The dual population of cells observed in the normal thymus is reflected in thymomas, which are composed of epithelial cells and lymphocytes in varying proportions. Most thymomas are encapsulated and benign (Fig. 37-3). The epithelial component of these tumors may vary from polygonal (Fig. 37-4A-D) to spindly cells (Fig. 37-5A-D). Rarely, rosettes and other variants have been described. An elaborate classification of thymomas is not relevant to the context of this book, and the interested reader is referred to other sources for additional information (Shimosato and Mukai, 1997; Rosai, 1999).

Some thymomas that appear histologically benign may invade adjacent lung and even metastasize to other sites. There has been considerable controversy over whether the histologic structure of the epithelial component is predictive of the behavior of the tumor. Thymomas with a predominantly spindly epithelial component are generally believed to be benign, whereas those with polygonal epithelial cells are said to be more aggressive; however, so far there is no conclusive evidence of this behavior pattern. In a review of 90 thymic tumors, Chalabreysse et al (2002) concluded that favorable prognostic factors are noninvasiveness, completeness of resection, younger age, and myasthenia gravis. Thymomas with clear-cut cytologic atypia and numerous mitoses, which are classified as thymic carcinomas by World Health Organization (WHO) criteria, are more aggressive
and invasive. In our experience, the best evidence of malignant potential is invasion through the capsule and into the lung or other tissues. The cytology of frankly malignant thymomas (carcinomas) is considered separately below.

The aspirates of thymic tumors are typically cellular and, as expected, they demonstrate a dual population of epithelial and lymphoid cells in variable proportions (Tao et al, 1984; Sherman and Black-Schaffer, 1990; Koss et al, 1992). The epithelial cells may be present singly (see Fig. 37-4B,C), in clusters (see Fig. 37-4D), or even as tissue fragments (Fig. 37-5C,D). A highly variable number of lymphocytes is intermingled with the epithelial cells. Fragments of fibrovascular tissue may be present. The epithelial cells are polygonal, oval (see Fig. 37-4), or spindly (Fig. 37-5), with moderate to abundant pale cytoplasm and bland, vesicular nuclei that are noticeably larger than the adjacent lymphocytes (see Fig. 37-4B-D). Chhieng et al (2000) estimated the size difference at three- to fourfold. Some degree of squamous differentiation of the epithelial cells may be apparent in an aspirate. We have seldom seen well-formed Hassall’s corpuscles in thymic tumors, and their presence in an aspirate is in favor of a benign hyperplastic thymus. Chhieng et al (2000) found no Hassall’s corpuscles in a recent review of aspirates from 31 patients with thymoma. They reported that thymomas with epithelial cells with round or oval nuclei appeared to be more aggressive than tumors with epithelial cells with spindle nuclei. Chalabreysse (2002) found no such difference, and we also have no evidence that the cell or nuclear shape of the epithelial cells has any prognostic significance (Koss et al, 1992). We agree with Chhieng et al (2000) that cytologic features in the aspirate do not correlate well with any of the histologic patterns.

Although the population of lymphoid cells in most thymomas consists of small, resting lymphocytes, it should be noted that intermixed reactive lymphoblasts may be present (Pak et al, 1982; Ali and Erozan, 1998; Shin and Katz, 1998). If the latter are numerous and prominent, one must consider the possibility of a non-Hodgkin’s malignant lymphoma, which may mimic thymoma, particularly in a child or adolescent (Friedman et al, 1996). For further discussion of thymic lymphomas, see below. In the absence of lymphocytes, the epithelial cells of thymoma may be mistaken for a primary or metastatic carcinoma.

Finally, while the presence of a spindle cell population,
intermixed with lymphocytes, should suggest the possibility of thymoma, Slagel et al (1997) reviewed 22 cases of mediastinal tumors in which the needle aspirate contained a predominant spindle cell component, and found only two thymomas and two thymic cysts. The remaining cases included nerve sheath tumors, granulomatous inflammation, Hodgkin’s disease, and a heterogenous group of other tumors.