Cases
65-year-old man with worsening shortness of breath   

Discussion

Thymic squamous cell carcinoma

Pathophysiology

Thymic squamous cell carcinomas (SCCs) show a highly prevalent recurrent loss of chromosome p16. Other alterations include loss of chromosomes 3p, 6, 16q, and 17p. KIT mutations have been noted in about 11% of thymic squamous cell carcinomas.

Epidemiology

Among thymic epithelial tumors, thymic carcinomas account for about 14% to 20% of all tumors, with SCC comprising 70% to 80% of all cases. They are most common in the sixth decade of life and men are more frequently affected than women.

Clinical presentation

Most patients with thymic carcinoma present with chest pain, cough, and/or shortness of breath. Some less commonly reported symptoms include fever, superior vena cava syndrome, and hoarseness. In approximately 35% of patients, it is an incidental finding.

Imaging findings

On imaging, thymic cancers appear as anterior mediastinal masses and have irregular lobular margins which are poorly defined. Necrotic or cystic changes can be seen on CT scans.

Microscopic description

Characteristic histologic findings in thymic carcinoma include infiltrative sheets, islands, and cords of large polygonal cells, surrounded by broad zones of desmoplastic stroma that is variably infiltrated by chronic inflammatory cells. Tumor islands are typically smooth in contour, but jagged islands can be seen. There are delicate blood vessels traversing the islands. The tumor cells have large vesicular or hyperchromatic nuclei and prominent nucleoli. Cytoplasm is eosinophilic, and intracellular bridges can sometimes be appreciated. Thymic carcinomas can be well to moderately and in some cases poorly differentiated, based on nuclear pleomorphism, squamous differentiation, and degree of keratinization.

Immunohistochemically, thymic carcinomas stain for pancytokeratins and p40. PAX8 is positive in a majority of cases. CD5, CD117, and EMA are frequently used to determine thymic origin. Some thymic carcinomas express neuroendocrine markers, as opposed to thymomas.

References

  1. WHO Classification of Tumours. 5th ed. Lyon, France: IARC, 2021.
  2. Marchevsky AM, McKenna RJ Jr, Gupta R. Thymic epithelial neoplasms: A review of current concepts using an evidence-based pathology approach. Hematol Oncol Clin North Am. 2008;22(3):543-562.
  3. Suster S. Thymic carcinoma: Update of current diagnostic criteria and histologic types. Semin Diagn Pathol. 2005;22(3):198-212.
  4. Suster S, Rosai J. Thymic carcinoma. A clinicopathologic study of 60 cases. Cancer. 1991;67(4):1025-1032.