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A 40-year-old male patient was diagnosed with invasive thymoma and myasthenia gravis in 2015. In 2016 and 2017, he experienced myasthenic crises, with an increase in size of invasive thymoma. In 2018, he received chemotherapy for the invasive thymoma. After 2 months, his symptoms rapidly progressed to myasthenic crisis with severe bulbar and respiratory symptoms, despite the significant effect of chemotherapy for the thymoma. High-dose corticosteroid, multiple plasma exchanges, and intravenous immunoglobulin did not improve the symptoms. Thus, eculizumab was administered, resulting in an improvement in his conditions. To our knowledge, this is the first report showing that eculizumab may improve myasthenic crisis with invasive thymoma.

Two 50s female patients with the taste disorder of sweet taste loss and stage IV a type B2 invasive thymoma underwent surgery at our hospital. One patient with myasthenia gravis (MG) developed postoperative myasthenic crisis and recovered by the treatment with plasma apheresis and steroid pulse therapy. Her taste disorder fully recovered together with her MG symptom. The taste disorder of the other patient without MG had persisted for 3 years after the surgery. The taste disorder of sweet taste loss was reported as one of non-motor symptoms caused by MG-related autoimmune mechanisms associated with thymoma, improving with the therapy for MG. Anti-Kv 1.4 antibody was reported to be positive in nearly half patients with the taste disorder and MG and is speculated to affect selectively the sweet taste receptor.

A 87-year-old female presented with subacute progression of cognitive decline. Fluid-attenuated inversion recovery images of brain MRI showed multifocal high-intensity lesions. Thoracic CT image revealed the presence of thymoma, and serum autoantibody screening showed positivity for anti-gamma aminobutyric acid (GABA) A receptor antibody. Histopathological analysis confirmed type B3 thymoma after thymectomy. The patient received both plasmapheresis and intravenous methylprednisolone therapy, and showed remarkable amelioration of clinical symptoms and MRI abnormal high intensity. However, after 2 month from the clinical recovery, the patient showed recurrence of brain lesions and intravenous methylprednisolone monotherapy was performed. Continuation of oral steroid therapy was required to maintain the quienscent state of inflammation within the central nervous system. Anti-GABA A receptor antibody is a recently discovered novel autoantibody associated with autoimmue encephalitis. Due to the limited number of literature reported, clinical course and therapeutic response of GABA A receptor antibody encephalitis remains elusive. Here we reported a rare case of GABA A receptor antibody encephalitis with type B3 thymoma. Clinical, radiological and therapeutic courses described in our report highlight the importance of immunotherapy for treatment of the disease.

A 43-year-old man was admitted to our hospital because of diplopia, ptosis, and dysphagia that had begun three years previously. He was diagnosed with myasthenia gravis (MG) and invasive thymoma and treated with corticosteroid, thymectomy, and radiation therapy. Ten years after the thymectomy, computed tomography (CT) showed metastasis of the thymoma in the left lower lobe of the lung. Two years after this recurrence, when the patient was 55, respiratory symptoms such as wheezing, persistent cough, and dyspnea appeared. Chronic sinusitis, diffuse centrilobular opacities on CT, and positivity for HLA-B54 led to a diagnosis of diffuse panbronchiolitis (DPB). Despite treatment with clarithromycin, the respiratory symptoms worsened. The patient developed alopecia and body hair loss at the age of 56 followed by dysgeusia, cholangitis, and myositis with positivity for anti-Kv1.4 antibodies. Although treatment with an increased dose of corticosteroid improved hair loss, dysgeusia, cholangitis, and myositis, he died of progression of DPB and serious respiratory infection at the age of 58. In this case, various autoimmune disorders occurred together with MG as complications of thymoma. Although alopecia, dysgeusia, and myositis are already known as complications of MG associated with thymoma, cholangitis is not well-recognized since there have been few reports suggesting a causal relationship between cholangitis and thymoma. Furthermore, DPB caused by immunodeficiency and respiratory tract hypersensitivity associated with thymoma and HLA-B54, respectively, is the distinctive feature of our case. Neurologists should be aware that various organs can be damaged directly and indirectly by abnormal T cells from thymoma in patients with MG.

