Our group has been closely involved in placental pathology since attending Dr. Doug Shanklin's groundbreaking CME course in Gatlinburg in 1978. We have given focused attention to placental pathology since then and consider that we have an actual "placenta program" concerning placenta evaluation for our patients. A main and valuable goal of the pathology exam of the placenta is to show that it was free of any currently-known abnormality. Should an abnormality be discovered, physicians are then provided "heads up" information that they can consider as they evaluate the progress of the baby's developmental milestone markers. That is, it is valuable to know that your baby's placenta was normal. 

On the other hand, the finding of one or more "severe" placental abnormalities does not doom your child to any definite adverse consequences at all. There were severe abnormalities in placentae of two of my grandchildren (severe ACA) and one of my partner's children (HEV). The youngest of those 3 is a fifth grade student, and all have developed normally...their doctors were able to be forewarned as they made decisions and gave advice as these children grew up. [back to placenta table of contents (TOC)] Dr. Virginia Apgar, anesthesiologist, devised the Apgar score in 1953; and an abnormal Apgar score is a good general reason for a pathology exam of the placenta.

1. Placental size:     On the basis of numbers alone, placentomegaly can be diagnosed when the weight is greater than 600 grams or the F/P ratio is 3:1 or lower.  Interpret abnormal ratios as you do WBC differentials: absolute or relative increases or decreases of "F" or "P" as reason for altered ratio.  Weigh after removal of membranes, cord, and attached clot (std. weight tables don't include membranes & cord & attached clot).
   • small placenta (placenta diminutivata): An unusually small or diminutive placenta [L09-2617, L09-4211, L09-4852] often has clinical significance. Low maternal pregravid weight, low pregnancy weight gain, and the absence of hand and facial edema in the gravida were all associated with small placentas. All these factors are associated with low maternal gestational blood volume expansion with resulting low blood flow from the uterus to the placenta. The most important risk factor is fetal growth retardation (SGA/IUGR). Other factors associated with small placentas include accelerated placental maturation and major fetal malformations. Unevenly accelerated placental maturation is the characteristic consequence of pre-eclampsia and chronic maternal hypertension (which reduce blood flow from the uterus to the placenta). Many of the major autosomal disorders are associated with placental growth retardation. Trisomy 21 is an exception, the fetus often being more growth-retarded than the placenta. Excessive obstruction of the villous chamber can cause small placenta.

   Small placentas are associated with increased frequency of stillbirths and mental retardation at 7 yrs of age, independent of the size of the fetus, malformations in the child, and the disorders that chronically reduce uteroplacental blood flow. The association with stillbirths raises the possibility that small placentas are sometimes functionally inadequate to supply all of the needs of the fetus for oxygen and nutrients. Maternal cigarette smoking during pregnancy is a well-known cause of fetal growth retardation; it does not cause a parallel retardation of placental growth, so the ratio of fetal to placental growth reduces.

   • large placenta (placentomegaly): Common causes of unusually large placenta are villous edema, maternal diabetes mellitus, severe maternal anemia, fetal anemia, congenital syphilis, large intervillous thrombi, and a large blood clot beneath the chorioninc (fetal surface) roof of the placenta (pathologist often cannot identify the specific cause [L09-3132]). Rare causes of unusually large placentae include toxoplasmosis, congenital fetal nephrosis, idiopathic fetal hydrops, and multiple placental chorioangiomata. Placental enlargement with diabetes mellitus and chronic fetal and maternal anemia are usually related to abnormally large villi. Villous edema is the most frequent cause of a preterm placenta being overweight. Recognizing placental villous edema is important because when its widespread and severe it makes fetuses hypoxic with resulting low Apgar scores, difficulty in resuscitation at birth, neonatal respiratory distress, a high neonatal mortality, and an increased frequency of long-term neurologic abnormalities.

