Answer: Complete hydatidiform mole

Histology:
– Typical CHMs are comprised of enlarged edematous villi with moderate to marked circumferential trophoblastic hyperplasia, often with cytologic atypia, prominent central cistern formation, and trophoblastic inclusions. The implantation site associated with CHM shows features similar to exaggerated placental site.
– CHMs are androgenetic diploid conceptions, arising by fertilization of an ovum without maternal DNA by 1 sperm that duplicates (most commonly) or 2 sperm; they thus contain 2 paternal and no maternal chromosomal complements.
– A CHM is characterized by androgenetic diploidy, so the maternal copy of chromosome 11 is absent. P57 therefore cannot be expressed, so by IHC the villous stromal cells and cytotrophoblast will be negative. Intermediate trophoblastic cells are always positive and therefore serve as an internal positive control.

Discussion: Gestational trophoblastic disease (GTD) incidence is much higher in Asia and Latin America than in Europe/ North America. Other risk factors include a history of GTD, and “extremes of age” (ie less than 20 and greater than 40). Elevation of hCG normal (usually above 100,000 mIU/mL). In the past, it was common for patients to present with uterine enlargement, but an increasing number of cases are now presenting at an earlier gestational age.

Differential Diagnosis:
– Partial Hydatidiform Moles: two populations of villi (large, irregular, hydropic villi and small, immature, fibrotic villi), cisterns in some enlarged villi, markedly irregular villi with scalloped borders and trophoblastic inclusions, and generally mild circumferential trophoblastic hyperplasia. P57+.
– (If you only have trophoblastic cells and no villi) Choriocarcinoma: Should contain syncitiotrophoblastic cells and cytotrophoblast (can highlight giant cells with hCG). Remember in small biopsies to suggest both, though clinical history and hCG can be helpful as well).

Persistent gestational trophoblastic disease occurs in approximately 17-20% of women who undergo curettage, and in 3-5% of patients who undergo hysterectomy. Risk of choriocarcinoma is 2-5% in the United States. Monitoring of patients with CHM with serial hCG levels can identify those patients at risk for persistent GTD.

Reference(s):
– Blaustein’s Pathology of the Female Genital Tract, 6th ed. Chapter 20.