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Colon Polyps

Colon Polyps

Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy polyps are growths of mucosal tissue in the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy, the most common site of polyps in the GI tract. Polyps can be classified as neoplastic or nonneoplastic and may be associated with genetic syndromes. Hyperplastic polyps are nonneoplastic and are the most common type overall, whereas adenomas are the most common type of neoplastic polyp and have the potential to progress to cancer. For most people without hereditary syndromes, colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer screening Screening Preoperative Care should begin at age 45 and in adolescence for those with the rare familial adenomatous polyposis Familial Adenomatous Polyposis Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis ( FAP FAP Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis) syndrome. Diagnosis is by biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma, and management includes frequent surveillance Surveillance Developmental Milestones and Normal Growth in people with adenomatous polyps Adenomatous polyps Benign neoplasms derived from glandular epithelium. Colorectal Cancer or screening Screening Preoperative Care every 10 years in the general population until age 75.

Last updated: 10 Feb, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Contents

Overview

Types of colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy polyps

  • Benign Benign Fibroadenoma:
    • Hyperplastic: no neoplastic potential
    • Hamartomatous: mixture of normal tissues but growing in a disorganized mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast
      • Juvenile: usually solitary, can be seen in children, not associated with an increased risk of colorectal cancer Colorectal cancer Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Colorectal Cancer (CRC)
      • Phosphatase and tensin homolog Phosphatase and TENsin homolog A lipid phosphatase that contains a C2 domain and acts on phosphatidylinositol-3, 4, 5-trisphosphate to regulate various signal transduction pathways. It modulates cell growth processes; cell migration; and apoptosis. Mutations in pten are associated with cowden disease and proteus syndrome as well as neoplastic cell transformation. Cowden Syndrome (PTEN) hamartoma Hamartoma A focal malformation resembling a neoplasm, composed of an overgrowth of mature cells and tissues that normally occur in the affected area. Colorectal Cancer tumor Tumor Inflammation syndrome: comprised of the Cowden and Bannayan-Riley-Ruvalcaba syndromes
      • Peutz-Jeghers polyps: usually associated with Peutz-Jeghers syndrome Peutz-Jeghers Syndrome Peutz-Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by GI polyps and mucocutaneous-pigmented macules. Peutz-Jeghers syndrome is 1 of the polyposis syndromes, a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract and associated with other extracolonic features. Peutz-Jeghers Syndrome
    • Inflammatory: common in ulcerative colitis Ulcerative colitis Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn’s disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis
  • Neoplastic:
    • Tubular adenoma
    • Villous adenoma Villous adenoma An adenoma of the large intestine. It is usually a solitary, sessile, often large, tumor of colonic mucosa composed of mucinous epithelium covering delicate vascular projections. Hypersecretion and malignant changes occur frequently. Colorectal Cancer
    • Mixed tubulovillous
    • Sessile serrated

Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy polyps

  • Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy polyps are found in 15%–40% of adults.
  • Most neoplastic colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy polyps are adenomas (approximately â…”):
    • 30%–50% of individuals with 1 adenoma ≥ 1 other adenoma.
    • Less common in Asia ASIA Spinal Cord Injuries, but increasing as Western diets are adopted.
  • Most colorectal cancers (CRCs) arise from sporadic Sporadic Selective IgA Deficiency adenomatous polyps Adenomatous polyps Benign neoplasms derived from glandular epithelium. Colorectal Cancer:
    • Early detection of adenomatous polyps Adenomatous polyps Benign neoplasms derived from glandular epithelium. Colorectal Cancer by screening Screening Preoperative Care decreases the risk of CRC.
    • Lifetime incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency (in individuals with average risk) of CRC in the United States: about 4%.

Risk factors

  • Increasing age is a risk factor for developing adenomas.
  • Diet: high in red meat and fat, low in fiber
  • Inflammatory bowel disease:
    • Ulcerative colitis Ulcerative colitis Ulcerative colitis (UC) is an idiopathic inflammatory condition that involves the mucosal surface of the colon. It is a type of inflammatory bowel disease (IBD), along with Crohn’s disease (CD). The rectum is always involved, and inflammation may extend proximally through the colon. Ulcerative Colitis
    • Crohn’s disease
  • Family history Family History Adult Health Maintenance
  • Tobacco and alcohol use
  • Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity
  • African heritage
  • Uncontrolled type 2 Type 2 Spinal Muscular Atrophy diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus

Hereditary polyposis syndromes

Each syndrome occurs in < 1% of the population and accounts for 5%–10% of CRCs.