2. Placental shape:
   • Unusually thin placenta: The antecedents of thin placentas are a placenta that was subnormal in weight, the gravida being short, and major fetal malformations. An unusually thin placenta increases the risk fro both fetal growth retardation, and for neonatal death, raising the possibility that very thin placenta are sometimes functionally insufficient. A thin placenta does not increase the risk for long-term neurological abnormalities.
   • Unusually thick placenta: They are usually an indication of health rather than of disease. They are associated with lower than expected frequencies of fetal growth retardation and neonatal death.
   • odd shapes:
3. Life-threatening placental lesions⁴ (usually visible & interpretable by naked eye exam):
   • placental abruption, extensive
   • placental infarction, extensive
   • truly knotted cord
   • umbilical vascular thrombosis
   • ruptured vasa previa
   • chorionic vascular thrombosis, extensive
   • giant chorangioma [&/or diffuse, severe chorangiosis or high volume chorangiomatosis]
   • choriocarcinoma
4. Placental implantation: The villo-decidual interface usually lyses to release the placenta. When decidua basalis is of deficient thickness or coverage, placenta removes/delivers with difficulty. The maternal surface findings often distorted by the desperate clinical attempts to remove the adherent placenta at time of delivery. Very early and patchy instances of accreta may be detected in cases labeled "manual removal of placenta" or "difficult placenta delivery". (Most common cause of disrupted normal maternal surface is the manual delivery of C-section.) Look on the maternal cotyledonal surfaces for areas where the smooth, barely shiney decidual surface is absent, especially at edges of disrupted cotyledons, & take sections at any transition between smooth (slightly shiney) and non-smooth ("dull") surfaces.
   • placenta creta: tends to be variably expressed & starts with loss of basal decidua.
     • placenta accreta: villous adherence to internal myometrial surface (attenuated &/or absent decidua)[L08-10441].
     • placenta increta: villous adherence into myometrium
     • placenta percreta: villous adherence to through the myometrium
   • placenta previa: situated too close to, maybe even partially or totally over the internal cervical os & has poor development of decidua.
5. The cord: is more liable to torsion or kinking if the diameter is too small, segmentally (coarctation) or diffusely, due to insufficient Wharton's jelly; a term birth with cord less than 32 cm long (less than 40 cm⁶) is short (too short for normal, uneventful vaginal delivery?) or greater than 100 cm long (>/= 70 cm prob. too long; >75 cm⁶) is too long & either short or long can be a problem.  Cord normally tends to be about the crown-heel length of baby.
   • Length: Short cord implies little fetal movement (hypokinesis or akinesis) & is occasionally associated with premature separation & hemorrhage...may impede fetal descent & may be associated with uterine inversion. Associations with IUGR, increased perinatal mortality, neurological abnormalities (CNS damage⁶), decreased IQ, and seizures⁴.Long cord implies excessive fetal movement (nuchal cord danger) & may lead to congestion & thrombosis...associated with hyperactivity syndromes.  
   • Insertion: 360 degree movement: is there anything about cord insertion restrictive and could lead to kinking (as can narrowing at anterior abdominal wall)? Insert as a tri-cornered twirl or as a three-pronged fork? Inserts with cord coarctation or furcation? Inserts centrally, eccentrically, paramarginally, marginally, or velamentously? (photo: birth hole in amnion sac is partly encircled by a large vessel...vasa previa...from closely velamentous cord). Velamentous insertion has 4x increased associations with multiple gestations or congenital syndromes, 4x associations with diabetes mellitus, 2x association with advanced maternal age &/or smoking, neurological disorders, and 2-3x assoc. with hyperactive syndromes⁴.  
   • Vessels: Is the artery (2) and vein (1) number normal? A one artery cord frequency is 1% of deliveries & associated with twice the incidence of renal anomalies, 4x the incidence of stillbirth, 2x the incidence of IUGR, and 2x the incidence of preterm delivery⁴.  
   • Twins have increased incidence of abnormal umbilical cord; twin chorionicity is routinely stated in our reports but does not determine identical vs. fraternal (that is done with DNA testing).
   • Nuchal cord: pathologists have to rely on being giventhe history of cord around the neck (nuchal cord); nuchal cord usually due to a long cord but can be due to a short cord [L07-7915]; ifthere is stillbirth, the presence of fetal erythroblastosis will be evidence that it was not a sudden death...fetus went through a stage of at least subacute severe hypoxia [L07-7915].
   • Knots or other evidence of nuchal or other compression, torsion, or stricture; true knots in 1% of deliveries and inconsequential unless they are an "occlusive true knot" (look for indentation when untied and/or edematous segment toward placenta due to vein obstruction)⁴. Too many helical turns per unit length (hypertwisted) may be abnormal, see below. Don't mistake a false knot (an aneurysm) for a real knot.   
