Placenta
Gestational trophoblastic disease
Incomplete / partial mole

Author: Aurelia Busca, M.D., Ph.D.
Editor: Carlos Parra-Herran, M.D.
Deputy Editor in Chief: Debra Zynger, M.D.

Revised: 15 May 2018, last major update April 2018

Copyright: (c) 2003-2018, PathologyOutlines.com, Inc.

PubMed Search: Incomplete mole[title] OR partial mole[title]

Cite this page: Busca, A. Incomplete / partial mole. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/placentaincompletemole.html. Accessed August 15th, 2018.
Definition / general
  • Gestational trophoblastic disease with abnormal chorionic villi (hydatiform mole) characterized by a spectrum of villous populations ranging from normal size to substantial enlargement, irregular contours and mild, focal trophoblastic hyperplasia
Essential features
  • Hydatiform mole resulting from fertilization of a normal egg by two spermatozoa or by one spermatozoa followed by duplication of the paternal chromosomal content
  • Low risk of persistent gestational trophoblastic disease
  • Two discrete populations of villi (enlarged, hydropic villi and small, fibrotic villi), with the larger villi showing irregular scalloped borders and cistern formation
  • Mild circumferential trophoblastic hyperplasia
  • p57+ in villous stromal cells and cytotrophoblast
  • Typically have a diandric triploid genotype
  • Main differential diagnosis includes complete mole (p57-, diandric diploid genotype) and hydropic abortus (p57+, biparental diploid genotype)
Terminology
  • Partial molar pregnancy, partial / incomplete mole
Epidemiology
  • Estimated rate of hydatidiform moles is 7.5 per 10,000 pregnancies (Am J Obstet Gynecol 1986;154:906)
  • More frequent than complete mole; in a study of pathological examination of first and second trimester abortions, the incidence of partial mole was 1:695 compared to complete mole, 1:1,945 (Int J Gynecol Pathol 1993;12:315)
  • Risk of partial mole was 11 cases per 10,000 live births (Gynecol Oncol 2016;143:73)
  • Variable incidence of hydatidiform mole reported throughout the world with increased rates in Asia and Middle East (Lancet Oncol 2003;4:670)
    • Asians were more likely than whites to develop complete mole and less likely to develop partial mole
    • Blacks and Hispanics were less likely than whites to develop both partial and complete mole
  • Established risk factors include advanced maternal age and previous history of molar pregnancy (Lancet Oncol 2003;4:670, J Reprod Med 2006;51:902, BJOG 2003;110:22)
Pathophysiology
  • Partial hydatidiform mole results from the fertilization of a normal egg by two spermatozoa (dispermic, 90%) or fertilization by one spermatozoa followed by duplication of the paternal chromosomal content (monospermic, 10%)
    • As a result, partial moles have a triploid genome, diandric and monogynic
  • Rare tetraploid partial moles have been reported, with three sets of paternal chromosomes and one set of maternal origin (Int J Gynecol Pathol 2012;31:73)
Clinical features
  • Can present with missed or spontaneous abortion
  • Other symptoms include vaginal bleeding, pelvic pressure, uterus enlarged for gestational age and hyperemesis gravidarum (Obstet Gynecol 1995;86:775)
Diagnosis
  • A combination of clinical, laboratory and imaging data raises the possibility of molar pregnancy
  • Poor interobserver agreement in differentiating between complete mole, incomplete mole and hydropic abortus when using histology alone, with discordance predominantly seen in partial mole vs. hydropic abortus (Am J Surg Pathol 2005;29:942)
  • An algorithmic approach, in conjunction with p57 immunohistochemistry, has been proposed by using morphological assessment in order to triage cases that would require genetic analysis
    • p57 negative cases with molar morphology would be diagnosed as complete hydatidiform moles without genotyping and all p57+ cases would be subjected to genotyping (Mod Pathol 2014;27:238)
Laboratory
Radiology description
  • Ultrasound is the main radiological modality for evaluating molar pregnancies, but the sensitivity is low in the first trimester: routine pre-evacuation ultrasound examination identifies less than 50% of hydatidiform moles before 14 weeks (Ultrasound Obstet Gynecol 2006;27:56)
  • Ultrasound detection rate was lower for incomplete moles (29%) compared to complete moles (79%) (Ultrasound Obstet Gynecol 2006;27:56)
  • Findings correlating with a diagnosis of partial mole include cystic changes in the decidual reaction / placenta and an increase in the transverse diameter of the gestational sac (Obstet Gynecol 1989;73:414)
Prognostic factors
Case reports
  • First trimester abortus with tetraploid triandric partial mole confirmed with genotyping and FISH (3 paternal and 1 maternal chromosome sets) (Int J Gynecol Pathol 2012;31:73)
Treatment
  • Evacuation and curettage, with followup with serum human chorionic gonadotropin (hCG) levels and contraception until undetectable levels are obtained (Am J Obstet Gynecol 2010;203:531)
  • Overall risk of requiring chemotherapy after a partial mole was 1.1% (compared with 13.6% for complete mole) (J Obstet Gynaecol 2013;33:406)
Gross description
  • Immature placental tissue admixed with vesicles that tend to be smaller and less numerous than those of a complete mole
  • Intermediate volume between that of a hydropic abortion and a complete mole
  • Fetal parts including nucleated red blood cells in villous capillaries, as well as a gestational sac may be present
Gross images

