Fine needle aspiration cytopathology of thymoma and thymic carcinoma

Thymic epithelial neoplasms, which include thymomas and thymic carcinomas, are rare malignancies, constituting less than 1% of all tumors. Fine needle aspiration (FNA) cytopathology offers a minimally invasive diagnostic approach, enabling early detection and treatment planning. However, the technique faces challenges, particularly in accurately subtyping thymomas due to sample heterogeneity and overlapping cytologic features with other mediastinal and non-mediastinal lesions. This review aims to provide a comprehensive overview of the cytologic characteristics of thymomas and thymic carcinomas and highlight common diagnostic pitfalls associated with FNA.

Thymoma

Thymomas are the most frequently occurring thymic epithelial tumors, with an annual incidence of approximately 0.13 cases per 100,000 people. These tumors can be asymptomatic or present with local compressive symptoms such as chest pain and superior vena cava syndrome, as well as paraneoplastic syndromes like myasthenia gravis. Histologically, thymomas consist of a mixture of neoplastic epithelial cells and non-neoplastic T lymphocytes. The World Health Organization (WHO) classifies thymomas into several subtypes: type A, type AB, and type B (B1, B2, B3), along with rare variants like metaplastic thymoma.

Morphology and Cytologic Features

• Type A Thymoma: Characterized by spindle-shaped epithelial cells with scant lymphocytic infiltration. The cytologic smears typically show uniform spindle cells with elongated nuclei and fine chromatin.
• Type AB Thymoma: Exhibits a combination of spindle and round/polygonal epithelial cells with a variable lymphocyte component. The cytologic smears reveal mixed cell populations, reflecting the histologic heterogeneity.
• Type B Thymoma: Subdivided into B1, B2, and B3 based on the epithelial-to-lymphocyte ratio. B1 thymomas have abundant lymphocytes with few epithelial cells, B2 thymomas show an equal mixture, and B3 thymomas predominantly consist of epithelial cells with sparse lymphocytes. Cytologically, B1 and B2 thymomas can be challenging to distinguish due to their lymphocyte-rich background, whereas B3 thymomas demonstrate cohesive epithelial clusters with less lymphoid content.

Immunohistochemistry

Immunohistochemical staining is crucial for diagnosing thymomas. Neoplastic epithelial cells consistently express cytokeratins (AE1/AE3, CK5/6) and p63. The reactive T lymphocytes within thymomas are positive for CD3. Additionally, markers such as CD1a and terminal deoxynucleotidyl transferase (TdT) are present in thymocytes but may be absent in specific thymoma subtypes, aiding in the differential diagnosis.

Differential Diagnosis

Accurate differentiation of thymomas from other mediastinal and spindle cell lesions is essential. For instance, type B1 thymoma must be distinguished from T-lymphoblastic lymphoma, which also presents with a lymphocyte-rich background. Type B3 thymoma needs differentiation from thymic carcinoma and metastatic carcinoma due to overlapping cytologic features. Immunohistochemical panels, including epithelial markers and lineage-specific markers, are indispensable in achieving an accurate diagnosis.

Thymic Carcinoma

Thymic carcinomas are more aggressive than thymomas and constitute about 20% of thymic epithelial neoplasms. These malignancies often present with symptoms related to local invasion or metastasis and generally have a poor prognosis. Histologically, thymic carcinomas display a wide range of morphologies, with squamous cell carcinoma being the most prevalent subtype. Other histologic variants include basaloid carcinoma, lymphoepithelioma-like carcinoma, and NUT midline carcinoma.

Conclusions

FNA cytopathology is a valuable diagnostic tool for evaluating thymic epithelial neoplasms due to its minimally invasive nature and high diagnostic yield. However, accurate subtyping of thymomas and differentiation from other mediastinal and non-mediastinal lesions can be challenging. A comprehensive understanding of the cytologic features, combined with judicious use of immunohistochemical stains, is crucial for accurate diagnosis and optimal patient management. Advances in FNA techniques and the identification of novel diagnostic markers may further enhance the diagnostic accuracy and clinical utility of this approach in the future.

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https://www.xiahepublishing.com/2771-165X/JCTP-2023-00014

The study was recently published in the Journal of Clinical and Translational Pathology.

Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.

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