Pathology of Trophoblastic Disease

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Pathology of Trophoblastic Disease

OS 215 Jose Ma. C. Avila, M.D.

Placenta and Umbilical Cord

Normal Maturation Sequence

7 days after fertilization,

blastocyst attaches to uterine wall

and implantation begins

As blastocyst invades the uterine

wall, two populations of

trophoblasts develop and form the

placenta

–Cytotrophoblast: a proliferating

population of individual trophoblasts

–Syncytiotrophoblast: nondividing

syncytium

Normal Maturation Sequence - 2

Cytotrophoblast (CT) remains

nearer the other enbryonic tissues,

whereas syncytiotrophoblast

invades the maternal tissues of the

endometrium

Syncytiotrophoblast (ST) is non-

antigenic (lacks MHCs), so as it

invades maternal tissue without

triggering immune response

As ST encounters maternal blood

vessels, it surrounds them and

digests vessel wall, forming cavities

called lacunae


Cords of CT and embryonic

mesenchyme then surround the ST

and lacunae and protrude into the

lacunae like fingers

In later pregnancy, CT

degenerates and mesenchyme

displaced by growth of fetal

capillaries, leaving the embryonic

blood supply separated from

maternal blood supply by only

capillary wall, a basement

membrane, and thin layer of CT

Patho Exam

September 15, 2008 | Monday Page 1 of 1 Kiev, Trix, Ace, Robert

GESTATIONAL TROPHOBLASTIC DISEASE

Term embraces the spectrum of trophoblastic disease characterized by abnormal proliferation and maturation of trophoblast, as well as neoplasms derived from the trophoblast

Fig.1 Villi Area. (A) outer syncitiotrophoblast (B) trophoblast

layer (C) inner cytotrophoblast MODIFIED WHO CLASSIFICATION OF GESTATIONAL TROPHOBLASTIC DISEASES

Hydatidiform mole – Complete – Partial

Invasive mole Choriocarcinoma Placental site trophoblastic tumor (PSTT) Epithelioid trophoblastic tumor Miscellaneous trophoblastic lesions

– Exaggerated placental site – Placental site nodule

COMPLETE HYDATIDIFORM MOLE

A placenta that has grossly swollen villi, resembling a bunch of grapes, in which there are various degrees of trophoblastic proliferation

Villi enlarged and exceed 1 mm diameter (commonly between 5-10 mm diameter)

No embryo Pathogenesis:

– Results from the fertilization of an empty ovum that lacks functional DNA

– Haploid (23X) set of paternal chromosomes duplicates to 46, XX

– Hence, most complete moles are homozygoud 46,XX but all chromosomes are paternal in origin

– Embryo dies early age before placental circulation develops, few chorionic villi develop blood vessels and fetal parts always absent

Risk factors

– Related to maternal age and has two peaks: <15 yrs has 20X higher risk than women 25-35 yrs

– Risk increases progressively for women older than 40 yrs; women over 50 have a risk 200x greater than women between 20-40

– Risk higher among Asian women than among white women (Taiwan risk 25X > than U.S.)

– Women with previous Hmole 20x greater risk than general population to have subsequent mole

Pathology

– Voluminous vesicular grape-like clusters, 1-2cm, grossly visible

– No fetal parts – Diffuse villous hydropic swelling, avascular, with

cisterns – Trophoblastic (cyto- and syncytio-) proliferation with

atypia Clinical Features

– Commonly present between 11th

and 25th weeks of

pregnancy – Complains of excessive uterine enlargement and

often of abnormal uterine bleeding, sometimes accompanied with passage of tissue fragments (grapelike)

– Serum hCG markedly elevated

Complications

– Uterine hemorrhage – DIC – Uterine perforation – Trophoblastic embolism – Infection – Development of choriocarcinoma (2%)

Treatment

- Suction curettage of the uterus - Monitoring of serum hCG levels

- 20% require adjuvant chemotherapy for persistent disease (depending on hCG levels)

- Presence of aneuploidy in molar tissue may help identify patients who require adjuvant therapy

- Rate of survival may approach 100% Fig. 2 Hyatidiform mole. (aka

“kyawa”) Note grape-like appearance.

Fig. 3 Hyatidiform mole Fig. 3 Hyatidiform mole

Lecture Outline:

I. Gestational Trophoblastic Disease

II. Complete Hyatidiform Mole

III. Partial Hyatidiform Mole

IV. Invasive Mole

V. Choriocarcinoma

IV. Placental Site Trophoblastic Tumor

V. Exaggerated Placental Site Reaction

A

B C

2











placenta




syncytium






endometrium








called lacunae














Patho Exam


Fig.4 Complete Hyatidiform mole. Note absence of blood

vessels. (A) cistern

Fig.5 Complete Hyatidiform mole. (A) Trophoblastic

proliferation PARTIAL HYDATIDIFORM MOLE

Now recognized to be a distinct form of mole Must distinguish from complete H. mole, since it does

not evolve into choriocarcinoma Karyotype: 69 chromosomes (triploidy) – results from

the fertilization of a normal ovum (23,X) by two normal spermatozoa, each carrying 23 chromosomes, or a single sperm that bears 46 chromsomes (has not undergone meiotic reduction)

Fetus associated usually dies at about 10 wks gestation and mole aborted shortly thereafter

Fetal parts commonly present Less tissues than complete mole Hydropic villi are admixed with normal villi, sometimes

with fetal parts Villi have scalloping, trophoblastic inclusions, stromal

vessels, villous fibrosis Mild circumferential trophoblastic proliferation around

the hydropic villi

Fig. 6 Partial Hyatidiform mole. Note scalloped appearance

of villi. Villi are relatively smaller.

