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Gestational trophoblastic disease

Complete mole

Reviewers: Mandolin Ziadie, M.D. (see Reviewers page)
Revised: 7 December 2011, last major update November 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.

Clinical features

● Caused by abnormal gametogenesis and fertilization, resulting in a diploid genome that is of paternal origin only
● No fetus is present
● Presents in second trimester with uterine enlargement, markedly elevated hCG without the normal fall that occurs by week 14
● Some women may present with pre-eclampsia or hyperemesis gravidarum in first trimester
● Ultrasound reveals a “snowstorm pattern”
● Molar tissue rarely secretes TSH, which causes hyperthyroidism, theca-lutein cysts
Risk factors: delivery in Asia, Africa or Latin America; age > 30; vitamin A deficiency; history of prior mole

Prognostic factors

● Large for date uterus
● Ovarian enlargement due to theca-lutein cysts (Obstet Gynecol 1988;72:247)
● Histologic grading is not predictive of risk of choriocarcinoma

● Fibrin-like material at tumor-host interface; abundant syncytiotrophoblasts


● D & C, chest Xray (for metastases), follow hCG levels for 60 days; if hCG still elevated, give chemotherapy (20% of cases)
● Post-D & C: 2-12% experience respiratory distress from “metastasis” to lung and fluid overload, 10-17% progress to invasive moles and 3-5% to choriocarcinoma; 1% will have another molar pregnancy

Gross description

● Abundant tissue; grape-like vesicles that fill the uterus and involve the entire placenta
● No fetal parts / cord / membranes are present

Gross images

Grape-like villi

Micro description

● Diffuse, circumferential trophoblastic (cytotrophoblast, syncytiotrophoblast and intermediate trophoblast) proliferation with avascular edematous villi that have central cisterns (acellular central space, often fluid filled and separated from surface by small rim of mesenchymal cells)
● Patchy villous calcification, atypia (nuclear and cytoplasmic enlargement, variable nuclear outlines and hyperchromasia) or necrosis may be present
● Note: some villi are surrounded by attenuated layer of degenerating trophoblast with sparse vessels and helper T cells at implantation site
● Implantation site often associated with hyperplasia of intermediate trophoblast resembling exaggerated placental site but with high Ki-67 staining (vs. 0 in exaggerated placental site)
● Presence of villi or atypical trophoblast after evacuation of molar pregnancy indicates persistent trophoblastic disease
● Very early features are redundant bulbous terminal villi, hypercellular villous stroma, labyrinthine network of villous stromal canaliculi, focal cytotrophoblast and syncytiotrophoblast hyperplasia on villi and the undersurface of the chorionic plate; also enlarged hyperchromatic implantation site trophoblast (Hum Pathol 1996;27:708)

Micro images

Atypical trophoblastic proliferation with chorionic villi

Positive stains

● hCG (stronger than partial mole, less than choriocarcinoma)
● p53 (Mod Pathol 1996;9:392)

Negative stains

● p57KIP2 (cyclin-dependent kinase inhibitor, paternally imprinted and expressed predominantly from maternal allele in most tissues; not expressed in complete hydatidiform moles, except in intervillous trophoblast islands)

Molecular description

● Ploidy analysis useful for diagnosis (Arch Pathol Lab Med 1998;122:1000)
● 50% are diploid, 43% tetraploid (Arch Pathol Lab Med 1996;120:569)
● Diploid moles - 85% are 46 XX and both X are androgenic (“daddy’s girl”, empty ovum is fertilized by sperm that duplicates without cytokinesis, no maternal nuclear DNA, but there is maternal mitochondrial DNA); 15% are 46 XY and also androgenic (possibly due to fertilization of empty ovum by 2 sperm)
● FISH analysis can establish dizygotic origin of twin pregnancies with complete mole and co-existing fetus (Hum Pathol 1995;26:1175)

Differential diagnosis

● Partial mole: biphasic histology, may have fetal parts, triploid, weaker staining for p53 and positive staining for p57 (Am J Surg Pathol 2001;25:1225, Hum Pathol 2002;33:1188)
● Spontaneous hydropic abortion: polarized trophoblastic proliferation, no trophoblast atypia, less edema and no central cistern formation

End of Placenta > Gestational trophoblastic disease > Complete mole

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