FINAL DIAGNOSIS -- NONINVASIVE THYMOMA, MIXED CELL TYPE WITH SPINDLE CELL RICH AREAS.
Based upon the histopathology and the flow cytometric immunophenotypic studies of the anterior mediastinal mass, the diagnosis of noninvasive thymoma, mixed cell type with spindle cell rich areas, was rendered.
Thymomas are infrequent, and usually exhibit localized growth. These thymic epithelial cell neoplasms are usually encapsulated (70-80%) and, therefore, lend themselves to complete excision. Thymomas are predominantly located in the anterior-superior mediastinum and appear as lobulated shadows on CT scans and MRI.
Almost all thymomas present in adulthood, however, they do occur in children. In younger children, an aggressive, highly malignant thymic neoplasm has been described.
Thymomas are associated with myasthenia gravis and several other autoimmune systemic disorders. Of patients with thymoma, 30-40% will develop myasthenia gravis. Those more likely to do so include males over 50 years and/or patients with constitutional symptoms. Thymomas have also been associated with systemic lupus erythematosus, rheumatoid arthritis, scleroderma, dermatomyositis, myocarditis, Sjögren's disease, inappropriate antidiuretic hormone secretion, multiple myeloma, T-cell chronic lymphocytic leukemia, and T-cell lymphoblastic leukemia.
Grossly, thymomas are predominantly solid, yellowish or tan, and lobulated. They may show cystic degeneration. Microscopically, thymomas are composed of two cell populations: lymphocytes, which are immature thymocytes of T-cell origin, and neoplastic thymic epithelial cells which are immunohistochemically positive for keratin, epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA).
Thymomas are classified according to the predominant cell population, thus the L-B (Lattes and colleagues) classification recognizes the following types: predominantly spindle cell , predominantly lymphocytic, predominantly epithelial, and predominantly mixed thymomas. A newer classification, the Müller-Hermelink (M-H) classification, not currently widely used, recognizes five categories of thymomas: medullary, mixed, predominantly cortical, and cortical thymomas, and additionally, well-differentiated thymic carcinoma. In the latter classification, well-differentiated thymic carcinoma, corresponds to the predominantly epithelial thymoma of the L-B classification. In such cases, epithelial cells exhibit some atypia as well as a decrease in the non-neoplastic lymphocyte population. Regardless, thymomas with aggressive behavior and showing signs of local invasion, pleural or pericardial implants, or distant metastases are categorized as malignant. Contrasted with thymomas, thymic carcinomas are rare and exhibit a greater propensity for local invasion and distant metastases. They exhibit areas with necrosis, hemorrhage, or calcification, and carry a poor prognosis.
Clinical staging, as proposed by Masaoka, describes four levels of tumor extent. Stage I thymomas are encapsulated with no evidence of microscopic capsular invasion. Stage II thymomas exhibit macroscopic invasion into surrounding adipose tissue or pleura or, microscopic capsular invasion. Stage III thymomas exhibit macroscopic invasion into adjacent organs. Stage IV thymomas exhibit, in type IVa, pleural or pericardial dissemination, or, in type IVb, angiolymphatic metastases.
The most important prognostic indicators for patients with thymoma are clinical stage at the time of diagnosis and the success of surgical resection. Schneider and colleagues (1997) reported that clinical staging affected survival prognosis as follows: Stage I thymomas exhibited 100% and 90.9% 5- and 10-year survival respectively; stage II, 95% and 88.2%; stage III, 55.9% and 46.6%; and stage IV 10.8% and 10.8% survival. They also reported 93.6% and 87.3% 5- and 10-year survival for patients with R0 resections (no residual tumor) compared to 0% at 5-years for patients with R1 and R2 resections (residual tumor remaining after surgical resection).
Finally, although surgical resection is the therapeutic mainstay for patients with thymoma, invasive or recurrent thymomas require chemotherapy and/or radiation therapy.
Contributed by Debra L. Callahan, MD