Colorectal polyp
A colorectal polyp is a small clump of cells that forms on the lining of the colon or rectum, often protruding into the intestinal lumen. Most colorectal polyps are benign and asymptomatic, but certain types can develop into colorectal cancer over time if not removed.[1] They affect approximately 20% of adults, with prevalence rising to 40% in those over age 50.[2] Colorectal polyps are classified into several types based on their shape, histology, and potential for malignancy. Neoplastic polyps, such as adenomas (including tubular, villous, and tubulovillous subtypes) and serrated polyps (like sessile serrated lesions), are precancerous and account for about 80% of cases, with roughly 5% already malignant at detection.[2] In contrast, non-neoplastic polyps, including hyperplastic, inflammatory, and juvenile types, are typically harmless and do not progress to cancer.[2] Polyps may appear as pedunculated (stalked, resembling a mushroom) or sessile (flat and broad-based), with the latter often harder to detect.[1] Most individuals with colorectal polyps experience no symptoms, leading to their discovery primarily through routine screening. When present, symptoms may include rectal bleeding (manifesting as blood on toilet paper, in the stool, or black/tarry stools), changes in bowel habits such as diarrhea or constipation, abdominal pain, fatigue from iron-deficiency anemia, or excess mucus in the stool.[1] The absence of symptoms underscores the importance of screening, such as colonoscopy starting at age 45 for average-risk individuals, which can detect and remove polyps to prevent cancer progression.[1] The exact cause of colorectal polyps remains unclear, but they arise from genetic mutations leading to abnormal cell growth in the intestinal lining. Risk factors include advancing age (most common after 45), a personal or family history of polyps or colorectal cancer, inflammatory bowel diseases like ulcerative colitis or Crohn's disease, obesity, smoking, heavy alcohol use, type 2 diabetes, and diets low in fiber or high in red/processed meats.[1] Hereditary syndromes, such as familial adenomatous polyposis (FAP) or Lynch syndrome, significantly elevate risk by causing multiple polyps.[1] Certain populations, including Black individuals in the United States, face higher incidence rates.[1] Treatment typically involves endoscopic removal (polypectomy) during colonoscopy for polyps larger than 5 mm or those with concerning features, which reduces the risk of developing colorectal cancer by up to 80%.[2] Larger or sessile polyps may require advanced techniques like endoscopic mucosal resection. Surveillance colonoscopies are recommended based on polyp number, size, and histology to monitor for recurrence. While prevention is not absolute, lifestyle measures—such as maintaining a healthy weight, exercising regularly, consuming a high-fiber diet rich in fruits and vegetables, limiting alcohol, and avoiding smoking—can lower risk.[2]Overview
Definition and characteristics
A colorectal polyp is defined as an abnormal growth that protrudes from the mucous membrane lining the colon or rectum. These growths are typically benign, though some have the potential to become malignant over time.[3] Polyps can occur anywhere along the large intestine, including the proximal colon (cecum, ascending, and transverse segments), distal colon (descending and sigmoid segments), or rectum, with their location influencing detection and management approaches.[4] Colorectal polyps vary in size, commonly classified as diminutive (less than 5 mm in diameter), small (6-9 mm), or large (10 mm or greater), which helps assess clinical significance.[4] Morphologically, they appear as either pedunculated, with a stalk connecting the growth to the mucosal surface, or sessile, featuring a broad-based attachment without a stalk.[5] In the general population, the prevalence of colorectal polyps is approximately 25-30% among adults aged 50 years and older, based on screening colonoscopy data, while autopsy studies indicate rates up to 50% by age 70.[6] The understanding of colorectal polyps advanced significantly with the introduction of colonoscopy in the 1960s, enabling direct visualization and removal, which marked a shift from earlier indirect diagnostic methods.[7] Certain polyps, particularly adenomatous ones, play a key role in the adenoma-carcinoma sequence leading to colorectal cancer.[8]Epidemiology and risk factors
