Coexisting Thymic Carcinoid Tumor and Thymoma Tsutomu Mizuno, MD, Akira Masaoka, MD, Takahiko Hashimoto, MD, Kazuo Shibata, MD, Yosuke Yamakawa, MD, Kei Torii, MD, Ichiro Fukai, MD, and Kazuko Ito, MD Second Department of Surgery, Nagoya City University Medical School, Nagoya, Japan Thymic carcinoid tumors are unusual neoplasms that are different from thymomas. We report a case of coexisting thymic carcinoid tumor and thymoma associated with myasthenia gravis. The clinicopathological findings are discussed with a review of the literature. (Ann T ~ O ~Surg U C 1990;50:650-2)
T
hymomas are composed of neoplastic, thymic epithelial cells and are associated with a variable number of lymphocytes. They are occasionally associated with clinical syndromes such as myasthenia gravis. Thymic carcinoid tumors, on the other hand, are unusual neoplasms that are composed of cells containing numerous neurosecretory granules. They show different morphological, functional, and behavioral characteristics than those of thymomas. We present the clinicopathological findings of a 60-yearold man with a thymic carcinoid tumor and a thymoma associated with myasthenia gravis.
A 60-year-old man was admitted to our hospital having been diagnosed with myasthenia gravis (moderate generalized type) associated with an anterior mediastinal mass. On admission, physical examinations were normal except for myasthenic symptoms. Serial hematological and chemistry profiles were normal. The level of acetylcholine receptor antibodies was 1.95 nmoVL (normal, less than 0.16 nmol/L). Computed tomography revealed a large cystic mass in the right anterior mediastinum and a small homogenous solid mass in the left adjacent region (Fig 1). A thymectomy was performed. In the right lobe of the thymus, a well-encapsulated cystic tumor measuring 6 x 5 x 4 cm, which contained a dark brown viscous fluid, was found. The wall of the cyst was irregularly thickened. In the left lobe of the thymus, a solid tumor measuring 2 x 2 x 2 cm was found (Fig 2). Microscopically, the cystic tumor was found to be thymoma, consisting of polygonal epithelial cells and a large number of lymphocytes. In contrast, the solid tumor was composed of anastomosing cords or solid nests of uniform round cells. The islands of tumor cells were surrounded by a fine fibrovascular stroma. Lymphocytes
were limited to small isolated foci (Fig 3). No argyrophilic cells were found in either tumor by Grimelius staining. Several lymphofollicles with germinal centers were present in the thymus. On electron microscopy, the neoplastic cells of the solid tumor had numerous neurosecretory granules in the cytoplasm (Fig 4). These pathological findings of the solid tumor were compatible with those of thymic carcinoid tumor. The patient recovered and no chemotherapy or radiotherapy was administered. A year after operation, there was no recurrence of the tumor.
Comment Thymomas are the most frequent tumors of the anterior mediastinum, and are defined as neoplasms originating from thymic epithelial cells associated with lymphocytes in various proportions [l]. Thymic carcinoid tumors have long been confused with thymomas. However, primary carcinoid tumors of the thymus were first described in detail by Rosai and Higa in 1972 [2]. Thymic carcinoid tumors are unusual neoplasms that show different morphological, functional, and behavioral characteristics than those of thymomas [3]. As described in the literature concerning morphological features, thymic carcinoid tumors are composed of anastomosing cords, ribbons, islands, and rosettelike formations. These are composed of uniform round cells sepa-
Accepted for publication April 4, 1990. Address reprint requests to Dr Mizuno, Second Department of Surgery, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467. Japan. 0 1990 by
The Society of Thoracic Surgeons
Fig I . Contrast-enhanced computed tomography of the chest reveals a large cystic mass (arrow) and a small solid mass (arrowhead) in the anterior mediastinum. 0003-4975/90/$3.50
Ann Thorac Surg 1990;50:650-2
Fig 2. Resected specimen shows a cystic thymoma farrow) in the right lobe of the thymus and a carcinoid tumor farrowhead)in the left lobe of the thymus.
rated by a fine fibrovascular stroma [l-61. Distinction between thymic carcinoid tumors and thymomas may be complicated, particularly if the pattern is unusual. Electron microscopic observation is helpful in diagnosing thymic carcinoid tumors. The essential diagnostic ultrastructural feature in excluding thymomas is the presence of numerous neurosecretory granules [l, 3-61. The clinical features of these tumors can also be recognized. Myasthenia gravis is the most common disease associated with thymomas [7], whereas endocrine abnormalities, including Cushing’s syndrome, are frequently found in patients with thymic carcinoid tumors [3, 4,61.
