Pathology Outlines

Colon

Inflammatory bowel disease

Dysplasia

Authors: Kenrry Chiu, M.D., C.M., David F. Schaeffer, M.D.

Editorial Board Member: Raul S. Gonzalez, M.D.

Editor-in-Chief: Debra L. Zynger, M.D.

Topic Completed: 7 February 2019

Minor changes: 17 March 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: Colon[TI] dysplasia[TI]

Page views in 2021 to date: 860

Table of Contents

Cite this page: Chiu K, Schaeffer DF. Dysplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonIBDdysplasia.html. Accessed April 18th, 2021.

Definition / general

Dysplasia of colonic epithelium identified in setting of colonic inflammatory bowel disease (IBD), usually in colonic biopsies from surveillance colonoscopies
Precursor of invasive carcinoma
Can be endoscopically visible or invisible
Aim of surveillance is to reduce morbidity and mortality from colorectal carcinoma by identifying dysplasia (or early invasive carcinoma)

Essential features

Precursor of invasive carcinoma in patients with inflammatory bowel disease
Dysplasia status should be reported for biopsies from surveillance colonoscopies of patients with inflammatory bowel disease:
- Negative for dysplasia
- Indefinite for dysplasia
- Low grade dysplasia
- High grade dysplasia
Management of dysplasia identified on colonoscopies is dependent on endoscopic appearance (visible [polypoid or nonpolypoid] or invisible) and resectability

Terminology

Previously used term dysplasia associated lesion or mass (DALM) and related terms (e.g. adenoma-like or nonadenoma-like DALM) should be avoided due to the historical connotation of a high risk of malignancy (Mod Pathol 2018;31:1180)
Endoscopic appearance based on standardized terminology as described by the Surveillance for Colorectal Endoscopic Neoplasia Detection and Management in Inflammatory Bowel Disease Patients: International Consensus Recommendations (SCENIC) is recommended (Gastroenterology 2015;148:639)

ICD coding

ICD-10: D12.0 - Benign neoplasm of cecum
ICD-10: D12.2 - Benign neoplasm of ascending colon
ICD-10: D12.3 - Benign neoplasm of transverse colon
ICD-10: D12.4 - Benign neoplasm of descending colon
ICD-10: D12.5 - Benign neoplasm of sigmoid colon
ICD-10: D12.6 - Benign neoplasm of colon, unspecified
ICD-10: D12.7 - Benign neoplasm of rectosigmoid junction
ICD-10: D12.8 - Benign neoplasm of rectum

Sites

Colon and rectum in areas of colitis

Pathophysiology

Cytotoxic effect of inflammation leads to repeated cycles of epithelial wounding and repair
Postulated selective pressure for mutant cells that can survive the inflammatory insult and rapidly repopulate the damaged mucosa
Epigenetic and genetic changes accumulate in morphologically nondysplastic colonic mucosa long before development of neoplasia
TP53 mutations and aneuploidy are early events in colitis associated neoplasia and have been identified in nondysplastic colonic mucosa (Carcinogenesis 2018;39:11, Nat Rev Gastroenterol Hepatol 2017;14:218, Gastroenterology 2009;136:542)
Accumulation of additional mutations, chromosomal abnormalities and epigenetic changes leads to dysplasia and invasive carcinoma
In comparison, sporadic colorectal neoplasia tends to have APC mutations early and TP53 mutations later in tumorigenesis

Etiology

Severe, extensive and longstanding chronic inflammation in the setting of ulcerative colitis is associated with an increased risk of colorectal neoplasia (Nat Rev Gastroenterol Hepatol 2017;14:218)
Extensive colitis related to Crohn's disease is associated with an increased risk of dysplasia and neoplasia (Gastroenterology 2001;120:820)

Clinical features

Surveillance colonoscopies typically start at 8 years after onset of inflammatory bowel disease (IBD) (Gastrointest Endosc 2015;81:1101, J Crohns Colitis 2017;11:649)
Chromoendoscopy, the application of dye to help visualize lesions, increases the sensitivity in detecting dysplasia
- Advocated as the preferred means of endoscopy, if available (Gastrointest Endosc 2015;81:1101, J Crohns Colitis 2017;11:649, Gastroenterology 2015;148:639)
Most dysplasia identified in surveillance colonoscopies are endoscopically visible but some dysplasia is endoscopically invisible, i.e. indistinguishable from macroscopically unremarkable colonic mucosa (Gastrointest Endosc 2007;65:998)
Endoscopic appearance of dysplasia based on descriptors from the Paris classification recommended by the SCENIC panel and other major societies (Gastrointest Endosc 2015;81:1101, J Crohns Colitis 2017;11:649, Gastroenterology 2015;148:639, Gastrointest Endosc 2003;58:S3):
- Visible dysplasia
  - Polypoid: pedunculated or sessile
  - Nonpolypoid: superficial elevated, flat or depressed
- Invisible dysplasia
Visible lesions are endoscopically resected or biopsied
- Biopsies adjacent to endoscopically resected lesion may also be taken to ensure complete removal
Random biopsies may be taken to detect endoscopically invisible dysplasia

