The classification of thymic cancers has been a subject of debate. Several different systems have been suggested.
One of the earliest systems divided them into three types: benign encapsulated thymomas, type 1 malignant thymomas (invasive thymoma) and type 2 malignant thymomas (thymic carciniomas). There were no histological subclassifications.
Another system used the lymphocyte-to–epithelial cell ratio and the shape of epithelial cells to create four subtypes: predominantly spindle cell, predominantly lymphocytic, predominantly mixed, and predominantly epithelial. However, many investigators consider that this classification has failed to reveal the relationship between the pathologic types and the clinical behaviors.
Müller-Hermelink proposed a system that was once widely used. It is based on histologic resemblance to the cortex or medulla of the normal thymus. According to that criterion, thymomas were classified into six categories from well-differentiated to poorly differentiated tumors: medullary thymomas, mixed thymomas, predominantly cortical (organoid) thymomas, cortical thymomas, well-differentiated thymic carcinoma, and high-grade thymic carcinoma.
One other system uses the classification well-differentiated thymic epithelial neoplasm (thymoma), moderately differentiated thymic epithelial neoplasm (atypical thymoma), and poorly differentiated thymic epithelial neoplasm (thymic carcinoma).
To help bring some order to the issue, the World Health Organization has created a classification system for thymomas and thymic carcinomas. Rather than appear as a “new system” it is an effort to translate the different terminologies currently in use into their equivalent terms in alternate classification systems.
The classification system is based on the histologic type:
Type A thymoma accounts for approximately 4% to 7% of all thymomas. Approximately 17% of cases 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. However, some 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, with long-term survival rates (15 years or more) reported to be close to 100% in retrospective studies.
Type AB thymoma accounts for approximately 28% to 34% of all thymomas. Approximately 16% of cases 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 there is a wide range in the relative amount of the 2 components. The prognosis for this tumor type is good, with long-term survival rates (15 years or more) recently reported to be approximately 90% or better in 2 large retrospective studies.
Type B1 thymoma accounts for approximately 9% to 20% of all thymomas, depending on the study cited. 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, with a long-term survival rate (20 years or more) of around 90%.
Type B2 thymoma accounts for approximately 20% to 36% of all thymomas, depending on the study cited. 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 on the order of 60%.
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 cases 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 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%.
Thymic carcinoma is a thymic epithelial tumor that exhibits a definite cytologic atypia and a set of histologic features no longer specific to the thymus, but rather similar to those histologic features observed in carcinomas of other organs. In contrast to type A and B thymomas, thymic carcinomas lack immature lymphocytes. Any lymphocytes that are present are mature and usually admixed with plasma cells. It has been hypothesized that thymic carcinoma may arise from malignant transformation of a pre-existing thymoma. This hypothetical evolution could account for the existence of thymic epithelial lesions that exhibit combined features of thymoma and thymic carcinoma within the same tumor. Thymic carcinomas are usually advanced when diagnosed and have a higher recurrence rate and worse survival compared with thymoma. The 5-year and 10-year actuarial overall survival rates are typically 38% and 28%, respectively. In contrast to the thymomas, the association of thymic carcinoma and autoimmune disease is rare.
Histologic subtypes of thymic carcinoma include the following (combinations of the following types can occur):
- Squamous cell (epidermoid) thymic carcinoma This type of thymic carcinoma exhibits clear-cut cytologic atypia. In routinely stained sections, the keratinizing form exhibits equally clear-cut evidence of squamous differentiation in the form of intercellular bridges and/or squamous pearls, while the nonkeratinizing form lacks obvious signs of keratinization. Another subtype, basaloid carcinoma, is composed of compact lobules of tumor cells that exhibit peripheral palisading and an overall basophilic staining pattern due to the high nucleocytoplasmic ratio and the absence of keratinisation.
- Lymphoepithelioma-like thymic carcinoma This type of thymic carcinoma has morphologic features indistinguishable from those of lymphoepithelial carcinoma (lymphoelithelioma) of the nasopharyngeal.. The differential diagnosis with germ cell tumors, particularly seminomas, can be difficult but important for treatment. It is considered a type of poorly differentiated squamous cell carcinoma.
- Sarcomatoid thymic carcinoma (carcinosarcoma) This is a type of thymic carcinoma in which part or all of the tumor resembles 1 of the types of soft tissue sarcoma
- Clear cell thymic carcinoma This is a type of thymic carcinoma composed predominantly or exclusively of cells with optically clear cytoplasm.
- Mucoepidermoid thymic carcinoma This type of thymic carcinoma has an appearance similar to that of mucoepidermoid carcinoma of the major and minor salivary glands.
- Papillary thymic adenocarcinoma This type of thymic carcinoma grows in a papillary fashion. This histology may be accompanied by psammoma body formation, resulting in a marked similarity with papillary carcinoma of the thyroid gland.
- Undifferentiated thymic carcinoma This is a rare type of thymic carcinoma that grows in a solid undifferentiated fashion but without exhibiting sarcomatoid (spindle cell or pleomorphic) features.