Endometrial Stromal Sarcoma of the Rectosigmoid

Colon Arising in Extragonadal Endometriosis and

Revealed by Portal Vein Thrombosis
Najat Mourra, MD; Emmanuel Tiret, MD; Yann Parc, MD; Paul de Saint-Maur, MD; Rolland Parc, MD;
Jean-Francois Flejou, MD

Malignant transformation is an infrequent complication

of endometriosis. The ovary is the primary site in 76% of
cases, and extragonadal sites are identified in 24%. Endometrioid carcinoma is the most common histologic type;
sarcoma is very rare. We report a case of low-grade endometrial stromal sarcoma of the rectosigmoid colon presenting with epigastric pain due to portal vein thrombosis.
This tumor arose from extragonadal endometriosis in a 61year-old woman and was treated by surgical resection. The
main differential diagnosis of this unusual colonic neoplasm includes primary mesenchymal tumors, such as gastrointestinal stromal tumors.
(Arch Pathol Lab Med. 2001;125:10881090)

ndometriosis is one of the most common benign gynecologic conditions and has been estimated to affect
approximately 10% to 25% of women presenting with gynecologic symptoms in the United States. Intestinal involvement occurs in 3% to 37% of cases and involves areas
where the peritoneum is irregularly folded, such as the
antimesocolic border of the sigmoid colon. It also affects
those parts of the bowel that lie in proximity to the genital
organs. The sigmoid colon and rectum are involved in
15% to 72% of the cases with intestinal involvement.1
Malignant transformation is a rare but well-documented complication of endometriosis, occurring in 0.7% to 1%
of cases. The ovary is the primary site in 76% of the cases,
whereas extragonadal sites represent 24%.2,3 The colorectum is involved in only 5% of cases.2 Theoretically, any
histologic pattern can arise in endometriosis, but endometrioid adenocarcinoma is the most frequent. Endometrial
stromal sarcoma is extremely rare, particularly in the rectosigmoid colon.
In this article, we present an endometrial stromal sarcoma of the rectosigmoid colon arising in extragonadal
endometriosis. To our knowledge, this is the first case revealed by portal vein thrombosis.
Accepted for publication February 20, 2001.
From the Departments of Pathology (Drs Mourra, Saint-Maur, and
Flejou) and Surgery (Drs Tiret, Y. Parc, and R. Parc), Hopital Saint-Antoine, Paris, France.
Reprints: Najat Mourra, Department of Pathology, Hopital Saint-Antoine, AP-HP, 184 rue faubourg St-Antoine, 75012 Paris, France (e-mail:
najat.mourra@free.fr).
1088 Arch Pathol Lab MedVol 125, August 2001

REPORT OF A CASE
A 61-year-old woman, para 1, presented with epigastric pain
in December 1997. She had no history of, or symptoms to suggest, the presence of endometriosis and had been receiving hormone replacement therapy for 13 years.
Abdominal ultrasound revealed a portal vein thrombosis, and
computed tomographic scan of the pelvis revealed a malignant
tumor in the rectosigmoid colon. Her serum carcinoembryonic
antigen and CA 125 levels were within normal limits. Colonoscopic examination showed an unusual polypoid tumor with stenosis of the lumen at the rectosigmoid junction, but endoscopic
biopsy showed only nonspecific inflammation.
Because a metastatic workup was negative, the patient underwent laparotomy with rectosigmoid colon resection and low anterior reanastomosis. At the time of surgery, there appeared to
be tumor nodules (12 cm in diameter) on the posterior wall of
the right board ligament of the uterus. Frozen section examination of these granulations showed endometrial glands and surrounding stroma, in keeping with endometriosis (Figure 1). In
addition, a postoperative hysterography and curetting biopsy revealed no mass lesion, making a uterine primary unlikely.
The patient did not receive any adjuvant treatment. She was
alive without evidence of disease for 30 months of follow-up.

