Corticomedullary differentiation and maturational arrest in thymomas.
OBJECTIVE
Morphological complexity hampers the histological classification of thymomas. Our aim was to determine whether the use of novel differentiation and maturation markers of cortical and medullary thymic epithelial cells (cTECs and mTECs) might provide an approach to understanding the underlying biology of these tumours.


RESULTS
Fifty-seven thymomas were studied by immunohistochemistry. The cortical markers used were B5T, PRSS16, and cathepsin V. The medullary markers used were CD40, claudin-4, AIRE, and desmin. Involucrin and cytokeratin 10 were used to study terminal mTEC maturation. Irrespective of histological subtype, most thymomas contained distinct areas with cortical and medullary differentiation. Type B1, type B2 and type AB thymomas showed marked bi-lineage differentiation, with lack of terminal mTEC maturation in type AB. Type AB thymomas were unique in showing areas where cells with either cortical or medullary differentiation were intimately 'mixed' at the single-cell level. Type B3 and type A thymomas showed only abortive lineage differentiation and maturation.


CONCLUSIONS
Thymomas show highly characteristic patterns of bi-lineage TEC differentiation that reflect the histological subtypes recognized by the WHO classification. We hypothesize that thymomas arise from thymic precursor cells with different cortical and/or medullary maturation defects.
Institute of Pathology, University Medical Centre Göttingen, University of Göttingen, Göttingen, Germany.
Philipp
P
Ströbel
Elena
E
Hartmann
Andreas
A
Rosenwald
Jörg
J
Kalla
German
G
Ott
Godehard
G
Friedel
Berthold
B
Schalke
Masanori
M
Kasahara
Utano
U
Tomaru
Alexander
A
Marx
D014408:Biomarkers, Tumor / Q000378:metabolism; D019013:CD40 Antigens / Q000378:metabolism; D002294:Carcinoma, Squamous Cell / Q000145:classification / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D019070:Cell Lineage; D062506:Claudin-4 / Q000378:metabolism; D004847:Epithelial Cells / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D053550:Keratin-10 / Q000378:metabolism; D009375:Neoplasms, Glandular and Epithelial / Q000145:classification / Q000378:metabolism / Q000473:pathology; D014411:Neoplastic Stem Cells / Q000473:pathology; D013945:Thymoma / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D013953:Thymus Neoplasms / Q000145:classification / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000378:metabolism; D055815:Young Adult; D000096927:AIRE Protein
D014408:Biomarkers, Tumor; D019013:CD40 Antigens; D062506:Claudin-4; D053550:Keratin-10; D014157:Transcription Factors; D000096927:AIRE Protein; C568157:CLDN4 protein, human; C507493:KRT10 protein, human
classification; cortex; differentiation; medulla; stem cell; thymoma; thymus