Thymomas are neoplasms arising from or exhibiting organotypic (thymus-like) architectural features, regardless of the presence and relative numbers of nonneoplastic lymphocytes.¹ Although the prognosis of thymomas is in general good, these tumors are considered malignant as they can metastasize and recur.

The overall incidence of thymoma in the United States is 0.13 to 0.¹⁵ per 100,000 person-years.² They represent 50% of all tumors of the anterior mediastinum.³

Thymoma is exceedingly uncommon in children and young adults, rises in incidence in middle age, and peaks in the seventh decade of life.⁴ Thymoma incidence is especially high among Asians and Pacific Islanders in the United States.⁴

While many patients are asymptomatic, others may exhibit symptoms due to local complications (chest pain, superior vena cava syndrome, cough, dyspnea, and wheezing due to compression/obstruction of adjacent organs), as well as systemic symptoms (fever or weight loss). The neoplasms often manifest clinically by causing autoimmune diseases, in particular myasthenia gravis. In fact, 15% of patients with myasthenia gravis develop a thymoma. Thymoma patients have an increased risk of additional extrathymic malignancies, in particular non-Hodgkin lymphoma.^4,5

The histologic typing of thymomas is complex and remains a challenge for surgical pathologists due to the various existing classification schemes that are in clinical use (Table 98.1).^6,7 The first practical histopathologic categorization of thymoma was proposed in 1961 by Bernatz et al.⁸ These authors divided thymomas based on their relative proportion of epithelial cells to lymphocytes and on the shape of the epithelial cells.⁸ Their classification recognized four basic histopathologic variants: thymoma of predominantly lymphocytic type, epithelial type, mixed type, and spindle cell type.⁸

An additional approach to the classification of thymoma was introduced in 1985. It was proposed by Marino and Müller-Hermelink based on the premise that thymoma represents a neoplastic proliferation of cells that are derived from the cortex or the medulla of the thymus or from a combination thereof.⁹ These authors thus classified thymoma into cortical, medullary, and mixed types.⁹ This classification subsequently was modified by Kirchner and Müller-Hermelink to include two additional categories, the predominantly cortical thymoma (later renamed “organoid”) and the well-differentiated thymic carcinoma.¹⁰

In 1999, the World Health Organization (WHO) devised five thymoma entities (type A, AB, B1, B2, B3 thymomas) and the more heterogeneous group of thymic carcinomas (collectively called type C thymomas).^11,12 There are two major types of thymoma depending on whether the neoplastic epithelial cells and their nuclei have spindle or oval shape and are uniformly bland (type A) or whether the cells have a round or polygonal appearance (type B).¹ Type A thymomas contain few or no intratumoral immature T cells. The type B thymomas are further subdivided on the basis of the extent of the infiltrate of immature T cells and the degree of atypia of the neoplastic epithelial cells into three subtypes: B1 (richest in immature T cells, areas of medullary differentiation), B2, and B3 (richest in epithelial cells). Thymomas combining type A with B1 or B2 features are designated type AB.

Thymomas of A, AB, and B1 to three types exhibit organotypic (thymus-like) architectural features. These tumors have not been observed in organs other than the thymus, though they may arise from heterotopic thymic tissue.

Thymic carcinomas (obsolete designation is “type C thymoma”) exhibit clear-cut cytologic atypia, lack the lobulated architecture of thymomas, shows desmoplastic stromal reaction, and, in contrast to B thymomas, lack immature T lymphocytes. They are indistinguishable from extrathymic carcinomas, that is, they demonstrate morphologic features that are encountered also in organs other than the thymus.

Numerous studies demonstrated that the WHO classification is a prognostic factor.^{12,13,14,15,16,17,18} However, reproducibility is an issue, particularly for those who may not encounter many thymomas in routine practice.^6,7,19 Suster and Moran proposed a simplified schema in 1999, which essentially condensed thymic epithelial tumors into three histologic groups based on architectural morphology and epithelial cytology: thymoma, atypical thymoma, and thymic carcinoma.^17,20,21 The Suster-Moran “thymoma” includes WHO subtypes A, AB, B1, and B2, whereas “atypical thymoma” corresponds to WHO subtype B3. This simplified scheme has been shown to have good reproducibility and, more importantly, carries adequate prognostic power with regard to survival and recurrence.^6,18

For the sake of uniformity and clinical implications, it is recommended that either the WHO or the Suster-Moran nomenclature (or both) be parenthetically added to the report if another classification system is being used.⁶

The most frequent genetic alterations in thymomas affect chromosome 6q25.2-25.3. In type A thymomas, genetic alterations other than on chromosome 6 are rare.¹ In type AB thymoma, deletion of chromosome 6 with or without formation of ring chromosome 6 as well as complex multiple chromosomal aberrations have been identified.²² Genetic alterations in type AB thymomas have been described as intermediate between those of type A and those of type B.²³ A few type A and AB thymomas with a clinically benign course may show genetic imbalances (e.g., on chromosome 8p11.21) that are associated with a poor prognosis if encountered in type B2 and B3 thymomas or thymic squamous cell carcinomas.²²