According to the guidelines of the Royal College of Pathology, samples of diagnostic value removed from the human body should be histologically examined, with only a few exceptions.¹ One of the exceptions is the healthy human placenta, but even with valid indications the human placenta is one of the most underexamined specimens.² There is also evidence that the quality of reports on the investigation of the placenta is very variable.³ According to a recent study, there is a considerable discrepancy rate in the diagnosis of placental disease, and it is common for general surgical pathologists not to recognise placental lesions that may have clinical relevance.⁴ In this best practice article, we summarise those circumstances in which it is recommended that the placenta should be examined, the minimum criteria of sampling, and the acknowledged clinicopathological correlations.

“It is common for general surgical pathologists not to recognise placental lesions that may have clinical relevance”

Lesions of the placenta often reflect or explain the condition in which the baby was born and some have clinicopathological implications. However, in most cases, there is no clinicopathological relevance to a placental examination, such as in the case of normal pregnancy and delivery.

CLINICAL APPROACH

What do we expect from the pathological examination?

The placenta forms a functional unit between the mother and the fetus. Therefore, any pathological event that concerns the mother or the fetus will influence the normal function of the placenta, occasionally resulting in morphological change. Severe abnormalities of the placenta may lead to adverse fetal outcome. However, placental lesions are not necessarily the cause of unfavourable outcome, and some structural changes may be the consequences of poor fetal condition. The placenta is an easily available specimen and the costs of a routine pathological examination are moderate.

The benefits that can be expected from the examination include revealing the aetiology of stillbirth, preterm delivery, intrauterine growth restriction (IUGR), and neurodevelopmental impairment. It may be possible to decide whether the pathological condition that endangered the well being of the fetus was an acute or a chronic process.^5,6

In the case of twin pregnancies, the type of twinning can be identified and pathological aspects of twin pregnancy (for example, twin-to-twin transfusion syndrome) can be studied.

Conditions with the risk of recurrence can be recognised, resulting in adequate treatment and preventive measures during subsequent pregnancies.

Placental examination may have medicolegal aspects—for example, concerning the aetiology of longterm neurodevelopmental sequelae or the approximate timing of an intrauterine death.^7,8

Which placentas should be examined?

There are different approaches to the examination of the placenta. It would produce a pointless increase in workload if all placentas, including those from normal pregnancies and normal deliveries resulting in a healthy infant, were examined in a routine pathology laboratory setting.

Because it is the decision of the midwife and/or obstetrician which placentas to send to the pathology department, a clinically oriented approach (fig 1) may be used to define the indications for histopathological examination.

Referral is not indicated for:

• cholestasis of pregnancy

• hepatitis B, human immunodeficiency virus, etc

• other maternal disease with normal pregnancy outcome

• normal pregnancy

• placenta praevia

• postpartum haemorrhage.

A RATIONAL SORTING OF THE REFERRED PLACENTAS

Figure 2 is an algorithm for selecting which of the referred placentas should be subjected to further study. Figure 3 contains a recommendation for sampling the placentas based on the clinical context.

NORMAL VARIANTS

As mentioned above, many features can be judged only in the clinicopathological context. This is partly because of the loose correlation between some histological changes and clinical symptoms, and partly because of the large reserve capacity of the placenta.

To record the macroscopic appearance of the placenta we recommend the use of a worksheet as shown in fig 4. This proforma can be useful to describe normal placentas; however, each abnormality should be documented individually.

Umbilical cord

The normal length of the umbilical cord at term varies between 40 and 70 cm and cords of less than 32 cm are considered to be short and those more than 100 cm are considered long. The importance of length and coiling should be treated cautiously, because the proportion of the umbilical cord received in pathology laboratories varies and is thus not reliable. Umbilical cords normally show a degree of coiling. The normal coil index is said to be one coil/5 cm.^9,10 The normal cord contains three vessels, and this has to be assessed at least 5 cm from the placental insertion.¹¹ False knots may be the site of thrombosis, or rarely bleeding, but most often they have no clinical relevance.

Embryonic remnants of the vitelline duct and urachus are normal findings. Cysts may arise from these vestigial remnants. It may be necessary to differentiate the embryonic remnants of the cord from teratomas and haemangiomas.¹²

Extraplacental membranes and the fetal surface^12–14

The importance of circummarginate and circumvallate placentas is uncertain, although an association with IUGR and acute and chronic maternal haemorrhage has been proposed in circumvallate placentas. Amnion nodosum (granular grey/white nodules, consisting of keratin and vernix) are a sign of oligo/anhydramnios, but squamous metaplasia of the amnion is a normal feature.

A small amount of subchorionic fibrin deposition (Langhans fibrinoid) is not pathological, because it accumulates from eddying of the intervillous flow.

Placenta

A low placental weight is found in “small for gestational age” placentas. Normal values of fetal to placenta weight ratio change during the course of gestation, and vary between 1 at 14 weeks and 7.23 at term. Hydrops or congestion can result in a high placental weight, but the placenta weight can vary to some degree (a table of normal values can be found in Benirschke and Kaufmann¹³). Deviation from the round or oval shape such as an irregularly shaped, bilobed, or multilobed placenta can be attributed to disturbed implantation or uterine abnormalities, but it can be assessed only in the clinicopathological context. Increased calcification has been mentioned in association with maternal smoking and high socio-economic status, but the feature itself has no clinical relevance.

