Diagnosis: Carcinoid tumor of the thymus with extensive recent ischemic necrosis. Satellite tumor (probable lymph node metastasis).

Comment: Although focal necrosis is a common features of thymic carcinoid tumors, extensive infarction has not been described. Furthermore, necrosis was absent in the satellite tumor. It is probable that the infarction of the tumor resulted from vasoconstriction associated with smoking crack cocaine several hours before the chest pain developed.


Thymic Carcinoid Tumors

Classification: Thymic carcinoid tumors are rare tumors that most closely resemble well-differentiated neuroendocrine carcinomas (atypical carcinoid tumors) of the lung in their histologic appearance and behavior. In the thymus, they have a category of their own separate from thymic carcinoma, which includes small cell neuroendocrine carcinoma (table). It has been argued by some that carcinoid tumors should also be classified as a type of thymic carcinoma for the following reasons [1].

Table: Tumors of the Thymus [2]

Epithelial

Thymoma
Thymic carcinoma

Low grade
Well-differentiated squamous carcinoma
Well-differentiated mucoepidermoid carcinoma
Basaloid carcinoma

High-grade
Lymphoepithelioma-like
Small cell neuroendocrine carcinoma
Other: Adenocarcinoma, undifferentiated, sarcomatoid, and clear cell types

Other elements

Carcinoid tumor
Germ cell tumors
Lymphomas

Clinical features: Patients with thymic carcinoid tumors may present with symptoms related to compression of normal structures, or tumors may be found incidentally on chest radiographs (see table). The average age is 48.3 y, and the ratio of men to women is 4.3 to 1. About 10% of patients have Cushing's syndrome, and a similar fraction have a multiple endocrine neoplasia syndrome. Weight loss or the superior vena caval syndrome may be present. Other rare manifestations include Eaton-Lambert syndrome, the syndrome of inappropriate production of antidiuretic hormone, and hypertrophic osteoarthropathy [3]. An incidental thymic carcinoid tumor was described in a man with a thymoma that was associated with myasthenia gravis [4]. The carcinoid syndrome has not been described.

Differential diagnosis includes tumors of the thyroid or ectopic thyroid tissue, parathyroid tumors, paragangliomas, metastatic tumors, thymolipoma, soft tissue tumors, germ cell tumors, and the thymic tumors listed above. Carcinoid tumors metastatic to the thymus from another site are usually not occult, but search for an extrathymic primary site should be done before diagnosing a thymic carcinoid tumor [3].

Gross features: Tumors do not have a capsule and the cut surface is homogeneous rather than lobulated, as is characteristic of thymomas. The cut surfaces are usually firm and grey. Focal necrosis and hemorrhage are common [5].

Histologic features: Several variants include a usual form and diffuse, spindled, desmoplastic (fibrotic), and mucinous types, as well as a variant resembling medullary carcinoma of the thyroid [5]. A proliferation of pigmented thymic melanocytes darkened the gross appearance of one tumor [6].

Immunohistochemistry: Tumors react with antibodies to cytokeratin and chromogranin A, as well as other neuroendocrine markers including synaptophysin and Leu-7. Additionally, tumors may show reactivity for ACTH, serotonin, calcitonin, gastrin, cholecystokinin, or somatostatin, even if there is no clinical evidence of their presence. Parathyroid tumors can be distinguished by their staining with antibody to parathormone. Paragangliomas express neuroendocrine markers but do not react with cytokeratin. Lymphomas will show reactivity with leukocyte common antigen, and germ cell tumors will react with placental alkaline phosphatase [5].

Electron microscopy: Just as carcinoid tumors of the lung, thymic carcinoid tumors have neurosecretory granules. These range in size from 100 to 400 nm [5].

Treatment and outcome: Surgical excision is the preferred method of treatment with postoperative radiation and/or chemotherapy for tumors that cannot be removed completely [9,10]. Response to chemotherapy or radiation alone is poor. Embolic metastases occur in up to 3/4 of patients. Metastatic sites include mediastinal lymph nodes, but distant metastases (bone, liver, skin) occur in 30-40% of cases [3]. Five-year survival for cases without an associated endocrinopathy was about 70% and for those with an endocrinopathy was 35% in one report [3]. A more recent report indicated an overall survival of 31% at 5 years; all 14 patients were dead of disease by 109 months [1]. Late recurrence after 8 years has been reported [3].

