Search

A case was 73-year-old man, who had history of laparoscopic high anterior resection surgery for rectal cancer, followed by adjuvant chemotherapy 2 years ago. Preoperative diagnosis was anterior mediastinal tumor, with multiple intrapulmonary nodules noted, though no increasing tendency. During adjuvant chemotherapy for colorectal cancer, the anterior mediastinal tumor showed some shrinkage, while that and 3 intrapulmonary nodules slowly increased in size after completion, thus rectal cancer pulmonary and mediastinal metastasis were suspected. Complete resection of the intrapulmonary nodules and anterior mediastinal tumor was considered feasible. Thoracoscopic observation revealed multiple small pleural seeding lesions and all speculated to be intrapulmonary metastases before surgery were also pleural lesions. Intraoperative rapid diagnostic findings of a biopsy section revealed possible colorectal cancer metastasis, though histological type was not revealed. Final histopathological diagnosis was pleural dissemination of thymic carcinoma. Lenvatinib was introduced 2 months later for thymic carcinoma with pleural dissemination. Two years after surgery, the anterior mediastinum primary tumor had slightly decreased and the pleural nodules also showed a shrinking tendency. In such cases of small tumor with increasing tendency and irregular margins, thymic carcinoma should be considered when planning treatment.

We present a case of a 54-year-old woman. She was attending our department for thymoma-associated generalized myasthenia gravis. While she was treated with intravenous immunoglobulins for the exacerbation of myasthenic symptoms, she suddenly lost her consciousness for the first time and continued to have mild disorientation along with anterograde and retrograde amnesia afterwards. The symptoms improved after steroid pulse therapy. After searching for autoantibodies, she was diagnosed with anti-VGKC complex antibody-associated limbic encephalitis. As one-third of cases are complicated by thymoma, anti-VGKC complex antibody-positive limbic encephalitis has the aspect of a paraneoplastic neurological syndrome. In this case, masses suspected to be a recurrence of thymoma were found. In cases of thymoma, involvement of anti-VGKC complex antibodies should be considered when central nervous system symptoms appear, and when anti-VGKC complex antibodies are positive, recurrence or exacerbation of thymoma should be considered.

A 74-year-old Japanese woman, who had been previously diagnosed as ocular myasthenia gravis (MG), presented to our hospital complaining of dropped head and increased fatiguability while eating. The edrophonium test was positive and decremental response was recorded on repetitive nerve stimulation. Her clinical presentation was compatible with generalized MG, and anti-AChR, Kv1.4 and titin antibodies turned out positive. Contrast enhanced CT scan showed no tumorous lesion such as thymoma. We initiated her treatment with a minimum dose of oral prednisolone. However, her condition got worse even after intravenous immune globulin and experienced myasthenic crisis twice, the former of which led to cardiopulmonary arrest. As she did not respond to traditional treatments, we determined to perform extended thymectomy. The histopathology showed atrophic change but her condition rapidly improved in several days after the operation, and soon she was weaned off the ventilator. Shortly thereafter her symptoms disappeared, followed by the titers of the antibodies above found all markedly decreased. It remains unclear how the atrophic thymus acted on the pathogenesis of refractory generalized MG.

A 51-year-old Japanese man presenting with a several-month history of parasomnia, orthostatic hypotension and generalized myokymia was admitted to our hospital. He had a past medical history of unresectable recurrent thymoma, but chemotherapy for thymoma was discontinued according to the patient's decision four years before this hospitalization, and the thymoma had enlarged. He exhibited symptoms of the peripheral nervous system (myokymia), central nervous system (parasomnia, short-term memory impairment), and autonomic nervous system (orthostatic hypotension), and his serum was positive for voltage-gated potassium channel (VGKC)-complex antibodies. Based on the above findings, Morvan syndrome was diagnosed. Resumption of chemotherapy for thymoma resulted in shrinkage of the thymoma accompanied by remission of Morvan syndrome. Subsequently, discontinuation of chemotherapy led to aggravation of thymoma with recurrence of Morvan syndrome. This clinical course suggests a strong correlation between the disease activity of thymoma and Morvan syndrome. In the present case of Morvan syndrome associated with unresectable thymoma, chemotherapy contributed to the remission of Morvan syndrome. Our patient suggests a possibility that chemotherapy for thymoma is a useful treatment for Morvan syndrome.

