Pathology Of Trophoblastic

Diseases

Guide:Lt Col V.Srinivas

Trophoblastic Diseases
Overview of morphology and
differentiation
History, Classification
Role of the pathologist in diagnosis of
GTD
Biopsy and differential diagnosis
Early development of placenta
Blastocyst Implantation-24 th day
of menstrual cycle
The embryonic or implantation
pole of the blastocyst is attached
to the endometrium
Prelacunar stage
Prelacunar stage
Early Lacunar Stage
Primary Villous Stage
Secondary villous stage
Tertiary villous stage
EM
Trophoblast
Crucial role in implantation and
placentation

Wide range of metabolic,

endocrinologic, and invasive functions

Previllous trophoblast
 Cytotrophoblast Syncytiotrophoblast
Nucleus Single Multiple
Shape Round Irregular,highly
variable
Cytoplasm Scant,clear to Abundant,dense
granular, multiple
prominent cell vacuoles,lacunae
borders
Cytokerati ++++ ++++
n
hCG - ++/++++
Mel-CAM - -
PLA P - ++++
 Intermediate trophoblast
Features intermediate

Discrete single cells ,round to oval to

spindle

Uni/Bi/Multinucleate

Cytoplasm like ST
Trophoblast
Villous CT, ST, IT
Extravillous- Used to make
nonvillous parts of placenta e.g.
chorion
Extravillous ST
Extravillous CT
 Gestational Trophoblastic
Diseases
Spectrum of pregnancy related
trophoblast proliferation
abnormalities.
 GTD
Originate from placental tissues and can be
cured even in the presence of widespread
metastasis
Persistent gestational trophoblastic tumors
develop most commonly after a molar
pregnancy
HCG correlates well with the amount of viable
trophoblast and serves as an ideal tumour
marker.
History
Hertig & Edmonds 1940-Hydropic
swelling type I,II,III

Ewing 1910 chorioadenoma

destruens

Marchand - choriocarcinoma
Modified WHO Classification
Hydatidiform mole-complete,partial
Invasive mole
Choriocarcinoma
Placental site trophoblastic tumor
Epithelioid trophoblastic tumor
Exaggerated placental site
Placental site nodule
Unclassified trophoblastic lesions
Clinical Classification
Gestational Trophoblastic Disease
Gestational Trophoblastic Tumours
Invasive Mole
Choriocarcinoma
PSTT
Metastatic Trophoblastic Disease
Metastatic-Low vs High risk
hCG in urine hCG in urine
<100,000IU/24 hrs >100,000IU/24 hrs
and serum and serum
<40,000mIU/ml >40,000mIU/ml
Symptoms <4 mths Symptoms >4 mths
No brain or liver Brain or liver mets
mets
No prior Prior chemotherapy
chemotherapy failure
Pregnancy event Term Pregnancy
Aetiology
Epidemiology-1:160 India
Ethnicity-More in Blacks and
Orientals
Oncogenic viruses?
Cytogenetics esp in H. mole
ABO Blood groups
Differential Diagnosis Of
Trophoblastic Lesions
Specimen

Obstetric history and clinical

features

Factors influencing the assessment

of the curettings
 Trophoblast in curettings

Biphasic trophoblast(Cyto+Syn) Uniphasic(Int)

Villous Nonvillous
Products of conception
Hydropic abortus

Susp of chorio simple trophoblast Defi of

chorio
Villous trophoblast
Uterine curettings containing
products of conception

Villi of early abortion

Postpartum haemorrhage
Molar villi
Hydropic abortion vs Hydatidiform
mole
 Nonvillous Trophoblast :Antecedent Pregnancy

Past H/O HM Past H/O Abortion or

H/O FTND

Prior 6 months More than 6 months

Persistent molar disease

Susp of chorio Defi of

chorio
Hydropic Abortion vs Hydatidiform Mole

Hydropic Hydatidiform
Abortion Mole
Gross findings +/- on gross Diffuse
of villous involvement
swelling on gross
Hydropic Focal Diffuse
degeneration
Cistern Not seen Marked
formation
Foetal vessels Seen +/-
Hyperplasia of Attenuated/pol Hyperplasia
trophoblast ar Min/No and atypia
NonVillous TrophoblasticTissue
Curetting mostly represents
retained products of conception

