Colonic adenomas are raised protrusions of colonic mucosa, i.e., polyps formed by glandular tissue. Although a tumor of benign nature, these adenomas are usually considered precancerous and can transform into malignant structures, in contrast to hyperplastic polyps, with no malignant potential.[1]
Depending on the pattern of growth, these tumors can be villous, tubular, or tubulovillous. A polyp with more than 75% villous features, i.e., long finger-like or leaf-like projections on the surface, is called a villous adenoma, while tubular adenomas are mainly comprised of tubular glands and have less than 25% villous features. A tubulovillous adenoma is referred to as an adenoma with both features. Tubular adenomas are the most common type of colonic adenomas, comprising a prevalence of more than 80%.[2]
Although villous adenomas are more likely to become cancerous, this reflects the fact that they generally have the largest surface area due to their villous projections. If adjusted for surface area, all types of adenomas have the same potential to become cancerous.[3]
Community-based estimates reveal an increased prevalence with age and male gender while several studies have also reported a higher risk of colon cancer in patients with a first-degree relative family history, smoking history, excess alcohol intake, diabetes mellitus and higher body-mass index which can be a reflection of high-fat, low-fiber diet, and limited physical activity. Historically, research has reported the prevalence of colonic adenoma and colorectal cancer to be higher in blacks versus white populations. However, several recent studies have had conflicting results.[4][5] This entity also represents a lower prevalence in developing countries compared to North America, Australia, and Europe; however, its prevalence is on the increase in recent years worldwide due to the westernization of diet and lifestyle.[6]
Colorectal cancer is the fourth most common cancer and the second leading cause of cancer-related death in the United States (US), thus representing a significant public health problem. Adenoma detection rate (ADR) evaluated by colonoscopy, has been used to estimate colorectal cancer risk, which is defined as the percentage of patients aged above 50 years who undergo colonoscopy for colorectal cancer screening for the first time and have at least one detected adenoma. ADR is reportedly approximately 12% by the fifth decade of life, which increases to 50% throughout a lifetime. ADR is also profoundly different among populations, reaching about 22% in a large screening population. ADR is a vital risk estimation score and is inversely associated with the risk of cancer as each 1% increase in ADR corresponds to a 3% decrease in cancer risk.[7]
Adenocarcinoma Development
Adenoma-carcinoma sequence explains the molecular changes that lead to the formation of carcinoma from adenomas. More than 95% of colon adenocarcinomas arise from colonic polyps, while approximately 1.5% to 9.4% of adenomas turn to a malignant lesion within an interval of 8 to 10 years. The length of the adenoma-adenocarcinoma interval depends on the size of the adenoma, its morphological features, and the pathological type.[8][9] In patients with reported advanced adenoma, i.e., higher dysplasia grade and higher villosity in the first colonoscopy, the probability of advanced adenocarcinomas are higher later in life. Thus, they need more aggressive and frequent colonoscopic surveillance. In general, the size of adenoma correlates with both its histopathological type and degree of dysplasia. Tubular adenomas comprise smaller adenomas (less than 1 cm) mainly, in contrast to villous adenomas that tend to have a larger polyp size. The small tubular adenomas have a lower incidence of high-grade dysplasia.[10] Excluding the cases with a diagnosis of juvenile polyps, there are still reports of coexisting adenoma-adenocarcinomas in 2 to 15% of children and teenagers who had an initial diagnosis of polyp in colonoscopy.[11]
Adenoma-Carcinoma Transformation