Diagnosis

Detected with colonoscopies, typically as part of surveillance
- Chromoendoscopy increases sensitivity of detection of dysplasia
Targeted biopsies, endoscopic resections or polypectomies of visible lesions
Random biopsies may be taken to detect endoscopically invisible dysplasia

Prognostic factors

Polypoid dysplasia treated by endoscopic polypectomy:
- Low rate of invasive carcinoma on followup (Clin Gastroenterol Hepatol 2004;2:534, Gastroenterology 1999;117:1295, Clin Gastroenterol Hepatol 2014;12:756)
- Increased rate of dysplasia on followup (Clin Gastroenterol Hepatol 2014;12:756)
Nonpolypoid dysplasia:
- In general, associated with a high rate of metachronous and synchronous carcinoma (J Crohns Colitis 2017;11:649, Am J Gastroenterol 2015;110:1461)
- Subset can be endoscopically resected:
  - Two studies including such lesions with a median followup of 28 and 21 months showed no local recurrence (Inflamm Bowel Dis 2018;24:1196, Gastrointest Endosc 2018;87:1079)
Invisible high grade dysplasia:
- High risk of synchronous and metachronous invasive carcinoma (Am J Gastroenterol 2015;110:1022)
Invisible low grade dysplasia:
- Prognosis is controversial
- Some studies report a low rate of progression to carcinoma while others suggest a high rate (Clin Gastroenterol Hepatol 2017;15:665, Gastroenterology 2003;125:1311)
Indefinite for dysplasia:
- Subset will show bonafide dysplasia on followup (Inflamm Bowel Dis 2010;16:1352)

Case reports

19 year old woman with 6 year history of ulcerative colitis with invasive carcinoma and high grade dysplasia (BMJ Case Rep 2013 Jul 2;2013)
42 year old man with polypoid dysplasia in Crohn's colitis (Can J Gastroenterol 2009;23:477)
45 year old man with ileorectal anastomosis, low grade dysplasia and invasive adenocarcinoma (SAGE Open Med Case Rep 2017;5:2050313X17692902)
76 year old woman with longstanding ulcerative colitis with low and high grade dysplasia (J Gastroenterol Hepatol 2016;31:1797)
Dysplasia in 5 patients with ulcerative colitis (Intern Med 2016;55:911)

Treatment

Depends on endoscopic appearance and resectability
Polypoid dysplasia:
- Endoscopic polypectomy and followup with continued surveillance
Nonpolypoid dysplasia:
- Endoscopically resectable:
  - Endoscopic mucosal resection or submucosal dissection and followup with continued surveillance
- Not amenable to endoscopic resection:
  - Cannot exclude underlying invasive carcinoma
  - Should be surgically resected
Invisible dysplasia:
- Refer for chromoendoscopy, if feasible and not already done, as this may help visualize endoscopically the dysplastic lesion (Gastroenterology 2015;148:639)
- Invisible high grade dysplasia:
  - Resection, due to high risk of invasive carcinoma
- Invisible low grade dysplasia:
  - Continued surveillance or colectomy; multifocal disease may be indication for surgery (Gastrointest Endosc 2015;81:1101, J Crohns Colitis 2017;11:649, Gastroenterology 2003;125:1311)
Indefinite for dysplasia:
- Repeat endoscopy posttreatment to reduce inflammatory background (Gastrointest Endosc 2015;81:1101)

Clinical images

Images hosted on other servers:

Polypoid dysplasia identified on chromoendoscopy

Nonpolypoid dysplasia

Gross description

Can be macroscopically (endoscopically) unapparent
Can be polypoid (pedunculated or sessile) or nonpolypoid (superficially elevated, flat or depressed)

Gross images

Contributed by Adela Cimic, M.D.

