Patients with inflammatory bowel disease may develop dysplasia in the cryptal epithelium, polypoid neoplasias, and nonpolypoid (flat) adenomas, lesions at risk to proceed to colorectal carcinoma. The onset of invasion in nonpolypoid adenomas may occur without changes in the shape or the size of the lesion. In experimental animals, some colonotropic carcinogens induce polypoid and nonpolypoid neoplasias and others induce polypoid neoplasias exclusively. Some of the biologic attributes of nonpolypoid adenomas in humans can be demonstrated in laboratory animals.
Key points
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Patients with inflammatory bowel disease may develop dysplasia in the cryptal epithelium, polypoid neoplasias, and nonpolypoid (flat) adenomas, lesions at risk to proceed to colorectal carcinoma.
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The onset of invasion in nonpolypoid adenomas may occur without changes in the shape or the size of the lesion.
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In experimental animals, some colonotropic carcinogens induce polypoid and nonpolypoid neoplasias and others induce polypoid neoplasias exclusively.
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Some of the biologic attributes of nonpolypoid adenomas in humans can be demonstrated in laboratory animals.
Introduction
Patients with inflammatory bowel disease (IBD) (an acronym that includes both ulcerative colitis [UC] and Crohn’s colitis [CC]) are at risk to develop dysplasia in the cryptal epithelium, polypoid and nonpolypoid adenomatous growths, and IBD-independent sporadic polypoid and nonpolypoid adenomas. All these lesions may proceed to colorectal carcinoma (CRC).
Introduction
Patients with inflammatory bowel disease (IBD) (an acronym that includes both ulcerative colitis [UC] and Crohn’s colitis [CC]) are at risk to develop dysplasia in the cryptal epithelium, polypoid and nonpolypoid adenomatous growths, and IBD-independent sporadic polypoid and nonpolypoid adenomas. All these lesions may proceed to colorectal carcinoma (CRC).
The histogenesis of CRC in IBD
Information concerning the histogenesis of CRC in IBD is derived from studies done in patients with UC. At present, 7 alternative pathways have been proposed: (1) from UC-dependent histologically detected dysplastic gland, referred to as dysplasia in flat mucosa in the literature; (2) from UC-dependent adenomatoid neoplastic growths ; (3) from UC-independent, age-dependent, sporadic adenomas ; (4) from gut-associated lymphoid tissue (GALT) ; (5) from nonpolypoid (UC-dependent and UC-independent) adenomas ; (6) from UC-dependent discrete villous dysplastic changes ; or (7) from apparently nondysplastic mucosa ( de novo carcinomas).
Histologically detected dysplasias in IBD
Histologically detected dysplasia in IBD may be found in colorectal glands exhibiting parallel tubules or bifurcations; in those instances, the dysplasia is initially found in the basal aspect of the crypts and progresses gradually toward the superficial aspect of the crypts (base-to-surface progression). In mucosa with advanced atrophy without crypts, dysplasia may be found in the superficial epithelium.
A recent search in the literature revealed that most of the publications on flat adenomas in IBD concerned dysplasia in flat mucosa, flat dysplasia, flat dysplastic tissue, or flat low-grade dysplasia. These terms should not be confused with nonpolypoid adenomas, as these adenomas are also flat dysplasias albeit showing a circumscribed clustering of abnormal crypts lined with dysplastic cells. It is crucial to distinguish between these 2 different histologic alterations, as cases of nonpolypoid adenomas are even today being referred to in the literature as flat adenomas. In this article the term “flat” is reserved for nonpolypoid adenomas.
An early illustration of nonpolypoid adenomas
In 1975, Mr Bussey from the St. Mark’s Hospital, London, UK published a monograph on colectomy specimens from patients with familial adenomatous polyposis (FAP). The caption in one of the illustrations reads as follows: “a lesion consisting of adenomatous tubules, which have not produced any thickening of the mucosa”. This appears to be the first description of nonpolypoid (flat) colonic adenomas in FAP.
The Western-Japanese controversy
Hurlstone postulated that the variability in histologic diagnostic criteria used by Western and Japanese pathologists have made comparative studies difficult. To by-pass that difficulty, one of the authors (C.A.R.) sought in 1995, histologic guidance and training on sporadic flat colonic adenomas by Dr Tetsuichiro Muto, Tokyo University, Japan. Subsequently, one of the authors reviewed all sporadic flat adenomas filed at Muto’s Department and later examined all sporadic flat adenomas filed at other hospitals in the Tokyo area. A total of 1014 flat colorectal lesions were reviewed in Tokyo, which were compared with 600 lesions in Sweden. Those studies revealed that sporadic flat (nonpolypoid) adenomas were more advanced (in terms of high-grade dysplasia [HGD]) and more aggressive (in terms of intramucosal and submucosal invasion) in Japan than in Sweden. Although the causes for the difference in those disparate geographic regions remains debatable, the findings helped us to understand some of the unclear points and discussions that appeared in the literature on this subject.
