Mimics in Gastrointestinal Pathology
Case 1 -
Colitis Cystica Profunda and Eroded Polypoid Hyperplasia Associated with Mucosal Prolapse
Alyssa Krasinskas, Jeffrey Goldsmith and Susan Abraham
This 45-year-old woman underwent excision of a villiform-appearing tumor in the rectum along with
excision of internal and external hemorrhoids.
Three main abnormalities are seen in the specimen. First, the submucosa is expanded by multiple mucin
pools. These are acellular but in many areas are lined by non-dysplastic rectal epithelium and lamina
propria. Second, the overlying rectal mucosa contains heaped-up, polypoid tissue with superficial
erosions. The colonic crypts in the polyp have a serrated appearance, but the polyp is larger than a
typical hyperplastic polyp and the intervening fibrosis of the lamina propria and overlying
ischemic-appearing erosions are also both unusual features of hyperplastic polyps. The third histologic
abnormality is seen in the rectal mucosa away from the polyp, where the lamina propria is fibrotic and
- Colitis cystica profounda vs. invasive adenocarcinoma
- Eroded polypoid hyperplasia vs. tubulovillous adenoma, serrated adenoma, or hyperplastic polyp
- Mucosal prolapse changes vs. idiopathic IBD
Colitis cystica profunda: Colitis cystica profunda is a benign
condition characterized by cystic dilatation and downgrowth of mature colonic glands through the
muscularis mucosa and into the submucosa or deeper layers of the bowel wall. The term "colitis cystica
polyposa" was first used by Virchow in 1863 to describe a case in which multiple polypoid lesions were
produced by submucosal cysts . The term "colitis cystica profunda" subsequently came into use in 1957
; most affected patients have both submucosal cysts and associated polypoid lesions. Similar lesions
are found in the stomach ("gastritis cystica profunda"), where they are most frequently associated with
gastroenterostomy sites ,
and in the small bowel ("enteritis cystica profunda") where they are often
associated with Peutz-Jeghers syndrome .
Rarely, colitis cystica profunda occurs as an isolated lesion in an otherwise apparently normal colon
However, most cases of colitis cystica profunda occur in association with some form of colonic
abnormality. The most common association is with solitary rectal ulcer syndrome
in which case
the lesions are rectosigmoid in their location. Distal lesions (sometimes termed "proctitis cystica
profunda") have also been reported in paraplegics
, in a patient with a history of self-inflicted
rectal trauma ,
and in patients with post-irradiation colonic strictures
diffuse or pancolonic lesions of colitis cystica profunda occur in patients with inflammatory bowel
disease – including ulcerative colitis, Crohn's disease, and unclassified forms  – or infectious
A predominant pathogenic mechanism for colitis cystica profunda, especially in distal colorectal
lesions, is probably ischemia produced by mucosal trauma . In the case of solitary rectal ulcer
syndrome, mucosal prolapse can result in ischemia and ulceration by virtue of traction exerted on the
local vasculature . In cases of colitis cystica profunda in patients with infectious or idiopathic
inflammatory bowel diseases, inflammatory mucosal ulcerations may allow for the downgrowth of benign
regenerative glands into the submucosa, which subsequently become entrapped during re-epithelialization
of the ulcers.
Guest and Reznick  reviewed the clinical features of 144 cases of colitis cystica profunda reported
in the literature before 1989. The reported age range is quite wide, from 4 to 76 years (median, 30
years), and males and females are approximately equally affected. The most common presenting symptoms
include blood in the stool (68%), mucoid stool (43%), diarrhea (27%), tenesmus (13%), and abdominal
discomfort (12%); rarely, it can present as intestinal obstruction
. Endoscopically, colitis cystica
profunda can be a focal, segmental, or diffuse abnormality. Focal or segmental lesions can mimic
mucinous adenocarcinoma. Transrectal ultrasound and other imaging modalities can aid in the distinction
between malignancy and colitis cystica profunda by demonstrating multiple cysts limited to the submucosa
and lack of lymph node involvement .
