Biomedical Journal of Indonesia Vol 7 Issue 1 2021

Biomedical Journal of Indonesia

Journal Homepage: https://www.jurnalkedokteranunsri.id/index.php/BJI/index

Molahidatidosa from Pathophysiology to Clinical: Literature Review

Rachmat Hidayat1*, Irawan Sastradinata2
1Department of Biology, Faculty of Medicine, Universitas Sriwijaya, Palembang, Indonesia
2Department of Obstetric and Gynecology, Faculty of Medicine, Universitas Sriwijaya, Palembang, Indonesia

A R T ICL E IN FO A B ST R A CT
Keywords: Hydatidiform is a gestational trophoblast disease which is histopathologically
Molahidatidosa characterized by the proliferation of avascular trophoblast cells and corial villi and
undergoing hydrophic degeneration. The proliferation of trophoblast cells in
Trophoblast
hydatidiform moles can be in the form of cytotrophoblast, syncytiotrophoblast or
Gestational intermediate trophoblast proliferation.

Corresponding author:
E-mail address:
dr.rachmat.hidayat@gmail.com

All authors have reviewed and

approved the final version of the
manuscript.

https://doi.org/10.32539/BJI.v7i1.10

1. Introduction chromosomes), paternal and maternal factors. 1-21

Molahidatidosa may occur due to cytogenetic Pathophysiology of molahidatidosa is still
abnormalities, abnormalities in gene / protein unclear, chromosome analysis of molahidatidosa
expression and nutritional factors. 1 Genetic tissue yields several possibilities that occur in the
studies of molahidatidosa show that fertilization process. 1 22-24 Fertilization of
molahidatidosa can originate or occur from hydatidiform mole occurs due to the absence of
androgenetic fertilization but also normal chromosomes in the ovum, chromosome analysis
fertilization. 1 Complete and partial of complete hydatidiform mole trophoblast tissue
molahodatidosa has histology, morphology, only expresses paternal chromosomes (father
clinical features or causes. different. Complete chromosomes), maternal chromosomes are only
hydatidose, diploidy with a 46-XX karyotype, the found on partial trophoblast mole hydatidose
chromosomes are entirely paternal. Some cases chromosomes. 1,25 Initially it was thought that
have a triploidy or tetraploidy karyotype. There are molahidatidosa was a continuation of the blighted
no embryos or fetuses clinically, the fetus can only ovum, but in the study it was found that the
be seen if the pregnancy is multiple / multiple mother and father DNA contained the mother's
pregnancies with one fetal pregnancy and one and the father's DNA, while the hydatid was not
being a non-malignant. Partial molahidatidosa the mother's DNA. This study disputes the
generally with triploidy karyotype (69 relationship between blighted ovum and
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molahidatidosa mole. 1 26 differentiation is still unclear. It is suspected that
the role of vitamin A in controlling proliferation is

Gene / Protein Expression Abnormalities through p53 which causes G1 arrest, pRb which
causes S-phase arrest. And there are many more
Several other studies were conducted to
mechanisms that are affected by vitamin A. 1 28
determine the pathophysiology of molahidatidosa
Research on vitamin A levels in molahidatidosa
by looking at differences in gene expression in
patients, got lower levels of vitamin A in
molahidatidosa trophoblast cells with normal
molahidatidosa patients compared to normal
placental trophoblast cells. Increased expression
pregnant women, and found that the risk of
of genes in proto-oncogenes or decreased
developing molahidatidosa in women suffering
expression of tumor suppressor genes on
from vitamin A deficiency increased to 6.29 times. 1
trophoblast cells. Mutations may lead to
degeneration of the corial villi and proliferation of
trophoblast cells. This expression abnormality Molahidatidosa diagnosis
only answers molahidatidosa with paternal and Symptoms and signs of pregnancy in general,
maternal DNA but has not answered but there are specificities in the form of nausea,
molahidatidosa which only comes from paternal vomiting that is excessive or more severe than
DNA. 1 pregnancy in general, symptoms of bleeding in
Meanwhile, 90% of molahidatidosa have only early pregnancy with mild to heavy bleeding. In
paternal DNA without having maternal DNA. some cases accompanied by symptoms of
Research on the expression of type IV collagen thyrotosikosis. 1
protein, which has a role in the stability of cell Clinically an enlarged uterus that is greater
adhesion in tissues, found that the difference in than the gestational age. Uterine size greater than
type IV collagen expression was higher in gestational age occurs in 50% of cases of
molahidatidosa trophoblast cells compared to molahidatidosa mole, one third of whom have a
placental trophoblast cells. However, there was no uterus smaller than their gestational age.
difference in the expression of collagen types I and Hyperemesis gravidarum is found in 5-25% of
III. Collagen protein expression also increases in cases of molahidatidosa mole. Hyperemesis is
the wound healing state, collagen protein usually in a molahidatidosa pregnancy with a
increases in the healing process to increase large uterus and high HCG levels. Preeclampsia is
adhesion and regeneration of injured tissue. found in 12-27% of cases of molahidatidosa mole.
Whereas in hydatid mole, the collagen protein Preeclampsia is rare in molar pregnancies with a
increases due to cause or as a result of hydatid small uterus. Symptoms of thyrotoxicosis
mole. 1 (tachycardia, febrile, tremor and other symptoms
of thyrotoxicosis) are found in 2-4% of cases of