   • Membranous cord insertions: velamentous cord...look for torn vessels in these insertions.   
   • Look for thrombi [L-05-8676], hematomata (watch out for clamp and other delivery artifacts) or other compressive lesion. Thrombi likely reflect a genetic thrombophilia from such as Protein C deficiency.  
   • Look for lacerations (from, say, C-section).  
   • "Cooked macaroni" segment: necrotizing vasculitis - [check serology-RPR].  
   • Edema: may indicate maternal diabetes, B. strep infection, Rh/HDN disease, fetal demise⁶  
   • Thin, skinny, diameter (coarctation; stricture): associated with IUGR. Is it entirely thin [L09-2859] or just segmentally thin or multisegmentally thin?; (photo: the 5 cm @ insertion is 50% thinner than rest of cord in this 2-vessel cord).  Occultly thin segments can tortion & cause fetal death [L09-2296]; thin zones can tear during interventions such as C-section [L09-4109].
   • Massive diameter: Beckwith-Wiedemann macrosomy syndrome?  
   • Thrombi involving veins are more important because can fragment to embolize to fetal CNS. See 3g, above. [artery L07-5096] Additional venous thrombosis risk with maternal lupus anticoagulant and with maternal diabetes mellitus⁵.  
   • Furcate cord: (as in "bifurcation" or "trifurcation") = absent or severly deficient Wharton's (usually at @ insertion) to the point of the vessels beginning to separate. (extreme example) [other cases are LMC-02-3467; LMC-03-1187 twins; LMC-03-8751; L07-11588 & L07-11588 stillbirth].  
   • Battledore placenta: oval with marginally (toward one of the poles) inserted cord.  
   • Barber-pole, candy-cane striped cord: suppurative vasculitis.  
   • Premature division of vessels at insertion: see furcate cord, above.  
   • Hypertwisted (hypercoiled) cord </= 40 cm may be functionally too short for vaginal delivery...probably indicated fetal hyper-movement. Normally have 1 twist per 5 cm.; hypertwisting assoc. with IUGR⁵.
   •  Few or no twists (hypocoiled...achirality⁵) = hypo-movement. See 2e, above. High assoc. with IUFD⁵.
6. Acute chorioamnionitis (ACA) & funisitis:
   • Frozen section of cord and fetal surface of placenta for rapid diagnosis.  
   • Routine blocks: Permanent  section wad of membranes to include the edge of the birth rupture hole; section of cord at both ends and the middle; placental sampling to include two or more blocks reflecting the villi and the fetal surface membrane layers (any degree of WBCs in vessel wall of cord is diagnostic; more than a few WBCs underneath the fetal amnion surface of the placenta, particularly if infiltrating the membrane stroma)   .
   • Organisms: If a placenta is unfixed, air-dried touch preps or smears from the under surface of the placental roof of the fetal  surface of the placenta can be used for diagnosis of various organisms (the same site for obtaining cultures) .     
   • Extent of cord involvement:
   1. is it segmental, regional, total? [degree or severity of ACA]
   2. vein only - phlebitis...funicular phlebitis (vein drains placenta back into fetus). 
   3. one artery, two arteries = funicular arteritis (hematogenous from fetus?...arterial blood from fetus to placenta). 
   4. Wharton's-jelly stroma involved = funisitis. 
   5. "funisitis" implies vessel/vessels plus Wharton's stromal involvement (see above). 
   6. cord segmental inflammation...with negativity for inflammation in the several centimeters at both insertion ends...likely reflects cord prolapse ahead of the head and over the endocervix.
   7. yellowish dots/nodules on surface indicate candida; longstanding can calcify; lymphoplasmacytic assoc. with lues or HSV⁴.
   • Because predisposing factors likely to remain, recurrence risk is high.  
   • Route: Whether infect is hematogenous, ascending from birth canal, or from endometritis/myometritis, exudate progresses through decidua, to intervillous space, to chorionic roof, through stroma to involve vessels & then fetus or to fetus and then to vessels.
7. Artifacts:
• extrusions of squames: fetal squamous debris extruded between amnion and either decidua parietalis or chorionic roof during L&D or postpartum placental manipulation [L09-894] is not to be confused with "amnion Nodosum".
8. Vasculopathies (blood flow obstruction in fetal blood "supply line"¹¹):
• Hemorrhagic endovasculitis (HEV): Also called "fetal thrombotic vasculopathy". As high as 86% of HEV placentae are stillborn; HEV = 50% recurrence rate (and 1/3 of those will be stillbirths); as many as 40% of HEV live births will have some developmental retardation (especially if associated with pregnancy-induced hypertension and chronic villitis)...very important for pediatrician to know this and to pick up on any developmental retardations and manage as soon as begin to be manifest. I (EBS) have seen "early" HEV change in one stillbirth definitely caused by a true cord knot [LMC-05-6783]. So, there is a pseudo-HEV: some have speculated that some HEV is the viable-endothelial-cell reaction attempting to organize the stagnant blood in the circulation following a fetal death [L08-11493] & not the cuase of it. I believe those cases are the pseudo-HEV cases, and I see pseudo-HEV in some stillbirths [L09-2016].