Colorectal polyps are detected in approximately 20-30% of screening colonoscopies in Western countries, with prevalence rates reaching up to 30% in population and autopsy studies among middle-aged and elderly individuals.[9] In contrast, detection rates are lower in Asia and Africa, estimated at 10-15%.[10] Globally, the prevalence of colorectal adenomas, a common type of polyp, is about 23.9% based on systematic reviews of screening data.[11] These geographic variations reflect differences in dietary habits, screening practices, and genetic factors. The incidence of colorectal polyps increases with age, remaining rare under 40 years but rising sharply thereafter, with detection rates of 21-28% in individuals aged 50-59 years, 41-45% in those aged 60-69 years, and 53-58% in those over 70 years.[12] Recent expansions in screening to age 45 have led to increased polyp detection in younger adults, with rates of approximately 25-27% in ages 45-54 as of 2025, aligning with rising early-onset colorectal cancer trends.[13][14] Demographic patterns show higher prevalence in males compared to females, with men exhibiting an odds ratio of approximately 1.68 for distal lesions.[15] Racial and ethnic differences also influence risk, with higher rates observed among Caucasians and African Americans relative to Hispanic or Asian populations; for instance, African Americans have a 1.2- to 2-fold increased risk for proximal lesions.[15] Familial clustering is evident, where a family history of polyps elevates individual risk independent of specific syndromes.[16] Modifiable risk factors significantly contribute to polyp development. Obesity, particularly with a BMI greater than 30 kg/m², increases the risk by 1.5- to 2-fold, with even higher odds (up to 4.26) for severe obesity (BMI ≥40).[15] Smoking, especially with 20 or more pack-years, approximately doubles the risk, with relative risks around 2.14 for current smokers.[15] Dietary factors play a key role, as high consumption of red and processed meats is associated with a relative risk of 1.2-1.5, while low fiber intake exacerbates this vulnerability.[16] Protective factors include regular physical activity, which can reduce polyp risk by about 30%.[17] Recent trends indicate declining rates of advanced neoplasia and colorectal cancer in populations with widespread screening programs, attributed to the preventive effect of polypectomy. In the United States, post-2000 screening initiatives contributed to a 20-30% drop in advanced neoplasia rates (as observed in early 2010s studies), though overall colorectal cancer incidence declines have slowed to approximately 1% per year as of 2023.[18][19]Clinical Presentation
Signs and symptoms
Most colorectal polyps are asymptomatic, especially when small, and are typically discovered incidentally during routine screening for colorectal cancer. The vast majority—over 90%—of such polyps are detected in asymptomatic individuals via procedures like colonoscopy.[1][20] When symptoms arise, they often stem from bleeding or the physical presence of larger polyps. Rectal bleeding is the most frequent manifestation, appearing as bright red blood on toilet paper or in the stool for distal polyps located in the sigmoid colon or rectum, while proximal polyps in the ascending colon may cause occult (hidden) bleeding or dark, tarry stools (melena) due to slower blood transit and degradation.[1][20] Changes in bowel habits, including persistent constipation or diarrhea lasting more than a week, can occur with sizable polyps that partially obstruct the bowel lumen or produce excess mucus.[1][2] Chronic, low-grade blood loss from any polyps may lead to iron-deficiency anemia, presenting with symptoms such as fatigue, pallor, and shortness of breath. Chronic or acute bleeding from polyp ulceration may result in severe anemia.[20][2] Rare acute presentations are associated with giant polyps exceeding 4 cm, which can trigger intestinal obstruction or intussusception—a condition where one segment of bowel telescopes into another—resulting in crampy abdominal pain, bloating, vomiting, and constipation.[21] Pedunculated polyps, with their stalk-like attachment, may also cause localized abdominal pain if they twist or become torsed.[1][2] Symptom profiles differ by polyp location: distal lesions more commonly produce noticeable bright red bleeding owing to their nearer position to the anus, whereas proximal polyps are generally less likely to cause overt symptoms and instead contribute to insidious issues like anemia from undetected blood loss.[20][2]Complications
