placental pathology: a general overview and review of the ... · 1. chronic fetal vascular...

Placental Pathology: A General Overview and

Review of the Most Common Mis(sed)

Diagnoses Session 1031 Janice Lage, MD, FASCP

University of Mississippi medical center, jackson, ms

J. Rick McEvoy, MD, FASCP, MT(ASCP) Roper st francis healthcare, charleston, sc

September 20, 2013

Placental Pathology Session 1031

• No Disclosures – Dr. Lage and McEvoy • In the past 12 months, I have not had a significant

financial interest or other relationship with the manufacturer(s) of the product(s) or provider(s) of the service(s) that will be discussed in my presentation.

• No Disclosures – Dr. McEvoy • In the past 12 months, I have not had a significant

financial interest or other relationship with the manufacturer(s) of the product(s) or provider(s) of the service(s) that will be discussed in my presentation

Placental Pathology Session 1031

• Outline – Brief overview of placenta – gross and microscopic – Discussion of 10 most common mis(sed)

diagnoses • Images • Associations • Comments • References

– Questions

Placenta

http://php.med.unsw.edu.au/embryology/images/0/0d/Placenta_cartoon.jpg

Review of the Most Common Mis(sed) Diagnoses

1. Chronic fetal vascular obstruction 2. Chronic villitis 3. Multiple Intervillous thrombi 4. Short umbilical cord 5. Meconium staining and meconium associated

vascular necrosis 6. Acute chorioamnionitis 7. Vascular abnormalities: Fetal and Maternal 8. Fetal NRBCs 9. Lesions associated with cerebral palsy 10. Lesions associated with recurrent gestation loss

Poll Everywhere Question

CHRONIC FETAL VASCULAR OBSTRUCTION

1. Chronic fetal vascular obstruction

• Constellation of lesions also called fetal thrombotic vasculopathy

• Lesions associated with interruption and/or cessation of fetal blood flow

• Most commonly identified in chorionic plate and stem villous blood vessels

• Often represent vascular damage with associated thrombus formation

• Examples: – Intimal cushion defects – Fetal artery thrombosis – Hemorrhagic endovasculitis – Eosinophilic/T-cell vasculitis


• 64 term infants with cerebral palsy – 52% demonstrated at least one of four placental

vascular lesions (p<0.0001): • Fetal thrombotic vasculopathy • Chronic villitis with obliterative fetal vasculopathy • Chorioamnionitis with severe fetal vasculitis • Meconium-associated fetal vascular necrosis

Am J Obstet Gynecol. 2005 Feb;192(2):452-7


• 93 cases of neonatal encephalopathy* – Defined clinically on constellation of findings** – “… the pathway from an intrapartum hypoxic-ischemic injury to

subsequent cerebral palsy must progress through neonatal encephalopathy”**

• Fetal thrombotic vasculopathy, funisitis, and accelerated villous maturation independently associated with NE

• No independently associated antenatal factors • NE important cause of morbidity and mortality in term

infants and many cases have an antepartum etiology

*Hum Pathol. 2004 Jul;35(7):875-80

**ACOG's Task Force on Neonatal Encephalopathy and Cerebral Palsy


• AKA: fetal artery thrombosis • Thrombus formation in fetal blood vessels of

umbilical artery/chorionic plate/stem villi • Generally fibrin thrombi or intimal cushions (mural

thrombi), calcify • Muscularization of fetal stem veins • Acute arteritis-CMV, syphilis, rubella • (Hemorrhagic endovasculitis) • May only see downstream effect of thrombosis

Intimal Cushion Defect

Intimal cushion defect Mural thrombus, calcified

Fetal Artery Thrombosis

• Most often recognized by downstream avascular chorionic villi

• Occlusion/thrombosis normally occurs in stem villous or chronic plate blood vessels

Hemorrhagic endovasculitis • Thrombosis and recanalization of chorionic/villous stem

vessels • Increased perinatal morbidity and mortality • Abnormalities of neonatal growth and development • Unknown etiology • Altered umbilical blood flow or villous perfusion may be an

initiating event1 • May recur in subsequent pregnancies

Am J Obstet Gynecol. 1988 Jul;159(1):48-51.

Hemorrhagic endovasculitis

• Associated clinical conditions in livebirth and stillbirth – Chronic villitis of unknown etiology – Chorionic vessel thrombi – Increased fetal nucleated rbcs – Meconium staining – Maternal hypertension

Hemorrhagic endovasculitis in livebirths--associations

• Chronic villitis of unknown etiology • Chorionic thrombi • Villous stromal fibrosis • Infarcts

Obstetric and Gynecology Vol. 89, No. 4, April 1997.

Example of Comment • Chronic fetal vascular obstruction, as called fetal

thrombotic vasculopathy, denotes a group of lesions (fetal artery thrombosis, hemorrhagic endovasculitis, intimal/endothelial cushion defects, fetal stem vessel fibrin thrombi, and avascular fibrotic villi) that has been associated with maternal diabetes, maternal thrombophilia (including Factor V Leiden mutation, Protein C and S deficiencies, antiphospholipid antibody production, and lupus anticoagulant, among others), chorioamnionitis, and umbilical cord abnormalities. When extensive, chronic fetal vascular obstruction has been associated with intrauterine growth restriction, neurologic impairment (including cerebral palsy), prenatal injury, vascular compromise, and stillbirth.

