Ovarian Endometrioma Associated With Extremely Elevated Serum CA-125 Levels: Utility of Imaging in a Diagnostic Dilemma

Introduction
Serum CA-125, a tumor associated antigen, is elevated in
epithelial ovarian carcinomas, and mildly elevated in some
women with benign gynecologic disorders. Despite the low
positive predictive value for malignancy, CA-125 levels greater
than 300 IU/ml are usually associated with malignancy
even in premenopausal patients. However, serum CA-125 levels
greater than 1000 IU/ml has occasionally been reported
in patients with ovarian endometriosis (1,2). Elevated CA-
125 levels in patients with endometrioma can cause a diagnostic
dilemma mimicking ovarian cancer. Moreover, endometrioma
has occasionally been shown to be accompanied
by malignant ovarian tumors (3,4). We report a rare case of
ovarian endometrioma with extremely elevated serum CA-
125 levels, and discuss the utility of imaging features in the
assessment of potential malignancy.
Case Report
A 26-year-old nulligravid woman without previous history
of gynecologic disorder was seen for preconceptional counseling.
Her menstrual cycle was regular (30/5/2), and she
was on day 23 of her cycle. Physical and pelvic examinations
were unremarkable. The complete blood count and blood
biochemistry were within normal limits. Transvaginal ultrasonography
examination showed a well-delineated 4x3 cm
biloculated cystic mass within right ovary with low-level internal
echoes (Figure 1). The serum CA-125 level was 2229
IU/ml (Enzyme immunoassay, upper reference limit, <35
IU/ml). CA 19-9 and CA 15-3 levels were normal. Transabdominal
Doppler ultrasound revealed no abnormal vascularity.
Magnetic resonance (MR) imaging of the pelvis showed
the mass to be homogeneously hyperintense on T1-weighted
images (Figure 2A), which shaded on T2-weighted sequences.
The wall and the septum were hypointense on both T1-
and T2-weighted images. The internal signal remained high
on fat-saturated sequences (Figure 2B). There was no evidence
for a mural nodule, solid component or enhancement
after intravenous injection of gadolinium. Based on the imaging
features, the lesion was considered to be an endometrial
cyst without evidence of associated malignancy. Subsequ-
244 Artemis, Vol. 5(3); 2004
Ovarian Endometrioma Associated With Extremely Elevated
Serum CA-125 Levels: Utility of Imaging in a Diagnostic
Dilemma
Aysun KARABULUT1, Nevzat KARABULUT2, A. Baki YA⁄CI2
1Clinic of Obstetrics and Gynecology, Denizli State Hospital, Denizli, Turkey
2Department of Radiology, Pamukkale University Hospital, Denizli, Turkey
CASE REPORT
Abstract
Elevated CA-125 levels in patients with endometrioma can create a diagnostic dilemma. We report the sonographic and
magnetic resonance imaging findings in a case of ovarian endometrioma with a serum CA-125 level of 2229 IU/ml, and discuss
the utility of imaging features in the assessment of potential malignancy.
Keywords: endometrioma, endometriosis, CA-125, ultrasonography, magnetic resonance imaging
Özet
Yüksek Serum CA-125 Düzeyinin Efllik Etti¤i Ovaryan Endometrioma: Tan›sal ‹kilemde
Görüntüleme Yöntemlerinin Yararlar›
Endometriomal› hastalarda afl›r› yüksek CA-125 düzeyleri tan›sal zorluk ç›karabilir. Bu çal›flmada serum CA-125 düzeyi
2229 IU/ml olan over endometriomal› bir olguda sonografik ve manyetik rezonans görüntüleme bulgular› sunulmufl ve potansiyel
malignitenin tayininde görüntüleme yöntemlerinin yararl›l›¤› tart›fl›lm›flt›r.
Anahtar sözcükler: endometriyoma, endometriozis, CA-125, ultrasonografi, manyetik rezonans görüntüleme
Corresponding Author: Dr. Aysun Karabulut
Hastane Cad. Umut Apt. No: 5/3 20010 Denizli, Türkiye
Phone : +90 (258) 262 32 52
+90 (532) 569 33 57
Fax : +90 (258) 373 86 97
E-mail : aysunkarabulut@yahoo.com
ent CA-125 level on day of 3 of her next cycle was 738
IU/ml. At laparoscopy, a right ovarian endometrioma with
brown fluid was detected. Adhesions were seen in the fimbrial
end of the right ovarian tube. The uterine serosa and the
left adnexa were normal. A right cystectomy was performed
and adhesions were lysed along with neosalpingostomy. Histopathologic
examination confirmed the diagnosis of endometrioma.
On the 15th postoperative day, serum CA-125 level
dropped to 79 IU/ml.
Discussion
Endometriosis is a common gynecologic disorder that affects
women of reproductive age, and characterized by endometriomas
(chocolate cysts), peritoneal implants and adhesions.
Endometriomas are complex lesions containing multiple hemorrhagic
cysts that have blood products of different ages
within them. Although the disease is recognized as benign,
endometriosis is occasionally accompanied by malignant
ovarian tumors, especially endometrioid and clear cell adenocarcinoma
(3,4). CA-125, a high molecular weight
glycoprotein, was reported to be elevated in moderate-to-severe
endometriosis (5). CA-125 levels increase with the stages
of endometriosis, omental adhesions and rupture of endometrioma.