Colorectal polyps, particularly adenomatous types, pose a significant risk of malignant transformation via the adenoma-carcinoma sequence, where benign growths progressively accumulate genetic alterations leading to invasive cancer.[8] This process typically spans 10 to 25 years from adenoma inception to cancer development, though high-risk adenomas—such as those with villous histology, high-grade dysplasia, or size greater than 1 cm—may progress within 5 to 10 years.[22] The malignancy risk escalates with polyp size: approximately 1% for lesions under 1 cm, 10% for those 1 to 2 cm, and up to 50% for polyps exceeding 2 cm in diameter.[23] Non-malignant complications from untreated polyps are less common but can be serious. Chronic or acute bleeding from polyp ulceration may result in severe anemia. Intestinal obstruction occurs rarely, though it is more frequent in juvenile polyps or polyposis syndromes due to polyp bulk or multiplicity. Perforation during polyp growth is extremely rare, typically limited to isolated case reports involving large or inflammatory lesions. Sessile serrated lesions follow a distinct serrated neoplastic pathway to cancer, often driven by early BRAF mutations, which promote CpG island methylator phenotype progression and microsatellite instability.[24] These polyps contribute to 15-30% of colorectal cancers and carry a slower but insidious risk if undetected.[25] Undetected colorectal polyps account for over 95% of colorectal cancers, underscoring their role in preventable mortality when screening and removal are neglected.[26]Pathology
Histological structure
Colorectal polyps arise from the epithelial lining of the colonic mucosa, forming exophytic or sessile projections that can be neoplastic or non-neoplastic in nature.[27] Neoplastic polyps, primarily adenomas, exhibit glandular architecture derived from dysplastic colonic epithelium, while non-neoplastic polyps display reactive or disorganized mucosal components without dysplasia.[28] Microscopically, these lesions are evaluated for architectural patterns and cellular atypia to distinguish their potential behavior. In adenomatous polyps, the hallmark is a proliferation of dysplastic glands resembling colonic mucosa but with aberrant growth. Tubular adenomas feature closely packed, branching tubular glands with round to oval lumina, often showing a pedunculated or sessile configuration.[29] Villous adenomas display elongated, finger-like villous fronds with fibrovascular cores lined by tall columnar cells, whereas tubulovillous adenomas combine both patterns, with 25-75% villous component.[30] Dysplasia is graded using a two-tiered system: low-grade dysplasia involves mild architectural distortion, such as pseudostratification and loss of nuclear polarity, with cytological features like hyperchromasia and small nucleoli; high-grade dysplasia shows marked atypia, including complex glandular crowding, cribriforming, increased nuclear-to-cytoplasmic ratios, and prominent nucleoli, indicating a higher risk of progression.[31] Non-neoplastic polyps lack dysplastic changes and include hyperplastic, inflammatory, and hamartomatous types. Hyperplastic polyps demonstrate a serrated glandular architecture with saw-tooth-like crypts confined to the upper half of the epithelium, featuring microvesicular mucin in cells and no basal crypt branching.[32] Inflammatory pseudopolyps consist of inflamed and eroded surface mucosa with expanded lamina propria containing mixed inflammatory infiltrates, crypt abscesses, and granulation tissue featuring dilated thin-walled vessels and fibrosis.[33] Hamartomatous polyps, such as juvenile polyps, are characterized by disorganized, cystically dilated glands filled with mucus and inflammatory debris, embedded in edematous stroma rich in lymphocytes and plasma cells.[34] Histological diagnosis relies primarily on hematoxylin and eosin (H&E) staining, which highlights epithelial architecture, glandular patterns, and cytological atypia for routine evaluation.[27] Special stains, such as Ki-67 immunohistochemistry, assess proliferative activity by revealing nuclear staining in epithelial cells, often showing an expanded basal proliferative zone in adenomas or irregular foci in serrated lesions to aid in distinguishing subtle dysplasia.[35]Genetic and molecular basis
