Posting Date: June 1, 2002

[Recurrence of thymoma accompanied withhypogammaglobulinemia 20 years after surgery: a case report]

Oncological significance of WHO histological thymoma classification. A clinical study based on 286 patients.

[Malignant thymoma: a strange goiter]

[A 42-year-old man with cardiac systolic murmur and a mediastinal tumor. Invasive thymoma (predominantly epithelial type, clinical stage IVa)]

Good's syndrome: the association of thymoma and hypogammaglobulinemia.

Good's syndrome: the association of thymoma with immunodeficiency.

1
UI - 11974900
AU - Naniwa T; Kakihara H; Zen-nami S; Tomita H; Sugiura Y; Yoshinouchi T;
TI - Sato S; Ueda R [Recurrence of thymoma accompanied with hypogammaglobulinemia 20 years after surgery: a case report]
SO - Nihon Kokyuki Gakkai Zasshi 2002 Mar;40(3):241-4
AD - Second Department of Internal Medicine, Nagoya City University Medical School.
We reported a case of recurrence of localized thymoma accompanied with hypogammaglobulinemia (Good's syndrome) 20 years after surgery. A 74-year-old man was admitted to this hospital because of mediastinal tumor and chronic pulmonary infection. He had been thymectomised at the age of 55 because of spindle cell thymoma. After that, he had been productive cough, and low-grade fever. Laboratory findings revealed hypogammaglobulinemia. Percutaneous needle biopsy of the mediastinal tumor revealed spindle cell thymoma. Therefore, hypogammaglobulinemia with thymoma (Good's syndrome) accompanied with a chronic lower respiratory tract infection was diagnosed. Immunologic studies revealed a marked decrease of CD 20 positive cells and decreased lymphocyte activation under the stimuli of phytohemagglutinin and concanavalin A. The thymoma was resected in Dec 1997, but the serum immunoglobulin showed no increase at al.

2
UI - 12048910
AU - Okumura M; Ohta M; Miyoshi S; Mori T; Yasumitsu T; Nakahara K; Iuchi K;
TI - Tada H; Maeda H; Matsuda H Oncological significance of WHO histological thymoma classification. A clinical study based on 286 patients.
SO - Jpn J Thorac Cardiovasc Surg 2002 May;50(5):189-94
AD - Thoracic Surgery Study Group, Division of General Thoracic Surgery, Department of Surgery, Interventional Medicine (E-1), Osaka University Graduate School of Medicine, 2-2 Yamadaoka, Suita- City, Osaka 565-0871, Japan.
OBJECTIVES: The clinical significance of thymoma histology remains controversial because of the numerous histological classifications of thymic epithelial tumors. Universal classification of such tumors was achieved by the World Health Organization (WHO) in 1999. We studied the prognostic significance of this classification. METHODS: We studied clinical features and postoperative survival in cases of thymoma, but not thymic carcinoma, based on WHO histological classification in 286 patients undergoing surgery between 1958 and 2001. RESULTS: Tumors were 19 type A, 79 type AB, 59 type B1, 102 type B2, and 27 type B3. The proportion of invasive tumors increased by type--from A to AB, B1, B2, and B3. The great vessels were involved more frequently in type B2 and B3 tumors than in type A, AB, and B1 tumors. The 20-year survival was 100% in type A, 87% in type AB, 91% in type B1, 65% in type B2, and 38% in type B3 tumors. Multivariate analysis showed Masaoka staging and WHO histological classification to be significant independent prognostic factors, while age, gender, myasthenia gravis association, resection completeness and great vessel involvement were not. In stage III patients, 13 of 45 patients with type B2 and B3 tumor died of their tumors, while no tumor deaths occurred in 11 patients with type A, AB, and B1 tumors. CONCLUSION: WHO histological classification realistically reflects the oncological behavior of thymoma.

3
UI - 11557903
AU - Forterre O; Houze JP; Picard A
TI - [Malignant thymoma: a strange goiter]
SO - J Chir (Paris) 2001 Aug;138(4):232
AD - Service de Chirurgie Digestive, Endocrinienne et Thoracique, Centre Hospitalier, Belfort, France.

4
UI - 12048906
AU - Sugihara M; Gomyo Y; Sumii K; Tadehara F; Yoshida Y
TI - [A 42-year-old man with cardiac systolic murmur and a mediastinal tumor. Invasive thymoma (predominantly epithelial type, clinical stage IVa)]
SO - J Cardiol 2002 May;39(5):281-3
AD - Division of Cardiology, Mazda Hospital, Aosaki, Minami 2-15, Fuchu-cho, Akigun, Hiroshima 735- 8585.

5
UI - 11170933
AU - Arend SM; Dik H; van Dissel JT
TI - Good's syndrome: the association of thymoma and hypogammaglobulinemia.
SO - Clin Infect Dis 2001 Jan 15;32(2):323-5

6
UI - 11462204
AU - Tarr PE; Lucey DR; Infectious Complications of Immunodeficiency with
TI - Thymoma (ICIT) Investigators Good's syndrome: the association of thymoma with immunodeficiency.
SO - Clin Infect Dis 2001 Aug 15;33(4):585-6

Epidermal growth factor receptor expression in invasive thymoma.

Relationship between expression of cancer-related proteins and tumor invasiveness in thymoma.

[Cox multivariate analysis of prognosis and proposal on a modified staging system of thymoma]

[Thymoma-report of 166 patients]

[Thymoma and somatostatin analogs. Biology, diagnostic and clinical practice]

Clinical and pathologic predictors of survival in patients with thymic tumors.

Autoimmune-like pancreatitis in thymoma with myasthenia gravis.

Tc-99m MIBI, Tc-99m tetrofosmin, and Tc-99m (V) DMSA accumulation in recurrent malignant thymoma.

Uptake of Tc-99m pertechnetate in thymoma.

1
UI - 11935304
AU - Henley JD; Koukoulis GK; Loehrer PJ Sr
TI - Epidermal growth factor receptor expression in invasive thymoma.
SO - J Cancer Res Clin Oncol 2002 Mar;128(3):167-70
AD - Department of Pathology, Indiana University School of Medicine, Clarian Health Partners, 550 North University Blvd., Rm 3465, Indianapolis, IN 46202, USA. jhenley@iupui.edu
PURPOSE: Epidermal growth factor receptor (EGFR) is a transmembrane glycoprotein with intrinsic tyrosine kinase activity. Activation results in a variety of cellular responses including cell proliferation and differentiation. In clinical trials, anti-EGFR is showing promise in the treatment of solid tumors expressing EGFR. Thus, we assessed EGFR expression in a series of thymic epithelial tumors. METHODS: Tumors from 37 patients seen at Indiana University School of Medicine (IUMC) for treatment of thymoma (31 patients) or thymic carcinoma (six patients) were assessed for EGFR expression. Five-micron sections of formalin-fixed, paraffin-embedded tumor (28 invasive and/or metastatic thymomas, six thymic carcinomas, and three non-invasive thymomas) were stained with anti-EGFR. Any degree of cytoplasmic membrane staining of tumor cells was considered positive; furthermore, staining was scored 0 to 3+ using criteria as standardized for HER-2/neu assessment of breast carcinoma. Appropriate controls were performed. RESULTS: Positive staining of tumor was observed in 28 tumors (23 invasive and/or metastatic thymomas, two thymic carcinomas, and three non-invasive thymomas). CONCLUSIONS: EGFR is expressed in a high percentage of thymic epithelial tumors. EGFR is often strongly expressed and is a potential therapeutic target in patients with malignant thymic tumors. We are pursuing additional studies to assess anti-EGRF in the treatment of patients with advanced thymoma.

2
UI - 11888800
AU - Tomita M; Matsuzaki Y; Onitsuka T
TI - Relationship between expression of cancer-related proteins and tumor invasiveness in thymoma.
SO - Eur J Cardiothorac Surg 2002 Mar;21(3):596

3
UI - 11859721
AU - Li J; Wang L; Zhang D
TI - [Cox multivariate analysis of prognosis and proposal on a modified staging system of thymoma]
SO - Zhonghua Zhong Liu Za Zhi 2001 Nov;23(6):500-2
AD - Department of Thoracic Surgical Oncology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
OBJECTIVE: To investigate the clinicopathologic features, prognostic factors and propose a new modified staging criteria for thymoma. METHODS: The data of 159 patients operated for thymoma collected were retrospectively analyzed as to their prognostic factors and criteria of clinical staging through comparison of survival rates by the actuarial method, Log-rank and Cox multivariable model. RESULTS: Thorough resection (OR = 2.10), and extent of tumor invasion (OR = 1.73) were the most important prognostic factors. Tumor with peritumoral adhesion and absence of a complete capsule but without external invasion belonged to the criteria of stage II (II a). According to the prognosis and state of resection, lesions with obvious peritumoral invasion into the nearby organs but were thoroughly resected belonged to stage II (II b) and those incompletely resected belonged to III a. The unresectable lesions belonged to III b. CONCLUSION: According to the Cox prognostic multivariable model, the criteria of clinical staging of thymoma are defined as: Stage I-completely encapsulated non-invasive tumor without tight fibrous adhesions to the surroundings. Stage II a-only capsular invasion or capsule incomplete or with tight fibrous adhesions to the surroundings. II b-invasion into the surrounding fatty tissue, pleura, partial pericardium or lung, Stage III a-invasion into the great vessels, heart, trachea or hilus, which are resected with difficulty, or only palliatively. III b-extensive invasion into the nearby organs, and resection is impossible. Stage IV a-pleural or pericardial dissemination, IV b-lymphatic or hematogenous metastasis.

4
UI - 11859722
AU - Ge D; Zheng R; Fan H
TI - [Thymoma-report of 166 patients]
SO - Zhonghua Zhong Liu Za Zhi 2001 Nov;23(6):503-4
AD - Department of Thoracic Surgery, Zhong Shan Hospital, Fu Dan University, Shanghai 200032, China.
OBJECTIVE: To discuss the characteristics of operation and the prognosis of 166 patients with thymoma. METHODS: 166 thymoma patients were treated were 102 (61.4%) stage I, 28 (16.9%) stage II, 24 (14.5%) stage III, 12 (7.2%) stage IV a and 0 stage IV b lesions. The relation between stage and survival rate was analyzed. RESULTS: One (0.6%) patient died of the operation. 137 (82.5%) patients underwent radical operation. Thirty patients were lost to follow-up. With the life table method, the 10-year survival rate was 56.8%, with 79.8% for stage I, 51.6% for stage II, 33.5% for stage III and 0% for stage IV patients. CONCLUSION: Diagnosis of thymoma still depends on both clinical and pathological findings, which are correlated with stage. The principal treatment is to resect the tumor as completely as possible so as to relieve the symptoms and prolong the life of the patient.

5
UI - 11753243
AU - Palmieri G; Montella L; Lastoria S
TI - [Thymoma and somatostatin analogs. Biology, diagnostic and clinical practice]
SO - Minerva Endocrinol 2001 Sep;26(3):193-5
AD - Dipartimento di Endocrinologia e Oncologia Molecolare e Clinica, Universita degli Studi Federico II, Naples, Italy.
Thymic tumours are rare neoplasms which generally follow a slow pattern of growth, showing their aggressiveness locally through the infiltration of adjacent organs and they rarely metastasise hematogenically. In the presence of locally advanced, metastatic or inoperable disease, combined strategies including chemotherapy, radiotherapy and surgery are now being evaluated. Scintigraphy with 111In DTPA-D-Phe 1 octreotide was used for the first time in a relevant series of patients with thymic tumour (13 cases) by our research group. The presence of somatostatin receptors (ss-R) assayed in vivo provided the rationale for the use of a treatment based on the octreotide analog in a patient with thymoma and aplasia of the erythroid series (pure red cell aplasia, PRCA) in whom a complete response for the tumour and the remission of anemia was obtained. The efficacy of this treatment was confirmed by our series of patients with chemoresistant thymic tumour and by national and international confirmations. These data, ranging from in vivo diagnosis to treatment and the in vitro study of receptor expression, confirm that somatostatin plays a major role in thymic tumours.

6
UI - 11887069
AU - Lequaglie C; Giudice G; Brega Massone PP; Conti B; Cataldo I
TI - Clinical and pathologic predictors of survival in patients with thymic tumors.
SO - J Cardiovasc Surg (Torino) 2002 Apr;43(2):269-74
AD - Department of Thoracic Surgery, Istituto Nazionale Tumori, Milano, Italy. lequaglie@istitutotumori.mi.it
BACKGROUND: The aim of this study is to evaluate the impact of thymectomy in patients with thymic neoplasms and to identify clinical and histopathological factors associated with improved long-term outcome cases, all non-myasthenic, had benign thymomas (n=30) but 6 had thymic carcinomas. Nine tumors were no-resected (5 thymomas and 4 thymic carcinomas). Minimum follow-up by Department of Thoracic Surgery Istituto Nazionale Tumori was 60 months after thymectomy. We divided the specimens according to Marino and Muller-Hermelink's classification: 54 thymomas, 18 thymic carcinomas and 2 no-diagnosis specify thymomas. There were 53 stage I, 1 stage II, 13 stage III, 5 stage IVa and 2 stage IVb according to Masaoka. RESULTS: Forty-six patients with treated thymoma were alive without disease at the end of follow-up, the remaining 8 died from recurrence in 6, a new tumor in 1 and a heart attack in the last. Of 18 thymic carcinomas 9 were alive at the end of follow-up (1 with recurrence), only 4 dead from recurrence. The actuarial survival of patients with thymomas was 88.5% at 5 years, (73.6% in cortical type, 85.7% in medullary type, 93.9% in mixed type, 100% in predominantly cortical type). Myasthenia gravis didn't influence the survival: 87.3 (no MG) vs 90%. Advanced stage thymomas significantly increased the risk of death from early stage I: 32.4 vs 100% at 5 years. In thymic carcinoma patients with well-differentiated thymic carcinoma (WDTC) died less than others: the actuarial probability of survival at 5 years was 90 vs 68%. CONCLUSIONS: Thymectomy was the best treatment to long term outcome. In our experience, survival was related to histotype and to local extension of tumor.

7
UI - 11942018
AU - Colaut F; Toniolo L; Sperti C; Pozzobon M; Scapinello A; Sartori CA
TI - Autoimmune-like pancreatitis in thymoma with myasthenia gravis.
SO - Chir Ital 2002 Jan-Feb;54(1):91-4
AD - Dept. of Thoracic Surgery, City Hospital of Castelfranco Veneto, 31033 Castefranco Veneto, Treviso.
A patient with thymoma and myasthenia gravis admitted for surgery presented increased serum levels of pancreatic amylase and lipase. Suspecting a thymoma-related autoimmune disorder, autoantibody serum titers were determined: increased autoantibody titers to acetylcholine receptors, thyroglobulin, thyroperoxidase and pancreatic insulin were detected. After thymectomy the serum levels of pancreatic enzymes decreased rapidly. Myasthenia gravis symptoms also improved. To the best of our knowledge no similar cases have been reported in the literature.