MATERIALS AND METHODS

Routine hematoxylin-eosin sections were prepared from formalin-fixed, paraffin-embedded tumor tissue. Immunohistochemical studies were performed by indirect staining methods
using antibodies against cytokeratin (clone KL1, 1:50, Immunotech, Marseille, France), vimentin (3B4, 1:100, Dako, Glostrup,
Denmark), epithelial membrane antigen (E29, 1:75, Dako),
smooth muscle actin (1A4, 1:50, Dako), desmin (D33, 1:20, Dako),
S100 protein (polyclonal, 1:200, Dako), neurofilaments (2F11, 1:
75, Dako), CD34 (QBEnd 10, 1:50, Dako), CD117 (polyclonal, 1:
100, Santa Cruz Biotechnology, Santa Cruz, Calif), estrogen receptor (1D5, 1:75, Dako), and progesterone receptor (PR88, 1:40,
BioGenex, San Ramon, Calif).

PATHOLOGIC FINDINGS
The specimen consisted of a 20-cm resection of rectosigmoid colon with attached mesenteric fat. A 2.7-cm tumor was found at 3 cm of rectal margin and was responsible for stenosis of the lumen. The tumor grossly involved
all layers of the rectal wall and was associated with overlying polypoid bluish mucosa. Ten lymph nodes were
identified in the attached mesentery.
Microscopic examination revealed a typical tonguelike
growth of tumor nodules that invaded all layers of the
rectal wall (Figure 2). These nodules were composed of
Endometrial Stromal Sarcoma of the Rectosigmoid ColonMourra et al

Figure 1. Focus of benign endometriosis.

Note endometrial gland surrounded by benign stroma (hematoxylin-eosin, original
magnification 3200).
Figure 2. Tumor nodules, composed of
densely packed spindle cells, involved the
mucosa and submucosa (hematoxylin-eosin,
original magnification 350).
Figure 3. High-power view showing uniformity, bland cytology of spindle tumor cells,
and prominent arterioles (hematoxylin-eosin,
original magnification 3200).
Figure 4. Tumor cells are positive for vimentin (original magnification 3400).

densely packed, plump spindle cells in short fascicles, interspersed with prominent small arterioles (Figure 3). The
tumor cells resembled those of normal endometrial stroma
of proliferative phase, with scanty ill-defined cytoplasm
and round or ovoid nuclei with dispersed chromatin. The
cells exhibited little nuclear pleomorphism and few mitotic figures were identified, the mitotic count being less
than 1 in 10 high-power fields. There was 1 area of epithelial-like configuration. Prominent lymphatic, vascular,
and perineural invasion was seen. The histologic features
were typical of low-grade endometrial stromal sarcoma.
There was no lymph node metastasis, and all surgical
margins were free of disease.
Tumor cells were strongly positive for vimentin (Figure
4), estrogen receptor, and progesterone receptor, but were
negative for cytokeratin, epithelial membrane antigen,
S100 protein, neurofilament, CD34, and CD117. A few tumor cells in an area of epithelial-like configuration were
positive for desmin and smooth muscle actin.
COMMENT
Malignant transformation of endometriosis has been
well documented since it was first reported by Sampson4
in 1925, who recommended 3 criteria for a definitive diagnosis of malignancy arising in endometriosis: (1) close
proximity of benign endometriosis to the malignant tumor, (2) no other primary site identified, and (3) tumor
histology compatible with an endometrial primary. In
1953, Scott5 suggested that a more stringent qualification
should be applied, requiring that microscopic benign endometriosis was contiguous with malignant tissue. For the
extraovarian case, adequate evidence for such an association is coexistence of the tumor and endometriotic tissue,
even without demonstrable continuity, if the 2 processes
appear in an uncommon site or at an unusual age, and
the malignant tumor is of a histologic type that has been
well established to arise from endometrial-type tissue.6
These less strict criteria are justified, because transitional
areas between endometriosis and cancer can be destroyed
by the growth of the tumor and therefore are shown only
Arch Pathol Lab MedVol 125, August 2001

