Cellular Classification of Gestational Trophoblastic Disease
Gestational trophoblastic disease (GTD) may be classified as follows:
- Hydatidiform mole (HM).
- Gestational trophoblastic neoplasia.
Choriocarcinoma, PSTT, and ETT are often grouped under the heading gestational trophoblastic tumors.
HM is defined as products of conception that show gross cyst-like swellings of the chorionic villi that are caused by an accumulation of fluid. There is disintegration and loss of blood vessels in the villous core.
A complete mole occurs when an ovum that has extruded its maternal nucleus is fertilized by either a single sperm, with subsequent chromosome duplication, or two sperm, resulting in either case in a diploid karyotype. The former case always yields a mole with a karyotype of 46 XX, since at least one X chromosome is required for viability and a karyotype of 46 YY is rapidly lethal to the ovum. The latter case may yield a karyotype of 46 XX or 46 XY. About 90% of complete HMs are 46 XX. On ultrasound examination, complete moles rarely reveal a fetus or amniotic fluid.
A partial mole occurs when the ovum retains its nucleus but is fertilized by a single sperm, with subsequent chromosome duplication, or is fertilized by two sperm; the possible resulting triploid karyotypes are 69 XXY, 69 XXX, or 69 XYY. Therefore, in contrast to a complete mole, the partial mole chromosomes of a partial mole are only two-thirds paternal in origin. In contrast to complete moles, partial moles usually show a fetus, which may even be viable, and amniotic fluid is visible.
Complete HMs have a 15% to 25% risk of developing into an invasive mole, but transformation to malignancy is much more rare (<5%) in the case of partial moles.
Gestational Trophoblastic Neoplasias
Invasive moles (chorioadenoma destruens) are locally invasive, rarely metastatic lesions characterized microscopically by trophoblastic invasion of the myometrium with identifiable villous structures. These may be preceded by either complete or partial molar pregnancy. They are usually diploid in karyotype, but may be aneuploid. Microscopically, these lesions are characterized by hyperplasia of cytotrophoblastic and syncytial elements and persistence of villous structures. They may resemble choriocarcinoma in histologic appearance. Invasive moles have more aggressive behavior than either complete or partial HMs, and they are treated similarly to choriocarcinoma (i.e., with chemotherapy). However, unlike choriocarcinoma, they may regress spontaneously.
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 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, whereas immunoperoxidase staining for human chorionic gonadotropin (hCG) is positive in only scattered cells, and elevations in serum hCG are relatively low compared with the marked elevations seen in choriocarcinoma. hCG is not a reliable marker of tumor volume.[2,3] PSTTs have much lower growth rates than choriocarcinoma, and presentation after a full-term pregnancy is often delayed by months or years. They are generally resistant to chemotherapy. Therefore, hysterectomy is the standard primary treatment if the tumor is confined to the uterus. However, about 35% of PSTTs have distant metastases at diagnosis.[3,4] Common sites of metastasis include the lungs, pelvis, and lymph nodes. Central nervous system, renal, and liver metastases have also been observed.
ETT is an extremely rare gestational trophoblastic tumor.[5,6] 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. Its clinical behavior appears to be closer to that of PSTT than to choriocarcinoma. It has a spectrum of clinical behavior from benign to malignant. About one-third of patients present with metastases, usually in the lungs.
- Altieri A, Franceschi S, Ferlay J, et al.: Epidemiology and aetiology of gestational trophoblastic diseases. Lancet Oncol 4 (11): 670-8, 2003. [PUBMED Abstract]
- Lurain JR: Gestational trophoblastic tumors. Semin Surg Oncol 6 (6): 347-53, 1990. [PUBMED Abstract]
- Feltmate CM, Genest DR, Goldstein DP, et al.: Advances in the understanding of placental site trophoblastic tumor. J Reprod Med 47 (5): 337-41, 2002. [PUBMED Abstract]
- Schmid P, Nagai Y, Agarwal R, et al.: Prognostic markers and long-term outcome of placental-site trophoblastic tumours: a retrospective observational study. Lancet 374 (9683): 48-55, 2009. [PUBMED Abstract]
- Shih IM, Kurman RJ: Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma. Am J Surg Pathol 22 (11): 1393-403, 1998. [PUBMED Abstract]
- Palmer JE, Macdonald M, Wells M, et al.: Epithelioid trophoblastic tumor: a review of the literature. J Reprod Med 53 (7): 465-75, 2008. [PUBMED Abstract]