Conventional cytologic criteria

diagnostic of malignancy not
applicable for diagnosis of
choriocarcinoma
Hydatidiform Mole
Known since 1600 AD

Hydatid

Close association with

choriocarcinoma
Hydatidiform Mole
Hydatidiform mole - an abnormal
placenta characterized by marked
enlargement of chorionic villi
Hydatidiform moles categorized on
the basis of karyotype, gross
morphology, and histopathology
 Cytogenetics
46,XX karyotype, chromosomes entirely
of paternal origin
Fertilized by a haploid (23,X) sperm,
which then duplicates its own
chromosomes; the nucleus of the ovum
may be either absent or inactivated
10 percent of complete moles 46,XY
chromosomal pattern
mitochondrial DNA is of maternal origin
 Complete Mole Partial Mole
Cistern +++ +
Formation
Trophoblastic Not seen Seen
inclusions
DNA content of Diploid levels Equivalent
nuclei of villous polypoid levels
stroma
HCG titres Higher,remaini Comparatively
ng elevated low
longer
Malignant Well accepted Not accepted.
potential
Grading of Hydatidiform Mole
(Driscoll 1977)
Degree of Differentiation
hyperplasia of trophoblast
Grade I Minimal Well
hyperplasia of differentiated
trophoblast
Grade II Moderate to Well
marked differentiated

Grade III marked Undifferentiate

d
Gross
Bunch of grapes

Weight of placenta increased

No fetal parts
Marked generalised villous hydrops
Villous swelling with circumferential
hyperplasia of trophoblastic cells
Cytological atypia with
trophoblastic proliferation
 Complete mole in a twin gestation
D/d from partial mole-
Much more exuberant CT, ST hyperplasia
Extensive pronounced cisterns
No scalloping,trophoblastic inclusions
One population of villi
Diagnosis of a partial mole is usually made
after a histologic review of curettage
specimens
Partial Mole
Clinical presentation less severe

Mostly triploid

Extrahaploid component is
paternal
Gross
Variable no of vesicles

Amt of tissue more than

expected for gestation

Fetal parts present

Partial Mole
Morphologic Feature:-

Large ,edematous villi and small

normal sized villi without edema.

Villi have irregular,scallopped

outlines.
Mixture of small and large hydropic
villi
Irregular trophoblastic
proliferation .
 Diploid partial mole

Phenotypic resemblance to partial

moles
Differential Diagnosis
Hydropic Hydatidiform
Abortion Mole
Gross findings +/- on gross Diffuse
of villous involvement
swelling on gross
Hydropic Focal Diffuse
degeneration
Cistern Not seen Marked
formation
Foetal vessels Seen +/-
Hyperplasia of Attenuated/pol Hyperplasia
Invasive H.Mole
Chorioadenoma destruens

Molar gestation in which hydropic

villous trophoblast penetrates the
myometrium or its blood vessels
Invasive Mole
Sequela of a complete
hydatidiform mole or a partial mole
Gross Irregular haemorrhagic
lesion penetrates into myometrium
Pathological diagnosis:Molar villi
with trophoblastic proliferation
within myometrium
Invasive mole
Pathological diagnosis
Presence of molar villi with associated
trophoblastic cells in the myometrium and
broad ligament or at distant sites

Clinical diagnosis
hCG titers plateau or rise following
evacuation of a mole.
Differential diagnosis
Intracavitary noninvasive
hydatidiform mole-Marked
trophoblastic proliferation

Choriocarcinoma-Absence of true
chorionic villi
 Differential diagnosis
Placenta acreta Molar villi superficially
attached on myometrium,without
intervening decidua
Placenta increta-Extend deep,without
serosa
Placenta percreta-Full thickness involved
 Exaggerated Placental Site
Benign nonneoplastic lesion

