin lamellae was present in numerous fibers, 88% in one of them. Frequently, there was a major widening of some myelin lamellae with dilated lamellae present in the inner part of the myelin sheath. Certain lamellae were more dilated, up to 50 nm. Occasionally, enlarged lamellae were not compacted with each other. The authors also examined nerve biopsies from 36 patients with IgM monoclonal gammopathy of undetermined significance and anti-MAG activity, but found only one case with major widening of some myelin lamellae. Five other cases with major widening of some myelin lamellae, 4 Waldenström's macroglobulinemia and 1 IgM monoclonal gammopathy of undetermined significance, have been reported. Given that demyelinating neuropathies are far more numerous in cases with IgM monoclonal gammopathy of undetermined significance, it is likely that cases of indolent Waldenström's macroglobulinemia are prone to develop major myelin modifications, possibly due to another mechanism, added to the classic anti-MAG activity.

Since 1979, the authors have studied 49 peripheral nerve biopsies presenting uncompacted myelin lamellae (UML). Based on the ultrastructural pattern of UML they propose a 3-category classification. The first category includes cases displaying regular UML, which was observed in 43 cases; it was more frequent in 9 cases with polyneuropathy organomegaly endocrinopathy m-protein skin changes (POEMS) syndrome as well as in 1 case of Charcot-Marie-Tooth 1B with a novel point mutation in the P0 gene. The second category consists of cases showing irregular UML, observed in 4 cases with IgM monoclonal gammopathy and anti-myelin-associated glycoprotein (MAG) activity. This group included 1 benign case and 3 B-cell malignant lymphomas. The third category is complex UML, which was present in 2 unrelated patients with an Arg 98 His missense mutation in the P0 protein gene. Irregular and complex UML are respectively related to MAG and P0, which play a crucial role in myelin lamellae compaction and adhesion.

A case of amyloid neuropathy associated with a multiple myeloma IgG light chain is reported. Under light microscopy the peripheral nerve exhibited several amyloid deposits. Electron microscopy revealed numerous amyloid deposits; at their periphery, macropha-gic histiocytes were observed, containing a few tufts of parallel fibrils in their cytoplasm. A few plasma cells were scattered in the endoneurium and did not exhibit such a relationship. These findings resemble those recently observed in stem-cell cultures of IgG lambda chain human myeloma.