Two main molecular pathways lead to adenocarcinoma of the colon. The chromosomal instability (CIN) pathway is the most attributed pathway and accounts for almost 80% of colorectal adenocarcinomas in the U.S. In this pathway, cancer develops within adenomas through a series of progressive mutations in several genes, including adenomatous polyposis coli (APC), K-ras, SMAD4, and p53, as follows: The first step in the adenoma-carcinoma sequence is sporadic or germline inactivation of the tumor suppressor gene, APC, that increases the likelihood of developing a polyp due to β-catenin accumulation, which can then translocate to the nucleus and drive cell proliferation. K-ras mutation occurs afterward and leads to the formation of the polyp. Inactivation of the other tumor suppressor gene, p53, and increased expression of COX allow for progression to carcinoma. Aspirin may play a role in this process by impeding the progression from adenoma to carcinoma, which leads to improved survival outcomes in colorectal cancer. Carcinomas that develop in this pathway exhibit CIN are microsatellite stable (MSS), and mismatch repair proficient (MMR-P). In the second pathway, which is called the serrated pathway, cancer develops through the malignant transformation of sessile serrated adenoma/polyp (SSA/P) precursor lesions. This pathway is not the focus of the present report.[10]
Colonic tubular adenomas characteristically demonstrate nuclear hyperchromatism (i.e., dark purple nuclei), nuclear crowding (i.e., nuclei are bunched-up), elliptical/cigar-shaped nuclei, and loss or reduction in the number of goblet cells. They may not show dysplasia at first, but will gradually develop dysplastic features and may eventually transform to colorectal cancer.[3]
Adenomas are primarily located in the rectosigmoid region of the colon and might occasionally present in the proximal colon. Patients are commonly asymptomatic, and these growths are usually found on screening colonoscopies. If symptomatic, the most frequent symptom is hematochezia, i.e., painless bright or dark red blood per rectum on wiping or with bowel movements mixed with stools or dripping. Occasionally patients might have a history of alterations in bowel movements (either diarrhea or constipation), weight loss, loss of appetite, abdominal pain, symptoms of partial bowel occlusion, or iron deficiency anemia due to bleeding. A physical exam is usually non-contributory; however, clinicians may rarely find rectal polyps on the digital rectal exam.[1]
Based on the latest U.S. Preventive Services Task Force, the recommendation is to initiate the screening at age 50 in all individuals and continuing until age 75 years. For adults aged 76 to 85 years, the decision should be individualized, considering the patient’s overall health and screening history. Screening for polyps is usually performed by testing for fecal occult blood and the gold-standard colonoscopy. As mentioned earlier, polyps are mostly asymptomatic but can bleed. Colorectal polyps can be detected using a fecal occult blood test, digital rectal examination, flexible sigmoidoscopy, colonoscopy, virtual colonoscopy, barium enema, or a pill camera. Colonoscopy and the subsequent pathological examination are necessary for definitive diagnosis of the type of the tumor. Apart from the screening, surveillance colonoscopy should continue for the previously detected polyps.[12]
If no polyps appear on the initial colonoscopic evaluation, the suggested follow-up colonoscopy is within ten years. Surveillance of previously detected polyps includes follow-up colonoscopy in three to five years based on the initial resected polyp size and microscopic dysplastic features. If the examiner detects more than ten adenomas or even an adenoma showed villous features, screening is recommended in less than three years, while for 3 to 10 adenomas, repeat screening should take place in 3 years. If only 1 to 2 small tubular adenomas are present, the interval can extend for 5 to 10 years.[13][14][15] Recent studies have revealed that despite these surveillance guidelines, the adherence to the follow-up evaluations is low and more must be done to increase this value.[3]
There have been reports of up to 25% of missed adenomas during colonoscopy because of poor colon preparation and suboptimal visualization behind mucosal folds. Flat lesions on the right side of the colon can be particularly difficult to detect. Recent studies have aimed to detect more cases using accessory diagnostic devices (cap assistance, third eye retro-scope, endo-cuff) and by improving the endoscope design with a full spectrum endoscopy system, balloon-assisted colonoscopy, and confocal laser endo-microscopy.[16]