• vasculitis as part of ACA, either or both as chorionic roof vessel vasculitis or funicular (cord) vessel vasculitis of funisitis.
• VUE cases with obliterative fetal vasculopathy (vasculitis & perivasculitis with downstream avascular terminal villi) ¹¹. See more VUE info, below
• meconium-induced vasospasm as evidenced by vascular myonecrosis (myo-apoptosis).
• chorionic vessel thromboses, otherwise, of uncertain etiology: [L07-5508].
9. Chorangiosis of villi: Major congenital malformations found in 28% of chorangiosis births [L07-5499]; 27% of chorangiosis diagnoses are associated with neonatal death.  We are usually alerted to this diagnosis by microscopic visual inspection (don't be fooled by instances of capillary congestion); if you suspect it, the convention for diagnosis is: 10X power exam of three different blocks (the sites in no way related to any infarcts) and eval. of 10 or more micro fields in each block site, with each field averaging 10 or more villi in which there are 10 or more vascular channels per villous (very rarely diagnosed).  In practice I usually "eyeball" screen rather than count fields.  If screen is suspect, then count.  As the attached article reveals, this diagnosis prompts a careful exam of the live baby and alerts to ischemic or diabetic problems for subsequent pregnancies.
10. Villous edema: Dr. Naeye thinks any degree of villous edema might, in the future, be found to be associated with significant findings in the child and should be searched for.  True edema makes Hofbauer cells more obvious.  Hydrops is now most often non-immunological in etiology. 
11. Chronic villitis: Alone, it may or may not be significant, but should alert one for further clinico-pathologic case review. 
    • Specific villitis: infection associated variety; "diffuse sclerosing villitis" (DSV)...uniform villous involvement.   
    • Nonspecific villitis: Villitis of uncertain etiology (VUE); patchy villitis. Apparently not infection-associated, appears to be associated with (1) disorders which decrease maternal flow to placenta (such as eclampsia) and (2) those of unknown etiology.  Because of former, isolated finding could herald recurrence in subsequent pregnancy. 
12. Chronic hypoxic...low flow...villous changes: While very uncertain, an increase in syncytial knots with some cytotrophoblastic proliferation [LMC-05-6232] is thought by some to reflect decreased...low flow...villous chamber perfusion (one is required to find greater than 125 to 150 knots per 100 terminal villi) [LMC-06-1557].  BM thickening in central placenta possibly reflects hypoxia. Villous "hypermaturity" (thin & fibrous-like) may be a (more sustained & chronic ?) low flow hypoxic change. These changes suggest retarded flow in the maternal vascular supply line¹¹. And one finds it in midtrimester stillbirths due to poor flow following the demise & not causing the demise [L09-2016]. "Tenney-Parker" changes of the terminal villi, an increase in syncytial nuclear clumping and basophilia, are common in cases of chronic uteroplacental malperfusion, whether fetal flow or maternal . Expected in patients with sickle cell disease [LMC-06-10695].  
13. Brownish to pale subchorial "thrombi" beneath the fetal surface of the placenta: are related to increased fetal movement; associated with longer cords; reflect stasis (?).
14. Intrachorionic thrombi: may think it is an infarct on gross exam; indicate feto-maternal hemorrhage but may be insensitive [LMC-01-5295, term/near-death fetal demise, Hb2.0, K-B test 3%, fetal RBCs & not any intrachorionic thrombi. LMC-03-2803 6-8cc of intrachorionic thrombi.]. These may tip off to testing the mother with such as the K-B test for circulating fetal RBCs in mother's blood. Identifying these thrombi helps the obstetrician be forewarned to the possible generation of maternal antibodies against one or more fetal RBC, WBC, or Platelet antigens then detectable in a subsequent pregnancy.
15. Meconium: Hardly ever sufficient rectal accumulation prior to 28-30 weeks & likely that membrane pigmentation prior to then is hemosiderin⁶. Can often be found as macrophage pigmentation in the stroma of the fetal surface amnion and chorion stroma.  Meconium expulsion can be cleared in 2-3 weeks so fluid becomes clear again.  Location of pigmented macrophages not yet reliably relatable to time after meconium expulsion. Stillbirth placentae with some greenish color grossly may have undergone compacting of the usually loose subamnionic stroma and rendering the meconium macrophages harder to visualize [L09-2016]. Don't confuse with hemosiderin which is abnormally present prior to near term.  Look for amnion cell necrosis and vessel muscle necrosis in cord...assoc. with poor fetal outcome. 
