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Pathology of the placenta

3  Atlas of fetal pathology

3.5  Pathology of the placenta

3.5.1  Normal placenta

3.5.2  Extrauterine gravidity

Introduction:

Implantation of the fertilized ovum outside uterine endometrium:

  • tuba uterina 90%
  • ovary, peritoneum

Clinical signs:

  • amenorhea
  • changes in hormonal levels correspond to normal pregnancy
  • fertilized ovum does not implant in suitable location
  • placenta cannot develop normally
  • new placenta seeks blood supply, arteries are opened
  • possibilites of future development:
    • hematoma (tuba), rupture of the hematoma, peritoneal bleeding
    • regression of the fertilized ovum or gravidity (calcified fetus may remained within the peritoneal cavity — lithopedion)

Etiology:

  • closed Fallopian tubes (postinflammatory condition)
  • fertilization of the ovum within the ruptured follicle
  • unknown reasons

Histology:

The Fallopian tube contains blood (Fallopian tube hematoma), placenta (cytotrophoblast, syncitiotrophoblast) and fetus. Not always all these can be identified bioptically.

New placenta produces HCG and corpus luteum graviditatis develops, therefore corresponding endometrial changes develop as well: hypersecretory endometrium, AS phenomenon, decidual changes of endometrial stroma. However, these changes are not present in all cases of extrauterine gravidity. Therefore it is important to evaluate histologically all cases of abraded endometrium, when there was any suspition for gravidity. In case no unequivocal signs of gravidity are found (fragments of placenta or embryo), it is necessary to rule out extrauterine gravidity clinically (ultrasound, HCG levels).

3.5.3  Gestational trophoblastic disease (GTD)

Introduction:

Group of disorders which are associated with pregnancy and arise from abnormal growth of placental trophoblast.

They occur in women in reproductive age.

The common feature of these disorders is that they produce hCG (chorionic gonadotropin), which is a useful marker for diagnostics, evaluation of the clinical course and response to therapy.

Both benign nonneoplastic disorders (hydatidiform mole) and malignant aggresive neoplasms (choriocarcinoma) are included.

Classification:

  • Nonneoplastic disorders (tumor — like masses resembling placenta)
    • Hydatidiform mole
  • Neoplams:
    • Choriocarcinoma
    • Placental site trophoblastic tumor and epithelioid trophoblastic tumor  —  both are very rare
3.5.3.1  Hydatidiform mole

Clinical signs:

  • Risk factors:
    • age: Hydatidiform mole occur in women durign the whole reproductive period, the highest incidence (per pregnancy) is in women over 40
    • ethnicity: Asian ethnicity is a significant risk factor. The occurence of hydatidiform mole is several fold greater in Indonesia, Japan, Philippines than in Europe
    • prior molar pregnancy: Prior molar pregnancy increases the risk of reccurence up to 1 : 100, two prior molar pregnancies mean the risk of reccurence 1 : 30
  • general incidence: The estimated occurence of hydatidiform mole in our population is 1 in 2500 — 3000 of recognised pregnancies
  • therapy: Suction evacuation of mole and revision of the uterine cavity by curretage afterwards are performed. hCG titers must be followed up after the evacuation of mole until the levels return to normal. Serum hCG titers are assesed weekly until normal, then monthly for 1 year in complete mole, for half year in partial mole. A period of 6 to 12 months is reccomended betweeen the hCG drop and another conception. There is a significant risk of reccurent molar pregnancy (see above).
  • Persistent gestational trophoblastic disease: Increasing or plateuing hCG titers after evacuation of mole mean that a trophoblastic cells population persists in the body. This is called persistent gestational trophoblastic disease. Residual hydatidiform mole retained in the uterine cavity, residual trophoblast, invasive mole or choriocarcinoma explain the persistent hCG titres. The definite histologic diagnosis is often never confirmed. The guidelines for therapy are based on future risk assessment: stage of GTD (stage 1is disease confined to uterus clinically, stage 2 — 4 metastatic disease) and known risk factors for poor outcome.

Classification:

  1. Complete mole
  2. Partial mole

These subtypes have different clinical, pathologic and genetic features and particularly prognosis.