Increased number of implantation site

intermediate trophoblastic cells,that
infiltrate endometrium and myometrium
Exaggerated placental site vs PSTT
No mitotic activity Mitotic activity high
Intermediate Confluent masses
trophoblastic cells of implantation site
separated by intermediate
hyaline material. trophoblastic cells

CK 18,hPL,Mel- CK 18,hPL,Mel-
CAM ++++ CAM,Ki-67 ++++
Placental Site Nodule
Well circumscribed hyalinized
lesion composed of chorionic type
intermediate trophoblastic cells
Pathologic features
Gross-Yellow ,tan or haemorrhagic
nodule in endometrium or
superficial myometrium
Placental Site Nodule
Cluster of hyperchromatic and vacuolated
chorionic type intermediate trophoblastic
cells in a hyaline matrix
 Choriocarcinoma
Gods first cancer and mans first cure
Highly aggressive malignant tumor from
previllous trophoblast of early
implantation or villous surface of placenta
50% develop from a complete H.mole
Metastasis may be the first sign of
tumour
Pathogenesis
Influence of maternal environment

Genetic abnormalities

Viruses? SV40. Retrovirus ERV-3

Gross-Multiple,circumscibed
hemorrhagic masses
Biphasic mixture of ST,CT and intermixed IT
Alternating arrangement of ST
and mononucleate trophoblast
Immunostaining Mel-CAM ,Ki-67
Early placenta vs choriocarcinoma
cells less atypia
 Choriocarcinoma PSTT
Clinical Hge ,preceding Amenorrhoea
features history of H.mole
Gross Hgic areas prominent -
HPE CT and ST ,Bilaminar IT. Monotonous,
pattern, venous sinus
and capillary venous sinus
destroyed and capillary
Preserved
IHC hCG abundant,hPL hCG focal ,hPL
small amt,CK CEA + abundant,diffus
e
Treatmen chemo Surgery,curetta
t ge
D/d
Normal trophoblastic tissue,early
gestation
Trophoblastic proliferation of H mole
Invasive mole

Chorionic villi
Metastasis to lungs >75%,brain,
liver gastrointestinal tract
Poor prognostic factors
Non gestational choriocarcinoma
 Placental site trophoblastic tumor

Neoplastic transformation of
implantation site intermediate
trophoblast
Sheets of implantation site intermediate trophoblastic cells
separating smooth muscle cells of myometrium
Replacement of vascular wall by implantation site
intermediate trophoblastic cells,fibrinoid material in
vessel wall.
Implantation site intermediate trophoblastic
cells,pale to clear cytoplasm.
 Choriocarcinoma PSTT
Clinical Hge ,preceding Amenorrhoea
features history of H.mole
Gross Hgic areas prominent -

HPE CT and ST ,Bilaminar IT.Monotonous,

pattern venous sinus
and capillary
destroyed Preserved
IHC hCG abundant,hPL hCG focal ,hPL
small amt,CK CEA + abundant,diffus
e
Treatmen chemo Surgery,curetta
t ge
Epithelioid trophoblastic tumor
Distinct trophoblastic tumor,
develops from neoplastic
transformation of chorionic type
intermediate trophoblastic cells
Necrosis in the nests of
trophoblastic cells
Mononucleate cells in nests and
cords in myometrium
Replacing and reepithelializing
glandular epithelium
HCG
Glycoprotein hormone produced by
placenta,excreted intact by kidneys
Composed of noncovalently linked
and subunits.
Measurement of free subunit
useful for detection of recurrence of
metastasis for
choriocarninoma,when intact hCG
normal.
 Follow-Up after a Molar Pregnancy

After molar evacuation, hCG levels monitored weekly until they

have been undetectable for three consecutive weeks

Monthly monitoring until they have been undetectable for six

consecutive months.

The average time to the first undetectable human chorionic

gonadotropin level after evacuation of a complete or partial mole is 9
to 11 weeks.
Thank You