In placentas of noncomplicated pregnancies, the Hofbauer cells
disappear or become scarce after the fourth to fifth month of gestation.
Based on RT-PCR, ISH and histopathology findings described in the study, CDC researchers concluded that Zika virus replicates in fetal brain and placental tissues and Hofbauer cells
may play an important role in the dissemination or transfer of Zika virus to the fetal brain.
(a) and (b) Placental histopathological results showing a rather loose villous stroma with numerous foamy/vacuolated Hofbauer cells
. Periodic Acid-Schiff (PAS) stain; original magnifications: x200 (a) and x1000 (b).
 demonstrated p24 antigen within scattered Hofbauer cells
but not within trophoblast cells or vascular endothelium, in 5/19 term placentas (26%) from HIV-positive women.
We directly localized Zika virus negative-sense replicative intermediates in Hofbauer cells
of placenta and neural cells and neurons by using ISH.
(82) Immunohistochemical detection of ZIKV in maternal leukocytes, Hofbauer cells
, and fetal endothelial cells, along with demonstration of ZIKV replication in primary human placental macrophages in vitro, suggests transfer across the syncytiotrophoblast as the major route of fetal ZIKV infection.
Trophoblast and hofbauer cells
were stained with CD68.
CD163 and CD68 immunostains demonstrated intensely positive staining in the hyperplastic population of stromal cells of both secondary and tertiary villi, confirming their identity as stromal macrophages, or Hofbauer cells
. The CD163 highlighted the intensity of the Hofbauer cell
hyperplasia--in some villi, the macrophages were tightly packed and confluent (Figure 2, A through F).
Viral antigens were present in the maternal pulmonary system, and virus was detected in placental Hofbauer cells
(histiocytes), cytotrophoblast, fetal lung, circulating mononuclear cells, and liver macrophages (10).
Similar to placentas from infants with some congenital TORCH infections, placentas from second- and thirdtrimester infants with Zika virus infection demonstrate increased numbers of Hofbauer cells
within the stroma of chorionic villi.
The results also indicate that as in group 1, when in addition to hypervascularity other histologic features of diffuse preuterine placental hypoxia were present (delayed maturation, decreased extracellular matrix of chorionic villi, increased Hofbauer cells
, increased villous cytotrophoblasts), the frequency of clinical risk factors and abnormal outcomes is higher than that in pure chorangiosis (group 3), that is, placentas without the additional histologic findings mentioned in Figure 2 in which chorangiosis was most commonly focal.
The knowledge that, as pregnancy advances, terminal villi and syncytial knots become numerous, villous cytotrophoblasts and Hofbauer cells
become less visible, the number of vascular profiles decrease, and the extracellular matrix of chorionic villi becomes denser, is of little help in individual cases, and the pathologist's experience is what matters.