A striking degree of hyperplasia of the medulla of the thymus characterized by lymphoid follicles with active germinal centers is found in the majority of cases. Hyperplasia is even more frequent in younger patients in the third and fourth decades. The cells in the centers of the follicles are histiocytes surrounded by helper T lymphocytes, B lymphocytes, and plasma cells; immunoglobulin G (IgG) is elaborated in the germinal follicles. These resemble the cellular reaction observed in the thyroid tissue of Hashimoto thyroiditis. Because the latter disease has been reproduced in animals by injecting extracts of thyroid with Freund adjuvants, it had long ago been suggested that the so-called thymitis of myasthenia gravis is the result of a similar autoimmune sensitization but the inciting events for this process are entirely unknown. Immunosuppression with steroids causes involution of the thymus.
With regard to thymic tumors, two forms have been described: one composed of histiocytic cells like the reticulum cells in the center of the follicles, and the other predominantly lymphocytic and considered to be lymphosarcomatous. Some of the tumors have a high proportion of spindle-shaped cells. Overlapping types have been common. Thymic tumors may be unattended by myasthenia, though myasthenia has eventually developed in all of the cases under our observation, sometimes 15 to 20 years after the tumor was removed surgically. According to Bril and colleagues, the severity of myasthenic symptoms is no different in patients with thymoma than it is from that in patients without a tumor, but our impression has been that patients with tumors, particularly children, often have a peculiar clinical course. For example, we have observed unexpected sudden remissions and severe relapses, as well as resistance to medications.
Many contemporary studies, including more than 40 autopsies at our hospitals, have confirmed Erb’s original contention that myasthenia gravis is a disease without a central nervous system lesion. The brain and spinal cord are normal unless damaged by hypoxia and hypotension from cardiorespiratory failure. Furthermore, the muscle fibers are generally intact, although in fatal cases with extensive paralysis, isolated fibers of esophageal, diaphragmatic, and eye muscles may undergo segmental necrosis with variable regeneration (Russell). Scattered aggregates of lymphocytes (lymphorrhages) are also observed, as originally noted by Buzzard, but none of these changes in muscle explains the widespread and severe weakness.
The main ultrastructural alterations occur in the motor endplate. These changes, elegantly demonstrated by A.G. Engel and associates (1976, 1977, 1987), consist of a reduction and simplification in the surface area of the postsynaptic membrane (sparse, shallow, abnormally wide, or absent secondary synaptic clefts) and a widening of the synaptic cleft (Fig. 46-1). The number and size of the presynaptic vesicles and their quanta of acetylcholine (ACh) are normal. The observation of regenerating axons near the junction, the many simplified junctions, and the absence of nerve terminals supplying some postsynaptic regions suggested to Engel and coworkers (1976, 1977, 1987) that there was an active process of degeneration and repair of the neuromuscular junction, particularly of the postsynaptic side.