16. Vasculo-syncytial membrane (V-S membranes): The normal term placenta has syncytial trophoblasts with nuclear knots and attenuated cytoplasm over the villous surface.  Terminal villous cross-sections typically show most of the cross-section occupied by capillary profiles (1-6) and with one or more peripheral ones bulging under attenuated trophoblastic cytoplasm with essentially no stroma between maternal and fetal blood may produce chronic hypoxia and fetal death.  
17. "Massive" or "excessive" perivillous fibrin deposition: This type of grossly massive deposition may result from immune rejection and lead to intervillous space occlusion and hypoxic fetal injury, IUGR [LMC-92-7437; LMC-94-1458; LMC-03-4820; LMC-04-6078; LMC-04-11106] or SGA, or death if affects enough volume.  It may be associated with recurrent fetal problems in subsequent pregnancies.  A variant where deposition is at maternal-aspect base is "maternal floor infarction"; avoid having too high of a diagnostic threshold (we have offered the warning of possible maternal thrombophilia with as low as about 5% floor involvement...LMC-06-5615; or atypical excessive involvement [L08-12153]). Implies maternal thrombophilia or hypercoagulation state¹⁰ (from such as "lupus anticoagulants or protein C or S deficiency).  
18. Infarcts & thrombi of parenchyma: DDX also includes chorangioma & nodular chorangiomatosis [L-07-2053]. If, in every other respect, the maternal blood supply to the placenta appears to be adequate, then the fetus is likely to survive infarction of up to 20-30%. If it involves over 10-15% of the placenta [L09-628 25%], it is almost invariably confined to patients with hypertensive disease in pregnancy...look for PIH-associated "acute atherosis" in membrane-roll decidua capsularis vessels. In 5-15% of placentae; and, specially if infarcts are more central, they tend to be associated with pre-eclampsia, diabetes, SLE, and utero-placental (maternal flow circuit) insufficiency [L07-11588]...may see consequences such as IUGR, fetal distress, or IUFD⁴.  You have to decide whether there is enough residual normal placenta and intervillous chamber space to support fetus.  "Maternal floor infarction" and/or "massive perivillous fibrin" can cause stillbirth and can recur; and such are most often associated with pre-eclampsia, particularly the HELLP syndrome variety (hemolysis, elevated LFTs, low platelets with RBC fragments).  When volume of infarcts is over 50% of placental volume, think of lupus anticoagulant etiology.
    Presence of infarcts implies acute vascular occlusion by some process.
    • Central and floor infarcts more important than peripheral perimeter infarcts.  
    • Infarcts of same (one episode) or variable (chronic on-going problem) ages?  
    • Infarcts are geographic, sharply delineated, reddish (fresh) to pale brown to yellowish white (older).
    • Subchorial or intervillous (intrachorionic) thrombi are brownish, firm, and more vague. Intrachorionic [LMC-04-891], if space occupying, probably reflect feto-maternal hemorrhage (a baby has about 70cc blood). Can be grossly mistaken for infarcts.
    • Breus' mole (massive subchorionic hematoma) is a rare entity associated with IUGR.
    • Intervillous/perivillous fibrin thrombosis: normally involves all term placentas, can be seen grossly on cut surface as faint laciness of a paler color in 25%, & excessive when more obvious grossly on cut surface as definitely lacy or "marbled" with paleness; & massive lesions are heavier & pale & may rim & outline a cotyledonous lobule ("gitterinfarct")⁹. Villitis may have a lacy or marbled cut surface⁹.
    • "X cell island" nodules caused by island expansion as fibrin accumulates in island centers rather than centers becoming cystic [L07-6650].  
    • Intraplacental vascular thromboses give softer, tan, slightly outlined foci.  
19. Cysts:
    • amnionic: protrude from amnion surface into cavity.
    • placental surface cysts: at maternal surface & often associated with subchorial fibrin & lined by subchorial trophoblasts & when numerous or larger, tend to be associated with IUGR¹³ [L08-13515].
    • chorionic (cystic cavitation of X cell islands): round to oval by U/S and contain a gelatinous fluid & can be just beneath the chorionic roof (subchorionic) or intrachorionic (septal) cysts [LMC-06-4298]. Subchorionic ones may impinge on blood flow of a roof vessel or may impinge on flow of blood at cord insertion site.
20. Focal amnion surface lesions: over placenta or cord (must very carefully examine so as not to miss):
    • Whitish dots: 
      • squamous metaplasia (insignificant)
      • Amnion nodosum (AN):  absolutely means severe oligohydramnious; always seen in renal agenesis cases (superficial lanugo debris & squames form amnion surface stromal nodules that displace amnion surface epithelium). Associated with poor fetal lung development. AN is not fetal squamous debris extruded between amnion and either decidua parietalis or chorionic roof during L&D or postpartum placental manipulation [L09-894].
    • Yellowish dots: 
      • candida amnionitis.
21. Amnion bands and loss of amnion membrane: infant abnormalities such as loss of finger should always have high intensity search for bands in placenta. 