8
UI - 11805481
AU - Kim SJ; Kim IJ; Kim YK
TI - Tc-99m MIBI, Tc-99m tetrofosmin, and Tc-99m (V) DMSA accumulation in recurrent malignant thymoma.
SO - Clin Nucl Med 2002 Jan;27(1):30-3
AD - Department of Nuclear Medicine, College of Medicine, Pusan National University, Korea.
Thymoma is the most common primary tumor of the anterior mediastinum, accounting for 20% to 30% of all mediastinal tumors. The recurrence rate after total resection of the thymoma ranges from 8% to 18%. The authors describe a patient with recurrent malignant thymoma imaged with Tc-99m MIBI, Tc-99m tetrofosmin, and Tc-99m (V) DMSA. Early and delayed Tc-99m MIBI and Tc-99m tetrofosmin scintigraphy showed increased uptake in the mediastinal area, as did Tc-99m (V) DMSA scintigraphy. Coronal SPECT images obtained with Tc-99m MIBI, Tc-99m tetrofosmin, and Tc-99m (V) DMSA showed increased uptake in the mediastinal lesion seen on a computed tomograph of the chest. However, the normal blood-pool activity of the heart and great vessels imaged with Tc-99m (V) DMSA obscured the recurrent malignant thymoma. Although Tc-99m (V) DMSA is a useful tumor-seeking agent, Tc-99m MIBI and Tc-99m tetrofosmin SPECT are preferred to Tc-99m (V) DMSA to detect primary and recurrent malignant thymoma.

9
UI - 11805485
AU - Squires RS; Smith M; Rohatgi PK
TI - Uptake of Tc-99m pertechnetate in thymoma.
SO - Clin Nucl Med 2002 Jan;27(1):47-8
AD - Department of Medicine, Washington Hospital Center, DC, USA.

[Surgery as an element of the complex therapeutic approach to myasthenia gravis and thymoma]

Limbic encephalitis associated with thymic cancer: a case report.

Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients.

Clinicopathologic reports, case reports, and small case series: cytomegalovirus retinitis in patients with Good syndrome.

Malignant thymoma invading the right atrium: a rare echocardiographic finding.

[Current problems of surgical treatment of thymoma in children]

Co-existent cutaneous cryptococcosis of the forearm and cutaneous alternariosis of the leg in patient with metastatic thymoma.

Histologic typing of thymoma according to the new World Health Organization classification.

Surgery for thymoma.

Chemotherapy of thymomas and thymic carcinomas.

The radiotherapeutic management of invasive thymomas.

1
UI - 11484288
AU - K'tev N
TI - [Surgery as an element of the complex therapeutic approach to myasthenia gravis and thymoma]
SO - Khirurgiia (Sofiia) 2000;56(2):40-4

2
UI - 11757949
AU - D'Avino C; Lucchi M; Ceravolo R; Mussi A; Malandrini A; Annunziata P;
TI - Siciliano G Limbic encephalitis associated with thymic cancer: a case report.
SO - J Neurol 2001 Nov;248(11):1000-2

3
UI - 11920495
AU - Ogawa K; Uno T; Toita T; Onishi H; Yoshida H; Kakinohana Y; Adachi G;
TI - Itami J; Ito H; Murayama S Postoperative radiotherapy for patients with completely resected thymoma: a multi-institutional, retrospective review of 103 patients.
SO - Cancer 2002 Mar 1;94(5):1405-13
AD - Department of Radiology, University of the Ryukyus School of Medicine, Okinawa, Japan. kogawa@med.u-ryukyu.ac.jp
BACKGROUND: Optimal management of postoperative radiotherapy for patients with completely resected thymoma remains controversial. This study was conducted to assess the efficacy of postoperative mediastinal irradiation in patients with completely resected thymoma. METHODS: The records of 103 patients with completely resected thymoma who received postoperative mediastinal irradiation during the period between 1979 and 1998 were reviewed. The distribution according to Masaoka stage was Stage I in 17 patients, Stage II in 61 patients, and Stage III in 25 patients. Fifty-two patients were treated with involved field (IF) irradiation, and 51 patients were treated with irradiation of the whole mediastinal field with or without boost (WM irradiation). The total radiation dose to the primary tumor bed was 30-61 grays (Gy), with a median dose of 40 Gy. No patients received chemotherapy during the initial treatment. The median follow-up of the 82 living patients was 112 months (range, 24-244 months). RESULTS: The 10-year actuarial overall and disease free survival rates for all patients were 81% and 79%, respectively. The 10-year actuarial overall survival rate was 100% for patients with Stage I disease, 90% for patients with Stage II disease, and 48% for patients with Stage III disease. In the analysis, clinical stage alone had a statistically significant impact on both overall survival and disease free survival (P < 0.0001 for both). Recurrent disease was observed in 17 patients, and the pleura was the most frequent site of first recurrence. Of 12 patients who had pleural recurrences, 11 patients had pleural dissemination remote from the initial tumor site. No recurrence was observed in any of the 17 patients with Stage I disease, and 6 of 61 patients (10%) with Stage II disease and 11 of 25 patients (44%) with Stage III disease experienced recurrences. With regard to intrathoracic recurrences, there were no recurrences within the irradiated field in any of the 103 patients, and no dose response correlation was seen in intrathoracic control (incidence of intrathoracic recurrence: 2 of 19 patients in the group that received < 40 Gy, 6 of 45 patients in the group that received 40 Gy, and 7 of 39 patients in the group that received > 40 Gy). With respect to treatment field, mediastinal recurrences were observed in 4 of 52 patients (8%) who were treated with IF irradiation, whereas 0 of 51 patients who were treated with WM irradiation experienced mediastinal recurrences. Pleural-based recurrences were observed both in patients who were treated with IF irradiation (7 of 52 patients) and in patients who were treated with WM irradiation (5 of 51 patients). According to the degree of pathologic tumor invasion, 0 of 71 patients without pleural invasion had pleural-based recurrences (0 of 17 patients with Stage I disease, 0 of 51 patients with Stage II disease, and 0 of 3 patients with Stage III disease), whereas 12 of 32 patients (38%) with pleural invasion had pleural-based recurrences (4 of 10 patients with Stage II disease and 8 of 22 patients with Stage III disease). CONCLUSIONS: The current results indicated that WM irradiation with a total dose of 40 Gy was effective in preventing mediastinal recurrence for patients with completely resected thymoma. However, in patients with pathologic pleural invasion of the tumor, mediastinal irradiation alone was insufficient to avoid pleural-based recurrence. Copyright 2002 American Cancer Society.

4
UI - 11934330
AU - Assi AC; Lightman S
TI - Clinicopathologic reports, case reports, and small case series: cytomegalovirus retinitis in patients with Good syndrome.
SO - Arch Ophthalmol 2002 Apr;120(4):510-2
AD - Moorfields Eye Hospital, City Road, London EC1V 2PD, England.

5
UI - 11884256
AU - Ozer N; Can I; Aytemir K; Atalar E; Erman M; Ovunc K; Aksoyek S;
TI - Demirkazik F; Kes S Malignant thymoma invading the right atrium: a rare echocardiographic finding.
SO - Echocardiography 2002 Jan;19(1):61-2
AD - Department of Cardiology, Faculty of Medicine, Hacettepe University, Ankara, Turkey. neclaozer@hotmail.com
Malignant thymoma is a rare tumor. We report a case of malignant thymoma with intracaval extension and direct invasion of the right atrium presenting as superior vena cava syndrome.

6
UI - 11785409
AU - Slepov AK
TI - [Current problems of surgical treatment of thymoma in children]
SO - Klin Khir 2001 Sep;(9):57-9

7
UI - 11841520
AU - Courville P; Favennec L; Viacroze C; Barrel A; Young P; Abboud P;
TI - Thomine E; Metayer J; Nouvet G Co-existent cutaneous cryptococcosis of the forearm and cutaneous alternariosis of the leg in patient with metastatic thymoma.
SO - J Cutan Pathol 2002 Jan;29(1):55-8
AD - Service d'Anatomie Pathologique, CHRU Charles Nicolle Rouen, France. philippe.courville@chu-rouen.fr
BACKGROUND: Cryptococcosis and alternariosis are rare opportunistic infections often observed in immunocompromised patients. Because Cryptococcus and Alternaria are ubiquitous fungi found in soil, the presence of fungi in the dermis has to be observed on histological examination to confirm a real cutaneous, invasive, infection. PATIENT: We report the first case of concomitant cutaneous cryptococcosis and cutaneous alternariosis, in an immunocompromised patient treated for a metastatic thymoma. CONCLUSION: This observation underlines the fact that the possible co-existence of several rare infections in immunocompromised patients should take into consideration pathogen identification in order to adapt the therapy to individual patient requirements.

8
UI - 11413764
AU - Dadmanesh F; Sekihara T; Rosai J
TI - Histologic typing of thymoma according to the new World Health Organization classification.
SO - Chest Surg Clin N Am 2001 May;11(2):407-20
AD - Department of Pathology, Cedars-Sinai Medical Center, Los Angeles, California, USA.
The new WHO classification scheme provides a set of simple and easily reproducible morphologic criteria for an accurate and consistent categorization of thymic epithelial tumors. This scheme should facilitate interobserver reproducibility and lead to a more precise assessment of prognosis when used in combination with the staging system.

9
UI - 11413765
AU - Port JL; Ginsberg RJ
TI - Surgery for thymoma.
SO - Chest Surg Clin N Am 2001 May;11(2):421-37
AD - Department of Cardiothoracic Surgery, New York-Presbyterian Hospital, New York, New York, USA.
Although thymoma is an uncommon tumor, it represents the most frequently encountered tumor of the anterior mediastinum. These tumors represent an interesting and even peculiar group of lesions by virtue of their association with paraneoplastic disorders, their relatively indolent course, and their predisposition for local recurrence. The initial treatment of choice for patients with thymoma that do not present with unresectable local or diffuse metastatic disease is complete surgical resection. The goals of surgery are complete excision of the lesion with total thymectomy and complete exploration to rule out the presence of noncontiguous disease that may be resectable. Often, complete resection may require the resection of surrounding involved structures including pericardium, pleura, lung, and even major vascular structures. Some authors have suggested VATS or VATS-assisted techniques for small thymomas. Capsular invasion, however, often can be subtle, and the completeness of resection is of prime importance in countless studies. With recurrences appearing up to 5 and even 10 years postoperatively, time will tell if these minimally invasive techniques are comparable with current standard approaches. Multiple studies have failed to determine conclusively the role of induction chemotherapy and adjuvant radiation. Prospective multi-institutional trials are required to elucidate further the role of such therapies in these rare tumors. In the interim, the authors continue to recommend postoperative radiation for all patients undergoing resection with the exception of stage I patients. Some promising reports on response to chemotherapy have led them to develop an induction chemotherapy protocol for patients with clinically advanced disease.

10
UI - 11413767
AU - Chahinian AP
TI - Chemotherapy of thymomas and thymic carcinomas.
SO - Chest Surg Clin N Am 2001 May;11(2):447-56
AD - Division of Medical Oncology, Department of Medicine, Mount Sinai School of Medicine, New York University, New York, New York, USA.
Thymomas are chemosensitive tumors with overall response rates of about 70% to various chemotherapy regimens. A fraction of patients (up to 25%-30%) will obtain a CR after chemotherapy. These results justify the use of chemotherapy in a multimodality fashion for the treatment of patients with advanced tumors. With radiotherapy added to chemotherapy, if necessary and if technically feasible, inoperable tumors may become resectable, leading to excellent long-term survival. On the other hand, thymic carcinomas are more refractory to chemotherapy, and their prognoses remain poor.

11
UI - 11413768
AU - Dziuba SJ; Curran WJ Jr
TI - The radiotherapeutic management of invasive thymomas.
SO - Chest Surg Clin N Am 2001 May;11(2):457-66
AD - Department of Radiation Oncology, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
The role of radiation therapy has been well established for selected patients with thymoma. Among patients with stage I tumors that have undergone a complete surgical excision, there is no indication for postoperative RT. There is also no need for postoperative RT for patients with completely excised stage II tumors when there is no transgression of the tumor through the thymic capsule. If there is transgression of the tumor through the capsule, postoperative RT is recommended even in the presence of complete surgical resection. For totally or partially resected stage III tumors, postoperative RT, to a total dose in excess of 50.4 Gy, is recommended. CT scan-based treatment planning is recommended for all of these indications. The role of preoperative RT is currently less certain. For bulky, unresectable tumors, preoperative chemotherapy and postoperative RT seem to be a promising trimodality approach. There also will be a need for preoperative RT among partial responders.

The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients.

[Effective combined treatment of thymus carcinoma with complete eradication of tumor after neoadjuvant therapy in a patient with severe

Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural

Chemotherapy of thymic carcinoma: analysis of seven cases and review of the literature.

Prognostic factors in thymic epithelial neoplasms.

Expression status of E-cadherin and alpha-, beta-, and gamma-catenins in thymoma.

1

UI - 11857293

AU - Okumura M; Ohta M; Tateyama H; Nakagawa K; Matsumura A; Maeda H; Tada H;

TI - Eimoto T; Matsuda H; Masaoka A The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients.

SO - Cancer 2002 Feb 1;94(3):624-32

AD - Division of General Thoracic Surgery, Department of Surgery, Osaka University Graduate School of Medicine, Osaka, Japan. meinosin@surg1.med.osaka-u.ac.jp

BACKGROUND: Although the histologic classification of thymic epithelial tumors has been confusing and controversial, an agreement on the universal classification system for thymic epithelial tumors was achieved by the World Health Organization (WHO) in 1999. The authors previously reported that the WHO histologic classification system reflects invasiveness and immunologic function of thymic epithelial tumors. In this subsequent study, they examined the prognostic significance of this classification system. METHODS: Clinical features as well as postoperative survival of patients with thymoma, but not thymic carcinoma, were examined with reference to WHO histologic classification based on an experience with 273 patients over a 44-year period. RESULTS: There were 18 type A tumors, 77 type AB tumors, 55 type B1 tumors, 97 type B2 tumors, and 26 type B3 tumors. In patients with type A, AB, B1, B2, and B3 tumors, the respective proportions of invasive tumor were 11.1%, 41.6%, 47.3%, 69.1%, and 84.6%; the respective proportions of tumors with involvement of the great vessels were 0%, 3.9%, 7.3%, 17.5%, and 19.2%; and the respective 20-year survival rates were 100%, 87%, 91%, 59%, and 36%. According to the Masaoka staging system, the 20-year survival rates were 89%, 91%, 49%, 0%, and 0% in patients with Stage I, II, III, IVa, and IVb disease, respectively. By multivariate analysis, the Masaoka staging system and the WHO histologic classification system were significant independent prognostic factors, whereas age, gender, association with myasthenia gravis, completeness of resection, or involvement of the great vessels were not significant independent prognostic factors. CONCLUSIONS: This study showed that histologic appearance reflects the oncologic behavior of thymoma when the WHO classification system is adopted. The WHO classification system may be helpful in clinical practice for the assessment and treatment of patients with thymoma. Copyright 2002 American Cancer Society. DOI 10.1002/cncr.10225

2

UI - 11523416

AU - Sokolov AN; Savchenko VG; Trakhtenberg AKh; Andreev IuN; Tochenov AV;

TI - Isaev VG; Skidan NI; Chemis AG; Vishnevskaia ES; Togonidze DK [Effective combined treatment of thymus carcinoma with complete eradication of tumor after neoadjuvant therapy in a patient with severe form of hemophilia A]

SO - Ter Arkh 2001;73(7):70-2

3

UI - 11834661

AU - de Bree E; van Ruth S; Baas P; Rutgers EJ; van Zandwijk N; Witkamp AJ;

TI - Zoetmulder FA Cytoreductive surgery and intraoperative hyperthermic intrathoracic chemotherapy in patients with malignant pleural mesothelioma or pleural metastases of thymoma.