Thymoma with metastasis to the central nervous system is extremely rare. Herein, three rare cases of thymoma with intracranial metastasis are reported. Case 1 (thymoma, B3 in the WHO classification); cranial magnetic resonance imaging (MRI) revealed a mass lesion with a ring enhancement effect in the right temporal lobe. The cystic and hemorrhagic lesion was subtotally removed and radiation therapy of 40 Gy was administered to the tumor cavity containing the remains of the tumor around the ependyma. The patient received combination chemotherapy with carboplatin and gemcitabine hydrochloride, and he was discharged 3 months after the operation. Case 2 [(thymoma, C (thymic carcinoma)]; multiple cerebral metastases of 8 lesions were found and whole brain irradiation of 40 Gy was performed. Three months later, rapid development of 2 metastatic lesions resulted in the patient's death. At autopsy, neoplastic lesions were found in the neck lymph node, right shoulder, chest frame, pleural cavity, diaphragm, lung, periaortic lymph node, liver and pancreas. Case 3 (thymoma, B2); computed tomography (CT) scan and MRI showed a tumorous lesion over the cerebellar hemisphere. At operation, a vascular, elastic-soft and grey tumor was found to originate from the dura mater and had invaded the occipital bone. The tumor had also invaded the arachnoid membrane and sinus wall but the pia mater was free from invasion. Thereafter local irradiation of 40 Gy was performed to the tumor cavity containing the remains of the tumor around the sinus. However local recurrence reoccured 3 years later. After stereotactic irradiation of 40 Gy to the recurrent tumor, the tumor diminished. The patient is wheelchair-bound 3 years and 4 months after the operation. Most cerebral metastases are extremely rare. Outcome remains poor and life expectancy is very short when brain metastasis is present. Treatment for thymoma is multimodal, including surgery, irradiation and chemotherapy.

A 37-year-old woman diagnosed with ocular myasthenia gravis was referred to our department. Chest computed tomography (CT) showed anterior mediastinal tumor and right pleural dissemination. Extended thymectomy and right intraoperative-intrapleural perfusion hyperthermo-chemothrapy (IPHC) were performed. Pathological diagnosis was invasive thymoma type B2 and stage IVa based on Masaoka's classification. The post operative course was uneventful. The patient underwent 4 cycles of adjuvant chemotherapy with doxorubicin, cisplatin, vincristine, and cyclophosphamide (ADOC), and is free from recurrence at 12 months postoperatively.

A 62-year-old man was admitted to our hospital with a 2-month history of progressive cough and dyspnea. He had undergone thymectomy for thymoma with myasthenia gravis. Adjuvant radiation of 50 Gy had been performed until 6 months before the symptoms developed. Chest computed tomography showed infiltrative findings even outside the irradiated area. We diagnosed radiation-related pneumonia, and 30 mg per day prednisolone was initiated. On the final day, he developed bilateral tension pneumothorax. After chest tube drainage, the right S5 bulla was resected with video-assisted thoracoscopic surgery (VATS). The right pneumothorax caused the bilateral tension pneumothorax, because the right and left thoracic cavity communicated in the anterior mediastinum after thymectomy. We should be aware of the risk of bilateral tension pneumothorax following radiation-related pneumonia after extended thymectomy and adjuvant radiation in patients with myasthenia gravis.

A 39-year-old woman was presented with a mediastinal tumor and some pleural tumors. A computed tomography (CT)-guided needle biopsy of the pleural tumor was undertaken which showed thymoma, type B1 according to the World Health Organization classification. She had underwent extended-thymectomy and resection of all pleural tumors. Histopathology confirmed these lesions to be type B2 thymoma and pleural dissemination. She received adjuvant chemotherapy. Two years after surgery the patient is alive without recurrence.

A 75-year-old-woman had undergone extended thymectomy, right upper and middle lobe resection, and radiation therapy (40 Gy) for thymoma at the age of 63. She visited our hospital complaining of low grade fever, cough, anorexia and a sore throat. Peripheral blood count revealed agranulocytosis. Agranulocytosis associated with thymoma was diagnosed, because there were no other possible causes of agranulocytosis such as drugs, infection, recent radiation therapy, or bone marrow invasion. In spite of giving G-CSF, steroid therapy and immunosuppressants, she died of pneumonia caused by agranulocytosis. We consider that agranulocytosis is a very rare complication of thymoma.