Descending colon lesion

Images hosted on other servers:

Dysplasia in a Crohn's colitis pseudopolyp

Microscopic (histologic) description

Correlate with endoscopic appearance, as this influences management
- Visible dysplasia (polypoid or nonpolypoid)
- Invisible dysplasia
Low grade dysplasia:
- Preserved nuclear polarity
- Pseudostratified, crowded, elongated and hyperchromatic nuclei
- Lack of surface maturation, i.e. abnormalities persist to surface
High grade dysplasia:
- May show complex architecture, such as cribriform glands
- Loss of nuclear polarity
- Nuclear pleomorphism, vesicular nuclei and prominent nucleoli
Indefinite for dysplasia:
- Reserved for cases when distinction between dysplasia and reactive epithelial atypia cannot be made
- Mucosal erosion or ulceration (precluding assessment of surface maturation) or prominent inflammation may be sources of difficulty
Features distinguishing IBD associated polypoid dysplasia and sporadic adenomas have been described but are not reliable and have no therapeutic implications
- Include lamina propria inflammation, mixture of benign and dysplastic glands at the surface and dysplasia in stalk of polyp (Hum Pathol 1983;14:931, Am J Surg Pathol 1998;22:275)
- Distinction is also not clinically significant as endoscopic polypectomy suffices either way

Microscopic (histologic) images

Contributed by Kenrry Chiu, M.D., C.M.

Low grade dysplasia

High grade dysplasia

Contributed by Elaine Alt, M.D.

Low grade dysplasia

Low grade dysplasia - pancolitis

Virtual slides

Images hosted on other servers:

High grade dysplasia in ulcerative colitis

Low grade dysplasia in ulcerative colitis

Cytology images

Images hosted on other servers:

High grade dysplasia

Positive stains

Various immunohistochemical stains have been evaluated to help distinguish dysplasia from nondysplastic epithelium but lack of sensitivity and specificity and limited data limit their use
p53 and Ki67: increased nuclear staining extending to the surface has been suggested to favor dysplasia over regenerative atypia but lack of specificity limits their diagnostic use (Arch Pathol Lab Med 2013;137:338, Semin Diagn Pathol 2015;32:334)
CK7: positive staining may be a marker of dysplasia but sensitivity and specificity are limited (Mod Pathol 2014;27:303)
AMACR: strong cytoplasmic staining reported to favor dysplasia (Semin Diagn Pathol 2015;32:334, Hum Pathol 2009;40:166)

Molecular / cytogenetics description

TP53 mutations and aneuploidy occur early in IBD associated neoplasia (Nat Rev Gastroenterol Hepatol 2017;14:218)

Molecular / cytogenetics images

Images hosted on other servers:

Model of carcinogenesis in ulcerative colitis

Sample pathology report

Presence or absence of dysplasia should be reported for biopsies from surveillance colonoscopies as follows (Hum Pathol 1983;14:931, Gut 2000;47:251):
- Negative for dysplasia
- Indefinite for dysplasia
- Low grade dysplasia
- High grade dysplasia
Polypoid lesion within colitic mucosa, endoscopically resected:
- Colon (sigmoid), polypectomy:
  - Polypoid low grade dysplasia
Nonpolypoid lesion, endoscopically resected piecemeal:
- Colon (ascending), biopsy:
  - High grade dysplasia
  - Completeness of excision cannot be determined (specimen fragmented)
Invisible dysplasia identified on random biopsy:
- Rectum, biopsy:
  - Low grade dysplasia
Note: a comment noting that endoscopically resectable lesions that are completely removed can be managed with continued surveillance rather than colectomy may be helpful

Differential diagnosis

Reactive epithelial atypia:
- May show mild nuclear stratification and crowding, nuclear enlargement and hyperchromasia and nucleoli
- Surface maturation is present
- Nuclear polarity is preserved
- Inflammatory background may be present
Sporadic adenoma:
- Occurs in colonic segments outside colitic mucosa
- Not related to IBD
- Otherwise similar epithelial changes as those in IBD associated dysplasia

Board review style question #1

Which of the following statements regarding surveillance colonoscopies for patients with inflammatory bowel disease is true?

Complete endoscopic resection of colitis associated polypoid high grade dysplasia can be followed up with continued surveillance
Most colorectal dysplasia identified in surveillance colonoscopies is endoscopically invisible
Nonpolypoid dysplasia is never endoscopically resectable and should therefore prompt colectomy
Polyps with dysplasia present in mucosa outside of mucosa affected by chronic colitis are not considered sporadic adenomas

Board review style answer #1

A. Complete endoscopic resection of colitis associated polypoid high grade dysplasia can be followed up with continued surveillance.

Comment Here

Board review style question #2

Which of the following statements regarding dysplasia associated with inflammatory bowel disease is true?

Early genetic changes present in colitis associated neoplasia are similar to those in sporadic neoplasia
Indefinite for dysplasia may be diagnosed if the distinction between reactive atypia and dysplasia cannot be established
Loss of nuclear polarity is a feature of low grade dysplasia
Only patients with ulcerative colitis and not Crohn's disease have an increased risk of colorectal carcinoma

Board review style answer #2

B. Indefinite for dysplasia may be diagnosed if the distinction between reactive atypia and dysplasia cannot be established.

Comment Here