SO - Chest 2002 Feb;121(2):480-7

AD - Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.

STUDY OBJECTIVES: No established curative treatment is available for pleural thymoma metastases and malignant pleural mesothelioma (MPM). Recently, peritoneal malignancies have been treated by cytoreductive surgery and intraoperative hyperthermic intracavitary perfusion chemotherapy (HIPEC). We investigated the feasibility and safety of this multimodality treatment in the thoracic cavity. DESIGN: Patients with pleural thymoma metastases or early-stage MPM were enrolled in a feasibility study. Morbidity, recurrence, and survival rates were recorded. SETTING: The Netherlands Cancer Institute. PATIENTS: Three patients with pleural thymoma metastases and 11 patients with pleural mesothelioma were treated. INTERVENTIONS: Cytoreductive surgery and intraoperative hyperthermic intrathoracic perfusion chemotherapy (HITHOC) with cisplatin and adriamycin were performed. The mesothelioma patients received adjuvant radiotherapy on the thoracotomy wound and drainage tracts. MEASUREMENTS AND RESULTS: Morbidity and mortality rates were 47% and 0%, respectively. Reoperation was necessary in four cases. Severe chemotherapy-related complications were not observed. A solitary mediastinal and a contralateral pleural thymoma recurrence were successfully treated by radiotherapy and a contralateral HITHOC procedure. All thymoma patients were alive and free of disease after a mean follow-up period of 18 months. After a mean follow- up period of 7.4 months, nine mesothelioma patients are alive. Two mesothelioma patients died of contralateral pleural and peritoneal recurrent disease, while one patient is alive with locoregional recurrence. CONCLUSIONS: Cytoreductive surgery and HITHOC with cisplatin and adriamycin is feasible in patients with pleural thymoma metastases and early-stage MPM, and is associated with acceptable morbidity rates. Early data on locoregional disease control are encouraging, and a phase II study will be conducted.

4

UI - 11902491

AU - Kitami A; Suzuki T; Kamio Y; Suzuki S

TI - Chemotherapy of thymic carcinoma: analysis of seven cases and review of the literature.

SO - Jpn J Clin Oncol 2001 Dec;31(12):601-4

AD - Department of Thoracic and Cardiovascular Surgery, Showa University Fujigaoka Hospital, Yokohama, Japan. kitami.a@showa-university- fujigaoka.gr.jp

BACKGROUND: Thymic carcinoma has a dismal prognosis compared with thymoma, because most of such tumors have locoregional invasion when diagnosed. Thus the important step in the management of thymic carcinoma is the introduction of systemic chemotherapy. However, as thymic carcinoma is a rare neoplasm, treatment with chemotherapy has not been studied systematically. METHODS: We analyzed seven cases of primary thymic carcinoma, treated with various chemotherapy regimens in our hospital from 1990 to 1999, and carried out a literature review of case reports of thymic carcinoma successfully treated with chemotherapy. RESULTS: All four cases who received modified ADOC therapy obtained partial responses. Other chemotherapeutic regimens (CHOP-E, PVB) were not effective. CONCLUSION: Based on the results of this study and the literature review, we feel that a positive response is obtainable with chemotherapy for thymic carcinoma. Modified ADOC therapy showed consistent efficacy in thymic carcinoma in this study.

5

UI - 11825741

AU - Rios A; Torres J; Galindo PJ; Roca MJ; Rodriguez JM; Sola J; Parrilla P

TI - Prognostic factors in thymic epithelial neoplasms.

SO - Eur J Cardiothorac Surg 2002 Feb;21(2):307-13

AD - Department of General Surgery and Digestive Apparatus I, Virgen de la Arrixaca University Hospital, 30120, El Palmar, Murcia, Spain. azrios@teleline.es

OBJECTIVES: The primary thymic epithelial neoplasms (PTENs) are uncommon tumours with a broad spectrum of both biological and morphological features. The aim of this study is to analyse the prognostic factors that influence survival. METHODS: Forty-four patients with a complete follow-up were analysed. Nine patients (20.5%) were asymptomatic, the most common symptoms in the rest being myasthenia gravis and dyspnoea. All the patients underwent surgery, 30 cases (68.2%) receiving total thymectomy and the rest a partial resection or biopsy. Marino-Muller's histological classification showed the mixed type to be the most common (52.3%). Clinical staging was done according to the Masaoka classification, which gave the most common stage as stage III (34.1%). RESULTS: Twelve patients died during a mean follow- up of 8.2 +/- 3.5 years. The accumulated survival rate was 77% at 5 years and 60% at 10 years. Analysis of the survival curves shows significant differences (P<0.05) when considering surgical technique, clinical staging and histological subtype. The multivariate analysis shows the only parameters with prognostic significance in PTENs to be clinical staging and histological type (P<0.001). CONCLUSIONS: The most important prognostic factors in PTENs are Masaoka's clinical staging and Marino-Muller's histological subtype.

6

UI - 11899204

AU - Yoshino I; Kase S; Yano T; Sugio K; Sugimachi K

TI - Expression status of E-cadherin and alpha-, beta-, and gamma-catenins in thymoma.

SO - Ann Thorac Surg 2002 Mar;73(3):933-7

AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. iyoshino@surg2.med.kyushu- u.ac.jp

BACKGROUND: A loss or dysfunction of E-cadherin or catenins, which maintain tissue integrity, is associated with an invasive phenotype of various solid tumors. Therefore, we analyzed the expression of E-cadherin and alpha-catenin, beta-catenin, and gamma-catenin in thymoma tissue specimens to investigate its clinical significance. METHODS: The expressions of E-cadherin and alpha-catenin, beta- catenin, and gamma-catenin in thymoma tissues were evaluated in 21 patients, including 9 epithelial predominant type, 5 lymphocytic predominant type, and 7 mixed type patients based on an immunohistochemical analysis using monoclonal antibodies, and the relationship between the expression status and clinicopathologic features was investigated. RESULTS: Reduced expressions were observed in 11 patients (52%) for E-cadherin, 10 (45%) for alpha-catenin, 6 (27%) for beta-catenin, and 10 (45%) for gamma-catenin. Such an expression status (reduced or preserved) of the molecules closely correlated with each other. The expression of E-cadherin was well preserved in 5 of 5 patients with lymphocyte predominant type whereas E-cadherin was reduced in 11 of 17 patients with other histologic subtypes. All of the 9 cortex type thymomas (B1 to 3) showed preserved expression of beta-catenin. There was no significant relationship among the expressions of the molecules and the Masaoka stage classification (I versus others). CONCLUSIONS: The status of expressions for these molecules may affect the degree of lymphoid infiltration while not affecting the degree of invasiveness in thymoma.

[Preoperative chemotherapy and operation for invasive

Masaoke stage III and IV a thymoma]

Enhanced expression of telomerase activity in thymoma and thymic carcinoma tissues: a clinicopathologic study.

Three-color flow cytometric study on lymphocytes derived from thymic diseases.

Measurement of antiacetylcholine receptor antibody in patients with thymoma without myasthenia gravis complications.

Immunohistological analysis of thymoma by molecules differentially expressed in the thymic cortex and medulla, and its application in the

[The kaleidoscope of autoimmune disorders: thymoma and systemic lupus erythematosus]

Surgical treatment of thymoma.

[An analysis of clinicopathologic features affecting prognosis of thymoma]

Elevated serum vascular endothelial growth factor and basic fibroblast growth factor levels in patients with thymic epithelial neoplasms.

CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity.

1

UI - 11778563

AU - Tan L; Qiu D; Wang Q

TI - [Preoperative chemotherapy and operation for invasive Masaoke stage III and IV a thymoma]

SO - Zhonghua Zhong Liu Za Zhi 2000 Jul;22(4):327- 9

AD - Department of Thoracic Surgery, Zhong Shan Hospital, Shanghai Medical University, Shanghai 200032, China.

OBJECTIVE: To assess the effect of preoperative chemotherapy on invasive thymoma. METHODS: Fourteen patients with invasive thymoma (12 cases in Masaoka stage III and 2 cases in stage IV a) were treated with 3- 4 cycles of CAVP (cyclophosphamide 600 mg/m2 D1, adriamycin 30 mg/m2 or epi-adriamycin 40 mg/m2 D1, vincristine 0.6 mg/m2 D1 or vindestine 3 mg/m2 D1, D8, cisplatin 30 mg/m2 D1, 2, 3). Following chemotherapy, patients were operated within 1-3 months. In 10 patients, sternotomy was performed and in 4 patients, anterolateral thoracotomy was performed. Radiotherapy was given with a total dose of 50-60 Gy in all patients except in those who were pathologically in complete remission. The patients were followed up for 6 months to 3 years. RESULTS: After chemotherapy, complete response was observed in 5 patients (35.7%) and partial response in 9 patients (64.3%). Nine patients received radical tumor resection and 5 patients received partial resection. Histologic/examination of the surgical specimens showed fibrosis of the remnant thymus in 5 patients. All but two patients survived in the follow-up period. Patient died from distant metastases at 18 and 24 months after treatment, respectively. CONCLUSION: Preoperative chemotherapy helps increase the resectability of stage III and IV a invasive thymoma. A longer follow-up period and more patients are needed to ascertain the impact of this treatment strategy on long- term survival.

2

UI - 11815982

AU - Watanabe M; Yu SK; Sawafuji M; Kawamura M; Horinouchi H; Mukai M;

TI - Kobayashi K Enhanced expression of telomerase activity in thymoma and thymic carcinoma tissues: a clinicopathologic study.

SO - Cancer 2002 Jan 1;94(1):240-4

AD - Department of Surgery, School of Medicine, Keio University, Tokyo, Japan. masazumi@med.keio.ac.jp

BACKGROUND: Telomerase is a nucleoprotein complex that caps the physical termini of all eukaryotic chromosomes. Because most malignant cells and reproductive cells have telomerase activity, which elongates telomeric DNA, telomerase may play important roles in unlimited cell division acquisition of the malignant phenotype. The current study examined the relation of telomerase activity in thymoma and thymic carcinoma with the clinicopathologic features of these lesions. METHODS: Tissue specimens were surgically resected from patients with thymoma and thymic carcinoma. Telomerase activity was evaluated according to a modified telomeric repeat amplification protocol assay. Paraffin sections of tumor were immunostained by MIC2 antibody, a marker of immature T cells. RESULTS: Telomerase activity was detected in all thymic epithelial tumors. The activity (mean +/- SD; unit per microg protein) in thymoma (n = 17) was significantly higher than that in thymic carcinoma (n = 7) (431.8 +/- 400.1 vs. 68.8 +/- 39.8; P < 0.01). Telomerase activities in thymoma and thymic carcinoma were significantly higher than that in primary lung adenocarcinoma (33.5 +/- 39.2, n = 47), studied as a control (P < 0.01). In patients with thymoma, telomerase activity did not correlate with tumor stage according to Masaoka classification (P = 0.776). In patients with thymic carcinoma, however, telomerase activity positively correlated with tumor stage (P = 0.02). In thymoma, telomerase activity positively correlated with the ratio of induced lymphocytes according to Rosai's classification (P = 0.045). MIC2- positive lymphocytes were identified in all cases of thymoma (n = 12). In contrast, lymphocytes infiltrating thymic carcinoma did not react with MIC2. CONCLUSIONS: In thymoma, telomerase activity reflects the presence of immature T-cell lymphocytes in tumor tissue rather than tumor stage or malignant phenotype. In thymic carcinoma, telomerase activity derived directly from cancer cells may relate to tumor stage. Copyright 2002 American Cancer Society.

3

UI - 11735267

AU - Okumura M; Fujii Y; Miyoshi S; Shiono H; Inoue M; Kadota Y; Fukuhara K;

TI - Matsuda H Three-color flow cytometric study on lymphocytes derived from thymic diseases.

SO - J Surg Res 2001 Dec;101(2):130-7

AD - Department of Surgery (E-1), Graduate School of Medicine, Osaka University, Suita-City, Japan. meinosin@surg1.med.osaka-u.ac.jp

BACKGROUND: Anterior mediastinal masses derive from a variety of diseases. Thymomas have been shown to commonly hold CD4(+)CD8(+) double- positive (DP) lymphocytes, and identification of this subset by two-color flow cytometric study was suggested to help diagnosis of thymoma. Several other thymic diseases, however, possibly hold CD4(+)CD8(+) DP lymphocytes. In this study, we utilized the three-color flow cytometric method for further examination of the phenotypes of lymphocytes in the thymic diseases. MATERIALS AND METHODS: One hundred eight specimens (77 primary and 10 metastatic thymomas, 10 thymic carcinomas, 2 thymic carcinoids, 4 malignant lymphomas, 2 seminomas, an inflammatory pseudotumor, and 2 nonneoplastic thymic hyperplasias) were subjected to the study. The expressions of CD3, CD4, and CD8 on tumor- associated lymphocytes were evaluated by three- color flow cytometric study. RESULTS: The proportion of the CD4(+)CD8(+) DP subset was more than 30% in all 78 lymphocyte-rich thymomas, in 2 malignant lymphomas, and in both thymic hyperplasias. CD3 expression of the CD4(+)CD8(+) DP subset ranged from a negative to a high level in thymomas and thymic hyperplasias, while it was restricted to a particular level in CD4(+)CD8(+) DP-type malignant lymphomas. The proportion of CD3(+) cells in the CD4(+)CD8(-) single-positive subset was consistently less than 90% in the lymphocyte-rich thymomas, while it was more than 90% in the thymic hyperplasias. CONCLUSION: Although identification of the CD4(+)CD8(+) DP subset in the tumor-associated lymphocytes does not necessarily indicate thymoma, a further characterization of thymic neoplasms possessing the CD4(+)CD8(+) DP subset was enabled by three-color flow cytometric study, suggesting the utility of this method as an ancillary tool for differential diagnosis of these diseases.