One hundred and twenty-three cases with primary thymoma have undergone an operation from 1972. Sixteen elderly patients (over 70 years old) were compared with 107 young patients in clinical appearance, pathological findings and outcome. There were no differences in Masaoka's classification, World Health Organization (WHO) pathological classification and frequency of complications as myasthenia gravis in both groups. In elderly patients different kinds of neoplasms often occurred during follow-up periods compared to in young patients. In both groups, basically policy of treatment is same. In the case of stage I or II, (extended) thymothymomectomy is performed. In the case of stage IIl, partial resection of invaded surrounding organs is added. We often perform preoperative corticosteroid therapy to shrink the tumor. In the case of stage IV a with pleural dissemination, thymothymomectomy with resection of all dissemination lesions is performed. The case with widespread invasion to pericardium and pericardial dissemination are considered as inoperable and undergo chemoradiotherapy. Postoperatively radiotherapy is added in the case of stage III and IV. In elderly patients 5 and 10 year survival rates were 60.2 and 48.1%. These were significantly worse compared to young patients. It depended on postoperative complications as sternomyelitis and different kinds of critical complications.

Thymic carcinoma is rarer than thymoma and carries a very poor prognosis. No standard treatment has yet been established. Chemotherapy and radiation therapy are usually given to patients in whom surgery is not indicated. We clinically review six patients with thymic carcinoma (three men and three women) who were admitted to our hospital from 1992 through 2002. Their ages ranged from 56 to 81 years (median 70.5). Four patients had chest pain, two were unable to swallow, and in one, who was asymptomatic, the tumor was detected by chance. Histologically, five cases were squamous cell carcinomas, and one was a lymphoepithelioma-like carcinoma. Four of the six patients had distant metastasis at diagnosis. Only one patient was able to undergo surgery, two received radiation therapy alone, and three were administered chemoradiation. The response to the chemoradiation was progression of the disease in two patients and no change in one. The response to radiation therapy was partial response in one patient and no change in one. In summary, chest pain is the most common symptom of thymic carcinoma. A symptomatic case suggests a poor prognosis resulting from the clinical behavior of thymic carcinoma, such as early distant metastasis or direct invasion of surrounding organs. Histologically, squamous cell carcinoma is the most common, and thymic carcinoma appears to be generally resistant to chemotherapy and radiotherapy.

Thymic carcinoma was indistinct for criteria of clinicopathological diagnosis. Recently it gets easier to diagnose thymic carcinoma, because of progression of WHO classification and immunohistochemical technique. Commonly, patients are men and in sixties. Common symptoms are chest pain and dyspnea. Most cases are advanced, over Stage III of the Masaoka's classification. Combined therapies e.g. operation, chemotherapy and radiation were done, but complete resection is difficult. Prognosis is poor, the 3- and 5-year survival is 48.7% and 40.6%.

This study reports clinicopathologic features, treatment, and outcome of 107 thymomas, especially focusing on a combined modality program using hemithorax irradiation (HI) and restaging surgery using corticosteroid for advanced thymoma showing disseminative lesions. The use of HI after presumably total resection of the dissemination under posterolateral thoracotomy had no effect on reducing the incidence of relapsing. On the other hand, our own experience revealed that corticosteroid caused degenerative changes in the epithelial cells and lymphocytes of thymomas. The fact led us administer corticosteroid not only in preoperative setting but during postoperative HI. A better prognosis may be anticipated, although the follow up period is short and the number of patients involved is small.

From June 1975 to March 2002, we experienced 339 patients with myasthenia gravis (MG). Ninety-four patients (81 generalized MG and 13 ocular type) had associated with thymoma. Extended thymectomy including thymoma was performed in all patients. The thymomas were classified as stage I (n = 46), II (n = 31), III (n = 14), and IV a (n = 3). Histopathological findings of the thymoma indicated polygonal cell type in 75 cases, mixture of polygonal and spindle cell type in 14, and spindle cell type in 3, respectively. Three cases in stage II, 12 in III, and 3 in IV a received postoperative radiation therapy. Twenty-two patients required prolonged respirator management for respiratory crisis. Complete remission of MG was seen in 15 cases (17%), and good therapeutic results were obtained in 55 cases (58%) with combined corticosteroid therapy. On the other hand, recurrences of the invasive thymoma were seen in 12 cases (13%), and six of them (6%) died of the tumor. In conclusion, early extended thymectomy including thymoma is markedly effective therapy for MG associated with thymoma, although careful attention should be paid for recurrence of the invasive thymoma.

