MULTI-FOCAL EXTRA-UTERINE ENDOMETRIAL STROMAL SARCOMA (ESS): A VERY RARE COMPLICATION OF ENDOMETRIOSIS ASSOCIATED WITH ELEVATED SERUM CA-125

Endometrial stromal sarcomas (ESS) in the female
genital tract are uncommon and are usually of
uterine origin.1,2,3 Extra-uterine ESS are extremely
rare. Only 86 cases have been reported in the
literature.2,4 More than 50% of the cases were associated
with pre-existing endometriosis. We report a case of
extrauterine low grade ESS associated with extensive
endometriosis of the pelvis. We suspected that the tumor
was a primary ovarian carcinoma due to elevated serum CA-
125.
Case Report
The patient was a 45-year old premenopausal, multiparous
female (8 + 2). The patient presented with lower
abdominal pain of 6 months duration associated with nausea
and constipation.
Her medical history included myomectomy for
leiomyomas 17 years prior to this presentation. The patient
was diabetic and hypertensive. Physical examination
revealed a mass in the abdominal-pelvic region measuring
15 x 12 centimeters. Serum CA-125 was three times the
normal range (197 mmol/L). Abdominal pelvic
ultrasonography revealed an abdomino-pelvic mass of mixed
echogenecity measuring 13 x 13 centimeters and located on
the right side of the pelvis. The uterus was normal in size. A
CT scan of the abdomen and pelvis showed a large
heterogenous pelvi- abdominal mass with the epicenter in
the region of the pelvic wall (Figure 1). The mass appeared
adherent to the uterus and bowel wall. Laparotomy was
performed and a mass adherent to the fundus of the uterus,
the pelvic cul-de-sac and the bowel was found. There were
multiple variable-sized nodules found in the wall of the
pelvis, fallopian tubes and pelvic peritoneum. Total
abdominal hysterectomy and bilateral salpingooophorectomy
with debulking was performed. The patient
was given progesterone therapy (MegaceR ) and was
discharged.
Grossly the tumor was
composed of multiple yellow-tan
fleshy nodules with focal cystic
areas. Focal areas of hemorrhage
and necrosis were identified. The
tumor was near the right adnexa.
The uterus, fallopian tubes and
MULTI-FOCAL EXTRA-UTERINE ENDOMETRIAL STROMAL SARCOMA (ESS):
A VERY RARE COMPLICATION OF ENDOMETRIOSIS ASSOCIATED WITH
ELEVATED SERUM CA-125
W.A. Mourad, MD FRCPC; B. Abdelghaffar, MD; A.Tulbah, MD FRCPA; M.Tulbah, MD; J. Subhi, MD
From the Department of Pathology and Laboratory Medicine, King Faisal Specialist
Hospital and Research Centre, Riyadh, Saudi Arabia
Correspondence to:
Dr. W. Mourad
P.O. Box 3354 MBC 10
Riyadh 11211
Saudi Arabia
Accepted for publication:
December 2002
Figure 1. Pelvic CT scan showing a heterogenous mass
attached to the left pelvic wall.
CASE REPORT
181 ¥ Annals of Saudi Medicine ¥ 2003 May-July, Volume 23 www.kfshrc.edu.sa/annals
ovaries showed multiple tumor nodules. Microscopically, the
tumor consisted of diffuse sheets of small closely packed
cells with uniform round oval nuclei with coarse, evenly
dispersed chromatin and small inconspicuous nucleoli. The
cytoplasm was scanty and its boundaries were not well
defined. A distinct vascular pattern was identified (Figure
2). This pattern was more prominent on the reticulin stain
(Figure 3). Mitotic figures were less than 1 in 10 /high power
field. No cellular atypia or pleomorphism were identified.
The tumor was strongly positive for estrogen and
progesterone receptors (Figure 4). Multiple deposits of the
tumor were identified in the omentum. The ovaries and tubes
showed multiple foci of tumor and endometriosis (Figure
5). The endometrium showed cystic hyperplasia without
evidence of ESS.
Discussion
Extra-uterine ESS are very rare neoplasms. We found
86 cases in the literature.2,4,8-10 Young et al. studied 23 cases
of ovarian ESS and found 9 cases to be primarily in the
uterus.10 In his study only 10 cases appeared to be well
documented extra-uterine ESS. Chang et al. reported 20
cases.4 We found that 48 of the 86 reported cases arose in
the ovary and 33 were of extra-ovarian origin, including the
vaginal septum, fallopian tube, broad ligament, and
abdominal cavity. Thirty seven cases were documented as
associated with endometriosis.2,4,8,10 It seems from the
Mourad et al.
Multi-Focal Extra-Uterine ESS
2 3
4 5
www.kfshrc.edu.sa/annals Annals of Saudi Medicine ¥ 2003 May-July, Volume 23 ¥ 182
literature and from our case that ESS is closely related to
endometriosis and represents an exceedingly rare
complication of that common disease.
Our patient presented with abdominal and back pain,
constipation, a pelvic mass and ascites. Radiological
investigation showed a multi-cystic pelvic mass close to the
ovary with an associated elevation of serum CA-125. This
clinical and radiographic presentation is suggestive of an
ovarian neoplasm. Eighty-two percent of ovarian epithelial
tumors are associated with elevated levels of serum CA-125.