  • Hereditary nonpolyposis colorectal cancer Colorectal cancer Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Colorectal Cancer ( HNPCC HNPCC Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Lynch syndrome, or Lynch syndrome Lynch syndrome Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Lynch syndrome):
    • Most common inherited cause of cancer 
    • Accounts for 2%–4% of CRCs
    • Autosomal dominant inheritance Autosomal dominant inheritance Autosomal Recessive and Autosomal Dominant Inheritance
    • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 1 in 279 people
    • DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure mismatch repair Mismatch repair A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Exonucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome ( MMR MMR A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome) gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutations
    • Cancer occurs at multiple sites.
    • Slightly higher number of neoplastic polyps than normal; also, higher rate of progression to CRC
    • Associated cancers in individuals with HNPCC HNPCC Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Lynch syndrome and/or in 1st-degree relatives, especially endometrial, ovarian
  • Familial adenomatous polyposis Familial Adenomatous Polyposis Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis ( FAP FAP Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis) syndrome and variants: 
    • Autosomal dominant inheritance Autosomal dominant inheritance Autosomal Recessive and Autosomal Dominant Inheritance or sporadic Sporadic Selective IgA Deficiency mutations
    • Gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics affected: APC APC A polyposis syndrome due to an autosomal dominant mutation of the apc genes on chromosome 5. The syndrome is characterized by the development of hundreds of adenomatous polyps in the colon and rectum of affected individuals by early adulthood. Familial Adenomatous Polyposis
    • Classic FAP FAP Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis: prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency 1 in 7000 people; each has ≥ 100 polyps.
    • Attenuated FAP FAP Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis: a mild form of FAP FAP Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis (10–99 polyps) 
  • Juvenile polyposis syndrome Juvenile polyposis syndrome Familial juvenile polyposis, also known as juvenile polyposis syndrome, is an autosomal dominant condition characterized by the growth of hyperplastic, hamartomatous polyps in the colon. Polyposis syndromes are a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, and are associated with other extracolonic features. Familial Juvenile Polyposis:
  • Peutz-Jeghers syndrome Peutz-Jeghers Syndrome Peutz-Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by GI polyps and mucocutaneous-pigmented macules. Peutz-Jeghers syndrome is 1 of the polyposis syndromes, a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract and associated with other extracolonic features. Peutz-Jeghers Syndrome ( PJS PJS Peutz-Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by GI polyps and mucocutaneous-pigmented macules. Peutz-Jeghers syndrome is 1 of the polyposis syndromes, a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract and associated with other extracolonic features. Peutz-Jeghers Syndrome): 
Colorectal polyp types

Colorectal polyp Colorectal polyp Discrete tissue masses that protrude into the lumen of the colon. These polyps are connected to the wall of the colon either by a stalk, pedunculus, or by a broad base. Colorectal Cancer Screening types, approximate relative incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency (I), and malignancy Malignancy Hemothorax risk (M) (2019)

Image: “Pie chart of colorectal polyp Colorectal polyp Discrete tissue masses that protrude into the lumen of the colon. These polyps are connected to the wall of the colon either by a stalk, pedunculus, or by a broad base. Colorectal Cancer Screening etiologies” by Mikael Häggström. License: CC0 1.0

