Dr. Nathan Helgert provides the anatomic pathology perspective on this thymoma case.
Thymoma is an uncommon neoplasm of thymic epithelial origin that is rarely reported in dogs.1 These tumors arise within the cranial mediastinum (Figure 1) and can cause compression and dysfunction of the heart and lungs. Typically, thymomas are multilobular masses with fluid-filled cysts, acute or chronic hemorrhage, or foci of necrosis (Figure 2). Because of this heterogeneity, multiple biopsy samples should be collected to ensure representative sampling of the mass.1
Figure 1. Canine thymoma (Figures 1-6 are not the patient in this case). Thymomas are multilobulated tumors typically arising within the cranial mediastinum (star). H: heart, E: esophagus, L: lung, T: trachea.
Figure 2. Canine thymoma. Thymomas may be quite heterogeneous with cystic areas (arrows), hemorrhage and necrosis.
Dr. Nathan HelgertNormally, thymic lobules have a well-defined cortex and medulla, but in cases of thymoma, this distinction is lost.1,2 Normal thymic epithelial cells are polygonal with moderate amounts of clear cytoplasm and round-to-oval vesiculate nuclei. These cells are present around blood vessels, scattered throughout each lobule, in a one- or two-cell thick rim around each lobule, and as medullary aggregates known as Hassall's corpuscles.3
Neoplastic thymic epithelial cells range from polygonal to spindloid and are arranged in bundles, sheets, or clusters or occur individually and have round, oval, or fusiform nuclei with moderate to abundant amounts of clear to eosinophilic cytoplasm (Figures 3 & 4). Histologically, thymomas are a heterogeneous group of neoplasms and, thus, have resisted consistent histologic classification. Historically, thymomas have been classified based on the appearance of the neoplastic epithelial cells and were classified as spindle cell, clear cell, pigmented, or lymphocyte-rich thymomas.1,2
Figure 3. Canine thymoma, type A. The neoplastic thymic epithelial cells are spindle-shaped, have oval to fusiform nuclei and moderate amounts of eosinophilic cytoplasm (arrowheads). The neoplastic cells are arranged in bundles and streams. There is loss of the underlying thymic architecture. There are few lymphocytes (arrows). (Hematoxylin-eosin, 400X.)
Figure 4. Canine thymoma, type B2. The neoplastic thymic epithelial cells are round to polygonal, have round to oval nuclei and moderate to abundant amounts of clear cytoplasm. The neoplastic cells are arranged in clusters (arrowheads) and occasionally occur as individual cells (arrows). There is loss of the normal corticomedullary architecture. (Hematoxylin-eosin, 400X.)In people, the World Health Organization recommends classification of these neoplasms by morphology of the neoplastic cells in addition to the proportion of non-neoplastic lymphocytes (Table 1).2,4 This classification scheme has been shown to be applicable to canine thymomas4; however, unlike in people, there is no prognostic significance associated with histologic type in dogs.2,4 This lack of prognostic differences between classifications of thymomas in dogs is likely due to the lack of large-scale studies of canine thymomas, or it may indicate that regardless of the histologic features, the biologic behavior is similar.4
Table 1. WHO classification of thymic epithelial neoplasms
Spindleoid epithelial cells with few lymphocytes
Nodules of spindleoid epithelial cells with abundant B cells; likely a subtype of type A
Lymphocyte-rich type A
Recapitulates normal thymic corticomedullary architecture
Polygonal epithelial cells with abundant lymphocytes
Polygonal epithelial cells with few lymphocytes
Combination of many of the above
Cytologic atypia without immature lymphocytes; >10 mitotic figures in ten 400x fields
X with anaplasia
Morphologic features of both thymoma and thymic carcinoma
Source: References 2, 4
Malignant thymomas (thymic carcinomas) are rare, and are subclassified as: squamous cell carcinoma, adenosquamous carcinoma, and clear cell carcinoma. These neoplasms carry a poorer prognosis than nonmalignant thymomas do.1
Thymic epithelial neoplasms with a pronounced lymphocyte population must be differentiated from thymic lymphoma.1,4 Immunohistochemistry is useful for making this distinction. Thymic epithelial cells are immunoreactive to the epithelial marker cytokeratin (Figure 5) but not the T cell marker CD3 (Figure 6). In cases of thymoma, individual or groups of cytokeratin immunoreactive thymic epithelial cells should be prominent and should be rare to absent in thymic lymphoma.1
Figure 5. Canine thymoma, type B2. Neoplastic thymic epithelial cells (arrowheads) are immunopositive for cytokeratin. Non-neoplastic lymphocytes (arrows) are immunonegative for cytokeratin. (AE1/AE3 cytokeratin IHC with hematoxylin counterstain, 600X.)
Figure 6. Canine thymoma, type B2. Non-neoplastic lymphocytes are immunopositive for CD3 (arrows). Neoplastic thymic epithelial cells are immunonegative for CD3 (arrowheads). (CD3 IHC with hematoxylin counterstain, 600X.)No samples from the patient in this case were submitted for histologic examination.
1. Meuten DJ. Tumors in domestic animals. 5th ed. Ames, Iowa: John Wiley & Sons Inc, 2017.
2. Maxie MG. Hematopoietic system. In: Jubb, Kennedy, and Palmer's pathology of domestic animals. 6th ed. St. Louis: Elsevier, 2016.
3. Pearse G. Normal structure, function and histology of the thymus. Toxicol Pathol 2006;34:504-514.
4. Burgess KE, DeRegis CJ, Brown FS, et al. Histologic and immunohistochemical characterization of thymic epithelial tumours in the dog. Vet Comp Oncol 2016;14:113-121.