4

UI - 11808089

AU - Sakuraba M; Onuki T; Nitta S

TI - Measurement of antiacetylcholine receptor antibody in patients with thymoma without myasthenia gravis complications.

SO - Jpn J Thorac Cardiovasc Surg 2001 Dec;49(12):690-2

AD - Department Surgery I, Tokyo Women's Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan.

OBJECTIVE: Some patients with thymoma reported to show higher antiacetylcholine receptor antibody titers without the preoperative occurrence of myasthenia gravis and some have suffered postoperative complications of myasthenia gravis despite being negative for antiacetylcholine receptor antibody preoperatively. We evaluated changes in antiacetylcholine receptor antibody titers and the occurrence of myasthenia gravis in thymoma patients. METHODS: Subjects were 31 of 44 patients with thymoma undergoing thymothymectomy at Tokyo Women's Medical University Hospital between 1987 to 1999 in whom antiacetylcholine receptor antibody titers were measured preoperatively. We studied postoperative changes in antiacetylcholine receptor antibody titers and the presence or absence of myasthenia gravis. RESULTS: Eight patients were positive for antiacetylcholine receptor antibody preoperatively, suggesting the presence of subclinical myasthenia gravis. Neither postoperative changes in antiacetylcholine receptor antibody titers nor the occurrence of myasthenia gravis was observed in these 8 patients. Recurrent thymoma and rapid elevation of antiacetylcholine receptor antibody titers were observed postoperatively in 1 patient negative for antiacetylcholine receptor antibody preoperatively, resulting in manifestation of myasthenia gravis symptoms. CONCLUSION: We found no correlation between preoperative titers and myasthenia gravis symptoms. Rapid titer elevation indicates the occurrence of myasthenia gravis symptoms or the recurrence of thymoma.

5

UI - 11569925

AU - Shiraishi J; Utsuyama M; Akashi T; Nemoto T; Ohashi K; Akamatsu H;

TI - Sunamori M; Kitagawa M; Hirokawa K Immunohistological analysis of thymoma by molecules differentially expressed in the thymic cortex and medulla, and its application in the differential diagnosis of thymoma from esophageal and lung cancer.

SO - Pathol Res Pract 2001;197(9):611-9

AD - Department of Pathology and Immunology, Tokyo Medical and Dental University Graduate School, Japan.

The purpose of this study was to verify the WHO classification of thymic tumors using immunohistological methods, and to discover whether these methods can be applied to differentiate thymoma from squamous cell carcinoma (SCC) of the esophagus and the lung. Twenty-nine thymoma cases were classified according to WHO and were then immunohistologically examined for the positivity of these molecules. All thymoma cases investigated in this study were positive for IL-1R, and most of them were also positive for bek. In contrast, UH-1 was highly positive in B1 and B2 type thymomas, but negative or weakly positive in A, AB and B3 type thymomas. Twelve esophageal cancers and 21 lung cancers were also examined for the positivity of the same molecules. All esophageal cancers were negative for UH-1. Three of 12 cases were weakly positive for IL-1R, and four of these 12 cases were also weakly positive for bek. Twelve of 21 lung cancer cases were adenocarcinomas, all of them negative for IL-1R, bek and UH-1. Nine of 21 lung cancer cases were SCCs, all of them negative for UH- 1. Eight of nine SCC cases were strongly positive for IL-1R, while seven of these were weakly positive for bek. We conclude that the WHO classification of thymic tumors is still valid as demonstrated by immunohistological analysis and that the positivity of UH-1, IL- 1R and bek might be helpful in differentiating thymoma from SCC of the esophagus and the lung.

6

UI - 11789012

AU - Martinek V; Matousovic K; Dvorak D; Bartunkova J; Stejskal J; Chadimova

TI - M [The kaleidoscope of autoimmune disorders: thymoma and systemic lupus erythematosus]

SO - Vnitr Lek 2001 Oct;47(10):715-9

7

UI - 11837917

AU - Mehran R; Ghosh R; Maziak D; O'Rourke K; Shamji F

TI - Surgical treatment of thymoma.

SO - Can J Surg 2002 Feb;45(1):25-30

AD - Division of Thoracic Surgery, University of Ottawa, Ont.

OBJECTIVE: To describe experience with the surgical treatment of thymoma. DESIGN: A retrospective study. Setting: A teaching hospital at the University of Ottawa. PATIENTS: Over 25 years, 42 consecutive patients (22 men, 20 women) who had a thymoma requiring operation. INTERVENTIONS: Thymectomy. OUTCOME MEASURES: Age, sex, association with myasthenia gravis, presence of a paraneoplastic syndrome, extent of surgical resection, tumour size, histologic features of the tumour, clinical staging of the thymoma and short- and long-term outcome after surgery. RESULTS: The mean (and standard deviation) age of the patients was 52.8 (12.5) years. Thirteen patients had myasthenia gravis. With respect to tumour staging, 24 patients had stage I, 7 had stage II and 11 had stage III disease. Three patients were lost to follow-up. Radiotherapy was used as an adjunct to surgical treatment in 83% of patients with stages II and III disease. Fifty-one percent of patients available for follow-up survived 175.1 months, and the cumulative 5- and 10-year overall survival rates were 87.3% and 81.4% respectively. Only 1 patient died of metastatic thymoma. Complete or partial remission of myasthenia gravis was seen in 10 (77%) affected patients. Mixed cellular histologic features and a tumour size of less than 115 cm3 were more commonly seen with stage I disease. CONCLUSIONS: Thymomas are characterized by slow growth and prolonged survival even in patients with invasive disease as long as the tumour is resected completely and treatment is accompanied by radiotherapy.

8

UI - 11783072

AU - Lin D; Lu N; Zhang R

TI - [An analysis of clinicopathologic features affecting prognosis of thymoma]

SO - Zhonghua Zhong Liu Za Zhi 2001 Jan;23(1):57-9

AD - Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.

OBJECTIVE: To discuss the relationship between the clinicopathologic characteristics and prognosis of thymoma. METHODS: One hundred and thirty cases of thymoma were analyzed in terms of myasthenia gravis(MG), tumor size, necrosis, mitosis, capsule, histologic type according to the Lattes-Bernatz(L-B) classification and Muller-Hermelink(M-H) classification, staging according to Masaoka. RESULTS: Association with MG, size of tumor, necrosis, mitosis and L-B classification were of no prognostic significance. The survival rate was higher in patients with a well encapsulated tumor. According to the M-H subtypes, the prognosis was better in patients in medullary type than in patients with cortical type thymoma. In patients with well- differentiated thymic carcinoma(WDTC), their 5-year survival rate was 43.4%, and none survived at 10 years. The survival of patients decreased with the increase in clinical stage of the disease. Cell atypia and invasion of neighboring organs were of prognostic impact on survival. CONCLUSION: Histologic typing according to M-H classification and clinical staging according to Masaoka, cell atypia and invasion to neighboring organs are of prognostic value in patients with thymoma.

9

UI - 11766079

AU - Sasaki H; Yukiue H; Kobayashi Y; Nakashima Y; Moriyama S; Kaji M;

TI - Kiriyama M; Fukai I; Yamakawa Y; Fujii Y Elevated serum vascular endothelial growth factor and basic fibroblast growth factor levels in patients with thymic epithelial neoplasms.

SO - Surg Today 2001;31(11):1038-40

AD - Department of Surgery II, Nagoya City University Medical School, Nagoya, Japan.

Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors, among which vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF), are considered to exert potent angiogenic activity. In this study, we investigated whether serum VEGF and bFGF levels could be predictors of the development and extension of thymic epithelial neoplasms. The subjects of this study were 37 patients with thymoma, 6 with thymic carcinoma, and 23 healthy volunteers. Serum samples were collected before clinical treatment. Serum VEGF levels were significantly (P < 0.05) elevated in the patients with thymic carcinoma (1,080 +/- 1,185pg/ml) compared with those in the healthy volunteers (407 +/- 589 microg/ml). Serum bFGF levels were also significantly (P < 0.05) elevated in the patients with thymic carcinoma (2740 +/- 631 pg/ml) compared with those in the healthy volunteers (1728 +/- 1,192 pg/ml). However, the serum VEGF and bFGF levels did not significantly differ between the patients with thymoma and the healthy volunteers. Serum VEGF and bFGF levels did not significantly differ according to the stage and pathological subtype of thymoma. Moreover, there was no correlation between the serum levels of VEGF and those of bFGF. Thus, while serum VEGF and bFGF levels may serve as markers for thymic epithelial tumors, it is unlikely that circulating VEGF and bFGF could be used as markers for assessing the progression of thymoma tumors.

0

UI - 11220734

AU - Yu Z; Kryzer TJ; Griesmann GE; Kim K; Benarroch EE; Lennon VA

TI - CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity.

SO - Ann Neurol 2001 Feb;49(2):146-54

AD - Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA.

We have defined a new paraneoplastic immunoglobulin G (IgG) autoantibody specific for CRMP-5, a previously unknown 62-kd neuronal cytoplasmic protein of the collapsin response- mediator family. CRMP-5 is in adult central and peripheral neurons, including synapses, and in small-cell lung carcinomas. Since 1993, our Clinical Neuroimmunology Laboratory has detected CRMP-5- IgG in 121 patients among approximately 68,000 whose sera were submitted for standardized immunofluorescence screening because a subacute neurological presentation was suspected to be paraneoplastic. This makes CRMP-5 autoantibody as frequent as PCA-1 (anti-Yo) autoantibody, second only to ANNA-1 (anti-Hu). Clinical information, obtained for 116 patients, revealed multifocal neurological signs. Most remarkable were the high frequencies of chorea (11%) and cranial neuropathy (17%, including 10% loss of olfaction/taste, 7% optic neuropathy). Other common signs were peripheral neuropathy (47%), autonomic neuropathy (31%), cerebellar ataxia (26%), subacute dementia (25%), and neuromuscular junction disorders (12%). Spinal fluid was inflammatory in 86%, and CRMP-5-IgG in 37% equaled or significantly exceeded serum titers. Lung carcinoma (mostly limited small-cell) was found in 77% of patients; thymoma was in 6%. Half of those remaining had miscellaneous neoplasms; all but two were smokers. Serum IgG in all cases bound to recombinant CRMP-5 (predominantly N-terminal epitopes), but not to human CRMP-2 or CRMP-3.

[Achalasia secondary to radiotherapy in a patient with thymoma and myasthenia gravis]

[Thymectomy in myasthenia gravis]

[Experience of surgical treatment of thymoma]

Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis.

Detection of malignant thymoma in primary tumor and metastatic lesions using 99mTc-tetrofosmin scintigraphy.

Limbic encephalitis associated with recurrent thymoma: a postmortem study.

The potential role of bcl-2, bax, and Ki67 expression in thymus of patients with myasthenia gravis, and their correlation with

High-dose carboplatin with etoposide in patients with recurrent thymoma: the Indiana University experience.

Pure red cell aplasia with thymoma.

Thoracoscopic thymomectomy with the da Vinci computer- enhanced surgical system.

[Intrahepatic extramedullary hematopoiesis as a manifestation of a malignant thymoma: an unusual cause of nodular hepatomegaly]

Thymic carcinoma: a report of 13 cases.

Thymoma with pseudosarcomatous stroma.

Type B1 thymoma in multiple endocrine neoplasia type 1 (MEN-1) syndrome.

Expression of the MTA1 mRNA in thymoma patients.

Thymic epithelial tumors can develop along two different pathogenetic pathways.

Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence?

Minimal change nephrotic syndrome associated with malignant thymoma: case report and literature review.

Recurrence of thymoma: clinicopathological features, re- operation, and outcome.

Pseudodicentric (16;12)(q11;p11.2) in a type AB (mixed) thymoma.

[Comparative characteristics of surgical treatment of thymoma with the clinical signs of myasthenia and without them]

[The significance of Titin antibody in diagnosing myasthenia gravis with thymoma]

Thymoma is associated with an increased risk of second malignancy.

In vivo and in vitro expression of somatostatin receptors in two human thymomas with similar clinical presentation and different histological

Thymoma with osseous metaplasia.

An ectopic thymoma with spontaneous infarction.

[Familial thymoma and translocation t (14;20) (q24;p13)]

[CD7, HLA-DR, CD38 positive acute undifferentiated leukemia with subcutaneous tumor and thymoma]

Cytogenetic profile of a thymoma. A case report and review of the literature.

[Clinico-pathologic characteristics of malignant thymoma]

[Clinico-pathological characteristics and prognosis of thymoma: an analysis of 159 cases]

Flow and image cytometry in thymic neoplasia: correlation with clinical outcome.

Stiff-person syndrome associated with invasive thymoma: a case report.

[A case of thymoma with pure red cell aplasia]

1

UI - 11471225

AU - Prieto JL; Soria MJ; Pena JA; Infantes JM; Navas CJ; Martin L

TI - [Achalasia secondary to radiotherapy in a patient with thymoma and myasthenia gravis]

SO - Rev Esp Enferm Dig 2001 Feb;93(2):125-6

2

UI - 11412515

AU - Leon Atance P; Gonzalez Aragoneses F; Moreno Mata N; Garcia Fontan E;

TI - Leon Medina D; Naranjo Gomez J; Munoz Blanco J; Orusco Palomino E; Folque Gomez E [Thymectomy in myasthenia gravis]

SO - Arch Bronconeumol 2001 May;37(5):235-9

AD - Cirugia Toracica. Hospital General Universitario Gregorio Maranon. Madrid.

OBJECTIVE: To analyze outcome after thymectomy in patients with myasthenia gravis (MG). MATERIAL AND METHODS: Thirty-five patients with had associated thymomas. Preoperative Osserman classification showed 2 at level I, 20 at level IIA, 11 at level IIB and 2 at level III. Extended thymectomy through a medial sternotomy was performed in all. RESULTS: Postoperative complications developed in three patients (1 medullary aplasia, 1 postoperative reintubation, 1 myasthenic crisis). Mean follow-up was 89 months, with 22.8% achieving complete remission and 97.1% reporting improvements. The results were similar in the 10 patients with thymomas (20% full remission and 90% showing improvement). By DeFilippi classification, 22.8% were in class 1, 22.8% in class 2, 51.4% in class 3 and 2.8% in class 4. By Osserman classification, 9 were in the same category before and after surgery, 12 had improved one level, 10 had improved 2 levels, 3 had improved 3 levels and 1 patient had improved 4 levels. CONCLUSION: Thymectomy is an appropriate therapeutic procedure in the multidisciplinary treatment of patients with MG and it is the approach of choice for patients with associated thymomas. The intra- and post-operative complication rate is low and the rate of clinical improvement is high.

