Patozone

Placenta Gross

Placenta histology

IntraUterine Growth Restriction (IUGR)

Necrotizing funisitis

Syphilis

CMV

Parvovirus B19

Villitis of Unknown Etiology (VUE)

Maternal Floor Infarct (MFI)

Retroplacental hemorrhage

Chorangioma

Chorangiosis

Decidual vasculopathy

Vacuolated amnionic epithelial changes

Trophoblastic tumors

• Exaggerated Placental Site
• Placental Site Nodule
• Placental site trophoblastic tumor (PSTT)
• Epithelioid Trophoblastic Tumor
• Choriocarcinoma

Molar Pregnancy

• Complete Hydatidiform Mole (CHM)
  • Early CHM, Invasive CHM
• Partial hydatidiform mole (PHM)

Hydropic Abortus

Early abortus (EA) c trophoblastic hyperplasia

Abnormal villous morphology (AVM)

Androgenic / biparental mosaic conceptions (MOS), some with CHM

Metastasis to Uterus

Placenta Gross

Cord

35-75 cm at term, 55 cm avg (can tell long [from accidents, knots, proapse], but not really short [oligohydramnios, body wall defects, arthrogyropsis]), 2 umbilical arteries carrying de-oxygenated blood from fetus

- can insert velamentous (in membranes), vasa previa (if inserts over the cervical os), furcate

- knots (not always significant), look for dilated vessels on one side and

- coiling index: 0.2 cm - measure 10 cm and count twists, or just subjectively say it looks more twisted (hypercoiled)

- right twist less common?

- should do US on GI tract if single umblical artery

other cord problems: nuchal cord, torsion, stricture, marginal insertion (aka "battledore placenta" - not always significant), hematoma, iatrogenic puncture (look for hx of cordocentesis)

Membranes

- cover th fetal surface of the disk

- point of rupture (can help to know where the placenta was implanted in the uterus)

get bubbly and tall amniotic epithelium when meconium present

- artery crosses vein, in monochor twins may have A-A, V-V, A-V (last most sig in TTT)

- amniotic bands??

- can get amputation of extremites

Amnion nodosum - white/yellow dots that dont rub off, most apparent in oligohydramnios / Potts syndrome

- acute chrioamnionitis - icky yellow

Meconium staining - icky green; from fetal intestinal contents; passage prior to birth assoc c inc GA; timing innacurate and multiple episodes can occur - not able to really say if it means anything, physiologic response to birth - brown pigment fades under fluorescent lights (ie when left out on trays... look for the study...) - though meconium is vasoactive, causes cytokine release and vasoconstriction (but cant tell these unless have vascular muscle necrosis [meconium has to be there at least 15 hours, arteries affected 1st])

-- fetal inflam response: umbilical vasculitis, assoc c later CP esp in small infants; fetal IL-6 inc in these infants

Villi

"basal plate" of placenta that attaches to uterine wall, c infarcts and hemorrhages

- marked histo changes in villus morphoogy over inc GA

- size and stroma content dec as branching occurs

- inc % of area occupid by vessels

- syncytiotrophoblast nuclei aggregate c vasculosyncytial membranes

- Paleness and edema ssoc c syphilis

- infarction - white fibrous tissue that is usually MC on periphery of placenta since edges are usually more hypoxic

- reduced utero-placental blood flow - syncytiotrophoblast most sensitive, causing aggregation and smudging of nuclei; poor growth of placenta c reduced weight, villi become small from excessive branching

Decidua - plasma cells?

- implantation site vessels - intermed trophoblasts invade uterine arterioles and destroy muscle nd elastica; waves of invasion in first nd second trimesters; "physiologic remodeling"

- changes in pre-eclampsia - atherosis (foamy macrophages)

Shape variations:

bilobed

succenturiate

circumvallate (assoc c growth restriction and preterm labor - has a little pocket that you should be able to stick a probe in)

circummarginate

membranacea

(though they are more or less ameboid)

Fetal surface

- shiny, smooth, flat,

- cord insertion c branching vessels (A over V)

- chorioamnionitis, meconium

Placenta histology

Earliest trophoblastic stage if a cell recognizable by the 12 to 16 cell stage as the outermost cell mass of the morula

