Case 5 -
Endometrioid Carcinoma Arising in Endometriosis in the Sigmoid Colon
University of Michigan
Ann Arbor, MI
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The patient is a 63 year old woman who presented with symptoms caused by a
partially obstructing mass in the sigmoid colon. A colonoscopic biopsy of the mass was reportedly
"inconclusive for carcinoma". The patient underwent a proctosigmoidectomy.
All figures show the same glandular proliferation in the wall and mucosa of the sigmoid colon. It is
a complex epithelial proliferation composed of closely packed tubules. This proliferation is present
beneath and adjacent to benign colorectal mucosa. The tubules are lined by tall columnar epithelial
cells with eosinophilic cytoplasm devoid of mucin. The lumens of the tubules contain scant eosinophilic
material that appears more like proteinaceous secretions than necrotic cellular debris.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
depict a complex epithelial proliferation composed of closely packed tubules. This proliferation is
present beneath and adjacent to benign colorectal mucosa. The tubules are lined by tall columnar
epithelial cells with eosinophilic cytoplasm devoid of mucin. The lumens of the tubules contain scant
eosinophilic material that appears more like proteinaceous secretions than necrotic cellular debris.
The differential diagnosis includes colorectal carcinoma, carcinoma
secondarily involving the colon from another site, a benign glandular condition such as endometriosis, or
another form of primary colorectal carcinoma.
Endometriosis was located elsewhere in the specimen. Diagnosis: Endometrioid carcinoma arising in endometriosis in the sigmoid colon.
Endometriosis in the gastrointestinal tract, and endometriosis-associated intestinal
tumors (EAIT) Gastrointestinal endometriosis Clinical presentation: Patients with pelvic endometriosis
are reported to have gastrointestinal tract involvement in 15% to 37% of cases. Most patients have their
gastrointestinal endometriosis discovered in the reproductive years, and have known endometriosis of
other sites, but post-menopausal women and patients without known endometriosis elsewhere are also
affected. The most common gastrointestinal sites are those in or closest to the pelvis, including
rectosigmoid colon, cecum, appendix and distal ileum. Neither stomach nor esophagus is a site that has
been reported to harbor endometriosis. It is not known how many patients with gastrointestinal tract
endometriosis are asymptomatic, but there may be many. For those who are symptomatic, the clinical
presentation depends largely on the site of involvement. Patients with rectosigmoid endometriosis
present with altered bowel habits such as decreased stool caliber, diarrhea, or bloody stools. Small
intestinal involvement may cause abdominal pain, bloating, or symptoms of partial obstruction.
Appendiceal endometriosis may cause pain, obstruction, or intussusception. Endometrial lesions at any
site may result in a mass. Thus, the clinical considerations for the causes of the patients' symptoms
include diverticulitis, appendicitis, Crohn's disease, ischemia, irritable bowel syndrome, or neoplasm.
Rarely, pregnant patients with colonic endometriosis have presented with bowel perforation and
peritonitis. Gross findings: When endometriosis affects the intestine, it usually does so in one
location, although multifocal involvement can occur. Ill-defined mass-like lesions, some containing
cysts, with foci of hemorrhage, rarely larger than 5 cm, may be present in the bowel wall, usually in the
muscularis propria or subserosa. Serosal disease may result in adhesions. The bowel wall may be
thickened in the area of involvement, and the lumen may be narrowed. Extension to submucosa and even
into the mucosa occurs in a minority of cases, and in these cases the mucosa may be indurated, elevated,
and/or ulcerated. Rarely, mucosal endometriosis may be polypoid. Indurated, polypoid, and ulcerated
mucosal disease mimics carcinoma, as may endometriosis causing a mural mass detected by endoscopy or
medical imaging. Histologic findings: The histologic diagnosis of gastrointestinal involvement by
endometriosis depends upon the finding of endometrial glands and stroma, although some examples,
especially in small biopsies, may have only one component. In resection specimens the diagnosis is
generally straightforward. Associated findings include muscular and nerve hypertrophy, and fibrosis.
