An unusual assortment of polyneuropathies has been associated with non-Hodgkin lymphomas of both Tand B-cell types and with several related conditions, such as Castleman disease (angiofollicular lymphoid hyperplasia), intravascular T-cell lymphoma (and the related lymphomatoid granulomatosis; see Chap. 30), hypersensitivity lymph node hyperplasia (angioimmunoblastic or immunoblastic lymphadenopathy), and Kimura disease (lymphoid hyperplasia with eosinophilia mainly involving skin). In most of these neuropathies, particularly the one associated with Castleman disease, there is a paraproteinemia, often polyclonal, thereby relating this group to the paraproteinemic neuropathies and to osteosclerotic myeloma, discussed later. In several of our patients, the neuropathic manifestations appeared simultaneously with lymph node enlargement in the groin, axilla, or thorax. Clinically, the illness may take the form of GBS, chronic demyelinating polyneuropathy, subacute motor polyneuropathy or anterior horn cell disease, lumbar and brachial plexopathy, or a polyradiculopathy—each occurring as a paralymphomatous condition clearly separable from cases of meningeal and neural infiltration by tumor. Corticosteroids have been helpful in some of our patients with the lymphoid diseases; in others, the neuropathy resolves spontaneously or with radiation of the lymph nodes but otherwise progresses for months. Vallat and colleagues have summarized their experience with the more conventional types of neuropathy accompanying non-Hodgkin lymphoma. Intravascular lymphoma, a widespread neoplastic and vascular disease (described in Chap. 30), may infiltrate the peripheral nerves in a multiple mononeuropathy pattern.
The various forms of paraneoplastic polyneuropathy are manifest clinically in 2 to 5 percent of patients with malignant disease. The figures are higher if one includes the neuropathies accounted for by malnutrition and pressure palsies that occur in the later stages of cancer and those identified by EMG in asymptomatic patients (Henson and Urich). Carcinoma of the lung accounts for approximately 50 percent of the cases of paraneoplastic sensorimotor polyneuropathy and for 75 percent of those with pure sensory neuropathy (Croft and Wilkinson); nevertheless, these neuropathies may be associated with neoplasms of all types.
Although anti-Hu binds to the peripheral nerve, the immunopathology of the paraneoplastic polyneuropathies has not been completely defined. In the purely sensory type, there is not only a loss of nerve cells in the dorsal root ganglia but also an inflammatory reaction (Horwich et al)—much the same changes as occur with the sensory neuronopathy of Sjögren syndrome. In the mixed sensorimotor polyneuropathy, degeneration is greater in the distal than it is in the proximal segments of the peripheral nerves, but it extends into the roots in advanced cases. Dorsal root ganglion cells may be reduced in number in both types. If the histologic examination is performed early in the course of the neuropathy, sparse infiltrates of lymphocytes are observed distributed in foci around blood vessels. No tumor cells are seen in the nerves or spinal ganglia, unlike the rare instances of carcinomatous and lymphomatous mononeuropathy multiplex, in which tumor cells actually infiltrate nerves. Degeneration of the dorsal columns and chromatolysis of anterior horn cells are secondary to changes in the peripheral nerves and roots.
The prognosis of the paraneoplastic neuropathies is poor. Even though the polyneuropathy may stabilize or even remit to some extent on its own or with therapy, most patients succumb to the underlying tumor within a year.