These images are both from placentas with preterm labor at 34 week gestation with similar birth weights, one with and one without chorioamnionitis. After looking at the complete case, I diagnosed the placenta without chorioamnionitis as having advanced villous maturation for gestation. From the very limited sample above, would anyone else venture such a conclusion, and if so which image is advanced, the top or the bottom. I selected the images from comparable areas from the slides, and tried to avoid the variation that occurs with spiral artery flow in the placentone.
I often hear obstetricians state that chorioamnionitis causes preterm labor. I disagree. I don’t doubt that once a patient has chorioamnionitis, or once a monkey uterus has been injected with bacteria, that labor will progress. My concerns are that approximately a quarter of patients with preterm labor do not have chorioamnionitis, antibiotics do not have much tocolytic effect, and there is no mechanism that explains why some patients acquire chorioamnionitis.
Proposed mechanisms for developing chorioamnionitis include low grade endometritis prior to pregnancy, abnormal vaginal flora such as bacterial vaginosis, high levels of ureaplasma or even trichinosis, and acquired or genetically weakened defense mechanisms against infection ascending from the uterus. In sheep, hormonal changes can lead to cervical labor without uterine labor. An equivalent isolated cervical labor in humans might provide the vulnerability for the ascent of vaginal microorganisms.
In sheep, the lamb’s secretion of cortisol causes maturational changes and reduces the progesterone estrogen ratio in the ewe that initiates the myometrial cell cascade that leads to labor. Unfortunately, the mechanism in humans is more complex. A human mechanism that would lead to preterm labor based on fetal stress would seem to be adaptive, for example in response to utero-placental ischemia. There is some clinical basis for this as I can recall studies using low abdominal diameter to predict preterm labor. Dr. Fred Krauss made the observation some time ago that preterm labor seems to divide itself into those cases with chorioamnionitis and those with advanced maturation or ischemic changes of the villi. Certainly, just in a day to day reading of placentas this observation seems borne out. A formal study would need to have strict clinical criteria for determining gestational age, and be “blinded” to the inflammation on the slide. Then using either measurable criteria or comparison of multiple pathologists reading the “blinded” slides, the hypothesis of a maturational villous difference between types of preterm labor could be tested. The outcome would likely need to be stratified by gestation.

umbilical vein injury, follow-up acute atherosis

The photomicrograph is from one of the cases for the perinatal care committee meeting at one of the hospitals that sends us placentas. This previously uncomplicated term pregnancy required an emergency Cesarean section for non-reassuring fetal heart rate tracing. The infant Apgars were 1 at 1 minute and 5 at minutes. The loss of muscle in the section of umbilical vein can be found on random sections of umbilical vein in uncomplicated pregnancies. I have more examples and a discussion on the web site (pediatricperinatalpathology.com) under umbilical cord hemorrhage. The unusual feature in this case is the subendothelial pink material. This could be the lesion that caused underlying ischemic atrophy of the media, or it could be evidence of an active injury of endothelium with fibrin and serum protein. I can not directly relate the lesion to the history of fetal distress, but is tempting to think that weakness in the media could lead to kinking and collapse of the lumen with fetal distress.

More on acute atherosis without preeclampsia: Yesterday, I signed out a placenta with an old retroplacental hemorrhage with overlying infarction of 40% of the surface (essentially an old abruption or premature placental separation). This mother had acute atherosis in a previous pregnancy with multiple infarctions, a second pregnancy with multiple placental infarctions, and the current case which did not have infarctions, but had this separation at 31 weeks. I will post a discussion of retroplacental hemorrhage on the web site soon.