Thymic epithelial tumors are mainly consisted of thymoma, thymic carcinoma, and thymic carcinoid. And thymic carcinoma is very rare neoplasm. The classification of thymic carcinoma has remained a subject of controversy for many years. The outline of thymic carcinoma has been clarified by "Atlas of Tumor Pathology: Tumors of the Mediastium (AFIP)" and "Histrogical Typing of Tumours of the Thymus (WHO)" published recently. Squamous cell carcinoma is by far the most common in Japan. Thymic carcinoma is a predilection for male. The peak of age was 40-60 years. Thymic carcinoma already had contiguous invasion around neighbor organs, dissemination, and lymph node metastases or distant metastases at diagnosis. Two third of patients with thymic carcinoma performed surgery, and most of them performed adjuvant radiotherapy or chemotherapy. 5-year survival of thymic carcinoma was 33-50%. Histologic tumor type, type of tumor margin, growth pattern, nuclear atypia, necrosis and mitotic activity were correlated with survival. In this paper thymic carcinoma is reviewed mainly based on recently literatures and results obtained from a questionnaire on thymic epithelial tumors in Japan.

Six cases of thymic carcinoma (mean age 48.5 years old, one male and 5 females) were treated in our hospital from September 1990 to September 1998. The histological subtypes of thymic carcinoma were squamous cell in 4, undifferentiated in one, and small cell in one. All cases underwent midsternal thoracotomy, 4 had total resection of the tumor and 2 had exploratory thoracotomy due to tumor invasion of the aorta and the main pulmonary artery. Within 2 years after operation, 2 cases without radiation therapy were died of the carcinoma and one case was died of asthma. However, two cases of squamous cell carcinoma have been alive and disease free for 3 and 5 years since the operation followed by mediastinal irradiation. We think that radiation therapy is very effective to control the disease because one of them underwent only exploratory operation prior to irradiation. Another one case who survives 5 years after total resection of the tumor following irradiation revealed swelling of numerous mediastinal lymph nodes, pathologically consisted of non-caseating epithelioid cell granulomas without metastasis of carcinoma, at the time of operation. These lymph nodes were diagnosed as "sarcoid-like reaction" because there was no clinical evidence of generalized sarcoidosis. The "sarcoid-like reaction" may contribute to the 5-year survival of the patient because it is thought to be a local immune response against the cancer cells. A remaining patient, alive 6 months after total resection of the thymic small cell carcinoma following irradiation, received preoperatively three cycles of the intra-arterial administration using CBDCA via bilateral internal mammary arteries. This induction chemotherapy had no response of the tumor size, but it was considered to have a possibility of reducing the size of thymic carcinoma by the use of other agents (CDDP, VDS etc.) because the tumor was fed mainly by the highly developed internal mammary arteries.

Surgery is the first-line therapy for thymoma. Postoperative radiotherapy should be given for all invasive thymomas, followed by chemotherapy in some cases. Even if the resection is not complete, surgery is effective therapy because most thymomas are local and slow growing. Multidrug chemotherapy including cisplatin is effective against thymoma. Thymic cancer is histologically varied. Surgery is only one effective therapy for thymic cancer. Although no definitive chemotherapy regimen for thymic cancer has yet been established, we feel that the cisplatin, doxorubicin, cyclophosphamide, vincristine 4-drug combination regimen is effective in thymic cancer patients. Seminoma out of mediastinal germ cell tumor (GCT) is expected to have a good prognosis after surgery and radio-/chemotherapy. Although the prognosis for those with nonseminomatous GCT has recently improved due to chemotherapy and surgery, it is still poor.

An operated case of inflammatory pseudotumor of the lung is reported. A 27-year-old female was pointed out a coin lesion in the left lower lung field on chest X-ray and the size of mass increased. She had a history of thymomectomy for thymoma, and resection of right intrathoracic dissemination. Therefore operation was performed on suspicion of metastasizing thymoma. A partial resection including the mass with VATS was performed and histopathologic examination revealed inflammatory pseudotumor. The postoperative course was uneventful, and there has been no evidence of recurrence thereafter. In Japan, sixty-eight cases of inflammatory pseudotumor of the lung including our case have been reported in the literature.

