Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2867_Библиотеки_им_академика_М_И_Перельмана.pdf
31 Gestational Choriocarcinoma Misdiagnosed asOvarian Ectopic Pregnancy
219
surgery. There was no abnormality in the fallopian tube and uterus, and a purple
mass measuring 5–6cm on the right ovary was suspected to be a pregnancy outcome. The patient’s ẞ-hCG level was 33,827mIU/mL after surgery. Due to continuous coughing, the patient had a chest X-ray, which revealed scattered patchy
opacities in the lower lobes. She was diagnosed with choriocarcinoma and underwent further testing to rule out further metastatic sites. Multiple widespread pulmonary nodules, pleural effusion, and partial consolidation in the lower lobes were
seen on lung CT (computed tomography) scan, indicating metastasis.
Abdominopelvic CT scan with intravenous (IV) and oral contrast revealed a large
increased tissue mass with necrotic components in the left pelvic cavity, measuring
101×96mm, as well as deterioration of the surrounding left iliac bone spreading to
the left paracolic gutter. Both the kidneys and the spleen revealed some metastatic
lesions. A solitary occipital lobe metastasis was also discovered on a brain CT scan.
All of this evidence pointed to choriocarcinoma in its fourth stage with many metastases, which was veried by pathology of the ovarian lesion and biopsies of the
abdominal lesions. The data ndings showed that she was suitable for chemotherapy, and she was admitted to the intensive care unit 3 days after her initial visit.
After four cycles of EMA-EP (etoposide, methotrexate, and actinomycin D/etoposide and cisplatin) and ve cycles of EMA-CO (etoposide, methotrexate, actinomycin D, cyclophosphamide, vincristine), the patient responded to treatment, and
ẞ-hCG was undetectable after 2 months of treatment. During her 3-month followup, the patient’s ẞ-hCG level was elevated again, indicating relapse. Chemotherapy
was restarted with three cycles of paclitaxel, cisplatin, and etoposide, followed by
four cycles of liposomal doxorubicin and carboplatin and then ve cycles of uorouracil and dactinomycin, as well as brain radiotherapy. As a reaction to the chemotherapy, the patient developed a fever and neutropenia. The woman appeared with
stomach pain, bloody ascites, and shock at our emergency department after 25 sessions of chemotherapy and 10 sessions of radiotherapy, 8 months after her initial
diagnosis, and she died [13].
Differential Diagnosis
When considering the patient’s history and physical exam ndings, one should
begin to build a differential diagnosis.
1. Acute appendicitis: Its symptoms prior to surgery include fever, abdominal pain,
pelvic pain, nausea, and vomiting.
2. Adnexal torsion: This causes nausea, vomiting, and sudden, intense pelvic discomfort. Women may experience intermittent, colicky discomfort for days or
even weeks prior to the abrupt pain, which is likely caused by intermittent torsion that gradually resolves.
3. Tubo-ovarian abscess: Lower abdomen pain that begins suddenly, chills, dyspareunia, fever, and vaginal discharge are some of the typical symptoms. There
220
R. Myneni
have also been reports of nausea, vomiting, and unusual vaginal bleeding as
additional symptoms.
4. Hemorrhagic corpus luteum: Small cysts typically don’t exhibit symptoms
unless they rupture and begin bleeding or torsion happens. These disorders result
in excruciating pelvic pain, excruciating nausea and vomiting, or excruciating
weakness.
5. Ovarian cyst rupture: The majority of cysts are harmless; however ruptured ovarian cysts can cause abrupt, severe abdominal discomfort, pain accompanied by
fever or vomiting, feeling chilly with clammy skin, rapid breathing, lightheadedness, or weakness.
6. Miscarriage: Symptoms include light to heavy bleeding, intense cramps, back
pain that gets worse or is unbearable, fatigue, fever, weight loss, white-pink
mucus, contractions, and tissue that resembles blood clots owing from
your vagina.
