Ovarian cancer in a woman previously diagnosed with endometriosis and an extremely high serum CA- 125 level

Ovarian cancer in a woman previously diagnosed
with endometriosis and an extremely high serum CA- 125
J. H. Check’, M. L. Check’, D. Kiefer’, J. Aikins* Jr.
‘The lJniversi@ of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School at Camden,
Cooper Hospital/University Medical Centel; Department of Obstetrics and Gynecology,
Division of Reproductive Endocrinology & Infertility, Camden, New Jersey (USA);
‘Department of Gynecologic Oncology
Summary
83
level
Purpose: Follow-up of a woman with a serum CA-125 level > 1000 U/mL where laparoscopy only found endometriosis.
Methods: Case report - re-evaluation several years later.
Results: Extensive clear-cell carcinoma of ovary with metastases leading to death.
Corklusion: This case suggests that bilateral oophorectomy should be performed in women not desiring any more children if the
serum CA-125 level is very high even if only endometriosis is found initially.
Key words: CA-125; Clear cell carcinoma;‘Ovary; Endometriosis.
Introduction
Elevations in serum CA-125 levels have been associated
with epithelial ovarian cancer [2-41. However, an elevation
of this glycoprotein has been found in benign conditions
of the pelvis [5-II].
One of the benign conditions associated with elevated
CA-125 levels is endometriosis [6, 7, 10-161. Some cases
have been reported with serum CA-125 levels over 1,000
U/mL in women without ovarian cancer but with a diagnosis
of endometriosis [ 1, 16-211. The highest level to
date recorded was 9,300 IU/mL in a woman with a rnptured
endometriotic cyst [20], and the highest recorded
level without cyst rupture was 6,114 IU/mL [21].
The question arises as to whether women with very
high CA-125 levels and endometriosis have any greater
risk of developing subsequent ovarian carcinoma. When
high CA-125 levels are present in women no longer considering
pregnancy, the demonstration of endometriosis
involving the ovaries would normally result in oophorectomy
as performed by Nagara et al. [22]. The first case
report of a woman presenting with a serum CA-125 level
>I ,000 IU/mL was reported by Check et al. [ 11. However
for this patient who had a CA-125 level as high as 1,385
IU/mL, oophorectomy was refused by the 46-year-old
woman and she insisted on laparoscopy only with laser
fulguration of endometriosis for pelvic pain [I]. Unfortunately,
this woman, who was the first one described with
these extremely high levels, subsequently developed
ovarian carcinoma as described herein.
Case Report
A 46-year-old nulligravida with amenorrhea presented with
severe recurrent pelvic pain in 1989. She demonstrated a
24x23~22 mm cyst with low level internal echoes on the right
ovary. CA-125 was 149 IU/mL. Her levels were watched for five
Revised manuscript accepted for publication February 26,200 1
Clm. Exp. Obst. & Gyn. - MN: 0390.6663
XXVIII, n. 2, 2001
consecutive months and the levels rose to 231, 274, 267, 400,
and 1,385 IU/mL, respectively, as previously described [I].
Based on the very high CA-125 levels, the presumptive diagnosis
was possible ovarian cancer and referral to a gynecologic
oncologist with probable exploratory laparotomy was recommended
[l]. However the patient, who was a nun and a medical
technologist, refused laparotomy stating that she had almost
died from an arrhythmia related to her lupus cardiomyopathy
when having previous surgery.
She found a reproductive endocrinologist who was willing to
perform a laparoscopy with Yag laser fulguration of endometriosis
[ 11. The ovarian biopsy revealed ovarian stroma with
hemosiderin-laden macrophages, consistent with, but not diagnostic
of, endometriosis [1], since endometrial glands and
stromas were not identified. Postoperatively the CA- 125 level
was 122 IU/mL and five months later it was 150 IU/mL and
there was a recurrence of a right ovarian cyst [l]. Four years
following surgery her CA-125 dropped to 64 IU/mL.
The woman stopped coming for evaluation of the CA-125
level or pelvic sonography until May of 1999 (5 years from her
CA- 125 level of 64 IU/mL in 1994) complaining of marked
fatigue. An abdominal mass was easily palpated. Abdominal
ultrasound (she could not withstand the vaginal probe) showed
a 177x101~129 mm mass with complex echoes with an irregularly
shaped dense area and fluid seen inside of the mass. Fluid
was found in the left lower quadrant measuring 53x67~60 mm.
Hydronephrosis of the right kidney was found.
A CT scan of the abdomen and pelvis showed a large pelvic
mass measuring 14.4x10.7x12.0 cm with cystic and solid components
noted. The mass had septations and two foci of calcifications.
The mass was anterior to the uterus and midline. Also
severe right hydroureteral neophrosis and dilatation of the left
ureter secondary to this large mass was also noted.
Laparotomy was performed and the large tumor was excised
and identified as a clear cell carcinoma. The woman died one
year later.
Discussion
One of the problems with using the CA-125 assay to
diagnose ovarian cancer is that some ovarian cancers do
not demonstrate high CA-125 levels until they become
84 J. H. Check, M. L. Check, D. Kiefer; .I. Aikins Jr.
very advanced and some benign lesions, e.g. endometriosis,
may present with extremely high serum CA-125
levels. One study found that if the serum CA-125 level
was >I,000 IUlmL, 89% had gynecologic cancer, 7%
non-gynecologic cancers and 3% benign conditions [ 181.
One could certainly question that had bilateral oophorectomy
been performed when the CA-125 was so high ten
years earlier, might early cancer have been detected in the
patient described and could advanced metastatic disease
have been averted? Unfortunately, the patient refused
bilateral oophorectomy [I]. Frequent co-occurrence of
endometriosis in the same ovary has been found [23, 241.
However, it is possible that histopathological evaluation
of both ovaries might have found nothing more than
endometriosis.
There have been several publications suggesting that
the presence of endometriosis is associated with a greater
chance of developing carcinoma of the ovary [25-311.
The first case of suspected malignant transformation in
endometriosis was published in 1925 [32]. According to
15 published reports to date the incidence of ovarian
endometriosis in ovarian cancer is closely related to
histologic type, 3.3% - serous type, 3.0% - mutinous
type, 39.2% - clear cell type, and 21.2% - endometroid
type [24, 29, 33-451.
The number of reported cases of endometriosis and
very high CA-l 25 levels are small [ 1,221 and at least one
of them has already presented with advanced carcinoma
of the ovary several years later. It is possible that some
clinicians might use the aforementioned case report as an
example of how benign endometriosis can present with
very high CA- 125 levels and thus use this case as a precedent
for merely ablating endometriotic implants if they
are present [I]. The IO-year follow-up of this case, as
reported herein, strongly suggests that bilateral oophorectomy
be performed if the woman has finished child
bearing. For those who still desire another child this case
could suggest unilateral oophorectomy on the side of
endometriosis (if bilateral disease is not present) with
subsequent removal of the contralateral ovary after delivery.
For those patients not adhering to these suggestions
then close monitoring every six months with pelvic sonography
should be performed.
Now that the first case reported with serum CA-125
levels >l,OOO IU/mL has subsequently developed ovarian
cancer, it is imperative to aggressively follow all subsequent
cases with such high levels with serial ultrasound
and perhpas consider prophylactic oophorectomy if no
further children are desired.
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Address reprint requests to:
JEROME H. CHECK, M.D., Ph.D.
7447 Old York Road
Melrose Park, PA 19027