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Recurrent Thymoma With Stiff-Person Syndrome and Pure Red Blood Cell Aplasia

2014; Elsevier BV; Volume: 97; Issue: 5 Linguagem: Inglês

10.1016/j.athoracsur.2013.07.103

1552-6259

Rei Kobayashi, Masahiro Kaji, Sho Horiuchi, Naofumi Miyahara, Yumi Hino, Keiichi Suemasu,

Neuroblastoma Research and Treatments

Stiff-person syndrome (formerly known as stiff-man syndrome) is a very rare autoimmune and neurogenic disorder, thought to present as a paraneoplastic variant in association with thymoma. Pure red blood cell aplasia is also a paraneoplastic disorder associated with thymoma. Although separate cases of stiff-person syndrome and pure red blood cell aplasia have been reported, we describe here what is to our knowledge the first case of recurrent thymoma with both stiff-person syndrome and pure red blood cell aplasia. We describe the successful treatment of the neurogenic symptoms of stiff-person syndrome and the progressive anemia associated with pure red blood cell aplasia by tumor excision. Stiff-person syndrome (formerly known as stiff-man syndrome) is a very rare autoimmune and neurogenic disorder, thought to present as a paraneoplastic variant in association with thymoma. Pure red blood cell aplasia is also a paraneoplastic disorder associated with thymoma. Although separate cases of stiff-person syndrome and pure red blood cell aplasia have been reported, we describe here what is to our knowledge the first case of recurrent thymoma with both stiff-person syndrome and pure red blood cell aplasia. We describe the successful treatment of the neurogenic symptoms of stiff-person syndrome and the progressive anemia associated with pure red blood cell aplasia by tumor excision. Thymoma with two synchronous paraneoplastic diseases is very rare. Resection of the recurrent thymoma may resolve the two paraneoplastic syndromes at once and alleviate the associated symptoms. Here, we report a case of recurrent thymoma with both paraneoplastic stiff-person syndrome (SPS) and pure red blood cell aplasia. An 81-year-old woman with a growing recurrent mass on the left thoracic wall was referred to our department. She was experiencing slightly impaired ambulation caused by SPS and suffering dyspnea from progressive anemia, and she required frequent transfusions. Thirteen years earlier, the patient had symptoms of muscle spasms of the axial and bilateral upper and lower extremities, lumbago resulting from deformities of the trunk caused by the spasm, and general asthenia. Computed tomography (CT) of the chest led to a diagnosis of thymoma, and an extended thymectomy was performed. The patient had no history of diabetes, epilepsy, or other neurologic diseases. However, the first day after the operation, she experienced severe pain in her bilateral legs and trunk on slight physical contact and cramping pain even in the absence of physical contact. Her condition deteriorated to the point at which she was unable to walk or maintain a sitting position unaided. The neurologist in our hospital examined her, and clinical laboratory tests revealed an elevated level of anti–glutamic acid decarboxylase (GAD) antibody; however, the patient was not diabetic. SPS was diagnosed, and glucocorticoids were administered. The patient then recovered gradually and was discharged from the hospital when she regained ambulatory function. She was followed up regularly by the neurologist. In relation to the current admission, 13 years after thymectomy, CT of the chest revealed a recurrent chest wall mass, which had been slowly enlarging for 6 months (Fig 1). At this point, the patient presented with slightly progressive breathlessness and ambulatory disturbance, necessitating the use of a wheelchair. She had no other symptoms of SPS, for example, bilateral severe pain due to leg stiffness. Therefore, SPS was considered to be almost completely controlled with steroid administration (prednisolone, 10 mg/day). Subsequently, the patient had progressive and refractory anemia, requiring frequent transfusion with concentrated red blood cells before the second operation. Her anemia was normocytic and normochromic, with a reduced percentage of reticulocytes. In addition, bone marrow aspiration revealed erythroid aplasia and a normal level of myelocytes. Her levels of serum iron, antiacetylcholine receptor antibody, antinuclear antibody, and immunoglobulin M against parvovirus B19 were all within normal limits, although the percentage of reticulocytes was decreased. At this stage, pure red blood cell aplasia, in addition to SPS, was diagnosed. We decided to resect the tumor to control these paraneoplastic