References:

1. de Montpréville V, Macchiarini P, Dulmet E. Thymic neuroendocrine carcinoma (carcinoid): a clinicopathologic study of fourteen cases. J Thorac Cardiovasc Surg 1996; 111:134-141.

2. Shimosato Y, Mukai K. Tumors of the Mediastinum. Atlas of Tumor Pathology, Third Series, Fascicle 21, Washington, D.C., Armed Forces Institute of Pathology, 1997, 158-183.

3. Wick M, Rosai J. Neuroendocrine neoplasms of the thymus. Path Res Pract 1988; 183:188-199.

4. Mizuno T, Masaoka A, Hashimoto T, Shibata K, Yamakawa Y, Torii K, Fukai I, et al. Coexisting thymic carcinoid tumor and thymoma. Ann Thorac Surg 1990; 50:650-652.

5. Wick M, Rosai J. Neuroendocrine neoplasms of the mediastinum. Sem Diagn Pathol 1991; 8:35-51.

6. Ho F, Ho J. Pigmented carcinoid tumour of the thymus. Histopathology 1977; 1:363-369.

7. Kuo T-T. Carcinoid tumor of the thymus with divergent sarcomatoid differentiation: report of a case with histogenetic consideration. Hum Pathol 1994; 25:319-323.

8. Suster S, Moran C. Thymic carcinoid with prominent mucinous stroma. Report of a distinctive morphologic variant of thymic neuroendocrine neoplasm. Am J Surg Pathol 1995; 19:1277-1285.

9. Economopoulos G, Lewis Jr J, Lee M, Silverman N. Carcinoid tumors of the thymus. Ann Thorac Surg 1990; 50:58-61.

10. Wang D-Y, Chang D-B, Kuo S-H, Yang P-C, Lee Y-C, Hsu H-C, Luh K-T. Carcinoid tumors of the thymus. Thorax 1994; 49:357-360.

11. Rosai J, Higa E. Mediastinal endocrine neoplasm, of probable thymic origin, related to carcinoid tumor. Clinicopathologic study of 8 cases. Cancer 1972; 29:1061-1074.

12. Rosai J, Higa E, Davie J. Mediastinal endocrine neoplasm in patients with multiple endocrine adenomatosis. A previously unrecognized association. Cancer 1972; 29:1075-1083.

13. Tanaka T, Tanaka S, Kimura H, Ito J. Mediastinal tumor of thymic origin and related to carcinoid tumor. Acta Path Jap 1974; 24:413-426.

14. Wick M, Scott R, Li C-Y, Carney J. Carcinoid tumor of the thymus. A clinicopathologic report of seven cases with a review of the literature. Mayo Clin Proc 1980; 55:246-254.

15. Wick M, Carney J, Bernatz P, Brown L. Primary mediastinal carcinoid tumors. Am J Surg Pathol 1982; 6:195-205.

16. Birnberg F, Webb W, Selch S, Gamsu G, Goodman P. Thymic carcinoid tumors with hyperparathyroidism. AJR 1982; 139:1001-1004.

17. Wick M, Scheithauer B. Thymic carcinoid. A histologic, immunohistochemical, and ultrastructural study of 12 cases. Cancer 1984; 53:475-484.

18. Takayama T, Kameya T, Inagaki K, Nonaka M, Miyazawa H, Ogawa N, Yano M, et al. MEN type 1 associated with mediastinal carcinoid producing parathyroid hormone, calcitonin and chorionic gonadotropin. Path Res Pract 1993; 189:1090-1096.

19. Valli M, Fabris G, Dewar A, Chikte S, Fisher C, Corrin B, Sheppard M. Atypical carcinoid tumour of the thymus: a study of eight cases. Histopathology 1994; 24:371-375.

Clinical summary

Comments: mw6825@itsa.ucsf.edu

Copyright 1998 by Martha L. Warnock. All rights reserved.

Last revised 9/30/00

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