Myasthenia gravis: clinical and histological features in relation to thymectomy.

Abstract

SYNOPSISThe clinical and thymic histological features of 23 patients who underwent thymectomy for myasthenia gravis have been examined and compared. Eighty-two per cent of patients with a nonneoplastic gland containing numerous germinal centres improved postoperatively, whereas 83% of patients with a non-neoplastic gland containing no germinal centres deteriorated or died. Glands with only slight involution and containing numerous germinal centres were more commonly seen in young female patients. The evidence relating thymic histological appearances with the postoperative progress of patients with myasthenia gravis is reviewed.An association between myasthenia gravis and the thymus gland was first suggested by Weigert in 1901. Although Schumacher and Roth (1913) reported the clinical improvement of a patient with myasthenia after removal of an enlarged non-neoplastic gland, it was not until the reports of Blalock et al. (1939) and Keynes (1949) that the beneficial effect of thymectomy was fully appreciated. Keynes concluded that, although the connection between myasthenia and abnormalities of the thymus gland was well established, there was no clue to how or why the gland acquired its abnormal function.Only recently have the histological appearances of the thymus gland and their relation to the clinical progress of patients after thymectomy received greater attention (Castleman and Norris, 1949;Mackay et al., 1968;Alpert et al., 1971;Seybold et al., 1971;Reinglass and Brickel, 1973;Vetters and Simpson, 1974). Opinions have varied from a clearly demonstrable association between thymic hyperplasia and postoperative improvement to a complete dissociation of these two parameters. It therefore seemed appropriate to make a clinical and pathological study of 23 myasthenic patients who had undergone thymectomy at the Manchester Royal Infirmary during the past 10 years. (Accepted 14 August 1975.) 38 METHODS PATIENTS Twenty-three patients with myasthenia gravis underwent thymectomy. Surgery was performed because of either increasing weakness despite treatment with anticholinesterases and in some cases steroids (19 patients) or the presence of a thymoma (four patients). At the time of operation all patients had evidence of ocular, bulbar, and limb weakness.The average age at onset of symptoms of patients without a thymoma was 32.6 years (range, 16-68 years) and the mean duration of symptoms before thymectomy was 4.9 years. The sex distribution showed a predominance of females with a ratio of 2.2: 1. Patients with a thymoma developed symptoms at 39, 49, 56, and 65 years and the mean preoperative duration of symptoms was 1.0 year. Three of these patients were male.HISTOLOGY Haematoxylin and eosin stained sections from all the paraffin blocks from each surgical section were examined by one of the authors (H.R.) without knowledge of the clinical details. The average number of sections to each specimen was three with a range of two to 10. The criteria used for assessment included the degree of gland involution, the overall ...

Tumours and tumour‐like conditions of the thymus other than thymoma; a practical approach

“…There are no firm criteria for diagnosing follicular thymic hyperplasia. Although finding lymph follicles with germinal centres is typical in myasthenia, this is not always the case, as the thymus gland in myasthenic patients may be devoid of lymphoid follicles and may even show an atrophic appearance altogether with only subtle changes 149–151 . Five grades of follicular thymic hyperplasia were distinguished by the myasthenia study group in Japan (grade 0, involuted thymus; grade I, accumulation of lymphocytes in the distended medulla; grade II, one follicle in one section; grade III, two to four follicles in one section; and grade IV, more than five follicles in one section or more than one follicle in each lobule) 152 .…”

“…Although finding lymph follicles with germinal centres is typical in myasthenia, this is not always the case, as the thymus gland in myasthenic patients may be devoid of lymphoid follicles and may even show an atrophic appearance altogether with only subtle changes. [149][150][151] Five grades of follicular thymic hyperplasia were distinguished by the myasthenia study group in Japan (grade 0, involuted thymus; grade I, accumulation of lymphocytes in the distended medulla; grade II, one follicle in one section; grade III, two to four follicles in one section; and grade IV, more than five follicles in one section or more than one follicle in each lobule). 152 It should be pointed out that the severity of myasthenia does not correlate with the grade, although data from Mori et al suggest that this may be dependent on the intrathymic topographical distribution of the lymphoid infiltrate and parenchyma.…”

Controversies about the treatment of myasthenia gravis.

“…'20 There had been reports of immunosuppressive drug therapy in only 46 patients and 38 of them had improved,'20 but 38 of these patients (including 32 who improved) had been reported from one centre by Mertens et al '12 By means of a poll of centres in the US, we could obtain information about 14 cases treated with immunosuppressive drugs, but without detailed data; improvement was reported in four of these cases and the drug was discontinued in three. In sum, at that time, 60 patients were known to have been treated and 36 had improved.…”

Thymic Abnormalities: Antigen or Antibody? Response to Thymectomy in My Asthenia Gravis*

“…Two groups reported a better prognosis in those with normal or involuted 37 Two series indicated that the presence of germinal centers tended to correlate with a good response to surgery. 38,39 Four others reported no orr relation.^^-^^ Germinal centers have been shown to be collections of B-cells and isolated thymocytes from hyperplastic glands produced anti-AChR antibodies in culture. 44-4a Our series tends to support a correlation between the presence of hyperplasia with an excellent response (remission 14/ 16, asymptomatic 3/4).…”