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Histology of gestational trophoblastic disease

Mola hydatidosa is an abnormal pregnancy of paternal origin that is divided into the following entities (according to WHO):

Benign

  • Complete hydatidiform mole – genetically diploid, both chromosome sets are from the father. The complete mole lacks embryo and membranes. The placental tissue is completely changed and consists of large chorionic villi, and hyperplastic trophoblasts, that produce vesicles.
  • Partial hydatidiform mole – often genetically triploid with two chromosomal sets from the father and one from the mother. There is often an embryo with malformations that dies early in the pregnancy. The placental changes are focal and less pronounced compared to a complete mole.

Microscopically it can be difficult to separate complete from partial mole. In addition degenerative changes in the placenta can simulate these conditions.  In complete mole chorionic villi demonstrates hydropic swelling and central cisternas, and a general growth of trophoblasts on the surface of the chorionic villi. Partial mole often shows two populations of chorionic villi, one with ordinary and the other with hydropic villi. Also in the partial mole there is trophoblast proliferation. In addition indentations into the surface of the chorionic villi are seen and it can look like "Norwegian fjords". Embryonic tissue can sometimes appear in partial mole. The microscopic diagnosis requires experience and often additional methods such as immunohistochemistry (p75 kip2), DNA ploidy or molecular methods

Malignant

Photomicrograph demonstrating a choriocarcinoma. Click to enlarge.
  • Persistent trophoblastic disease – after evacuation of a mola hydatidosa serum hCG will  spontaneously normalize. This is a sign of remaining trophoblastic  tissue that must be further investigated.
  • Invasive mola –the molar tissue invades the myometrium and can result in a uterine perforation and intraabdominal bleeding. Metastases can appear in the pelvic region or distant organs.
  • Choriocarcinoma  – can appear in all forms of pregnancies (including birth, abortion, extrauterine pregnancy complete mole or partial mole). It differs from invasive mole by lacking chorionic villi  and growing in a biphasic pattern with syncytio- and cytotrophoblasts. There is often bleeding a large necrosis. This tumor grows rapidly and metastasizes early. 
  • Placenta-site-trophoblasic tumor   – originate from trophoblasts in the placental implantation site. This is a rare tumor with malignant differentiation of mainly cytotrophoblasts, and to some degree also of the syncytiotrophoblasts, and thus demonstrate a lower serum hCG compared to choriocarcinomas. It can be associated with an elevated HPL level.
  • Epithelioid  trophoblastic tumor – supposed to originate from specialized intermediate trophoblastic cells in the implantation site and chorion leave similar to placental site tumor. These tumors are difficult to diagnose and require special pathologic expertise.

Common for the two types of moles is the trophoblastic proliferation producing the increased level of hCG in serum. Moles are considered a premalignant condition. About  2–5 % of the partial and 8–15 % of complete moles develop into persistent trophoblastic disease or choriocarcinoma. 

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