Phyllis C. Huettner
I. NORMAL ANATOMY. The normal, unfixed term placenta weighs 350 to 550 g, trimmed of membranes and cord. The placenta consists of three parts: fetal membranes, umbilical cord, and placental disk.
The fetal membranes insert at the edge of the disk and envelop the fetus and amniotic fluid. Microscopically, they are composed of a cuboidal amniotic epithelium with underlying connective tissue, a chorionic layer (composed of connective tissue, intermediate trophoblast, and degenerated villi), and sometimes a layer of decidua (gestational endometrium) (e-Fig. 37.1).*
The umbilical cord is composed of two umbilical arteries (e-Fig. 37.2) and one umbilical vein (e-Fig. 37.3) surrounded by Wharton’s jelly, a paucicellular connective tissue matrix. Its outer surface is lined by a layer of cuboidal amniotic epithelium.
The placental disk is typically oval and microscopically composed of chorionic villi surrounded by maternal blood in the intervillous space. The chorionic villi contain vessels of the fetal circulatory tree embedded in mesenchymal stroma (e-Fig. 37.4). A layer of cytotrophoblast encompasses the villous stroma, and this is surrounded by a layer of syncytiotrophoblast that is in contact with the intervillous space. The maternal surface of the placental disk, which is adjacent to the uterine wall, contains variable amounts of fibrin, intermediate trophoblast, and decidua. The umbilical cord inserts near the center of the placental disk, and branches of the umbilical cord vessels arborize over the shiny fetal surface of the disk. Microscopically, the fetal surface of the disk is lined by amnion and chorion.
II. GROSS EXAMINATION, TISSUE SAMPLING, AND HISTOLOGIC SLIDE PREPARATION
A. Fetal membranes. The fetal membranes should be assessed for completeness. The presence of green, blue, or brown staining, indicating meconium or hemosiderin staining, should be noted. The membranes should be inspected for amniotic bands, nodules of amnion nodosum or squamous metaplasia, and hemorrhage. The distance from the insertion to the disk edge should be measured as this gives a rough estimate of where the placenta was implanted in the uterus. A strip of membranes should be cut from the rupture site to the disk insertion site, one end grasped by a forceps, and the strip rolled around the forceps; this membrane roll should be eased off the forceps into formalin. At least one cross-section of this membrane roll should be examined.
B. Umbilical cord. The length of the cord is measured, including any detached segments. Note should be made of marginal insertion (at the disk edge), or velamentous/membranous insertion (into the membranes). Abnormalities of cord color (meconium staining) should be noted. Focal abnormalities such as stricture, hematoma, knots, nodules, plaques, or amniotic bands should be noted and measured. Cross-sections should be made at regular intervals throughout the cord length, and the number of vessels and the presence of thrombi should be noted. At least two cross-sections of cord should be examined microscopically, avoiding the area just above the insertion site where the two umbilical arteries fuse.
C. Disk. The disk should be assessed for completeness and measured in three dimensions. After examining and removing the membranes and cord, the unfixed disk should be weighed. The fetal surface of the disk, which is covered by amnion and chorion, is examined for the same abnormalities as the membranes. The branches of the umbilical cord vessels are examined for lacerations, calcifications, and thrombi. The maternal surface of the disk is examined for retroplacental hematomas, indentations, or other focal abnormalities. The disk is then sliced at 1-cm intervals, and each slice is examined and palpated. The color, location (central vs. peripheral), size, texture (firm vs. spongy), demarcation (whether well circumscribed or ill defined), and number of all focal lesions are recorded. An estimate of the percentage of the placental parenchyma involved by each type of process is noted. Any organized blood clot in the container is measured. At least two sections of central placenta that include fetal and maternal surfaces as well as sections of focal lesions should be submitted.
D. Multiple gestation. Placentas from twin gestations may have completely separate disks, a fused disk with two gestational sacs, or a fused disk and just one gestational sac (monoamniotic). If present, the dividing membranes should be inspected. The percentage of placental parenchyma associated with each twin should be determined. A roll of the dividing membranes should be made as for the fetal membranes, and at least one cross-section of the roll should be examined microscopically to confirm the gross and ultrasound impression of chorionicity. The chorionic plate vessels should be inspected for anastomoses. In monochorionic or monoamniotic placentas, the type of anastomoses (artery to artery, artery to vein, vein to vein) should be investigated by air injection and recorded, keeping in mind that arteries cross over veins. Note should be made of unpaired large vessels as these likely represent areas of physiologically important deep artery-to-vein anastomoses.