7. Pelvic inammatory disease: Symptoms include severe pain and discomfort in
the pelvic area, fatigue, vomiting, fever, irregular menstruation, bleeding or spotting between periods, pain in the lower back pain, dyspareunia, and atypical
vaginal discharge.
These are all important differential diagnoses to consider with ectopic pregnancies. The patient’s history and hemodynamic status at the time of clinical presentation will determine the order of these differential diagnoses as well as the lab testing
required to exclude such differentials.
Discussion
Gestational choriocarcinoma is a type of gestational trophoblastic illness that begins
in the uterus. The ovaries, fallopian tubes, cervix, vagina, and other pelvic organs
may also be affected. Choriocarcinoma most usually develops after a molar pregnancy; however, it can also develop after a term pregnancy, abortion, or ectopic
pregnancy. A series of diagnostic tests is done to diagnose the gestational choriocarcinoma: urinalysis, cancer antigen 125 blood test (CA-125 blood test), ẞ-hCG
blood test, and pelvic ultrasound. Additional tests may be done to see if the cancer
has spread to other parts of the body; some of the tests are chest X-ray, abdominal
and pelvic CT scans, magnetic resonance imaging (MRI), and lumbar puncture [13].
Cardiopulmonary problems brought the most patients to clinical attention, followed by gastrointestinal and central nervous system signs. In addition, several
cases were discovered as a result of fetal-maternal hemorrhage, renal, and ophthalmic symptoms [14]. Figure 31.1 shows a quick review of the numerous clinical
manifestations associated with choriocarcinoma.
Choriocarcinoma is distinguished by very high levels of human chorionic gonadotropin (ẞ-hCG), necessitating a careful distinction from pregnancy [15]. Because
of increased ẞ-hCG, early-stage ovarian choriocarcinoma poses a considerable
31 Gestational Choriocarcinoma Misdiagnosed asOvarian Ectopic Pregnancy
221
Fig. 31.1 Clinical manifestations associated with choriocarcinoma
diagnostic problem in the reproductive-aged patient [16]. While ectopic pregnancy
and gestational trophoblastic illness are both possible diagnoses, non-gestational
choriocarcinoma is rarely considered. Abnormal vaginal bleeding, abdominal pain,
and the discovery of a pelvic mass are all common symptoms and indicators associated with high ẞ-hCG levels [17].
Gestational trophoblastic neoplasia (GTN) was classied as a neoplasm with a
strong proclivity for hematogenous spread and dissemination. As a result, extra pelvic metastases should be recognized as a possible concern [14, 18, 19]. Outside of
the pelvis, the most common locations of metastases were the lung, liver, and brain.
Renal involvement was uncommon; however renal metastasis was frequently subsequent to lung metastasis in certain patients. Surgery in the treatment of patients with
metastatic choriocarcinoma is debatable. Furthermore, it appears that a selective
fraction of patients can be treated with local resection of metastatic illness. Control
of hemorrhage, infection, blockage, and removal of chemotherapy-resistant residual
illness have all been common surgical reasons in GTN. Remission has been achieved
in some patients quickly after the removal of the uterus and cervical metastases
[14]. Even in advanced disease, GTN is generally very sensitive to treatment.
Single-agent chemotherapy (reduced side effects) has been used to treat this condition in patients with early stages of disease, and it has proven to be highly effective.
222
R. Myneni
Multi-agent chemotherapy regimens, on the other hand, were accessible for
advanced-stage management. However, it should be noted that despite its high
effectiveness this regimen may be linked to an increased risk of recurrent cancers.
In our research it is shown that all advanced-stage disease patients had received
combination chemotherapy (EMA-CO) regimen, and the results were positive [14].
A review of case reports from the last 10 years gathered from the PubMed database
on choriocarcinomas that were rst diagnosed with ectopic pregnancy. A total of 24
women with ectopic pregnancy symptoms were assessed at the time of admission.
The patients were between the ages of 12 and 46, with an average age of 28. Tubal
ectopic pregnancy was the most prevalent symptom, which was often accompanied
by ovarian ectopic pregnancy and inclusion of the serous and uterine myometrium.
