Case Conference February 28th 2018
28-Feb-2018, Divisi Ginekologi Onkologi RSCM
Case Description
Mrs. J, 49 yo, 4102198
2/2/2016
Chief complain:
Patient complain of spotting from vagina
(reffered from Agi Darma Hospital, Rangkas Bitung)
History:
Patient had history of curettage due to molar pregnancy on July 2015. She had curettage due to there was remnant in the uterine cavity. But there was no histopathology result for the curettage. Then after 2 weeks, patient was discharge.
On January 2016 she complained abdominal pain and she came to the hospital and on ultrasound examination said that suspected choriocarcinoma with bHcg result was 1476 and patient was reffered to RSCM.
Married 1x, 1985
P5A1, spontaneous delivery
Curettage due to mola pregnancy (2015)
Physical exam (2/2/2016)
Fully alert
BP 110/70, Pulse 88 x/min, Temp 36.5 C, RR 18x/min
BW 57 kg, BH155 cm, BMI 23,7
General condition
Eyes - no pale conjungtiva, no icteric sclera
Lung - Vesicular, no rhales, no wheezing
Heart - normal S1S2, no murmur, gallop
Abdomen - Supel, no mass palpable, normal intestinal sound
Extrimity - warm, no edema
Gynecological status
Inspection: normal vulva and urethra
Inspeculo: postio smooth, no fluor albus, no fluxus
RVT: Uterine enlarge as 12 weeks pregnancy, both parametrium loose, no mass palpable on both adnexa
Auxilary examination
US examination (2/2/2016)
Uterus AF bigger than normal size.
On the left cornu there was echogenic mass, vesicular with irregular border size 50x30x50.
There was no vascularization on the mass.
There was no abnormal mass in the uterine cavity
Endometrium regular
Both ovaries are normal
Vesicular mass on the left cornu suspected Thropoblastic maligna disease DD/ tubal pregnancy
Thorax X-ray (3/2/2016)
There was no infiltrate/nodul
Laboratory result (4/2/2016)
CBC: 12/37/6180/282000
PT/APTT 0,9x/1,1x
OT/PT 14/7
Ur/Cr 28/0,7
bHcg 761
Working diagnosis
Gestational Thropoblastic Neoplasia low risk
Therapy (11/2/2016)
MTX
24/3/2016
Total laparoscopy hysterectomy, bilateral salphingectomy
Histophatology result:
Uterine with necrotic tissue (abcess) and fibrotic.
No clear mass on this tissue
19/4/2016
MTX
16/1/2018
Chief complain
No complain
Control
Physical exam
Fully alert
BP 120/80, Pulse 84 x/min, Temp 36.5 C, RR 18x/min
General condition
Eyes - no pale conjungtiva, no icteric sclera
Lung - Vesicular, no rhales, no wheezing
Heart - normal S1S2, no murmur, gallop
Abdomen - Supel, no mass palpable, normal intestinal sound
Extrimity - warm, no edema
Gynecological status
Inspection: normal vulva and urethra
Inspeculo: vaginal stump was normal
RVT: No mass palpable
Auxilary examination
Lab result (16/1/2018)
bHcg: 3,68
20/2/2018
Thorax X-ray
No infiltrate or nodule
No abnormal feature
23/2/2018
Abdominal US exam
There was no abnormal feature
Working diagnosis
Gestational trophoblastic disease low risk post TLH and methotrexate therapy
Plan
Observation
This table show this patient’s level of bHcg since 2016 until February 2018
Date |
BhCG |
27/1/2016 |
1476 |
3/2/2016 |
761 |
19/2/2016 |
349 |
21/3/2016 |
3,08 |
1/4/2016 |
1,78 |
3/5/2016 |
<0,1 |
8/6/2016 |
<0,1 |
18/7/2016 |
<0,1 |
11/8/2016 |
0,26 |
14/9/2016 |
<0,1 |
27/12/2016 |
1,03 |
23/3/2017 |
<0,1 |
14/6/2017 |
<0,1 |
15/9/2017 |
<0,1 |
16/1/2017 |
3,68 |
19/1/2017 |
2,3 |
Discussion
HCG is a dimer consisting of a 145 amino acid beta-subunit that is unique to hCG, and a 92 amino acid alpha-subunit. The alpha-subunit is not unique and is identical to that for luteinizing hormone (LH), follicle stimulating hormone (FSH) and thyroid stimulating hormone (TSH). The alpha and beta-subunits are coded by separate genes on separate chromosomes (chromosomes 6 and 19, respectively) and noncovalently bound before being released into the circulation.