Nonpolypoid adenomatous lesions in IBD detected at endoscopy
In 1996, Jaramillo and colleagues detected at endoscopy 104 small polyps in 38 of 85 Swedish patients with UC: 74% were endoscopically flat, 23% polypoid (20% sessile and 3% pedunculated), and in 3% the endoscopic appearance was not recorded. The pathologic examination revealed nonpolypoid (flat) adenomas in 14%, tubular or villous structures with dysplastic cells in the lower part of the crypts in 5%, nonpolypoid hyperplastic polyps in 34%, mucosa with inflammation in 7%, and mucosa in remission in 40%.
Synchronous polypoid and nonpolypoid adenomatous lesions in IBD in colectomy specimens with carcinoma
Data show that nonpolypoid adenomatous lesions are commonly found in IBD colectomy specimens with carcinoma. One of the authors has previously reviewed 96 colectomy specimens with UC and carcinoma filed at the Department of Pathology, St Mark’s Hospital, London, UK ( Fig. 1 ). A total of 3049 sections were available in the 96 colectomy specimens; the mean number of sections/colectomy studied was 31.8 (range 7–97 sections). In addition to carcinomas, several circumscribed adenomatous lesions were found elsewhere in the colon or rectum; they will be referred to as synchronous adenomatous lesions (SALs). Using a low-power examination (4x), the histologic profile of these circumscribed lesions was classified into polypoid and nonpolypoid, both in areas with UC and in areas without inflammation. A total of 104 SALs were found in the 96 colectomies: 73 SALs, which occurred in areas with inflammation, and 31 SALs, in areas without inflammation.
Polypoid SALs were recorded in 35% (n = 34) of the 96 colectomies. Polypoid SALs in areas with inflammation exhibited irregular dysplastic glands with a jigsaw pattern having irregular bands in the interspersed lamina propria. The mucosa adjacent to these adenomatous lesions showed irregular, dysplastic crypts. Polypoid SALs were found in 47% (n = 34) of the 73 SALs occurring in areas with inflammation.
Polypoid SALs in areas without inflammation had a more regular glandular pattern and the interspersed lamina propria was more regularly distributed, and the adjacent mucosa showed no dysplasia. These polypoid lesions were regarded as sporadic (polypoid) adenomas. Polypoid sporadic adenomas were found in 19% (n = 18) of the 96 colectomies and 58% (n = 18) of the 31 SALs in areas without inflammation.
Nonpolypoid SALs were slightly elevated ( en plateau ), had discrete villous changes, or were flat-flat. These lesions correspond to type 0 of The Paris endoscopic classification of superficial neoplastic lesions. Nonpolypoid SALs were found in 41% (n = 39) of the 96 colectomies: 53% (n = 39) in the 73 SALs found in areas with inflammation and sporadic adenomas in 42% (n = 13) of the 31 SALs present in areas without inflammation.
Invasive carcinomas were detected in 52% (n = 38) of the 73 SALs found in areas with inflammation and sporadic adenomas in 32% (n = 10) of the 31 SALs recorded in areas without inflammations.
Confirmatory data have been recently collected. In a more recent survey done in Florence, Italy, out of the 39 colectomy specimens with IBD and carcinoma, polypoid SALs were found in 21% (n = 4) of the 19 specimens with UC and in 30% (n = 6) of the 20 colectomies with CC. Nonpolypoid SALs were recorded in 11% (n = 2) of the 19 specimens with UC and in 5% (n = 1) of the 20 colectomies with CC (Rubio, Nesi, in preparation).
Histologic classification of nonpolypoid (flat) lesions removed at endoscopy in patients without IBD
Because of the relative scarce number of cases of nonpolypoid lesions in IBD reported in the literature, much of the available information on their histologic classification is based on endoscopically removed flat lesions in patients without IBD. The cause of the flat lesions varies greatly. Endoscopically removed flat lesions may disclose nonpolypoid hyperplastic polyps, nonpolypoid serrated polyps, nonpolypoid adenomas (tubular, villous, or serrated), or invasive carcinomas. In this regards, prior observations showed that invasive carcinomas can arise de novo – without surrounding adenomatous tissue.
Nonpolypoid hyperplastic polyps ( Fig. 2 ) exhibit a group of tall, straight crypts without serrations, not surpassing twice the thickness of the surrounding mucosa. Nonpolypoid serrated polyps are classified into type 1 ( Fig. 3 ), having epithelial serrations in the superficial aspect of the crypts, and type 2, displaying similar glands as those described for sessile serrated polyps ( Fig. 4 ). However, because type 2 is usually an intramucosal lesion, the term sessile serrated polyp cannot be applied.
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