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P. Bhatt and R. Myneni
and Latin America. Molar pregnancy affects about 1–2in every 1000 or 2000 pregnant women in North America [2]. The incidence of complete mole is more marked
in adolescent and advanced maternal age [3]. In developed countries incidence of
complete hydatidiform mole (CHM) is approximately 1–3 per 1000 pregnancies,
and those of the partial hydatidiform mole (PHM) is about 3 per 1000 pregnancies
[4]. Molar pregnancies are more marked in upper and lower extremes of maternal
age. Among the younger group between 13 and18 years and among the older group
between 45 and 50 years are more prevalent [5]. The ratio of complete mole to partial mole changes signicantly with age, while the overall gure is 42% for those
aged 13–18 years, 63% are complete mole; aged 18–40 years 39%; aged 41–49
years, 54% and aged 50, 93% [5]. The migrated Hispanic and Asian populations in
the USA have increased incidence of molar pregnancy. Global disparity in the incidence is related to various genetic, demographic, environmental, and host- related
factors [6]. Indonesia is reported to have the highest incidence rate which is 1 per 77
pregnancies and 1 per 57 deliveries [7, 8]. The incidence in India and the Middle
East is 1 per 160 pregnancies [9]. Since the late 1970s, hydatidiform moles have
been categorized as a complete or partial hydatidiform mole based on the genetic
and histopathologic features [10]. According to the World Health Organization
(WHO), hydatidiform mole is considered gestational trophoblastic disease (GTD).
GTD is a group of rare diseases in which abnormal trophoblast cells grow inside the
uterus after conception. It is usually due to two sperm fertilizing one normal ovum
(that usually should not happen). It means plenty of genetic materials are present
leading to excess trophoblastic tissue. The trophoblastic tissue grows and dominates
the growth of fetal tissue; therefore the fetus residual tissue may or may not present.
There are two types of benign molar pregnancy, complete molar pregnancy and partial molar pregnancy. In a complete hydatidiform mole, there are no fetal parts present; in partial hydatidiform moles, there are some fetal remaining tissues [11, 12].
Clinical Case Presentation
This is a case of 19-year-old, G0, P0, who presented to a Baitadi Hospital to establish care for an emergency visit, with the complaint of bleeding per vagina and
worsening shortness of her breath. She stated that she never had a history of asthma
ever since, and outdoor exercise activities seemed to exacerbate her symptoms, and
she generally felt “normal” while sitting. She did not have any chest pain, and the
review of systems was negative for fever, chills, diarrhea, musculoskeletal pain, and
dysuria but was positive for headache, mild nausea and vomiting, and slight lower
abdominal pain. Her family history was nonsignicant. She was currently sexually
active with her husband, and they did not use any barrier contraceptive method. The
patient had no known drug allergies, and she used to take contraceptives for painful
menstrual cycles each month for 6 months but was told that she had stopped taking.
Four months prior, her periods had stopped completely. Further questioning revealed
that the patient was pregnant, it was conrmed pregnancy test, and she had not had
30 Hydatidiform Mole Misdiagnosed asaThreatened Abortion
209
any antenatal care. At this stage, the patient also mentioned that she had off and on
irregular bloody-brown vaginal discharge that occurred for the past 3 months.
Pregnancy and vaginal bleeding immediately prompted to concentrate more on
obstetric history and physical examination on that line. During her emergency visit,
the routine tests were conducted, and in addition, a speculum exam was done as her
complaint of the bloody-brown discharge, and an abdominal examination to assess
the fetal well-being and speculum examination was conducted and was further supplemented with a urine pregnancy test to conrm the initial positive result from the
home pregnancy test. On the physical exam, the patient had stable vitals. Lungs
were mostly clear to auscultation bilaterally, with some wheezing noted on both
inspiration and expiration, without any rhonchi. An abdominal exam showed fundal
height is more than amenorrhea and mild suprapubic tenderness. The uterus was
palpable and was smooth without irregularities and was consistent with a 28–30week gestation (palpable above the umbilicus), though her last menstrual period was
16 weeks prior. The speculum exam showed a dilated nulliparous cervix with brown
discharge with fresh bleeding present in the vaginal vault area. On auscultation there
was no sign of fetal heart sound. The rest of the exam was insignicant. Her hemoglobin level was 7.4g%. The serum ẞ-HCG levels were not available immediately;
later it was found to be 172,000mIU/m. Lipid prole and liver function test were
normal. She was kept under observation as a case of threatened abortion. To exclude
pulmonary edema and other respiratory illnesses, X-ray chest was performed. She
was given complete bed rest, with intravenous (IV) uid and intravaginal progesterone tablets inserted. Three hours later after the insertion of progesterone, she had
profuse bleeding like some structures were expelled out with no fetal tissues.
