A variety of studies have considered the impact of biologic factors on the staining patterns of cytologic
specimens evaluated by IHC. Examples of unexpected IHC staining patterns in cytologic specimens include the
impact of exfoliation on individual cell expression of intermediate filaments.28-30 In certain aspirates
and effusion samples cells which generally express cytokeratin intermediate filaments on tissue biopsies
will stain negatively for this intermediate filament and become immunoreactive for vimentin when obtained
from a fluid into which they have exfoliated. Vimentin expression appears to reflect the up-regulation of
the intermediate filament which is associated with cell attachment, a feature regularly observed in
malignant epithelial cells maintained in cell culture. Another example of a biological factor influencing
IHC in cytology specimens is the ability to immunostain factor VIII related antigen in malignant epithelial
cells due to phagocytosis of this protein in areas of hemorrhagic tumor necrosis. Although immunolocalized
to the tumor cells, in this situation, the factor VIII related antigen staining is not indicative of
endothelial differentiation and should not lead to a mis-classification of the lesion as a malignant
vascular neoplasm. Prostate specific antigen staining, for example, was originally regarded as specific for
prostate cancer, but has now been identified in other neoplasms such as parotid oncocytoma31 and lung
tissues.32 Even the presumed more specific prostate specific membrane antigen has been now identified in
tumor vascular endothelial cells of a variety of malignancies.33
