Hajime Isomoto, Noriko Nomura, Ikuo Murata, Shigeru Kohno,
Second Department of Internal Medicine, Nagasaki University School
of Medicine, 1-7-1 Sakamoto, Nagasaki, Japan
Chun-Yang Wen, Department of Digestive Disease, Nanjing Drum
Tower Hospital, Medical School of Nanjing University, Nanjing
210008, Jiangsu Province, China
Fumitaka Akama, Haruhiko Nakao, Department of Surgery,
Zeshinkai Hospital, 7-9 Furukawa, Nagasaki, Japan
Kan Toriyama, Department of Pathology, Institute of Tropical
Medicine, Nagasaki University School of Medicine, 12-4 Sakamoto,
Correspondence to: Dr. Hajime
Isomoto, Second Department of Internal Medicine, Nagasaki University
School of Medicine, 1-7-1 Sakamoto, Nagasaki, Japan.
A 49-year-old woman, who had undergone hysterectomy for
low-grade endometrial stromal sarcoma (ESS) 3 years ago, presented
with a 2-wk history of lower abdominal pain. Barium enema and
sigmoidoscopy disclosed a polypoid submucosal tumor. Histopathologic
features of biopsy specimens from the lesion were similar to those
of the resected uterine ESS. Under the diagnosis of metastatic ESS
of the sigmoid colon, sigmoidectomy was performed. Microscopic
examination demonstrated dense proliferation of spindle cells with
little nuclear atypia, which were sometimes arranged in whorled
pattern around abundant arterioles. Mitotic count is below 1 in 10
high-power fields. Immunohi-stochemically, the neoplastic cells were
strongly positive for vimentin, estrogen receptor and progesterone
receptor but negative for a-smooth
muscle actin, S-100 protein and CD34. Thus, a final diagnosis of
low-grade ESS metastasis to the sigmoid colon was made. Her
postoperative course was uneventful and hormonal therapy with
progestational agents is entertained.
� 2005 The WJG Press and Elsevier Inc. All rights reserved.
Key words: Endometrial stromal sarcoma; Metastasis;
Asada Y, Isomoto H, Akama F, Nomura N, Wen CY, Nakao H,
Murata I, Toriyama K, Kohno S. Metastatic low-grade
endometrial stromal sarcoma of the sigmoid colon three years after
hysterectomy. World J Gastroenterol
2005; 11(15): 2367-2369
Endometrial stromal sarcoma (ESS) is a rare neoplasm comprising only
0.2% of all uterine malignancies and 15-26% of primary uterine
It is classified into two distinct subtypes, low-grade and
high-grade, based on differences in morphological atypia and
High-grade ESS has an aggressive nature, whereas low-grade ESS,
which was formerly called endolymphatic stromal myosis, is a
slowgrowing tumor with much better prognosis[6-8].
However, approximately 50% of cases of low-grade ESS develop
recurrent disease and recurrences or metastases are often detected
many years after initial treatment[7,9].
The common metastatic sites of low-grade ESS are the vagina, pelvis
and peritoneal cavity.
Herein, we describe the first case of low-grade ESS metastasized to
the sigmoid colon three years after initial surgery.
A 49-year-old woman presented with lower abdominal pain of 2-wk
duration. She had undergone total hysterectomy for an alleged myoma
of the uterus three years before, which was found to be low-grade
ESS at postoperative pathologic examination. The family history was
unrem-arkable. Physical examination showed lower abdominal
tenderness, but no abdominal mass was palpable. Laboratory tests
were normal and her serum carcinoembryonic antigen and CA 125 levels
were within normal limits. Barium enema showed an irregular-shaped
polypoid lesion in the sigmoid colon. Total colonoscopy disclosed an
unusual polypoid tumor covered with normal-appearing mucosa with
slight vessel engorgement in the sigmoid colon (Figure 1). Biopsy
specimens from the lesion showed diffuse proliferation of
spindle-shaped cells with little nuclear atypia, resembling the
histology of previously excised uterine ESS. Computed tomograms of
the chest, abdomen and pelvis, upper gastroi-ntestinal endoscopy and
barium through of the small bowel showed no abnormalities. Thus, the
diagnosis was established as metastatic ESS of the sigmoid colon,
and sigmoidectomy was performed. Grossly, a well-circumscribed
whitish tumor 2 cm in diameter involved all layers of the colonic
wall and was associated with overlying polypoid mucosa. Microscopic
examination demonstrated that the tumor was composed of short
fascicles or sheets of monotonous plump spindle cells with round
nuclei and dispersed chromatin, which were sometimes arranged in
whorled pattern around abundant arterioles (Figure 2). Mitotic count
is below 1 in 10 high-power fields (HPF). Immunohistochemically, the
neoplastic cells were strongly positive for vimentin, estrogen and
progesterone receptors (Figure 3) but negative for a-smooth
muscle actin, S-100 protein and CD34. Based on these findings, a
final diagnosis of low-grade ESS metastasized to the sigmoid colon
was made. Her postoperative course was uneventful. She was free of
symptoms at the last follow-up, 4 mo after the abdominal surgery,
with no evidence of recurrence.