III. DIAGNOSTIC FEATURES OF COMMON DISORDERS OF THE PLACENTA
A. Fetal membranes
1. Meconium. With recent meconium passage the fetal plate and membranes will be yellowish-green and slimy. With longstanding meconium passage, the membranes, fetal plate, and even the umbilical cord will be dull brown. Microscopically, the amniotic epithelium is stratified and tufted with pyknotic nuclei. There is marked edema between the amnion and chorion. Macrophages in this area are filled with yellowish-brown, waxy, meconium pigment (e-Fig. 37.5). Pigmented macrophages may also be seen in the chorion and decidua.
Meconium passage may be the result of neurologic maturity in the fetal intestines, but may also be associated with chronic in utero hypoxia, or stressors closer to delivery. Rarely, meconium induces vascular necrosis in umbilical vessels.
2. Hemosiderin deposition may stain the fetal plate and membranes brown or green. Often there is old blood clot where the disk meets the fetal membranes. Circumvallation (see Section III.D) may also be present. Microscopically, the membranes do not show the epithelial stratification, tufting, and edema seen with meconium. Membrane macrophages contain refractile pigment that is positive with an iron stain. Sometimes a layer of hemosiderin is deposited in the basement membrane beneath the amniotic epithelium (e-Fig. 37.6). Diffuse chorioamniotic hemosiderosis is an indication of chronic peripheral separation and is associated with oligohydramnios in the absence of membrane rupture, preterm delivery, and chronic lung disease.
3. Amnion nodosum forms small, grayish-white, discrete nodules or plaques that may occur anywhere on the cord or fetal membranes but are most common on the fetal plate near the cord insertion. These nodules, which represent vernix caseosa, are easy to remove with a cotton swab. Microscopically, they consist
of fetal squamous cells, amniotic epithelial cells, and sometimes fetal hair (e-Fig. 37.7). Sometimes nodules of amnion nodosum become reepithelialized by contiguous amniotic epithelium.
Amnion nodosum is the result of oligohydramnios. It therefore serves as a marker of conditions such as renal agenesis that may cause decreased fluid production, and can also alert to possible complications of oligohydramnios such as pulmonary hypoplasia and limb positioning abnormalities.
4. Squamous metaplasia. Plaques or nodules of squamous metaplasia are present in nearly every placenta. They are tan-white and may be seen anywhere on the cord, membranes, or fetal plate of the disk but are most common on the fetal plate near the cord insertion. Squamous metaplasia is difficult to remove with a cotton swab. Microscopically, squamous metaplasia in the placenta is identical to that present elsewhere in the body. Squamous metaplasia is not clinically significant.
5. Amniotic bands may appear as shredded amnion on the fetal surface of the placenta or as thin adhesion-like threads connecting one part of the fetal plate to another, connecting the fetal plate to the umbilical cord, or attached to the fetal digits or other fetal parts. Microscopically, they are composed of fibrous tissue often with no attached amnion. Amniotic bands are associated with a wide variety of abnormalities in the fetus including digital amputations (e-Fig. 37.8), cleft lip and palate, and body-wall defects. Characteristically, the defects are asymmetric, no two cases are identical, and the spectrum of defects in any given case does not fit into a recognizable genetic syndrome. Amniotic band syndrome only extremely rarely recurs in a subsequent gestation.
6. Fetus papyraceous. Occasionally, a mummified remnant of an embryo from much earlier in gestation will be compressed on the fetal membranes (e-Fig. 37.9), referred to as fetus papyraceous. It may represent an unrecognized twin gestation or may be the result of selective termination of a higher order gestation.
B. Umbilical cord
1. Length abnormalities. The normal umbilical cord is 55 to 60 cm long. Short cords (<35 to 40 cm) occur in about 5% of cords; they are usually associated with conditions of decreased fetal movement such as amniotic bands, oligohydramnios, body-wall defects, fetal neuromuscular disorders, and arthrogryposis. Long cords (>80 cm) occur in about 5% of cords; long cords are associated with an increased likelihood for encirclement around the fetal neck or other body part, knots, cord prolapse, and marked cord twisting.
2. Single umbilical artery (SUA). The incidence of SUA (e-Fig. 37.10) is about 1%, and SUA is about 4 times more common in twins. There is a strong association between SUA and congenital malformations, mortality, and low birth weight. SUA is likely an acquired defect as the incidence is lower earlier in gestation; in fact, the absence of the artery may be the cause of associated malformations. In some cases of SUA, a small, atrophic remnant of the second artery can be seen (e-Fig. 37.11). SUA is also strongly associated with other cord and placental abnormalities such as velamentous insertion, marginal insertion, extrachorialis, and shape abnormalities.
3. Abnormal cord insertion
a. Marginal insertion. In marginal insertion, the umbilical cord inserts at the edge of the disk (e-Fig. 37.12). This occurs in 6% to 18% of placentas and is not clinically significant.
b. Velamentous insertion. In velamentous insertion, the umbilical cord inserts into the fetal membranes (e-Fig. 37.13). This insertion abnormality is seen in about 1% of placentas. In about 75% of these cases, the vessels branch within the membranes before the branches insert into the placental disk;
in 25% of cases, the cord vessels run through the membranes without branching. Because the branches of the umbilical cord are not protected by Wharton’s jelly, they are at risk for compression, thrombosis, and laceration.