A 42-year-old man was admitted with chest pain. A large mass in the anterior mediastinum was seen on a chest X-ray film and confirmed by CT. Surgery was performed, but the tumor was nonresectable because it had invaded the aorta and pulmonary artery, and had disseminated to the pericardium. Invasive thymoma (stage IVa) was diagnosed He initially received two courses of ADOC (50 mg/m2 of cisplatin, 40 mg/m2 of doxorubicin, 0.6 mg/m2 of vincristine, and 700 mg/m2 of cyclophosphamide) at 3-week intervals. Four weeks after the 2 causes of ADOC, he was given 300 mg/m2 of etoposide for five days followed by G-CSF subcutaneously for peripheral blood stem cell collection. After the two courses of ADOC, he received high-dose ICE (1.5 g/m2 of ifosfamide for four days, 400 mg/m2 of carboplatin for three days, and 200 mg/m2 of etoposide for five days) followed by peripheral blood stem cell transplantation (PBSCT). He was given G-CSF after PBSCT, with subsequent rapid neutrophil and platelet recovery. The tumor diminished remarkably in size and complete remission was confirmed pathologically at subsequent thoractomy. Postoperatively, 50 Gy of irradiation was given. These observations suggest that high-dose ICE followed by PBSCT in combination with an ADOC regimen, surgery, and radiotherapy is highly effective and well tolerated in patients with advanced nonresectable thymoma.

A 43-year-old woman with a history of Sjögren's syndrome was admitted to our hospital because of dyspnea due to anemia. Her chest X ray film on admission revealed an anterior mediastinal tumor. We diagnosed this tumor as a thymoma based on a chest CT scan and magnetic resonance imaging. Because the latter indicated that the thymoma may have involved the mediastinal great vessels, preoperative chemotherapy with cisplatin, doxorubicin hydrochloride, vincristine sulfate and cyclophosphamide. Thereafter the tumor was successfully resected along with part of the right pleura. Thymoma as a complication of Sjögren's syndrome is rare. Here we also discuss the treatment of thymoma and the combination of these two diseases.

A 58-year-old man was admitted to our hospital because of recurrent pulmonary infections that began three years previously. Laboratory data showed hypogammaglobulinemia and a chest computed tomogram showed diffuse bilateral micronodular shadows and an anterior mediastinal tumor. Immunodeficiency with thymoma (Good's syndrome) was diagnosed. After undergoing a thymectomy, he received intravenous gamma-globulin injections once a month for prophylaxis. Good's syndrome occurs rarely in Japan. A solid tumor-like shadow is not necessarily observed in routine chest X-ray studies, and hypogammaglobulinemia is one sign of this syndrome. The hypogammaglobulinemia of Good's syndrome should be carefully differentiated from that of other immunodeficiency diseases such as common variable immunodeficiency, the acquired immunodeficiency syndrome, chronic lymphocytic leukemia, non-Hodgkin's lymphoma, and multiple myeloma (non-secretory type).

We report a detailed analysis of the clinical courses and the immunological examinations in seven patients with myasthenia gravis (MG) and invasive thymoma (Ossermann's type I: 3 cases, IIa: 1 case and IIb: 3 cases), who underwent a transsternal extended thymectomy and postoperative radiation therapy. Two patients with Ossermann's type IIb showed the deterioration of MG after the irradiation. Immunological examinations by an analysis of the subsets of peripheral blood lymphocytes demonstrated a significant decrease of the proportion in CD4 + CD45RA+ T (naive) cells and a significant increase in CD4 + CD45RA-(memory) T cells. Further, the percentage of activated (HLADR+) CD4T cell subsets were increased. The present study suggests that post-thymectomized irradiation may change the balance of the proportion in CD4+ T cell subsets, thereby resulting in the deterioration of MG.

