OMFP CASE O WEEK 1 OMFP 2 14 18This placental lesion an example of (Figure 1)

 What is the most likely diagnosis?

A. 1⁰ placental choriocarcinoma
B. Chorangioma
C. Diffuse multifocal chorangiomatosis
D. Segmental localized chorangiomatosis.
E. Chorangiosis.

 OMFP COW 2a cut surface OMFP 2 2018 OMFP COW 2b cut surface SERIES FIXEDOMFP COW 3 LP MICROOMFP COW 4 LPnecrosis hemorrh Ca


Answer is B, Chorangioma.

OMFP COW 5 LP MICRO necrosis chorangioma necrosis 28034938Discussion
This is a very large chorangioma (Fig. 1). Chorangiomas are vascular hamartomas of the chorionic villous tree. They are not true neoplasms but are often referred to as tumors and, as such, they are the most common tumors of the placenta. They are seen in approximately 1% of term placentas and believed to arise as an excessive, hamartomatous capillary response to hypoxia within proximal and mature stem villi. This likely explains why they are more common in gestations complicated by hypoxic maternal malperfusion of the placental bed (e.g., preeclampsia, chronic hypertension. high altitude) OMFP COW 6B LP MICRO RETIC.jpgChorangiomas are well circumscribed, nodular masses of capillaries contained within a layer of trophoblast that expand the dimension of the stem villus. The stroma is of varying density and contains fibroblasts, macrophages and collagen. Most are small (<0.5 cm) if not microscopic, and may be mistaken for a focus of infarction, grossly. Larger chorangiomas have a vascular pedicle arising from the underside of the chorionic plate and are most commonly located near the placental margin. OMFP COW 6C HP MICRO.jpg 2 28034349The gross photograph of the example presented shows large feeder vessels coursing toward the mass and over its surface, confirming its subchorionic intraparenchymal origin. Larger chorangiomas tend to bulge from the fetal and they often have regions of hemorrhage, auto-infarction as they outstrip their vascular supply of thrombose, and my show foci of dystrophic mineralization, and thrombosis. Tumor tissue necrosis and thrombosis may lead to disseminated intravascular coagulation in the fetus. Figures 2A and 2B show the characteristic nodular circumscription of these lesions and their variegated fleshy tan to pink-red and firm appearing cut surface. The center of the mass also shows an ectatic branch of a “feeder” vessel. The variegated gross appearance reflects the alternating microscopic areas of dense capillarization, (Fig 3) infarction, calcification and hemorrhage (Fig 4) stromal collagenization, hypocellular mucinous stroma and/or thrombosis (Fig 5),that typify these lesions. Large chorangiomas (>6 - 9 cm in diameter) such as seen in this case, are associated with gestational complications due to their shunt effects. The lesions are perfused by the fetus but there is no exchange for oxygen and nutrients across its capillaries. Such fetuses are at risk for congestive heart failure, nonimmune hydrops, intrauterine growth restriction, neurodevelopmental injury, preterm birth, and intrauterine death; rates of intrauterine fetal demise range from 40%-66%. Large chorangiomas are detectable on prenatal ultrasound late second to early third trimester, and serial ultrasonographic surveillance of affected gestations has been recommended. Large chorangiomas may also encroach upon the base of the umbilical cord, especially in placentas with marginal cord insertions. In these cases, they can be associated with massive peri-insertional edema of Wharton’s jelly, cord vessel obstruction, and polyhydramnios, as well as preterm birth. These adverse effects, particularly for congestive heart failure and sequelae of lesional hemorrhage and infarction, may have implications for the newborn. Thus, the pathologist should notify the physician caring for the newborn, of these risks, when the placental gross examination reveals the presence of a suspected large chorangioma.(1) This said, some newborns, surprisingly, will have no sequelae, despite the presence of a massive and even an acutely hemorrhagic chorangioma (author’s experience).

