HIGH RISK OF GESTATIONAL TROPHOBLASTIC
NEOPLASIA DEVELOPMENT IN RECURRENT
HYDATIDIFORM MOLES WITH NLRP7
PATHOGENIC VARIATIONS
Kocabey M.1,a, Gulhan I.2, Koc A.1,b, Cankaya T.1, Karatasli V.2, Ileri A.3
*Corresponding Author: MD Mehmet Kocabey, Address: Güzelburc District Kıbrıs Street No: 81,
31175 Antioch/Hatay, e-mail: mehmet_kocabey@hotmail.com
page: 45
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RESULTS
Case 1
The first case was a gravida 3, para 0 (one early pregnancy
loss and two consecutive HMs) 25-year-old woman.
Her main complaint was amenorrhea. β-hCG level was
measured as 271,793 mIU/mL. Ultrasonography (USG)
revealed a 50 mm empty gestational sac with an irregular
contour and there was no yolk sac. Several hypoechoic
areas in the endometrial cavity were seen. Suction evacuation
was performed without complications. Pathologic
investigation revealed HM. Monitoring of β-hCG levels
was initiated. Eighteen days after the evacuation, β-hCG
levels lowered to 365 mIU/mL, but 7 days later it rose to
586 mIU/mL. The increase of β-hCG is considered as a
sign of GTN development. The diagnosis was stage 1, low
risk GTN with a WHO score of 1. Single agent chemotherapy
protocol consisting of four doses of methotrexate
and four doses of folinic acid was started. After 3 cycles of
chemotherapy, β-hCG levels returned to the normal range
after 40 days, and the treatment was concluded with one
additional cycle of chemotherapy.
One and a half years after the initial management of
the case, the patient was admitted to our clinic again, due
to the suspicion of another pregnancy. The β-hCG level
was 258,164 mIU/mL. A hyperechogenic lesion (50x32
mm) containing multiple millimetric cystic areas was seen
in USG evaluation. Evacuation procedure was performed
without complications and the β-hCG level was normal
after two months. The material derived from evacuation
was reported as HM by the pathology laboratory.
Because the case had four consecutive HM without
any live births, genetic consultation was needed. Family
history revealed that the patient had 9 siblings. Only one of
her siblings was married and although she had 7 children,
she had no history of molar pregnancy.
Sanger sequencing of the patient’s DNA identified
homozygous, c.2471+1G>A (rs104895505) pathogenic
variation (Guideline criteria: PVS1, PM2, PP3) [8] in 7th
intron of the NLRP7 gene (Figure 1).
Case 2
The second patient was a gravida 3, para 0 (three
consecutive HMs) 19-year-old woman. The first admission
of the patient was on suspicion of pregnancy. Her β-hCG
level was 440,873 mIU/mL. During USG, there was a HM
in nodular form (81x47x84 mm) which included numerous
millimetric cystic degeneration areas. It was located
at corpus and fundus filling the endometrial cavity, with
deep myometrial infiltration close to the serosa. Thyroid
function related hormones were measured out of the normal
range due to an increase in the β-hCG level: free T3
was 7.19 pg/mL, free T4 was 2.17 ng/dL, TSH was 0.02
mIU/mL. Two months after the evacuation of the products
of conception, her β-hCG level was 9.63 mIU/mL. The
pathology report was consistent with HM.
Eight months later, she had another admission because
of amenorrhea. The USG revealed a 66x52 mm lesion in the endometrial cavity, compatible with HM. The
β-hCG level was 197,328 mIU/mL and thyroid function
tests were also impaired: free T3 was 4.53 pg/mL, free T4
was 1.86 ng/dL and TSH was 0.02 mIU/mL. One and a
half months after the evacuation procedure, her hormone
profile was normal. Pathology confirmed HM.
Her third admission was made 2 years later, due to a
suspected pregnancy. The β-hCG value was 272,283 mIU/
mL. Free T3 was 5.19 pg/mL, free T4 was 1.48 ng/dL and
TSH was 0.02 mIU/mL. The lesion measured 66x40 mm
and it was consistent with HM again. Evacuation of the
products of conception was performed, and β-hCG monitoring
was initiated. The β-hCG level was 2.98 at week 3
and increased to 3.66 at week 4. It increased again to 9.35
at week 5. The lesion was considered as post-molar stage
1, low risk GTN and single agent chemotherapy (methotrexate)
was planned. After two cycles of chemotherapy,
β-hCG was normal and two more cycles of chemotherapy
were given. After treatment, free T3 was measured as 3.97
pg/mL, free T4 was 0.83 ng/dL and TSH was 0.37 mIU/
mL.
The patient had homozygous c.2471+1G>A
(rs104895505) pathogenic variation in the NLRP7 gene.
This variation was identical to the variation found in case
1. Although the patients were specifically questioned, no
blood relation was found between them.
Case 3
The third patient was a gravida 2, para 0 (two consecutive
HMs) 33-year-old woman. She was admitted to
the hospital because of a suspected pregnancy. Her β-hCG
level was 573,347 mIU/mL. USG revealed 70x80 mm
HM with cystic areas and without any fetus. One week
after the evacuation procedure the β-hCG level measured
11,758 mIU/mL. The patient chose not to be followed-up
after the procedure. The pathology report confirmed HM.
One and half months later, the patient was readmitted to
another hospital where curettage was performed. Monitored
β-hCG showed a decrease to 137 mIU/mL, followed
by a plateau and consequent increase to 166 mIU/mL. The
case was considered a Stage 1 Low Risk GTN, and single
agent chemotherapy was started. A total of two cycles of
methotrexate were given. After one year of a contraception
period, the patient decided to try another pregnancy and
folic acid prophylaxis was given. Following conception,
the β-hCG level was 276,400 mIU/mL and USG revealed
HM with cystic areas and a diameter of 50 mm. Following
evacuation, the β-hCG values were normal after 1.5
months. Pathology confirmed HM. Genetic evaluation by
Sanger sequencing identified a homozygous c.2571dupC,
p.Ile858HisfsTer11 (rs766731093) pathogenic (Guideline
criteria: PVS1, PM1, PM2) frameshift variant in 8th exon
of the NLRP7 gene (Figure 2).
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