Placental pathology

1. PLACENTAL PATHOLOGY
Moderator – Dr.Navya B.N
Speaker –Dr.Ashwini K.T

2. PLACENTA
• Shape : Discoid
• Diameter : 15-20cm
• Weight : 450gm-600gm
• Thickness : 2- 2.5cm at its
center and gradually
tapers towards periphery
• Position : In the upper
uterine segment (99.5%).
• Surfaces : Fetal surface
and maternal surface .

3. Foetal Surface
• Smooth , glistening and
is covered by the
amnion which is
reflected on the cord.
• The umblical cord is
inserted near or at the
center of this surface
and its radiating
branches can be seen
beneath the amnion .

4. Maternal Surface
• Dull greyish red in
colour and is divided
into 15-20 cotyledons .
• Each cotyledon is
formed of the branches
of one main villus stem
covered by decidua
basalis .

5. Structure :
• Chorionic plate on fetal side
• Basal plate on maternal side
• Stem villi between the plates
• Intervillous space between stem villi filled
with maternal blood.

7. Development
Prelacunar stage :
• Blastocyst implantation :24th day of menstrual
cycle on upper posterior uterine wall .
• The embryonic pole of the blastocyst is
attached to the endometrium.
• Syncytiotrophoblast (ST) proliferates towards
decidua basalis & capsularis.
• Cytotrophoblast (CT) differentiates to primary
mesoderm.

8. Early lacunar stage :
• Lacunar spaces from within ST around
trabeculae (cords of ST)
• Lacunae enlarge and erode branches of uterine
arteries & veins – uteroplacental circulation
Primary lacunar stage :
• Trabeculae convert into primary villi with
invasion by CT in central axis.

9. LACUNAR STAGE

10. Secondary villous stage :
• Primary mesodermal
cells invade the primary
villi.
Tertiary villous stage :
• Fetal vessels derived
from umbilical vessel
appear within primary
mesoderm .
• Numerous villi branch
from tertiary villi in to
intervillous space
( Labyrinthine structure )

12. • Chorionic villi at embryonic pole proliferate
rapidly to form chorion frondosum.
• Rest of the embryonic villi degenerate &
disappear – chorion leave (CL).
• 3RD month of pregnancy – decidua capsularis
& parietalis fuse with regression of CL .
• Persistent chorionic frondosum +decidua
basalis = HUMAN PLACENTA .

13. • Primary villi – when trabeculae between
lacunae of syncytiotrophoblast and intermediate
trophoblast are invaded by cytotrophoblastic
cells.
• Secondary villi – extraembryonic mesoderm
invades primary villi which thus develops
mesenchymal core.
• Tertiary villi –when the mesenchymal cores of
villi gets vascularized.

14. TROPHOBLAST CELL TYPES
Layer Location Description
Cytotrophoblast Inner layer Single celled ,inner layer of
the trophoblast forms
syncytiotrophoblast villous
IT and implantation site IT.
syncytiotrophoblast Outer layer Thick layer of
multinucleated syncytium
that lacks cell boundaries
and grows into the
endometrial stroma secretes
hCG.
Intermediate trophoblast Implantation site ,chorion
,villi(dependent on
subtype)
Anchor placenta

15. FUNCTIONS OF:
• Villous intermediate trophoblast: - it
maintains the structural integrity of the villi
that anchor placenta to basal plate.
• Implantation site intermediate trophoblast –
establishes the maternofetal circulation by
invading the spiral arteries .
• Chorionic type intermediate trophoblast :-
mechanical barrier to the maternal immune
system.