3.5.3.1.1  Complete mole

Etiology, pathogenesis:

Complete mole has a diploid DNA content  —  46 XX, less often 46 XY complete mole is a result of pathologic fertilization.

There are 2 known pathways:

  1. Fertilization of an empty egg (own chromosomes lost) by a single haploid sperm which undergoes duplicatation.
  2. Fertilization of an empty egg by two sperms

All genetic information is paternal in origin.

Macroscopic appearance:

An enlarged uterus is filled with voluminous grape  —  like mass. These grape  —  like vesicles are in fact swollen chorionic villi.

No fetus is present.

Clinical signs:

  • because of widespread use of ultrasonography most cases of complete mole are now recognized early in first trimster
  • ultrasonography: snow storm (multiple echos); fetus is absent
  • Complete mole presents in the early 2nd trimestr, advanced clinical presentations is an exception nowadays:
    • uterine enlargment greater than expected ofr the gestational age
    • vaginal bleeding, anemia
    • spontaneous abortion of the mole
    • markedly elevated hCG level
    • hyperemesis gravidarum
    • early onset pre-eclampsia
    • abortion of molla fragments
    • ovarian theca luetal cysts
  • therapy: evacuation of the mole, hCG monitoring
  • prognosis: 15 – 20% of patients with complete mole develop persistent trophoblastic disease
  • about 2 – 3% of patients with complete mole develop malignant choriocarcinoma

Histology:

Typical histologic features are found in the 2nd trimester:

  • all chorionic villi are edematous
  • cistern formation (central cavitation) in many of the swollen villi
  • no blood vessels
  • roundish shape of villi
  • diffuse, circumferential trophoblastic hyperplasia
  • trophoblastic atypia

Histologic features are subtle in the 1st trimester, which makes the diagnosis more difficult (so called early complete mole).

  • slightly swollen villi, no cisterns visible
  • hypercellular bluish stroma, karyorrhexis
  • bulbous round villi
  • focal to diffuse trophoblastic hyperplasia
3.5.3.1.2  Partial mole

Etiology, pathogenesis:

  • partial mole has a triploid DNA content: 69 XXX, 69 XXY
  • fertilization of a haploid egg by two haploid sperms
  • fertilization of a haploid egg by one diploid sperm (rarely)
  • the rate of maternal to paternal genetic information is 1 : 2.

Note: not all triplod gestations are partial moles  —  see chromosomal aberrations and fetal triploidy.

Macroscopic appearance:

  • nothing remarkeble
  • malformed embryo is present and is aborted in the 1st trimester

Clinical signs:

  • clinical presentation is that of missed abortion
  • hCG is slightly eleveted or within normal range for that time in pregnancy
  • therapy: evacuation of the mole, monitoring of hCG levels
  • prognosis:
    • about 0.5 — 5% of patients with partial mole develop persisent gestational trophoblastic disease
    • risk of development of choriocarcinoma following the partial mole is essentially nill

Histology:

  • two populations of villi: swollen enlarged villi and normal small villi without edema
  • irregular scalloped villous shape, trophoblastic invaginations (fiords) and round trophoblastic stromal inclusions
  • focal trophoblastic hyperplasia
  • no trophoblastic atypia
  • blood vessels are present
3.5.3.2  Invasive mola (mole proliferans, mole destruens)

Introduction:

Complete or partial mole characterized by aggresive tumor — like behaviour.

In spite of this behaviour invasive mole is not a neoplasm.

Clinical signs:

  • chorionic villi are found within myometrium or vascular spaces
  • molar villi may embolize to the lung, vagina or brain (so called metastatic mole); these emboli are not real metastases because they undergo regression and do not form a secondary focus
  • hCG titres are high
  • therapy: invasive mole is managed by chemotherapy

Histology:

The diagnosis of invasive mole can be confirmed only when surgical resection is examined. Surgery is not a standard procedure. That is why treatment is usually applied without definitive pathologic confirmation.

3.5.3.3  Gestational choriocarcinoma

Introduction:

Malignant tumor derived from trophoblast.