Nutritional Factors molahidatidosa mole. Most cases of

molahidatidosa having thyrotoxicosis have a large
Another possibility that explains the
uterus. Thyrotoxicosis sometimes causes heart
occurrence of molahidatidosa is a factor of vitamin
failure. 1
A deficiency. Vitamin A is a vitamin that has a role
Symptoms of impaired lung function occur in
in regulating cell proliferation, cell differentiation,
2% of cases of molahidatidosa mole. Lung function
and apoptotic activity. Low levels of vitamin A
disorders generally occur after evacuation, this
cause interference with the control mechanism for
condition may be due to trophoblast pulmonary
cell proliferation and differentiation. 1 27 28
embolism. 1
How vitamin A works on cell proliferation or
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 On ultrasound examination has a fairly specific histological examination. Sometimes the diagnosis
picture. Ultrasound examination is a noninvasive is still difficult to determine, then a karyotype can
examination used to detect early hydatidosa. strengthen the diagnosis. Ninety percent of cases
Theca lutein cysts are common in molahidatidosa of complete molahidatidosa have a 46XX
mole. Some of the lutein cysts are 6 cm in size, karyotype resulting from duplication of the
14% of cases have cysts larger than 8 cm, uterine father's X chromosome. In 6-10%, complete
rounds that do not see prisoners, and discharge of molahidatidosa has 46 XY chromosome. Thus, if
hydatid bubbles are pathognomonic clinical the 46XX or 46XY karyotype is paternal without a
signs. 1 maternal chromosome, a diagnosis of
molahidatidosa can be determined, but if a 46XY
Histologic Diagnosis karyotype is with paternal and maternal

Histologic diagnosis is possible on chromosomes, it is not necessarily a non-fatal

molahidatidosa mole, histopathological form, maybe even a normal pregnancy. 1

examination with molar tissue specimens Gynetic examinations are not required in

obtained during the evacuation. Evacuation is routine care, either for diagnosis or management

enough to do once, but if with one evacuation of non-biological pathogens. This is because in the

there is still residue (clinical and imaging) then a management of molahidatidosa mole, the most

second curette can be performed. 1 important thing is the observation to detect the

The trophoblast cells in the residue cause occurrence of postmenidatidiform malignant

bleeding, infection and allow the trophoblast cells degeneration. 1 29

to survive. On histopathologic examination,

complete molahidatidosa has characteristics of Molecular Diagnosis
hydropic chorial villi degeneration and trophoblast In some circumstances it is difficult to
cell proliferation without embryonic components. distinguish molahidatidosa trophoblast cells from
Partial molahidatidosas have an embryonic or trophoblast cells in normal pregnancy with
fetal component. In some dubious circumstances, hydrophic degeneration. Examination of protein or
then imonohistochemical examination and gene expression may be performed to distinguish
keriotype examination can help. 1 a molahidatidosa tissue from normal placental
Molahidatidosa trophoblast cells consist of tissue. 1
cytotrophoblast, syncytiotrophoblast and One way to distinguish molahidatidosa
intermediate trophoblast. Cytotrophoblasts have trophoblast cells from normal pregnancy placental
proliferative activity, proliferative activity is the trophoblast cells can be done by examining
main activity, cytotrophoblast cells will degenerate Cytokeratin 20 (CK20) by means of
into syncytiotrophoblast cells having hormonal immunohistochemical examination.
activity, and hormonal activity is the main activity Molahidatidosa trophoblast cells will express CK
of syncytiotrophoblast cells. Syncytiotrophoblast 20, whereas normal placental trophoblast cells
cells will degenerate into trophoblast intermediate will not express CK20. 1 30
cells, the main activity of trophoblast intermediate P53 gene expression can also be used to
cells is invasion and migration. 1 differentiate trophoblast cells, non-mutant p53. In
this study, by analyzing the DNA sequencing of the
Kariotype Diagnosis p53 gene, there was no mutation or mutant p53.