16. FUNCTIONS OF PLACENTA
• 1.Respiratory function
• 2.Nutritive function
• 3.Excretory funcion
• 4.Production of enzymes
• 5.Production of pregnancy associated plasma
proteins
• 6.Barrier function
• 7.Endocrine function

17. EXAMINATION OF PLACENTA
Indications for Comprehensive Gross and Microscopic Examination by a
Pathologist
• Maternal conditions
• Diabetes mellitus (or glucose intolerance)
• Hypertension (pregnancy-induced)
• Prematurity (pregnancy <32 weeks)
• Postmaturity (pregnancy >42 weeks)
• Maternal history of reproductive failure (defined as one or more
previous stillbirths, spontaneous abortions, or premature births)
• Oligohydramnios
• Fever
• Infection
• Maternal history of substance abuse
• Repetitive bleeding (other than minor spotting of the first trimester)
• Abruptio placentae

18. • Fetal and neonatal conditions
• Stillbirth or perinatal death
• Multiple birth
• Congenital abnormalities
• Fetal growth retardation
• Prematurity (<32 weeks)
• Hydrops
• Viscid/thick meconium
• Admission to a neonatal intensive care unit
• Severe central nervous system depression (Apgar score of <3
at 5 minutes)
• Neurologic problems, including seizures
• Suspected infection
• Placental conditions
• Any gross abnormality of the placenta, its membranes, or the
umbilical cord

19. STORAGE & PROCESSING
• Placentas should never be frozen. Freezing
distorts the villi, obscures meconium, and
compromises diagnosis.
• For fixation, the specimen should be placed in
at least 10 times its volume of formalin.
• If samples are taken fresh for fixation before
trimming, they should be no more than 2 cm
thick.

20. Examination of placenta in
ABORTION
• 1ST TRIMESTER –
MOST COMMON CAUSES : chromosomal
abnormalities &“TORCH” infections
Other causes – mechanical disturbances
,endocrine diseases.
Grossly: Gestational sac – intact or ruptured
Fetal parts
Viable chorionic villi

21. MICROSCOPY:
Fetal parts ,Chorionic villi or
trophoblast – main criteria
- Enlarged hyalinized spiral artery &
fibrinoid matrix – suggestive of
intrauterine implantation.
- Other endometrial patterns strongly
suggestive of gestation : gestational
hyperplasia and Arias stella reaction .

22. • SEPTIC ABORTION –
Most common organisms- coliform &
streptococci
Diagnosis – is made by identifying the organism.
• HYDROPIC ABORTUS : villous swelling and
cistern formation is absent .Villi are
surrounded by attenuated trophoblast .

23. • 2nd TRIMESTER :
Can be spontaneous ,surgically induced or
prostaglandin induced
Degenerative changes – focal decidual necrosis
,intradecidual hemorrhage ,congestion &
thrombosis of maternal vessels.

24. ANOMALIES
OR
NON NEOPLASTIC
LESIONS

25. TWIN PREGNANCY
Monochorionic
placenta:indicative of
monozygotic twins
.Stripping of amnion
reveals a continuous
chorionic plate beneath
the septum and vascular
anastomoses between
the twins.

26. • Dichorionic placenta –
compatible with either
monozygotic or
dizygotic
twinning.rough
chorionic ridge at the
base of the septum and
lack vascular
anastomoses.

28. PLACENTA BILOBATA
• The placenta is separated into lobes
• Division is incomplete and vessels of fetal
origin extend from one lobe to the other before
uniting to form the umbilical cord.

29. SUCCENTURIATE LOBES
• Small accessory lobe
≥1,develop in the
membranes at a distant from
the periphery of main
placenta , to which they
usually have vascular
connections of fetal origin
• Incidence :5%
• Retained in uterus after
delivery and may cause
serious hemorrhage
• Accompaning vasa previa –
dangerous fetal hemorrhage.

30. PLACENTA MEMBRANACEA
• All of the fetal
membrane are covered
by functioning villi and
the placental develops
as a thin membranous
structure occupying the
entire peiphery of the
chorion.

31. • Circummarginate
placenta - a flattened
edge with a ridge of
fibrin demarking the
edge of the vascular
plate. It often only
involves a portion of the
circumference.
• Circumvallate placenta -
a peripheral cuplike
insertion of the
membranes at the
placental surface.

32. Fenestrated Placenta :
• Central portion of a
discoidal placenta is
missing
• The defect involves
only villous tissue with
the chorionic plate

33. • 1.Placenta accreta :
placenta villi adhere to
myometrium without an
intervening layer of
decidua.
 A. Placenta increta : villi
within the myometrium
usually involving
previous cesarean
section.
 B.Placenta percreta :villi
penetrate through the
uterine wall to the serosa
.