Etiology, pathogenesis:

50% cases of choriocarcioma arise in complete mole, 25% follow normal term pregnancy, 25% follow spontaneous abortion. Extremely rare are cases arising in ectopic pregnancy.

Clinical signs:

  • abnormal bleeding from uterine cavity in women of reproductive age
  • there is a latent period from 1 month up to 2 years from the antecedent pregnancy
  • hCG level is always elevated
  • metastasatic disease with involvement of the lungs, brain and vagina occurs very early
  • in 20% the primary in uterus undergoes complete necrosis and only metastastatic foci are detected then
  • metastatic disease may be the first clinical symptom  —  brain hemorrhage, hemoptysis
  • incidence: 1 : 25 000 of recognized pregnancies (5 women per year in the Czech republic)
  • therapy: chemotherapy; choriocarcinoma was the first solid neoplasm which was succesfully treated by chemoteraphy
  • prognosis:
    • excellent (5-year survival exceding 90% in metastatic disease)
    • fertility can be saved in most cases; hysterectomy is an exceptional therapeutic procedure

Macroscopic appearance:

Hemorrhagic nodule in the uterine cavity.

Pictures

Choriocarcinoma, uterus:
Choriocarcinoma of the uterus, Macro, autopsy (71342)

Brain hemorrhage, metastasis of choriocarcinoma:
Choriocarcinoma, metastases to the brain, Macro, autopsy (71315)

Histology:

  • dimorphic pattern
  • neoplastic cytotrophoblastic and syncytiotrophoblastic cells with prominent atypia
  • no chorionic villi
  • areas of bleeding and necrosis
  • epithelial tumor (cytokeratin stains are positive)
3.5.3.4  Placental site trophoblastic tumor

Introduction:

Rare tumor derived from intermediate trophoblast of implantation site (not from villous trophoblast as choriocarcinoma).

Clinical signs:

  • women in reproductive years
  • abnormal bleeding resembling spontaneous abortion is a common clinical presentation
  • hCG titers are generally low (in contrast to choriocarcinoma)
  • prognosis:
    • usually benign
    • 15% of reported cases show aggresive behaviour with disseminated metastases

Histology:

  • monomorphic pattern: intermediate trophoblastic cells, fibrinoid, necrosis
  • tumor cells extensively infiltrate the endometrium and myometrium

3.5.4  Placenta and major chromosomal abnormalities

Introduction:

Placentas in late abortions associated with chromosomal abnormalities (trisomy 13, 18, 21 and monosomy X in particular) may show abnormal gross or histologic features.

Macroscopic appearance:

The placenta may be either large or small for gestational age. Rarely cysts may be grossly recognizable.

Pictures

Placenta in trisomy 13, pregnancy termination at 23 w.g.; placenta with scattered large vesicles:
Placenta, syndrome Patau, Macro, autopsy (72868)
Placenta, syndrome Patau, Macro, autopsy (72869)

Histology:

  • immature villi.
  • dysmorphic features of chorionic villi include cystic villi, irregular villous outline, trophoblastic inclusions, stromal karyomegaly, aberrant capillary pattern, chorangiosis (hypercapillarization)
  • Rare cases mimicking partial mole were described in association with trisomy 13. A population of large hydropic poorly vascularized villi is present. Trophoblastic hyperplasia is absent. The risk of persisting trophoblastic disease is not increased.

These features are not neither specific or constant in chromosomal abnormalities and cannot be used for diagnosis as the only sign.

Pictures

Placenta mimicking partial mole, huge hydropic villi, poor vascularization, no trophoblastic hyperplasia, normal villi:
Placenta, trisomy 13, HE 20x (72806)
Placenta, trisomy 13, HE 40x (72807)

Placenta in trisomy 21, 40-week stillborn infant, retardation of villous maturation, aberrant vasculary pattern, choriangiosis:
Dystrophic placenta, Down syndrome, HE 20x (72866)

3.5.5  Hydropic placenta

Introduction:

Hydrops of the placenta usually accompanies hydrops of the fetus. Etiology is variable (Rh incompatibility, chomosomal abberations) and others.

Pictures

Hydropic placenta, unknown etiology:
Placenta, HE 20x (13848)
Placenta, HE 20x (13849)


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