Cytokeratin profiles of the thymus and thymomas: Histogenetic correlations and proposal for a histological classification of thymomas

Aims: Since cytokeratins (CKs) are useful as differentiation markers for histogenetic and classification studies, we investigated the CK profiles of the thymus and thymomas in an attempt to understand the histogenetic correlation and to propose a histological classification. Methods and results: Nine thymuses and 34 thymomas were immunostained for various CKs of different molecular weights and involucrin. Based on cytomorphology and histoarchitecture, thymomas were classified into spindle cell (SC), small polygonal cell (SPC), mixed, organoid, large polygonal cell (LPC) and squamoid (SQ) thymomas for compiling CK profiles. The thymus was shown to comprise four epithelial compartments, each expressing a different CK profile. Different histological types of thymoma expressed different CK profiles. By correlating the CK profiles of the thymus and thymoma, SPC, SC and LPC thymomas appeared to be related to subcapsular, medullary and cortical cells, respectively. Organoid thymoma recapitulated the structure and CK profile of the normal thymus, while SQ thymoma acquired additional squamous type CK. The applicability and usefulness of the proposed histological classification were evaluated on 147 thymomas by correlating the results with their invasive behaviour. One hundred and thirty-nine cases (95%) could be classified and different histological types correlated strongly with their invasive behaviour. Conclusions: The thymus is a complex epithelial organ composed of heterogeneous cell types giving rise to various related histological types of thymoma. The results of the CK profile study supports the proposed histological classification, which is pathologically applicable and clinically useful in correlating with invasiveness. This cytomorphological classification, supported by the CK expression patterns, is comparable to Muller-Hermelink classification and the new WHO histological classification except that a separate group of SPC thymoma expressing only CK14 and CK19 was identified and separated from mixed thymoma.