34. PLACENTA ACCERTA

35. AMNION NODOSUM
• Small nodules <1mm on the extraplacental
membrane –pathognomic of oligohydramnios.

36. PLACENTAL INFLAMMATION
• SUBCHORIONIC CYST
:
 “UNDER THE FETAL
PLATE”
 Origin from trophoblastic
X cells
 Associated with diabetes
mellitus or maternal fetal
Rh incompatibility.

37. • NECROTIZING VILLITIS FROM LISTERIA
INFECTION

38. ACUTE INTERVILLOSITIS
CHRONIC INTERVILLOSITIS

39. CHORIOAMNIONITIS
• Inflammation of the fetal membranes is usually
manifestation of intrauterine infection.
• Associated with prolonged membrane rupture and
long labor.
• Characteristic : clouding of the membranes
Foul odor
• Definition : mono and polymorphonuclear leukocytes
infiltrate the chorion
• Leucocytes are found in amnionic fluid (amnionitis )
or the umbilical cord (funisitis ).
<20weeks almost all polymorphonuclear leukocytes :
maternal origin.
>20weeks: inflammatory response : maternal & fetal

40. Acute chorioamniontis

41. Intensive inflammatory infiltrate of
the umblical cord (Funisitis)

42. PLACENTAL INFARCTS
• most commom placental leisons
• Etiology : preeclamptic toxemia ,essential
hypertension , Rh incompatibility and non toxic
antepartum hemorrhage
• Types (by leison types)
Located at the placental margin(90%),size <1cm
(90%)
Underneath the chorionic plate
Intercotyledonary septa

43. PLACENTAL INFARCT
• 1.fresh infarct :
dark red and
firmer
consistency.
• 2.old infarct :
hard , white mass
of granular
appearance.

44. GHOSTS OF CHORIONIC VILLI IN
A LONG STANDING PLACENTAL
INFARCT
Microscopic :
• 1.crowding of villi
• 2.virtual obliteration of
intervillous space
• 3.marked congestion of
villous vessels.
• 4. old infarcts : mass of
crowded ghost villi are
seen.

45. PLACENTAL SITE SUBINVOLUTION : SHOWING THICK
WALLED VESSELS WHOSE LUMEN IS PARTIALLY
OBLITERATED BY ORGANIZING THROMBI
• Curettage specimen :
large maternal vessels
from placental site
partly filled with
thrombi.

46. TUMORS and TUMOR LIKE
CONDITIONS
Chorioangioma (Hemangioma):
• Benign tumor of placenta
• Incidence : 1%
• Hamartomas of primitive chorionic mesenchyme.
Diagnosis :
• Larger choriongiomas – sonographic findings
• Associated symptoms
• Small growths : asymptomatic
• Larger tumors : hydramnios or antepartum hemorrhage
• Complication : associated with low birth weight
Fetal death and malformations are
uncommon .

47. • GROSS:
 Well circumscribed and
purplish mass
 May protrude on fetal
surface or may remain
localized in the
placental substance .

48. MICROSCOPY : composed of
network of proliferating
capillaries
• Mitosis may be present
• Degenerative changes are
common

49. ASSOCIATIONS :
Hydromnios
Hemorrhage
Premature delivery
Premature placental seperation
Placenta previa

50. • CHORANGIOSIS: condition characterized by
an increase in the number of vascular channels
per villus.
• CHORANGIOMATOSIS : is as diffuse as
chorangiosis but the vessels have thicker wall
containing actin positive smooth muscle
• TERATOMAS of the placenta are very rare.

51. TUMOR METASTIC TO THE
PLACENTA:
• Malignant tumors rarely metastasize to the
placenta
• Melanoma , Leukemias and Lymphomas
• Tumor cells usually are confined within the
intervillous space.