Later flattens and forms embryoblast in the blastocyst stage

- invades the endometrial lining by the end of the 1st WGA

- lacunae form within the syncytiotrophoblastic layer as continues to invade into endometrium

Placental anatomy established by 2nd trimester, but continues to undergo changes

- the decidua comes from the parent, the chorion and amnion comes from the baby

-- small potential space bwt the amnion and chorion come from the remnant of the extraembryonic coelom

- trophoblastic cells of the chorion have variable sizes and shapes and are occasionally multinucleated

Retroplacental hemorrhage

- Premature separation

- blood acuumulates begind placenta

- assoc c pre-eclampsia, trauma, infx, smoking, cocaine

-extent of lesion (early lesions hard to dx)

MC findings in placentas:

- Preterm: ischemia and chorioamnionitis

- Term: ischemia nd meconium changes

- Post term: meconium changes and ischemia

Monochorionic placentas are identical, dichorionic can be anything

- mono mono dangerous bc cords usually get crossed

Chorangiosis ... other lesions ???

PreTerm Labor

- MCC is ascending chorioamnionitis

- circumvallate placenta is a cause of PTL and IUGR (but is actually caused by chronic peripheral abruption and fetal hypoxia)

Hematomas

- Retroplacental

- Subamniotic

- Subchorionic

- Marginal

- Intervillous

Placental implantation pathology

Placenta previa

- Placenta covers cervix and prevents a proper birth

Placenta Accreta

-

Placenta Increta

-

Placenta Percreta

- goes through the serosa

Twins

Comparison of zygote development in monozygotic and dizygotic twins. In the uterus, a majority of monozygotic twins (60–70%) share the same placenta but have separate amniotic sacs. In 18–30% of monozygotic twins each fetus has a separate placenta and a separate amniotic sac. A small number (1–2%) of monozygotic twins share the same placenta and amniotic sac. Fraternal twins each have their own placenta and own amniotic sac.

Early Gestational Sac

Can see the trophoblastic shell around the outside edge, the stalk with the embryonic sac and the yolk sac

- is easily recognized when you see the embyo, but that is relatively uncommon

Chorangioma

most common type of placental neoplasm, with an

overall incidence of <1%. Typically, they are asymptomatic and are discovered incidentally at birth through gross examination of the placenta revealing a wellcircumscribed, spongy, red-brown nodule within the placental parenchyma, commonly at the periphery of the disc or directly below the cord insertion. Occasionally, multiple chorangiomas can be present. Most are discovered in mature placentas at 32-37 weeks’ gestation in mothers over the age of 30. Increasing maternal age has been correlated with increased incidence of chorangiomas. They are thought to develop as a reactive proliferation to hypoxia resulting in increased vascular endothelial growth factor production and angiogenesis. While most are incidentally found and have no clinical consequences, large chorangiomas (>4 cm)

may be associated with intrauterine growth restriction (IUGR), arterio-venous shunting, and fetal cardiac failure. Chorangiomas express GLUT1, similarly to

infantile hemangiomas, and may occur concurrently. While debated in the literature, some studies have shown a possible association between infantile hemangiomas and chorangiomas and even speculate that infantile hemangiomas may result from endothelial cell shedding from chorangiomas or hormonal influence during development.

Micro: well-circumscribed vascular proliferation composed of numerous capillaries. Examination of the nodule under high power reveals that the capillaries are surrounded by pericytes with no cytologic atypia. Mitotic figures are not readily identifiable. Surrounding the nodule, there are benignappearing cytotrophoblasts and syncytiotrophoblasts with appropriate syncytial knotting for gestational age. The few villi present surrounding the nodule are small,

mature, and appropriately developed for a third trimester placenta with a normal amount of vessels present

Decidual vasculopathy

Normally, arteries transform into big channels through trophoblasts that invade and destroy arterial walls, making the vessel unable to vasoconstrict (muscular layer destroyed later)

- called lack of physiologic constriction if this doesn't happen

- also see atherosis, fibrinoid necrosis and vasculitis

- assoc c Gestational hypertension (as in pre-eclampsia or HELLP syndrome)

Fetal Vascular Malperfusion (FVM)

- in ~6% of placentas, increases in prevalence with adverse perinatal outcomes - up to 16%

