Gestational trophoblastic neoplasia pathophysiology

Template:Choriocarcinoma Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Shivali Marketkar, M.B.B.S. [2]Monalisa Dmello, M.B,B.S., M.D. [3]

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 mass of cells inside the primordial embryo that will eventually give rise to the fetus). 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 process called androgenesis). 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 (since all chromosomes are derived from the sperm), 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)

Microscopic Pathology

Gestational Trophoblastic Neoplasias

Choriocarcinoma

Choriocarcinoma is a malignant tumor of the trophoblastic epithelium. Uterine muscle and blood vessels are invaded with areas of hemorrhage and necrosis. Columns and sheets of trophoblastic tissue invade normal tissues and spread to distant sites, the most common of which are lungs, brain, liver, pelvis, vagina, spleen, intestines, and kidney. Most choriocarcinomas have an aneuploid karyotype, and about three-quarters of them contain a Y chromosome. Most follow an HM pregnancy, spontaneous abortion, or ectopic pregnancy; but, about one-quarter of them are preceded by a full-term pregnancy. Nearly all GTDs that are preceded by nonmolar pregnancies are choriocarcinomas; the rare exceptions generally are PSTTs.

PSTT

PSTT disease is the result of a very rare 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. Human placental lactogen is present in the tumor cells.

ETT

ETT is an extremely rare gestational trophoblastic tumor. Although originally termed atypical choriocarcinoma, it appears to be less aggressive than choriocarcinoma and is now regarded as a distinct entity. Pathologically, it has a monomorphic cellular pattern of epithelioid cells and may resemble squamous cell cancer of the cervix when arising in the cervical canal.

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
Clear cell carcinoma	1. Common to all clear cells visible 2. Distinct cell membranes
Mucinous carcinoma	Well-differentiated columnar cells organized into glands with the characteristic mucin in the cytoplasm.
Mixed or undifferentiated carcinoma	Sheets of identical epithelial cells with no identifiable pattern

Microscopic Pathology

On light microscopy, there is malignant trophoblastic proliferation without hydropic villi.Characteristic feature is the identification of intimately related syncytiotrophoblasts and cytotrophoblasts without formation of definite placental type villi.Syncytiotrophoblasts are large multi-nucleated cells with eosinophilic cytoplasm. They often surround the cytotrophoblasts, reminiscent of their normal anatomical relationship in chorionic villi. Cytotrophoblasts are polyhedral, mononuclear cells with hyperchromatic nuclei and a clear or pale cytoplasm. Extensive hemorrhage is a common finding. Shown below is an image of choriocarcinoma.

The image shows a micrograph of choriocarcinoma showing both of the components necessary for the diagnosis - cytotrophoblasts and syncytiotrophoblasts. The syncytiotrophoblasts are multinucleated and have a dark staining cytoplasm. The cytotrophoblasts are mononuclear and have a pale staining cytoplasm.

Choriocarcinomas consist of two cell populations:

1. Cytotrophoblasts
   • Pale/clear cytoplasm
2. Syncytiotrophoblasts
   • Hyperchromatic cytoplasm
   • Typically multinucleated.

Traditionally, the syncytiotrophoblasts are said to produce the beta-hCG;however, it has been determined that cytotrophoblast also produce some.The syncytiotrophoblasts are often arranged around the outside of cytotrophoblast cell clusters, reminicent of the arrangement in the placenta. On placental Chorionic_villi, the syncytiotrophoblasts are superficial to and, early in pregnancy, cover the cytotrophoblast.Choriocarcinoma is classified as a germ cell tumour. It can arise in the testis or ovary and from a hydatidiform mole. It may be part of a mixed germ cell tumour.

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