Section 1 -

Introduction Phyllis C. Huettner, M.D.

The placenta is an amazing organ. It undergoes rapid growth and profound changes in structure to supply the needs of a rapidly growing fetus. It serves as the lungs, gastrointestinal tract, circulatory, endocrine and excretory systems for the first 40 weeks of development. Placental examination can be very rewarding in determining the cause of an intrauterine or perinatal death. In a study of perinatal autopsies, placental abnormalities were found in 92% of cases. The cause of death was a placental or cord abnormality in almost a third of cases and in 16% of cases a placental or cord abnormality was a contributing factor to the death. Examination of the placenta may help explain the etiology of a preterm delivery, a congenital anomaly or other adverse neonatal outcome. Obstetrical management of subsequent pregnancies may be altered if conditions that show a risk of recurrence are identified on placental examination. Information that may help explain the outcome of a neurologically impaired child and be useful in the legal defense of these cases may be obtained from placental examination. In a general way, examination of placentas has provided insight into the pathophysiology of various important maternal and neonatal disorders. The information obtained from placental examination may be immediately useful in the care of a sick neonate and may also be useful to parents and pediatricians caring for impaired children later in life. In order to maximize the usefulness of placental examination, pathologists need to develop ways to ensure that the results reach and are understood by the neonatologists and general pediatricians caring for children and communicating most directly to parents, in addition to the obstetrician who sent the placenta for examination. Indications for Placental Examination The Practice Guideline for Examination of the Placenta was developed and endorsed by the College of American Pathologists in 1997. The Practice Guideline recommends that all placentas be examined briefly then triaged. Those that fulfill specific indications should be examined more completely, usually by a pathologist. The Practice Guideline recommends that the delivering doctor record the total cord length, number of cord vessels, disk dimensions, and estimated disk weight, integrity of maternal surface and abnormalities of the free membranes. This information, along with previous obstetric history, estimate of gestational age, route of delivery, birth weight, sex, one and five minute Apgar scores, maternal and fetal complications of pregnancy, labor and delivery, and indications for placental examination should be communicated with the examining pathologist. To address how well these guidelines are adhered to, Spence and Khong reviewed the medical records from nearly a thousand deliveries over a three-month period at a tertiary care center. Although conditions listed by the CAP guidelines as recommended or other were present in 53.8% of cases, in only 17.8% of these cases was a placental examination performed. The indications with the lowest rates of placental examination were meconium staining of amniotic fluid (9.7%), maternal fever (13.7%), suspected neonatal infection (24.8%), intrauterine growth restriction (26.7%), and maternal diabetes (29.2%). Less than a third of pathology requisition sheets correctly and completely listed the recommended maternal indications for examination and less than one-tenth of forms correctly and completely listed the recommended neonatal indications. Clearly we have much work to do to educate our clinical colleagues about which placentas need a complete examination and the importance of clinical history to the pathologist. Basic Examination The basic gross examination of the placenta can be performed on either the fresh or fixed organ; each has advantages and disadvantages. It is easier to make a fetal membrane roll in the fresh state. Vascular injection studies in twin placentas can only be performed on fresh specimens. Certain abnormalities, such as infarcts, chorangiomas, and single umbilical artery are more easily appreciated in the fixed state. The fixed placenta may be less infectious. The three main placental components, the fetal membranes, the umbilical cord and the placental disk, should be examined systematically. The following approach can be used as a guide. All of these abnormalities will be discussed in greater detail in other sections. Fetal Membranes: assess completeness of membranes record distance from point of rupture to placental disk assess color, opacity, nodules, bands/adhesions, hematoma, fetus papyracea record type of insertion - margin, circummarginate, circumvallate % of circumference involved if extrachorial Umbilical Cord: measure