Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Prognostic factors | Case reports | Treatment | Clinical images | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Virtual slides | Cytology images | Positive stains | Molecular / cytogenetics description | Molecular / cytogenetics images | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite 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 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
- Endoscopically resectable:
- 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
Gross description
- Can be macroscopically (endoscopically) unapparent
- Can be polypoid (pedunculated or sessile) or nonpolypoid (superficially elevated, flat or depressed)
Gross images
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
Virtual slides
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
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
- Colon (sigmoid), polypectomy:
- Nonpolypoid lesion, endoscopically resected piecemeal:
- Colon (ascending), biopsy:
- High grade dysplasia
- Completeness of excision cannot be determined (specimen fragmented)
- Colon (ascending), biopsy:
- Invisible dysplasia identified on random biopsy:
- Rectum, biopsy:
- Low grade dysplasia
- Rectum, biopsy:
- 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.
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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.
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