22. Fetal & maternal RBCs & WBCs: there should be very few NRBCs in villous circulation of a normal term birth; if find, consider causes of hypoxia, alpha Thal., hemolytic problems.  Sickle cells [LMC-03-1535; LMC-04-1866 trait;], spherocytes and possibly other abnormal RBCs [LMC-03-8791], when in sufficient number, may be discernable in fetal villous circulation or maternal intervillous chamber blood. Congenital leukemia [L06-8166] with a WBC count of nearly 200,000 is surprisingly deceptive...WBC clumps most readily noted in larger fetal vessels (therefore, placenta not pale).
23. Decidual changes in basal decidua:
• Acute inflammatory cells are abnormal, though significance depends on quantity and presence elsewhere (see ACA, above).  
• If lucky enough to see efferent ends of spiral arterioles, retention of muscular wall, perivascular acute cells, atherosis, and thrombi are always abnormal and imply a reduction in uterine-to-placenta maternal blood flow.  
• Lymphocytes probably simply reflect a fetal-maternal immunological battle and are of no significance unless so prominent as to extend through floor to involve basal villi.  
• Lymphocytes plus plasma cells (with or without eosinophiles) probably not normal but of uncertain significance.  
• Can offer "compatible with" or "suggestive of" placenta accreta (in a placenta which was clinically abnormally tightly attached) if see basal decidua absent or only 1-3 cells thick or with some attached strands of myometrium.  Cannot flatly diagnose accreta on a delivered placenta.  Placental floor infarction as well as severe basal villitis are two additional causes of difficult placental separation.[LMC-03-2618]
24. Placenta previa: very hard for pathologist to diagnose; maybe see some micro-organization of exposed basal placental surface (and admixed WBCs) with elsewhere more normal. A membranous (very thin toward one edge) zone is nearly always a placenta previa⁶.
25. Abruption of placenta: in a variable percentage of cases it leaves its pathological mark as a retro-placental hematoma, fresh to variably organized. Careful histological exam to be sure not an intrachorionic thrombus.  
26. Lobation: placenta is normally a round to oval disc.
    • succenturiate lobation: an extra lobation  still based on the placenta proper (can be a reflection of an abnormal uterine cavity...septation or fibroid, etc.)⁶.
    • accessory lobation: an extra lobation totally detatched from the placenta proper and associated with risk of vasa previa⁶ situation (as the vessels connecting the accessory lobe to placenta proper course through the interconnecting membranes, which zone might overly the uterine exit through the cervix).
27. Villous cells:
    • Langhan's Cytotrophoblast = cuboid, polyhedral or ovoid with well marked borders; clear to slightly granular cytoplasm; pale, finely granular nucleus; PAS + ; and can be in stroma; mature villi = compressed between syncytial trophoblast and BM.  
    • Hofbauer = round, ovoid or reniform; 25 micro diameter; eccentric nucleus; usually coarsely vacuolated cytoplasm; they are tissue macrophages; is alpha-1 antichymotrypsin & CD68 positive.  Can be stellate shaped.    
    • Syncytial trophoblast = differentiated multinucleated.  
    • Stromal cell = stellate, fibroblast-like.  
    • Lymphocyte = as identified in any other tissue.  
    • Mast cell = in small numbers and identified as in other tissues.  
    • Plasma cell = coarse nuclear chromatin and RNA-rich cytoplasm.  
    • Decidual cell = large epithelioid cell and ID by location external to trophoblast.
28. Ultrasound grades and gross path correlates:
    • I : u/s diagnosis as early as 12 weeks and is c/w 1st and 2nd trimesters (suspect diabetes if >4cm thick, GO).  
    • I: most often 30-32 weeks but can be seen at term.  
    • II: doesn't bracket so well and can also be seen at term.  
    • III: term placenta and gross exam reflected by deep clefting around cotyledons and/or presence of calcium speckling over cotyledon basal surfaces.  
    • thin placentas - IUGR, juvenile diabetic mothers with retinopathy.  
    • thick placentas - > 4 cm often normal but see it with gestational diabetes, non-immune hydrops, & congenital anomalies.
29. Villous maturity retardation or acceleration:
    • Retarded = "maturitas retardata placentae"[L08-13363]: see very widespread and obvious lack of histological maturity for gestational age.
    1. in some diabetics
    2. in some HDN
    3. in some luetic
    4. in some Down's; in some anencephalics
    5. in some apparently normal pregnancies 
    • Accelerated = "maturitas praecox placentae": see very widespread and obvious histological maturity for gestational age.
    1. in some pre-eclamptics
    2. in some essential hypertension and PIH cases: may reflect an attempt to increase villous oxygen-grabbing efficiency in cases of low or reduced intervillous maternal blood flow [LMC-06-1557; L09-7698].
    3. skinny terminal villi with exaggerated syncytial trophoblasts look hypermature and indicate reduced utero-placental blood flow (low flow) in the sense of the fetal load demanding more blood than the uterus can supply¹⁴ (as in large fetuses, multiple gestation pregnancy, preterm delivery, and PIH).
• uneven maturation = tends to recur and suggests higher risk pregnancy [LMC-05-6232].  
30. Clinical abbreviations:
    HDN = hemolytic disease of newborn
    