4. Umbilical cord knots. About 1% of umbilical cords have a true knot (e-Fig. 37.14), which may be loose or tight. Differences in the diameter and color of the cord on either side of the knot should be noted. Cords with size differences, particularly with a dusky appearance between the knot and the fetus, are likely to be associated with an adverse outcome. The cord on either side of the knot should be examined microscopically for thrombi, a feature that suggests a clinically important knot. The knot should be untied in the fresh state to look for persistent grooving of Wharton’s jelly, a feature that suggests chronic tightening. The fetal mortality rate for umbilical cord knots is reported to be between 5% and 11%.
5. Umbilical cord coiling. The normal cord has a left-handed twist, a feature that is thought to increase turgor, preventing compression of cord vessels. A coiling index can be determined by counting the number of complete turns divided by the length of the cord (which can be compared to a standard reference). About 5% of cords will have no twist, a finding that has been correlated with increased fetal mortality, operative delivery for fetal distress, abnormal karyotype, preterm delivery, and fetal heart rate abnormalities. Hypocoiled cords, with a coiling index below the 10th percentile, and hypercoiled cords, with a coiling index above than 90th percentile, have also been associated with a variety of adverse outcomes.
6. Umbilical cord stricture is a focal area of cord that is markedly narrowed with a depletion of Wharton’s jelly, fibrosis, and often thrombosis of the umbilical cord vessels. The most common location for a stricture is the area adjacent to the umbilicus. There is a high association between cord stricture and stillbirth, especially early in gestation. Most cases also show excess twisting.
7. Umbilical cord hematomas occur once in every 5500 deliveries, although small hematomas have been documented in 1.5% of cases following ultrasoundguided cord blood sampling. Hematomas nearly always occur in the portion of cord closest to the fetus and present as a fusiform swelling with a dark, hemorrhagic color. It is important not to confuse a true hematoma, which will be obvious at the time of delivery, with blood accumulation in the cord as a result of clamping, blood drawing, or other manipulation during or after delivery. Large hematomas have a perinatal mortality rate of 50%, whereas small ones have very low fetal morbidity or mortality.
C. Circulatory disorders
1. Infarcts are firm and well circumscribed, with one edge usually abutting the maternal surface of the disk (e-Fig. 37.15). Early infarcts are red whereas older infarcts are white. Sometimes there is central hemorrhage. Microscopically, there is collapse of the intervillous space, which crowds the villi together (e-Fig. 37.16). Depending on the age, the trophoblast may be pale and degenerative (recent) or show little staining with only ghost outlines of villi (longstanding).
Infarcts are common, occurring in 10% to 25% of term placentas from normal pregnancies, typically at the periphery. Extensive infarction, infarcts >3 cm, infarcts that occur in the central placenta, and infarcts in the first or second trimester of pregnancy are clinically significant and often indicate significant underlying maternal disease such as pre-eclampsia, collagen vascular disease, or a hereditary thrombophilic condition. Infarcts are caused by an interruption in the maternal blood supplied by a given spiral artery to an area of placental tissue.
The normal placenta can lose 15% to 20% of the parenchyma without adversely affecting the fetus. However, in placentas that are chronically underperfused, such as in pre-eclampsia, a lesser degree of infarction may be clinically significant. Extensive infarction may cause fetal hypoxia, intrauterine growth restriction, periventricular leukomalacia in preterm infants, or fetal death.
2. Massive perivillous fibrin deposition. When large amounts of fibrin are deposited in the placenta, a firm, white or yellow, slightly gritty, ill-defined mass is formed (e-Fig. 37.17). Often small pockets of red, villous tissue are interspersed within strands of white fibrin. Microscopically, there is expansion of the intervillous space by eosinophilic fibrinoid material pushing the villi away from each other (e-Fig. 37.18); clusters of cytotrophoblast proliferate in the fibrinoid material, and the villi entrapped in this fibrinoid material become ischemic. The amount of fibrin deposition needed for diagnosis of massive perivillous fibrin deposition or to be associated with an adverse outcome for the fetus is not well established. Some studies have found that entrapment of 20% of the central-basal terminal villi is associated with adverse outcomes (Arch Pathol Lab Med. 1994;18:698); others have defined clinically significant fibrin deposition as fibrin extending from the fetal to maternal surface and entrapping 50% of villi on at least one slide (Pediatr Dev Pathol. 2002;5:159). Massive perivillous fibrin is associated with intrauterine growth restriction, periventricular leukomalacia in preterm infants, and fetal death, and may recur in subsequent pregnancies.
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