October 2020 — Gynecological

The correct answer is complete hydatidiform mole.

A complete hydatidiform mole (CHM) typically presents as heavy vaginal bleeding, β-hCG level out of proportion to normal, and significantly enlarged uterus when compared with gestational age. Histologic examination will demonstrate uniformly large, hydropic villi with central cisterns and karyorrhectic debris within the villous stroma. Additionally, the abnormal villi will have trophoblastic hyperplasia in a concentric distribution, rather than in a polar distribution as would be seen in normal villi.

Partial hydatidiform moles, in contrast to CHM, should have two populations of villi. One population would appear normal and the other would appear large and atypical with syncytiotrophoblastic hyperplasia. Villous blood vessels may have evidence of fetal development with the presence of nucleated red blood cells in circulation¹.

Hydropic abortions are typically distinguishable from molar pregnancies from morphologic features, however, due to earlier imaging detection of a molar pregnancy, this distinction may be challenging as the characteristic features of a hydatidiform mole are seen beginning in the second trimester².

Except in very rare occasions, CHM are known to be a result of diandry (paternal fertilization of an empty egg; monospermic or dispermic), thus lacking maternal genetic material. When the morphologic features are not diagnostic of a CHM, this genetic variation can be helpful in making a definitive diagnosis. CDKN1C/P57 gene is maternally expressed and paternally imprinted (due to methylation), therefore, immunohistochemical stain for p57 will be immunoreactive in maternally derived proteins. In a CHM, p57 reactivity will be lost in the villous stroma and cytotrophoblastic nuclei. Decidua and extravillous intermediate trophoblast will always have nuclear immunoreactivity for p57 and can serve as an internal control¹.

References
1. Horii Mariko, Kindelberger David, Quade Bradley, Boyd Theona, Crum Christopher, Parast Mana. (2018).‘Trophoblast Neoplasia’, in Crum, C.P. (ed.) Diagnostic Gynecologic and Obstretic Pathology. Philadelphia: Elsevier. pp. 1103-1136.
2. Rita L. Romaguera, Maria M. Rodriguez, Jocelyn H. Bruce, Tania Zuluaga, Ana Viciana, Manuel A. Penalver* & Mehrdad Nadji (2004) MOLAR GESTATIONS AND HYDROPIC ABORTIONS DIFFERENTIATED BY p57 IMMUNOSTAINING, Fetal and Pediatric Pathology, 23:2-3, 181-190, DOI: 10.1080/15227950490890351