The goal is to remove the adenomatous polyps before progression to adenocarcinoma. Hyperplastic and adenomatous polyps cannot be differentiated without pathological evaluation. Thus all polyps are usually resected during colonoscopy and examined microscopically. Total colectomy is necessary if there is evidence of malignancy or lymph node metastasis.[13]
Pseudopolyps which harbor an intermediate risk of malignancy might present with bleeding or cause additional complications such as obstruction. Although a broad spectrum of medical and surgical treatment approaches have gotten introduced, debate still exists about the treatment of choice.[17]
Treatment of familial juvenile polyposis is the surgical approach and depends in part on the degree of rectal involvement. If the rectum is relatively spared, total abdominal colectomy with ileorectal anastomosis may be performed with subsequent close surveillance of the retained rectum. If the rectum is carpeted with polyps, a total proctocolectomy is a more appropriate operation. These patients are candidates for ileal pouch-anal reconstruction to avoid a permanent stoma.[18]
There are three different main surgical approaches known for the definitive treatment of those affected with familial adenomatous polyposis: total colectomy plus ileorectal anastomosis, total proctocolectomy with ileostomy, and restorative proctocolectomy with or without mucosectomy and ileal-pouch anal anastomosis.[19]
Tubular adenomas are the most common types of adenomas and have the potential to turn malignant. Recommendations include educating the general population on the nature of polyps and their outcomes. All people should be aware that colon cancer is generally asymptomatic, and if symptomatic presents with hematochezia. Due to the silent presence of the disorder, all people must undergo screening colonoscopy after 50 years of age. Individuals with a positive family history are the target population for earlier and more frequent screening processes. An interprofessional team can improve patient outcomes. Primary care providers must stress screening. Gastroenterologists perform endoscopy needed for diagnosis. Gastroenterology nurses provide patient education and arrange appropriate follow up and referrals. [Level 5]
[1] | Mărginean CO,Mărginean MO,Simu I,Horvath A,Meliţ LE, Giant tubular adenoma with malignancy clinical characteristics in a female teenager: Case report and a review of the literature. Medicine. 2016 Oct; [PubMed PMID: 27749532] |
[2] | Myers DJ,Arora K, Villous Adenoma 2019 Jan; [PubMed PMID: 29262150] |
[3] | Bujanda L,Cosme A,Gil I,Arenas-Mirave JI, Malignant colorectal polyps. World journal of gastroenterology. 2010 Jul 7; [PubMed PMID: 20593495] |
[4] | Imperiale TF,Abhyankar PR,Stump TE,Emmett TW, Prevalence of Advanced, Precancerous Colorectal Neoplasms in Black and White Populations: A Systematic Review and Meta-analysis. Gastroenterology. 2018 Dec; [PubMed PMID: 30142339] |
[5] | David Y,Ottaviano L,Park J,Iqbal S,Likhtshteyn M,Kumar S,Lyo H,Lewis AE,Lung BE,Frye JT,Huang L,Li E,Yang J,Martello L,Vignesh S,Miller JD,Follen M,Grossman EB, Confounders in Adenoma Detection at Initial Screening Colonoscopy: A Factor in the Assessment of Racial Disparities as a Risk for Colon Cancer. Journal of cancer therapy. 2019 Apr; [PubMed PMID: 31032142] |
[6] | Jemal A,Bray F,Center MM,Ferlay J,Ward E,Forman D, Global cancer statistics. CA: a cancer journal for clinicians. 2011 Mar-Apr; [PubMed PMID: 21296855] |
[7] | Corley DA,Jensen CD,Marks AR,Zhao WK,de Boer J,Levin TR,Doubeni C,Fireman BH,Quesenberry CP, Variation of adenoma prevalence by age, sex, race, and colon location in a large population: implications for screening and quality programs. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2013 Feb; [PubMed PMID: 22985608] |
[8] | Steele SR,Johnson EK,Champagne B,Davis B,Lee S,Rivadeneira D,Ross H,Hayden DA,Maykel JA, Endoscopy and polyps-diagnostic and therapeutic advances in management. World journal of gastroenterology. 2013 Jul 21; [PubMed PMID: 23885138] |
[9] | Paggi S,Radaelli F,Repici A,Hassan C, Advances in the removal of diminutive colorectal polyps. Expert review of gastroenterology [PubMed PMID: 25155348] |
[10] | Gibson JA,Odze RD, Pathology of premalignant colorectal neoplasia. Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2016 Apr; [PubMed PMID: 26861656] |