In a series of 685 women with endometriosis,
Cheng et al. (5) reported that patients with preoperative CA-
125 levels higher than 65 IU/ml were at high risk for advanced
stages of endometriosis or severe pelvic adhesions or
rupture. They reported a mean CA-125 level of 427.47 IU/ml
in patients with ruptured endometrioma and that of 77.96
IU/ml in patients with unruptured cysts. Associated peritoneal
inflammation is a strong contributor of elevated CA-125
levels. In our patient, there was no sign of rupture at laparoscopy,
but the fimbrial adhesions might in part be the cause of
the abnormally high tumor marker.
Extremely elevated serum CA-125 levels are occasionally
associated with endometriosis (1,2). A serum CA-125 level
of 3890 IU/ml was reported in a patient with endometriosis
(1), and that of 6114 IU/ml and 9357 IU/ml in a patient with
ruptured endometrioma (2). The size of the endometriomas
associated with elevated CA-125 levels is generally large. In
our case, the size of the lesion was 4x3 cm, smaller than the
previously reported cases. The timing of blood sample for
CA-125 is crucial, because elevated CA-125 levels greater
than 1000 IU/ml have been reported during menstruation (6).
Therefore, sampling should not be done during or immediately
after menstruation when tumor marker determination is
required. However, serum samples were obtained during
menstruation in most of the case reports showing extremely
high CA-125 levels (1,2). The CA-125 level was 2229 IU/ml
during luteal phase in our patient and 738 IU/ml during
menstruation. We cannot explain the reason of decline of the
marker during menstruation.
Elevated CA-125 levels in patients with endometriosis can
create diagnostic problems mimicking ovarian cancer. Furthermore,
malignant transformation has been reported as a rare
complication of endometriosis, with an incidence of 0.6-
245
Figure 1. Transvaginal sonography shows biloculated cystic
mass with low-level internal echoes.
Figure 2. T1-weighted MR images without (A) and with (B)
fat-suppression reveals bilobed cystic mass in the right adnexa
containing hyperintense fluid and surrounded by hypointense
wall. Fat-suppression (B) increases lesion conspicuity
and differentiates endometrioma from fatcontaining ovarian
masses.
a
b
Artemis, 2004; Vol 5(3)
1.0% (3,4). Imaging findings can aid to diagnose or exclude
an associated ovarian cancer. Ultrasound is usually performed
as an initial study in the evaluation of pelvic diseases
during reproductive years. Endometriomas have been described
as having a homogeneous low-level echogenicity within
loculated cysts and they are better appreciated by transvaginal
ultrasound over transabdominal ultrasound in part by the
better definition of the degree of internal echogenicity. Although
the absence of mural nodule or solid components is
helpful in the exclusion of carcinoma, sonographic evaluation
is limited in ruling out ovarian malignancy (7). It may also
be difficult on sonography to detect echogenic endocystic
vegetations. Conversely, blood clot or focal fibrosis caused
by recurrent hemorrhage may show focal wall nodularity on
sonography, which is difficult to differentiate from malignant
findings (7). The value of Doppler ultrasound is limited
and confusing because low resistance blood flow was reported
in cases of endometrioma (1-3). MR imaging is superior
to ultrasound in the characterization of adnexal masses with
sensitivity and specificity of greater than 90% in the detection
of endometriomas (8). Therefore, patients with indeterminate
sonographic findings and in whom there is suspicion of
endometriosis may benefit from MR imaging. The addition
of fat-saturated T1-weighted imaging has improved diagnostic
accuracy in the evaluation of both endometriomas and peritoneal
implants by augmenting lesion conspicuity, and differentiating
lipid-containing ovarian masses from those containing
blood (8). Endometriomas are characteristically homogeneously
hyperintense on T1-weighted images and heterogeneous
high and central low signal intensity or shading on
T2-weighted sequences. They are surrounded by a low signal
intensity wall representing hemosiderin or fibrous capsule.
The presence of blood degradation products such as methemoglobin
and hemosiderin, protein and the viscosity of the
cyst contribute to MR imaging signal. Chronicity of cyst
contents is directly proportional to the iron concentration and
viscosity with a corresponding decrease in the T2 relaxation
times. Tanaka et al. (4) reported MR imaging features of
ovarian carcinoma in 10 patients with endometriosis. The
presence of low signal intensity mural nodule on T1-weighted
images, the absence of low signal intensity on T2-weighted
images and enhancement of nodule on postcontrast T1-
weighted images were shown in endometriomas associated
with carcinoma. The sonographic features of the lesion in our
case were consistent with endometrial cyst and Doppler investigation
did not reveal abnormal vascularity. MR imaging
confirmed the diagnosis of endometrioma without evidence
of malignant transformation such as low signal intensity
mural nodule enhancing on postcontrast T1-weighted
images. The exclusion of associated malignancy by the
complementary imaging findings in our case helped us undertake
laparoscopic cystectomy protecting the ovary instead
of an extensive surgery for ovarian carcinoma.
This case illustrates the diagnostic dilemma clinicians’ encounter
when a CA-125 level is abnormally high in the presence
of pelvic mass. Imaging findings are helpful in the diagnosis
of endometriomas and the assessment of malignancy in
patients with an adnexal mass and extremely elevated tumor
markers. In a daily practice, ultrasound is adequate for diagnosis
and planning operative approaches in most cases. MR
imaging can be used as problem-solving tool in patients with
indeterminate clinical and sonographic findings due to its superiority
in the characterization of adnexal masses.
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