However, the expulsion of complete mole by itself, and IV uids continued and
central venous pressure (CVP) was monitored. Tissue was sent for histopathology in
India and found to be a complete vesicular mole. After 7 days of symptomatic treatment with antibiotics and rest, she was discharged with following instructions. Oral
contraceptives were initiated to ensure that any ẞ-HCG being monitored would be
from remnant mole alone, and not a new intrauterine or ectopic pregnancy. The
patient was advised to follow-up every 2 weeks, and she agreed to this plan of action.
She was advised to abstain from pregnancy till her ẞ-HCG level is low, and she was
given oral contraceptives for 5 months. After 2 years she conceived a male baby.
Discussion
Bleeding in the rst trimester of pregnancy can be fatal. Patients often overlook
vaginal spotting. Because timing matters, antenatal clinic providers should be wellversed in recognizing early signs and symptoms, as well as the repercussions of
bleeding throughout early pregnancy. We will focus here on a case of molar pregnancy, where the patient was initially treated for threatened abortion vesicular mole
in this discussion with differential diagnosis to threatened abortion. A threatened
abortion happens when a little quantity of vaginal bleeding occurs before the
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P. Bhatt and R. Myneni
pregnancy reaches 28 weeks. Paroxysmal gastrointestinal pain or lower back pain is
frequently associated with the hemorrhage [13]. However, if the vaginal bleeding or
lower abdominal pain worsens, the pregnancy may end in an unavoidable abortion.
A threatened pregnancy occurs in 25% of all pregnancies [14], and this rate has been
rising in recent years. The majority of occurrences occur during the rst 8–12 weeks
of pregnancy, with only a handful after 12 weeks. Approximately 14.3–50% of
women who have been threatened with abortion will have a full miscarriage [15]. As
a case of hydatidiform mole, all patients present with amenorrhea, severe fundal
enlargement, and bleeding. A hydatidiform mole (also known as a molar pregnancy)
is a type of gestational trophoblastic disease (GTD) that begins in the placenta and
can spread throughout the body. This tumor is derived from prenatal tissue rather
than maternal tissue [16], to avert a potential miscarriage. Vaginal bleeding occurs
during pregnancy, while the cervical os stays closed in threatening abortion. A
threatened abortion, according to the World Health Organization (WHO) , is dened
as pregnancy-related vaginal bleeding in the rst half of pregnancy without cervical
dilatation. A hydatidiform mole, also known as a GTD, is a nonviable pregnancy
caused by the fertilization of a potentially empty ovum with one or more sperm in
an atypical way. The resulting mole is a benign but quickly expanding cystic tumor,
culminating in a characteristic pregnant image with no pregnancy outcome. Vaginal
bleeding with lower abdomen pain and the discharge of grape-like vesicles are the
most typical symptoms. This instance was unconcerned about bleeding and spotting. Anemia was caused by bleeding. Complete molar pregnancy is associated with
anemia, bleeding, and respiratory problems [10, 17]. All of these issues were present in this case. Anemia is caused by continuous occult per vaginal bleeding and
signicant blood loss in molar pregnancy. Acute cardiac distress has been found in
27% of instances after molar pregnancy evacuation, particularly in individuals with
a uterine size of over 16 weeks and above. The severity of the clinical indications
varies, and several fatalities have been reported. Within 96h, the patient is usually
back to normal [18]. Our patient made a full recovery in 36h with no severe complications. When a complete pregnancy diagnosis is suspected, the patient should be
checked for medical problems such as anemia, hypertension, and hyperthyroidism.
A baseline serum ẞ-HCG level, thyroid function tests, and a complete blood count
with platelets should be performed on all patients. ẞ-HCG is produced by the
hyperplastic syncytiotrophoblastic cells typical of molar pregnancy, and patients
with full hydatidiform mole frequently have ẞ-HCG levels in excess of 100,000mIU/
ml. Ultrasound pregnancy assessment during the rst trimester can conrm suspected cases of molar pregnancy. Whereas in full molar pregnancies, the snowstorm
pattern is more prominent, with an echogenic intrauterine mass comprising many
tiny cystic gaps (grape-like structures), as shown in Figs.30.1 and 30.2. Complete
moles are usually easier to detect with ultrasonography than incomplete moles.