Long-term results of the surgical treatment for 27 cases of thymoma were studied. The clinical stages according to Masaoka's classification were: 7 cases of stage I, 9 cases of stage II, 8 cases of stage III, 1 case of stage IVa and 2 cases of stage IVb. The histological classifications were: epithelial cell type in 10 cases, lymphocytic type in 9 cases and mixed type in 8 cases. Complications consisted of 18 cases of myasthenia gravis (MG). The long-term survival at 5 and 10 years were as follows: 90.6%, 74.8% in all cases; 100.0%, 50.0% in the non-invasive type; 88.2%, 80.2% in the invasive type; 72.0%, 72.0% in the epithelial cell type; 100.0%, 75.0% in the lymphocytic type; 100.0%, 80.0% in the mixed type; 88.9%, 44.4% in cases not complicated with MG; 92.9%, 84.4% in cases complicated with MG. Complete resection and adjuvant therapy improved prognosis even in cases of invasive thymoma, but one case died due to local recurrence of thymoma at 10 years after operation, so we emphasize it is important to follow up for the long time period more than 10 years.

The patient is 62-year-old female. When she was 43 years old, MG occurred. At age of 49 years thymoma was found and complete thymectomy (stage III) and postsurgical irradiation were performed. At age of 57 years pleural dissemination of the thymoma was found. Chemotherapy was effective but did not obtain total tumor cell kill. Though chemotherapy has been repeated for each tumor regrowth, the regimen used at first recurrence became ineffective and the interval between tumor regrowth became shorter. This year, when she is 62 years old, PRCA and hypogammaglobulinemia were accompanied with the forth tumor regrowth.

We experienced 24 cases of thymoma in the past 17 years. Associated syndromes as myasthenia gravis and pure red cell anemia (PRCA) were found in 7 patients. Preoperative therapies were done for the cases of stage IV. Total resection of the tumor was performed except 3 cases which ended in exploratory thoracotomy. Postoperative therapies were done except the cases of stage I. Each one case of stage III and IV a whose operation ended in exploratory thoracotomy died of tumors, but latter case had some period of PR after chemotherapy. A case of stage I with PRCA died from pneumonia but other cases of autoimmune disease had been well controlled by medical treatment. A case of stage IVb was first admitted to the hospital for paralysis of bilateral lower limb. After resecting the epidural tumor of thoracic spine, chemotherapy (CAV 1 kur) and radiotherapy (4,200 rad) was performed which was effective for minimizing the antero-mediastinal tumor. Though operation ended in exploratory thoracotomy, majority of the tumor was found to be replaced for fibrous tissue which suggested the effectiveness of the combination therapy. But this case died from pancreatitis during the postoperative therapy. In conclusion, combination therapy of surgical resection and adjuvant radiotherapy & chemotherapy including the care for autoimmune disease is important in the treatment of thymoma.

Clinicopathologic aspects of 52 thymomas were reviewed. Masaoka staging revealed stage I in 32, stage II in 2, stage III in 12, stage IV a in 3, and stage IV b in 3. Eleven patients (21%) had associated myasthenia gravis (MG), and three (6%) had pure red cell aplasia (PRCA). Operation was complete resection in 39 patients (stage I 32, stage II 2, stage III 2, and stage IV b 3), subtotal resection in 4 patients (stage III 2, stage IV a 2), partial resection or simple biopsy in 7 patients (stage III 6, stage IV a 1). Survival rates at 5 years and 10 years were 88%, 88% in noninvasive thymomas, and 65%, 45% in invasive thymomas, respectively. Statistical analysis indicated that patients with noninvasive thymomas had significantly longer survival than those with invasive thymomas. Significant difference was not found in survival on the basis of tumor cell type according to lymphocyte/epithelial cell ratio. Associated MG had no influence on the survival of thymoma patients, however, the presence of PRCA was an adverse factor in survival. In cases of invasive thymomas, there was statistically significant difference in the survival rates between the group of patients undergoing complete or subtotal resection and the group undergoing partial resection or only biopsy. Irradiation was of value in local control of thymoma, but lymphogeneous or hematogeneous recurrence occurred in 21% of patients with invasive thymomas from 3 months to 12 years postoperatively. Lifelong follow-up should be necessary in thymoma patients since late recurrence is not so rare.