3

UI - 11482190

AU - Peliukhovskii SV

TI - [Experience of surgical treatment of thymoma]

SO - Klin Khir 2001 Apr;(4):35-6

For period from 1992 to 2000 years 72 patients with thymoma were operated. In 29 (40.2%) patients lymphocytic thymoma was revealed, in 10 (13.8%)- -"benign". Postoperative mortality was 4.1%. In term from 1 to 1.5 years 5 (6.9%) patients died.

4

UI - 11456312

AU - Buckley C; Douek D; Newsom-Davis J; Vincent A; Willcox N

TI - Mature, long-lived CD4+ and CD8+ T cells are generated by the thymoma in myasthenia gravis.

SO - Ann Neurol 2001 Jul;50(1):64-72

AD - Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.

Antibodies to muscle acetylcholine receptors, to other muscle antigens, and to some cytokines are found in the majority of patients with thymic tumors (thymomas) and myasthenia gravis (MG). The role of the tumor in initiating autoimmunity, however, is unclear; in particular, it is not known whether the thymoma exports mature and long-lived T cells, which could provide help for antibody production in the periphery. Here, we quantified recently exported thymic T cells using the approach of measuring episomal DNA fragments [T-cell receptor excision circles (TRECs)], generated by T-cell receptor gene rearrangement. Compared to values in healthy individuals (n = 10) or in patients with late-onset MG (n = 8), TREC levels were significantly raised in both the CD4+ and CD8+ peripheral blood compartments of patients with thymoma and MG (n = 14, p = 0.002 and p = 0.0004 compared to healthy controls) but only in the CD8+ compartment of the three patients with thymoma without MG (p = 0.4 and p = 0.01 for CD4+ and CD8+). TREC levels decreased following thymectomy to values similar to controls but were substantially raised in patients who had developed tumor recurrence (n = 6, p = 0.04 and p = 0.02 for CD4+ and CD8+); this was associated with increased antibodies to interferon-alpha and interleukin-12 in the one case studied serially. Collectively, these results support the hypothesis that the neoplastic thymoma tissue itself can generate and export mature, long-lived T cells and that these T cells reflect the thymic pathology and are likely to be related to the associated autoimmune diseases. The results also provide a new approach for early diagnosis of thymoma recurrence.

5

UI - 11467386

AU - Hashimoto T; Takahashi K; Goto M; Endo H; Kono T; Nishiyama H; Iimura F;

TI - Kuwashima S; Sawada H; Saiki N; Yamato M; Fujioka M Detection of malignant thymoma in primary tumor and metastatic lesions using 99mTc- tetrofosmin scintigraphy.

SO - Radiat Med 2001 May-Jun;19(3):169-72

AD - Department of Radiology, Dokkyo University School of Medicine, Tochigi, Japan.

99mTc-tetrofosmin was developed as a myocardial perfusion imaging agent and can also be used to depict tumors. We have experienced five cases of malignant thymoma delineated on 99mTc- tetrofosmin SPECT. In one case significant activity was clearly detected in the primary tumor and metastatic lesions. In quantitative analysis, similar 99mTc-tetrofosmin and 201Tl-chloride uptake ratios were obtained (1.95+/-0.57 versus 2.27+/-0.85, respectively; n.s.). The ability of 99mTc-tetrofosmin to detect malignant thymoma was comparable to that of 201Tl-chloride. Therefore, 99mTc-tetrofosmin might be a useful tracer for the detection of malignant thymoma, although more studies will be required to evaluate its diagnostic accuracy.

6

UI - 11468328

AU - Fujii N; Furuta A; Yamaguchi H; Nakanishi K; Iwaki T

TI - Limbic encephalitis associated with recurrent thymoma: a postmortem study.

SO - Neurology 2001 Jul 24;57(2):344-7

AD - Department of Neurology, Iizuka Hospital, Iizuka, Japan. fujii@tikugo.hosp.go.jp

The authors report an autopsied patient with limbic encephalitis and recurrent thymoma. The immunohistochemical study showed selective depositions of immunoglobulin G on the neurons in the limbic system and the tumor cells of the recurrent thymoma. The immunoblotting study detected two types of antibodies that react with the human brain, rat brain, and rat thymus.

7

UI - 11574213

AU - Salakou S; Tsamandas AC; Bonikos DS; Papapetropoulos T; Dougenis D

TI - The potential role of bcl-2, bax, and Ki67 expression in thymus of patients with myasthenia gravis, and their correlation with clinicopathologic parameters.

SO - Eur J Cardiothorac Surg 2001 Oct;20(4):712-21

AD - Department of Neurology, University of Patras, School of Medicine, Patras, Greece.

OBJECTIVE: The aim of this study was to evaluate bcl-2, bax (apoptotic-oncoproteins), and Ki67 (cell proliferation-marker) expression in thymus of patients with myasthenia gravis (MG) and to determine the potential correlation with clinicopathologic parameters. METHODS: The study was done on 38 patients (16 males, 22 females; mean age 38+/-10 years) with MG who underwent modified maximal thymectomy (MMT). Clinical staging (Osserman classification) included stage I in three, IIA in 19, IIB in 13 and III in three. Microscopic examination of thymus showed thymic hyperplasia in 19, atrophy in eight, thymoma in nine and thymic carcinoma in two. On paraffin sections, the streptavidin-biotin technique, using antibodies to bcl-2, bax, and Ki67, was employed, and in situ hybridization with digoxigenin-labeled probes to bcl- 2 and bax was performed. In addition, the apoptotic body index (ABI) was assessed via the TUNEL method. Staining results were correlated with clinicopathologic parameters. RESULTS: Bcl-2 expression was higher in hyperplasia and thymoma cases, compared to thymic carcinomas (P<0.001). Higher expression in carcinomas, compared to hyperplasia and thymomas, was observed for bax (P<0.001), Ki67 (P<0.001) and ABI (P<0.001). Statistical analysis demonstrated: (A) positive correlation of bax+ cells with MG stage (P<0.001), ABI and %Ki67+ cells with MG stage (P<0.001, respectively), %Ki67+ and %bax+ cells with ABI (P<0.05); and (B) reverse correlation between %bcl-2+ cells and MG stage (P<0.05). CONCLUSIONS: In patients with MG who underwent MMT, bcl-2, bax, and Ki67 expression correlates positively or reversibly with the microscopic findings of thymus. Increased apoptosis and proliferation accompany advanced disease stage and possible worse prognosis.

8

UI - 11593315

AU - Hanna N; Gharpure VS; Abonour R; Cornetta K; Loehrer PJ Sr

TI - High-dose carboplatin with etoposide in patients with recurrent thymoma: the Indiana University experience.

SO - Bone Marrow Transplant 2001 Sep;28(5):435-8

AD - Indiana University, Indianapolis, IN 46202, USA.

Thymoma is a chemotherapy-sensitive tumor with a 30-50% 5-year survival in previously untreated patients. Unfortunately, durable CRs with salvage chemotherapy are rarely observed. We initiated a phase II trial of high-dose carboplatin and etoposide in patients with relapsed thymoma or thymic carcinoma. All patients had progressive disease (PD) after initial or salvage chemotherapy, but were not cisplatin-refractory. PBSCs were mobilized using 10 microg/kg/day G-CSF. Patients received carboplatin 700 mg/m(2) and etoposide 750 mg/m(2) i.v. on days -5, -4, -3. Five patients were enrolled and evaluated after tandem transplants 4 weeks apart. All patients had pleural-based and lung parenchymal metastasis, one or two prior surgeries and two or more courses of prior cisplatin-based chemotherapy regimens. Chemotherapy was well tolerated, although grade IV hematological toxicity occurred in all patients. Progression-free survival following HDC ranged from 3.5 to 16.5 months. One patient maintained a CR for 12.8 months, then died from an unrelated cause. With a minimum of 2 years follow- up for all patients, three of five patients remain alive at 26+, 36+, and 49+ months. High-dose carboplatin and etoposide in relapsed thymoma is feasible with acceptable toxicity; however, these limited data do not appear superior to standard-dose salvage therapy.

9

UI - 11584960

AU - Samaiya A; Chumber S; Kashyap R; Subramaniam R; Vashisht S;

TI - Vijayaraghavan M; Srivastava A Pure red cell aplasia with thymoma.

SO - J Assoc Physicians India 2001 Jun;49():679-80

0

UI - 11581613

AU - Yoshino I; Hashizume M; Shimada M; Tomikawa M; Tomiyasu M; Suemitsu R;

TI - Sugimachi K Thoracoscopic thymomectomy with the da Vinci computer-enhanced surgical system.

SO - J Thorac Cardiovasc Surg 2001 Oct;122(4):783- 5

AD - Department of Surgery and Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. iyoshino@surg2.kyushu-u.ac.jp

1

UI - 11673738

AU - Herve S; Savoye G; Savoye-Collet C; Behbahani A; Auliac JB; Bota S;

TI - Francois A; Lerebours E [Intrahepatic extramedullary hematopoiesis as a manifestation of a malignant thymoma: an unusual cause of nodular hepatomegaly]

SO - Gastroenterol Clin Biol 2001 Jun-Jul;25(6- 7):711-3

2

UI - 11669591

AU - Lucchi M; Mussi A; Ambrogi M; Gunfiotti A; Fontanini G; Basolo F;

TI - Angeletti CA Thymic carcinoma: a report of 13 cases.

SO - Eur J Surg Oncol 2001 Nov;27(7):636-40

AD - Cardiac and Thoracic Department, Division of Thoracic Surgery, University of Pisa, Via Paradisa 2, Pisa 56124, Italy. m.lucchi@med.unipi.it

OBJECTIVE: Thymic carcinoma is a rare thymic neoplasm. It is more invasive and has a poorer prognosis than thymoma. We report our experience in the treatment of 13 thymic carcinomas. METHODS: Thirteen patients with histologically confirmed thymic carcinoma were treated therapy. Seven patients underwent neoadjuvant chemotherapy, followed by surgery and post-operative radiotherapy. RESULTS: The diagnosis of thymic carcinoma was achieved in six cases by a mediastinotomy, in three cases by a ultrasound- guided or a CT-guided fine needle aspiration and in three cases the pre-operative diagnosis was thymoma. In one case we did not have the histological diagnosis. All seven patients treated with neoadjuvant chemotherapy responded. The surgical resection was complete in seven cases. Eight patients are still alive 8-142 months from the diagnosis, and six are disease-free. CONCLUSIONS: Our experience supports the role of surgery and post-operative radiotherapy in thymic carcinomas. Pre-operative treatment of such neoplasms by multi-drug chemotherapy may improve the resectability and the survival rate. Copyright 2001 Harcourt Publishers Limited.

3

UI - 11675689

AU - Noh TW; Kim SH; Lim BJ; Yang WI; Chung KY

TI - Thymoma with pseudosarcomatous stroma.

SO - Yonsei Med J 2001 Oct;42(5):571-5

AD - Department of Pathology, Yonsei University College of Medicine, C.P.O. Box 8044, Seoul 120-752, Korea.

Thymoma with psuedosarcomatous stroma is a recently described, rare variant of thymomas that are characterized by having a biphasic histologic pattern which consists of both an epithelial and a spindle cell stromal component. So far only 11 cases having similar histologic findings have been reported worldwide. At this time we report a case of this rare variant of thymoma which occurred in a 53-year-old Korean man. This previously healthy patient presented with coughing and an anterior mediastinal mass was then detected radiographically. Mediastinal exploration revealed a 9 x 8 x 8 cm- sized well- encapsulated, ovoid, cystic mass. Histological examination showed a biphasic neoplasm composed of anastomosing nests of epithelial cells and somewhat cellular stromal spindle cells that had advanced degenerative changes. Immunohistochemical staining using the antibodies for cytokeratins, EMA, e-cadherin, and p75NGFR showed a strong expression of these markers in the epithelial component but no expression in the spindle stromal cells. The epithelial tumor cells showed no reactivity to CD5 and L26 and a high proportion of the infiltrated lymphocytes were the cortical type that expressed CD99 and terminal deoxynucleotidyl transferase. Ultrastructural examinations revealed tonofilaments in the spindle cells. Follow up has been done for 5 years after the surgical excision and the patient has been free of disease during that period. Similar to previous reports, this patient had a benign clinical course that was unassociated with myasthenia gravis which appears to be a characteristic of this histologic variant of thymoma. However, our case also showed advanced degenerative features and we could demonstrate ultrastructural evidence of epithelial differentiation in the stromal spindle cells that were not mentioned in the previously reported cases. Based on the results of our studies, we suggest this entity is a distinct type of organotypic thymoma that shows cortical differentiation and abundant cellular stroma.

4

UI - 11693806

AU - De Toma G; Plocco M; Nicolanti V; Brozzetti S; Letizia C; Cavallaro A

TI - Type B1 thymoma in multiple endocrine neoplasia type 1 (MEN-1) syndrome.

SO - Tumori 2001 Jul-Aug;87(4):266-8

AD - Department of Surgery Pietro Valdoni, University of Rome La Sapienza, Italy. detoma@uniroma1.it

AIMS AND BACKGROUND: Multiple endocrine neoplasia (MEN) syndromes include a group of disorders characterized by the neoplastic transformation of two or more endocrine tissues. In type 1 syndrome (MEN-1), pituitary, parathyroid and pancreatic islet tumors are most frequently represented. Thymic neoplasms are also rarely associated, and thymectomy during subtotal or total parathyroidectomy should always be considered. STUDY DESIGN: The authors describe a rare case of a 22-year-old male who presented a type B1 thymoma without myasthenia gravis associated to hyperparathyroidism, corticoadrenal adenoma and three neuroendocrine pancreatic lesions (somatostatinoma, glucagonoma and insulinoma).

5

UI - 11689291

AU - Sasaki H; Yukiue H; Kobayashi Y; Nakashima Y; Kaji M; Fukai I; Kiriyama

TI - M; Yamakawa Y; Fujii Y Expression of the MTA1 mRNA in thymoma patients.

SO - Cancer Lett 2001 Dec 28;174(2):159-63

AD - Department of Surgery II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. hisasaki@med.nagoya-cu.ac.jp

The MTA1 gene is a recently identified metastasis- associated gene which has been implicated in the signal transduction or regulation of gene expression. We examined the mRNA expression levels of the MTA1, the human homologue of the rat mta1 gene in thymoma. Expression of MTA1 mRNA was evaluated by reverse transcription polymerase chain reaction (RT-PCR) in 30 thymoma samples using LightCycler. The data was analyzed in reference to clinicopathological data. There was no relationship between MTA1 gene expression and age and gender. MTA1/GAPDH mRNA level in stage IV thymoma (6.431+/-3.404) was significantly higher than the level in stage I thymoma (2.592+/-1.902, P=0.0081). There was a tendency towards higher MTA1/GAPDH mRNA level in stage IV thymoma when compared to stage II thymoma (3.746+/-3.292, P=0.072). Thus our results show that the expression of the MTA1 gene is closely related to invasiveness in thymoma. The gene MTA1 could potentially provide information on the mechanism of tumor invasion and metastasis.