CASE REPORT MIZUNO ET AL THYMIC CARCINOID AND THYMOMA
651
Fig 4 . Electron micrograph: neoplastic cells of thymic carcinoid tumor are characterized by numerous dense-core, membrane-bound neurosecretoy granules. (Uranyl acetate and lead citrate, xZ5,OOO before 36% reduction.)
The presented case of the 60-year-old man was associated with myasthenia gravis. In contrast to the behavioral attributes of thymomas, thymic carcinoid tumors show metastases to regional lymph nodes or distant sites in a high percentage of cases [3, 4, 61. The primary treatment of thymoma or thymic carcinoid tumor is operation. When the tumor is totally encapsulated, surgical excision is usually an effective cure [l,31.
Fig 3. Microscopic photograph: thymoma ( A ) is composed of polygonal epithelial cells and large numbers of lymphocytes. Thymic carcinoid tumor (B) is composed of anastomosing cords or solid nests of uniform round cells. fHematoxylin and eosin, x50 before 34% reduction.)
652
Ann Thorac Surg 1990:50:650-2
CASE REPORT MIZUNO ET AL THYMIC CARCINOID AND THYMOMA
In summary, we present a unique case of coexisting thymic carcinoid tumor and thymoma. Although the significance of coexisting thymic carcinoid tumor and thymoma remains unclear, the case indicates at least the possibility of coexistence.
2. Rosai J, Higa E. Mediastinal endocrine neoplasm, of probable
3. 4.
We gratefully acknowledge Akemi Nagata for technical assistance.
5.
References
6.
1. Rosai J, Levine GD. Tumors of the thymus, 2nd series. Washington, DC: Armed Forces Institute of Pathology, 1976:
7.
34-181.
thymic origin, related to carcinoid tumor: clinicopathologic study of 8 cases. Cancer 1972;29:1061-74. Levine GD, Rosai J. Thymic hyperplasia and neoplasia: a review of current concepts. Hum Pathol 1978;9:495-515. Wick MR, Carney JA, Bernatz PE, Brown LR. Primary mediastinal carcinoid tumors. Am J Surg Pathol 1982;6:195-205. Wick MR, Scheithauer BW. Thymic carcinoid: a histologic, immunohistochemical, and ultrastructural study of 12 cases. Cancer 1984;53:475-84. Wick MR, Rosai J. Neuroendocrine neoplasms of the thymus. Pathol Res Pract 1988;183:188-99. Rosenow EC 111, Hurley BT. Disorders of the thymus: a review. Arch Intern Med 1984;144:763-70.
Important Announcement for Authors Elsevier Science Publishing Company has recently instituted electronic publishing for certain of their journals, including The Annals of Thoracic Surgery. Beginning September 1st the final version of accepted manuscripts submitted on diskettes will be converted electronically directly to page proof, with a considerable saving of time and expense. Authors are encouraged to use this option if they wish to do so. Both 3 . 5 and 5.25" diskettes in either MS-DOS or Macintosh format may be submitted. Files created with the current or near-current revisions of the following word processing programs are acceptable:
IBM Displaywrite Executive Writer Leading Edge Microsoft Word Multimate Officewriter PC Write PFS: Write PFS: Professional
Q & A Write Samna Sp e11binder Volkswriter Wordperfect WordStar WordStar 2000 Xywrite
Macintosh MacWrite Microsoft Word WordPerfect All diskettes must be accompanied by the final revision of the manuscript and a duplicate copy, including two clearly separated and labeled sets of illustrations. All materials must be sent to the Editorial Office in St. Louis. Before submitting your diskettes, make certain to comply with the Guidelines for Electronic Manuscripts in the Information for Authors section of this journal. Should you have additional questions, please communicate with the Editorial Office: telephone (314) 361-6084; FAX (314) 367-0585.