disorders. Preoperatively, we reduced the dose of steroid (prednisolone) to 5 mg every 2 days. Resection of the mass was achieved by the strategy of simultaneous chest wall resection and wedge partial resection of the left upper lung lobe, with the patient under general anesthesia combined with epidural anesthesia. The tumor was strongly fixed to the chest wall and the adjacent lung. We recognized that the tumor was invasive. However, adhesion of the other visceral pleura to the chest wall and mediastinum was small, so the operative procedure was achieved by video-assisted thoracotomy. Postoperatively, the patient recovered and was discharged from the hospital with no major morbidity 2 weeks after the operation. Her progressive anemia had substantially improved. She needed transfusion only a few times for 6 months after the second operation, whereas she had previously needed transfusion once or twice a week for 6 months before the second operation. She was able to walk well using a stick 3 months after the operation. On the basis of histologic examination, the tumor was classified as type B1 thymoma, predominantly a lymphocytic tumor, according to the World Health Organization criteria. The completely resected tumor had involved the lung and parietal pleura. A two-color flow cytometric examination revealed that 84.9% of all lymphocytes were CD4+ and CD8+, the typical phenotype of cortical thymocytes. After the second operation, the level of anti-GAD antibody in serum decreased to 13,000 U/mL (preoperative level, 19,000 U/mL; normal range, <1.5 U/mL). Several kinds of disease are associated with thymoma, but thymoma with two synchronous paraneoplastic diseases is very rare, although the exact incidence is unknown. Resection of the recurrent thymoma may also resolve the paraneoplastic syndrome and alleviate the associated symptoms [1Dropho S.J. Neurologic paraneoplastic syndrome.J Neurol Sci. 1998; 153: 27-33Google Scholar]. Here, we report a case of recurrent thymoma with both paraneoplastic SPS and pure red blood cell aplasia. To our knowledge, this is the first report of thymoma resection under these circumstances. Thymoma is a slow-growing but malignant tumor, and surgical treatment to prolong survival should be adopted after careful consideration [2Okumura M. Shiono H. Inoue M. et al.Outcome of surgical treatment for recurrent thymic epithelial tumors with reference to World Health Organization histologic classification system.J Surg Oncol. 2007; 95: 40-44Crossref PubMed Scopus (66) Google Scholar]. In particular, surgical treatment may not be suitable for elderly patients with cardiac diseases and impaired respiratory function. However, in cases such as the present one, in which thymoma was associated with paraneoplastic syndromes, the potential benefits of surgical treatment are greater because this can improve symptoms and self-sufficiency. In this case, tumor resection led to an improvement of anemia, and the patient regained mobility. Additionally, the histologic type of the primary lesion was B1 thymoma, and thus, surgical resection of the recurrent mass may have significantly contributed to survival [3Lucchi M. Davini F. Ricciardi R. et al.Management of pleural recurrence after curative resection of thymoma.J Thorac Cardiovasc Surg. 2009; 137: 1185-1189Abstract Full Text Full Text PDF PubMed Scopus (70) Google Scholar]. The causes and mechanism of SPS are unknown. However, elevated levels of anti-GAD antibody are thought to be present in approximately 60% of SPS cases. Anti-GAD antibodies may reduce γ-aminobutyric acid production in cerebrospinal fluid and thus induce symptoms such as spasm and pain [4Solimena M. Folli F. Aparisi R. et al.Autoantibodies to glutamic neurons and pancreatic beta cells in stiff-man syndrome.N Engl J Med. 1990; 322: 1555-1560Crossref PubMed Scopus (570) Google Scholar, 5Dinkel K. Meinck H.M. Jury K.M. et al.Inhibition of gamma-aminobutyric acid synthesis by glutamic acid decarboxylase autoantibodies in stiff-man syndrome.Ann Neurol. 1998; 44: 194-201Crossref PubMed Scopus (203) Google Scholar]. In the present case, the serum level of anti-GAD antibody decreased postoperatively. Accordingly, the level of anti-GAD antibody might reflect the severity of paraneoplastic symptoms. Acquired pure red blood cell aplasia is often idiopathic. An antibody produced in patients with thymoma, which is yet to be identified, might also cause progressive anemia. In conclusion, surgical treatment should be considered for thymoma, even in cases in which two paraneoplastic disorders occur together. In such cases, the plural paraneoplastic symptoms can be resolved simultaneously.