Only one instance had myometrial involvement, while most of the cases were ovarian and tubal ectopic pregnancy. The other 14 people developed choriocarcinoma,
either secondary or prenatal. The majority of the gestational type ovarian involvement happened after a normal pregnancy. The time between the previous pregnancy
and the onset of symptoms ranged from 23 days to 5 years. The majority of patients
initially complained of stomach pain and irregular uterine hemorrhage. Amenorrhea,
shock, a steady ẞ-hCG titer, a palpable mass, and fever were among the other symptoms. The average ẞ-hCG concentration was 308,634IU/mL (international units
per milliliter), with values ranging from 13IU/mL to 4,000,000 IU/mL.During the
surgery, ultrasounds of 13 patients revealed pelvic free uid that was bloody. At the
time of diagnosis, 14 patients had metastasis, with lung metastasis being the most
prevalent. There was no evidence of brain metastases. Salpingo-oophorectomy and
hysterectomy were the most common operations performed. Twenty patients
received chemotherapy before or after surgery, 21 recovered completely, 2 patients’
outcomes were unknown, and only 1 patient died from an uncontrolled intraabdominal bleeding from the liver [20].
Conclusion
The recent growth of conservative care for ectopic pregnancy highlights the importance of pathological testing in conjunction with ẞ-hCG level monitoring, not only
to diagnose recurrent ectopic pregnancy but also to avoid potential malignant trophoblastic disease. When a patient is being treated for an ectopic pregnancy, they
should be informed of the likelihood of choriocarcinoma. The importance of pathologic examination in conjunction with serial ẞ-hCG concentration monitoring in
the treatment of ectopic pregnancy will be critical not only to determine trophoblastic disease but also to avoid a surprise like choriocarcinoma. An early correct diagnosis of postpartum choriocarcinoma can improve the outcome greatly. Although
the risk of postpartum choriocarcinoma is relatively low, it must be monitored on a
frequent basis. Careful postpartum placental examination, histological investigation
in patients with anomalies, and ẞ-hCG monitoring in high-risk pregnant women
can all help with early identication and prognosis of postpartum choriocarcinoma.
31 Gestational Choriocarcinoma Misdiagnosed asOvarian Ectopic Pregnancy
223
The International Federation of Gynecology and Obstetrics staging and World
Health Organization prognostic grading systems should be used to deliver stratied
treatment. Furthermore, ẞ-hCG is a sensitive marker for assessing therapy success
and monitoring postpartum choriocarcinoma remission. Following GTN treatment,
ẞ-hCG monitoring every month for at least 12 months is required to monitor for
relapse. During this time, reliable contraception must be used.
References
1. Savage J, Adams E, Veras E, Murphy KM, Ronnett BM.Choriocarcinoma in women. Am J
Surg Pathol. 2017;41(12):1593–606.
2. Murshed KA, Kanbour A, Akhtar M, Al Hyassat S.Primary mediastinal choriocarcinoma presenting as cutaneous metastasis with resistance to chemotherapy: case report and literature
review. J Cutan Pathol. 2020;48(1):81–5. https://doi.org/10.1111/cup.13777.
3. Meddeb S, Rhim MS, Zarrouk W, Bibi M, Yacoubi MT, Khairi H.Unusual gestational choriocarcinoma arising in an interstitial pregnancy. Int J Surg Case Rep. 2014;5(11):787–8.
4. Sharami SRY, Saffarieh E.A review on management of gestational trophoblastic neoplasia. J
Fam Med Prim Care. 2020;9(3):1287.
5. Mehrotra S, Singh U, Goel M, Chauhan S.Ectopic tubal choriocarcinoma: a rarity. BMJ Case
Rep. 2012;2012:bcr-2012-006318.