immature intermediate villi at term

On all three parenchymal samples, this placenta from an uncomplicated term pregnancy had numerous villi with clear channels. This type of villus with channels has been designated immature intermediate villus by Kaufmann, and should be very infrequent by term. (This villous terminology can be found in Pathology of the Human Placenta by Benirschke, Kaufmann, and Baergen.) The infant was just above the 10 th percentile for birth weight and the placenta was small at 330 g., an 8.2 fetus to placenta ratio, which is abnormal. This villous appearance could be mistaken for hydrops, but I think the low placental weight and numerous channels at term distinguish it. Immature intermediate villi are precursors to the development of stem villi, and their persistence may be a marker for a lack of growth of the placental villous tree. However, there is no real data. As usual, all I could do was write a comment: “There are numerous immature intermediate villi present at term. The significance of this observation is unknown”.

eosinophilic streaks in membrane decidua

This image is from the membrane sample of a 33 week gestation infant with preterm labor (10x objective). There is an eosinophilic streak parallel to the chorion in the superficial decidua. This is not an uncommon finding. Is this old hemorrhage, fibrinoid from above chorion, old coagulative necrosis of the decidua, ruptured secretory gland material or seepage of protein from capillaries? Immunostains for fibronectin, fibrin etc. could narrow the type of material. Without hemosiderin, it is hard to prove old hemorrhage. There is no contact with chorion to suggest fibrinoid which can be prominent at the junction. Superficial decidual necrosis is common but usually includes the chorion epithelium, and does not leave a layer of intact decidua above it. Secretory gland material usually has a lighter pink more fluid appearance, and would not be linear. The presence of lymphocytes in the material suggests possible cell injury perhaps from natural killer cells. Anyone know what causes this common appearance?

Membranes in retroplacental hemorrhage/abruption

I have been reviewing cases of retroplacental hemorrhage/ abruption. As a result, I have become more conscious of the spiral arteries in the membranes away from the basal site of hemorrhage. I recently came across the above photographed case from a 20 week gestation stillborn with a 20% older retroplacental hemorrhage with adherent hematoma that had marked congestion and intravillous hemorrhage, and a basally directed neutrophil response. This size separation alone would not be lethal. The vessels in the membranes showed multiple laminated non-occlusive thrombi. The vessels are dilated and I can not be certain whether they are arteries or veins. There is a small amount of decidual hemorrhage. Could this be a case of maternal thrombophilia and abruption? Does thrombotic disease cause abruption by venous thrombosis and backpressure, or by arterial thrombus and subsequent hemorrhage into a basal infarction? Are these thrombi simply epiphenomenon of the abortion/ very preterm labor process?

Acute atherosis, early

I was looking at membranes from a mother with preeclampsia, and I guess I was just paying more attension, but certainly looks like the endothelium is lifted in the spiral arteries. In the first photograph there is even a small area of darker, fibrinoid appearing, condensation. This does not prove that acute atherosis is a lesion of increased endothelial permeability, but it does support the idea. There was acute atherosis in other arteries.

Surface Chorionic Vasculitis

Today I had a case of what appears to be insudation of protein or possibly mural fibrin in the superficial chorionic vessels with acute inflammation. The lesion has some resemblance to acute atherosis or TTP. This placenta is from a 25 week, 825 g birth weight infant with purulent chorioamnionitis, but not very intense three vessel funisitis or chorionic vasculitis, at least in terms of neutrophil density. The membranes show a marked thickening of the amnion connective tissue with neutrophils and neutrophil debris.
This vessel lesion is very distinctive, although it probably falls under the SPP category of fetal inflammatory response with thrombus. There must be specific factors causing this pattern of vascular injury. The localization suggests a direct effect either from surrounding inflammatory cells, or even amniotic fluid components. Serum factors may be detectable in umbilical vein blood. Serum factors injuring this vessel (one of several seen in this placenta) might be capable of causing similar vascular injury in the fetus, especially if the umbilical venous blood adjacent to the lesion is going directly to the fetal brain via the foramen ovale. Dr. Redline and colleagues were able to demonstrate an association of chorionic non-occlusive thrombi with cerebral palsy and other neurologic impairment1. I could not tell from this article, since it was retrospective based on neurologic impairment, the predictive value of thrombi in the chorionic vessels for neurologic impairment. I am willing to bet it is high.
The Society for Pediatric Pathology created provisional guidelines for staging and grading chorioamnionitis2. Dr. Redline led the group based on his experience and publications investigating chorioamnionitis in very low birth weight infants. These guidelines were meant to be validated through further research. The problems with obtaining research and HIPPA protocols for follow-up are daunting, and I know I shall not pursue this case. However, these advanced inflammatory placental lesions are still an area in need of better clinical pathological correlation.