T
hymomas are composed of neoplastic, thymic epithelial cells and are associated with a variable number of lymphocytes. They are occasionally associated with clinical syndromes such as myasthenia gravis. Thymic carcinoid tumors, on the other hand, are unusual neoplasms that are composed of cells containing numerous neurosecretory granules. They show different morphological, functional, and behavioral characteristics than those of thymomas. We present the clinicopathological findings of a 60-yearold man with a thymic carcinoid tumor and a thymoma associated with myasthenia gravis.
A 60-year-old man was admitted to our hospital having been diagnosed with myasthenia gravis (moderate generalized type) associated with an anterior mediastinal mass. On admission, physical examinations were normal except for myasthenic symptoms. Serial hematological and chemistry profiles were normal. The level of acetylcholine receptor antibodies was 1.95 nmoVL (normal, less than 0.16 nmol/L). Computed tomography revealed a large cystic mass in the right anterior mediastinum and a small homogenous solid mass in the left adjacent region (Fig 1). A thymectomy was performed. In the right lobe of the thymus, a well-encapsulated cystic tumor measuring 6 x 5 x 4 cm, which contained a dark brown viscous fluid, was found. The wall of the cyst was irregularly thickened. In the left lobe of the thymus, a solid tumor measuring 2 x 2 x 2 cm was found (Fig 2). Microscopically, the cystic tumor was found to be thymoma, consisting of polygonal epithelial cells and a large number of lymphocytes. In contrast, the solid tumor was composed of anastomosing cords or solid nests of uniform round cells. The islands of tumor cells were surrounded by a fine fibrovascular stroma. Lymphocytes
were limited to small isolated foci (Fig 3). No argyrophilic cells were found in either tumor by Grimelius staining. Several lymphofollicles with germinal centers were present in the thymus. On electron microscopy, the neoplastic cells of the solid tumor had numerous neurosecretory granules in the cytoplasm (Fig 4). These pathological findings of the solid tumor were compatible with those of thymic carcinoid tumor. The patient recovered and no chemotherapy or radiotherapy was administered. A year after operation, there was no recurrence of the tumor.
Comment Thymomas are the most frequent tumors of the anterior mediastinum, and are defined as neoplasms originating from thymic epithelial cells associated with lymphocytes in various proportions [l]. Thymic carcinoid tumors have long been confused with thymomas. However, primary carcinoid tumors of the thymus were first described in detail by Rosai and Higa in 1972 [2]. Thymic carcinoid tumors are unusual neoplasms that show different morphological, functional, and behavioral characteristics than those of thymomas [3]. As described in the literature concerning morphological features, thymic carcinoid tumors are composed of anastomosing cords, ribbons, islands, and rosettelike formations. These are composed of uniform round cells sepa-
Accepted for publication April 4, 1990. Address reprint requests to Dr Mizuno, Second Department of Surgery, Nagoya City University Medical School, Mizuho-cho, Mizuho-ku, Nagoya 467. Japan. 0 1990 by
The Society of Thoracic Surgeons
Fig I . Contrast-enhanced computed tomography of the chest reveals a large cystic mass (arrow) and a small solid mass (arrowhead) in the anterior mediastinum. 0003-4975/90/$3.50
Ann Thorac Surg 1990;50:650-2
Fig 2. Resected specimen shows a cystic thymoma farrow) in the right lobe of the thymus and a carcinoid tumor farrowhead)in the left lobe of the thymus.
rated by a fine fibrovascular stroma [l-61. Distinction between thymic carcinoid tumors and thymomas may be complicated, particularly if the pattern is unusual. Electron microscopic observation is helpful in diagnosing thymic carcinoid tumors. The essential diagnostic ultrastructural feature in excluding thymomas is the presence of numerous neurosecretory granules [l, 3-61. The clinical features of these tumors can also be recognized. Myasthenia gravis is the most common disease associated with thymomas [7], whereas endocrine abnormalities, including Cushing’s syndrome, are frequently found in patients with thymic carcinoid tumors [3, 4,61.
