Anomalous immunostaining of 'optically clear' nuclei in gestational endometrium. A potential pitfall in the diagnosis of pregnancy-related herpesvirus infection.

A distinctive morphologic alteration originally described as nuclear "clearing" has been observed in endometrial epithelium during pregnancy. Affected nuclei have a clear center and a rim of marginated chromatin, imparting a "glassy" appearance reminiscent of herpesvirus inclusions. We observed this change in gestational endometrium attached to the membranes of an otherwise normal-term placenta. Because of the morphologic suggestion of herpesvirus infection, immunoperoxidase studies using the avidin-biotin method were performed, resulting in intense staining of nuclear inclusions. An identical pattern of nuclear staining was also noted in negative controls. This anomalous staining reaction was replicated with the streptavidin-biotin method but not with the peroxidase-antiperoxidase method. Furthermore, nuclear staining was abolished after sequential preincubation with free avidin (0.05%) and free biotin (0.05%). Using the peroxidase-antiperoxidase method, positive nuclear staining was identified with monoclonal antibodies to biotin. Similar results were obtained in nine additional cases of optically clear nuclei associated with term placentas. We conclude that staining of optically clear nuclei is the result of avidin and streptavidin binding to intranuclear biotin. This anomalous staining pattern could potentially result in the misdiagnosis of herpesvirus infection.