OMFP COW 7 LP MICRO pericyte stain Primary Choriocarcinoma of the placenta is very rare and often tiny microscopic lesion of diagnostic sheets highly atypical syncytiotrophoblasts and cytotrophoblasts without villous formations(1). Chorangiomatosis has been referred to as “multifocal chorangiomas” but sites of chorangiomatosis, instead of forming the centrally expanding nodular configurations of capillaries of chorangiomas, show penetrating (“permeative”) patterns of capillary and stromalproliferations within normal proximal villous structures.(2) Both chorangiomas and chorangiomatosis show areas of collagenization, and positive lattice-like staining for reticulin fibers (Fig 6b and 6c), immunostaining by smooth muscle actin for pericytes (Fig7), and GLUT-1 in endothelial cells (Fig 8) OMFP COW 8 HP MICRO GLUT 1 CHORANGIOMA 1(glucose transporter normally present only on endothelial cells with a blood-tissue barrier function as in the brain and placenta.) The diffuse, multifocal form of chorangiomatosis is associated with delayed villous maturation, severe to extreme preterm birth (delivery before 32 weeks of gestation), congenital malformations and fetal growth restriction while the localized, segmental form is not. However, chorangiomas and both forms of chorangiomatosis are associated with preeclampsia.(1,2) Chorangiosis (Fig 9) OMFP COW 9 20x MICRO chorangiosis is a capillary proliferative lesion of terminal chorionic villi that only develop at about 34 weeks of gestation and involve the smallest, most mature distal villi that have vasculosyncytial membranes. (VSMs show apposition of capillary endothelium to a very thin layer of syncytiotrophoblast cytoplasm without intervening stroma. This reduces the diffusional distance between blood in the maternal space and fetal blood in the villous capillaries to ~2 micra) Normal terminal villi have ≤5-7 capillaries per villus. Chorangiosis is defined as the finding of ≥10 terminal villi, using a 10 x objective (low power), with ≥ 10 capillaries/villus, in ≥ 10 areas of uninfarcted villi in ≥3 fields on a slide.(3) Capillaries in chorangiosis do not have pericytes.(2) When considering a diagnosis of chorangiosis, it is important to exclude mere villous congestion that accentuates the presence of villous capillaries due to their distension. In most instances chorangiosis is related to chronic maternal underperfusion of the placental bed and low grade hypoxia, such as in cases of preeclampsia, maternal anemia, and high altitude gestations. However, chorangiosis is also seen in conditions of aneuploidy (Trisomy 21), fetal intrauterine growth restriction (IUGR), diabetes mellitus and placentomegaly associated with underlying disorders such as Beckwith-Wiedemann Syndrome(1), umbilical cord abnormalities (4), and in cases with chorangioma, chorangiomatosis (2), and fetal vascular thrombosis not associated with cord abnormalities (6 and author’s experience). The underlying pathogenesis seems to reflect alterations in growth factor mediated angiogenesis due to villous hypoxia.(5) It is plausible that cord abnormalities and fetal IUGR related hypovolemia may change the hemodynamics of fetal blood delivery to the villous tree and, in cases with chorangioma, chorangiomatosis, and fetal vascular malperfusion lesions (e.g. thrombi), the distribution of chorionic villous blood within the other parts of the villous tree.

1-Faye-Petersen O, Heller DS, Joshi VV. Handbook of Placental Pathology, Oxford, England: Taylor and Francis Medical Publishers. 2006:115-120.
2-Ogino S, Redline RW. Villous capillary lesions of the placenta: distinctions between chorangioma, chorangiomatosis, and chorangiosis. Hum Pathol. 2000;31:945-954.
3-Altshuler G. Chorangiosis. An important placental sign of neonatal morbidity and mortality. Arch Pathol Lab Med. 1984;108:71-4.
4-Chan JS, Baergen RN. Gross umbilical cord complications are associated with placental lesions of circulatory stasis and fetal hypoxia. Pediatr Dev Pathol. 2012;15:487-494..
5-Barut A, Barut F, Kandemir NO, Aktunc E, et al. Placental chorangiosis: the association with oxidative stress and angiogenesis. Gynecol Obstet Invest. 2012;73:141-151.
6- Levytska K, Higgins M, Keating S, Melamed N, Walker M, Sebire NJ, Kingdom JC. Placental Pathology in Relation to Uterine Artery Doppler Findings in Pregnancies with Severe Intrauterine Growth Restriction and Abnormal Umbilical Artery Doppler Changes. Am J Perinatol. 2017;34:451-457.

Author information

1 -Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Mount Sinai Hospital, Toronto, Ontario, Canada.
2 -Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, Canada.
3 -Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynaecology, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada.
4 -Department of Histopathology, Institute of Child Health, Great Ormond Street Hospital, University College London, London, United Kingdom.


Objectives -Current guidelines for diagnosis and management of early-onset intrauterine growth restriction (IUGR) rely on umbilical artery Doppler (UAD), without including uterine artery Doppler (UtAD). We hypothesized that IUGR cases with abnormal UAD but normal UtAD has a different spectrum of placental pathology compared with those with abnormal UtAD. Study Design Retrospective review of pregnancies with sonographic evidence of IUGR and abnormal UAD prior to delivery. Cases with ≥ 1 UtAD record(s) after 18+0 weeks' gestation and placental pathology were included. Cases were stratified according to initial UtAD pulsatility index (PI) values (n = 196): normal (n = 19; PI < 95th centile for gestational age/no notching), intermediate (n = 69; PI ≥ 95th centile/no/unilateral notching) and abnormal (n = 108; PI ≥ 95th centile/bilateral notching). Pregnancy outcomes and placental pathology were compared between groups. Results Women in the normal group delivered later than those in the abnormal group (30.1 ± 3.5 vs. 28.0 ± 3.5 weeks; mean ± standard deviation; p = 0.03). Their placentas exhibited higher rates of chronic intervillositis (15.8 vs. 0.9%; p = 0.01), chorangiosis (15.8 vs. 0.9%; p < 0.0001), and massive perivillous fibrin deposition (21.1 vs. 7.4%; p = 0.05), but had lower rates of uteroplacental vascular insufficiency (26.3 vs. 79.6%; p < 0.0001). Conclusion Approximately 10% of pregnancies with early-onset IUGR and abnormal UAD exhibited normal UtAD waveforms. They delivered later, and their placentas exhibited unusual placental pathologies.

 Contributed by
Ona Marie Faye-Petersen, M.D.