Several isoforms of HCG exist in the circulation; some are synthesized and others are degradation products. The two most common forms of hCG synthesized by cells are regular hCG and hyperglycosylated hCG (hCG-H). The additional sugar residues increase the molecular weight from 36,700 to as high as 41,000 and are the basis of the term "hyperglycosylated" hCG.
Hyperglycosylated hCG free beta-subunit is the only other hCG molecule containing a beta-subunit synthesized by cells.
The other 10 types of hCG molecules containing a beta-subunit are not synthesized directly; instead, they are products of:
- dissociation of intact hCG dimers (hCG free beta-subunit), or
- cleavage (nicked regular hCG, nicked hCG-H, nicked hCG free beta-subunit, nicked hcg-H free beta-subunit, nicked hCG missing the C-terminal peptide, nicked hCG-H missing the C-terminal peptide, nicked hCG free beta-subunit missing the C-terminal peptide, nicked hCG-H free beta-subunit missing the C-terminal peptide), or
- renal degradation of hCG free beta-subunit (free beta-subunit core fragment [only detectable in urine])
In addition to the two hCG dimers and the 11 hCG variants containing the beta-subunit, there are two hCG variants that contain only the alpha-subunit: free alpha-subunit and O-glycosylated free alpha-subunit.
The two intact dimers of hCG are biologically active; the products of dissociation and cleavage and the free alpha-subunit are inactive, but have a role as tumor markers.
Low levels of HCG can be a normal physiological phenomenon in peri- and postmenopausal women. Pituitary hCG is more commonly detected in women greater than 55 years of age but can be detected in women as young as 41 years. Pituitary hCG therefore needs to be excluded in peri or postmenopausal women.
Common hCG-related molecules in serum samples include regular hCG, hyperglycosylated hCG (ITA), nicked hCG, nicked ITA, hCG missing the β-subunit C-terminal extension, free α-subunit, free β-subunit, free β-subunit missing the C-terminal extension, hyperglycosylated free β-subunit, and nicked free β-subunit. The same molecules plus β-core fragment are present in urine samples. While ITA and regular hCG predominate in pregnancy samples, one of these multiple hCG related molecules may be the principal source of immunoreactivity in GTD, gestational trophoblastic neoplasm, choriocarcinoma, and placental site tumor cases as well as in testicular cancer and germ cell tumor. As such, it is critical to appropriately detect all these isoforms in the management of these diseases. Only two tests, the Immulite (DPC, Inc., Los Angeles, CA, USA) and UK radioimmunoassay (RIA; used at Charing Cross Hospital, London) appropriately detect all these hCG-related molecules.
Therapy for low level BhCG should be initiated only if overt trophoblastic neoplasia appears. Patients with low level, real hCG require sophisticated imaging to exclude the presence of extra uterine sites of trophoblast. Although false-positive serum hCG results are rare, if recognized they may lead to unwarranted clinical interventions for conditions such as persistent trophoblastic disease.
Results may also be confirmed by performing serial dilution of the sample. In other words, for diagnostic purposes, results should be used in conjunction with other data, such as symptoms, results of other tests, and clinical impressions. An elevated serum hCG, for example, more than 25 mIU/mL, may represent a normal pregnancy and it’s complications such as abortion or ectopic pregnancy, a GTD or tumor, and a possibly false-positive or so-called phantom hCG.
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