Villous Adenoma

Article Author:
David Myers
Article Editor:
Komal Arora
Updated:
6/18/2019 2:33:14 AM
PubMed Link:
Villous Adenoma

Introduction

Adenoma refers broadly to any benign tumor of glandular tissue. This article will address specifically adenomas of the colon, occurring within polyps. Colon polyps are a common entity, increasing in prevalence with age. Adenomatous polyps are the most common type of polyp in the colon, accounting for about 60% to 70% of all colonic polyps. Conventional type adenomatous polyps can be classified as tubular, villous, or tubulovillous. Villous adenomas are characterized by more than 75% villous features, where villous refers to finger-like or leaf-like epithelial projections. Tubulovillous adenomas have between 25% and 75% villous features. Less than 25% villous features indicate a tubular adenoma. Adenomas are usually asymptomatic and found on routine colorectal cancer screening. Adenomas with villous features may be associated with a slight increase in development of more advanced neoplasia or dysplasia compared to other types of adenomas.[1][2][3]

Etiology

The risk of developing colorectal polyps is related to both environmental and genetic factors. The majority of polyps in the colon arise sporadically even though genetics play the most important role in influencing the individual risk of developing colon polyps and subsequent colorectal cancer. Personal history of colon adenomas places a patient at increased risk for future development of colon cancer.[4][5][6]

Colorectal cancer has been shown to arise mainly from pre-existing adenomatous colon polyps. Adenomatous polyps form as mentioned above primarily in a sporadic fashion. The sporadic nature of these polyps is a result of either a mutation in the adenomatous coli pathway or DNA mismatch repair.

Familial adenomatous polyposis (FAP) is a genetic disorder which, in particular, predisposes affected patients to the development of multiple adenomatous polyps. FAP is an autosomal dominant disorder caused by a mutation in the tumor suppressor APC gene, located on chromosome 5q. This mutation can either be inherited or in as many as one out of three patients, can present as a new germline mutation. The frequency of FAP is from 1 in 8,000 to 1 in 14,000, with large numbers of adenomas occurring beginning in late childhood. Classically, patients with FAP have over 100 colorectal adenomatous polyps, but many patients have several hundred, or even thousands, of polyps. These patients usually develop adenocarcinoma by the age of 30 to 40. Even given the likely development of colon cancer in these patients, FAP only accounts for around 1% of colon cancers.

Adenomas are defined as possessing at least the characteristics of low-grade dysplasia. Some adenomas may progress over an extended period from low-grade dysplasia to high-grade dysplasia, carcinoma in situ, or invasive adenocarcinoma. Although physicians debate this, and the evidence does not completely confirm, thus far, if villous features indicate an increased risk of developing colorectal cancer, multiple studies demonstrate that histologic villous features of adenomas may be associated with developing advanced forms of neoplasia. Size at baseline of adenomas has been shown in some studies to influence future advanced disease; lesions greater than 1 cm increase a patient's risk. One source states that villous lesions have an increased risk of containing adenocarcinoma correlated to size specifically, with a 10% to 20% risk in adenomas larger than 2 cm, and a 5% risk in adenomas from 1 cm to 2 cm in size. However, these findings are inconsistent when considered across multiple studies regarding the subject. A recent study proposes using the overall sum of all adenoma diameters (called the adenoma bulk) at initial surveillance colonoscopy to stratify patients as either high or low-risk for predicting the development of advanced neoplasia. This study states that the adenoma bulk is comparatively predictive as the conventional current model using histology features when using a risk stratification cutoff of 10mm for the adenoma bulk, with high-risk adenoma bulk being greater than or equal to 10 mm. [4][5][6]

Epidemiology

The incidence of colon polyps increases in direct correlation with age. By age 50, colorectal cancer screening studies have demonstrated a prevalence of 25% to 30%, increasing to 50% by age 70 in high-risk Western countries such as the United States. Colon polyps are rare in the younger population, present in only one to four percent of 20 to 30-year-olds. Villous adenomas account for 5% to 15% of all adenomas.[7][8]

Histopathology

Before discussing what constitutes villous features of adenomas, it is important to differentiate degree of dysplasia present in adenomas. The degree of dysplasia present in an adenoma is determined by both cytological and architectural features. Adenomas are tumors of dysplastic epithelium which can be characterized as having a low grade or high-grade dysplasia, which indicates the level of maturation of the epithelium. By definition, adenomas have at least low-grade dysplasia.