52. GESTATIONAL TROPHOBLASTIC
DISEASE
DEFINITION : is a spectrum of proliferation
abnormalities of trophoblasts associated with
pregnancy .
3 MAIN TYPES
• 1. HYDATIDIFORM MOLE
• 2.PLACENTAL SITE TROPHOBLASTIC
TUMOR
• 3.CHORIOCARCINOMA

53. NIH classification of Gestational
Trophoblastic Disease
I . BENIGN GTD
A. Complete hydatidiform mole
B. Partial hydatidiform mole
II . Malignant GTD
A. Non metastatic GTD
B. Metastatic TD
1.Good prognosis , low risk –absence of any risk factor
2.Poor prognosis ,high risk – presence of any risk factor
a.Duration >4months
b. Pretherapy level of beta hCG in serum >40,000mIU/mL.
c. Brain or liver metastasis
d. GTD after term gestation
e. Prior to failed therapy

54. GTN(modified WHO classification
1998)
• Non metastatic ( confined to uterus)
• Metastatic
LOW RISK
-< 4 months duration
-initial serum HCG levels < 40,000miu/ml
-metastasis limited to lungs and vagina
-no prior chemotherapy
-no preceding term delivery
HIGH RISK
-duration > 4 months
-serum HCG levels > 40, 000
-brain or liver metastasis
-failure of prior chemotherapy
-Following term pregnancy
-WHO score>7

55. HYDATIDIFORM MOLE
• The trophoblastic proliferation is associated
with swelling of the villi
• Subdivided into
 complete
 partial
 invasive.

56. COMPLETE MOLE
• Caused by abnormal gametogenesis and fertilization .
• nuclei contains paternal chromosome
• Cytoplasmic DNA is maternal derived
• 46XX / 46XY
• Incidence : 1 in 2000
• “Repetitive “ moles are usually complete mole
• Clinically : toxemia of pregnancy is seen (HTN ,edema
,albuminuria ) , the affected uterus is disproportionately
large for the stage of pregnancy, serum hCG levels
raises even after 14 weeks.

57. GROSSLY :
• typically described as
“ Bunch of grapes “
• Villi showing hydropic
degeneration
• No identifiable embryo
,cord , amniotic
membrane.

58. MICROSCOPIC :
• Tophoblastic
hyperplasia –
characterstically has a
circumferential but
haphazard arrangement
• Vesicular swelling
• CISTERN formation

59. • Immunohistochemically : hCG is widely
distributed , PLAP is patchily distributed , both
the alpha and beta inhibin are evident.
• Potential marker p57kip2 absent .
• P53 darkly stained in complete mole.

60. • Treatment : initial curettage
• serum hCG levels at 10,20,30,45,and 60 days
after the termination of molar gestation .
• If there is rising titre after 60 days
chemotherapy is administered.

61. PARTIAL MOLE
• Associated with the presence of embryo.
• 69XXX or 69XXY and few show trisomy 16.
• GROSSLY : vesicular villi admixed with
normal appearing ones .

62. MICROSCOPICALLY :
• focal edema leading to
central CISTERN
formation and stromal
inclusions.
• Scalloping of villi .
• Trophoblastic
proliferation.
• fibrosis of the villous
stroma.

63. • IMMUNOHISTOCHEMICALLY :
localization of Hcg and hPL
• P57kip2 potential marker .

65. INVASIVE MOLE
Refers to Nearly always of the complete type but
occasionally of the partial type .
• villi penetrate deeply the myometrium and / or its blood
vessels.
• myometrial penetration is extensive lead to persistent
hemorrhage , serosa is intact.
• Vascular invasion as trophoblastic nodules outside the
uterus such as vagina brain lung and spinal cord
• Distinguished from other moles by its invasiveness and
the presence of villi which are also present in the
metastatic foci.

66. GROSS
MICROSCOPY

67. CHORIOCARCINOMA
• This is extremely
malignant form of
trophoblastic tumour may
be considered a
carcinoma of chorionic
epithelium, although
growth and metastasis
behave like sarcoma .
• Characterized by
abnormal trophoblastic
hyperplasia and anaplasia ,
absence of chorionic villi

68. • Incidence: 1: 250-5000 pregnancies in Asia and
1:4000 in the west.
• Origin:
* Choriocarcinoma is a malignant tumour of the
trophoblast .
1- About 50% of cases follow molar pregnancy.
2- 25% follow abortion
3- 23% follow normal pregnancy
4- 2% follow ectopic pregnancy.
* In rare cases, the tumour arises as a teratoma in
the ovary or testicle.

