Thymoma is a rare disease, with an incidence of only 0.13 per 100,000 person-years (1). However, it is the most common tumor of the anterior mediastinum, representing approximately 30% of anterior mediastinal lesions and 20% of all mediastinal tumors in adults. Based on Surveillance, Epidemiology and End Results (SEER) data from 1973 to 2006 the incidence is similar between males and females. Interestingly, the incidence in the United States is higher in African Americans and especially Asian/Pacific Islanders compared to whites or Hispanics. The median age at presentation is around 50 years and it peaks in the seventh decade. Approximately one-third of patients are asymptomatic at presentation, one-third have symptoms from local extent of their tumor, and one-third present with paraneoplastic syndromes, typically myasthenia gravis (MG).
Thymomas are tumors derived from the thymic epithelium. In 1989 Muller-Hermelink and Kirchner proposed a classification based on the similarity of the morphologic appearance of the tumor to normal thymic compartments. This classification subdivided tumors into medullary, mixed, predominantly cortical, cortical, and well-differentiated thymic carcinoma.
In an attempt to standardize the histologic diagnosis of thymoma, the World Health Organization (WHO) published its own classification in 1999, which subdivided tumors into six types: A, AB, B1, B2, B3, and C. Type A tumors have neoplastic cells with spindle or oval appearance, whereas type B tumors have cells with an epithelioid or dendritic appearance. Types B1, B2, and B3 correspond to the predominantly cortical, cortical, and well-differentiated thymic carcinoma, respectively. Tumors combining type A and type B1 or rarely B2 features are classified as type AB. In the 2004 WHO classification update, thymic carcinomas (type C tumors in the 1999 WHO classification) include tumors with histology foreign to thymic tissues and are termed according to their differentiation (such as squamous cell carcinomas, mucoepidermoid, basaloid carcinoma, etc.), including carcinomas with neuroendocrine histology (2).
Thymic carcinomas have distinct morphology and immunophenotype; they present at more advanced stages and have a significantly inferior prognosis compared to other thymoma types. For that reason, some authors propose that well-differentiated thymic carcinomas should be designated as "atypical thymomas," not to be confused with (type C) thymic carcinomas, which will not be considered in this chapter.
In an era of personalized medicine and targeted treatment, thymomas remain for the most part outside of the spotlight. Although genetic alterations do occur, there has been no specific molecular target identified, which would be appropriate for therapeutic interventions. Random case reports have described responses to various tyrosine kinase small molecule inhibitors, but these were mostly confined to thymic carcinomas, and for those patients with thymoma who responded, no corresponding genetic alteration was identified in the tumor (3, 4). Allelic imbalances are very low for types A and AB (7%–8%), but increase to 20% for more advanced histologic ...