The cytological features of low-grade dysplasia include crowded, pseudo-stratification to early stratification of spindled or elongated nuclei which occupy 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.

High-grade dysplasia cytologically boasts increased nucleus to cytoplasm ratio, more significant loss of polarity, more "open" appearing nuclei with increasingly prominent nucleoli. Other features which distinguish a high grade from low-grade dysplasia include significant pleomorphism, rounded nuclei, atypical mitoses, and significant loss of polarity. Mitotic figures may be observed as in low-grade dysplasia. Cribriform and crowding, back-to-back glands indicate high-grade dysplasia and can be important architectural features to aid in differentiating some cases of low vs. high-grade dysplasia which may have less distinct cytological features.

The villous component of adenomas refers to epithelial finger-like projections away from the muscularis mucosae. There should be deep crypts, and the projections should contain fibrovascular cores lined by dysplastic epithelium. As stated above, the amount of villous differentiation distinguishes villous adenomas (over 75% villous features) versus tubulovillous adenomas (mixed tubular and villous features with 25% to 75% villous features). 

History and Physical

The majority of patients will not present symptomatically and subsequently, have a colonoscopy which identifies colorectal polyps. Rather, polyps are found on screening or surveillance colonoscopy. If patients do present with symptoms, commonly they will endorse a history of blood per rectum. 

Evaluation

Current US Preventive Services Task Force recommendation for average-risk adults is that beginning at age 50 patients should initiate regular colon cancer screening. Methods include a fecal occult blood test, fecal immunochemical test, and direct visualization methods. Direct visualization through colonoscopy, biopsy, and histologic examination of colon lesions is necessary to examine and diagnose colorectal polyps and cancers. 

Treatment / Management

Surgeons should excise adenomatous polyps of any type completely and confirm clear margins. [9][10][11]Based on the morphology and a number of lesions removed, surveillance guidelines according to the American Cancer Society are as follows:

  • Average risk (no first-degree relative to colon cancer): Colonoscopy at age 50
  • No adenoma or carcinoma, repeat in 10 years
  • One to two small (no more than 1 cm) tubular adenomas with low-grade dysplasia, repeat in 5 to 10 years
  • Three to ten adenomas, or a large (at least 1 cm) adenoma, or any adenomas with high-grade dysplasia or villous features, repeat in 3 years.
  • More than ten adenomas on a single exam, repeat within 3 years
  • Increased risk (positive family history in the first-degree relative before age 60, or in two or more first-degree relatives at any age if not a hereditary syndrome) Colonoscopy at age 40, or 10 years before the youngest case in the immediate family (whichever is earlier). Repeat with above surveillance guidelines with the caveat that maximum time between screening should be 5 years.
  • High-risk (hereditary colon cancer/polyposis syndromes): 
  • FAP: Annual flexible sigmoidoscopy; if genetically proven FAP, consider colectomy.

Enhancing Healthcare Team Outcomes

Patients with colonic adenomas may be asymptomatic or present with rectal bleeding. In any patient over the age of 50 and no familial polyposis syndrome, one should always consider the possibility of a malignancy. The primary care giver and nurse practitioner should refer these patients to a gastroenterologist or general surgeon for further workup and removal of the lesion. While the majority of colonic polyps are benign, villous adenomas tend to have a high rate of malignancy.



