The morphologic distinction of ependymomas with epithelial cytology from me
tastatic carcinoma may pose a significant problem in differential diagnosis
. The known presence of keratin in glioma cells further complicates the iss
ue. Using the labeled streptavidin-biotin method with automated staining, w
e studied epithelial and glial marker expression in 52 ependymomas of varyi
ng type and grade, including 20 epithelial-appearing, 14 glial-appearing, e
ight mixed pattern, and 10 myxopapillary tumors; 38 were low grade and 14 a
naplastic. All tumors were immunoreactive for glial fibrillary acidic prote
in (GFAP), and S-100 protein. Diffuse staining for GFAP was noted in glial-
appearing ependymomas featuring perivascular pseudorosettes. Diffuse immuno
staining for 8-100 protein was seen in cellular lesions exhibiting epitheli
al-like features. Staining was more diffuse for GFAP than S-100 protein in
anaplastic ependymomas. Keratin (AE1/AE3) reactivity was seen in 98% of cas
es, the pattern being similar to that of GFAP. The frequency of staining fo
r other keratins varied: wide-spectrum keratin (35%), cytokeratin (CK)7 (20
%), CAM 5.2 (19%), CK903 (14%), and CK20 (8%); as a rule, it was scant and
limited to occasional cells and processes. epithelial membrane antigen (EMA
) staining was seen in 36% of all cases and in 67% of epithelial-appearing
tumors wherein it often highlighted microlumina. Aside from AE1/AE3 stainin
g and very infrequent wide-spectrum keratin and EMA reactivity, expression
of epithelial markers was not seen in anaplastic ependymomas. No carcinoemb
ryonic antigen (CEA) positivity was noted in any case. Collagen IV reactivi
ty was limited to tumor cell-stroma interfaces. Although variable, S-100 pr
otein and GFAP staining is seen in all ependymomas, particularly in true an
d perivascular pseudorosettes. Widespread reactivity for keratin AE1/AE3 co
rresponds closely to the pattern of GFAP staining. Significant staining for
other keratins or for CEA is inconsistent with a diagnosis of ependymoma.
EMA reactivity is largely limited to luminal staining of rosettes and tubul
es.