© 2007 Foundation for Promotion of Cancer Research
Three Cases of Multiple Thymoma with a Review of the Literature
Department of Thoracic Surgery and Department of Surgical Pathology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
For reprints and all correspondence: Hiroaki Nomori, Department of Thoracic Surgery, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. E-mail: hnomori{at}qk9.so-net.ne.jp
Received June 17, 2006; accepted July 27, 2006
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Abstract |
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Three cases of patients with synchronous multiple thymoma are reported. Two patients had two thymomas each and the remaining patient had three. The thymomas in each patient all displayed similar histological findings, of which the WHO histological classification were type B2, A and B1, respectively. With a modified Masaoka staging system, the thymomas were determined to be stages II-1 and I in patient 1, one of stage III and two of stage I in patient 2, and two of stage II-1 in patient 3. We reviewed nine reported cases of multiple thymoma in which histological findings were provided and discuss whether they developed from multi-centric origin or from intra-thymic metastasis.
Key Words: thymoma • multiple developments • multi-centric development • recurrence
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INTRODUCTION |
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TOPAbstractINTRODUCTIONMATERIALS AND METHODSCASE REPORTDISCUSSIONReferences |
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Although it is well known that multiple thymoma can develop in a single patient, its actual incidence is very low. Also it remains controversial whether the cases represent disease of multi-centric origin or intra-thymic metastasis. To address this issue, we present three cases of patients with multiple thymoma and also review the reported cases of which histological findings have been provided (1–8).
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MATERIALS AND METHODS |
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From 1981 to 2005, 96 patients with thymoma were treated by thymo-thymomectomy in the Department of Thoracic Surgery of Kumamoto University Hospital. Of these, three patients (3.1%) had multiple thymomas. The histological type of each thymoma was classified according to the World Health Organization (WHO) classification system (9). The tumor stage was classified by a modified Masaoka classification (10).
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CASE REPORT |
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Patient 1
A 69-year-old male with ocular type myasthenia gravis (MG) was admitted to our hospital for surgical treatment of an anterior mediastinal tumor. The serum level of anti-acethylcholine receptor antibody (AchR Ab) was elevated to 8 nmol/l (normal level < 0.2 nmol/l). Computed tomography (CT) showed a well-defined mass bounded on the ascending aorta (Fig. 1). Thymo-thymomectomy was performed via median sternotomy. While pathological examination diagnosed the tumor as type B2 thymoma 23 x 12 mm in size, pathological examination revealed another type B2 thymoma 2 x 2 mm in size located within the same lobe (Fig. 2). While the intra-operative findings showed no invasion of the main tumor, microscopic invasion into the surrounding thymic tissue was obserbed, i.e. the tumor stage was II-1. The patient is now alive without recurrence of thymoma and with complete remission of MG 5 years after surgery.
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Patient 2
A 74-year-old male without MG was admitted to our hospital for surgical treatment of an anterior mediastinal tumor. The serum AchR Ab level was within normal limits. CT revealed a small, ill-defined mass bounding on the ascending aorta (Fig. 3). The intra-operative findings revealed invasion of the tumor into the right middle lobe of the lung and also two additional tumors within the right thymic lobe. A thymo-thymomectomy was performed with wedge resection of the right middle lobe. Pathological diagnosis was type A thymoma in all three of the tumors, the respective sizes were 58 x 35, 24 x 7 and 10 x 8 mm. The patient was treated with post-operative radiotherapy (50 Gy). He is now alive without recurrence of thymoma 10 months after surgery.
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Patient 3
A 46-year-old male with ocular type MG was admitted to our hospital for surgical treatment of an anterior mediastinal tumor. The serum level of AchR Ab was elevated to 9.5 nmol/l. Computed tomography revealed a well-defined mass on the left upper side of the anterior mediastinum. Thymo-thymomectomy was performed via median sternotomy. During the operation, another tumor was found within the right lower thymus. The sizes of the two tumors were 22 x 15 and 15 x 8 mm, respectively. Pathological diagnosis was type B1 thymoma in both tumors. While intra-operative findings did not show any invasion by the tumors, pathological examination revealed microscopic invasion into the surrounding thymic tissue in both, i.e. both were stage II-1. The patient is now alive without recurrence of thymoma and with complete remission of MG, 6 years after surgery.
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DISCUSSION |
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TOPAbstractINTRODUCTIONMATERIALS AND METHODSCASE REPORTDISCUSSIONReferences |
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Multiple thymoma is a well-known phenomenon, but its occurrence is very rare. Bernatz et al. reported just three out of 138 (2.2%) thymomas to be multiple (11). Jaretzky et al. reported one (1.1%) multiple thymoma out of 95 cases of thymoma (12). However, these reports did not describe any histological differences between the multiple thymomas documented. In 1990, Nomori et al. reported one case of multiple thymoma and suggested the possibility of intra-thymic metastasis rather than multi-centric development based on histological, morphometrical and immunohistochemical findings (1). Since their report, nine cases with multiple thymoma have been reported with their histological findings provided (1–8). We reviewed these reports and present their respective clinicopathological characteristics in Table 1. Histological subtypes of thymoma by WHO classification were judged from the histological findings included in each report (9). The characteristics are as follows: (i) mean age was 57 ± 11-year-old (range: 28–81); (ii) there were eight males and four females; (iii) the numbers of thymomas were two in 11 patients, and three in one; (iv) of the total of 25 thymomas, three (12%) could be histologically classified as type A, 13 (52%) as type B1, eight (32%) as type B2, and one (4%) as type B3; (v) histological findings of the multiple thymomas in each patient were similar in 10 patients (83%), while the remaining two (17%) displayed different subtypes; (vi) the difference in tumor size between the thymomas in each patient was such that the smaller ones were usually larger than 25% of the main ones, except for case numbers 1 and 10, which displayed a greater than 10 times size difference between the tumors. Of the 25 thymomas, 20 were stage I (80%), three stage II-1 (12%), and the remaining two were stage III (8%).
