|The big deal for the clinician is binary: (1) non-molar
POC vs. (2) molar (PHM or CHM) products of conception (POC). PHM
has 2% risk of persistent GTD, CHM risk is 20%6.
They follow partial and complete moles the same (except clinicians
are braced for a higher rate of recurrence-in-the-first-year in complete
moles): checking for persistent GTD which could have an invasive
component or toxemia. Refraining from pregnancy for about a year...easier
in younger age groups... allows time to detect signs of persistent
GTD. A molar pregnancy having a subsequent molar pregnancy
is about a 1% risk. Follow-up serum HCGs for 6-12 months. There is
no need to follow hydropic abortions (HA).
|The big deal for pathologists, therefore, is the
correct distinction of all three: (1) regressively hydropic
spontaneous blighted ovum or embryo abortions vs. (2) partial molar
(PHM) pregnancies AND the separation of partial molar pregnancies
vs. (3) complete (hydatidiform) molar pregnancies (CHM). Proper
gross exam (1) in search of hydropic villi & (2) submission
of adequate tissue is highly important! To settle follow-up needs
in cases of HA vs. PHM (especially in older and/or infertile mothers
where any delays at attempting pregnancy again are frustrating),
ploidy studies may be valuable (diploidy essentially excludes PM6).
|Unlike decades ago when molar pregnancies came to the lab in large-volume
containers, routine early-gestation follow up of all pregnancies
with ultrasound has us evaluating early stages of gestational POCs
with no ultrasound evidence of heart motion. So the histological
distinctions are less flagrant in currently modern times. Villous
capillaries form normally from yolk sac elements and regress with
absence of embryo (embryo absence of any etiology). So one could
see villous capillaries very early in a complete mole; then such
villi with capillaries become quickly "diluted out" early
in complete mole which never had an embryo1. Vessels
may be "diluted" into the stem villi. Yolk-sac-derived
hematopoietic cells can be seen in capillary lumens in HAs, PHMs,
|"As always, a cautionary comment pertains to a situation of
multiple gestation pregnancy with a mix of placental types in the
POC specimen. Those can be very confusing, and the immunoprofile
could also be confusing
|The standard dictum of refraining from pregnancy for one year following
diagnosis of molar pregnancy (complete or incomplete) is being liberalized
by modern technology, especially in the older age group of women "whose
biological clock is running out". Should the molar patient become
pregnant (in months or years), a quantitative HCG can be done at
the earliest chance along with an ultrasound. If HCG elevation is
concordant with ultrasound dates and ultrasound detects a sac (as
early as 4-5 weeks), a non-molar pregnancy is the initial working
diagnosis and pregnancy allowed to continue. D&C is performed
if HCG clearly high for dates and/or no evidence of sac by ultrasound
Is It Molar?:
||hydropic POC (HA)
||partial molar (PHM)
||complete molar (CHM)
|clinical follow-up needed?
|has grossly visible vesicular villi
||+ to +++
|has increased villous stroma cells
||not increased cellularity; maybe a little karryorrhectic4 nuclei.
||a bit/focally cellular; maybe a some karryorrhectic4 nuclei.
||Cellular/primitive stroma. Patches of karyorrhectic
nuclei even in very early5.
|has villi with acellular central cisterns
||yes, rarely in a few villi4
||yes, widespread; but may be scant in very
|character of villous population
||mix of 2 types (ordinary &
only microscopically5 hydropic/edematous)
||mix of two (& non-microscopically
visible hydrops leans toward molar)
||Pretty much one population. Generalized
villous hydrops5....but. don't forget the potential
situation of multiple gestational POC.
|shape of villous cross-sectional outlines
||less frequently complex; but see frequent cross-sections
("inclusions")4 of trophoblast cords in stroma
||Round & simple & few or no inclusions.
||No atypia. Not much if any circumferential hyperplasia
(which, if present, is non-cytotrophoblastic). Lack of troph proliferation & trophs
||finding of even focal mild mild cyto-syncyt. troph
some circumferential is essential to DX of mole
||atypia (especially of intermediates) & excessive5
cyto-syncyt. troph. hyperplasia
& lots circumferential5
|embryonic/yolk-sac-blood cells present
||yes, often (somatic & other)
(except early villous vessels, sometimes; some
yolk-sac-derived blood cells if D&C as early as 6-10 weeks4)...don't
forget the potential situation of multiple gestational POC.
|IHC Ki-67 nuclear-positive trophs
||HA is regressive; no good pattern of
proliferating zones, centers, or clusters
|IHC p57 nuclear-positive trophs3
||high % +
||high % +
||Various (4-14% triploid6). Majority
Diploidy essentially excludes PHM6.
||always (>90%5) triploid;
normal ovum plus two sperm7. [see CN06-73; L11-3666 by SISH]
||not triploid (usually diploid6);
empty ovum plus a sperm that undergoes duplication7. STR
by PCR can discern HA from CHM7.
|Placental Site Nodule (PSN): can
be retained for years
|Exaggerated placental site reaction
(EPSR): also known as syncytial endometritis; is a
proliferation of intermediate trophoblasts with identical immunophenotype
of normal implantation site intermediate trophoblasts. May see
villi; rare or absent mitoses5; it may be impossible
to differentiate this from PSTT5. May occur
in association with a normal pregnancy, abortion, or molar pregnancy.
No treatment or follow up needed if one can solve the nightmarishly
difficult DDX between EPSR & PSTT5.
|Placental Site trophoblastic Tumor
(PSTT): may be diagnosed long after any previously
known pregnancy; has extensive deposition of fibrinoid material;
malignant behavior when Ki67 >50% & benign behavior when
14% or less5.
|Epithelioid Trophoblastic Tumor: may
be diagnosed long after any previously known pregnancy; HCG always
elevated at time of diagnosis; discrete expansile nodule.
(posted 2 April 2005;
latest update 13 Oct 2006)
Lage JM & McEvoy R, Unknown cases: GTD cases,
MUSC McKee-PT Seminar, 6 April 2005 (EBS).
discussions with OB-GYN members of our local
Crum CC, et. al., Discrimination of Complete
Hydatidiform Mole From its Mimics by Immunohistochemistry of
the Paternally Imprinted Gene Product p57KIP2.
personal e-mails or discussions from experts & "focused" practitioners.
Daya, Dean M, Professor of Pathology & Molecular
Med. & OB-GYN, McMaster U., Ontario; Interpretation of
Endometrial Biopsies & Curettings, 12th Annual Seminar
in Pathology, 28 April-1 May 2005, Pittsburgh (EBS)
Fukunaga M, et. al., Interobserver and Intraobserver
Variability in the Diagnosis of Hydatidiform Mole, AJSP 29(7):942-947.
Leonard DGB, Diagnostic Molecular Pathology,
208 pages, 2003.
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