There are two alternative ways in which the entire mole can appear [19]. Normal
fertilization takes place right away, but the mother’s genetic material is quickly
absorbed. A sperm repeats itself at this point, with the chromosomal conguration
giving rise to 46XX to the entire mole. The remaining 5–10% two sperm can fertilize a normal oocyte that is originally devoid of maternal genetic material, resulting
30 Hydatidiform Mole Misdiagnosed asaThreatened Abortion
Fig. 30.1 Transabdominal complete mole USG showing snowstorm appearance
211
Fig. 30.2 Transvaginal incomplete mole with snow storm pattern
in 46XY genotype manifestations across the entire mole [20]. Sperm multiply to
prepare for fertilization, and syncytiotrophoblasts are generated by the proliferation
process [21]. The ovum keeps its genetic material during fertilization to generate a
zygote. Although maternal genes are deleted after fertilization and the fetus stops
growing in the absence of fetal cells, trophoblasts proliferate to form a cystic formation in the uterus. There is a minimal dissociation of the placenta within the decidual
lining in the case of threatened abortion, resulting in vaginal bleeding in the form of
spotting or scanty bleed without discomfort in the abdomen or risk to the mother’s
life. However, there have been cases of poor pregnancy outcomes, notably intrauterine growth restriction (IUGR) [15]. In the rst trimester, people with hydatidiform
mole sparse vaginal hemorrhage experience extreme nausea and vomiting, as well
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P. Bhatt and R. Myneni
as occasional grape-like vesicles passing through per vagina. With anemia, the
uterus may appear to be larger than the gestation term. Thyrotoxicosis manifests
itself in a variety of ways [22].
Choriocarcinomas are malignant trophoblastic tumors that arise from villous
GTD cells in the uterus. A complete molar gestation causes 50% of all choriocarcinomas, 25% after a normal pregnancy, and 25% after a spontaneous miscarriage or
ectopic pregnancy. Choriocarcinomas release a lot of angiogenic growth factors and
can alter the uterine vasculature, resulting in bleeding. Irregular vaginal bleeding, an
enlarged uterus, cough, hemoptysis, headache, and vomiting are the most common
clinical manifestations. Although choriocarcinoma in the vaginal canal can cause
purple/blue nodules and asymmetrical uterine enlargement, not all women will have
all of these symptoms. There’s also intraperitoneal bleeding and elevated ẞ-HCG
levels in the blood [23]. Chromosomal anomalies characterize hydatidiform moles,
allowing for choriocarcinoma malignant transformation. Activation of oncogenes,
inactivation of tumor suppressors, and changes in telomerase regulation are the
most prevalent changes that contribute to malignant transformation [24].
According to a Nepalese study, irregular uterine bleeding was the most common
complaint in vesicular moles (86.3%). Pain (33.8%) and hyperemesis (26.5%) were
the other presenting symptoms, respectively [25]. Dilatation and curettage (D&C)
are the rst line of treatment for vesicular moles, followed by symptomatic treatment and follow-up. The majority of cases of threatening abortion respond effectively to early pregnancy therapy with bed rest, sedation, and progesterone
suppositories. Progesterone 100mg is taken twice daily in the form of a vaginal
tablet up to 10–12 weeks of pregnancy [26]. Patients who have had a past molar
pregnancy should utilize oral contraception to delay pregnancy until their ẞ-HCG
level returns to normal [15]. When ẞ-HCG levelsl are zero for 6 months after treatment for a hydatidiform mole, the patient may become pregnant, even if pregnancy
occurs before the 6 month follow-up period is completed. Termination of pregnancy
should not be recommended until the ẞ-HCG levels are negative [26].
Conclusion
In conclusion, complete molar pregnancy can present with an enlarged fundal and
then the actual gestational period. Bleeding can lead to severe anemia. Molar pregnancy with bleeding presents a challenges in diagnosis generally misdiagnosed as a
case of threatened abortion. Molar pregnancy should be included in the differential
diagnosis for rst trimester vaginal bleeding. The distinction between complete
hydatidiform mole and partial hydatidiform mole is important for determining the
appropriate line of treatment. For complete hydatidiform mole, USG ndings along
with high ẞ-HCG are alone helpful in establishing the diagnosis with a typical
snowstorm presentation in USG, but to conrm the diagnosis histopathological
examination is must. Follow-up for treated cases of HM is important and required
careful evaluation for serum ẞ-HCG level. If the ẞ-HCG level falls to normal within
30 Hydatidiform Mole Misdiagnosed asaThreatened Abortion
213
56 days (8 weeks) of the evacuation, then the monitoring continues for a total of 6
months from the day of the evacuation. It is advised that a further pregnancy is postpended with oral contraceptives until the end of the follow-up period, because early
new pregnancy may relapse the condition.
Permission toUse Images Letter
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P. Bhatt and R. Myneni
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11. Hui P, Baergen R, Cheung AN, et al. Gestational trophoblastic neoplasia. In: Kurman RJ,
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26. Cao JQ, Zhao Y, Ma Y, Wang QM, Niu LN, Qiao S. A case of unplanned pregnancy
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215
Chapter 31
Gestational Choriocarcinoma
Misdiagnosed asOvarian Ectopic
Pregnancy
RevathiMyneni
Learning Objectives
By the end of this presentation, the clinician will be able to:
• Analyze ways in which choriocarcinoma can be more accurately diagnosed to
prevent misdiagnosis.