Images hosted on other servers:

Partial hydatidiform mole

Microscopic (histologic) description
  • Heterogeneity in villous size with two discrete populations of villi (large, hydropic villi and small, fibrotic villi)
  • Enlarged villi are irregularly shaped with scalloped borders and secondary trophoblastic pseudoinclusions
  • Cistern formation can be seen in enlarged villi
  • Circumferential mild trophoblastic hyperplasia
  • Presence of at least 3 of the above histologic features of partial mole correlates with triploidy on FISH and flow cytometry analysis (Hum Pathol 2000;31:914, Int J Gynecol Pathol 2001;20:315)
Microscopic (histologic) images

Images hosted on PathOut server:

Contributed by Aurelia Busca, M.D., Ph.D.
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Two population villi

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Edematous hydropic villi with inclusions

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Hydropic villi with cystern formation and minimal trophoblastic prolifearion


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p57 nuclear staining



Images hosted on other servers:
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Minimal trophoblastic proliferation; some have hydropic villi

Virtual slides

Images hosted on other servers:
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20 year old woman, missed abortion

Positive stains
  • p57
    • Paternally imprinted maternally expressed gene
    • Expression in villous stromal cells and cytotrophoblasts (complete mole is p57-)
    • Requires internal positive control in maternal decidua and syncytiotrophoblast
    • p57 cannot distinguish partial mole from nonmolar specimens (both p57+) as both have maternal DNA (Hum Pathol 2005;36:180)
    • Rare cases of incomplete moles may lack p57 expression because of loss of the maternal copy of chromosome 11; genotypic analysis would confirm diandric triploidy (Am J Surg Pathol 2011;35:1586)
Flow cytometry description
  • Flow cytometry with determination of ploidy can be used on paraffin embedded samples
  • Cannot distinguish between maternal and paternal origin of genetic material
  • A triploid karyotype by flow cytometry is consistent with partial hydatidiform mole in conjunction with morphological features
  • Would require additional DNA testing to establish if triploidy is diandric vs. digynic (Utah.edu: Triploidy [Accessed 26 March 2018], Iran J Reprod Med 2015;13:269)
Molecular / cytogenetics description
    Genotyping:
  • PCR amplification of short, tandem and repeat (STR) loci
  • Testing of both maternal decidua and villous tissue can identify diandric triploid genotype (Int J Gynecol Pathol 2011;30:101, Obstet Gynecol 2010;115:784)
  • In a study of 158 partial moles, 155 were diandric triploid (83 cases XXY, 59 cases XXX, 13 cases XYY) and 3 were triandric tetraploid (2 cases XXYY and 1 case XXXY) (Mod Pathol 2014;27:238)

  • Fluorescence in situ hybridization (FISH):
  • Uses fluorescently labeled DNA probes targeting regions of various chromosomes, including X and Y
  • Can be used to determine sex chromosome and copy number
  • Cannot differentiate between maternal and paternal origins of genetic material (Prenat Diagn 2005;25:314)
Differential diagnosis
  • Complete mole: p57- and androgenetic diploidy
    • Early complete mole (less than 12 weeks); no embryonic development, may have morphological overlap with incomplete mole, as molar features are not well developed (villi are smaller, cisterns and cavitation not well developed, some degree of trophoblastic proliferation and atypia)
    • Well developed complete mole: no embryonic development, one population of villi with extensive hydrops, more trophoblastic hyperplasia and atypia
  • Hydropic spontaneous abortion
    • Only mildly enlarged and edematous villi, occasionally cistern formation
    • Tissue is usually less voluminous than partial mole
    • p57 is not helpful in differentiating the two, as both will be p57+
    • Biparental diploidy
  • Beckwith-Wiedemann syndrome
    • Placenta often has gross abnormalities, including edema with enlarged villi and centrally cavitated stem villi
    • Scalloping and syncytiotrophoblastic hyperplasia should be absent
    • Diploid (Obstet Gynecol 1994;83:813)
  • Mosaic / chimeric conceptions: can exhibit a spectrum of morphologic alterations, some of which can suggest a hydatidiform mole
  • Nonmolar placentas with cytogenetic abnormalities such as trisomies can show abnormal villi suggestive of an incomplete mole
    • Distinction on morphologic grounds alone is difficult and poorly reproducible
    • Would require genetic testing to identify the exact cytogenetic abnormality (J Mol Diagn 2010;12:525)
  • Twin gestation with complete mole and coexisting fetus, rare
    • Typically shows two villous populations which may be mistaken for partial mole
    • Molar villi show typical features for complete mole: atypia, cavitation, marked trophoblastic proliferation
    • Fetus has a normal karyotype and is normally developed
    • p57 will be absent in the molar villi only (J Matern Fetal Neonatal Med 2007;20:175, J Ultrason 2017;17:299)
Additional references
  • Metastatic trophoblastic disease after an initial diagnosis of partial hydatidiform mole (Cancer 2004;100:1411)
  • Placental site trophoblastic tumor arising from a partial hydatidiform mole (Lancet 2005;366:688)
Board review question #1
    What is the typical genetic profile of incomplete mole?

  1. Biparental diploidiy
  2. Diandric triploidy
  3. Digynic triploidy
  4. Triandric tetraploid
Board review answer #1
B. Diandric triploidy