Gestational trophoblastic neoplasia pathophysiology

Template:Choriocarcinoma Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Monalisa Dmello, M.B,B.S., M.D. [2]

Overview

Gestational trophoblastic neoplasia arises from the trophoblastic tissue, which provide nutrients to the embryo and develop into a large part of the placenta. On gross pathology, dark, shaggy, focally hemorrhagic & friable/necrotic-appearing, and invasive border are characteristic findings of gestational trophoblastic neoplasia. The pathophysiology of gestational trophoblastic neoplasia depends on the histological subtype.

Pathophysiology

A hydatidiform mole is characterized by a conceptus of hyperplastic trophoblastic tissue attached to the placenta. The conceptus does not contain the inner cell mass. The hydatidiform mole can be of two types: a complete mole, in which the abnormal embryonic tissue is derived from the father only, and a partial mole, in which the abnormal tissue is derived from both parents.

• Complete moles usually occur when an empty ovum is fertilized by a sperm that then duplicates its own DNA. A 46, XY genotype may occur when 2 sperm (one 23, X and the other 23, Y) fertilize an empty egg. Their DNA is purely paternal in origin, and is diploid. Ninety percent are 46,XX, and 10% are 46,XY. In a complete mole, the fetus fails to develop.
• Partial moles can occur if a normal haploid ovum is fertilized by two sperm, or if fertilized by one sperm, if the paternal chromosomes become duplicated. Thus their DNA is both maternal and paternal in origin. They can be triploid (e.g. 69 XXX, 69 XXY) or even tetraploid.

Choriocarcinoma of the placenta during pregnancy is preceded by:

• Hydatidiform mole (50% of cases)
• Spontaneous abortion (20% of cases)
• Ectopic pregnancy (2% of cases)
• Normal term pregnancy (20-30% of cases)

Genetics

• Invasive mole- diploid or aneuploid karyotype
• Choriocarcinomas- aneuploid karyotype

Gross Pathology

• Dark, shaggy, focally hemorrhagic & friable/necrotic-appearing
• Invasive border

Microscopic Pathology

Gestational trophoblastic neoplasia classification

Types of Gestational Trophoblastic Neoplasia	Histopathological features
Invasive mole	The lesions are characterized by hyperplasia of cytotrophoblastic and syncytial elements and persistence of villous structures The lesions are characterized by trophoblastic invasion of the myometrium with identifiable villous structures
Choriocarcinoma	The lesions are characterized by columns and sheets of trophoblastic tissue invading uterine muscle and blood vessels
Placental-site trophoblastic tumor	The tumor arising from the placental implantation site and resembles an exaggerated form of syncytial endometritis Trophoblastic cells infiltrate the myometrium, and there is vascular invasion
Epithelioid trophoblastic tumor	The tumor has a monomorphic cellular pattern of epithelioid cells and may resemble squamous cell cancer of the cervix when arising in the cervical canal