Gestational trophoblastic disease

The term gestational trophoblastic disease is a spectrum of disorders with abnormal trophoblast proliferation and maturation, as well as neoplasms derived from trophoblast (see Chapter 66).

Complete hydatidiform mole

Complete hydatidiform mole is a placenta with grossly swollen chorionic villi, resembling bunches of grapes, and showing varying degrees of trophoblastic proliferation. Villi are enlarged, often ex­ceeding 5 mm in diameter.

Molecular pathogenesis and aetiological factors

Complete mole results from fertilization of an empty ovum that lacks functional maternal DNA. Most commonly, a haploid (23,X) set of paternal chromosomes introduced by monospermy dupli­cates to 46,XX, but dispermic 46,XX and 46,XY moles also occur. Moles characteristically lack maternal chromosomes. Paternally imprinted genes, such as p57 (also known as CDKN1C), in which only the maternal allele is expressed, are not expressed in villous trophoblasts of androgenetic-derived complete moles. Since the embryo dies at a very early stage, before placental circulation has developed, few chorionic villi develop blood vessels and fetal parts are absent. Women with a prior hydatidiform mole have a 20-fold greater risk of a subsequent molar pregnancy than the general population (1, 2).

Pathology

Microscopically, many individual villi have cisternae. Trophoblast is hyperplastic and composed of syncytiotrophoblast, cytotrophoblast, and intermediate trophoblast. Considerable cellular atypia is present.

Clinical features

Serum hCG levels are markedly elevated, and increase rapidly. Complications of complete mole include uterine haemorrhage, disseminated intravascular coagulation, uterine perforation, and trophoblastic embolism. The most important complication is development of choriocarcinoma, which occurs in about 2% of patients.

Treatment consists of suction curettage of the uterus under ultra­sound guidance and an oxytocic infusion and subsequent moni­toring of serum hCG levels.

Invasive hydatidiform mole

The villi of a hydatidiform mole may only enter the superficial myometrium or they may invade the uterus, and even the broad ligament. They tend to enter dilated venous channels of the myome­trium and one- third spread to distant sites, mostly the lungs. Uterine perforation is a major complication, but occurs in only a minority of cases (1, 2).

Gestational choriocarcinoma

Choriocarcinoma occurs in 1 of 160,000 normal gestations, 1 of 15,000 spontaneous abortions, 1 of 5000 ectopic pregnancies, and 1 of 40 complete molar pregnancies. Unlike most other cancers, choriocarcinomas lack intrinsic tumour vasculature. Thus, the tu­mours are typically necrotic and haemorrhagic and viable tumour is confined to the rim of the neoplasm. There is a dimorphic popu­lation of cytotrophoblast and syncytiotrophoblast, with varying degrees of intermediate trophoblast. hCG is localized to the syncytiotrophoblastic element. By definition, tumours containing any villous structures, even if metastatic, are considered hydatidi­form mole and not choriocarcinoma (1, 2).

Choriocarcinoma invades mainly through venous sinuses in the myometrium. It metastasizes widely via the bloodstream, especially to lungs (over 90%), brain, gastrointestinal tract, liver, and vagina. With current chemotherapy, recognition of risk factors (high hCG levels and prolonged interval since antecedent pregnancy), and early treatment, most patients are cured.

Placental site trophoblastic tumour

Placental site trophoblastic tumours are the least common trophoblastic tumours, and are mainly composed of intermediate trophoblastic cells. Mononuclear and multinuclear trophoblast may be present as sheets of cells interspersed among myometrial cells. No chorionic villi are seen. Placental site trophoblastic tumour is distinguished from choriocarcinoma by its mono­morphic (intermediate) trophoblastic proliferation, unlike the dimorphic pattern of trophoblast in choriocarcinoma. Most trophoblastic cells express human placental lactogen, but a few express hCG (1, 2).

Placental site trophoblastic tumour must be excised com­pletely (hysterectomy) to prevent local recurrence. It sometimes metastasizes and may be fatal. Large tumours and mitotic indices of more than five mitoses/10 HPFs are associated with worse prognosis.