69. GROSSLY :
The tumor arises in the
endometrium as
1. Classically a soft,dark red,
hemorrhagic,round nodular
tumour with a marked
tendency to form large pale
areas of ischemic necrosis,
foci of cystic softening .
2. Malignant tissue may be
buried within the
myometrium , inaccessible
to the curette, or hidden in
a distant metastasis.
3. However, any of these
tumor patterns secretes
(hCG) which causes cystic
changes of the ovaries in
about 30% of cases..

70. MICROSCOPICALLY :
• The classic pattern of
choriocarcinoma has been
described as “ BILAMINAR “,
“DIMORPHIC, OR
BIPHASIC “.
• Tumor is composed of clusters
of cytotrophoblast separated by
streaming masses of
syncytiotrophoblast leads to
“Dimorphic plexiform pattern “.
• Villi are characteristically
absent this differentiates
Choriocarcinoma from invasive
mole.
• Choriocarcinoma lacks the
intrinsic endothelium-lined
vascular channels in the centre
of a tumour, making it a unique
malignant solid tumour.

72. • IMMUNOHISTOCHEMICALLY : positive
for hCG and keratin
• Mode of spread:
1. direct spread: to the parametrium, tubes and
ovaries.
2. Blood spread: occurs early to distant organs.
The commonest sites are lungs (80%), vagina
(30%), brain (10%) and liver (10%)

73. Diagnosis:
• A- symptoms:
1- Persistent or irregular vaginal bleeding: it is the
commonest symptom occurring after labor,
abortion or evacuation of a vesicular mole.
Bleeding can occur within days or months but
rarely after 2 years.
2- Vaginal discharge: which is blood stained and
offensive due to ulceration and infection of the
growth .
3- amenorrhea: may be present due to continuous hCG
production.
4-Dyspnoea and haemoptysis are noticed with lung
metastasis.
5-The appearance of neurological symptoms like
hemiplegia, epilepsy, headache and visual
disturbances suggest brain metastasis.

74. • B- signs:
(1) cachexia and severe anaemia.
(2) fever may be present due to infection and
necrosis
(3) the uterus may be normal size or enlarged and
soft.
(4) the ovaries: may be enlarged and cystic.
(5) metaststic nodules: in the vulva or vagina

75. C- investigations:
(1) uterine curettage: should be done in every case
of persistent or irregular uterine bleeding after
labour, abortion or molar pregnancy. However,
intramural tumour cannot be detected by
curettage.
(2) serum β- subunit of hCG: persistent or rising
titres in absence of pregnancy are indicative of
trophoblastic neoplasia.
(3) biopsy: from metastatic vulvar or vaginal
lesions.

76. • (4) imaging:
a- plain X-ray chest: may show
secondaries in the form of "
cannon balls" or "snowstorm"
appearance.
b- ultrasonography: to detect
tumour, cystic ovaries and
exclude remnants of conception.
c- CT scan: for lungs, liver, brain
and bone.
• (5) lumbar puncture: plasma
hCG/ CSF hCG ratio less than 60
strongly CNS involvement -
metastases
• (6) blood studies:
a- complete blood picture including
platelet count
b- Renal, liver and thyroid function
tests
c- Blood group

77. FIGO STAGING SYSTEM FOR
GESTATIONAL TROPHOBLASTIC
TUMOUR
Stage I : Disease confined to
uterus
Stage II : GTT extending
outside uterus but limited to
genital str. (adenexa vagina
broad ligaments)

78. Stage III : GTT extending of
lung with or without
Known genital tract
involvement
Stage IV: All other metastatic
sites

79. Managment
• Chemotherapy.
• Surgery.
• Radiation.

80. FOLLOW UP
All patients with stage I through stage III disease should
receive follow up with-
1. Weekly measurement of HCG level until they are
normal for 3 consecutive weeks.
2. Monthly measurement of HCG value until level are
normal for 12 consecutive months.
3. Effective contraception during the entire interval of
hormonal follow up.