length and diameter including separate segments record site of insertion record distance of velamentous insertion from edge of disk and inspect connecting vessels for thrombosis, laceration assess number of vessels assess for true knots, excess torsion, stricture, discoloration, hematoma, edema, webs, needle puncture sites Placental Disk: assess shape measure in three dimensions measure accessory lobes and inspect connecting vessels examine fetal surface for color, opacity, amnion nodosum, bands/adhesions, hematomas, subchorionic fibrin examine chorionic plate vessels for thrombi, lacerations or other abnormalities assess maternal surface for completeness, color, texture record size and location of adherent clot and any associated placental changes (i.e. indentation, infarction) breadloaf placenta at 1 cm intervals and visually inspect and palpate cut surfaces for focal lesions record the number, color, shape, size, texture and location* measure accompanying clot *When abnormalities are more than focal, record the percentage of placental parenchyma involved by each process. Weight: after examining and removing clot, membranes and cord. Compare with standard charts Sample Section Code * umbilical cord 1 cassette with 3 sections of cord from different areas fetal membrane roll 1 cassette with 1 section in cases without membrane process 1 cassettes with 2 or 3 sections of membrane roll if suspicion of chorioamnionitis, history of preeclampsia, oligohydramnios, or meconium passage placental parenchyma 4 cassettes total** 2 cassettes of central area without lesions and 2 cassettes of focal lesions or 2 additional of central areas. At least 2 of these cassettes should include the basal plate and 2, the fetal plate. * CAP Practice Guideline recommends one cassette with one section of membrane roll and two sections of cord, and two cassettes of central placenta including fetal and maternal surfaces, in normal placentas ** if lesions are numerous, more cassettes may be necessary to sample all lesion types Report Quality and Accuracy Khong and Gordijin addressed the issue of the quality of pathology reports for placental specimens by examining 218 pathology reports and giving points for inclusion of multiple items in the gross examination, histologic assessment, and commentary on the presence or absence of findings in relation to the clinical history. One-third of reports from singleton placentas and 41% of reports from the placentas of multiple gestations scored less than 75%. Elements that were poorly reported were completeness of the membranes, trimmed weight, zygosity in multiple gestations, birth order of twins and commentary on gross or histologic findings. Studies addressing the reliability of diagnosis in the placenta have shown that discrepancies may be seen in about 40% of cases. Nearly all of these are due to underdiagnosis and the lesions most frequently underdiagnosed include hemorrhagic endovasculitis, fetal thrombotic vasculopathy, massive perivillous fibrin deposition, maternal floor infarct, retroplacental hematoma, intervillous thrombohematoma and atherosis. Fewer discrepancies were noted in inflammatory conditions such as chorioamnionitis, villitis and funisitis. All of these lesions may have important fetal and maternal implications and a major goal of this course will be to ensure that participants can recognize these conditions and understand their clinical implications. Agreement will almost certainly be improved with standardization of diagnostic criteria for placental abnormalities. This is an ongoing project undertaken by a subcommittee in the Perinatal Division of the Society for Pediatric Pathology. We look forward to their recommendations. Normal Placental Development The ovum is fertilized in the fallopian tube and rapidly proliferates to form the blastocyst. The outer cell layer of the blastocyst forms the trophoblast, and completely surrounds the developing inner cell mass that will form the embryo. On postovulatory day 6 to 7, the blastocyst attaches to and penetrates the endometrium. By postovulatory day 10 to 11 the blastocyst is completely embedded in endometrial stroma and the defect in the surface epithelium at the site of penetration has been re-epithelialized. The trophoblast differentiates into an inner layer of cytotrophoblast (CT) and an outer layer of syncytiotrophoblast (ST). The CT has distinct cell borders, clear cytoplasm and vesicular nuclei. CT is the germinative trophoblastic population giving rise to all the other populations of trophoblast. The ST is a syncytium with multiple, pyknotic nuclei and abundant amphophilic cytoplasm. ST produces hormones that support the endometrium and pregnancy as well as the enzymes needed for nutrient transfer between the maternal and fetal circulations. Intermediate