• Refs: Am J Obstet Gynecol 2005 Feb;192(2):452 7

Eosinophilic/T-cell vasculitis

• Distinct pattern of inflammation often limited to one chorionic surface vessel

• Associated with other vaso-occlusive lesions in the fetal vasculature, including mural thrombi or intramural fibrin away from the location of vasculitis

• Also associated with chronic villitis (villitis of unknown etiology)

• There were no significant differences in the frequencies of other placental lesions studied,

Eosinophilic/T-cell vasculitis: CD3 CD3

Example of Comment

• Eosinophilic/T-cell vasculitis is an uncommon vaso-occlusive and vaso-destructive lesion associated with a fetal inflammatory response largely confined to the surface vessels of the placenta. Eosinophilic/T-cell vasculitis has been associated with other vaso-occlusive lesions and may represent a localized fetal inflammatory reaction to vascular damage resulting from umbilical cord/chorionic plate blood vessel compromise.

• Refs: Pediatr Dev Pathol 2011 May

http://www.ncbi.nlm.nih.gov/pubmed/21050080

Poll Everywhere Question

CHRONIC VILLITIS

2. Chronic villitis

• (VUE vs infections)

2. Chronic villitis-Clinical associations

• Congenital fetoplacental infection • Passes through placenta and affects baby • TORCH, parvovirus, coxsackie and echoviruses,

syphilis, TB, histo, cocci, etc. • May be result of “maternal placental rejection” • IUGR, increased perinatal morbidity and mortality,

IUFD

2. Chronic villitis

• Associated with recurrent reproductive loss*, cerebral palsy, and neurologic impairment**

*Hum Pathol. 2000 Nov;31(11):1389-96.

**Arch Pathol Lab Med. 2000 Dec;124(12):1785-91.

2. Chronic villitis

• Lymphocytes, plasma cells and histiocytes (including multi-nucleated giant cells) in villi

• T cells (CD3+) of maternal origin • Focal or diffuse • Usually small placenta (growth restricted)

Congenital syphilis • Gross: large, bulky placenta, or normal • Micro: classic triad:

– Large, hypercellular villi – Proliferative fetal vascular changes – Villitis, chronic or active, usually acute

• Classic triad: 43%; 2 of 3, 47%; 1 of 3, 10% • Other helpful features: intra- or perivillous polys, lymphocytic

deciduitis, necrotizing funisitis • Best place to find spirochetes: cord, membranes, decidua, sclerotic

villi adjacent to villitis

Case #17

• Term delivery with neonatal seizures, periventricular calcifications seen on CT scan, developmental delay

Coxsackie viruses

• Group of small RNA viruses • Hand, foot and mouth disease • Grey vesicles with a red halo on the vulva • Normal to edematous placenta with or without

inclusions • Fetal myocarditis and thyroiditis with many plasma

cells (B6) or myocarditis with meningitis (A9) • Fetal hydrops and death due to heart failure

Example of Comment

• In some instances, chronic villitis is associated with congenital infections by the following organisms: Toxoplasma gondii, Rubella virus, Cytomegalovirus, Herpes simplex virus (TORCH infections), Parvovirus, Treponema pallidum, Mycobacterium tuberculosis, Histoplasma, Varicella zoster virus, and Enteroviruses, including Coxsackievirus, among others. In the majority of cases, an infectious cause cannot be demonstrated (villitis of unknown etiology, VUE) and a maternally-derived immune reaction occurring within fetal tissue has been observed. Recurrence has been documented in subsequent pregnancies. Clinicopathologic correlation and

tib d tit d d if

MULTIPLE INTERVILLOUS THROMBI

3. Intervillous thrombus

• Blood clot in intervillous space (maternal circulation)

• Fresh hemorrhage—grossly red and firmer than surrounding placenta, collections of rbc’s widen the intervillous space

• Older thrombus-yellow to white, usually does not organize

3. Intervillous thrombus • Midway in placental parenchyma between maternal floor and

chorionic plate • Older clot becomes laminated over time—lines of Zahn • Septic intervillous thrombi—Listeria, among others • Multiple thrombi associated with increased likelihood of fetal

maternal hemorrhage (FMH) • Likelihood of finding clot(s) esp with FMH increases with

fetal/maternal blood group incompatibilities

3. Intervillous thrombus

• Most likely results from chorionic villous (stromal) hemorrhage rather than to extension of a retroplacental hemorrhage, though both may occur*

• Does not demonstrate associations with SGA, pregnancy-induced hypertension, age at first pregnancy, and ethnicity (as seen with infarcts)**

*Semin Thromb Hemost. 1998;24(5):497-501

**Pediatr Dev Pathol. 2004 Jan-Feb;7(1):26-34.

Example of Comment

• Multiple intervillous thrombi (intraplacental hematomas) suggest the possibility of fetomaternal hemorrhage and have been associated with fetal anemia, fetal thrombocytopenia, hydrops, stillbirth, maternal sensitization, and reduced fetal circulation with end-organ damage. A Kleihauer-Betke test is recommended if clinically indicated.

R f Pl l P h l (A l f N T

SHORT UMBILICAL CORD

Example of Comment

• Short umbilical cords (variably defined as 35-40 cm) have been associated with decreased fetal in utero movement (as may be seen with amniotic bands, oligo-hydramnios, body wall defects, and fetal neuromuscular disorders, among others), low Apgar scores, small for gestational age, umbilical cord abnormalities (including single umbilical artery), fetal distress, and psychomotor abnormalities. Clinicopathologic correlation with length of umbilical cord left on the baby and any used for blood gas analysis is recommended to evaluate overall cord length.

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