  • (Move Mouse on Image to Enlarge)
    • Image 7290 Not availableImage 7290 Not available
      Image courtesy Dr D Myers MD

References

[1] Chubak J,McLerran D,Zheng Y,Singal AG,Corley DA,Doria-Rose VP,Doubeni CA,Kamineni A,Haas JS,Halm EA,Skinner CS,Zauber AG,Wernli KJ,Beaber EF, Receipt of Colonoscopy Following Diagnosis of Advanced Adenomas: An Analysis within Integrated Healthcare Delivery Systems. Cancer epidemiology, biomarkers     [PubMed PMID: 30459208]
[2] Jin Y,Yao L,Zhou P,Jin S,Wang X,Tang X,Peng X,Hua P,Ren Y,Gong L, [Risk analysis of the canceration of colorectal large polyps]. Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery. 2018 Oct 25     [PubMed PMID: 30370516]
[3] Rezasoltani S,Asadzadeh Aghdaei H,Dabiri H,Akhavan Sepahi A,Modarressi MH,Nazemalhosseini Mojarad E, The association between fecal microbiota and different types of colorectal polyp as precursors of colorectal cancer. Microbial pathogenesis. 2018 Aug 22     [PubMed PMID: 30142468]
[4] Grunwald D,Landau A,Jiang ZG,Liu JJ,Najarian R,Sheth SG, Further Defining the 2012 Multi-Society Task Force Guidelines for Surveillance of High-risk Adenomas: Is a 3-Year Interval Needed for All Patients? Journal of clinical gastroenterology. 2018 Jul 20     [PubMed PMID: 30036239]
[5] Click B,Pinsky PF,Hickey T,Doroudi M,Schoen RE, Association of Colonoscopy Adenoma Findings With Long-term Colorectal Cancer Incidence. JAMA. 2018 May 15     [PubMed PMID: 29800214]
[6] Carvalho B,Diosdado B,Terhaar Sive Droste JS,Bolijn AS,Komor MA,de Wit M,Bosch LJW,van Burink M,Dekker E,Kuipers EJ,Coupé VMH,van Grieken NCT,Fijneman RJA,Meijer GA, Evaluation of Cancer-Associated DNA Copy Number Events in Colorectal (Advanced) Adenomas. Cancer prevention research (Philadelphia, Pa.). 2018 Jul     [PubMed PMID: 29685877]
[7] Zhou H,Shen Z,Zhao J,Zhou Z,Xu Y, [Distribution characteristics and risk factors of colorectal adenomas]. Zhonghua wei chang wai ke za zhi = Chinese journal of gastrointestinal surgery. 2018 Jun 25     [PubMed PMID: 29968244]
[8] Wong S,Lidums I,Rosty C,Ruszkiewicz A,Parry S,Win AK,Tomita Y,Vatandoust S,Townsend A,Patel D,Hardingham JE,Roder D,Smith E,Drew P,Marker J,Uylaki W,Hewett P,Worthley DL,Symonds E,Young GP,Price TJ,Young JP, Findings in young adults at colonoscopy from a hospital service database audit. BMC gastroenterology. 2017 Apr 19     [PubMed PMID: 28424049]
[9] Park SK,Yang HJ,Jung YS,Park JH,Sohn CI,Park DI, Risk of advanced colorectal neoplasm by the proposed combined United States and United Kingdom risk stratification guidelines. Gastrointestinal endoscopy. 2018 Mar     [PubMed PMID: 28986265]
[10] Dessain A,Snauwaert C,Baldin P,Deprez P,Libbrecht L,Piessevaux H,Jouret-Mourin A, Endoscopic submucosal dissection specimens in early colorectal cancer: lateral margins, macroscopic techniques, and possible pitfalls. Virchows Archiv : an international journal of pathology. 2017 Feb     [PubMed PMID: 27933386]
[11] van Heijningen EM,Lansdorp-Vogelaar I,van Hees F,Kuipers EJ,Biermann K,de Koning HJ,van Ballegooijen M,Steyerberg EW, Developing a score chart to improve risk stratification of patients with colorectal adenoma. Endoscopy. 2016 Jun     [PubMed PMID: 27167762]