A pelvic mass with elevated levels of CA-125 would suggest
ovarian carcinoma. The latter, however, is associated with
levels of CA-125 above 1000 mmol/L in most reported cases.
Elevation of serum CA-125 in endometriosis is usually less
than 1000 mmol/L. Mild elevation of CA-125 in our case
(197 mmol/L) is probably related to pelvic endometriosis.
There have been reports showing evidence of elevated serum
CA-125 in association with extensive endometriosis.3,6
These reports suggest that endometriosis may cause
mesothelial hyperplasia, which may lead to elevation of
serum CA-125. Barbieri et al. found elevated serum levels
of CA-125 in half of the patients with advanced endometriosis
they have studied. They also found that the levels could be
raised in pregnancy, leiomyomata and pelvic inflammatory
disease
Extra-uterine ESS usually behaves like its endometrial
counterpart,1,4,10 but its behavior is dependent on the grade
of the tumor. Low grade tumors with a low mitotic rate and
lacking atypia and pleomorphism behave in a more benign
manner than the high grade neoplasms.7,8,10
The role of hormonal therapy is well documented in these
low grade tumors.1,2,5,7,8 Steroid receptor detection by
immunohistochemistry is valuable. It was also noted that
tumors that expressed both estrogen and progesterone
Figure 2. Section of pelvic tumor showing polygonal cells with indistinct cell boundaries with coarse nuclear chromatin and a
prominent vascular pattern. Figure 3. Prominent vascular pattern of the tumor as seen on the reticulin stain. Figure 4. Strong
expression of the tumor cells for estrogen receptors. Notice the lack of expression in the blood vessels. Figure 5. Focus of
andometriosis in soft tissue adjacent to the fallopian tube.
2 3
4 5
Mourad et al.
Multi-Focal Extra-Uterine ESS
183 ¥ Annals of Saudi Medicine ¥ 2003 May-July, Volume 23 www.kfshrc.edu.sa/annals
3. Barbeiri R, Niloff J, Bast J, Schatzel E, Kistner R, Knapp R.
Elevated serum concentrations of CA 125 in patients with advanced
endometriosis.Fertil Steril 1986;45: 630-4.
4. Chang K, Crabtree G, Lim-Tan S, Kempson R, Hendrickson M.
Primary extra-uterine endometrial stromal neoplasms: A
clinicopathologic study of 20 cases and review of the literature. Int J
Gynecol Pathol 1993;12:282-96.
5. Katz L, Merino M, Sakamoto H, Schwartz P. Endometrial Stroma
Sarcoma: A Clinocopathologic study of 11 cases with determination
of Estrogen and Progestin Receptor Levels in Three cases. Gyn
Oncol 1987;26:87-97.
6. Myers T, Arena B, Granai C. Pelvic endometriosis mimicking
advanced ovarian cancer: Presentation with pleural effusion, ascites,
and elevated serum CA125 level. Am J Obstet Gyn 1995;173(3):
966-7
7. Nordal R, Kristensin G, Karen J, Stenwig A, Petersen E, Trope C.
The Prognostic Significance of Surgery, Tumor size, Malignancy
Grade, Menopausal Status, and DNA Ploidy in Endometrial Stroma
Sarcoma. Gyn Oncol 1996;62:254-9.
8. Shakfeh SM, Woodruff D. Primary Ovarian Sarcomas: Report
of 46 cases and review of the literature. Obstet Gynecol Surv 1987;
42:331-49.
9. Shiraki M, Otis C, Powell J. Endometrial Stromal Sarcoma arising
from ovarian and extraovarian endometriosis Ð Report of two cases
and review of the literature. Surg Pathol 1991;4(4):333-42.
10. Young R, Prat J, Scully R. Endometrioid Stromal Sarcoma of
the Ovary: A Clinicopathological analysis of 23 cases. Cancer 1984;
53: 1143-55.
receptors have benefited from progesterone therapy;
especially low grade tumors.1,5,8 Baggish et al. reported a
case of pulmonary nodule of low grade ESS which recurred
three years after surgery.1 The patient received progesterone
therapy and the lesion disappeared within 15 months. Katz
et al. followed four patients treated with progesterone.5 All
patients were free of disease after follow-up of 2 to 6 years.
Treatment by progesterone should be long term because
of the possibility of recurrence after discontinuation of
therapy.5,8 It also appears that treatment with total abdominal
hysterectomy and salpingo-oophorectomy with debulking of
any residual tumor in addition to hormonal therapy would
be sufficient treatment for these neoplasms.
We believe that extra-uterine ESS is an exceedingly rare
complication of endometriosis and that on rare occasion can
be associated with an elevated level of serum CA-125 if the
endometriosis is extensive. These levels, however, do not
reach the values reached in primary ovarian carcinomas.
References
1. Baggish M, Woodruff D. Uterine Stromatosis. Clinicopathologic
features and Hormone Dependency. Obstet Gynecol 1972; 40:4.
2. Baiocchi G, John J, Kavanagh J, Wharton J. Endometrioid
Stromal Sarcomas arising from ovarian and extraovarian
endometriosis: Report of two cases and review of the literature.
Gynecol Oncol 1990;36: 147-51.