6

UI - 11696445

AU - Zhou R; Zettl A; Strobel P; Wagner K; Muller- Hermelink HK; Zhang S; Marx

TI - A; Starostik P Thymic epithelial tumors can develop along two different pathogenetic pathways.

SO - Am J Pathol 2001 Nov;159(5):1853-60

AD - Institute of Pathology and Forensic Medicine, Zhejiang University Medical School, Zhejiang, China.

To investigate genetic abnormalities associated with the development of thymic epithelial tumors, we performed microsatellite analysis of 26 thymomas belonging to three different World Health Organization types (A, B3, and C) using 48 repeats. The most frequent aberration seen was loss of heterozygosity (LOH) in the region 6q23.3-25.3 detected in 11 tumors (45.8% of informative cases). Further consistent LOHs were detected in regions 3p22-24.2, 3p14.2 (FHIT gene locus), 5q21 (APC), 6p21, 6q21-22.1, 7p21-22, 8q11.21-23, 13q14 (RB), and 17p13.1 (p53). Microsatellite instability was extremely rare, occurring in one type B3 thymoma only, although, at 12.5% of the analyzed loci. Comparing the allelotypes of the analyzed thymomas, we were able to identify two pathogenetic pathways these tumors develop along, characterized by the 6q23.3-25.3 and 5q21 LOHs, respectively. The APC aberration on 5q21 showed significant associations with LOH in the 3p22-24.2, 13q14, and 17p13.1 regions. Interestingly, type A thymomas presented with consistent LOH in the region 6q23.3-25.5 only, they did not reveal any aberrations in the APC, RB, and p53 gene loci or regions 3p22-24.2 and 8q11.21-23. The absence of these aberrations might be the reason for the well- known benign behavior of type A thymomas as compared to types B3 and C tumors.

7

UI - 11706095

AU - Buckley C; Newsom-Davis J; Willcox N; Vincent A

TI - Do titin and cytokine antibodies in MG patients predict thymoma or thymoma recurrence?

SO - Neurology 2001 Nov 13;57(9):1579-82

AD - Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK.

BACKGROUND: Patients with MG often have other autoantibodies in addition to those against the acetylcholine receptor (AChR). It has been suggested that antibodies to the muscle protein titin may be diagnostic of a thymoma, but they have also been found in patients with late-onset MG. Antibodies to certain cytokines have also been detected in patients with MG and thymoma, and it is not clear whether these antibodies could be more useful clinically. The authors measured antibodies against titin and the cytokines interferon alpha (IFNalpha) and interleukin 12 (IL12) in patients with MG and thymoma or thymoma recurrence, and in patients with MG but without thymoma presenting before (early-onset MG) or after (late-onset MG) 40 years of age. METHOD: Levels of titin, IFNalpha, and IL12 antibodies were determined by radioimmunoassay in 191 patients with MG and 82 controls. RESULTS: As previously reported, titin antibodies were uncommon in patients with early- onset MG. However, in patients with late-onset MG, titin antibodies had similar prevalence and levels to those in patients with MG and thymoma, although the antibodies were uncommon in patients between 40 and 60 years of age presenting without a tumor. By contrast, cytokine antibodies were more common in patients with thymoma than in patients without thymoma, and cytokine antibodies typically increased substantially if the thymoma recurred. CONCLUSIONS: Measurement of titin antibodies has limited use in predicting the presence of a tumor, unless the patient is less than 60 years of age, but measurement of IFNalpha and IL12 antibodies may be helpful in identifying patients with a thymoma recurrence, particularly when mediastinal imaging is equivocal.

8

UI - 11725628

AU - Lee HC; Cheng YF; Chuang FR; Chen JB; Hsu KT

TI - Minimal change nephrotic syndrome associated with malignant thymoma: case report and literature review.

SO - Chang Gung Med J 2001 Sep;24(9):576-81

AD - Division of Nephrology, Department of Internal Medicine, Chang Gung Memorial Hospital, 123, Ta-Pei Road, Niaosung, Kaohsiung, Taiwan, R.O.C. resident@ms10.hinet.net

We report on a patient with nephrotic syndrome with myasthenia gravis and malignant thymoma status post thymectomy and radiotherapy. This 44-year- old woman underwent a thymectomy and localized radiotherapy for invasive thymoma in 1991. She also took azathioprine and pyridostigmine regularly for the control of her symptoms of myasthenia gravis following thymectomy. Neither evidence of recurrence of myasthenia gravis, nor enlargement of residual thymoma was noted following treatment in 1991. Unfortunately, this patient developed a pronounced nephrotic syndrome in 1999, a renal biopsy revealing a minimal-change glomerulonephritis as being present. The patient entered remission subsequent to steroid and cyclosporin therapy, whereas many previously- reported cases of a similar nature either died or remained with a persistent proteinuria. Herein, we review the literature pertaining to examples of nephrotic syndrome for those patients diagnosed with malignant thymoma, and discuss the possible mechanisms for this association, and emphasize the need for the aggressive treatment of the condition, recommending the early use of steroids and cyclosporins.

9

UI - 11745803

AU - Haniuda M; Kondo R; Numanami H; Makiuchi A; Machida E; Amano J

TI - Recurrence of thymoma: clinicopathological features, re-operation, and outcome.

SO - J Surg Oncol 2001 Nov;78(3):183-8

AD - Department of Surgery, Shinshu University School of Medicine, Matsumoto, Japan. masa24@hsp.md.shinshu-u.ac.jp

BACKGROUND: Even after complete resection, recurrence of thymoma is not infrequently observed, and treatment of recurrent thymoma remains controversial. STUDY DESIGN: One hundred and twenty-six patients underwent surgically complete resection for thymoma, and 24 of them had a recurrence. Surgical treatment of recurrent thymoma was attempted in 15 patients for a total of 18 times. In the present study, the relevance of clinicopathological features and the re-operation on the survival rate after the recurrence were determined. RESULTS: The most frequent recurrent type was pleural dissemination (92%), with local recurrence observed in 5%. Overall 5- and 10-year survivals after recurrence were 37 and 16%, respectively. Disease-free interval after initial operation and complication of myasthenia gravis had no significant effect on postrecurrent survival. The use of postoperative mediastinal irradiation had no effect on reducing the recurrence rate or improving survival after recurrence. Two of 15 patients who underwent re-operation died of major complications after It. pleuropneumonectomy for severe pleural dissemination. In the present study, the re- operation was not significantly effective for prolongation of postrecurrence survival. CONCLUSION: Our study showed that re-operation should not be attempted for all patients with recurrent thymoma. Because effect of subtotal resection for severe pleural recurrence is disappointing, total resection for minimal pleural dissemination or small local recurrence will be undertaken to improve postrecurrent survival. Careful follow-up for > 10 years will increase the chance of the total resection of the recurrent thymoma. Copyright 2001 Wiley-Liss, Inc.

0

UI - 11734317

AU - Goh SG; Lau LC; Sivaswaren C; Chuah KL; Tan PH; Lai D

TI - Pseudodicentric (16;12)(q11;p11.2) in a type AB (mixed) thymoma.

SO - Cancer Genet Cytogenet 2001 Nov;131(1):42-7

AD - Department of Pathology, Singapore General Hospital, Outram Road, 169608, Singapore, Singapore.

Genetic alterations of thymomas are rarely described in the literature. In this study, a previously unreported instance of aberrant karyotypic change consisting of 45,XX,pseu dic(16;12) (q11;p11.2) [cp23]/87-90,idemx2[cp4] in a Masaoka Stage II mixed thymoma or type AB thymoma affecting a 56- year-old Chinese woman is detailed. Abnormalities involving 12p containing important tumor suppressor-like genes have been documented especially in hematological malignancies. Recently, recurrent losses involving 16q, a locus known to harbor several tumor suppressor genes, have been described in type C thymomas (squamous cell carcinoma), suggesting a possible relationship between type AB thymoma and type C thymoma. Whether these genes are involved in the pathogenesis of type AB thymoma remain to be clarified and it is currently unclear if cytogenetic studies may eventually play a role in the classification of thymic tumors.

1

UI - 11688282

AU - Peliukhovskii SV; Gonshcherovskii L; Kaspshik M

TI - [Comparative characteristics of surgical treatment of thymoma with the clinical signs of myasthenia and without them]

SO - Klin Khir 2001 Jul;(7):38-40

Analysis of results of surgical treatment of 72 patients with thymoma, including 49 in combination with clinical signs of myasthenia and 23 without them, is presented. In group of patients with symptoms of myasthenia the women aged from 30 to 39 yrs prevailed and among those who had not-- the men, aged from 40 to 49 yrs. Histologic investigation in 29 (59.1%) of patients with symptoms of myasthenia showed lymphocytic thymoma, in 10 (43.4%) of patients without signs of myasthenia--benign thymoma was revealed.

2

UI - 11766610

AU - Chen X; Lu C; Qiao J

TI - [The significance of Titin antibody in diagnosing myasthenia gravis with thymoma]

SO - Zhonghua Yi Xue Za Zhi 2001 Sep 25;81(18):1118-20

AD - Department of Neurology, Huashan Hospital, Medical Center of Fudan University, Shanghai 200040, China.

OBJECTIVE: To investigate the clinical significance of Titin antibody (Titin-ab) in diagnosing myasthenia gravis with thymoma (MGT). METHODS: Titin-ab and acetylcholine receptor antibody (AChR-ab) in the sera of 73 MGT patients with different thymic pathological patterns and 58 MG patients without thymoma (NTMG) were detected by ELISA. RESULTS: The positive rate of Titin-ab in MGT group was 76.7%, significantly higher than those of NTMG group, other neurologic diseases group and healthy control group (P < 0.01). The sensitivity of Titin-ab in diagnosis of MGT was significantly lower than that of CT scan or MR of thymus (P < 0.05), but the specificity of Titin-ab in diagnosis of MGT was significantly higher than that of CT scan or MR of thymus (P < 0.05). The positive rate of Titin-ab was mainly related to the thymic pathology and was the highest in the thymic epithelial thymoma (TET) subgroup (95.1%). There was no significant correlation between the positive rate of Titin-ab and the Masaoka's stage of thymoma (P > 0.05). The titer of Titin-ab was highly correlated to the titer of AChR-ab in MGT group (r = 0.496, P < 0.01), but not in MGH group (r = 0.385, P > 0.05). CONCLUSION: Detection of Titin-ab is a rather sensitive, specific, handy method in diagnosis of MGT (especially TET). It may play an important role in the pathogenesis of MGT.

3

UI - 11745297

AU - Pan CC; Chen PC; Wang LS; Chi KH; Chiang H

TI - Thymoma is associated with an increased risk of second malignancy.

SO - Cancer 2001 Nov 1;92(9):2406-11

AD - Department of Pathology, Veterans General Hospital-Taipei, No. 201, Sec. 2, Shih-Pai Road, Taipei, 11217 Taiwan. ccpan@vghtpe.gov.tw

BACKGROUND: An association between thymoma and second malignancy has been suggested but has not been validated. Whether the relation is due to treatment or to other thymoma-associated conditions is unclear. METHODS: The authors studied 192 consecutive patients with thymoma and compared the incidence of second malignancies with those of 206 patients who underwent thymectomy for nonthymomatous conditions and 1426 patients with nasopharyngeal carcinoma (NPC). Detailed clinicopathologic features of thymoma patients with second malignancies were described. RESULTS: Additional malignancies were detected in 15 of 192 patients (8%) during their clinical courses. The risk for those patients was significantly greater compared with the risk for patients with nonthymomatous conditions (adjusted odds ratio [OR], 3.81; 95% confidential intervals [95%CI], 1.05-13.81; P = 0.042) and patients with NPC (adjusted OR, 4.89; 95%CI, 2.26-10.53; P < 0.0001) after adjustment for age, gender, length of follow- up, myasthenia gravis, and radiation therapy. The occurrence of second malignancies did not correlate with histologic type or stage of thymoma, radiation therapy, or myasthenia gravis. CONCLUSIONS: Thymoma is associated with an increased risk of second malignancy. The association cannot be attributed to the effect of thymectomy or radiation therapy. Patients with thymoma, even if it is benign, should be followed regularly to facilitate the early detection of other malignancies. Copyright 2001 American Cancer Society.

4

UI - 11508787

AU - Ferone D; Kwekkeboom DJ; Pivonello R; Bogers ADColao A; Lamberts SW; van

TI - Hagen PM; Hofland LJ In vivo and in vitro expression of somatostatin receptors in two human thymomas with similar clinical presentation and different histological features.

SO - J Endocrinol Invest 2001 Jul-Aug;24(7):522-8

AD - Department of Internal Medicine, Erasmus Medical Center Rotterdam, The Netherlands. dferone@hotmail.com

[(111)In-DTPA0]octreotide scintigraphy allows the in vivo visualization of several types of SS receptor (SSR)-expressing tumors. Among these, thymomas have been recently detected. Here we report on 2 patients admitted for myasthenia gravis and radiological evidence of thymic mass. Although these patients had similar clinical presentation, in vivo SSR scintigraphy displayed a difference in the degree of the [(111)In-DTPA0]octreotide uptake. Considering that both thymic masses had comparable volume, [(111)In-DTPA0]octreotide level was significantly higher in one of the 2 tumors (tumor/background ratio of 5.7 vs 2.6). The SSR subtype expression pattern was studied in vitro on the surgically resected specimens by ligand binding techniques, quantitative reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. According to the recent World Health Organization classification, the 2 tumors were classified A and B2 thymomas respectively. In membrane homogenates, we found a higher number of high affinity [125I-Tyr11]-SS-14 binding sites in the B2 thymomas (23.5+/-2.5 vs 12.0+/-0.4 fmol/mg membrane protein; p<0.05). RT-PCR analysis showed sst1, sst2A and sst3 mRNA in the 2 thymoma tissues, whereas SS mRNA was detectable only in the A thymoma. Quantitative evaluation of RT-PCR data showed a comparable expression of the relative amount of sst2A mRNA in both tumors, whereas a significant higher expression of sst3 mRNA in the B2 thymoma. Sst2A immunoreactivity was localized mainly on the endothelium of intratumoral vessels, whereas sst3 was present on either tumoral epithelial cells or normal reactive thymocytes. The expression of sst2A receptors in these tumors is in line with the in vivo visualization by [(111)In-DTPA0]octreotide, which is considered a sst2-preferring ligand. However, since radioligand uptake was significantly higher in the B2 thymoma, which expressed the largest sst3 mRNA levels, it might be possible that this subtype is involved in determining the tumor visualization during SSR scintigraphy. Apart from the affinity of the radioligand for the receptor, also the efficacy of the internalization of the radioligand- receptor complex might play a role in radioactivity accumulation during in vivo SSR scintigraphy. In fact, although octreotide binds with lower affinity to sst3 receptors, this subtype displayed the highest amount of agonist-dependent receptor internalization compared to the other SSR subtypes. Moreover, sst3 was localized on both tumor cells and reactive thymocytes, and these latter cells are characterized by a very active turnover of membrane molecules. Finally, although more cases need to be evaluated, the lack of detection of SS mRNA in the tumor presenting a more aggressive phenotype (B2 thymoma) might have physiopathological or prognostic significance.