From February 1988 to September 1992, six patients with Stage III or IV invasive thymoma were enrolled onto our study of multidisciplinary treatment, which included chemotherapy, surgery, and radiotherapy. The chemotherapy consisted of cisplatin (20 mg/m2 continuous 24-hour infusion on days 1 through 4), doxorubicin (40 mg/m2 on day 1), and methylprednisolone (1,000 mg on days 1 through 4 and 500 mg days 5 and 6). Two patients received surgery (incomplete resection) and postoperative chemo/radiotherapy, and four patients received induction chemotherapy followed by surgery and chemo/radiotherapy. All patients with induction chemotherapy showed a partial response and underwent complete (n = 2) or partial (n = 2) resection. Four patients are alive with no evidence of disease for 31 to 55 months after the diagnoses. But two with partial resection after chemotherapy died of recurrent disease. Multidisciplinary treatment including chemotherapy may be a new therapeutic choice in management of advanced invasive thymoma.

The treatment of thymoma, thymic cancer and thymic germ cell tumor was reviewed in the literature. The major treatment of thymoma is surgery with or without radiation. The chemotherapy for the thymoma is now investigated in the world. CDDP, ADM, VCR, CPA or BLM are usually used, but the most effective combination of these drugs is not known. Thymic cancer is a rarer and more malignant disease than thymoma. Though the postoperative treatment is investigated as well as thymoma, only a few successful cases by chemotherapy have been reported. Chemotherapy (PVB, VAB-6, PEB) for testicular germ cell tumor is also effective for thymic germ cell tumor including seminoma. Though the combination therapy of radiation and surgery has been popular, chemotherapy will be used more frequently for seminoma in future.

A 21-year-old male was admitted with SVC syndrome. Chest X-ray film showed an abnormal density on the upper mediastinum, that was recognized thymoma on the needle aspiration specimen. The large tumor, which extensively infiltrated the surrounding tissues (SVC, the right brachiocephalic vein, bilateral lungs and the pericardium) led us to choose preoperative chemotherapy. CDDP (cisdiammin-edichloroplatinum) was infused through the right IMA (internal mammary artery). After obtaining the major response the tumor mass was resected with adjacent structure accompised vessels reconstructions. Histological examination revealed totally necrosed tissue. Three years after initiation of therapy, the patient is doing well. The therapy with CDDP injection into selective IMA for invasive thymoma before operation was considered to be very useful utilized.

Intrathyroidal thymoma is a rare tumor that occurs in the thyroid gland. The present report describes a 62-year-old female patient with this tumor, who was treated with subtotal thyroidectomy with a wedge resection of the trachea followed by radiotherapy. She is now free from disease for 4 years after the operation. This tumor shows expansive growth, frequent invasion to the surrounding tissue, but relatively infrequent lymph node involvement. If this tumor is resected surgically, the prognosis is favorable.

Over the last 20 years, 6 patients with myasthenia gravis and invasive thymoma have been seen in our Department. These patients underwent non-total excision cases. This represents 2.5 percent of 242 myasthenia gravis patients in our series. We can see 17 such patients in the literature in Japan including our cases. The age ranged 20 to 77 years and the ratio of male to female was 10:7. Post-operative therapeutic methods for invasive thymoma included irradiation, steroid therapy and combination chemotherapy. Every method showed good therapeutic results, but steroid therapy and chemotherapy showed especially good therapeutic effects in the early stage of the disease. Though these therapeutic effects were better than those obtained in other malignant tumors, thymomas tended to reappear within several years, when tumors showed no response to any therapeutic method. It is well known that steroid therapy reduces the level of antiacetylcholine receptor antibody, whereas chemotherapy also reduces antiacetylcholine receptor antibody. Over all 5-year survival rate was 53%, and the 10-year survival rate was 29%. Three out of 6 cases of death were due to myasthenic crisis (50%) and 2 out of 6 cases were due to invasive tumor itself (38%). These results suggested that total excision of the thymoma, if possible, and for the remaining tumor, high doses of adrenocorticosteroids and combination chemotherapy seem to be treatments of choice.

Mediastinal tumors show many kinds of histology. Surgery is indicated in almost all cases with the exception of malignant lymphomas. This review is divided into 3 parts, Surgical procedures: Some available approaches and special techniques for each tumor are described. Radiotherapy: thymoma, malignant lymphoma, neuroblastoma, and seminoma are indicated for radiotherapy. Chemotherapy: malignant lymphoma, neuroblastoma, germ cell tumors, and thymoma are indicated for chemotherapy.

