Critical review
Thymic carcinoma: state of the art review

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Abstract

Thymic carcinoma is a rare neoplasm with distinct clinical and pathological characteristics. The prognosis is often poor with an aggressive course that belies its numerical rarity. Potentially prognostic factors for survival include histopathologic grade, clinical stage, and resectability of the tumor. Five-year survival rates for all patients are approximately 30–50%, with a significant survival time differential between low-grade and high-grade neoplasms. Owing to the paucity of cases, optimal management of thymic carcinoma has yet to be defined. At present, a multimodality approach involving aggressive surgical resection, platinum-based combination chemotherapeutic interventions, and radiotherapy represent the preferred therapeutic approach. Though our knowledge remains somewhat speculative at present, several scientific, technological and therapeutic innovations may have a potentially significant impact on the future of this disease.

Introduction

Thymic carcinoma is a rare carcinoma of the thymus arising in the thymic epithelium with overt features of malignancy similar to that of carcinoma arising in any other organ with propensity to capsular invasion and metastases. It is often confused with thymoma, which by definition has an admixture of varying number of lymphocytes and epithelial cells that lack cytologic features of overt malignancy (1). In thymomas, there is a much lower incidence of metastases and capsular invasion (invasive thymomas) than in thymic carcinoma, thus justifying the reason for separating the two. Thymic carcinomas represent less than 1% of thymic malignancies (2), and often present with advanced disease and have a 5-year survival of 30%–50% (3). Owing to the paucity of cases, optimal management of thymic carcinoma has yet to be defined. The purpose of this article is to review pertinent developments in the diagnosis and management of thymic carcinoma.

Section snippets

Clinical and radiographic presentation

Most thymic carcinomas present initially with cough, chest pain, phrenic nerve palsy, or superior vena cava syndrome 3, 4. Further exploration often reveals a mediastinal mass 4, 5, 6, 7, 8. Like thymoma, thymic carcinoma is most commonly located in the anterosuperior mediastinum. The anatomic location of origin of this malignant intrathoracic mass is critical since it is possible that an occult non–small-cell lung cancer (NSCLC) primary may directly extend into the thymus gland (9). Associated

Molecular pathology

The pathogenesis of thymic carcinoma has yet to be fully elucidated; however, several studies have observed an association with Epstein-Barr virus (EBV) within the lymphoepithelioma-like subtype 26, 27. Thymic carcinomas have shown increased expression of CD70, a surface marker that is a member of the TNF superfamily found in other neoplastic diseases associated with EBV, despite the fact that EBV was not detected in samples themselves using in situ hybridization 26, 27, 28. Consequently, CD70

Histopathology and staging

The histologic classification of thymic lesions is important for prognosis 7, 8. Currently, thymic carcinomas are classified as Type C in the consensus WHO classification of human thymic epithelial neoplasms (see Table 1) (50). This classification allows reproducible definition of thymic carcinoma based on morphologic features, an important step toward standardization of nomenclature and taxonomy (51). A separate system, the Marino, Kirchner, and Muller-Hermlink system designates two malignant

Treatment

The optimal treatment of thymic carcinoma remains undefined, owing to the paucity of cases. The challenge of obtaining a firm histologic diagnosis of (nonthymoma) thymic carcinoma is not uncommon before therapeutic intervention. At present, the favorable outcomes for intramediastinal disease may be maximized through an aggressive multimodality approach including surgical resection, radiotherapy, and cisplatinum-based chemotherapy 80, 81. Entry onto prospective protocols, if available, would be

Conclusion

Thymic carcinoma is a rare thymic neoplasm with an aggressive course that belies its numerical rarity. Potentially prognostic factors for survival include histopathologic grade, clinical stage and resectability of the tumor. Five-year survival rates for all patients are approximately 38–50%, with a significant survival time differential between low- and high-grade neoplasms 3, 58, 69, 98. Also, staging is prognostic, with early-stage patients exhibiting markedly better survival (80). Optimum

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      Citation Excerpt :

      Patients with thymic carcinomas often present with metastases [5]. However, the 5-year survival rate for thymic carcinomas is only 55% [6–8]. It is quite important to differentiate between thymic malignancies and other diseases (e.g., lung metastases, lymphoma, goiter, and germ cell tumors) before treatment, because disease management strategies differ for these conditions [9–11].

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    Supported in part by National Institutes of Health, Grant No. P30 CA54174 Cancer Center Core Grant to the San Antonio Cancer Institute.

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