- several histologic pattern seen, such as thrombosis, avascular villi, villous stromal-vascular karyorrhexis, intramural fibrin thrombi, stem villous vascular obliteration

- may be caused by abnormal cord insertion, length, and coiling

-- can be assoc c maternal vascular malperfusion, such as preeclampsia, hypercoagulable states, lupus anticoagulant, and sometimes diabetes

- fetal cardiac dysfunction/malformations and severe fetal inflam response in setting of ascending intrauterine infx have been attributed [1], as well as low apgar scores, fetal growth restriction, hypotonia, hyporeflexia, preterm birth, adverse neurologic sequelae (intracranial bleeding, stroke, CP)

- increased perinatal mortality, esp stillbirth

- increased prevaluence of congenital abnormalities

**Caveat: prior intrauterine fetal death with degenerative changes post demise in the placenta results in a similar picture

Sx: may cause IUGR, poor perinatal outcome, fetal demise, and neurodevelopmental sequelae

Gross: light or heavy placenta

- marginal or velamentous insertion of the cord

- other cord abnormalities, long cord >80 cm or <35 cm, or >3 coils per 10 cm with deep grooves in Wharton jelly, or thin cords (more prone to compression), or true knots, hypercoiling, visible thrombi

- avascular villi may appear as pale triangular foci, esp after fixation

Micro: multiple patterns may be seen, such as:

- thrombosis of the fetal chorionic plate or umbilical cord vessels (can be seen grossly)

- mural organizing thrombosis with lamination with vascular muscular degeneration and extasia

- calcifications in older thrombi, or complete luminal obliteration in remote thrombotic lesions

- stem vessel obliteration (fibromuscular sclerosis) with thickening of vascular walls with luminal obliteration, usually close to the cord insertion site

- intramural fibrin deposits (usually non-occlusive)

Avascular villi seen with prolonged occlusion

- terminal villi lose villous capillaries and get stromal fibrosis

- syncytiotrophoblasts preserved as intervillous maternal circulation is maintained

-- now classified as small foci if at least 3+ foci of 2-4 terminal villi with total capillary loss, and as large foci if >10 villi affected

Villous stromal-vascular karyorrhexis (aka hemorrhagic endovasculitis) also seen with villous endothelial karyorrhexis with congestion, RBC extravasation, stromal apoptosis, separation of endothelial lumens

- must be seen in 3+ foci of 2-4 terminal villi with karyorrhaxis of fetal cells

Vacuolated amnionic epithelial (change) cytoplasm

Assoc c gastroschisis and omphalocele

- amnionic epithelial cells have fine uniform extensive vacuolization

- doent affect placental func

- vacuoles are lipid-laden, but dont no y, vacuoles only seen later in gestation (after 20 wks)

Trophoblastic Tumors

There is a differentiation pathway, similar to hemepath

Previllous trophoblast --> villous cytotrophoblasts

Villous cytotrophoblasts to syncytiotrophoblats, transitional extravillous trophoblasts, and trophoblast column

All trophoblasts are GATA3 positive

Risk factors: Maternal age <20 (RR 1.5), or >40 (RR 5.2)

- Race: esp in Indonesia, Japan (Asian women in US still have higher risk)

- Prior molar pregnancy

Exaggerated Placental Site

IHC: (+) hPL (strong pos), Mel-CAM (strong pos), hCG, HLA-G, inhibin, CK18, CD10

- neg: p63, low Ki67 (<1%)

DDx:  PSTT )presence of villi or fetal parts; absence of proliferation; less cytological atypia; abundant multinucleated IT; b-hCG continues to decline)

Placental Site Nodule (PSN)

Lesions of chorionic-type intermediate trophoblasts (IT), usually small

- 40-50% of PSNs are found in cervix; Always incidental findings

IHC: (+) p63 (very strong pos), hCG, HLA-G, Mel-CAM, inhibin, CK18, CD10

- neg: Cyclin E, hPL (var), Mel-CAM (var),

- low Ki67 (<5-8%)

Tx: Complete excision after surgical procedures

No clinical follow-up required

DDx: ETT

Placental Site Trophoblastic Tumor (PSTT)