trophoblast (IT) with large, irregular, angulated nuclei and abundant, amphophilic cytoplasm are intermixed between the CT and ST. Between postovulatory day 8 and 13 the ST forms trabecular columns that radiate around the germ disc and chorionic cavity. These columns are separated by blood-filled lacunae derived from maternal blood vessels that have been eroded. An inner core of CT fills these columns. The CT is then penetrated by fetal mesenchyme in which small blood vessels form. These blood vessels eventually establish connections with blood vessels in the developing fetus itself to form a continuous fetal circulation. These structures are the primary stem villi from which all other villi form. CT and IT at the bottom of the stem villi anchor stem villi to the basal plate of the developing placenta. The CT and IT also form a circumferential shell around the developing conceptus. New villi form from these primary stem villi throughout gestation by the same process: syncytiotrophoblastic sprouts experience an ingrowth of CT which itself experiences in growth of fetal mesenchyme within which fetal vessels form and connect to the existing fetal circulation. The decidua (gestational endometrium) and myometrium become infiltrated by IT. In addition to anchoring the placenta to the uterine wall, IT significantly modifies the structure of maternal arteries to maximize blood flow to the implantation site. When this remodeling fails to occur, there are important consequences for the mother and fetus (see circulatory and maternal disease sections). The villi on the embryonic aspect of the chorion proliferate to form the placental disk (chorion frondosum). The villi in the rest of the chorion atrophy forming the free membranes (chorion laevae). You can still see remnants of these atrophic villi in histologic sections of the free fetal membranes. The chorionic cavity continues to grow until it obliterates the endometrial cavity, between 18 and 20 weeks. The chorionic cavity is obliterated by expansion of the amniotic cavity. Septae form in the placenta at about 3 months. These are folds in the basal plate that divide the maternal surface into about 15 to 20 physiologically insignificant areas called cotyledons composed of villous tissue derived from a single stem villous. These septae are the result of slower growth of the anchoring villi compared to the intervening parenchyma. The villous tree divides to eventually form the terminal villi, the main nutrient exchanging component of the placenta. Deoxygenated fetal blood enters the placenta through the two umbilical arteries. These branch and enter the villi where they continue to divide until they terminate in the complex capillary network of the terminal villi. Villi are bathed in the maternal blood that fills the intervillous space. Nutrient and gas exchange takes place across the fetal capillary endothelium, the endothelial and trophoblastic basement membranes (fused into a vasculosyncytial membrane) and the trophoblastic cells themselves. Oxygenated fetal blood returns via venous vessels to the umbilical vein and then to the fetus. Villous structure changes markedly over the course of gestation. This maturation process includes a decrease in the size of the villi, a decrease in the amount of villous stroma, an increase is the size and number of fetal capillaries, apposition of the fetal capillaries to the periphery of the villi, and a thinning of both the CT and ST layers. All of these changes serve to decrease the distance between the fetal and maternal circulations and facilitate nutrient and gas exchange. References: Beebe LA et al. Methods to improve the reliability of histopathological diagnoses in the placenta. Paediat Perinatal Epid 2000;14:172-178. Gersell DG and Kraus FT (2002). Diseases of the Placenta. In: Robert J. Kurman (ed).Blaustein's Pathology of the Female Genita Tract, 5th edition. New York, Springer-Verlag. Khong TY. From delivery suite to laboratory: optimizing returns from placental examination in medico-legal defense. Aust NZ J Obstet Gynecol 1997;37:1-5. Khong TY and Gordijin SJ. Quality of placental pathology reports. Pediatr Dev Pathol 2002;6:54-58. Kraus FT. Perinatal pathology, the placenta and litigation. Hum Pathol 2003;34:517-521. Langston C et al . Practice guideline for examination of the placenta. Arch Pathol Lab Med 1997:121:449-476. Spencer MK and Khong TY. Conformity to guidelines for pathologic examination of the placenta: rates of submission and listing of clinical indications. Arch Pathol Lab Med 2003;127:205-207. Stallmach T and Hebisch G. Placental pathology: its impact on explaining prenatal and perinatal death. Virchows Arch 2004;445:9-16. Sun CCJ et al. Discrepancy in pathologic diagnosis of placental lesions. Arch Pathol Lab Med 2002;126:706-709.