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Pathophysiology

Benign Benign Fibroadenoma polyps

  • Hyperplastic polyps: benign Benign Fibroadenoma reactive epithelial proliferation
  • Hamartomatous polyps: may occur sporadically or be genetically determined
    • Have different proportions and placement of normal colonic tissues
    • Cowden syndrome Cowden Syndrome Cowden syndrome, also known as multiple hamartoma syndrome, is an autosomal dominant inherited condition that presents with multiple, noncancerous growths on various parts of the body. The syndrome is classified as a phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome that is caused by mutations in the PTEN gene. Cowden Syndrome: mostly in PTEN hamartoma Hamartoma A focal malformation resembling a neoplasm, composed of an overgrowth of mature cells and tissues that normally occur in the affected area. Colorectal Cancer tumor Tumor Inflammation syndrome group 
    • Cronkhite-Canada syndrome: nonhereditary; unknown cause
    • Tuberous sclerosis Sclerosis A pathological process consisting of hardening or fibrosis of an anatomical structure, often a vessel or a nerve. Wilms Tumor: TSC1 ( hamartin Hamartin An intracellular signaling and tumor suppressor protein that forms a complex with tuberous sclerosis complex 2 protein (TSC2) and other signaling factors to negatively regulate mtorc1 signaling and affect cell growth and proliferation. Structurally, it interacts with TSC2 through its n-terminal, which also contains gsk-3beta phosphorylation sites and a rho-kinase activation domain. It also contains a c-terminal coiled-coil domain and ezrin-radixin-moesin (ERM) domain. Mutations in the TSC1 gene are associated with tuberous sclerosis. Tuberous Sclerosis, TSC TSC Tuberous sclerosis or tuberous sclerosis complex (TSC) is an autosomal dominant disorder with mainly neurocutaneous symptoms. Mutation in the tsc genes causes excessive tumor-like growths in the brain, eyes, heart, kidney, and lungs. Cutaneous manifestations include hypopigmentation (i.e., ash leaf spots, confetti lesions) or excessive growth (i.e., angiofibroma, shagreen patch). Tuberous Sclerosis ( tuberin Tuberin An intracellular signaling and tumor suppressor protein that forms a complex with tuberous sclerosis complex 1 protein (TSC1) and other signaling factors to negatively regulate mtorc1 and affect cell growth and proliferation. It can also function as GTPase-activating protein (gap) for rheb GTPase to activate mtorc1 independent of its role in the complex. Structurally, it interacts with TSC1 through its n-terminus, which also contains a leucine zipper and coiled-coil region. It also has multiple phosphorylation sites for different cell signaling kinases, a central coiled-coil region, a c-terminal gap domain and calmodulin binding domain. Mutations in the TSC2 gene are associated with tuberous sclerosis. Tuberous Sclerosis), mTOR mTOR Peutz-Jeghers Syndrome pathway)
    • Juvenile polyposis: sporadic Sporadic Selective IgA Deficiency or autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance, with mutations in SMAD4, BMPR1A BMPR1A A subtype of bone morphogenetic protein receptors with high affinity for bone morphogenetic proteins. They can interact with and undergo phosphorylation by type II bone morphogenetic protein receptors. They signal primarily through receptor-regulated SMAD proteins. Familial Juvenile Polyposis; transforming growth factor β 
    • PJS PJS Peutz-Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by GI polyps and mucocutaneous-pigmented macules. Peutz-Jeghers syndrome is 1 of the polyposis syndromes, a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract and associated with other extracolonic features. Peutz-Jeghers Syndrome: autosomal dominant Autosomal dominant Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal dominant diseases are expressed when only 1 copy of the dominant allele is inherited. Autosomal Recessive and Autosomal Dominant Inheritance
  • Inflammatory polyps: due to chronic cycles of injury and healing (e.g., inflammatory bowel disease)

Neoplastic polyps

  • Adenomatous polyp: low-grade dysplasia Dysplasia Cellular Adaptation
    • May transform to high-grade dysplasia Dysplasia Cellular Adaptation/carcinoma in situ (over several years to decades) and eventually to colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer as it gathers more mutations 
    • Precursors to the majority of colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancers
    • Usually follow the chromosomal instability Chromosomal instability An increased tendency to acquire chromosome aberrations when various processes involved in chromosome replication, repair, or segregation are dysfunctional. Colorectal Cancer ( APC APC A polyposis syndrome due to an autosomal dominant mutation of the apc genes on chromosome 5. The syndrome is characterized by the development of hundreds of adenomatous polyps in the colon and rectum of affected individuals by early adulthood. Familial Adenomatous Polyposis mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations) pathway
    • Can have tubular, villous, or tubulovillous architecture
    • Correlation Correlation Determination of whether or not two variables are correlated. This means to study whether an increase or decrease in one variable corresponds to an increase or decrease in the other variable. Causality, Validity, and Reliability with invasive CRC increases with:
      • Size (most important factor): rare if adenoma < 1 cm; 40% of adenomas > 4 cm contain foci of invasive cancer.
      • High-grade dysplasia Dysplasia Cellular Adaptation
      • Villous architecture
    • Initial mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations event causing adenoma/ dysplasia Dysplasia Cellular Adaptation: more common in regenerating epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium: Histology (e.g., inflammatory bowel disease)
  • Sessile serrated adenomas:
  • Hereditary polyposis syndromes with neoplastic polyps:
    • Lynch syndrome Lynch syndrome Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Lynch syndrome: mutations in MMR MMR A DNA repair pathway involved in correction of errors introduced during DNA replication when an incorrect base, which cannot form hydrogen bonds with the corresponding base in the parent strand, is incorporated into the daughter strand. Excinucleases recognize the base pair mismatch and cause a segment of polynucleotide chain to be excised from the daughter strand, thereby removing the mismatched base. Lynch syndrome genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure
    • FAP FAP Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis and variants: initial mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations in APC APC A polyposis syndrome due to an autosomal dominant mutation of the apc genes on chromosome 5. The syndrome is characterized by the development of hundreds of adenomatous polyps in the colon and rectum of affected individuals by early adulthood. Familial Adenomatous Polyposis gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics
Adenoma-carcinoma sequence

