Colon

Inflammatory bowel disease

Dysplasia


Editorial Board Member: Raul S. Gonzalez, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Kenrry Chiu, M.D., C.M.
David F. Schaeffer, M.D.

Topic Completed: 8 July 2021

Minor changes: 8 July 2021

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

PubMed Search: Colon[TI] dysplasia[TI]

Kenrry Chiu, M.D., C.M.
David F. Schaeffer, M.D.
Page views in 2021 to date: 5,736
Cite this page: Chiu K, Schaeffer DF. Dysplasia. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/colonIBDdysplasia.html. Accessed October 28th, 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
    • D12.2 - benign neoplasm of ascending colon
    • D12.3 - benign neoplasm of transverse colon
    • D12.4 - benign neoplasm of descending colon
    • D12.5 - benign neoplasm of sigmoid colon
    • D12.6 - benign neoplasm of colon, unspecified
    • D12.7 - benign neoplasm of rectosigmoid junction
    • 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
Clinical features
Diagnosis
  • Detected with colonoscopies, typically as part of surveillance
  • Targeted biopsies, endoscopic resections or polypectomies of visible lesions
  • Random biopsies may be taken to detect endoscopically invisible dysplasia
Prognostic factors
Case reports
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:
  • Indefinite for dysplasia:
Clinical images

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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



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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
  • More recently, Gui et al. reported features that can be seen in IBD associated nonpolypoid dysplasia but only rarely seen in polypoid dysplasia or sporadic adenomas (Hum Pathol 2020;100:24):
    • Dysplastic epithelium associated with a background of inflammatory polyp or granulation tissue, micropapillary or hobnailing surface epithelial cells, nuclear pleomorphism and disarray, and microvesicular or bubbling cytoplasm
  • IBD associated nonconventional dysplasia (i.e. not intestinal type) has been described and is relatively common in IBD patients:
    • 45% of IBD patients with colorectal cancer and of those, 46% did not have associated conventional dysplasia as reported by Choi et al. (Mod Pathol 2020;33:933)
    • 33% of IBD patients with dysplasia as reported by Lee et al. (Histopathology 2021;78:814)
    • 38% of carcinoma related lesions and 41% of nonpolypoid dysplasia compared to 7% of polypoid dysplasia as reported by Gui et al. (Hum Pathol 2020;100:24)
  • Nonconventional dysplasia subtypes (Histopathology 2021;78:814, Hum Pathol 2020;100:24, Mod Pathol 2020;33:933):
    • Hypermucinous (mucinous) dysplasia:
      • Tubulovillous or villous architecture with prominent mucinous differentiation
      • Usually mild nuclear atypia, especially towards the surface
    • Dysplasia with increased Paneth cell differentiation:
      • Tubular architecture with elongated, hyperchromatic nuclei
      • Foci of increased Paneth cell differentiation, defined by Choi et al. as involving at least 2 contiguous crypts in 2 different foci and increased relative to background mucosa (Mod Pathol 2020;33:933)
    • Goblet cell deficient (eosinophilic) dysplasia:
      • Goblet cells are nearly or completely absent
      • Eosinophilic cytoplasm
    • Serrated dysplasia, which includes:
      • Traditional serrated adenoma (TSA)-like
      • Sessile serrated lesion (SSL)-like
      • Serrated lesion not otherwise specified: does not meet criteria for SSL-like or TSA-like dysplasia
    • Dysplasia with terminal epithelial differentiation (differentiated dysplasia) (Hum Pathol 2020;100:24, J Clin Pathol 2020;73:391)
      • Nuclei are enlarged (can be mildly so), round to oval, slightly irregular, hyperchromatic and mostly nonstratified
      • Nucleoli can be present, inconspicuous and occasionally prominent
      • Some authors consider at least a subset of differentiated dysplasia as crypt cell dysplasia (see next heading) (Histopathology 2021;78:814, Hum Pathol 2020;100:24, J Clin Pathol 2020;73:391)
    • Crypt cell dysplasia:
      • Recently proposed to represent a high risk dysplastic lesion but the diagnosis based on histologic features alone is subject to significant interobserver variability and high rates of nondysplastic diagnoses, particularly indefinite for dysplasia (Histopathology 2021;78:814, Histopathology 2019;75:578)
      • Atypia is limited to crypt base and does not involve surface epithelium
      • Nuclei are round or oval, mildly enlarged, hyperchromatic and show slightly irregular contours
  • Dysplasia can show mixed histologic patterns (including mixed nonconventional and conventional dysplasia)
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

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High grade dysplasia in ulcerative colitis

Low grade dysplasia in ulcerative colitis

Cytology images

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High grade dysplasia

Positive stains
Negative stains
Molecular / cytogenetics description
Molecular / cytogenetics images

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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
    • Nonconventional dysplasia, e.g. increased Paneth cell differentiation or goblet cell deficient variant, can mimic reactive, metaplastic changes (Mod Pathol 2020;33:933)
      • Features such as lack of surface maturation and cytoarchitectural atypia help establish a diagnosis of dysplasia
  • Sporadic adenoma:
    • Occurs in colonic segments outside colitic mucosa
    • Not related to IBD
    • Otherwise similar epithelial changes as those in (conventional) IBD associated dysplasia
Board review style question #1
Which of the following statements regarding surveillance colonoscopies for patients with inflammatory bowel disease is true?

  1. Complete endoscopic resection of colitis associated polypoid high grade dysplasia can be followed up with continued surveillance
  2. Most colorectal dysplasia identified in surveillance colonoscopies is endoscopically invisible
  3. Nonpolypoid dysplasia is never endoscopically resectable and should therefore prompt colectomy
  4. 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

Reference: Dysplasia
Board review style question #2

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

  1. Early genetic changes present in colitis associated neoplasia are similar to those in sporadic neoplasia
  2. Indefinite for dysplasia may be diagnosed if the distinction between reactive atypia and dysplasia cannot be established
  3. Loss of nuclear polarity is a feature of low grade dysplasia
  4. 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

Reference: Dysplasia
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