International Journal of Radiation Oncology*Biology*Physics
Critical reviewThymic carcinoma: state of the art review☆
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
References (107)
- et al.
Squamous cell carcinoma of the thymus with paraneoplastic hypercalcemia
Clin Imaging
(1995) - et al.
Study of Epstein-Barr virus early RNA 1 (EBER1) expression by in situ hybridization in thymic epithelial tumors of Chinese patients in Taiwan
Hum Pathol
(1993) - et al.
Proliferative activity and apoptosis in thymic epithelial neoplasms
Mod Pathol
(2002) - et al.
Correlation between tumor angiogenesis and invasiveness in thymic epithelial tumors
J Thorac Cardiovasc Surg
(2002) - et al.
Differential diagnosis of thymic carcinoma and lung carcinoma with the use of antibodies to cytokeratins
J Thorac Cardiovasc Surg
(1995) - et al.
Prognostic relevance of Masaoka and Muller-Hermelink classification in patients with thymic tumors
Ann Thorac Surg
(2000) - et al.
Thymic carcinomaSpectrum of differentiation and histologic types
Pathology
(1998) - et al.
Thymic carcinoma. Ten years' experience in twenty patients
J Thorac Cardiovasc Surg
(1994) - et al.
Thymic carcinomaCurrent staging does not predict prognosis
J Thorac Cardiovasc Surg
(1998) - et al.
Postoperative radiotherapy in thymic carcinomaTreatment results and prognostic factors
Int J Radiat Oncol Biol Phys
(2002)
Therapy for thymic epithelial tumorsA clinical study of 1,320 patients from Japan
Ann Thorac Surg
Aggressive multimodality treatment of invasive thymic carcinoma
J Thorac Cardiovasc Surg
Thymic carcinomaA report of 13 cases
Eur J Surg Oncol
Thymic carcinomaInvolvement of great vessels indicates poor prognosis
Ann Thorac Surg
Primary thymic epithelial neoplasmsSpectrum of differentiation and histological features
Semin Diagn Pathol
Neoplasms of the mediastinum
Thymic carcinoma
Kyobu Geka
Malignant thymic epithelial tumorsCT-pathologic correlation
Am J Roentgenol
Thymic carcinoma—analysis of nineteen clinicopathological studies
Thorac Cardiovasc Surg
The pathology of thymic neoplasia
Monogr Pathol
Oncological significance of WHO histological thymoma classification. A clinical study based on 286 patients
Jpn J Thorac Cardiovasc Surg
The World Health Organization histologic classification system reflects the oncologic behavior of thymomaA clinical study of 273 patients
Cancer
Thymic malignancies
Cancer Treat Res
Parathyroid-hormone-related-protein-producing thymic carcinoma presenting as a giant extrathoracic mass
Respiration
Prognostic factors in thymic epithelial neoplasms
Eur J Cardiothorac Surg
Thymic carcinoma (report of 14 cases)
Chin Med Sci J
Squamous cell carcinoma of the thymus. An analysis of eight cases
Am J Surg Pathol
CT findings in primary thymic carcinoma
J Comput Assist Tomogr
Thymic carcinomaCase reports and review
J Thorac Imaging
Assessment of residual tumor viability in thymic carcinoma by sequential thallium-201 SPECTComparison with CT and biopsy findings
J Nucl Med
Using the World Health Organization classification of thymic epithelial neoplasms to describe CT findings
Am J Roentgenol
Differential diagnosis between thymoma and non-thymoma by dynamic MR imaging
Acta Radiol
MR imaging of thymomaRadiologic-pathologic correlation
Am J Roentgenol
Differential diagnosis of thymic tumors using a combination of 11C-methionine PET and FDG PET
J Nucl Med
Thallium-201 single photon emission computed tomography in the evaluation of thymic carcinoma
Radiat Med
Metabolic (PET) and receptor (SPET) imaging of well- and less well-differentiated tumoursComparison with the expression of the Ki-67 antigen
Nucl Med Commun
PET imaging of primary mediastinal tumours
Br J Cancer
Metastatic thymic carcinoma demonstrated by radionuclide bone scan
Clin Nucl Med
EBER-1 expression in thymic carcinoma
Acta Pathol Jpn
CD70 expression in thymic carcinoma
Am J Surg Pathol
CD5 expression in thymic carcinoma
Am J Pathol
Immunoreactivity of a new CD5 antibody with normal epithelium and malignant tumors including thymic carcinoma
Am J Clin Pathol
Thymic carcinomas, but not thymomas and carcinomas of other sites, show CD5 immunoreactivity
Am J Surg Pathol
The distribution of epithelial membrane antigen in thymic epithelial neoplasms
Cancer
Cytokeratins in normal thymus and thymic epithelial tumors
Cancer
p53 protein expression and p53 gene mutation in thymic epithelial tumors. An immunohistochemical and DNA sequencing study
Am J Clin Pathol
p53 alteration, proliferating cell nuclear antigen, and nucleolar organizer regions in thymic epithelial tumors
Int J Mol Med
Thymic carcinoma arising in thymoma is associated with alterations in immunohistochemical profile
Am J Surg Pathol
High frequency of p53 protein expression in thymic carcinoma but not in thymoma
Br J Cancer
Surgery for thymomas and thymic carcinomasTreatment results in terms of WHO histologic typing, Masaoka staging system, and p53 expression
Kyobu Geka
Cited by (145)
Invasive thymoma metastases to the pancreas: A case report
2023, International Journal of Surgery Case ReportsIs GRP78 (Glucose-regulated protein 78) a prognostic biomarker in differents types of cancer? A systematic review and meta-analysis
2023, Pathology Research and PracticeThymic cancer: A not-so-indolent cause of pericardial effusion
2021, Annals of Medicine and SurgeryThe safety and efficacy of Cyberknife® for thymic malignancy
2021, Cancer/RadiotherapieNext-generation sequencing in thymic epithelial tumors uncovered novel genomic aberration sites and strong correlation between TMB and MSH6 single nucleotide variations
2020, Cancer LettersCitation 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].
- ☆
Supported in part by National Institutes of Health, Grant No. P30 CA54174 Cancer Center Core Grant to the San Antonio Cancer Institute.