The development of colorectal polyps involves a series of somatic genetic mutations that drive initiation and progression, particularly in sporadic adenomas. Inactivating mutations in the APC gene occur in approximately 80% of sporadic adenomas and represent an early initiating event by disrupting the Wnt signaling pathway, leading to uncontrolled cell proliferation.[36] Progression to advanced adenomas is often marked by activating mutations in the KRAS oncogene in 30-50% of cases, which enhance downstream signaling in the MAPK pathway and promote growth.[37] In late-stage lesions approaching carcinoma, loss-of-function mutations in the TP53 tumor suppressor gene accumulate, impairing DNA repair and apoptosis, further destabilizing the genome.[38] Two primary molecular pathways underlie polyp formation and malignant transformation: the classic adenoma-carcinoma sequence driven by chromosomal instability (CIN) and the serrated neoplasia pathway characterized by epigenetic alterations. The CIN pathway, responsible for most conventional adenomas, features progressive accumulation of chromosomal aberrations, including aneuploidy and loss of heterozygosity, often initiated by APC inactivation and culminating in widespread genomic instability.[39] In contrast, the serrated pathway predominates in sessile serrated lesions and involves the CpG island methylator phenotype (CIMP), where hypermethylation silences tumor suppressor genes, combined with the BRAF V600E mutation in about 80% of sessile serrated polyps, activating the MAPK pathway independently of KRAS.[40] This pathway frequently leads to microsatellite instability through MLH1 promoter methylation. Hereditary syndromes account for a subset of polyps with distinct genetic bases, predisposing individuals to polyposis through germline mutations. Familial adenomatous polyposis (FAP) arises from germline APC mutations, resulting in hundreds to thousands of adenomas typically by the second decade of life, with near-certain progression to colorectal cancer if untreated.[41] Lynch syndrome, caused by germline defects in DNA mismatch repair genes such as MLH1 or MSH2, confers a 70-80% lifetime risk of colorectal cancer, often through fewer but rapidly progressing adenomas exhibiting microsatellite instability.[36] Peutz-Jeghers syndrome stems from STK11 germline mutations, leading to hamartomatous polyps throughout the gastrointestinal tract accompanied by mucocutaneous melanin pigmentation.[42] Juvenile polyposis syndrome involves germline mutations in SMAD4 or BMPR1A, which disrupt TGF-β signaling and cause multiple (typically 5 or more, but ranging from a few to hundreds) hamartomatous polyps primarily in the colorectum, increasing cancer risk over time.[43] Recent advances highlight the interplay of environmental factors and emerging detection technologies in polyp pathogenesis. By 2025, studies have elucidated the gut microbiome's role in promoting serrated lesion formation, with dysbiotic communities enriched in Fusobacterium nucleatum and certain Bacteroides species fostering inflammation and BRAF activation in susceptible individuals.[44] Additionally, liquid biopsy techniques detecting circulating tumor DNA (ctDNA) have shown promise for non-invasive polyp surveillance, with reported sensitivities for advanced adenomas around 23% in recent multimodal assays through methylation or mutation profiling, though specificity remains a challenge for early lesions.[45]Classification
Major types
Colorectal polyps are broadly classified into neoplastic and non-neoplastic categories based on their histological features and potential for malignant transformation. Neoplastic polyps, which are precancerous, include adenomas and serrated lesions, while non-neoplastic polyps lack this malignant potential and arise from various benign processes. Adenomas represent the most common neoplastic polyps and are subclassified by architecture into tubular, villous, and tubulovillous types. Tubular adenomas account for approximately 70% of cases, characterized by simple glandular structures with low malignant potential in small lesions but increasing risk with size and villous components. Villous adenomas comprise 5-15% and feature elongated, finger-like projections, conferring the highest risk of progression to adenocarcinoma among adenomas. Tubulovillous adenomas make up 20-25%, blending features of both and exhibiting intermediate risk. Serrated polyps form another key neoplastic subgroup, distinguished by a saw-tooth glandular pattern and varying cancer risk. Hyperplastic polyps, the most frequent serrated type, are typically small, distal, and carry a very low risk of malignancy (<1%). In contrast, sessile serrated lesions (also called sessile serrated adenomas or polyps) are larger, right-sided, and have a higher progression risk of 5-15% due to their precursor role in the serrated neoplasia pathway. Traditional serrated adenomas, rarer and often left-sided, show mixed serrated and adenomatous features with elevated malignant potential. Non-neoplastic polyps include hamartomatous and inflammatory variants, which do not typically progress to cancer. Hamartomatous polyps, such as juvenile polyps (often solitary in children) and Peutz-Jeghers polyps (multiple and associated with a hereditary syndrome), consist of disorganized normal tissue elements like cystic glands and smooth