6. Chau DB, Beavis AL, Ronnett BM, etal. Genetically related choriocarcinoma developing 5 Yr
after a complete hydatidiform mole and simulating a cornual ectopic pregnancy. Int J Gynecol
Pathol. 2020;39(4):367–72.
7. Mitrovic SL, Arsenijevic PS, Kljakic D, etal. Gestational choriocarcinoma of the cervix. Arch
Iran Med. 2014;17(11):783–5.
8. Bacalbasa N, Balescu I, Brasoveanu V, Anca AF. Debulking surgery for pelvic recurrence
after surgically-treated tubal gestational choriocarcinoma—a case report and literature review.
Anticancer Res. 2018;38(1):423–6.
9. Buza N, Rutherford T, Hui P.Genotyping diagnosis of nongestational choriocarcinoma involving fallopian tube and broad ligament: a case study. Int J Gynecol Pathol. 2014;33(1):58–63.
10. Alizadeh R, Aghsaeifard Z, Marzban-rad Z, Marzban-rad S.Pregnancy with diaphragmatic
and stomach rupture: lessons from a case report. Clin Case Rep. 2020;8(7):1206–8.
11. Su S, Chavan D, Song K, etal. Distinguishing between intramural pregnancy and choriocarcinoma: a case report. Oncol Lett. 2017;13(4):2129–32.
12. Karaman E, Çetin O, Kolusari A, Bayram I.Primary tubal choriocarcinoma presented as ruptured ectopic pregnancy. J Clin Diagn Res. 2015;9(9):QD17.
13. Kazemi SN, Raou M, Moghaddam NA, Tabatabaeefar M, Ganjooei TA. Ovarian ectopic
pregnancy misdiagnosed as gestational choriocarcinoma: a case report. Ann Med Surg (Lond).
2022;73:103236. https://doi.org/10.1016/j.amsu.2021.103236.
14. Youse Z, Mottaghi M, Rezaei A, Ghasemian S.Abnormal presentation of choriocarcinoma
and literature review. Iran J Cancer Prev. 2016;9(2):e4389. https://doi.org/10.17795/ijcp- 4389.
15. Mazina V, Morse C, Hadi R, Gray H. Heterotopic atypical trophoblasts mimicking ectopic
choriocarcinoma coexistent with a viable intrauterine pregnancy: a diagnostic dilemma.
Gynecol Oncol Rep. 2019;28:91.
16. Fatema N, Arora NV, Al Abri FM, Khan YMT.Pancreatic and hepatic metastasis of an undiagnosed choriocarcinoma: an exceptional cause of haemoperitoneum in young women—report
of a rare case. Case Rep Oncologia. 2016;9(3):633–8.
17. Heo EJ, Choi CH, Park JM, Lee J-W, Bae D-S, Kim B-G.Primary ovarian choriocarcinoma
mimicking ectopic pregnancy. Obstetr Gynecol Sci. 2014;57(4):330–3.
224
18. Mundkur A, Rai L, Hebbar S, Guruvare S, Adiga P.Fallopian tube choriocarcinoma presenting
as ovarian tumour: a case report. J Clin Diagn Res. 2015;9(1):QD01.
19. Sorbi F, Sisti G, Pieralli A, etal. Cervicoisthmic choriocarcinoma mimicking cesarean section
scar ectopic pregnancy. J Res Med Sci. 2013;18(10):914.
20. Jwa SC, Kamiyama S, Takayama H, Tokunaga Y, Sakumoto T, Higashi M.Extrauterine choriocarcinoma in the fallopian tube following infertility treatment: implications for the management of early-detected ectopic pregnancies. J Minim Invasive Gynecol. 2017;24(5):855–8.
R. Myneni
Chapter 32
Misdiagnosis ofMullerian Agenesis
inaPatient with46, XX Gonadal
Dysgenesis
RevathiMyneni
Learning Objectives
By the end of this presentation, the clinician will be able to:
1. Analyze the process of diagnosing a woman with primary amenorrhea.
2. Enumerate the blood tests that should be performed in a patient with primary
amenorrhea.
