Stanford School of Medicine

Surgical Pathology Criteria

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Colorectal Adenoma with Benign Misplacement of Glands / Pseudoinvasion


  • Benign epithelium in the stalk of an adenomatous polyp, simulating carcinoma

Alternate/historical Names

  • Adenomatous polyp with colitis cystica profunda
  • Pseudocarcinomatous entrapment

Covered Separately

Diagnostic Criteria

  • Nests of adenomatous epithelium in submucosa and/or stalk
    • Usually circumscribed
  • Lacks infiltrative pattern
  • Frequently surrounded by chronic inflammation and granulation tissue
    • Frequently accompanied by lamina propria
    • Lacks desmoplastic stromal response
  • Frequently demonstrable continuity with overlying adenoma
    • Traverses a gap in the muscularis mucosae
      • No infiltration of muscularis mucosae
      • Muscularis mucosae may be hyperplastic
      • May require multiple sections to demonstrate
  • Cytologically and architecturally bland, unless involved by high grade dysplasia
    • High grade dysplasia usually accompanied by ordinary adenoma in misplacement
    • Glands frequently show cystic dilation
  • Hemosiderin in stroma of stalk is frequent
    • Hemosiderin is common in the stroma of the head of polyps but unusual in the stroma of the stalk
    • Hemosiderin is uncommon around invasive carcinoma
    • Fresh hemorrhage is also frequent in stalk
      • Less reliable because of procedural trauma
  • Virtually restricted to left colon
    • Most in sigmoid
  • Stains for collagen type IV and E cadherin may be helpful, see Supplementary Studies at left
    • Infrequently required
  • Similar features of mucosal entrapment have been reported in hyperplastic polyps and small bowel Peutz-Jeghers polyps

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/update : 1/31/10, 11/13/11

Supplemental studies


  • Collagen type IV
    • Stains normal basement membrane strongly
    • Entrapped nests show strong, continuous staining of surrounding basement membrane
    • Invasive carcinoma shows only weak, discontinuous staining
    • Loss of staining reported to be 100% specific, 96% sensitive
  • E cadherin
    • Stains cell membranes of normal and adenomatous epithelium strongly
    • Carcinoma shows markedly decreased intensity
    • Loss of staining reported to be 100% specific, 65% sensitive
  • p53
    • Usually scattered nuclear staining in adenomas
    • Usually extensive nuclear staining in carcinoma
    • Reported to be 96% specific and 61% sensitive
  • Data from Yantiss 2002
  • Special stains are not generally required for diagnosis

Differential Diagnosis

Colorectal Adenoma Containing Invasive Adenocarcinoma Colorectal Adenoma with Benign Misplacement of Glands / Pseudoinvasion
Usually significant architectural and/or cytologic atypia Usually lacks significant architectural and/or cytologic atypia (high grade dysplasia may be misplaced occasionally but is typically accompanied by bland adenoma tissue)
Desmoplastic stroma Inflammatory or fibrotic stroma
Infiltrates through muscularis mucosae Frequently demonstrable continuity with surface through a gap in the muscularis mucosae
Hemosiderin restricted to head of polyp Hemosiderin common in stalk stroma
Glands not accompanied by lamina propria Glands may be accompanied by lamina propria
Usually infiltrative, non-circumscribed Frequently circumscribed
May occur throughout the colorectum Virtually restricted to left colon
Collagen type IV weak, discontinuous Collagen type IV strong, continuous around epithelial nests
E cadherin markedly decreased staining compared to overlying adenoma E cadherin same intensity as overlying adenoma (high grade dysplasia may show decrease)


  • No special significance to polyps with misplaced glands
    • Behavior, significance and therapy are simply that of the adenoma in which it occurs
  • The term misplaced is preferred over pseudoinvasion
    • It is less likely to be misinterpreted as needing aggressive therapy


  • Bosman FT, Carneiro F, Hruban RH, Thiese ND (Eds). WHO Classifiication of Tumors of the Digestive System, IARC, Lyon 2010.
  • Petersen VC, Sheehan AL, Bryan RL, Armstrong CP, Shepherd NA. Misplacement of dysplastic epithelium in Peutz-Jeghers Polyps: the ultimate diagnostic pitfall? Am J Surg Pathol. 2000 Jan;24(1):34-9.
  • Yantiss RK, Bosenberg MW, Antonioli DA, Odze RD. Utility of MMP-1, p53, E-cadherin, and collagen IV immunohistochemical stains in the differential diagnosis of adenomas with misplaced epithelium versus adenomas with invasive adenocarcinoma. Am J Surg Pathol. 2002 Feb;26(2):206-15.
  • Pascal RR, Hertzler G, Hunter S, Goldschmid S. Pseudoinvasion with high-grade dysplasia in a colonic adenoma. Distinction from adenocarcinoma. Am J Surg Pathol. 1990 Jul;14(7):694-7.
  • Muto T, Bussey HJ, Morson BC. Pseudo-carcinomatous invasion in adenomatous polyps of the colon and rectum. J Clin Pathol. 1973 Jan;26(1):25-31.
  • Yantiss RK, Goldman H, Odze RD. Hyperplastic polyp with epithelial misplacement (inverted hyperplastic polyp): a clinicopathologic and immunohistochemical study of 19 cases. Mod Pathol. 2001 Sep;14(9):869-75.
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