Fig. 7 Partial Hyatidiform mole. Villi are small and with

scalloped margins. Villous deportation flies out (usually out into the lungs). Note trophoblastic inclusion (encircled.)

INVASIVE HYDATIDIFORM MOLE

Diagnosed on a hysterectomy specimen Irregular hemorrhagic lesion within muscle bundles of

myometrium Must demonstrate hydropic villi within myometrium May result in villous deportation: often penetrates

venous channels (25-40%) and spread to distant sites (lungs)

Uterine perforation major complication but rare

Fig. 8a Invasive Hyatidiform mole. See villus (encircled).

A

A

3











placenta




syncytium






endometrium








called lacunae














Patho Exam


Fig. 8b Invasive Hyatidifom mole. Higher magnification of

previous picture. Encircled is a villus. CHORIOCARCINOMA

Malignant tumor derived from the trophoblast Actually a tumor allograft in the host mother 1 in 30,000 pregnancies in the U.S. (greater in the

Orient) Incidence seems to be related to the degree of

abnormality of the pregnancy (1 in 160,000 normal gestations, 1 in 15,000 spontaneous abortions, 1 in 5,000 ectopic pregnancies, 1 in 40 molar pregnancies)

Well-circumscribed hemorrhagic mass with central necrosis and hemorrhage

Dimorphic: cytotrophoblasts + syncytiotrophoblasts (no

villi) with extensive necrosis and hemorrhage Invades primarily through venous sinuses in

myometrium Metastasizes widely via hematogenous route, especially

to the lungs (90%), brain, GIT, liver, vagina (may be the first sign)

Most frequent initial indication is abnormal uterine bleeding

In some cases, evident after 10 years or more after the last pregnancy

Today, survival rates (with chemotherapy) above 70% with metastatic disease

100% remission if localized Serial serum hCG levels used to monitor effectiveness

of treatment

Fig. 9 Choriocarcinoma. Arrow points to choriocarcinoma

penetrating uterine wall.

Fig 10. Choriocarcinoma. Metastasis to the liver. Note

canonball appearance of metastatic lesions. Fig. 11 Choriocarcinoma Note dimorphic choriocarcinoma

(left darker staining area) invading the uterus (left pale area). Fig. 12a&b Choriocarcinoma Note intermingling of (A)

cytotrophoblast and (B) syncitiotrophplast.

A B

A

B

4











placenta




syncytium






endometrium








called lacunae














Patho Exam


PLACENTAL SITE TROPHOBLASTIC TUMOR

Least common among the forms of trophoblastic disease

Composed predominantly of intermediate trophoblasts Age and parity of patients resemble those of

choriocarcinoma Half report amenorrhea (vaginal bleeding in

choriocarcinoma) Fewer patients have preceding molar pregnancy (5%) Generally behaves in a benign fashion but occasionally

may metastasize and prove fatal Generally, conservative management suffices hCG more useful in monitoring response to treatment

(hPL has shorter half-life) Hysterectomy with chemotherapy in hCG persists even

at low levels Variable gross: nodular myometrial enlargement, well-

demarcated or ill-defined, polypoid, intramural, etc. Monomorphic: intermediate trophoblasts Single cell smooth muscle infiltration Invasion and replacement of blood vessel wall Abundant fibrin

Fig. 13 Placental Site Trophoblastic Tumor.

Fig. 14a Placental Site Trophoblastic Tumor, LPO. (A)

myometrial cells (B) tumor cells

Fig. 14b Placental Site Trophoblastic Tumor, HPO. (A)

myometrial cells (B) tumor cells Fig. 15 Placental Site Trophoblastic Tumor. (A)

trophoblastic tumor cells invading the wall of blood vessels, (B) blood vessel Fig. 16a LPO & b HPO Placental Site Trophoblastic Tumor. Note the wall of the blood vessel almost gone due to

tumor cell replacement (see arrow), (A) fibrin

A

B

B

A

A B

A

A

5











placenta




syncytium






endometrium








called lacunae














Patho Exam


EXAGGERATED PLACENTAL SITE REACTION

Microscopic and not a mass (gross) lesion An exuberant infiltration of endometrium and

myometrium at implantation site by intermediate trophoblasts and occasional syncytial trophoblasts

Fig. 17 Exaggerated Placental Site Reaction

Fig. 18 Exaggerated Placental Site Reaction. Note

combination of cells infiltrating the myometrium and endometrium. Additional Info (from 2011 trans):

Feature Complete Mole Partial Mole

Karyotype 46, XX Triploid

Villous edema All villi Some villi

Trophoblast proliferation

Diffuse; circumferential

Focal; slight

Atypia Often present Absent

Serum HCG Elevated Less elevated

HCG in tissue ++++ +

Behavior 2% choriocarcinoma

Rare choriocarcinoma

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Pathology of Trophoblastic Disease

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