CASE REPORT MIZUNO ET AL THYMIC CARCINOID AND THYMOMA
651
Fig 4 . Electron micrograph: neoplastic cells of thymic carcinoid tumor are characterized by numerous dense-core, membrane-bound neurosecretoy granules. (Uranyl acetate and lead citrate, xZ5,OOO before 36% reduction.)
The presented case of the 60-year-old man was associated with myasthenia gravis. In contrast to the behavioral attributes of thymomas, thymic carcinoid tumors show metastases to regional lymph nodes or distant sites in a high percentage of cases [3, 4, 61. The primary treatment of thymoma or thymic carcinoid tumor is operation. When the tumor is totally encapsulated, surgical excision is usually an effective cure [l,31.
Fig 3. Microscopic photograph: thymoma ( A ) is composed of polygonal epithelial cells and large numbers of lymphocytes. Thymic carcinoid tumor (B) is composed of anastomosing cords or solid nests of uniform round cells. fHematoxylin and eosin, x50 before 34% reduction.)
652
Ann Thorac Surg 1990:50:650-2
CASE REPORT MIZUNO ET AL THYMIC CARCINOID AND THYMOMA
In summary, we present a unique case of coexisting thymic carcinoid tumor and thymoma. Although the significance of coexisting thymic carcinoid tumor and thymoma remains unclear, the case indicates at least the possibility of coexistence.
2. Rosai J, Higa E. Mediastinal endocrine neoplasm, of probable
3. 4.
We gratefully acknowledge Akemi Nagata for technical assistance.
5.
References
6.
1. Rosai J, Levine GD. Tumors of the thymus, 2nd series. Washington, DC: Armed Forces Institute of Pathology, 1976:
7.
34-181.
thymic origin, related to carcinoid tumor: clinicopathologic study of 8 cases. Cancer 1972;29:1061-74. Levine GD, Rosai J. Thymic hyperplasia and neoplasia: a review of current concepts. Hum Pathol 1978;9:495-515. Wick MR, Carney JA, Bernatz PE, Brown LR. Primary mediastinal carcinoid tumors. Am J Surg Pathol 1982;6:195-205. Wick MR, Scheithauer BW. Thymic carcinoid: a histologic, immunohistochemical, and ultrastructural study of 12 cases. Cancer 1984;53:475-84. Wick MR, Rosai J. Neuroendocrine neoplasms of the thymus. Pathol Res Pract 1988;183:188-99. Rosenow EC 111, Hurley BT. Disorders of the thymus: a review. Arch Intern Med 1984;144:763-70.
Important Announcement for Authors Elsevier Science Publishing Company has recently instituted electronic publishing for certain of their journals, including The Annals of Thoracic Surgery. Beginning September 1st the final version of accepted manuscripts submitted on diskettes will be converted electronically directly to page proof, with a considerable saving of time and expense. Authors are encouraged to use this option if they wish to do so. Both 3 . 5 and 5.25" diskettes in either MS-DOS or Macintosh format may be submitted. Files created with the current or near-current revisions of the following word processing programs are acceptable:
IBM Displaywrite Executive Writer Leading Edge Microsoft Word Multimate Officewriter PC Write PFS: Write PFS: Professional
Q & A Write Samna Sp e11binder Volkswriter Wordperfect WordStar WordStar 2000 Xywrite
Macintosh MacWrite Microsoft Word WordPerfect All diskettes must be accompanied by the final revision of the manuscript and a duplicate copy, including two clearly separated and labeled sets of illustrations. All materials must be sent to the Editorial Office in St. Louis. Before submitting your diskettes, make certain to comply with the Guidelines for Electronic Manuscripts in the Information for Authors section of this journal. Should you have additional questions, please communicate with the Editorial Office: telephone (314) 361-6084; FAX (314) 367-0585.
