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The Large Intestine

The large intestine is the portion of the gastrointestinal tract from the ileocecal valve to the anus. It is 90 to 125 cm in length in adults and includes the colon and rectum. The proximal colon is supplied by the superior mesenteric artery. The distal half of the large intestine is supplied by the inferior mesenteric artery, and is mainly for storage.
Macroscopic Features: The large intestine is divided into six regions proceeding distally from the ileocecal valve:
(a) cecum,
(b) ascending colon,
(c) transverse colon,
(d) descending colon,
(e) sigmoid colon, and
(6) rectum. Q

Like the small intestine, the colon has outer longitudinal and inner circular muscle coats. However, in the colon, the longitudinal muscle has three separate bundles, the taeniae coli. Evaginations of the colonic wall between the taeniae, the haustra, appear as external sacculations. The appendices epiploicae are small serosal masses of fat. The vermiform appendix arises at the apex of the cecum and terminates as a blind tube; it averages about 8 cm in length but occasionally measures up to 20 cm. Q
  1. Congenital Disorders
Congenital Megacolon (Hirsch Prung Disease) Reflects a Segmental Absence of Ganglion Cells
Hirschsprung disease is a disorder in which colon dilation results from a defect in colorectal innervation: congenital absence of ganglion cells, in most cases in the wall of the rectum.
  1. The aganglionic rectum and the adjacent colon are permanently contracted because of the absence of relaxation stimuli, the fecal contents do not readily enter this stenotic area. The proximal bowel becomes dilated because of functional distal obstruction. Q
  2. Half of the familial cases and 15% of sporadic reflect inactivating mutations of the RET receptor tyrosine kinase gene on chromosome 10q. The incidence of congenital megacolon is 10 times higher than normal in infants with Down syndrome.
  1. The definitive diagnosis of Hirschsprung disease is made on the basis of absence of ganglion cells in a rectal biopsy specimen.
  1. Inflammatory Bowel Disease
    Inflammatory bowel disease is a term that describes two diseases:
    1. Crohn disease and ulcerative colitis. Although these two disorders usually differ enough to be clearly distinguishable, they have certain common features. Q
    2. Crohn Disease Is Chronic Segmental Transmural Inflammation of the Intestine
    3. Crohn disease occurs principally in the distal small intestine, but may involve any part of the digestive tract and even extraintestinal tissues. Q
    4. The colon, particularly the right colon, may be affected. Crohn disease has variously been referred to as terminal ileitis and regional ileitis when it involves mainly the ileum, and granulomatous colitis and transmural colitis when it principally affects the colon.
  1. A putative susceptibility locus for Crohn disease has been assigned to the centromeric region of chromosome 16.
  2. Other susceptibility loci may reside on chromosomes 3, 7, and 12. NOD2 mutation determine ileal disease.
  3. The possibility that Crohn disease reflects immunologically mediated damage to the intestine is suggested by the chronic and recurrent nature of the inflammation
Two major characteristics of Crohn disease differentiate it from other gastrointestinal inflammatory diseases.
  1. First, the inflammation usually involves all layers of the bowel wall and is, therefore, referred to as transmural inflammatory disease.
  2. Second, the involvement of the intestine is discontinuous; that is, segments of inflamed tissue are separated by apparently normal intestine.
  3. The disease involves (1) mainly the ileum and cecum in about 50% of cases, (2) only the small intestine in 15%, (3) only the colon in 20%, and (4) mainly the anorectal region in 15%. Disease of the ileum and cecum is more frequent in young persons; colitis is common in older patients.
The Macroscopic pathology of Crohn disease
  1. Grossly, the bowel and adjacent mesentery are thickened and edematous. Mesenteric fat often wraps around the bowel. