Muscle pathology, thymoma, and immunological abnormalities in patients with myasthenia gravis.

In 1901, Weigert described a patient with myasthenia gravis, thymoma, and lymphorrhages. He regarded these lymphocellular infiltrates in the muscles as metastases of the thymoma. Lymphorrhages have since been frequently described in patients with myasthenia, with or without thymoma (Link, 1903; Rowland, Hoefer, Aranow, and Houston Merritt, 1956; Mendelow, 1958; Genkins, Mendelow, Sobel, and Osserman, 1961). Fenichel and Shy (1963), Fenichel (1966), and Engel and McFarlin (1966) likewise mentioned the presence of lymphorrhages in muscle biopsies, but unrelated to the presence of a thymoma. In our own material (Oosterhuis 1963, 1964) a correlation between the presence of a thymoma and the lymphocellular infiltrations could be demonstrated. Antibodies against muscular tissue have been demonstrated in 30-40% of patients with myasthenia gravis, and in 95-100% of myasthenic patients with a thymoma (Van der Geld, Feltkamp, Loghem, Oosterhuis, and Biemond, 1963; Strauss, 1966; Oosterhuis, Van der Geld, and Feltkamp, 1967). This finding supported the assumption that myasthenia gravis might be included among the autoimmune diseases. In all idiopathic autoimmune diseases, lymphocellular infiltrates are found in the affected organs. The presence of such infiltrates in the muscles of patients with myasthenia gravis suggests that the muscle is involved in or the target of cellular immune reaction, in which circulating antibodies against muscular tissue might be of secondary importance. Besides lymphocellular infiltrates, other abnormalities have been described in the muscles of patients with myasthenia-for example, neurogenic muscular atrophy (Russell, 1953; Fenichel and Shy, 1963; Fenichel, 1966; Engel and McFarlin, 1966) and focal myositis (Russell, 1953; Genkins et al., 1961). The latter abnormality seems to occur chiefly in patients with a thymoma (Genkins et al., 1961). The neurogenic abnormalities, however, are believed not to correlate with the presence of a thymoma (Fenichel and Shy, 1963). The purpose of the present study was to establish whether some of the muscular changes most commonly found in patients with myasthenialymphorrhages, neurogenic changes, and focal myositis-correlate with the presence of a thymoma and/or the presence of circulating antibodies against muscular tissue or nuclei (A.N.F.).