We report a 62-year-old woman with thymoma associated myasthenia gravis (MG). She had significant dysphagia and was treated with corticosteroids, intravenous immunoglobulin (IVIG), immunoadsorption plasmapheresis (IAPP), and immunosuppressive drugs, and the extended thymectomy. Her symptoms gradually improved, but 3 weeks after thymectomy, her bulbar symptoms recurred. Although she was treated with repeated IVIG and IAPP, her symptom remained. Finally, after starting eculizumab did her symptoms go into complete remission. This case suggests the efficacy of anti-complement therapy for postoperative exacerbation of MG.

Acquired pure red cell aplasia (PRCA) develops in a variety of contexts and thus, should be regarded as a syndrome. The three major subtypes of acquired PRCA are idiopathic PRCA, T cell large granular lymphocytic leukemia (T-LGLL)-associated PRCA, and thymoma-associated PRCA. Although the Japanese National Research Group on Idiopathic Bone Marrow Failure Syndromes of the Ministry of Health, Labor and Welfare of Japan has made significant contributions to our understanding of PRCA, details of its clinical characteristics, and pathophysiological mechanisms remain largely unknown. A recent epidemiological analysis using the JSH Hematologic Disease Registry revealed that approximately 100 new cases with acquired PRCA were diagnosed annually in Japan, which was higher than previously thought to be. The median age of the patients was 73 years. A prospective observational study on chronic PRCA (PRCA2016) is currently ongoing, and it may provide new clinical insights into acquired PRCA. Dysregulation of T cells has been shown to play a central role in PRCA. We studied T cell clonalities and STAT3 mutations in 90 PRCA patients and discovered that clonal T cell expansions were frequently recognized and closely associated with STAT3 mutations in the three major types of PRCA.

We report herein the case of a 79-year-old woman who experienced difficulties in swallowing, dysarthria, dropped head, and muscle weakness associated with diurnal and day-to-day variation. We made a diagnosis of generalized myasthenia gravis (MG) with anti-acetylcholine receptor antibodies. Contrast-enhanced computed tomography showed no sign of thymoma. As the MG worsened, the patient presented with severe bradycardia. Chest compressions were performed on days 6 and 7 after admission and she underwent implantation of a temporary pacemaker. The arrhythmia resolved after strong immunosuppressive treatment, and anti-striational antibodies, including anti-muscular voltage-gated potassium channel-complex (Kv1.4) antibody and anti-titin antibody, were subsequently detected. This case implies the possible involvement of anti-striational antibodies in bradycardia.

We conducted a survey of the outpatient pharmacotherapy we administered from April 2016 to March 2019 to understand trends in chemotherapy for respiratory thoracic malignancies, such as lung cancer. Over the 3-year period, 19,408 were treated in the outpatient chemotherapy department. Of these, 1,270(6.5%)had respiratory thoracic malignancies. The total number of patients and the number of patients with thoracic malignancies(%) were 5,815 and 320(5.5%); 6,344 and 434(6.8%); and 7,247 and 516(7.1%)in FY2016, FY2017 and FY2018, respectively. This shows that both increased during the study period. Each patient was treated in the chemotherapy department multiple times, and treatment for thoracic malignancies was initiated in 161 patients. The female:male ratio was 27%:73%, and the patients' median age(range)was 68 years(range: 36-84 years). Lung cancer was the most common disease(91%), followed by malignant pleural mesothelioma(5%), thymoma(2%), thymic carcinoma(1%), and synovial sarcoma(1%). The most common histological type of lung cancer was adenocarcinoma(67%), followed by squamous cell carcinoma(17%), small cell carcinoma( 7%), and others(9%). Outpatient chemotherapy was introduced as a first-line, second-line, and third-line or later treatment in 46%, 28%, and 22% of cases, respectively. While the number of patients increased, the number of new patients with thoracic malignancies decreased from 58 in FY2016 to 52 in FY2017 and 51 in FY2018. Conversely, the number of visits to the chemotherapy department by each new patient almost doubled from 5.5 in FY2016 to 8.5 in FY2017 and 10.1 in FY2018. The proportion of patients for which immunotherapy was included in the induction treatment regimen increased from 28% and 24% in FY2016 and FY2017, respectively, to 39% in FY2018. The increase in the use of outpatient chemotherapy for respiratory thoracic malignancies was due to the increase in the proportion of patients undergoing immunotherapy and the number of visits to the chemotherapy department per patient. It is important to implement measures to help prolong and increase the use of outpatient pharmacotherapy for respiratory thoracic malignancies by cooperating with surrounding medical institutions and increasing the number of beds available.