However, problems may arise in endoscopic biopsies from areas of endometriosis. First, the endometrial
glands or stroma may be interpreted as neoplastic. Endometrial glands have cells with nuclei that are
larger and more hyperchromatic than normal colonic epithelium, and are devoid of mucin, thus resembling
an adenoma or even a carcinoma. The finding of ciliated cells in the endometrial glands and the
recognition of endometrial stroma establish the correct diagnosis. Immunohistochemical positivity of the
stroma with antibodies to CD 10 may be helpful. The second and more common diagnostic difficulty in
endoscopic biopsies from ares of endometriosis results from inflammatory and other changes in the mucosa
related presumably to the mass effect of the endometriotic foci. These include lamina propria and crypt
inflammation with distortion that resemble inflammatory bowel disease, prolapse changes that resemble
solitary rectal ulcer syndrome, and ischemic-type changes. Unusual presentations Appendiceal
endometriosis is present in about 3% of patients with endometriosis. In addition to the expected
symptoms of pelvic pain, and the occasional clinical presentation resembling appendicitis, patients with
appendiceal endometriosis may present in two other unique ways. Appendiceal intussusception has been
reported due to endometriosis, due to its mass effect. When endometriosis affects the proximal
appendiceal wall, it may cause obstruction of the appendiceal lumen and lead to non-neoplastic
mucin-filled cystic dilatation of the distal portion (so-called simple mucocele). There are a number of
case reports of intestinal or appendiceal rupture due to endometriosis occurring in pregnancy. This rare
event occurs in patients who have endometriosis affecting all layers of the bowel wall. Presumably,
decidualization in early pregnancy is followed by decidual necrosis or regression, weakening the bowel
wall in late pregnancy when these perforations occurred, Endometriosis-associated intestinal tumors
(EAIT) Clinical presentation: It is estimated that about 1% of women who have endometriosis will develop
an endometriosis-associated tumor. Most of these will be in the ovary, and most of the rest will be in
the pelvis. However, the next most common site is the gastrointestinal tract. EAIT occur, not
surprisingly, where endometriosis is most common, the rectosigmoid colon (77%), followed by the cecum and
distal ileum. Patients present with abdominal or pelvic pain and/or mass, bleeding, or signs of bowel
obstruction. Sometimes an EAIT is an incidental finding on the serosa during exploratory laparotomy for
an unrelated reason. EAIT are often associated with long term unopposed estrogen treatment, either after
another gynecologic operation or postmenopausal. Most EAIT occur in women in their mid 30s their mid
50s, about 10 years earlier that the incidence of colorectal carcinoma. They frequently, but not always,
give a history of endometriosis. Gross findings: 70% of EAIT involve the outer bowel wall, including
the perirectal soft tissue, or are transmural with a predominant growth in the outer part of the bowel
wall. 30% are intramural. The mucosa is free of tumor is about 30%; when the mucosa is involved it may
be flat and infiltrated by tumor or may result in a polypoid intraluminal growth simulating a colorectal
carcinoma. Transmural tumors tend to have a dumbbell configuration, with bulky tumor in the subserosa
and submucosa/mucosa connected by a narrower area of tumor extending through the muscularis propria.
Histologic features and differential diagnosis: Most EAIT are well- to moderately-differentiated
endometrioid adenocarcinomas. Other tumor types are also described, and include adenosquamous, squamous,
and clear cell carcinomas, carcinosarcomas, endometrial stromal sarcomas, germ cell tumors, and others.
Differentiated endometrioid carcinoma occurring in a colorectal biopsy may be confused with colorectal
carcinoma. Clues to the correct diagnosis in a resection specimen are the predominance of tumor in the
wall or serosa, and the presence of associated endometriosis. In limited material, such as a
colonoscopic biopsy, neither of these two features may be known. Endometrioid carcinomas will form
tubules with "clean" luminal contents (no dirty necrosis), and lined by cells that have no cytoplasmic
mucin. They will have an Alcian blue-positive glycocalyx. No colorectal adenoma will be present.
Endometrioid carcinomas often have foci of squamous differentiation; whereas, this is uncommon in
colorectal carcinoma. Immunohistochemical stains may be helpful in that most endometrioid carcinomas are
CK 7 + and CK 20 -, while most colorectal carcinomas will be CK 7 – and CK 20 +. Remember, however, that
colorectal carcinomas that are poorly differentiated and/or microsatellite unstable may lose CK 20
positivity, and rectal carcinomas may sometime be CK 7 positive, so this staining pattern will not be
definitive in all cases. Endometrioid carcinomas are generally immunohistochemically positive for
CA-125, and colorectal carcinomas for CEA, so these two antibodies may also lend support to a diagnosis.
Once the diagnosis of endometrioid carcinoma or another type of gynecologic tumor is established, it will
be necessary to determine whether it is arising in endometriosis (an EAIT) or is involving the intestinal
tract secondarily. The conclusion that the tumor is an EAIT requires the presence of endometriosis,
preferably in continuity with or very close to the tumor. This is not always possible to demonstrate if
the tumor is large and has obscured the endometriosis. The presence of endometriosis elsewhere in the
gastrointestinal tract constitutes presumptive evidence in that case. Another helpful, if not common,
feature is the finding of a transition from simple endometriosis to hyperplastic/premalignant lesion
Patients with low grade endometrioid carcinomas arising in endometriosis in the gastrointestinal tract
usually have a good prognosis. The carcinoma tends to be localized to the site. The 5-year survival for
those with hyperestrogenism-associated endometrioid EAIT is 83%. Those with high grade stromal sarcomas,
carcinosarcoma, germ cell tumors or other high grade cancers, however, generally have poor outcomes.
Adenocarcinoma, especially those in the rectosigmoid colon, that arise in relatively
young women and have an appearance different from colorectal carcinoma should be evaluated to determine
whether they might be endometriosis-associated intestinal tumors. Immunohistochemical stains that may be
useful include CK 7, CK 20, CA-125, and CEA. A careful search for associated endometriosis is important
to establishing this diagnosis.
- Driman DK, et al. Mucocele of the appendix secondary to endometriosis. Report of two cases, one with localized pseudomyxoma. Am J Clin Pathol 2000;113:860-864
- Jones KD, et al. Endometrial adenocarcinoma arising in endometriosis of the rectsigmoid colon. Gynecol Oncology 2002;86:220-222
- Liang H-H, et al. Endometriosis-induced appendiceal intussusception. Am J Surg 2009 ;197 :e66-e68
- Slavin RE, Krum R, Van Dinh T. Endometriosis-associated intestinal tumors: a clinical and pathological study of 6 cases with a review of the literature. Hum Pathol 2000;31:456-463
- Yantiss RK, Clement PB, Young RH. Endometriosis of the intestinal tract. Am J Surg Pathol 2001;25:445-454
- Yantiss RK, Clement PB, Young RH. Neoplastic and pre-neoplastic changes in gastrointestinal endometriosis. Am J Surg Pathol 2000;24:313-524