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It is controversial whether cases of multiple thymomas represent multi-centric origin or intra-thymic metastasis. From the characteristics of the 12 cases in Table 1, multi-centric development is suggested by the following characteristics: (i) the number of thymomas were usually less than three, which would be surprising if the source were in intra-thymic dissemination; (ii) there is little size difference between the thymomas in each case, except for case numbers 1 and 10; and (iii) most of the thymomas were stage I, which are essentially unable to spread into the thymic tissue.
However, the possibility of intra-thymic metastasis might be suggested by the finding that each of 10 patients (83%) were found to have similar histological characteristics in their thymomas. While it cannot be concluded at this point whether multiple thymomas are derived from multi-centric development or intra-thymic metastasis, we favor the former hypothesis because of the analysis presented above. While we cannot rule out the theory of intra-thymic metastasis, we believe that most multiple thymomas develop from identical tumor genesis events in each patient, thus resulting in the similar histological findings.
Denzinger et al. reported clonality analysis of multi-focal bladder tumors by examining the loss of heterozygosity (LOH) and fluorescence in situ hybridization (FISH) (13). However, it has not been clarified whether these chromosomal losses of primary tumors in epithelial tumors are also preserved in metastatic sites or not. In addition, while Inoue et al. reported the difference of LOH and FISH among histological types of thymoma by using micro-dissection or culture of thymoma-epithelial cells (14), thymoma is generally hard to examine by LOH and FISH owing to many lymphocytes among the thymoma-epithelial cells. Therefore, it is difficult to examine whether the multiple thymomas in our report are from multi-centric origins or metastasis by the clonality analysis, such as the LOH or FISH method.
Finally, it is reported that local recurrence sometimes takes place after resection of non-invasive thymomas (15–17). Maggi et al. reported that two of 133 (1.4%) encapsulated thymomas had recurred after surgery (16). Because these could be recurrences from small or even tiny thymoma remnants in thymic tissue, we recommend an extensive thymectomy even for stage I thymoma.
Conflict of interest statement
None declared.
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References |
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1 Nomori H, Kobayashi K, Ishihara T, Suito T, Torikata C. (1990) A case of multiple thymomas: the possibility of intra-thymic metastasis. Jpn J Clin Oncol 20 209–11.
2 Takeuchi S, Osada H, Nishikawa M, Mochizuki A, Takagi M. (1997) Resection of multiple thymoma: a case report. Jpn J Thorac Dis 35 1025–8.
3 Okada M, Tsubota N, Yoshimura M, Miyamoto Y, Sakamoto T. (1998) Two cases of synchronous multiple thymoma. Surg Today 28 1323–5.[CrossRef][ISI][Medline]
4 Gotoh N and Yokoi K. (2000) A case of resected multiple thymoma. J Jpn Assoc Chest Surg 14 62–6.
5 Hirai T, Yamanaka A, Fujimoto T, Takahashi A, Takayama Y, Yamanaka K. (2001) Multiple thymoma with myotonic dystrophy. Jpn J Thorac Cardiovasc Surg 49 457–60.[Medline]
6 Ishibashi H, Akamatsu H, Sunamori M. (2003) Multiple thymoma with myasthenia gravis: report of a case. Surg Today 33 49–51.[CrossRef][ISI][Medline]
7 Nonami Y and Moriki T. (2004) Synchronous independent bifocal orthotopic thymomas: a case report. J Cardiovasc Surg 45 585–7.[Medline]
8 Yoneda S, Matsuzoe D, Kawakami T, Tashiro Y, Shirahama H, Ohkubo K, et al. (2004) Synchronous multicentric thymoma: report of a case. Surg Today 34 597–9.[ISI][Medline]
9 Travis WD, Brambilla E, Müller-Hermelink HK, Harris CC. (2004) Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart. Lyon IARCPress.
10 Koga K, Matsuno Y, Noguchi M, Mukai K, Asamura H, Goya T, et al. (1994) A review of 79 thymomas: modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int 44 359–67.[ISI][Medline]
11 Bernatz PE, Harrison EG, Claget OT. (1961) Thymoma: a clinicopathologic study. J Thorac Cardiovasc Surg 42 424–44.
12 Jaretzky A III, Penn AS, Younger DS, Wolff, Olarte MR, Lovelace RE, et al. (1988) Maximal thymectomy for myasthenia gravis. J Thorac Cardiovasc Surg 95 747–57.[Abstract]
13 Denzinger S, Mohren K, Knuechel R, Wild PJ, Burger M, Wieland WF, et al. (2006) Improved clonality analysis of multifocal bladder tumors by combination of histopathologic organ mapping, loss of heterozygosity, fluorescence in situ hybridization, and p53 analyses. Hum Pathol 37 143–51.[CrossRef][ISI][Medline]
14 Inoue M, Starostik M, Zettl A, Ströbel P, Schwarz S, Scaravilli F, et al. (2003) Correlating genetic aberrations with World Health Organization-defined histology and stage across the spectrum of thymomas. Cancer Res 63 3708–15.
15 Fechner RE. (1969) Recurrence of noninvasive thymoma. Cancer 23 1423–7.[CrossRef][ISI][Medline]
16 Maggi G, Casadio C, Cavallo A, Cianci R, Morinatti M, Ruffini E. (1991) Thymoma: results of 241 operated cases. Ann Thorac Surg 51 152–6.[Abstract]
17 Nomori H, Horio H, Iga R, Kobayashi R, Morinaga S. (1996) Recurrence of a stage I thymoma after resection. Jpn J Chest Dis 34 833–6.
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