    SGA = small for gestational age
    
    IUGR = intrauterine growth retardation
    
    PIH = pregnancy induced hypertension (is this a maternal compensatory attempt to pressure over-ride obstructive deciduo-placental lesions which have given rise to decreased intervillous blood flow from mother?): uneven villous maturation, decidual lesions of acute atherosis, increased prevelance of intravillous fibrinoid (normally 3% or less of villi), infarcts, and "Tenney-Parker" changes of the terminal villi (an increase in syncytial nuclear clumping and basophilia).
    
    CVS = chorionic villous sampling
    
31. Fetal size:
    • Large: macrosomia...child of diabetic; a large for gestational age (LGA) baby.
    • Small: SGA...IUGR; lesions associated with IUGR:
      1. placental surface cysts (multiple or large¹³).
      2. acute atherosis, even if not PIH case.
      3. chronic villitis (both DSV & VUE).
      4. small placenta; thin placenta.
      5. short cord; thin cord; hypertwisted cord.
      6. definitely excessive or massive perivillous fibrin deposition.
      7. central infarcts sufficient to cause uteroplacental insufficiency.
      8. massive subchorial (under fetal surface) hematoma (Breu's mole).
32. Cardinal Rule: don't stop your diagnostic evaluation on discovery of one type of lesion.  It's fairly common to have multiple placental abnormalities.
33. Prenatal technology:
    • ultrasound of high quality can detect fetal sex, multiple fetuses, even differentiate monochorionic (thin) from dichorionic (thicker) septum, congenital anomalies, uterine and placental shape and placental location abnormalities, placental maturity, etc.  
    • doppler of high quality can detect intervillous space flow reductions.  
    • we should look for lesions of any invasive procedures such as amniocentesis.  
    • fetal heart rate and uterine contraction monitoring.
    • scalp electrodes.  
    • cord blood gases.
34. Importance of placental exam?
    • if we detect lesions prone to recur, the obstetrician will be able to monitor the subsequent pregnancy better.  
    • perinatal morbidity can be reduced when neonatologists and pediatricians know of such as chorioamnionitis.  
    • discovery of placental lesions (such as HEV) portending risk of developmental retardation need to be known by the pediatrician because better outcomes follow early detection and management as they manifest in the child.
35. Malpractice cases:
    • amazingly, stillbirth cases are "worth" much less than a damaged child or cerebral palsy case, and these are practically un-winnable by plaintiff if the placental exam is abnormal.    
    • damaged child cases have about a 20 year statue of limitations.  
    • for plaintiff to win a lawsuit [societal adverse impact of lawsuits], there must be:
    1. a damaged patient.
    2. negligent acts .
    3. cause of damage must be the negligent act or acts; therefore, it is very difficult, EVEN IF the doctor commits negligent acts, to win a suit for a damaged infant if abnormalities are found in the placenta!
36. Villous surface area: (fetal weight tends to be proportional)
    • Normal surface area data:
      1. Planimetric method, 6.5-14.7 sq. m.
      2. Point counting method, mean of 11 sq. m.
    • Associated with decreased surface area:
      1. placentae with infarcts associated with maternal hypertension (cases ave. 8.4 sq. m.).

      2. Normotensives with SGA babies (ave 6.4 sq. m.).

    • Increased in HDN and not merely due to edema.

    "No pathological examination of the placenta is really complete without measurement of the placental volume, the chorionic villous surface area, and the volume proportions of the intervillous space, villous tissue, and villous capillaries." This is, of course, an exam which cannot be done in the usual pathology lab.