[11] | Andrade DO,Ferreira AR,Bittencourt PF,Ribeiro DF,Silva RG,Alberti LR, CLINICAL, EPIDEMIOLOGIC, AND ENDOSCOPIC PROFILE IN CHILDREN AND ADOLESCENTS WITH COLONIC POLYPS IN TWO REFERENCE CENTERS. Arquivos de gastroenterologia. 2015 Dec; [PubMed PMID: 26840472] |
[12] | Bibbins-Domingo K,Grossman DC,Curry SJ,Davidson KW,Epling JW Jr,García FAR,Gillman MW,Harper DM,Kemper AR,Krist AH,Kurth AE,Landefeld CS,Mangione CM,Owens DK,Phillips WR,Phipps MG,Pignone MP,Siu AL, Screening for Colorectal Cancer: US Preventive Services Task Force Recommendation Statement. JAMA. 2016 Jun 21; [PubMed PMID: 27304597] |
[13] | Jover R,Dekker E,Schoen RE,Hassan C,Pellise M,Ladabaum U, Colonoscopy quality requisites for selecting surveillance intervals: A World Endoscopy Organization Delphi Recommendation. Digestive endoscopy : official journal of the Japan Gastroenterological Endoscopy Society. 2018 Nov; [PubMed PMID: 29971834] |
[14] | Tanaka S,Saitoh Y,Matsuda T,Igarashi M,Matsumoto T,Iwao Y,Suzuki Y,Nishida H,Watanabe T,Sugai T,Sugihara K,Tsuruta O,Hirata I,Hiwatashi N,Saito H,Watanabe M,Sugano K,Shimosegawa T, Evidence-based clinical practice guidelines for management of colorectal polyps. Journal of gastroenterology. 2015 Mar; [PubMed PMID: 25559129] |
[15] | Kang H,Thoufeeq MH, Size of colorectal polyps determines time taken to remove them endoscopically. Endoscopy international open. 2018 May; [PubMed PMID: 29756019] |
[16] | Patil R,Ona MA,Ofori E,Reddy M, Endocuff-Assisted Colonoscopy-A Novel Accessory in Improving Adenoma Detection Rate: A Review of the Literature. Clinical endoscopy. 2016 Nov; [PubMed PMID: 27133962] |
[17] | Politis DS,Katsanos KH,Tsianos EV,Christodoulou DK, Pseudopolyps in inflammatory bowel diseases: Have we learned enough? World journal of gastroenterology. 2017 Mar 7; [PubMed PMID: 28321155] |
[18] | Jelsig AM, Hamartomatous polyps - a clinical and molecular genetic study. Danish medical journal. 2016 Aug; [PubMed PMID: 27477802] |
[19] | Campos FG, Surgical treatment of familial adenomatous polyposis: dilemmas and current recommendations. World journal of gastroenterology. 2014 Nov 28; [PubMed PMID: 25469031] |
[20] | Kalady MF,Jarrar A,Leach B,LaGuardia L,O'Malley M,Eng C,Church JM, Defining phenotypes and cancer risk in hyperplastic polyposis syndrome. Diseases of the colon and rectum. 2011 Feb; [PubMed PMID: 21228663] |
[21] | Leoz ML,Carballal S,Moreira L,Ocaña T,Balaguer F, The genetic basis of familial adenomatous polyposis and its implications for clinical practice and risk management. The application of clinical genetics. 2015; [PubMed PMID: 25931827] |
[22] | Dipro S,Al-Otaibi F,Alzahrani A,Ulhaq A,Al Shail E, Turcot syndrome: a synchronous clinical presentation of glioblastoma multiforme and adenocarcinoma of the colon. Case reports in oncological medicine. 2012; [PubMed PMID: 23119205] |
[23] | Pilarski R,Burt R,Kohlman W,Pho L,Shannon KM,Swisher E, Cowden syndrome and the PTEN hamartoma tumor syndrome: systematic review and revised diagnostic criteria. Journal of the National Cancer Institute. 2013 Nov 6; [PubMed PMID: 24136893] |
[24] | Beggs AD,Latchford AR,Vasen HF,Moslein G,Alonso A,Aretz S,Bertario L,Blanco I,Bülow S,Burn J,Capella G,Colas C,Friedl W,Møller P,Hes FJ,Järvinen H,Mecklin JP,Nagengast FM,Parc Y,Phillips RK,Hyer W,Ponz de Leon M,Renkonen-Sinisalo L,Sampson JR,Stormorken A,Tejpar S,Thomas HJ,Wijnen JT,Clark SK,Hodgson SV, Peutz-Jeghers syndrome: a systematic review and recommendations for management. Gut. 2010 Jul; [PubMed PMID: 20581245] |
[25] | Yuan W,Tian L,Ai FY,Liu SJ,Shen SR,Wang XY,Liu F, Cronkhite-Canada syndrome: A case report. Oncology letters. 2018 Jun; [PubMed PMID: 29805581] |
[26] | Sant V,Reich E,Khanna L,Cao W,Kornacki S,Grucela A, Attenuated familial adenomatous polyposis (AFAP) in a patient associated with a novel mutation in APC. BMJ case reports. 2019 Nov 10; [PubMed PMID: 31712236] |
[27] | O'Connell BM,Crockett SD, The clinical impact of serrated colorectal polyps. Clinical epidemiology. 2017; [PubMed PMID: 28260946] |
[28] | Saraste D,Martling A,Nilsson PJ,Blom J,Törnberg S,Hultcrantz R,Janson M, Complications after colonoscopy and surgery in a population-based colorectal cancer screening programme. Journal of medical screening. 2016 Sep; [PubMed PMID: 26940962] |
[29] | Zwink N,Holleczek B,Stegmaier C,Hoffmeister M,Brenner H, Complication Rates in Colonoscopy Screening for Cancer. Deutsches Arzteblatt international. 2017 May 5; [PubMed PMID: 28587708] |