Rare, caused by transformation of intermediate trophoblast at implantation site to cancer, usually after a long normal term pregnancy in pts of reproductive age

- presents as amenorrhea or abnormal bleeding with slightly inc b-hCG that can produce virilization

- tend to involve LUS and can mimic primary cervical ca

Gross: poorly defined soft mass in myometrium that can perforate uterus

Micro: Medium-sized spindly to polygonal cells c irreg borders (intermed trophoblasts) invading myometrium in nests, can have intranuclear pseudoinclusions, rare syncytiotrophoblasts can be seen

- similar to what is seen in normal pregnancy, vessel walls are infiltrated by intermediate trophoblasts, and deposit fibrinoid material in vessel wall and interstitium

- may be surrounded by lymphs

- no cytotrophoblasts or villi

- lots of fibrinoid stuff deposited and invasion of BV's

- infiltrative margins, low mits

IHC: (+) hCG (multinucleated cells), HLA-G, hPL, keratin, Mel-CAM, inhibin, CK5/6 (focal)

- negative PLAP, p63 (low)

- Ki67 >10%

Genes: diploid

Tx: curretage / hysterectomy, monitor b-hCG,

- 1/10 die from mets to lung, liver, brain

Px: worse c >5 mits/hpf, high Ki67 (>50%), inc celluarity, lots of necrosis, lots of cells c clear cytoplasma dn irreg nuclei, mets

Epithelioid Trophoblastic Tumor (ETT)

Arises from chorionic-type intermediate trophoblastic cells

- b-hCG should not be as elevated as in chorioca ((?? per Webpath.com, levels of hCG are elevated ??)

Micro: atypical cells, tends to have a pushing pattern (vs PSTT which is infiltrative), very cellular and geographic necrosis,

IHC: (+) p63 (very strong pos), inhibin, CK18, Cyclin E (strong pos), hCG, HLA-G

- neg: hPL (var), Mel-CAM (var)

- low Ki67 (>10%, <25%)

DDx: may be mistaken for squamous cell carcinoma

Invasive Complete Hydatidiform Mole

Molar villi invade into myometrium

Partial Hydatidiform Mole (PHM)

- has normal placental tissue intermixed in grape-like villi and can see fetal parts

*** Mom and dad *** PT6 ***

Partial Tri-/Tetraploid

1/5 of all moles, low risk of choriocarcinoma, smaller than complete moles

- uterus can be small for date w/o enlarged uterus

- may accidentally be dx's as missed abortion by both clinician and pathologist

Gross: mix of vesicular and normal villi

Micro: mix of edematous and normal villi

- villous scalloping (irregular shape with trophoblast villi goes into villous stroma)

- do not develop uniformly hydropic villi, giving it a biphasic population of hydropic villi mixed c smaller fibrotic immature villi

- have stromal trophoblastic pseudoinclusions

- circumferential trophoblast proliferation less pronounced than in complete moles

- early partial mole suspected if some villi are dilated and not others, and borders usually more scalloped than late-term partial moles

IHC: (+) p57Kip2 (has maternal allele) in villous stromal cells and cytotrophoblasts, p53, hCG, CK, Inhibin, HLA-G

Genes: Diandric triploidy (~99% dispermic / heterozygous c 2 paternal and 1 maternal cr complements)

- tri- (>1/2 are XXY, <1/2 are XXX, few XYY) or tetraploid; 2 or 3 gene sets come from papi, 1 from mami

- some have trisomy 16

- good to get molecular to lock in dx

Tx: get CXR, monitor hCG

Px: <1/10 get gestational trophoblastic dz (GTD)

- low risk of choriocarcinoma or invasion

Hydropic Abortus

Presents as missed abortion c declining hCG levels

- grossly tissue scant, fetal parts usually not visible

- villi are uniform, round and occasionally fibrotic

- stromal vessels are rare and nonbranching, can have nRBCs

- trophoblastic hyperplasia is rare, but when present is polar

IHC: (+) p57 villous stromal cells and cytotrophoblasts

Genes: are diploid or aneuploid, occasionally triploid

Px: no inc risk of persistent dz

Early abortus (EA) c trophoblastic hyperplasia

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Abnormal villous morphology (AVM)

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Androgenic / biparental mosaic conceptions (MOS), some with CHM

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