picture showing a polypoid tumor in the sigmoid colon. The tumor was
covered with normal lining crypts, but had slightly engorged vessels
on the surface.
Microscopic picture of the surgical specimen showing dense
proliferation of spindle-like cells with ovoid or round nuclei,
dispersed chromatin and sparse cytoplasm, arranged in ill-defined
whorls centered on small arterioles. These showed features similar
to the primary uterine low-grade ESS.
showing strong diffuse immunoreactivity of the nuclei of neoplastic
cells for progesterone receptor.
Clinical characteristics of low-grade ESS include a slow growth
and indolent disease course with a tendency for late recurrence. One
large series, the intervals before recurrence varied from 3 mo to 23
years, with a median interval of 3 years.
Styron et al., reported a patient with recurrent disease of
low-grade ESS no less than 29 years after initial treatment.
In our case, the metastatic tumor of the sigmoid colon was detected
by colonoscopic and radiographic examination three years after
hysterectomy. Patients with low-grade ESS almost develop recurrences
or metastases in the vagina, pelvis and peritoneal cavity.
The less frequent sites were reported to be the lungs, liver,
bladder, breast, heart, brain and bones[13-17].
To the best of our knowledge, however, low-grade ESS metastasized to
the colon has not been previously documented.
There are two discernible subtypes of ESS, based
on differences in mitotic activity: more than 10 mitotic figures for
high-grade ESS and less than 10 mitotic figures per 10 HPF for
as observed in our case. Nuclear atypia such as enlargement,
increased and/or coarse chromatin and conspicuous nucleoli were
absent in both the uterine and colonic lesions, distinguishing our
case from high-grade ESS[6,18].
Given the gross appearance of colonic lesion at sigmoidoscopy, one
can propose a variety of submucosal tumors as the differential
diagnosis. Most of the mesenchymal neoplasms (leiomyoma, fibroma and
schwannoma) can be immediately excluded on the basis of the
However, the gastroin-testinal stromal tumor (GIST) may be confused
with low-grade ESS[18,19].
The presence of short fascicles or sheets of monotonous plump
spindle cells, prominent arterioles and perivascular whorl
arrangement of the tumor cells should argue against the diagnosis of
Finally, immunohistochemical analysis is useful in distinguishing
between these entities, as GIST is well known to stain diffusely for
CD34 and CD117
and ESS exclusively for estrogen receptor and progesterone receptor,
reflecting the high sensitivity of low-grade ESS to sex-steroid
Again, low-grade ESS arising in the gastrointestinal endometriosis
has been rarely docum-ented[18,19,23].
According a review in literature by Cho et al.,
most of the lesions were located in the rectosigmoid colon, which is
an area of bowel having the highest incidence of endometriosis.
Our patient has not suffered from endometriosis and there was no
evidence of underlying endometriosis in the surgical specimens.
Thus, the definite diagnosis of low-grade ESS metastasized to the
sigmoid colon was made in this case.
Surgical excision is the major therapeutic
procedure for the primary low-grade ESS, but the standard treatment
for its recurrent disease including radiotherapy and chemotherapy
has not been established[16,24,25].
Some surgeons recommended surgical cytoreduction of the ESS tumors
when the extrau-terine lesions were present[25,26].
On the other hand, Mansi et al., asserted that progesterone
therapy should be the treatment of first choice for relapsed
because there was resolution or stabilization of recurrent or
metastatic disease in more than 50% of patients treated with
In this regard, immunor-eactivity for estrogen receptor and
progesterone receptor should be routinely assessed in low-grade ESS,
in particular manifested by recurrence.
Adjunct progesterone therapy is now entertained in our patient,
since the primary and metastatic tumors showed strong and diffuse
staining against anti-estrogen receptor and progesterone receptor
antibodies. Considering highly recurrent nature of low-grade ESS,
sometimes many years later[7,9,11,12,15,22],
a life-long follow-up is necessary for this woman.
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Editor Elsevier HK