Minor perivillous fibrin deposition is almost always present in term placentas. This is of no clinical relevance if marginal, or if it does not exceed 10% of the villous tissue. A range of values is found in the literature with regard to the amount of the villous tissue loss required to define whether infarction or perivillous fibrin deposition is “extensive” or relevant—that is, large enough to account for adverse fetal outcome. The reported percentage of minimal villous tissue loss ranges from 10% to 30% in the case of significant placental infarcts and 20% to 30% in perivillous fibrin deposition. In general, there is no clinical relevance if the lesion is single, marginal, and/or involves less than approximately 5% of the villous tissue. Obviously, the functional reserve capacity of the placenta depends not only on the quantity, but also on the quality of the uninvolved tissue and the original size of the placenta. In the case of a small placenta, a smaller amount of parenchymal loss can lead to fetal demise or morbidity.

X cell islands (extravillous cytotrophoblast islands, X-cell proliferation) are considered to be a normal feature.

The origin of septal cysts is unknown. They are reported to occur more frequently in oedematous placentas, but are of no clinical relevance.¹³

Examination of twin placentas

Twin placentas should be labelled after the delivery to identify which cord belongs to which fetus. The examination of placentas from multiple gestations should establish the chorionicity of the sample and whether there are signs of twin-to-twin transfusion syndrome. Separated twin placentas have to be examined in the same way as those of singletons. Fused placentas can be monochorionic or dichorionic. The dividing membrane should be studied to identify the chorionicity. The dividing membrane in monochorionic pregnancy is thin and translucent (with no chorionic layer), whereas that of a dichorionic placenta is thicker, because it contains two chorionic layers between the amniotic sacs. The dividing membrane can be sampled as a membrane roll or in “T section” form. A properly oriented T section is the best sample to prove chorionicity. Fetal vessel anastomoses and inter-twin blood transfusion occur normally in monochorionic placentas. Imbalance in the blood flow may lead to acute or chronic twin-to-twin transfusion. Acute transfusion occurs either during labour or after the death of either of the twins, and frequently results in severe neurological damage or the death of the co-twin. Chronic twin-to-twin transfusion manifests as discordant fetal growth, oligohydramnios in the donor, and polyhydramnios in the recipient fetus, and is often associated with poor fetal outcome.¹⁵ Arterio–arterial anastomoses (AAA) may have a protective role against chronic twin-to-twin transfusion syndrome, but may be the route of acute blood loss after compromise or the death of one twin. Veno–venous anastomoses (VVA) are associated with poor outcome.¹⁶ The anatomical background of chronic twin-to-twin transfusion syndrome seems to be a unidirectional arteriovenosus shunt between the donor and the recipient twin. Injection studies can be performed in fresh specimens to clarify the type of the anastomosis.¹⁷ In fixed placentas, arteries may be identified by the fact that they are always superficial to the veins. Arterio–venous anastomosis (AVA) may be identified by the presence of an impaired vessel from one twin feeding an area drained by the co-twin. In monochorionic diamniotic placentas, it may be useful to record the sites of insertion and distance between the cord insertions, the relative size of the placental territories serving each twin, the number and minimum diameter of superficial anastomoses (AAA/VVA), and the number and direction of deep anastomoses (AVA).

“A properly oriented T section is the best sample to prove chorionicity”

It is recommended that fused dichorionic placentas should be separated. Evidence of a vanished twin might be found in singleton or twin placentas. This varies in appearance from an amorphous, fibrotic plaque to a well formed fetus papyraceous. Histological and x ray examinations are helpful to identify calcification.¹⁸

RECOGNISED CLINICOPATHOLOGICAL CORRELATIONS

Table 1 summarises the clinical relevance of placental abnormalities.

CONCLUSION

We recommend that relevant placentas are discussed regularly at perinatal mortality or morbidity meetings. This could reveal new clinicopathological correlations, would increase appreciation of the profession, and would serve team building and communication between the different medical teams. We have presented an algorithm of indications for placental examination and discussed the methods of histopathological examination. Common placental lesions with their clinicopathological correlation are reviewed. Our intent is to outline the acknowledged entities with their clinical consequences. Often, the clinicopathological correlation appears to be strong, significant, and well documented. In other instances, lesions may have a tendency to occur with clinical conditions and in the rest of the cases there is only an anecdotal association. A major problem with the literature related to the placenta is that most of it has been produced based solely on abnormal placentas, so that for many features it is not clear what is pathologically abnormal and what is a normal variant. Basic studies are necessary to analyse normal placentas statistically and to identify the normal variants of histological lesions during the course of pregnancy.

It is also apparent that because function depends on the reserve capacity of the placenta, several findings can be judged only in the clinical context: the importance of a particular lesion depends on its localisation and on the extent of the lesion (the proportion of the placenta involved and the size and the condition of the uninvolved placenta). Some features can be within normal limits in term placentas, whereas earlier in pregnancy they may be pathological. In addition, the assessment of the lesions is even more complex because several pathological conditions can coexist in the same placenta.