The diagnosis of non-molahidatidosa generally The results of this study showed the high

can be determined based on clinical and expression of non-mutant p53 in molahidatidosa

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trophoblast cells compared to normal placental role in the proliferation of trophoblast cells, and
trophoblast cells. To differentiate trophoblast cells molahidatidosa corial villi tissue. Thus,
by examining p53 certainly does not have high examination of GAP racial expression can also be
specificity because normal trophoblast cells used to differentiate molahidatidosa tissue from
express non-mutant p53 even though the normal placental tissue, because GAP is thought
numbers are not many. Thus, semquantitative to play an active role in the formation of corial villi
examination of p53 can still be used to distinguish in normal pregnancy. 1
trophoblast cells from molahidatidosa with
trophoblast cells from normal placenta. 1 31 Differential Diagnosis
In the histochemical examination, examining
A complete molar pregnancy can be
and analyzing cells that experience apoptosis
differentiated from a partial molahidatidosa
(TUNEL histochemical examination) shows the
histologically. The alpha feto protein test can be
apoptotic process that occurs mainly in
used to distinguish a complete from a
cytotrophoblast cells and stromal cells. Thus there
molahidatidosa with fetal parts. 1
is a possible role for p53 in cytotrophoblast cells,
HPL (human placental lactogen) examination
especially in apoptosis mechanisms. 1
can help differentiate complete molahidatidosa
In complete molahidatidosa and chorio
from PSTT (trophoblasic tumor placental site). 1
carcinoma, there was an increase in the
expression of c-myc, c-erbB2 and BCl-2, while the
Management
expression of c-mfs was not found any difference
in expression in normal pregnancy placental Midatid is an abnormal pregnancy, so molar

trophoblast cells and malignant trophoblast tissue must be evacuated immediately.

disease. Expression of EFGR (epidermal growt Trophoblast cells produce beta HCG so that the

factor receptor) was increased in molahidatidosa proliferation of trophoblast cells causes an

trophoblast cells and choriocarcinoma compared increase in beta HCG levels. 2

to normal placental trophoblast cells. With the act of evacuation, the hydatid tissue

Choriocarcinoma has an invasive nature, this is removed. This evacuation or discharge still has

property is consistent with extracellular protein trophoblast cell residues, both local cell residues

analysis. In karyocarcinoma, there is an increase and cell residues that circulate systemically in the

in the expression of MMP-1 and MMP-2 (matrix circulation. Immediately after evacuation, the

metalloproteinase) and there is a decrease in the HCG beta level will decrease, but because there is

expression of the MMP-1 inhibitor (TIMP-1) still trophoblast cell residue, the decrease in the

compared to normal molahidatidosa trophoblast HCG beta level has not yet reached normal levels.

cells and placenta. 1 However, with multifactorial immune

A proto-oncogene GTPase-activating protein mechanisms, such as biological process factors

(GAP) is a protein that is important for regulating and immune activity factors, the trophoblast cell

signal transduction in cell proliferation and cell residues will regress spontaneously. This

differentiation. Theoretically, the expression of situation is experienced by the majority of cases of

GAP may have increased in molahidatidosa tissue, molahidatidosa mole. 2 32 33

but the results showed different results. In the In clinical studies, it was found that the curve

GAP study, it was found that there was a lower for a reduction in beta HCG levels and generally

expression in the corial villi of molahidatidosa HCG levels reached normal before 20 weeks after

tissue compared to placental tissue in normal evacuation. Thus, the management of post-

pregnancy. These results indicate that GAP has no evacuation molahidatidosas is by clinical
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observation as well as monitoring of HCG beta Increased HCG levels indicate an increase in the
levels. Chemotherapy is only given if there are number of trophoblast cells. The presence of
indications due to malignant degeneration. A total clinical symptoms in the form of uterine
of 15-28% of cases still have trophoblast cell enlargement or uterine bleeding accompanied by
residues that remain alive and develop or abnormal levels of beta HCG indicates trophoblast
proliferate so that the number of trophoblast cells cell activity in the uterus. Moreover, if there is a
increases. 2 34 metastatic process in organs outside the uterus
This increase in the number of trophoblast cells accompanied by abnormal levels of beta HCG, this
is clinically manifested by an increase in the blood indicates trophoblast cell activity. These clinical
levels of beta HCG. Trophoblast cell proliferation signs and HCG beta levels form the basis for
can occur either locally in the uterus or in the determining the diagnosis criteria for PTG by
systemic circulation or perhaps both. Invasive WHO. 2 35
growth in the uterus can cause bleeding The role of beta HCG as a tumor marker for PTG
complications or uterine perforation so often to has been recognized by centers worldwide because
overcome these problems performed surgery to of its high sensitivity. Therefore, beta HCG is used
remove the uterus. This causes the failure of the by centers worldwide as a tumor marker for PTG.
patient's reproductive function, which ironically Prophylactic chemotherapy is not used in post-
the patient still needs reproductive function. 2 graduate patients. because the decrease in PTG
Conversely, if what develops is a trophoblast morbidity and mortality is not by giving PTG
cell that is in the systemic circulation, it is very therapy, the best therapy is to prevent the
likely that trophoblast cell embolism will form development of PTG. Thus, the morbidity,
which will implant in the body's organs. This mortality, and cost of treating malignancies which
situation is clinically manifested as a metastatic are known to be very expensive can be reduced
process. The complications that result from this and avoided. This effort has been pioneered by
condition, of course, really depend on the experts working in the trophoblast field, among
metastatic organs that are affected. 2 others, by conducting research to identify risk
Because these clinical manifestations are not factors for PTG. 2 36
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