3. Discuss how to assess appropriate hormone proles and karyotype analysis in
cases of suspected Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome or
Mullerian agenesis.
4. List the early detection of disorders of sex development (DSD).
5. Discuss how to provide psychological support to the patient and limit the risk of
associated complications.
Introduction
Gonadal dysgenesis with female morphology is characterized as a primary ovarian
failure that results in early ovarian failure in some of the healthier 46, XX females
as a result of gonadal failure or gonadotropin resistance. Depending on the degree
of gonadal maturation, it induces primary amenorrhea with varying hypogonadism
or impuberism [1]. The karyotype can be 46, XX; 45, X0; 46, XY or mosaicism 45,
X/46, XX; 45, X/46, X,del(X) (p22.2); and 46,X,i(Xq) [1–3]. In phenotypically and
karyotypically normal girls with functional ovaries, Mayer-Rokitansky-KüsterHauser (MRKH) syndrome is a type of Mullerian duct malformation dened by
agenesis or hypoplasia of the uterus and upper two-thirds of the vagina. It is 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_32
225
226
R. Myneni
second most prevalent cause of primary amenorrhea, following gonadal dysgenesis [4].
A correlation between these two disorders is extremely rare and appears to be
unrelated to chromosomal abnormalities. When patients with the 46, XX karyotype
present with primary amenorrhea, one of the differential diagnoses is MRKH syndrome or Mullerian agenesis. It is said to induce primary amenorrhea in up to 15%
of women [5]. Patients with Mullerian agenesis lack all Mullerian duct derivatives
(fallopian tubes, uterus, cervix, and upper vagina), but they do have ovaries and go
through puberty with breast development and pubic hair growth. In all cases of a
suspected diagnosis of this illness, hormone proles and concomitant congenital
defects should be thoroughly explored. A straightforward initial step in ensuring the
existence of circulating estrogen is to determine the presence or absence of secondary sexual characteristics, particularly breast development [6]. Other differential
diagnosis or the possibility of co-occurrence of other disorders is needed in teenage
or adult patients without secondary sexual features [7]. In patients with signicant
estrogen decit, the uterus may not be visible using several imaging modalities,
including laparoscopy [8]. Therefore, the diagnosis of Mullerian agenesis should be
re-evaluated after 6–12 months of exogenous estrogen treatment [9].
Clinical Case Presentation
A 23-year-old virgin female presented with primary amenorrhea and poor breast
development. Her prenatal and neonatal phase went ne. There was no history of
major congenital abnormalities in the patient’s family. She was diagnosed with primary amenorrhea by a local gynecologist when she was 16 years old. There were no
other tests other than karyotype and pelvic ultrasonography. The normal 46, XX
karyotype was conrmed by chromosomal analysis. Although no information on the
pelvic ultrasound was available, the patient had been told that her uterus was missing. The patient did not receive treatment at that time, and after a few ofce visits,
she was lost to follow-up. After being diagnosed with MRKH, she never menstruated and had no breast growth. At our hospital, her initial height and weight were
157cm and 49kg. There were no signs or symptoms of Turner syndrome, and no
skeletal deformities were observed. Breast Tanner stage I and pubic hair stage III
were found in the secondary sexual characteristics examination. The gynecological
exam revealed female external genitalia and a typical vagina that ended in a blind
pouch. The remainder of the physical examination was normal [9]. The probable
diagnosis of MRKH syndrome or Mullerian agenesis was questioned due to the lack
of breast development. Hypergonadotropic hypogonadism (FSH 130 IU/L, LH
2IU/L, serum estradiol 5pg/mL) with veried 46, XX karyotype was discovered
32 Misdiagnosis ofMullerian Agenesis inaPatient with46, XX Gonadal Dysgenesis
227
during the initial laboratory study at our clinic. On pelvic magnetic resonance imaging (MRI), the internal genitalia (ovaries, uterus, and upper two-thirds of vagina) and
