Cellular Classification of Thymoma and Thymic Carcinomas
The following cellular classification of thymoma and thymic carcinoma is largely based on the classification scheme presented in a World Health Organization (WHO) monograph published in 1999. Malignant thymoma is invasive disease (as defined either macroscopically or microscopically) that continues to retain typically "bland" cytologic characteristics. Thymomas are a mixture of epithelial cells and lymphocytes, often T-cells, and the malignant component is represented by the epithelial cells. Malignant cytologic characteristics are considered thymic carcinomas.
Both histologic classification of thymomas and stage may have independent prognostic significance.[2,3] A few series have reported the prognostic value of the WHO classifications. In large retrospective analyses of 100 and of 178 thymoma cases, disease-free survivals at 10 years were 95% to 100% for type A, 90% to 100% for type AB, 83% to 85% for type B1, 71% to 83% for type B2, 36% to 40% for type B3, and 28% for type C.[4,5] In both series, stage and complete resection were significant independent prognostic factors. An analysis of 273 patients treated over a 44-year period found 20-year survival rates of 100%, 87%, 91%, 59%, and 36% for patients with type A, AB, B1, B2, and B3 tumors, respectively.
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Recurrent karyotype abnormalities have been documented in thymomas. Type A thymomas have chromosome 6q deletions including the HLA locus and p21. Type B2 and B3 thymomas have additional chromosome 5q (adenomatous polyposis coli locus), 13q (retinoblastoma locus), and 17p (p53) deletions. Amplifications in regions of chromosome 16 (cadherin-encoding gene) and chromosome 18 (bcl-2) have also been seen. Gene expression profiling study has shown a correlation of expression of a number of genes including adhesion molecule cten, ets-1 oncogene and glycosylphosphatidyl inositol-anchored protein with thymoma stage.[9,10,11]
Thymoma is a thymic epithelial tumor in which the epithelial component exhibits no overt atypia and retains histologic features specific to the normal thymus. Immature non-neoplastic lymphocytes are present in variable numbers depending on the histologic type of thymoma. The histologic types of thymoma are as follows:
Type A thymoma
Type A thymoma (also known as spindle cell thymoma and medullary thymoma) accounts for approximately 4% to 7% of all thymomas.[2,3] Approximately 17% of this type may be associated with myasthenia gravis. Morphologically, the tumor is composed of neoplastic thymic epithelial cells that have a spindle/oval shape, lack nuclear atypia, and are accompanied by few, if any, nonneoplastic lymphocytes. The appearance of this tumor can be confused with that of a mesenchymal neoplasm, but the immunohistochemical and ultrastructural features are clearly those of an epithelial neoplasm. Most type A thymomas are encapsulated (see Stage Information). Some, however, may invade the capsule and, on rare occasion, may extend into the lung. Chromosome abnormalities, when present, may correlate with an aggressive clinical course. The prognosis for this tumor type is excellent and have long-term survival rates (15 years or more) that are reported to be close to 100% in retrospective studies.[2,3]
Type AB thymoma
Type AB thymoma (also known as mixed thymoma) accounts for approximately 28% to 34% of all thymomas.[2,3] Approximately 16% of this type may be associated with myasthenia gravis. Morphologically, type AB thymoma is a thymic tumor in which foci having the features of type A thymoma are admixed with foci rich in nonneoplastic lymphocytes. The segregation of the different foci can be sharp or indistinct, and a wide range exists in the relative amount of the two components. The prognosis for this tumor type is good and have long-term survival rates (15 years or more) that are recently reported to be approximately 90%.[2,3]
Type B1 thymoma
Type B1 thymoma (also known as lymphocyte-rich thymoma, lymphocytic thymoma, predominantly cortical thymoma, and organoid thymoma) accounts for approximately 9% to 20% of all thymomas and depends on the study cited.[2,3] Approximately 57% of cases may be associated with myasthenia gravis. Morphologically, this tumor resembles the normal functional thymus because it contains large numbers of cells that have an appearance almost indistinguishable from normal thymic cortex with areas resembling thymic medulla. The similarities between this tumor type and the normal active thymus are such that distinction between the two may be impossible on microscopic examination. The prognosis for this tumor type is good and has a long-term survival rate (20 years or more) of approximately 90%.[2,3]
Type B2 thymoma
Type B2 thymoma (also known as cortical thymoma and polygonal cell thymoma) accounts for approximately 20% to 36% of all thymomas and depends on the study cited.[2,3] Approximately 71% of cases may be associated with myasthenia gravis. Morphologically, the neoplastic epithelial component of this tumor type appears as scattered plump cells with vesicular nuclei and distinct nucleoli among a heavy population of nonneoplastic lymphocytes. Perivascular spaces are common and on occasion very prominent. A perivascular arrangement of tumor cells that results in a palisading effect may be seen. This type of thymoma resembles type B1 thymoma in its predominance of lymphocytes, but foci of medullary differentiation are less conspicuous or absent. Long-term survival is decidedly worse than for thymoma types A, AB, and B1. The 20-year survival rate (as defined by freedom from tumor death) for this thymoma type is approximately 60%.
Type B3 thymoma
Type B3 thymoma (also known as epithelial thymoma, atypical thymoma, squamoid thymoma, and well-differentiated thymic carcinoma) accounts for approximately 10% to 14% of all thymomas. Approximately 46% of this type of tumor may be associated with myasthenia gravis. Morphologically, this tumor type is predominantly composed of epithelial cells that have a round or polygonal shape and that exhibit no atypia or mild atypia. The epithelial cells are admixed with a minor component of nonneoplastic lymphocytes, which results in a sheet-like growth of neoplastic epithelial cells. The 20-year survival rate (as defined by freedom from tumor death) for this thymoma type is approximately 40%.