59. Pathology of pregnancy I (implantation disorders, gestosis, trophoblastic tumours)

From greek.doctor

Implantation disorders

Ectopic pregnancy refers to the implantation of the fertilized ovum at a site other than the uterine wall. Ectopic pregnancies occur in 1% of all pregnancies, and 90% of these occur in the fallopian tube. Other possible sites include the ovary and the abdominal cavity.

The main risk factor for this is scarring of the fallopian tube, which decreases the speed at which the egg is moved through the tube, increasing the risk that it will implant there. Scarring of the fallopian tube occurs in pelvic inflammatory disease and endometriosis, so these are risk factors for tubal ectopic pregnancy.

These pregnancies very rarely allow the foetus to survive and will eventually rupture. They must therefore be recognized and treated. Rupture of an ectopic pregnancy can cause sudden intense abdominal pain and acute abdomen, potentially even hypovolaemic shock and death.

Spontaneous abortion is defined as loss of pregnancy before 20 weeks of gestation. It occurs in around 10% of pregnancies. It is caused by:

  • Chromosomal abnormalities – most common cause
  • Hypercoagulability
    • Antiphospholipid syndrome (SLE)
  • Trauma
  • Toxins

Placenta praevia: Normally the placenta implants in the upper part of the uterine cavity, far away from the cervical os. If the placenta instead implants close to the cervical os and perhaps even obstruct the os, the condition is called placenta praevia. This is dangerous as the foetus will compress the placenta when delivered vaginally, which will deprive it of blood during delivery. These pregnancies are instead delivered by C-section.

Placental abruption refers to the case where the placenta separates from the uterus in utero. This causes bleeding and often stillbirth.

Hypertensive disorders of pregnancy (gestosis)

Hypertensive disorders of pregnancy, also called gestosis or toxaemia of pregnancy, refers to conditions where the mother develops hypertension during pregnancy. The two most important conditions are preeclampsia and eclampsia.

Preeclampsia refers to the development of hypertension, proteinuria and oedema of the mother during the third trimester of pregnancy. Multiple organs are involved and damaged, including the kidney, liver and lungs. In severe cases seizures and coma may also occur, in which case the condition is called eclampsia. These conditions occur in around 5 – 10% of pregnancies. The etiology is poorly understood. These conditions occur in the second or third trimesters.

Risk factors:

  • Nulliparity (first pregnancy)
  • Age > 35
  • African-American race

Pathogenesis: Despite the name “toxaemia” there are no toxins involved. The triggering event is unknown, but all cases are characterised by abnormal development of the spiral arteries in the placenta during implantation. The abnormal spiral arteries can’t deliver as much blood to the placenta, causing placental hypoperfusion.

The hypoxic placenta damages the foetus, and it also somehow increases the level of pro-inflammatory and anti-angiogenic molecules in the mother’s circulation. These cause endothelial dysfunction, which again causes hypercoagulability and vasoconstriction. Vasoconstriction causes hypertension.

Dysfunction of the glomerular endothelium along with hypertension-induced vasoconstriction of the renal arteries causes proteinuria and fluid retention, which causes further hypertension and oedema. The lung and liver may also be affected, causing pulmonary oedema and liver damage. In eclampsia vasoconstriction and endothelial damage affects the CNS and causes seizures.

Complications: Preeclampsia and eclampsia carry large risks both for the foetus and the mother. In the mother basically every organ can fail. Maternal death can occur, often due to acute respiratory distress syndrome or cerebral haemorrhage. Hypertension can cause placental abruption. Hypoxia of the foetus can cause abortion or permanent damage.

HELLP syndrome refers to the condition where there is haemolysis (H), elevated liver enzymes (EL) and low platelets (LP) and occurs in severe cases.

Diagnosis: These conditions are often detected during routine prenatal visits, which include blood pressure measurement, weighing and urine tests.

Treatment: The only treatment is delivery.

Gestational trophoblastic disease

Gestational trophoblastic disease, previously called trophoblastic tumors, include three lesions associated with pregnancy:

  • Hydatidiform mole
    • Complete mole
    • Partial mole
  • Invasive mole
  • Gestational choriocarcinoma

These conditions are associated with abnormal fertilization of the ovum and the development of tumors or tumor-like lesions that originate from placental cells. These conditions range from benign to highly malignant conditions. As the clinical symptoms, treatment and prognosis of these conditions are similar, they are clinically clumped together under the term “gestational trophoblastic disease”. Despite this, they are pathologically different. Moles are treated by curettage while choriocarcinoma is treated by chemotherapy.

Symptoms: Patients with gestational trophoblastic disease present with vaginal bleeding and pelvic tenderness.

Diagnosis is based on significantly elevated hCG, ultrasound and the absence of foetal heart sounds. The hCG is significantly elevated as these conditions are proliferations of syncytiotrophoblasts (and trophoblasts), which produce hCG.

Hydatidiform moles are benign gestational trophoblastic diseases that occur when an ovum is abnormally fertilized. There are two subtypes: the complete mole and the partial mole. In both types trophoblastic (placenta-like) tissue develops, but it’s abnormal. The chorionic villi are cystically dilated (hydropic) and look like grapes.

The complete mole develops when an ovum that contains no genetic material is fertilized by a sperm that subsequently duplicates its genetic material, or (rarely) if it is fertilized by two sperm at the same time. In most cases the result is a 46XX ovum, but 46XY can also occur.

The result is not compatible with life, so no embryo will develop. Trophoblasts and syncytiotrophoblasts however do develop, albeit abnormally. A placenta-like structure develops, where all the chorionic villi are oedematous and dilated.

The incomplete mole develops when a normal ovum is fertilized by a sperm that has its genetic material duplicated or (rarely) if it is fertilized by two sperm at the same time. The result is a 69XXX, 69XXY or 69XYY ovum.

This result is also not compatible with life, but some embryonal tissues will develop. Like for the complete mole, a placenta-like structure develops where some chorionic villi are dilated, and the rest are normal.

Feature Complete mole Partial mole
Karyotype Paternal diploid (46XX or 46XY) Triploid (69XXX, 69XXY or 69XYY)
Dilated villi All villi Some villi
Foetal tissue Absent Present

Invasive moles are complete moles that are locally invasive. Approx. 10% of complete moles become invasive. These moles don’t metastasize but deeply penetrate the uterine wall. This makes removal by curettage more difficult, so that chemotherapy may be needed.

Gestational choriocarcinoma is a very aggressive malignant tumor that arises from gestational chorionic epithelium. These occur:

  • In a complete hydatidiform mole – in 50% of cases
  • After a miscarriage – in 25% of cases
  • After a normal pregnancy – in 25% of cases

Unlike moles the choriocarcinoma doesn’t form villi. The tumor is composed of anaplastic cytotrophoblasts and syncytiotrophoblasts.

These gestational choriocarcinomas are very aggressive and metastasize very early and upon diagnosis most cases have already spread through multiple organs. Choriocarcinoma usually appear as hemorrhagic, necrotic uterine masses. Sometimes the necrosis is so extensive that practically nothing of the primary tumor lesion is left.

Luckily, they are very sensitive to chemotherapy, and almost 100% of cases are cured, even if they have metastases. This is in stark contrast to choriocarcinomas that arrise in the gonads (ovaries, testis). This contrast is belived to be due to the presence of paternal antigens on gestational choriocarcinomas.  The maternal immune response against the foreign (paternal) antigen helps remove the tumor along the chemotherapy. In the non-gestiational choriocarcinomas the tumors arrise from germ cells in the ovaries and as such these tumors dont have paternal antigen.