The utility of immunohistochemistry and in situ hybridization in placental pathology

It has long been recognized that routine histologic examination of the placenta has limitations, especially with regard to the diagnosis of infectious diseases and the concomitant cytokine response that may cause severe in utero fetal damage. Immunohistochemical testing of the placenta in such situations can be very useful in terms of identifying the infectious agent as well as in demonstrating a marked increase in cytokines such as tumor necrosis factor alpha and interleukin 8, produced primarily by cells native to the villi and fetal membranes. One hundred placentas (20 normal childbirths, 20 with severe neonatal morbidity of known cause, 25 idiopathic stillbirths where autopsy material was available, 35 with severe idiopathic neonatal morbidity) were examined for a wide variety of infectious diseases and cytokine production. An infectious agent was evident in 19 (76%) of 25 placentas from stillbirths and 28 (80%) of 35 placentas associated with idiopathic severe neonatal morbidity. No infectious agent was noted in the placentas from normal childbirths or cases of known neonatal morbidity. The most common infectious agent was coxsackie virus (51% of infections) followed by bacterial infections (24% of infections). The same infectious agent found in the placenta was found in the corresponding autopsy material from the stillbirths, with the spleen containing the greatest number of infected cells. There was a strong correlation between the number of cells demonstrating cytokine expression (tumor necrosis factor alpha and interleukin 8) and the presence of an infectious disease in the placenta and stillborn. No histologic feature was associated with an in utero infection. Immunohistochemical testing of placentas gives much insight into their structure and function, including, besides infectious disease detection, the marked diversity of function of trophoblasts, the rarity of committed B cell response, and the strong potential of contractility of villi.