DISCUSSION

Lewis P. Rowland, Moderator

College of Physicians & Surgeons Columbia University

New York, New York 10032

DR. JOHNS: Dr. Swick presented one patient, a young girl, who had a tumor in her hip. I wonder if that was histologically confirmed as being thymoma?

In the sample of thymus glands that Dr. Papatestas showed us, there were several that were in more than one piece. I wonder if that’s the situation that occurs frequently with suprasternal thymectomy?

DR. DAWKINS: Dr. Papatestas, is the distribution of extrathymic changes found akin to that found in any of the forms of immunodeficiency? In other words, are there any simularities between those forms of immunodeficiency where you find lymphomas, and IgA deficiency, where there are more epithelial changes?

DR. SCHLEIFER: Dr. Papatestas, from all we’ve heard today it seems that improvement in myasthenia gravis following thymectomy is not directly a con- sequence of your removing thymitis or thyrnoma. In your large series, did you see any improvement in any associated autoimmune condition following thy- mectorny, and, if so, maybe we should consider thymectomy in systemic lupus or other autoimmune diseases?

DR. DRACHMAN: Dr. Papatestas, I wonder if you could give us an overall figure for the percentage of patients who improved after thymectorny and those who have a remission after thymectomy? DR. OOSTERHUIS: I studied the histopathology of the thymus in over a

hundred patients * and also found germinal centers in about two-thirds of the patients under the age of 40. There was no relation with the duration of the disease before thymectomy. I didn’t find a correlation of histopathology with the effect of thymectomy during the first three years, with only one exception. Patients who had a complete remission during the first year after thymectomy had significantly more germinal centers. This is just the opposite of the findings of the Mount Sinai group.

DR. GROB: I wonder if Dr. Papatestas would clarify for us the types of tumors that were encountered in patients with myasthenia gravis and also explain to us the data on which the effect of thyrnectomy on the incidence of neoplasm is based? Obviously this has to be on a cumulative, year by year basis, and it may involve comparing patients of different ages. Thymectomy has, up to recently, been done in younger individuals. Patients who have been followed for a long period of time without thymectomy, or who develop myas- thenia gravis in advanced age and have usually not been subjected to thymec- tomy, are more likely to have higher rates of most neoplastic diseases because

’’ OOSTERHUIS, H. J . G . H. 1974. The relation between the histopathology of the thymus gland and the effect of thymectomy in myasthenia gravis. Proc. 3rd Int. Cong. Muscle Diseases, Newcastle-upon-Tyne. Excerpta Medica Congress Series 334.

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Discussion 575

of age alone. While the observations on the relationship of neoplasm to myas- thenia and to thymectomy are extremely interesting, most of us have failed to make this correlation, although we have not had the numbers of patients that Dr. Papatestas has.

DR. SWICK: In answer to Dr. Johns’s question, the lady with a tumor in her hip was one of our four patients with nonmyasthenic thymomas. She did not have histology from the hip itself, but she did from the primary tumor and from the liver at the time of the recurrent symptoms. She subsequently re- sponded quite well to a course of radiotherapy and chemotherapy, and is now doing well.

DR. PAPATESTAS: The first question concerned the suprasternal removal of some of the specimens of thymus in more than one piece. In young myasthenic patients, each of the two lobes easily comes out in one piece. In older patients, it’s not unusual to fracture one or both lobes. It’s very important to mobilize both lobes before attempting removal, so that the lower poles can be identified.

The second question was about the pattern of cancers in immunodeficiency disorders. The increases that were noticed in our series were in lymphomas and breast cancer. Bilateral breast cancer and multiple cancers are extremely common among the nonoperated myasthenics, and the age of presentation is at a much earlier age than you would expect for these types of cancer.

With regard to the associated immune disorders, there were a few patients who had associated rheumatoid arthritis and associated lupus. There was no exacerbation of these diseases following thymectomy. As a matter of fact the patients with the associated diseases have been doing well, but whether this is the result of thymectomy or is the course of the disease is very difficult to say. The Japanese claim that they have seen good results following thymectomy for autoimmune diseases, but we don’t have any data.

With regard to the effect of thymectomy on the course of myasthenia gravis, in patients with absent germinal centers and short duration of disease we have had approximately 20% remission the first year, 50% remission by the fifth year, and an overall improvement in 90%. The numbers of remissions decrease in relation to the numbers of germinal centers and duration of disease. In patients who have had a long duration of disease and many germinal centers, we don’t see any remission the first year, but the end result, approximately 5 or 6 years after thymectomy, is indentical in both groups. We don’t under- stand why there is such a difference with Dr. Oosterhuis’s observations. There have been other reports that patients with many germinal centers have a quicker response, and that’s one of the reasons we did electromyographic studies, in order to have a more objective evaluation.

Dr. Grob asked if the incidence of neoplasm may have been influenced by differences in the age of patients in the various groups. We had published our preliminary results in 1971 on the incidence of tumors in myasthenics, and at that time we had age-matched the groups, and the difference between the thy- mectomy and the nonthymectomy populations was not due to differences in age. We are aware that there have not been reports from other centers on this subject. However, in Manchester, England in the 1950s when they were not doing thymectomies at the time that Keynes was removing thymuses, there was a very high incidence of neoplasm among the patients that were not operated on, particularly of breast cancer. It now appears that we originally underesti- mated the occurrence of neoplasms in the nonthymectomy population of myas-

516 Annals New York Academy of Sciences

thenics, since many of our patients are from out of state and our early follow-up letters did not ask about this. Recently, when we started asking about other operations or associated conditions, we turned up a large number of neoplasms. We believe that in myasthenic patients who have not had thymectomy there is a 6 to ?'-fold increase in neoplasms over what you would expect, while after thymectomy, in the patients who don't have remission, you should expect to see some neoplasm according to the age distribution of these patients, and we didn't have any.