1. Redline RW, Wilson-Costello D, Borawski E, Fanaroff AA, Hack M. Placental lesions associated with neurologic impairment and cerebral palsy in very low-birth-weight infants. Arch Pathol Lab Med 1998;122(12):1091-8.
2. Redline RW, Faye-Petersen O, Heller D, Qureshi F, Savell V, Vogler C. Amniotic Infection Syndrome: Nosology and Reproducibility of Placental Reaction Patterns. Pediatr Dev Pathol 2003.

Acute Atherosis

Acute atherosis not in preeclampsia.

I had a case today, and periodically have had other cases, of the unexpected finding of acute atherosis in the spiral arteries in the placental membranes. This was a case of preterm premature rupture of membranes, and the infant was borderline small but there was no evidence of preeclampsia in the electronic medical record. I am puzzled as to what this finding means if anything to the future of the child or mother.

What is acute atherosis?

The lesion is most often found in pre-eclampsia but has been reported in unexplained intrauterine growth retardation and in a case of SLE. Acute atherosis appears to be a lesion of insudation of serum proteins including lipoproteins (hence foam cells) into the spiral artery media. Some have likened the lesion to that caused by angiotensin There are high concentrations of molecules in the renin angiotensin system in the decidua. However, injury to and serum leakage through the endothelium is perhaps a more plausible mechanism given the wide spread endothelial injury in pre-eclampsia. An understanding of the lesion should answer two critical questions: 1) why does the lesion occur only in spiral arteries, and 2) why is the lesion present in only some cases of preeclampsia?
Even large studies of maternal arteries have not found acute atherosis in other organs. It is not for lack of looking, e.g. 677 maternal autopsies reported by Sheehan and Lynch1. Perhaps it has something to do with the hormonal responsiveness of these vessels that constrict with menstruation, as elegantly demonstrated in endometrial transplants into the anterior chamber of monkey eyes. At the least, the arteries are unusual in that they shed with each menstruation and are surrounded in pregnancy by decidual cells.
Acute atherosis is present in only a minority of patients with preeclampsia. This is unlikely to be a sampling error, although not all membrane samples contain many or even any spiral arteries. I presented an abstract at our MAPS meeting showing little gain in diagnosis with 4 samples compared to one sample of membrane. Subsequently Yasser Morgan and I demonstrated that we could identify acute atherosis using a dissecting scope of the membranes stretched over a white card. Even with this technique spiral artery lesions may not be present. While a single sample of membranes may miss some cases of acute atherosis, the evidence suggests that in most cases the lesion is not really present. Perhaps acute atherosis is a marker for yet another preeclampsia associated angiopathic protein, like sFlt1 and endoglin.
Note to pathologists: A colleague tells me he never sees it! I suggest to novice pathologists that they should scan the entire membrane slide at low power for vascular lesions as part of the routine approach to placental slides. With experience acute atherosis will stick out like a pink highlighted text. I make the diagnosis if the bright pink fibrinoid of the media is present, and do not require foam cells. The diagnosis is more difficult in the basal decidua because most spiral arteries have been destroyed by trophoblastic invasion and are only fibrin lined shells lined with trophoblast. However, distinct acute atherosis does occur in the basal decidua, likely in vessels not invaded by tropphoblast.


1. Sheehan HL, Lynch JB. Pathology of Toxaemia of Pregnancy. Baltimore: The William and Wilkins Company; 1973.