5

UI - 11711802

AU - Funai K; Yokose T; Yoshida J; Nishimura M; Nagai K; Nishiwaki Y; Ochiai

TI - A Thymoma with osseous metaplasia.

SO - J Comput Assist Tomogr 2001 Nov- Dec;25(6):897-9

AD - Pathology Division, National Cancer Center Research Institute East, Chiba, Japan.

A 69-year-old woman with a 15-year history of abnormal chest shadow was referred to our hospital. An enhanced chest CT scan of the anterior mediastinum revealed a mass containing a high- density area. The preoperative radiologic diagnosis was thymoma. Operation was performed within the tumor. Intratumoral ossification has never been reported in thymoma. Therefore, we report the first case of thymoma associated with multiple foci of osseous metaplasia.

6

UI - 11726901

AU - Carr CS; O'Keefe PA

TI - An ectopic thymoma with spontaneous infarction.

SO - J Thorac Cardiovasc Surg 2001 Dec;122(6):1234-5

AD - Department Thoracic Surgery, Guy's Hospital, London, United Kingdom. noahalkh@talk21.com

7

UI - 7985981

AU - Deminatti MM; Ribet M; Gosselin B; Bauters F; Mencier E; Savary JB; Lai

TI - JL; Vasseur F; Morel P; Bisiau-Leconte S [Familial thymoma and translocation t (14;20) (q24;p13)]

SO - Ann Genet 1994;37(2):72-4

AD - Service de Genetique Humaine et Pathologie Foetale, Faculte de Medecine, Lille, France.

A familial lympho-epithelial thymoma with constitutional chromosomal translocation t (14;20) (q24;p13) is presented: the thymoma and its particular translocation are present in the mother and the two sons of her offspring. The small number of cases do not allow establishing any relation between thymoma and this particular translocation. Concerning genetic counseling, an annual thoracic radiography is necessary for all the other family members, carriers or not of the translocation.

8

UI - 8827877

AU - Doi T; Sakamaki S; Koike K; Matsunaga T; Kobayashi D; Muramatsu H; Sato

TI - T; Watanabe N; Kougo Y; Niitsu Y [CD7, HLA-DR, CD38 positive acute undifferentiated leukemia with subcutaneous tumor and thymoma]

SO - Rinsho Ketsueki 1996 Aug;37(8):676-81

AD - Forth Department of Internal Medicine, Sapporo Medical University.

A case of acute undifferentiated leukemia (AUL), accompanied by subcutaneous tumor and thymoma is reported. The analysis of immunophenotype showed that the leukemic blasts were positive for CD7, HLA-DR, CD38 and CD34 in 17.5% but negative results were obtained for other lymphoid and myeloid antigens. The leukemic blasts had a rearranged immunoglobulin heavy chain (IgH) gene and T cell receptor delta (TCR-delta) chain gene chromosomal abnormality, 47, XY, +8, t(13; 17) (q12; q21), -17, +M was observed. In general, the CR rate is low and prognosis is poor in patients with AUL. In our case, CR was not achieved by the therapy with JALSG-ALL87 protocol, but was achieved by subsequent treatment with high dose ara-C therapy and combination chemotherapy including intermediate-dose ara-C, mitoxantrone, etoposide and prednisolone.

9

UI - 11079034

AU - Mirza I; Kazimi SN; Ligi R; Burns J; Braza F

TI - Cytogenetic profile of a thymoma. A case report and review of the literature.

SO - Arch Pathol Lab Med 2000 Nov;124(11):1714-6

AD - Department of Pathology and Laboratory Medicine, Danbury Hospital, Danbury, CT 06810, USA.

Cytogenetic analysis of mixed lymphocyte and epithelial thymoma in a nonmyasthenic female patient revealed deletion of part of the short arm of chromosome 6. To our knowledge, this cytogenetic abnormality in a benign thymoma has not been previously described in the literature, which is reviewed.

0

UI - 11776857

AU - Lin D; Lu N; Feng X

TI - [Clinico-pathologic characteristics of malignant thymoma]

SO - Zhonghua Zhong Liu Za Zhi 1999 Mar;21(2):136- 8

AD - Department of Pathology, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021.

OBJECTIVE: To assess the histopathology, clinical staging and treatment of malignant thymoma in relation to prognosis. METHODS: Sixty four cases with malignant epithelial thymic tumors treated in the period of 1958-1995 were retrospectively studied. Archived specimens were categorized according to Levine and Rosai into type I malignant thymoma(MT) and type II thymic carcinoma (TC). MT was histologically classified according to Muller- Hermelink(M-H). Clinical staging was ascertained according to Masaoka's criteria. RESULTS: There were 41 cases of MT and 23 cases of TC. No medullary or mixed thymoma was observed in this series of MT. The 5-year survival rate of patients with MT of predominantly cortical, cortical, and well- differentiated thymic carcinoma (MDTC) subtypes was 75.3%, 44.7% and 43.3%, respectively. That of patients with TC of squamous-cell carcinoma and lympho-epithelioid subtypes was 27.5% and 60.0%, respectively. The 10-year survival rate of these 5 subtypes was 25.3%, 10.0%, 0, 0, 20.0%, respectively(P < 0.05). The 5-year and 10-year survival rates decreased with increase in staging. In 22 patients in stage III and IV who received thoracotomy with biopsy only, their survival rate was significantly lower than that in patients with their tumor resected. CONCLUSION: Histomorphology of the tumor, heterogeneity in cell types, clinical staging and the extent of tumor resection are factors affecting survival.

1

UI - 11776813

AU - Li J; Wang L; Zhang R

TI - [Clinico-pathological characteristics and prognosis of thymoma: an analysis of 159 cases]

SO - Zhonghua Zhong Liu Za Zhi 1999 Jul;21(4):272- 4

AD - Department of Thoracic Surgery, Cancer Institute (Hospital), Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021.

OBJECTIVE: To investigate the clinicopathologic features of thymoma and assess prognostic factors. METHODS: Data of 159 patients operated for thymoma were collected. A retrospective analysis was performed, through comparison of survival rate computed by the actuarial method and rate of recurrence and metastasis. RESULTS: (1) The 3-, 5-, and 10-year survival rate was 78.9%, 63.7% and 46.3%, respectively. All patients treated by subtotal thymoma resection with postoperative radiotherapy survived more than 3 years. (2) Patient's age, location and image density of tumor play important role in differential diagnosis. (3) Tumors with epithelial predominance were more frequently seen in late stage than those of other histologic types(P < 0.01). (4) The prognosis of patients whose tumors had incomplete or no capsule was poor as compared to that of stage I tumor (P < 0.05). (5) According to multivariate analysis, the most important prognostic variables included completeness of resection (OR = 2.10) and clinicopathologic stage (OR = 1.73). Myasthenic crisis was the most important factor influencing operative death. Sex, symptoms and histologic classification did not influence prognosis. (6) Recurrence and metastasis occurred in all stages, but more frequent in the later stages of the disease. CONCLUSION: Complete resection helps decrease recurrence of thymoma. Prognosis of patients receiving palliative resection of thymoma may be improved by postoperative radiotherapy.

2

UI - 11531146

AU - Kenny-Moynihan MB; DeRose PB; Gal AA; Chakraborty H; Cohen C

TI - Flow and image cytometry in thymic neoplasia: correlation with clinical outcome.

SO - Anal Quant Cytol Histol 2001 Aug;23(4):313-20

AD - Department of Pathology and Laboratory Medicine, Rollins School of Public Health, Robert W. Woodruff Health Sciences Center, Emory University, Atlanta, Georgia 30322, USA.

OBJECTIVE: To compare nuclear DNA by flow (FCM) and image cytometry (ICM) in thymic neoplasms and to relate results to clinical outcome. STUDY DESIGN: DNA ploidy of 44 thymomas and 6 thymic carcinomas was studied by FCM and ICM of single nuclear suspensions from paraffin blocks. RESULTS: By FCM, 33 thymomas (75%) and one thymic carcinoma (17%) were diploid; 6 thymomas (14%) and 4 thymic carcinomas (67%) were aneuploid. By ICM, 36 thymomas (82%) were diploid; 7 thymomas (16%) and 6 thymic carcinomas (100%) were aneuploid. Mean follow-up in 44 cases was 46.2 months (range, 1-162). Ten patients with persistent/recurrent disease included four with thymic carcinoma, who died of the disease (two aneuploid by both techniques, two aneuploid by ICM with unsatisfactory/diploid FCM). Four had invasive thymoma and recurrence after 13-150 months (two diploid and two aneuploid by both methods), one had diploidy and noninvasive thymoma that recurred at 92 months, and one had an epithelial thymoma that recurred at 144 months (aneuploid by FCM, diploid by ICM). CONCLUSION: The results obtained in this preliminary, retrospective study show a high concordance between FCM and ICM; aneuploidy correlated with poor outcome by both methodologies. While these findings are encouraging, larger numbers of cases will be needed to define the role of FCM and ICM in predicting outcome in thymic tumors.

3

UI - 11718752

AU - Hagiwara H; Enomoto-Nakatani S; Sakai K; Ugawa Y; Kusunoki S; Kanazawa I

TI - Stiff-person syndrome associated with invasive thymoma: a case report.

SO - J Neurol Sci 2001 Dec 15;193(1):59-62

AD - Department of Neurology, Division of Neuroscience, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Tokyo, 113-8655, Bunkyo, Japan.

We report a case of a 40-year-old female with continuous muscle stiffness and painful muscle spasms. The symptoms worsened over a two-week period after onset. Electrophysiological examinations revealed continuous muscle discharge, which was markedly reduced by intravenous administration of diazepam. High levels of anti-glutamic acid decarboxylase (GAD) antibodies were detected in both serum and cerebrospinal fluid, suggesting that the patient suffered from stiff-person syndrome. Steroid pulse therapy and immunoadsorption therapy alleviated the clinical symptoms and decreased the anti-GAD antibody titer. A chest CT revealed the presence of an invasive thymoma. Neither anti-acetylcholine receptor (AChR) antibodies nor symptoms of myasthenia gravis (MG) were observed. The patient underwent a thymectomy and postoperative radiotherapy. These treatments further alleviated the clinical symptoms. The present case is the first that associates stiff-person syndrome with invasive thymoma, and not accompanied by MG. The autoimmune mechanism, in this case, may be triggered by the invasive thymoma.

4

UI - 11761906

AU - Adachi K; Tanaka J; Sato T; Makino S; Hosaka N; Takao M; Yada I;

TI - Namikawa S [A case of thymoma with pure red cell aplasia]

SO - Kyobu Geka 2001 Dec;54(13):1153-5

AD - Department of Thoracic and Cardiovascular Surgery, Toyooka Hospital, Toyooka, Japan.

A 71-year-old man was admitted to the hospital because of general fatigue. There were few reticulocytes in the peripheral blood and no erythroblasts in the bone marrow. Chest CT revealed an anterior mediastinal tumor. Under a diagnosis of thymoma with PRCA, extended thymothymectomy was performed. Histological diagnosis was mixed type thymoma with no invasive growth beyond the capsule. Administration of predonisolone following surgery was not effective for PRCA. Otherwise, peripheral blood counts were significantly improved following occasional onset of acute bronchitis.

2
UI - 21426173
AU - Renaudineau E; Lobbedez T; Reman O; el Haggan W; Ryckelynck JP; Hurault
TI - de Ligny B [Glomerulonephritis revealing a thymus tumor in a patient with myasthenia gravis]
SO - Rev Med Interne 2001 Aug;22(8):763-4

3
UI - 21354347
AU - Tarr PE; Lucey DR; Infectious Complications of Immunodeficiency with
TI - Thymoma (ICIT) Investigators Good's syndrome: the association of thymoma with immunodeficiency.
SO - Clin Infect Dis 2001 Aug 15;33(4):585-6

4
UI - 21325441
AU - Kamikubo Y; Shiiya N; Kubota S; Yasuda K
TI - Thymic carcinoma with tumor thrombus into the superior vena cava.
SO - Jpn J Thorac Cardiovasc Surg 2001 May;49(5):327-9
AD - Department of Cardiovascular Surgery, Hokkaido University School of Medicine, Kita-14, Nishi-5, Kita-ku, Sapporo 060-8648, Japan.
Tumor thrombus into the vena cava have been reported in cases with renal cell carcinoma, thyroid tumor and in those with thymoma. These tumors are frequently invasive and continuous from the main tumor that shows direct vessel wall invasion. Here, we report a case of thymic carcinoma with superior vena cava syndrome, which was caused by a tumor thrombus in the superior vena cava without vessel wall invasion. The main mediastinal tumor did not show innominate vein invasion, and the superior vena cava syndrome was a result of separate tumor thrombus that was free of vessel wall invasion. The tumor thrombus could be removed through a simple venotomy. To prevent stenosis in the superior vena cava and the left innominate vein, we used a pericardial patch to close the venotomy site.

5
UI - 21369218
AU - Peliukhovskii SV
TI - [Application of videothoracoscopy in surgical treatment of thymoma and histological characteristics of the tumor]
SO - Klin Khir 2001 Jan;(1):54-5

6
UI - 21409364
AU - Tanio N; Kadokura M; Kataoka D; Yamamoto S; Nonaka M; Takaba T
TI - [A surgically treated case of capsulated thymoma with thymic cyst]
SO - Kyobu Geka 2001 Aug;54(9):801-4
AD - Department of Surgery, Showa University School of Medicine, Tokyo, Japan.
A 56-year-old woman was pointed out an abnormal shadow on chest roentgenogram. Chest CT and MRI showed a solid mass with a cyst at right anterior mediastinum. Clinical diagnosis was thymoma with cyst, and surgical excision was performed. The histopathological examination of the resected specimen demonstrated that the epithelia of the cyst wall was single cuboidal or squamous cells and contained some foci of thymic tissue. The solid mass was capsulated and predominantly composed of lymphocytes. The pathological diagnosis was a thymoma (predominantly lymphocytic type) with thymic cyst. She is doing well for 10 years postoperatively.