Twenty-eight patients with malignant tumors of the thymus were surgically treated during the 15-year period from 1969 to 1984. Twenty-six patients had far advanced disease when treatment was began. Of fifteen patients with malignant thymoma, the tumors were successfully removed in five patients by using the technique of combined resection of SVC. Of two patients with carcinoid, one is alive and another died two years after extended operation. Of two patients with malignant lymphoma, one with non Hodgkin's disease died three years after operation, and the other with Hodgkin's disease is alive with tumor bearing. It is important to distinguish malignant lymphoma from other types of thymic tumors, because chemo-radiotherapy is superior to surgical therapy. Of nine patients with germ cell tumor, two patients with seminoma have been well for 11 and 5 years. CDDP and radiotherapy were effective on their long survival. Three patients with embryonal carcinoma responded well to combined surgical and chemo-radiotherapy. But only one of them is alive with tumor free one year after operation. Prosthetic grafts were employed in 7 cases for replacement of the innominate and superior caval vein. Angiogram taken one month after operation disclosed the overall patency rate with 92% and the longest patent period confirmed was 4 years. Extended operation by using the prosthetic graft should be performed in the advanced cases to achieve a complete removal and to aim better prognosis for this kind of disease. In conclusion, aggressive surgical removal followed by radio-chemotherapy offers best cure of the malignant thymic tumor.

In the postoperative diagnosis of thymoma, the most important problem over the last 30 years has been whether the condition is benign or malignant. In this paper, we discussed the diagnosis of thymoma malignancy and its therapy based on our own experiences. All thymomas have the potential to be malignant. Some thymomas have low malignancy and others high malignancy. As the malignancy is therefore not uniform, it is impossible to divide thymomas into either benign or malignant categories. Masaoka, one of the present authors, introduced the concept of clinical stage to thymoma. We think that the difference between invasive and noninvasive thymomas is due to differences in the clinical stage. We also proposed a new classification of thymomas based on the degree of epithelial differentiation. This new classification reflects the malignancy of the thymoma. Both the clinical stage classification and the classification based on epithelial differentiation showed good correlations with the prognosis of thymoma can be surmised by an exact diagnosis based on these two new classifications. The most important point concerning the therapy of thymoma is radical resection of the tumor. However, reduction surgery can be the method of second choice, especially in myasthenic thymoma, because of its slow growth. We carried out irradiation in all patients with thymoma postoperatively, resulting in a low rate of recurrence of the thymoma. This indicates the effectiveness of radiation therapy for this condition.

Reported is the case of a 62-year-old man who was admitted to our hospital because of the presence of a left hilar mass found during a routine chest X-ray examination. Shortly thereafter, a left thoracotomy was performed. The tumor was located under the aortic arch in the left hilus of the lung and had invaded the pericardium and pulmonary trunk. There was no connection, however, to the anterior mediastinum. A histological examination revealed an invasive thymoma of epithelial cell of the predominant type. Seen scattered abroad were thymic tissue in the adipose tissue around the tumor of the left hilus. Postoperatively, a distant metastasis of the right lung was observed and the patient died due to respiratory failure.

Thymoma with extrathoracic metastasis is very rare, especially to the central nervous system. As far as we know, this is the 15th reported case of cerebral metastasis from malignant thymoma. The prognosis is very poor and almost all of them die in one to one and half years. We have experienced such a case, who is 56 years old man, presenting Gerstmann's syndrome and right-hemiparesis 8 months later after thoracotomy for removal of thymoma. At the admission time in this hospital, CT findings proved the tumor in the left temporoparietal area, left ventricle deformity and slight midline shift to right side. The average of CT density in the low density area was 20. Peripheral region of the tumor was enhanced by contrast CT. Left carotid angiography showed the ACA shift to the right side and abnormal vascularity of peripheral branches of angular artery (arterial phase) and also tumor strain in late artery (arterial phase) and also tumor strain in late arterial phase. Brain scintigram revealed accumulation in the left parietal region. The rt-hemiparesis was rapidly going to be rt-hemiplegia. Therefore, we have performed needle puncture to prevent rt-hemiplegia at the first time. In the course of needle puncture, 90 ml of dark and red fluid was gained at 3.0 cm depth from the cerebral surface. Immediately, the above two symptoms have improved remarkably. Post operative CT showed the reduction of tumor and improvement of the midline shift. The radical operation have been done 2 days after the needle puncture. The tumor was elastic-soft and hemorrhagic and appeared dark-red.(ABSTRACT TRUNCATED AT 250 WORDS)