streak gonad were not visible. Other laboratory evaluations, such as a complete
blood count, renal function, liver function, prolactin hormone, and thyroid function
test, all came back normal. A bone density examination, dual-energy X-ray absorptiometry (DEXA scan), revealed osteoporosis (T score 2.7) in the lumbar spine and
osteopenia (T score 1.5) in the hip. Due to the absence of a uterus and ovaries, the
diagnosis of 46, XX gonadal dysgenesis associated with MRKH syndrome was suggested. X-rays of the skeleton revealed no abnormalities in the spines. There were no
pathogenic mutations found in the deoxyribonucleic acid (DNA) sequence analysis
of putative genes (WNT4, WNT9, RSPO1, SOX9, NROB1, GATA4, STAR, WT1)
related with 46, XX gonadal dysgenesis [9]. The patient began hormone replacement
therapy with 0.625mg of oral estrogen every day (Premarin). The patient had developed Tanner breast stage III 6 months following therapy, which progressed to a
Tanner breast stage V 18 months later. To prevent additional bone loss, calcium and
vitamin D were given orally. At the 18-month follow-up DEXA scan, the bone mineral density had improved, although there was still osteopenia at the lumbar spine (T
score at the lumbar spine increased from 2.7 to 2.2, and T score at the hip increased
from 1.5 to 1.3) [9]. At 18 months, an ultrasound of the pelvis was performed again.
1.3×3.8cm rudimentary uterine buds were discovered with no evidence of the ovaries or upper section of the vaginal canal. Twenty-four months after starting estrogen
treatment, a pelvic MRI was performed to conrm the presence of a developing
uterus (uterine dimension 1.8×2.9× 4.9 cm, endometrial thickness 1.3 cm). The
reappearance of a normal uterus with the size of a normal 16-year-old girl conrmed
the diagnosis of pure 46, XX gonadal dysgenesis without Mullerian agenesis. To
prevent unopposed estrogen action on the uterus, the patient’s medication was
changed from estrogen only to cyclical oral estrogen/progesterone replacement therapy (10mg of cyclic medroxyprogesterone acetate 10 days each cycle). No breakthrough menstruation has yet occurred. She has been advised about the possibility of
having children through adoption or surrogacy in the future. The patient was capable
of dealing with her denitive diagnosis and had a thorough understanding of her illness [9].
Differential Diagnosis
Any diagnosis of a woman with primary amenorrhea should start with a thorough
physical examination and a thorough review of her medical history. A set of blood
tests, including female sexual hormones (estrogen and progesterone), folliclestimulating hormone (FSH), and luteinizing hormone (LH), should be included.
228
R. Myneni
In order to investigate the reasons of amenorrhea, it is necessary to determine the
existence or absence of secondary sexual features, particularly breast development.
If secondary sexual characteristics are present, an imaging examination (pelvis
ultrasonography or nuclear magnetic resonance) is recommended to conrm the
presence of the uterus. Mullerian agenesis (congenital absence of vagina and aberrant uterus development, often rudimentary) accounts for 15% of all cases of primary amenorrhea. If the uterus is present, an obstruction in the outow tract should
be considered (e.g., an imperforate hymen). If the uterus is missing or malformed,
the karyotype should be determined next.
A hormonal investigation should be undertaken in cases when breast growth
is insufficient. FSH levels in the plasma greater than 40UI/mL (hypergonadism) indicate ovarian failure due to a lack of active follicles in the gonadal
tissue. In 2% in 50% of cases of primary amenorrhea, this is the most prevalent cause.
Gonadal failure is usually linked to X-linked chromosomal deletions,
whether complete or partial. Thus, Turner syndrome (45 X0) accounts for 50%
of gonadal dysgenesis cases, mosaics for 25%, and pure gonadal dysgenesis
(46, XX) and Swyer syndrome (46 XY) for the other 25%. Our next diagnostic
step is to determine the karyotype for hypergonadotropic hypogonadism
(Fig.32.1).
Fig. 32.1 The assessment of women with primary amenorrhea