7
UI - 21436696
AU - Rotter G; Schneider U; Tunn PU
TI - [Thymoma with primary osseous and pulmonary metastases. Case report and review of the literature]
SO - Orthopade 2001 Aug;30(8):559-64
AD - Klinik fur Chirurgie und Chirurgische Onkologie, Universitatsklinikum Charite, Medizinische Fakultat, Humboldt-Universitat, Robert-Rossle-Klinik am Max-Delbruck-Centrum fur Molekulare Medizin, 13122 Berlin.
Bone metastases can be the first symptom of a tumor. The case of a 65-year-old patient with a thymoma exhibiting primary metastases in the lung and bone is presented. Initially, a tumor was suspected because of an osteolytic destruction of the right proximal femur posing a high risk of fracture. Further diagnostic procedures detected a partially sclerosing mediastinal bulk and bilateral lung metastases. The histological investigation of the resected proximal femur and needle biopsy of the mediastinal bulk showed an extrathoracically metastasized polygonal cell thymoma. This metastasizing pattern is common in thymic carcinoma but very rare in thymoma. In addition to the case presentation, a review of the current literature on histological classification, therapy, and prognosis is given.

8
UI - 21438641
AU - Alilovic M; Peros-Golubicic T; Tekavec-Trkanjec J; Bekic A
TI - [Thymoma--a case report of a patient with superior vena cava syndrome]
SO - Lijec Vjesn 2001 May-Jun;123(5-6):124-6
AD - Klinika za plucne bolesti-Jordanovac, Jordanovac 104, 10 000 Zagreb.
A 65-year old male patient was admitted to the hospital because of superior vena cava syndrome. Chest X-ray, CT of the thorax, phlebography and transesophageal echocardiography revealed a mediastinal tumor, which filled superior vena cava spreading to the right atrium and sinking to the right ventricle. The patient underwent incomplete surgical resection of the tumor that showed to be thymoma according to histopathologic analysis. In addition, the patient received chemotherapy during the following six months.

9
UI - 21409391
AU - Hirai T; Yamanaka A; Fujimoto T; Takahashi A; Takayama Y; Yamanaka K
TI - Multiple thymoma with myotonic dystrophy.
SO - Jpn J Thorac Cardiovasc Surg 2001 Jul;49(7):457-60
AD - Department of Chest Surgery, Fukui Red Cross Hospital, 2-4-1 Tsukimi, Fukui 918-8501, Japan.
A case of multiple thymoma associated with myotonic dystrophy is reported. The patient was a 42-year-old man who had two separate encapsulated thymoma in the anterior mediastinum, at 3 cm in diameter on the right side, and at 4 cm in diameter on the left. Extended thymo-thymomectomy was performed. Microscopically, the tumor in the right thymic lobe was predominantly mixed type, and that in the left predominantly epithelial type. Neuromuscular disease appeared to develop, with severe sputum retention in the larynx and he was referred to neurology at 6 months after surgery. On examination, he presented a characteristic hatchet face, muscle atrophy, muscle weakness, percussion myotonia and grip myotonia, and diagnosis was revised to be multiple thymoma associated with myotonic dystrophy. This association is extremely rare. It is difficult to clarify whether this association was a syndrome or coincidence.

10
UI - 21387644
AU - Baba M; Nomoto Y; Iyoda A; Saito H; Hiroshima K; Shibuya K; Haga Y;
TI - Hoshino H; Iizasa T; Horiuchi F; Fujisawa T Cytomorphologic features characteristic of tumor stages of thymomas.
SO - Oncol Rep 2001 Sep-Oct;8(5):1139-43
AD - Department of Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan.
The cytologic findings of the tumor cells characteristic of the stages of thymomas were investigated to assess the invasiveness of the tumors. Forty-six patients with thymoma who underwent extensive thymectomy without pre-operative corticosteroid therapy were included in this study. The histologic subtypes included 18 round/oval, 20 mixed, and 8 spindle type. The stages of thymoma classified according to Masaoka's clinicopathological classification included 16 stage I, 20 stage II, 6 stage III, 2 stage IVa, and 2 stage IVb, and myasthenia gravis was recognized in 5 patients. Cytologic findings were retrospectively analyzed in the Papanicolaou-stained stamp smears obtained from the cut surfaces of thymoma specimens. Morphometry of the epithelial tumor cells using Cosmozone-1A was performed to evaluate the validity of our cytologic categories. Compared with the cytologic findings of stage I or II thymomas, those of epithelial tumor cells in stage III or IV more frequently showed necrotic background (50.0%-stage III or IV vs 11.1%-stage I or II, p=0.006), large clusters of epithelial tumor cells (70.0% vs 36.1%, p=0.055), marked nuclear enlargement (90.0% vs 52.7%, p=0.033), marked anisokaryosis (100% vs 52.7%, p=0.006), marked nuclear polymorphism (40.0% vs 5.5%, p=0.004), hyperchromasia (50.0% vs 11.4%, p=0.007) and prominent nucleoli (50.0% vs 16.6%, p=0.028) whereas no significant correlation was observed between cytologic findings and tumor volume. Morphometric studies of thymoma tumor cells revealed that the nuclear size (mean values, 78.8 microm(3)-stage III or IV vs 58.2 microm(3)-stage I or II), the coefficient of variation of the nuclear size (0.326 vs 0.282), and the nuclear rotundity (0.849 vs 0.858) differed significantly between the two categories (p<0.05). Our findings demonstrated that there were significant differences between the cytologic findings of epithelial tumor cells of stage I or II thymomas and those of stage III or IV thymomas, and that the cytologic findings of thymoma tumor cells appear to be useful for distinguishing between non-invasive and invasive thymomas.

11
UI - 21433781
AU - Varley CL; Royds JA; Brown BL; Dobson PR
TI - Interleukin-1 beta induced synthesis of protein kinase C-delta and protein kinase C-epsilon in EL4 thymoma cells: possible involvement of phosphatidylinositol 3-kinase.
SO - Exp Clin Immunogenet 2001;18(3):135-42
AD - Institute of Endocrinology, Division of Genomic Medicine, University of Sheffield Medical School, Sheffield, UK.
We present evidence here that the proinflammatory cytokine, interleukin-1 beta (IL-1 beta) stimulates a significant increase in protein kinase C (PKC)-epsilon and PKC-delta protein levels and increases PKC-epsilon, but not PKC-delta, transcripts in EL4 thymoma cells. Incubation of EL4 cells with IL-1 beta induced protein synthesis of PKC-epsilon (6-fold increase) by 7 h and had a biphasic effect on PKC-delta levels with peaks at 4 h (2-fold increase) and 24 h (4-fold increase). At the level of mRNA, PKC-epsilon, but not PKC-delta levels, were induced after incubation of EL4 cells with IL-1 beta. The signalling mechanisms utilized by IL-1 beta to induce the synthesis of these PKC isoforms were investigated. Two phosphatidylinositol (PI) 3-kinase-specific inhibitors, wortmannin and LY294002, inhibited IL-1 beta-induced synthesis of PKC-epsilon. However, the PI 3-kinase inhibitors had little effect on the IL-1 beta-induced synthesis of PKC-delta in these cells. Our results indicate that IL-1 beta induced both PKC-delta and PKC-epsilon expression over different time periods. Furthermore, our evidence suggests that IL-1 beta induction of PKC-epsilon, but not PKC-delta, may occur via the PI 3-kinase pathway. Copyright 2001 S. Karger AG, Basel

12
UI - 21477993
AU - Zhang H; Lu N; Wang M; Gu X; Zhang D
TI - Postoperative radiotherapy for stage I thymoma: a prospective randomized trial in 29 cases.
SO - Chin Med J (Engl) 1999 Feb;112(2):136-8
AD - Department of Radiotherapy, Cancer Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100021, China.
OBJECTIVE: To determine the effect of postoperative radiotherapy on stage I thymoma. METHODS: Twenty-nine patients with stage I thymoma included in this study. All patients were randomly assigned into two groups: surgery alone (13 patients) and surgery with postoperative radiotherapy (16). Staging was based on the surgical and pathologic criteria that the tumor had a complete capsule and without capsular invasion microscopically. Adjuvant radiotherapy was started within 4 weeks after surgery. Megavolage radiation, using the isocentric technique, was administered through an anterior field and/or two anterior oblique wedge fields. For the patients with lymphocytic predominant type, the dose was 50 Gy in 25 daily fractions for 5 weeks; for the patients with epithelial cell type or mixed type, the dose was 60 Gy in 30 daily fractions for 6 weeks. The survival rates were estimated by the Kaplan-Meier method. RESULTS: There was no recurrence and metastasis in either group. No acute and late radiological injuries were found among the patients receiving radiotherapy postoperatively. The 5-year and 10-year survivals were both 92% for the patients treated by surgery alone. However, the survival rates for patients who received radiotherapy were both 88%. There was no difference in the survivals in these two groups. Of the 3 died patients, 1 died of myasthenia gravis and 2 of intercurrent illness. No significant correlation was found between myasthenia gravis and radiotherapy. CONCLUSIONS: Postoperative radiotherapy is unnecessary for the patients with stage I thymoma. No relation is found between radiotherapy and myasthenia gravis.

13
UI - 21321398
AU - Shimada T; Terashima H; Shimizu T; Hirayama K
TI - Invasive thymoma associated with lung cancer: report of a case.
SO - Surg Today 2001;31(6):507-9
AD - Department of Surgery, Hiraka General Hospital, Yokote, Akita, Japan.
We report herein a case of invasive thymoma simultaneously associated with lung cancer. A 64-year-old man presented with a cough and anterior chest pain, and preoperative examinations revealed an anterior mediastinal tumor as well as lung cancer. The patient underwent a total thymectomy, partial resection of the right lung, left lower lobectomy, and mediastinal lymph node dissection, followed by radiotherapy. Although it is well known that thymomas may be accompanied by nonthymic cancers, invasive thymomas occurring coincidentally with lung cancer are rarely reported in Japan. This case is very interesting in its relation to the oncogenesis of thymomas.

14
UI - 21479097
AU - Sasaki H; Auclair D; Kaji M; Fukai I; Kiriyama M; Yamakawa Y; Fujii Y;
TI - Chen LB Serum level of the periostin, a homologue of an insect cell adhesion molecule, in thymoma patients.
SO - Cancer Lett 2001 Oct 22;172(1):37-42
AD - Department of Surgery II, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan. hisasaki@med.nagoya-cu.ac.jp
Periostin protein shares structural and sequence homology with fasciclin I, which is an insect adhesion molecule. Periostin has a typical signal peptide at the N-terminal end suggesting it is a secreted protein. Recently, we developed a novel sandwich chemiluminescence assay to determine serum concentrations of periostin. We investigated the serum periostin level in thymoma patients, and attempted to determine the correlation between serum periostin level and clinicopathological factors of thymoma patients who had undergone surgery between January different between the thymoma patients (1264.4+/-122.9 ng/ml) and the normal control (962.0+/-118.6 ng/ml) (P=0.0877). There was no relationship between serum periostin level and age, gender or pathological subtype. However the serum periostin level of stage IV patients (1497.0+/-285.8 ng/ml) was significantly higher than normal control (P=0.0460). These data suggest that serum periostin level may indicate tumor invasion and progression of thymoma.

2
UI - 21406689
AU - Refaely Y; Simansky DA; Paley M; Gottfried M; Yellin A
TI - Resection and perfusion thermochemotherapy: a new approach for the treatment of thymic malignancies with pleural spread.
SO - Ann Thorac Surg 2001 Aug;72(2):366-70
AD - Department of Thoracic Surgery, Sheba Medical Center, Tel Hashomer, Israel.
BACKGROUND: Thymoma and thymic carcinoma with pleural spread have a high rate of locoregional recurrence and poor prognosis. Maximal debulking coupled with aggressive local treatment could offer a chance for cure. This study evaluates the early and midterm results of operation and hyperthermic pleural perfusion with cisplatinum for thymic malignancies. METHODS: Fifteen patients (11 men), 20 to 67 years old (10 thymoma, 4 thymic carcinoma, 1 carcinoma in thymic cyst) underwent resection and hyperthermic pleural perfusion between 1995 to 2000. All had pleural spread proven before or intraoperatively. Six of the thymoma cases were recurrent. Current operation included resection without pleurectomy (9 patients), resection with pleurectomy (5), and extrapleural pneumonectomy (1 patient) with intraoperative hyperthermic pleural perfusion in all. Intrapleural temperature reached 40.3 degrees C to 43 degrees C. The total dose of cisplatinum was 150 mg or more in 14 patients. RESULTS: Complete resection (R0) was achieved in 10 patients, subtotal (R1) in 3, and partial (R2) in 2. There was no operative mortality, no hemodynamic or respiratory disturbances during perfusion, and no hematologic, neurologic, or renal complications. Complications consisted of significant bleeding (2 patients), fever (2), and air leak (1 patient). Two patients with thymic carcinoma died after 27 and 34 months, and 1 is alive with no evidence of disease at 54 months. Two patients with thymoma died after 7 and 36 months. Eight are alive after 9 to 70 months. Four patients (all R0) are alive without local recurrence more than 60 months after operation and hyperthermic pleural perfusion. CONCLUSIONS: Operation and thermochemotherpy is feasible and safe in patients with thymic tumors. This method seems to offer excellent local control for patients with stage IV-a thymic malignancies. Midterm results suggest that operation plus hyperthermic pleural perfusion may lengthen survival in stage IV-a thymoma.

3
UI - 21406739
AU - Poullis M; Punjabi P
TI - Concomitant thymectomy and cardiac operation in a patient with pure red cell aplasia.
SO - Ann Thorac Surg 2001 Aug;72(2):621-3
AD - Department of Cardiothoracic Surgery, National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Hammersmith Hospital, London, England. mpoullis@rpms.ac.uk
Pure red cell aplasia is a rare condition resulting in severe anemia. Medical therapy is indicated, unless a thymoma is present. In patients with concurrent cardiac pathology requiring operation, simultaneous operation should be contemplated to avoid risky resternotomy. We describe an exceptionally rare case of a patient with pure red cell aplasia secondary to a thymoma who underwent concomitant thymectomy and coronary artery grafting with a successful surgical outcome.

4
UI - 21183437
AU - Hanul VL; Smolanka II; Ponomar'ova OV
TI - [Application of systemic enzyme therapy in combined treatment of patients with pulmonary cancer and malignant thymoma]
SO - Klin Khir 2000 Jun;(6):17-9
The systemic enzymotherapy using Wobe-Mugos E in the combined treatment of 32 patients with pulmonary cancer and of 21 patients with malignant thymoma was applied. After the chemotherapy and radiotherapy conduction the reduction of the postoperative septic-purulent complications, the pneumofibrosis occurrence prophylaxis was noted.