Thymomas are epithelial neoplasms of the thymic gland, with 96% arising in the anterior/superior mediastinum. The remaining are ectopic thymomas that mainly arise from ectopically dispersed thymic tissue, mostly in the neck, lungs, pleura, thyroid, pericardium, and middle/posterior mediastinum . The histogenesis of ectopic thymomas is widely considered to involve thymic tissue displaced during embryonic development. Embryologically, the thymus originates from the third and to a certain extent fourth pharyngeal sacs. During the eighth gestational week, the thymic primordia gradually migrates toward the anterosuperior mediastinum. One hypothesis for the origin of ectopic thymomas is that neoplasia arises from thymic tissue misplaced during the embryonic descent. However, the cardiac system develops during the third gestational week, earlier than the development of the thymus. This hypothesis thus cannot explain thymomas arising in cardiac tissue. Another hypothesis is that ectopic thymomas can derive from stem cells that have retained the ability to differentiate into various cell lineages. These two are the theories for the origin of ectopic thymomas that have been most widely accepted [1, 3].
The thymoma in our patient occupied the RA, SVC and LBCV, and had not spread outside the heart and vessels. The main mass was located in the RA lumen almost freely from which tumor branches extended in the lumen of SVC and LBCV. Because the original thymus had involuted into a small, solid tissue, the intracardiac thymoma was reasonably thought to have originated from the RA. To the best of our knowledge, four cases of intracardiac ectopic thymoma have been reported in the English literature [2,3,4]. However, two of them arose within cardiac myxomas , so only two cases of pure intracardiac thymoma have been reported [2, 3]. Ectopic thymomas are only sporadically linked with MG . This is the first report of MC associated with pure intracardiac ectopic thymoma.
Anti-AChR or anti-MuSK antibodies are found in over 80% of patients with MG. Cases of MG without detectable antibodies against AChR or MuSK are seen in around 15%, and are termed “double-seronegative MG” . In our patient, despite double-seronegativity, MC was able to be diagnosed according to the clinical signs and a positive result from the classic edrophonium test. The patient actually recovered and was weaned from prolonged mechanical ventilation after IVIg administration. The main therapies for MC are IVIg and plasma exchange (PE) . IVIg therapy may offer similar efficacy to PE, but with fewer complications. The effect of those therapies lasts for only a few weeks, so corticosteroids are often used concurrently with IVIg and PE [8, 9]. IVIg was simply used for treatment in this case without administration of corticosteroids, as she showed MC associated with mild pneumonia.
Approximately one-third of patients with thymoma display MG . Thymectomy plays a role as a primary treatment in thymoma patients with MG, who usually show excellent prognosis . Nevertheless, MG recurs in some patients with thymoma after thymectomy, and such post-thymectomy MG is attributed to high serum titers of auto-antibodies against AChR [11,12,13]. Our patient developed MG post-thymectomy despite no history or symptoms of MG pre-thymectomy and was negative for both AChR and MuSK antibodies post-thymectomy. Some studies have suggested that thymomas can actively export large numbers of mature autoantigen-specific T cells into the peripheral blood, and those cells can persist in stimulating autoantibody production . In our patient, a comparison of the number of T cells between pre- and post-thymectomy was not available. In addition, the test for low-density lipoprotein receptor-related protein 4 (LRP4) antibodies, which have been identified as a potential autoantibody target in several double-seronegative MG patients, was not performed on our patient. However, LRP4-positive patients tend to be < 50 years old and predominantly show ocular or mild disease , suggesting that this form may have been unlikely in our patient. The reason for the late onset of post-thymectomy MG remains unclear. Very subtle symptoms of MG that were overlooked preoperatively might be one possible explanation. Predicting the natural course of ectopic thymoma is difficult due to the low incidence of the disease. Therefore, the optimal treatment of patients with ectopic thymomas is currently considered to be complete surgical resection. Incomplete resection represents a risk factor for the development of the post-thymectomy MG . Recurrence of intracardiac invasive thymoma has been reported . We resected the intracardiac thymoma in the present patient radically and confirmed the absence of masses in the heart and vessels on postoperative CT. As of the time of writing, the patient has remained free of symptoms for more than 9 months since surgery. Long-term follow-up is required, given the possibility of late recurrence .