Tubulovillous / villous adenoma

Editorial Board Member: Raul S. Gonzalez, M.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Carolina Martinez Ciarpaglini, M.D., Ph.D.

Topic Completed: 12 November 2019

Minor changes: 7 May 2021

Copyright: 2003-2021,, Inc.

PubMed Search: Tubulovillous [title] adenoma colon , villous adenoma [title] colon

Carolina Martinez Ciarpaglini, M.D., Ph.D.
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Cite this page: Ciarpaglini C. Tubulovillous / villous adenoma . website. Accessed October 28th, 2021.
Definition / general
Essential features
  • Recognized as the precursor lesion of chromosomal unstable colorectal cancer
  • Low grade dysplasia is an intrinsic feature
  • Associated with oncogene KRAS mutation in 50% of cases
ICD coding
  • ICD-10: D12.6 - benign neoplasm of colon, unspecified
  • Conventional adenoma carcinoma sequence with oncogene (KRAS) activation and tumor suppressor (APC, SMAD4 and TP53) inactivation
  • Associated with chromosomal unstable colorectal cancer (Cancer Biol Med 2016;13:120)
Clinical features
  • Screening or surveillance colonoscopy identifies and removes lesion, followed by tissue diagnosis
Prognostic factors
  • Villous or tubulovillous histology is associated with increased risk of colorectal neoplasia: 16.8% versus 9.7% compared with tubular adenomas
  • Increased risk of malignant transformation in cases with high grade dysplasia (↑1.77x) (Gastroenterology 2012;143:844)
Case reports
  • Endoscopic resection
Gross description
  • Pedunculated or sessile polypoid lesions with macroscopic finger-like projections
Gross images

Contributed by Carolina Martinez Ciarpaglini, M.D., Ph.D.

Large villous polyp

Giant villous adenoma

Images hosted on other servers:

Villous adenoma

Adenocarcinoma arising in villous adenoma

Microscopic (histologic) description
  • Low grade dysplasia is a constituent feature
  • Epithelial finger-like projections away from the muscularis mucosae formed by fibrovascular cores lined by dysplastic epithelium (villous architecture)
    • Percentage of villosity defines diagnostic terminology
    • 20 - 80% = tubulovillous adenoma
    • > 80% = villous adenoma
  • Crowded pseudostratification of cells with elongated nuclei occupying the basal half of the cytoplasm
  • Pleomorphism and atypical mitoses should be absent or minimally present
  • Mitotic activity and minimal loss of cell polarity are allowed
  • Architecturally, the crypts should maintain a resemblance to normal colon, without significant crowding, cribriform or complex forms
  • Squamous metaplasia as solid nests of squamous cells in direct continuity with adenomatous glands may be seen
  • Ectopic crypt foci is a frequent finding (J Clin Pathol 2016;69:1063)
  • High grade dysplasia can be seen (carcinoma in situ or intraepithelial / intramucosal carcinoma are not recommended terms)
    • Increased nucleus to cytoplasm ratio
    • Significant loss of cell polarity: nuclear stratification through the entire thickness of the epithelium
    • Round nuclei with open appearing chromatin and increasingly prominent nucleoli
    • Significant pleomorphism and atypical mitoses
    • Abnormal architecture includes cribriform structures with back to back glands, prominent glandular budding and intraluminal papillary tufting (Myers: StatPearls, 2019)
  • Poor interobserver agreement for assessment of the villous component and high-grade dysplasia have been demonstrated (Am J Surg Pathol 2013;37:427)
Microscopic (histologic) images

Contributed by Carolina Martinez Ciarpaglini, M.D., Ph.D.

Villous architecture

Low grade dysplasia

Giant rectal villous adenoma

Squamous metaplasia

Focal eosinophilic change

Ectopic crypt foci

High grade dysplasia

Contributed by Jijgee Munkhdelger, M.D., Ph.D. and Andrey Bychkov, M.D., Ph.D.

Cut section

Low power

Virtual slides

Images hosted on other servers:

Villous adenoma

Positive stains
Negative stains
Molecular / cytogenetics description
Sample pathology report
  • Colon, polyp at 12 cm, endoscopic polypectomy:
    • Tubulovillous adenoma with high grade dysplasia
  • Colon, polyp at 14 cm, endoscopic polypectomy:
    • Villous adenoma
Differential diagnosis
  • Traditional serrated adenoma (TSA): exophytic tubulovillous or villous polypoid architecture with three constituent features (J Clin Pathol 2016;69:6):
    • Striking granular eosinophilic cytoplasm; prominent cytoplasmic eosinophilia occupying > 50% of tubulovillous / villous adenoma is uncommon (Am J Surg Pathol 2011;35:212)
    • Presence of ectopic crypt foci: more extensive small and short crypts with no relation to the underlying muscularis mucosae (Histopathology 2015;66:308)
    • Luminal serration defined as deep clefts and slit-like spaces, leading to broad luminal fronds imparting a "mushroom-like" appearance (not present in tubulovillous and villous adenoma) (Histopathology 2015;66:308)
  • Tubular adenoma: adenomatous polyp with disorganized glands (tubular appearance) and flat surface; may show some villous component representing between 0% to less than 20% of the lesion (Am J Surg Pathol 2011;35:212)
  • Adenoma-like adenocarcinoma: invasive carcinoma with architectural and cytologic features resembling villous adenoma; differential diagnosis with villous adenoma may be a challenge
Board review style question #1

A colon polyp is resected. The above image is representative of the lesion. What is your diagnosis?

  1. Composite adenoma neuroendocrine carcinoma
  2. Composite adenoma neuroendocrine tumor
  3. Tubulovillous adenoma with high grade dysplasia
  4. Tubulovillous adenoma with squamous metaplasia
Board review style answer #1
D. Tubulovillous adenoma with squamous metaplasia

Comment here

Reference: Tubulovillous adenoma and villous adenoma
Board review style question #2
Which of the following is true about villous adenoma?

  1. Frequently associated with KRAS mutations
  2. Precursor lesion in the serrated pathway of colorectal development
  3. Presents the same risk of malignant transformation than tubular adenoma
  4. Routine screening of MMR proteins for Lynch syndrome in this lesion is useful
Board review style answer #2
A. Frequently associated with KRAS mutations

Comment here

Reference: Tubulovillous adenoma and villous adenoma
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