37. Gestational-Dates Categories:
    • pre-term = <37 weeks  ("very pre-term" = <32 weeks).
    • normal term range 37-40 weeks.
    • post-dates, post term= >40 & up to 42 weeks. 
    • post-dates, post mature= >42 weeks
38. HELLP Syndrome: no placental findings other than possible PIH acute atherosis lesions [L-01-1457].
39. Amnion Nodosum = results from oligohydramnious and presence somewhat predictive of degrees of pulmonary hyperplasia. AN is not fetal squamous debris extruded between amnion and either decidua parietalis or chorionic roof during L&D or postpartum placental manipulation [L09-894].
40. Acute atherosis lesion in membrane-roll arterioles in decidua vera is highly suggestive of PIH/eclampsia/pre-eclampsia but can be seen in IUGR, lupus anticoagulant syndrome, and maternal renal disease.  The affected vessels have hyaline occlusion of some decidua vessels...more likely to be seen in the decidua capsularis vessels.
41. PIH: look for "low flow" skinny terminal villi (villous hypoplasia) with increased space around them (accelerated looking maturation), acute atherosis of decidual vessels, and an increased percentage of terminal villi with subtrophoblastic fibrin.
42. Blood cells:
    • Look for increased NRBCs (especially at >7500/mm³)¹¹ or WBCs.
    • Look for sickled RBCs [L02-1805] or other dysmorphic RBCs.
43. Nodules:
• non-yellow early infarcts
• chorangioma; chorangiomatosis placentae (multiple chorangiomata) [L09-3796].

Chronic Villitis (VUE or DSV)

TWINS & ZYGOSITY

"T" Block section of the dividing membranes:

mono chorionic

dichorionic

*********************************************************************************************

CHORIONIC-ROOF-PERIPHERY FIBRIN RINGS & EXTRACHORIAL PLACENTAS

Trace peripheral change & no extrachorial placenta

DEGREE/STAGES OF ACUTE CHORIOAMNIONITIS (ACA):

1. Acute inflammatory cell infiltrate at less than 18 weeks gestation is from the mother; after 18 weeks, is from the mother and infant.
2. Fetal death by other causes, followed by postmortem acute chorioamnionitis will show exudate in a maternal pattern only (no cord or chorionic vasculitis).
3. Acute chorioamnionitis ascends through intervillous space whether it originates through the cervix, hematogenously from the mother, or from the underlying endometrium.
4. If there is a slight acute villitis in association with a severe acute chorioamnionitis, then this suggests that the fetus is septicemic from septic amnionic fluid. 
5. Prominent acute villitis associated with a much less impressive chorioamnionitis is said to suggest origin from maternal hematogenous routes.
6. Characteristic pattern of cervical ascending-induced fetal chorionic vasculitis is with the perivascular infiltrate more eccentrically pronounced toward the direction of the amniotic cavity.
7. If amnionic fluid is rapidly populated with organisms, then ingested by fetus, one may see funisitis predominating in umbilical arteries and the chorionic roof membranes only little if any involved.
8. If only a single segment of cord shows funisitis not associated with acute chorioamnionitis, then prolapsed cord is highly likely.

References:

1. Perrin EVDK, Pathology of the Placenta,  1984.
2. Naeye RL, Disorders of the Placenta, fetus, and Neonate: Diagnosis and Clinical Significance, 1992.
3. Silverberg SG, Principals and Practice of Surgical Pathology and Cytopathology vol 3, 1997 p.2593-2628.
4. Lange JM, Placenta lecture at MUSC, Charleston, SC 3/03 [KRM]
5. Singh V, et. al., Umbilical Cord Lesions in Early Fetal Demise, Arch. Path. & Lab. Med. 127(7):850-853, July 2003.
6. Spark RP, The Placenta: the Rebirth of the Afterbirth, a Critical Assessment & Clinicopathologic Correlation Lecture, AAPA workshop handout, September 2003 Phoenix meeting.
7. Gersell DJ, May 1997 ASCP CME OB-Gyn Course, Savannah, Ga....handout. (EBS's office)
8. The Cedars-Sinai Medical Center in L. A., California, website in neonatology, placenta, as of 29 Sept. 2004.
9. Schuler-Maloney, Doris, The Placenta: To Know Me is to Love Me, spiral-bound 175 page manual and/or 400 photo CD, DMS Pathworks, Inc. (website has a nice introduction to placental exam triage).
10. Kraus FT, Redline RW, Gersell DJ, Nelson DM, Dicke JM, Atlas of Nontumor Pathology: Placental Pathology, AFIP, 331 pages 2004 [EBS's office].
11. Redline, WR, "Severe fetal vasular lesions in term infants with neurologic impasirment ", AJ Ob & Gyn 192:452-457, 2005.
12. Yetter JF, Examination of the Placenta, American Family Physician 57(5):16 pages, 1 March 1998, online as of 7/17/2006.
13. Brown DL, et. al., "Placental Surface Cysts Detected on Sonography", J. Ultrasound Med. 21:641-646, 2002.
14. Kaplan CC, "Placental Examination", LABMEDICINE 38(10):624-628, October 2007.