We report a case of preoperative spontaneous regression of thymoma in a 66-year-old woman who presented chest pain. Chest computed tomography revealed a well-defined tumor in the anterior mediastinum. The long axis of the tumor decreased from 25 to 18 mm during 1 month preoperatively. Video-assisted thoracoscopic thymothymectomy was performed for definitive diagnosis and treatment. Histopathologically, the tumor mainly comprised necrotic components with partially viable cells, and was diagnosed as a thymoma. The occlusion of the feeding artery by organized thrombus was found by pathology and it was considered to be the cause of coagulative necrosis.

This report presents the case of a 68-year-old female patient previously diagnosed with thymoma by her local doctor. She was referred to our hospital for surgery, and the thymoma was removed and diagnosed as a World Health Organization (WHO) classification type AB thymoma. After surgery, she experienced general malaise, a loss of appetite, and weight loss, so she visited our hospital in May 2019. A blood test showed hypogammaglobulinemia and low B lymphocytes. A bone marrow examination revealed no morphological abnormalities. Flow cytometric analysis indicated a marked decrease in both the B cell-related surface markers CD19 and CD20 and the T cell-related surface marker CD4, and the CD4/CD8 ratio was also low. She was diagnosed with Good's syndrome, and immunoglobulin replacement therapy was administered. She subsequently developed hemophagocytic lymphohistiocytosis (HLH) due to infection and was treated according to the HLH2004 protocol, but she finally succumbed to multiple organ damage as a result of sepsis. Given that Good's syndrome is associated with both humoral and cellular immune dysfunctions, affected patients tend to develop severe infections and have a poor prognosis. In such cases, early detection, regular immunoglobulin replacement therapy, and infection prevention therapies are important.

The case is 61 years old, female. The mediastinal mass was pointed out at a medical examination, and she visited our hospital. A plain computed tomography (CT) scan showed a 12×35 mm mass in the anterior mediastinum, and a thymoma was suspected. Magnetic resonance imaging( MRI) showed low signal at T1-weighted image and high signal at T2-weighted image. A benign cystic mass such as a thymic cyst and a pericardial cyst was suspected, and thoracoscopic resection was performed. Pathologically, a bronchogenic cyst was diagnosed.

A 74-year-old man was admitted to hospital due to suspected acute leukemia. He had a history of thymic carcinoma, which had been treated with carboplatin in combination with either paclitaxel or amrubicin. However, the tumor remained unresponsive to these treatments. Administration of tegafur/gimeracil/oteracil (TS-1) was initiated, which resulted in tumor size reduction and a partial response. However, leukopenia persisted after the last TS-1 treatment, and four years after the initial treatment, increased blast cell counts were found in a blood film . Bone marrow analysis showed blasts with Auer rods, faggot cells, and dysplastic promyelocytes. Flow cytometry was positive for CD13, CD33, CD34, CD117, and myeloperoxidase, but negative for HLA-DR. PML-RARA fluorescence in situ hybridization was positive. Cytogenetic analysis revealed 47,XY,t (15;17) (q22;q21),+21. Thus, therapy-related acute promyelocytic leukemia (tAPL) was diagnosed. The patient achieved and maintained complete remission for more than 20 months by a de novo APL-treatment regimen including all-trans retinoic acid, arsenic trioxide and tamibarotene. Moreover, the thymic carcinoma has remained stable. Although secondary malignancies of thymic carcinoma have been previously reported, therapy-related leukemia, especially tAPL, is very rare.

A 64-year-old male presented with a rapidly growing anterior mediastinal mass during the clinical course of atypical chronic myeloid leukemia. A needle biopsy performed for suspected myeloid sarcoma revealed the presence of Aspergillus abscess. Early diagnosis of mediastinal abscesses, which are associated with a high mortality rate, can prevent the progression of severity. Infectious abscesses should be considered for prompt qualitative diagnosis in patients with mediastinal masses. Thymoma, germ cell tumor, and malignant lymphoma are the most common anterior mediastinal tumors, whereas infectious abscesses should also be considered when myeloid sarcoma is suspected in patients with an underlying myeloid tumor.

A 69-year-old man was pointed out the anterior mediastinal mass on chest computed tomography (CT). Since the thymoma was suspected, thymectomy was performed through median sternotomy. The tumor was encapsulated and did not directly invade adjacent organs. The tumor was 8.3×5.3×8.2 cm in size. Histological examination of the resected specimen showed a large mucinous component and a small fibrous component, both containing many atypical spindle cells and multinuclear giant cells, and fat cells and atypical lipoblasts observed in a small part of the specimen. The postoperative pathological diagnosis was dedifferentiated liposarcoma. No relapse is observed without adjuvant therapy at 1 year after surgery.

