A gestational trophoblastic disorder

Synopsis

 Placenta with grossly swollen chorionic villi (hydropic villi)
 bunch of grapes aspect
 varying degrees of trophoblastic proliferation
 absence of embryo

Types

 complete hydatiform mole

• A complete mole contains no fetal tissue.
• Ninety percent are 46,XX, and 10% are 46,XY. All chromosomes are of paternal origin.
• An enucleate egg is fertilized by a haploid sperm (which then duplicates its chromosomes), or the egg is fertilized by 2 sperm.
• In a complete mole, the chorionic villi have grapelike (hydatidiform) swelling, and trophoblastic hyperplasia is present.

 A rare form of recurrent complete mole is biparental in origin and results from misexpression of imprinted genes. This type of mole occurs when maternal imprints in the ovum are lost.

• Although the resulting conceptus has genes from both parents, loss of maternal imprinting gives the functional equivalent of 2 paternal genomes.
• Recurrent molar pregnancies of this type are familial and appear to be inherited as an autosomal recessive trait. A candidate region of chromosome arm 19q13.4 has been identified.

 partial hydatiform mole

• With a partial mole, fetal tissue is often present. Fetal erythrocytes and vessels in the villi are a common finding.
• The chromosomal complement is 69,XXX or 69,XXY. This results from fertilization of a haploid ovum and duplication of the paternal haploid chromosomes or from dispermy.
• Tetraploidy may also be encountered. As in a complete mole, hyperplastic trophoblastic tissue and swelling of the chorionic villi occur.

Cytogenetics

 complete moles homozygous, XX 46 with all the chromosomes of paternal origin.

• second trimester of pregnancy with abnormal uterine bleeding
• excessive uterine enlargement
• high serum human chorionic gonadotropin concentration
• possible complication: choriocarcinoma

The p57(KIP2) protein is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation.

Molecular

Pathology

 mutations in the maternal gene NALP7 in individuals with familial and recurrent hydatidiform moles (HMs)

• NALP7 is a member of the CATERPILLER protein family involved in inflammation and apoptosis. NALP7 is the first maternal effect gene identified in humans and is also responsible for recurrent spontaneous abortions, stillbirths and intrauterine growth retardation.
• NALPs are cytoplasmic proteins that form a subfamily within the larger CATERPILLER protein family. Most short NALPs, such as NALP7, have an N-terminal pyrin (MEFV) (MIM.608107) domain (PYD), followed by a NACHT domain, a NACHT-associated domain (NAD), and a C-terminal leucine-rich repeat (LRR) region.
• NALPs are implicated in the activation of proinflammatory caspases (CASP1) (MIM.147678) via their involvement in multiprotein complexes called inflammasomes.

Immunochemistry

 p57KIP2 (CDKN1C) expression in molar pregnancy

• Negative p57KIP2 (CDKN1C) immunoreactivity (paternally imprinted, maternally expressed gene) is in perfect concordance with the androgenetic origin of molar pregnancies proven by DNA polymorphism. (#15971478#)
• p57KIP2 (CDKN1C) immunoreactivity, which can be performed in routine pathologic examinations, is a diagnostic tool to differentiate androgenetic complete moles from biparental conceptuses. (#15971478#)

Differential diagnosis

 hydropic abortion

See also

 gestational trophoblastic diseases

References

 Murdoch S, Djuric U, Mazhar B, Seoud M, Khan R, Kuick R, Bagga R, Kircheisen R, Ao A, Ratti B, Hanash S, Rouleau GA, Slim R. Mutations in NALP7 cause recurrent hydatidiform moles and reproductive wastage in humans. Nat Genet. 2006 Feb 5; PMID: #16462743#

 Romaguera RL, Rodriguez MM, Bruce JH, Zuluaga T, Viciana A, Penalver MA, Mehrdad N. Molar gestations and hydropic abortions differentiated by p57 immunostaining. Fetal Pediatr Pathol. 2004 Mar-Jun;23(2-3):181-90. PMID: #15768863#

 Jun SY, Ro JY, Kim KR. p57kip2 is useful in the classification and differential diagnosis of complete and partial hydatidiform moles. Histopathology. 2003 Jul;43(1):17-25. PMID: #12823708#