Gestational trophoblastic neoplasia pathophysiology

Gestational trophoblastic neoplasia Microchapters
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Sabawoon Mirwais, M.B.B.S, M.D.[2]Monalisa Dmello, M.B,B.S., M.D. [3]

Overview

Gestational trophoblastic neoplasia arises from the trophoblastic tissue, which provides nutrients to the embryo and develops into a large part of the placenta. On gross pathology, gestational trophoblastic neoplasia is characterised by a dark, shaggy, focally hemorrhagic & friable/necrotic-appearing mass with invasive borders. The pathophysiology of gestational trophoblastic neoplasia depends on the histological subtype.

Pathophysiology

Physiology

The normal physiology of pregnancy can be understood as follows:

• Pregnancy occurs when an egg, which is released from the ovary during ovulation, is fertilized by a sperm.
• After ejaculation, the released sperm must spend some time in the female reproductive tract and undergo capacitation, which is basically the acquisition of fertilization capability.
• The sperm then penetrates the egg after the acrosomal reaction and initiates the process of fertilization in the fallopian tube.
• The sperm breaks through the oocyte's plasma membrane and releases its haploid nucleus into the oocyte.
• Cortical reaction (changes in the oocyte membrane) prevents any further penetration by another sperm.
• Unification of the two haploid nuclei (one each from the sperm and egg) marks the completion of fertilization, resulting in the formation of a diploid zygote.
• The zygote undergoes multiple divisions called cleavage before its migration to the uterus.
• Human pregnancy takes approximately 40 weeks.

For more information on fertilization, click here. For more information on pregnancy, click here.

Pathogenesis

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