Adenoma–carcinoma sequence from normal colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy to carcinoma:
Colorectal cancer Colorectal cancer Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Colorectal Cancer (CRC) formation begins with APC APC A polyposis syndrome due to an autosomal dominant mutation of the apc genes on chromosome 5. The syndrome is characterized by the development of hundreds of adenomatous polyps in the colon and rectum of affected individuals by early adulthood. Familial Adenomatous Polyposis gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations (inherited or acquired) and methylation Methylation Addition of methyl groups. In histo-chemistry methylation is used to esterify carboxyl groups and remove sulfate groups by treating tissue sections with hot methanol in the presence of hydrochloric acid. . Glucocorticoids abnormalities. Other changes can include KRAS gene Gene A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. Basic Terms of Genetics mutation Mutation Genetic mutations are errors in DNA that can cause protein misfolding and dysfunction. There are various types of mutations, including chromosomal, point, frameshift, and expansion mutations. Types of Mutations. Late in the process, p53 deletion, loss of heterozygosity (LOH) at 18q21 (involving SMAD2 and SMAD4), with overexpression of COX-2 can contribute to further growth and progression to cancer. The accumulation of mutations, rather than the timing of occurrence, is most crucial in carcinogenesis Carcinogenesis The origin, production or development of cancer through genotypic and phenotypic changes which upset the normal balance between cell proliferation and cell death. Carcinogenesis generally requires a constellation of steps, which may occur quickly or over a period of many years. Carcinogenesis.

Image by Lecturio. License: CC BY-NC-SA 4.0

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Clinical Presentation

Most colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy polyps are asymptomatic and discovered on routine colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer screening Screening Preoperative Care.

  • Symptomatic polyps may present with:
    • Blood or mucus in stool
    • Change in bowel movements:
      • Constipation Constipation Constipation is common and may be due to a variety of causes. Constipation is generally defined as bowel movement frequency < 3 times per week. Patients who are constipated often strain to pass hard stools. The condition is classified as primary (also known as idiopathic or functional constipation) or secondary, and as acute or chronic. Constipation
      • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
    • Obstruction or intussusception Intussusception Intussusception occurs when a part of the intestine (intussusceptum) telescopes into another part (intussuscipiens) of the intestine. The condition can cause obstruction and, if untreated, progress to bowel ischemia. Intussusception is most common in the pediatric population, but is occasionally encountered in adults. Intussusception if polyp large enough
  • Hereditary syndromes:
    • Lynch syndrome Lynch syndrome Lynch syndrome, also called hereditary non-polyposis colorectal cancer (HNPCC), is the most common inherited colon cancer syndrome, and carries a significantly increased risk for endometrial cancer and other malignancies. Lynch syndrome has an autosomal dominant inheritance pattern involving pathogenic variants in one of the mismatch repair (MMR) genes or epithelial cell adhesion molecule (EpCAM). Lynch syndrome:
      • Present with a higher number of polyps than in the general population
      • CRC may develop without first forming a visible precursor polyp.
      • Typically, have sessile serrated adenomas in the right colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy
    • FAP FAP Familial adenomatous polyposis (FAP) is an autosomal dominant inherited genetic disorder that presents with numerous adenomatous polyps in the colon. Familial adenomatous polyposis is the most common of the polyposis syndromes, which is a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract, associated with other extracolonic features. Familial Adenomatous Polyposis:
    • PJS PJS Peutz-Jeghers syndrome (PJS) is an autosomal-dominant inherited disorder characterized by GI polyps and mucocutaneous-pigmented macules. Peutz-Jeghers syndrome is 1 of the polyposis syndromes, a group of inherited or acquired conditions characterized by the growth of polyps in the GI tract and associated with other extracolonic features. Peutz-Jeghers Syndrome:
      • May present with hamartomatous polyps elsewhere ( stomach Stomach The stomach is a muscular sac in the upper left portion of the abdomen that plays a critical role in digestion. The stomach develops from the foregut and connects the esophagus with the duodenum. Structurally, the stomach is C-shaped and forms a greater and lesser curvature and is divided grossly into regions: the cardia, fundus, body, and pylorus. Stomach: Anatomy and small bowel Small bowel The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy)
      • Pigmented skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions lesions: melanotic macules of the skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and mucous membranes
    • Cowden syndrome Cowden Syndrome Cowden syndrome, also known as multiple hamartoma syndrome, is an autosomal dominant inherited condition that presents with multiple, noncancerous growths on various parts of the body. The syndrome is classified as a phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome that is caused by mutations in the PTEN gene. Cowden Syndrome:
      • Presents with multiple hamartomas in the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy
      • Facial mucocutaneous lesions 