muscle. Inflammatory pseudopolyps arise in inflammatory bowel disease, representing islands of regenerating mucosa amid ulceration rather than true neoplasms. Rare non-neoplastic types encompass lipomatous polyps, composed of adipose tissue and usually asymptomatic, and lymphoid polyps, which are nodular aggregates of immune cells. Metaplastic polyps, sometimes termed mucosal prolapse polyps, feature fibromuscular changes due to mechanical stress and are not true polyps but reactive proliferations. The World Health Organization's 2019 classification, which remains the standard as of 2025, refined polyp taxonomy, particularly elevating sessile serrated lesions as a distinct entity from hyperplastic polyps owing to their differing molecular profiles and cancer risks, aiding in targeted surveillance. This update underscores the role of BRAF mutations and CpG island methylator phenotype in serrated pathways, distinct from the APC-driven adenoma-carcinoma sequence.Comparison of histological features
Colorectal polyps exhibit diverse histological features that distinguish their types and inform clinical risk assessment. Non-neoplastic polyps, including hyperplastic, inflammatory, and hamartomatous variants, generally lack dysplasia and show benign architectural patterns, whereas neoplastic polyps such as conventional adenomas and certain serrated lesions demonstrate cytological atypia and structural abnormalities indicative of malignant potential. These differences are critical for determining progression risk, with neoplastic types progressing through the adenoma-carcinoma sequence or serrated pathway to colorectal cancer.[4] Key histological differentiators center on the presence of dysplasia and architectural complexity. Neoplastic polyps like adenomas feature dysplastic epithelium—ranging from low-grade in tubular forms to high-grade in villous subtypes—arranged in glandular or frond-like patterns, conferring substantial malignant potential that escalates with villous components or size exceeding 1 cm (approximately 10-20% risk of harboring invasive cancer). In contrast, non-neoplastic polyps such as hyperplastic types display uniform serration without dysplasia, while inflammatory polyps exhibit stromal inflammation and surface erosion, both with negligible progression risk (<1%). Hamartomatous polyps, characterized by malformed but mature tissues, also lack dysplasia but may signal syndromic associations elevating overall cancer susceptibility. Among serrated polyps, sessile serrated lesions stand out with boot-shaped crypts and lateral growth, bridging non-neoplastic and neoplastic categories due to their potential for dysplasia development.[46][47][4] Prevalence among endoscopically detected polyps reflects these distinctions: conventional adenomas comprise 60-70%, hyperplastic polyps 20-30%, inflammatory polyps around 10-20% in inflammatory bowel disease contexts, hamartomatous polyps less than 1%, and serrated lesions (including sessile subtypes) approximately 20-30% overall, with traditional serrated adenomas rarer at 1-5%.[4][48] Diagnostic challenges are prominent in borderline cases, particularly differentiating hyperplastic polyps from sessile serrated lesions, where subtle features like crypt base serration or dilation may be overlooked in superficial sections, leading to interobserver disagreement rates of 20-40%; exhaustive sectioning and immunohistochemical aids are often necessary for accurate classification. Multidisciplinary review is recommended for complex or diagnostically challenging polyps, prioritizing histological confirmation to guide risk stratification without over-resection.[49][50]| Polyp Type | Histological Features | Malignancy Risk | Location Preference | Approximate Prevalence |
|---|---|---|---|---|
| Hyperplastic polyp | Serrated crypts with regular architecture, no dysplasia | Low (<1%) | Distal colon/rectum | 20-30% |
| Sessile serrated lesion | Serrated architecture with crypt dilation, horizontal extension, possible low-grade dysplasia | Intermediate (5-15% if ≥1 cm or dysplastic) | Proximal colon | 3-9% |
| Tubular adenoma | Branched tubular glands with low- to high-grade dysplasia | Variable (1% if <1 cm; 10-20% if >1 cm) | Throughout (distal for small) | 50-60% |
| Villous adenoma | Leaf-like villous projections with high-grade dysplasia | High (20-40%) | Distal colon | 5-10% |
| Hamartomatous polyp (e.g., juvenile) | Disorganized admixture of glands, stroma, and cysts; no dysplasia | Low (<1%) | Variable | <1% |
| Inflammatory polyp | Surface erosion with inflammatory granulation tissue and fibrosis; no dysplasia | Very low (<1%) | Areas of inflammation (e.g., IBD) | 10-20% in IBD contexts |