81. WHO Prognostic Scoring System
Score
Prognostic factor 0 1 2 4
Age(years) ≤39 >39 — —
Pregnancy history
Hydatidiform
mole
Abortion,
ectopic
Term
pregnancy
—
Interval (months) of
treatment
<4 4-6 7-12 >12
Initial hCG(mIU/ml) <103 103-104 104-105 >105
ABO Group O-A B-AB
Largest tumor(cm) <3 3-5 >5 —
Sites of metastasis Lung
Spleen,
kidney
GI tract, liver Brain
No. of metastasis — 1-4 4-8 8
Previous (treatment) — — Single drug 2 or more
0-4 low risk, 5-7 intermediate risk, >8 high risk for death

82. PROGNOSIS
• The cure rate is almost up to 100 percent in
low risk and about 70 percent in high risk
metastatic groups.

83. PLACENTAL SITE
TROPHOBLASTIC TUMOR
• RARE form
• Also known as atypical choriocarcinoma and
trophoblastic pseudotumor
• 75 % cases follow a normal pregnancy
• Paternally derived X chromosome may be
necessary for its formation
• GROSSLY : well localized mass or ill defined

84. • MICROSCOPICALLY :
• Large trophoblastic cells with abundant
eosinophilic cytoplasm and nuclear
pleomorphism invading the myometrium and
vessel lumina

85. IMMUNOHISTOCHEMICALLY : hPL is strong , hCG
is focal , positivity for keratin , CD66a ,
CD146,Pregnancy associated major basic protein ,
HLA-G
Distinction with choriocarcinoma is made based on:
• Lack of a dimorphic population of cytotrophoblast and
syncytiotrophoblast
• Lack of paucity of hemorrhage
• Presence of an interdigiting pattern of muscle invasion .

86. EPITHELIOID TROPHOBLASTIC
TUMOR
• OCCURS IN REPRODUCTIVE AGE
GROUP
• Primary tumor can be extra uterine and serum
hCG LEVELS ARE elevated.
• GROSSLY : solid and cystic ,discrete and
hemorrhagic

87. • MICROSCOPICALLY :
intermediate trophoblast
forming nests and solid
masses,necrosis is
extensive.
• IMMUNOHISTOCHE
MICALLY : diffuse
reactivity for keratin ,
alpha inhibin , EMA , E
–cadherin .

88. UMBILICAL CORD
• Length : 55 to 60 cm
• Diamter – 2cm
• Structure : consists of mesodermal connective
tissue called wharton‘s jelly , covered by
amnion .
• INSERTION : fetal surface of placenta near
the center.
“ eccentric insertion “ (70%) or at the center
(30%).

89. CONTAINS :
• 1. One umbilical vein
• 2. Two umbilical artery
• 3. Remnants of the yolk sac and allontois
• 4. Wharton ‘s jelly

90. Marginal insertion

91. Velamentous insertion

92. Abnormalities of the length of the
cord
• Long cord (> 90cm )is result of fetal activity .
• Umbilical true knot

93. Short cord
• <30cm
• delay in 2nd stage labor
• Rupture
• CNS dysfunction
• Psychomotor impairments
• Congenital neuromuscular diseases.

94. SINGLE UMBILICAL ARTERY
• May be associated with other fetal congenital
anomalies .
• Confirmed by microscopic examination .

95. CORD WITH OVERCOILING

96. FUNISITIS

97. REFERENCES
• 1.Mills SE , Carter D ,Sternberg diagnostic
pathology , 4th edition , Lipincott Williams and
Wilkins.
• 2. Rosai J , Rosai and Ackerman Surgical
pathology , 9th edition , Elsevier.
• 3.Tavassoli F.A.,Devilee P(Eds): World health
organization classification of tumors .Pathology
and genetics of tumors of the breast and female
genital organs. IARC Press : Lyon 2003.
• 4.Dutta DC : Textbook of obstretics .7th edition.
• 5.Internet sources.

98. THANK YOU