in 5% to 10% of cases.6 Our case is consistent with these

criteria.
In their review of preneoplastic and neoplastic changes
in gastrointestinal endometriosis, Yantiss et al7 found fewer than 50 cases of neoplasms arising in endometriosis of
the gastrointestinal tract, reported as small series or single
cases. The classic presentation is that of increasing abdominal pain, bloating, or rectal bleeding in a postmenopausal
patient with or without a history of endometriosis. Presenting symptoms due to vascular thrombosis, as in our
case, were reported only once in the literature.8 In that
case, a 52-year-old woman with sarcomatous change in
chronic pelvic endometriosis presented with a swollen
right leg due to an extensive right iliofemoral vein thrombosis. Epigastric pain due to portal vein thrombosis, resulting probably from extensive venous invasion, was the
first symptom in our patient.
The most common histologic type of cancer arising in
endometriosis is endometrioid adenocarcinoma. Endometrial stromal sarcoma is rare in gastrointestinal and other
sites of malignant transformation of endometriosis.3 Palladiano et al (cited in Yantiss et al7) reported 5 endometrial
stromal sarcomas involving the rectovaginal septum, rectum, and colon, and Mostoufizadeh and Scully6 reported
2 additional cases of sarcoma arising in endometriosis involving the gastrointestinal tract. Finally, Baiocchi et al
(cited in Yantiss et al7) reported 2 cases occurring in the
colon.
The differential diagnosis of endometrial stromal sarcoma arising in the gastrointestinal tract includes mesenchymal neoplasms, particularly if the underlying benign
endometriosis is obscured.7 Most of the mesenchymal neoplasms (fibromatosis, schwannoma, and leiomyoma) can
be immediately excluded from the differential diagnosis
based on their histologic features. However, given their
variable gross and histologic appearances, gastrointestinal
stromal tumors can be confused with endometrial stromal
sarcoma. In contrast to endometrial stromal sarcoma,
these tumors tend to be well-circumscribed with broad,
pushing borders and rare vascular invasion. The cells are

Endometrial Stromal Sarcoma of the Rectosigmoid ColonMourra et al 1089

arranged in short fascicles with a vaguely organoid arrangement reminiscent of smooth muscle neoplasms. Nuclear atypia and pleomorphism may be marked. Endometrial stromal sarcomas have characteristically invasive
tongues of tumor at the periphery and are usually composed of short regular fascicles or sheets of monomorphic
plump spindle cells. The presence of prominent arterioles
and extensive vascular invasion should argue against the
diagnosis of stromal tumor. Finally, immunohistochemical
stains are useful in distinguishing between these entities,
as stromal tumors are well known to stain diffusely for
CD117 and CD34,9 and endometrial stromal sarcoma for
estrogen and progesterone receptors.
The association between exogenous hormone therapy
and the development of malignancy in endometriosis is
well known and should alert both pathologists and clinicians to the possibility of malignant transformation of endometriosis in these patients.10 Our patient had received
hormone replacement therapy for 13 years.
The management of extrauterine endometrial stromal
sarcoma is difficult, but primary surgical treatment with
complete resection of all disease should be performed
when feasible.10 The prognosis correlates well with stage.
A 100% 5-year survival rate has been noted for malignant
transformation in extragonadal endometriosis, confined to
the site of origin.3 However, the 5-year survival rate was
only 12% in cases of disseminated intraperitoneal disease.2
In summary, this case of endometrial stromal sarcoma

1090 Arch Pathol Lab MedVol 125, August 2001

of the rectosigmoid colon arising from extragonadal endometriosis is of interest because the atypical clinical presentation was the epigastric pain probably due to a portal
vein thrombosis. Although rare, malignant transformation
of extragonadal endometriosis should be included in the
differential diagnosis of unusual colorectal tumors affecting postmenopausal patients, particularly if they have received hormone therapy.
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Endometrial Stromal Sarcoma of the Rectosigmoid ColonMourra et al