• Discuss why choriocarcinoma is often misdiagnosed or goes undiagnosed which
can lead to metastasis.
• Analyze the similarities and differences between choriocarcinoma and ectopic
pregnancy.
• Discuss as one of the misdiagnosed disorders (the case helps us understand the
consequences of a misdiagnosis or delay in reaching a correct diagnosis for the
individual patient’s progress).
• Emphasize the need for follow-up to prevent recurrence and metastasis.
Introduction
Choriocarcinoma is an uncommon and aggressive trophoblast neoplasm. It is most
likely to develop during pregnancy, indicating that it is of gestational origin.
Hydatidiform mole can induce abortion, ectopic pregnancy, and preterm birth. Nongestational choriocarcinoma is uncommonly reported since it is not linked to pregnancy [1]. In rare exceptional cases, it has metastasized to the lungs, brain,
gastrointestinal system, liver, and dermal tissues [2]. It’s hard to ascertain the distinction between these two types of tumors, and there are no signicant immunohistochemical or microscopic changes between them [3]. To differentiate between the
R. Myneni (*)
St. Martinus University Faculty of Medicine, Willemstad, Curacao
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023
H. Tohid et al. (eds.), The Misdiagnosis Casebook in Clinical Medicine,
https://doi.org/10.1007/978-3-031-28296-6_31
217
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R. Myneni
two entities, deoxyribonucleic acid (DNA) analysis and cytogenetic tests are used,
but if this is not possible, a history of pregnancy would be used for differential diagnosis [4]. According to the research, the outcome of these two forms of cancers can
be different. Choriocarcinoma occurs in 76% of cases and is associated with distant
metastases and in ectopic locations. It can appear anywhere from 5 weeks to 5 years
after conception, including after menopause [5]. At the time of diagnosis, almost
30% of choriocarcinoma patients have metastases [6]. The diagnosis of this disease
is difcult due to the diversity of signs and symptoms. The extent of the illness and
the location of metastases determine the clinical appearance of choriocarcinoma.
The clinical appearance of gestational choriocarcinoma is frequently related to
bleeding from the metastatic location [7]. After a full-term or preterm pregnancy,
choriocarcinoma can cause amenorrhea and abnormal uterine bleeding due to uterine cancer progression or bleeding from a metastatic location. Abdominal discomfort, hemoptysis, and melena can develop from uterine perforation or metastatic
lesions bleeding [8]. Patients with central nervous system (CNS) metastases frequently experience headaches, dizziness, seizures, or hemiplegia as a result of
increased intracranial pressure caused by intracerebral bleeding [9, 10]. Dyspnea,
cough, and chest pain are common symptoms in patients with widespread pulmonary metastases [11]. Because of its rapid growth, extensive distribution, and high
proclivity for hemorrhage, choriocarcinoma constitutes a valid medical emergency,
and early detection and treatment is a well-known driver of prognosis [12].
Clinical Case Presentation
A 35-year-old woman, gravida 6, para 4, and abortion 2, was admitted to the emergency room at Imam Hussein Hospital, Shahid Beheshti University of Medical
Science, Iran, with severe pelvic pain, fatigue, and cough. The patient had been
experiencing pelvic pain for a month, which had intensied at the time of referral,
and she mentioned feeling sick and vomiting three times over a period of 12hours.
She also noted a cough that began a month prior to her referral. Her cough did not
respond to any of the over-the-counter medications. The patient had a cesarean section and tubectomy 9 months prior and had been experiencing amenorrhea ever
since. Her blood pressure was 104/65mmHg at admission, her heart rate was 120
beats per minute (bpm), her respiration rate was 24 breaths per minute, and her body
temperature was 36.8°C.On physical examination, her abdomen was rm, with
diffuse discomfort in the right lower quadrant. Ultrasound revealed a 50×58mm
(millimeter) hyperechoic tumor in the right adnexa with moderate free uid in the
pelvis. Hemoglobin was 5.7g/dL (grams per deciliter), hematocrit was 18.4, mean
corpuscular volume (MCV) was 81.8, and ẞ-hCG was positive. Ectopic pregnancy
was diagnosed based on clinical symptoms and lab studies, and a gynecological
appointment was requested [13]. The patient had laparotomy with the suspicion of
a ruptured fallopian tube due to her unsteady symptoms. There was no blood in the
intra-abdomen and 200 cc of serosal uid in the abdomen was drained during