Morvan syndrome is a rare autoimmune neurological disease characterized by peripheral nerve hyperexcitability, autonomic dysfunction and encephalopathy. Morvan syndrome is often associated with thymoma as a paraneoplastic condition. Here we present a rare case of Morvan syndrome with ectopic hilar thymoma after extended thymectomy for myasthenia gravis.

A 76-year-old man was referred to our hospital because of an abnormal shadow on chest X-ray. His physical exams and laboratory data were not notable. Chest computed tomography (CT) showed 2 nodular lesions with clear margin in anterior mediastinum. The nodule at the left inferior pole of the thymus was 9 cm in diameter, and another one at the right inferior pole was 3.5 cm in diameter. We performed thymo-thymectomy by median sternotomy. Histological study revealed that the left tumor was type B2 thymoma and the other one was type A thymoma. Both were completely encapsulated without invasion, which means stage Ⅰ by Masaoka's classification. The patient has showed no evidence of recurrence for 11 years following the surgery. This is the 1st case in Japan that reported synchronous multicentric thymoma with apparently different histology of type A and B2.

Good syndrome is a rare condition in which thymoma is associated with hypogammaglobulinemia; it is characterized by repeated respiratory or systemic infections caused by bacteria, viruses, and fungi, as well as with various autoimmune disorders such as pure red cell aplasia. A 65-year-old woman was admitted to our hospital with ptosis and abdominal muscle weakness. Based on the presence of anti-acetylcholine receptor (Ach-R) antibodies, she was diagnosed with myasthenia gravis (MG). At that time, invasive thymoma of Masaoka stage IVa was also detected. Regression of thymoma and clinical remission of MG was achieved by chemotherapy followed by high-dose corticosteroid. However, several months later, the patient started developing repeated bacterial respiratory tract infections, cytomegalovirus infections, and esophageal and systemic candidiasis. Laboratory tests revealed a marked decrease of serum gamma-globulin levels (IgG 586 mg/dl, IgA 32 mg/dl, IgM 29 mg/dl) and severe reduction in the B cells ratio, as well as a decrease in the CD4+CD25+T cell to CD4+CD25-T cell ratio indicative of deregulation of CD4+T cell activation. These results suggested that the patient impaired humoral and cell-mediated immune responses. We continued the treatment with antibiotics and regular immunoglobulin supplementation through intravenous injections. Although autoimmune disorders are often observed in Good syndrome, the association with MG is quite rare. The case report is followed by the review of literature.

In August 2016, the results of the international randomized, controlled, trial that studied the safety and efficacy of extended trans-sternal thymectomy (ETTX) for patients with non-thymomatous myasthenia gravis (MG) was published. The inclusion criteria for this study were: 1) male and female subjects aged>18.0 and <60.0 years with non-thymomatous MG; 2) MG Foundation of America (MGFA) Clinical Classification Class II-IV at entry; 3) anti-acetylcholine receptor antibody (AChRAb) positive; and 4) receiving optimal oral anticholinesterase treatment with or without oral prednisone. Subjects were randomized to one of two protocols: prednisone alone or extended transsternal thymectomy (ETTX) plus prednisone. A total of 126 patients were randomized. The ETTX plus prednisone protocol improved the quantitative MG scores, decreased the total amount of prednisone, and decreased symptoms and side effects, resulting in a better quality of life compared with the prednisolone alone protocol. These results have required us to change our standard therapeutic protocol for MG. In addition, the safety and efficacy of ETTX with thymectomy via robotic methods needs to be considered. The MGTX study did not address the efficacy and safety of ETTX for younger or older patients, for MGFA Clinical Classification Class I or V patients, or for AChRAb-negative patients.

A 66-year-old man who underwent an extirpation of thymoma in stage I on September 16 1997 was followed in the outpatient clinic. In October 1998, a chest CT scan revealed a 2.0 x 1.0 cm faint frosted glass like shadow in the right S9. On September 13 1999, the patient was admitted to the hospital for close examination. Two times of transbronchial lung biopsy could not offer any clear diagnosis because the lesion was present so as to encircle the central segment of the B9 gronchus. A segmental resection (S9 + 10) under thoracotomy was performed. Intraoperative frozen section diagnosis was bronchioloalveolar carcinoma (type A according to Noguchi's classification), and a resection of the remnant lower lobe and mediastinal lymph nodes dissection (ND 2 a) were added. With expected increase in frequency of detecting early pulmonary cancer's through CT, clinical cases for which we are obliged to diagnosed the disease by segmental resection may increase, if the lesion develops in the vicinity of the hilum of lung like this case.