Diagnosis and Management

The definitive diagnosis and treatment of colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy polyps are achieved by endoscopic removal of the entire polyp.

Diagnosis

  • Screening Screening Preoperative Care colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening or other forms of colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer screening Screening Preoperative Care to detect polyps early:
    • Starting at age 45 years in people of average risk (earlier if 1st-degree family member has CRC at age < 60 years)
    • Earlier and more frequently in individuals at higher risk:
      • Inflammatory bowel disease
      • Hereditary at-risk syndromes 
  • Colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening is needed for polyp removal if detected by other studies:
    • CT colonography CT colonography A non-invasive imaging method that uses computed tomographic data combined with specialized imaging software to examine the colon. Colorectal Cancer Screening
    • Sigmoidoscopy Sigmoidoscopy Endoscopic examination, therapy or surgery of the sigmoid flexure. Colorectal Cancer Screening
    • Positive stool testing for occult blood and DNA DNA A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine). DNA Types and Structure mutations
  • Baseline colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening findings:
    • No adenomas: 3.3%
    • 1–2 adenomas < 10 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma: 4.9%
    • High-risk adenoma: 17.3%
  • Molecular testing indicated in suspected hereditary polyposis or CRC syndromes
  • Hyperplastic polyp of the rectum

    Hyperplastic polyp of the rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy

    Image: “Hyperplastic Polyp of the Rectum Rectum The rectum and anal canal are the most terminal parts of the lower GI tract/large intestine that form a functional unit and control defecation. Fecal continence is maintained by several important anatomic structures including rectal folds, anal valves, the sling-like puborectalis muscle, and internal and external anal sphincters. Rectum and Anal Canal: Anatomy (14060044206)” by Ed Uthman. License: CC BY 2.0
  • Colon polyp on a stalk

    Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy polyp on a stalk (pedunculated)

    Image: “Polyp” by Stephen Holland. License: 2.5
  • Multiple polyps in colon

    Multiple polyps in colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy, ranging from 0.5 to 1 cm in diameter

    Image: “Multiple polyps in colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy” by Agrawal N, Santra T, Kar A, Guha P, Bar M, Adhikary A, Datta S. License: CC BY 3.0
  • Biopsy revealed adenomatous polyp

    Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma from the sigmoid Sigmoid A segment of the colon between the rectum and the descending colon. Volvulus polyp revealing adenomatous polyp with no evidence of malignancy Malignancy Hemothorax

    Image: “ Biopsy Biopsy Removal and pathologic examination of specimens from the living body. Ewing Sarcoma from sigmoid Sigmoid A segment of the colon between the rectum and the descending colon. Volvulus polyp revealing adenomatous polyp without any evidence of malignancy Malignancy Hemothorax” by Agrawal N, Santra T, Kar A, Guha P, Bar M, Adhikary A, Datta S. License: CC BY 3.0
  • Histology of juvenile polyp

    Histology of juvenile polyp showing characteristic cystically dilated glands:
    Even at low power Power The probability that a test will correctly reject a false null hypothesis. Statistical Tests and Data Representation, the benign Benign Fibroadenoma and non-neoplastic nature is supported by seeing only 1 layer of epithelial cells on the surface and lining the glandular spaces.

    Image: “Histology of juvenile polyp” by Kelly S, Dwerryhouse S, Safranek P, Hardwick R. License: CC BY 2.0
  • 2. 5-cm adenomatous polyp

    A 2.5-cm adenomatous polyp was serendipitously found in a right colectomy specimen.