Gross features of colitis cystica profunda include a frequently polypoid appearance and enlargement of
the submucosa, which can appear mucoid. Histologically, the condition is characterized by the presence
of multiple cystically dilated, mucin-filled crypts in the submucosa, and occasionally in the muscularis
propria or serosa. The stroma surrounding misplaced crypts usually consists of lamina propria, which is
helpful in distinguishing it from adenocarcinoma, which often has a desmoplastic stroma. Furthermore,
misplaced glands in colitis cystica profunda often grow in a lobular configuration, without jagged
borders or unusual irregularly shaped glandular profiles more typical of adenocarcinoma. Misplaced
crypts show either normal or reactive appearing colonic epithelium. A mild degree of mucin depletion,
pseudostratification and increased mitotic activity may be present. However, loss of nuclear polarity,
increased N/C ratio and atypical mitosis should alert one to the possibility of adenocarcinoma. The
presence of lamina propria surrounding misplaced glands, and the lack of "dysplastic" appearing
epithelium, are key features that help distinguish colitis cystica profunda from invasive adenocarcinoma
Rectal prolapse/solitary rectal ulcer syndrome (SRUS): In complete
prolapse, all layers of the rectum visibly protrude through the anal orifice. In occult prolapse, there
is internal intussusception of the rectal mucosa without visible protrusion form the anus. Rectal
prolapse in adults is 3 – 10 times more common among women . Common clinical associations include
straining at defecation and poor tone of the pelvic musculature. Complete rectal prolapse usually
requires surgical correction in order to avoid further damage to the anal sphincter and pelvic floor
muscles. Commonly, anterior sling rectopexy is performed whereby the the rectum is mobilized to the tip
of the coccyx and is attached to the presacral fascia by means of a nonabsorbable plastic mesh .
SRUS is most common among women in their third and fourth decades and can be associated with either
overt or occult prolapse. Symptoms (typically chronic) include constipation, mucorrhea, bleeding, or
tenesmus. Endoscopically, ulcers in SRUS are most commonly single, small, and shallow; however,
~1/3 of patients lack an ulcer, and occasionally the ulcers are multiple or large. The ulcers in
~85% of patients are located in the anterior rectum, often in the distal aspect. Frequently, there
is also nodularity of the surrounding rectal mucosa. Histologically, the ulcers themselves have a
nonspecific appearance, but biopsies from non-ulcerated mucosa show characteristic fibromuscular
hyperplasia in the lamina propria. Strands of smooth muscle extend upward from the muscularis mucosa,
surrounding crypts and imparting an angulated contour to the crypts ("diamond-shaped crypts").
The etiology of ulceration in SRUS is hypothesized to relate to excessive straining at defecation:
the anterior rectal mucosa is forced downward against the pelvic floor, which causes trauma and focal
ischemia. Management is usually conservative – education to avoid straining at defecation, a high fiber
diet, and bulk laxatives – and leads to remission of symptoms in a majority of cases
options include local steroid applications or 5-ASA products. These do not treat the underlying
defecatory disorder but can promote macroscopic healing . Some patients undergo surgical resection
because of obstructing lesions , confusion with carcinoma, or severe symptoms.
Eroded polypoid hyperplasia: The mucosa in rectal prolapse/SRUS often
assumes a hyperplastic or villiform appearance. These polyps share characteristics of mucosal
prolapse-induced polyps throughout the GI tract. In the rectum, they are variably termed "polypoid
prolapsing mucosal folds ," "prolapse-induced inflammatory polyps
," or "eroded polypoid
hyperplasia ." Mucosal prolapse polyps in the anal-transitional zone are termed "inflammatory
cloacogenic polyps," in the colon proper as "inflammatory cap polyps," in the sigmoid as "diverticular
disease-associated polyps," and in the stomach as "gastric antral vascular ectasia" or "watermelon
stomach." The pathogenesis is related to traction, distortion and twisting of mucosa as a result of
peristalsis-induced trauma which leads to torsion of blood vessels and tissue damage, localized ischemia
and repair in the form of lamina propria fibrosis. The classic histologic features of prolapse-induced
polyps include: 1) Fibromuscular hyperplasia in the lamina propria, 2) Thickening, splaying, and
vertical extension of the muscularis mucosa into the lamina propria, 3) Crypt abnormalities (elongation,
hyperplasia, architectural distortion, and serration) and 4) Variable degrees of stromal and epithelial
Polyps in SRUS can at times mimic adenomas, hyperplastic polyps, or serrated adenomas. Gopal et al described a 36-year-old woman with many (50 – 60) small rectal polyps that
were clinically concerning for either rectal carpeting by a villous adenoma or juvenile polyposis .
Recently, Ball et al studied the histology in 26 patients with SRUS .
Ten (38%) cases had features mimicking serrated adenoma including hypermucinous epithelium, exaggerated
serration in the lower portion of crypts, branching of crypts, and horizontal extension of crypt bases
along muscularis mucosa. None were truly dysplastic. Unlike serrated adenomas, the mucosa in SRUS also
showed areas of ischemic change including erosion and fibrosis. Interestingly, in 2 of 10 (20%) cases
that mimicked serrated adenoma the authors found focal superficial loss of the hMLH1 DNA mismatch repair
protein. They hypothesized that this might indicate a propensity for neoplastic progression in some
cases of SRUS as a result of repeated trauma and repair. However, in practice it is much more important
to avoid overcalling dysplasia or neoplasia in SRUS than to be concerned about pre-neoplastic molecular
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