Final Diagnosis -- Invasive Pulmonary Thymoma




Thymoma, by definition, is a tumor of thymic epithelial cell origin. It is actually the most common neoplasm in the entire mediastinum. It usually occurs in adults older than 40 years of age and affects males and females equally. Most arise in the anterosuperior mediastinum; however, ectopic sites have been described, including neck, thyroid, lung parenchyma, pleura, etc.. About 30-50% of thymomas are associated with myasthenia gravis. Clinical symptoms include cough, chest pain, dyspnea, weight loss, fever, dysphagia and hoarseness.

In most instances, the presence of thymoma is revealed by plain chest roentgenograms. CT scan can confirm the location and may reveal some characteristics of the tumor such as cystic changes or involvement of surrounding structures. Grossly, 70-80% of thymomas are encapsulated. Cut surface is usually grey-tan with bulging and lobulated appearance. Occasionally, cystic necrosis and calcification can be seen. Microscopically, the tumor typically consists of jigsaw puzzle-type lobules that are separated by fibrous bands. There is an admixture of neoplastic epithelial cells and non-neoplastic lymphocytes in varying proportions. The polygonal epithelial cells usually have bland vesicular nuclei with inconspicuous nucleoli. Another histologic feature seen in two thirds of thymomas is the presence of perivascular spaces, which are formed and bordered by palisading epithelial cells. In these spaces, there is a suspension of erythrocytes, lymphocytes, plasma cells, mast cells and plasma fluid. Immunostain of cytokeratin is characteristic and features an arborizing network of interconnecting epithelial cell processes. The immature lymphocytes in thymomas can be identified by their positivity for terminal deoxynucleotide transferase (TdT) and OKT6 (CD1a). Electron microscopy reveals elongated cytoplasmic processes, a large number of desmosomes and bundles of tonofilaments in the cytoplasm.

Four histologic types have been described for thymomas: lymphocyte-predominant, epithelial-predominant, mixed lymphoepithelial and spindle-cell types. Among them, the spindle-cell type is usually encapsulated with minimal invasion and correlates to excellent prognosis. The epithelial-predominant type and mixed type are associated with poor prognosis.

The main differential diagnoses of thymoma include: (1) Malignant lymphoma---lymphocyte-predominant thymomas can be mistaken for lymphomas. However, the lobular configuration and the biphasic cell composition should establish the diagnosis of thymoma. The demonstration of keratin positivity in the epithelial component is particularly useful. (2) Small cell carcinoma and atypical carcinoid tumor---these tumors do not show lobulation or two-cell population. They are positive for neuroendocrine markers such as neuron-specific enolase (NSE), synaptophysin and chromogranin. (3) Lymphoepithelioma-tumor cells in lymphoepithelioma grow in syncytial pattern with ill-defined borders. Sheets or islands of cells are surrounded by dense mature lymphoplasmacytic infiltrates, negative for TdT or OKT6. For our case, we also need to consider malignant mesothelioma as a differential, because of the gross appearance of this tumor (extensively involving the pleura and encasing the entire lung). In typical mesothelioma, the tumor cells exhibit some areas of tubular and/or papillary growth. The cells have more abundant eosinophilic cytoplasm with sharp borders, and the lymphoid component is absent or inconspicuous. Calretinin is positive in 40-50% of mesotheliomas.

Although rare, there have been scattered reports about ectopic thymomas, including intrapulmonary and pleural thymomas. Ectopic thymomas are usually considered to result from aberrant descent of the thymic tissue from the third pharyngeal pouch during early development. Before diagnosing ectopic thymoma, one needs to be certain that there is no primary mediastinal thymoma present. In this case, the absence of mediastinal involvement is shown by the negative radiologic and gross autopsy findings in the anterosuperior mediastinum. However, it is not absolutely clear whether this tumor is intrapulmonary or pleural in origin, since both lung and pleura are massively involved.

Finally, a surprising finding is revealed on sections of left and right ventricles, which is eventually the immediate cause of death for this patient. The etiology of the presence of abundant eosinophils and scattered multinucleated giant cells is not clear. It is unlikely that the heart is directly invaded by the tumor, for cytokeratin stain is negative on these sections. There have been a couple of reports about giant cell myocarditis in patients with malignant thymomas. Autoimmune processes have been suggested in these cases. It is possible that in our patient, the activated T cells produce some kinds of cytokines that eventually trigger an intense reaction in the myocardium.


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Contributed by Su Zheng, MD, PhD and Mona Melhem, MD


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