    Image: “Adenomatous Polyp of the Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy 1” by Ed Uthman. License: Public Domain
  • Tubulovillous polyp

    Tubulovillous polyp

    Image: “Tubulovillous Polyp of the Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy 2” by Ed Uthman. License: Public Domain
  • Sessile colon polyp

    Sessile colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy polyp seen on colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening

    Image: “Endomucosal resection 1” by Stephen Holland. License: 2.5

Management

Follow-up guidelines after colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening and polypectomy (based on 2020 Consensus Update by the U.S. Multi-Society Task Force on Colorectal Cancer Colorectal cancer Colorectal cancer (CRC) is the 2nd leading cause of cancer-related deaths in the United States. Colorectal cancer is a heterogeneous disease that arises from genetic and epigenetic abnormalities, with influence from environmental factors. Colorectal Cancer):

  • Based on the findings at 1st colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening:
    • Risk of CRC in the 10 years following a normal colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening: < 0.5%, based on findings in 4.3 million individuals
    • Quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement assumptions: 
      • Complete exam to cecum Cecum The blind sac or outpouching area of the large intestine that is below the entrance of the small intestine. It has a worm-like extension, the vermiform appendix. Colon, Cecum, and Appendix: Anatomy
      • Adequate prep
      • Skilled colonoscopist with adequate adenoma detection rate 
  • Normal colonoscopy Colonoscopy Endoscopic examination, therapy or surgery of the luminal surface of the colon. Colorectal Cancer Screening → repeat in 10 years
    • No adenomatous polyps Adenomatous polyps Benign neoplasms derived from glandular epithelium. Colorectal Cancer
    • Hyperplastic polyps < 10 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
  • Low-risk adenomas → repeat in 7–10 years
    • Number: only 1 or 2 found
    • Size: < 10 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
    • Histology: low-grade dysplasia Dysplasia Cellular Adaptation
  • Sessile serrated polyps (SSPs) → repeat in 5–10 years
    • 1–2 SSPs
    • Size: < 10 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma 
  • Abnormal findings below → repeat in 3–5 years
    • > 3 adenomatous polyps Adenomatous polyps Benign neoplasms derived from glandular epithelium. Colorectal Cancer < 10 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
    • 3–4 SSPs < 10 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
    • Hyperplastic polyp > 10 mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
  • Advanced neoplasia or high-risk adenomas → repeat in 3 years
    • 5–10 adenomas
    • 5–10 SSPs
    • Adenoma or SSP > 10  mm MM Multiple myeloma (MM) is a malignant condition of plasma cells (activated B lymphocytes) primarily seen in the elderly. Monoclonal proliferation of plasma cells results in cytokine-driven osteoclastic activity and excessive secretion of IgG antibodies. Multiple Myeloma
    • Histology:
  • > 10 adenomas → repeat in 1 year
  • Segmental colonic resection for large (> 2 cm) polyps or lymphovascular invasion
Segment of resected colon in the unfixed state containing an invasive colorectal carcinoma and two adenomatous polyps

Segment of resected colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy in the unfixed state containing an invasive colorectal carcinoma and 2 adenomatous polyps Adenomatous polyps Benign neoplasms derived from glandular epithelium. Colorectal Cancer

Image: “ Colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy cancer” by Emmanuelm. License: CC BY 3.0

References

  1. Kumar, V., Abbas, A. K., Aster, J.C. (Eds.). (2020). The gastrointestinal tract. In: Robbins & Cotran Pathologic Basis of Disease, 10th ed. Elsevier, pp. 807–812.
  2. Nguyen, L. H., Goel, A., Chung, D. C. (2020). Pathways of colorectal carcinogenesis. Gastroenterology 158:291–302. https://doi.org/10.1053/j.gastro.2019.08.059
  3. Grover, S., Stoffel, E. (2020). MUTYH-associated polyposis. UpToDate. Retrieved November 12, 2020, from https://www.uptodate.com/contents/mutyh-associated-polyposis
  4. Macrae, F.A. (2021). Overview of colon polyps. UpToDate. Retrieved July 20, 2021,from https://www.uptodate.com/contents/overview-of-colon-polyps
  5. Peltomäki, P., Olkinuora, A., Nieminen, T. T. (2020). Updates in the field of hereditary nonpolyposis colorectal cancer. Expert Review of Gastroenterology & Hepatology 14:707–720. https://doi.org/10.1080/17474124.2020.1782187
  6. Gupta, S., et al. (2020). Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US multi-society task force on colorectal cancer. Retrieved July 20, 2021, from https://www.asge.org/docs/default-source/guidelines/recommendations-for-follow-up-after-colonoscopy-and-polypectomy-a-consensus-update-by-the-us-multi-society-task-force-on-colorectal-cancer

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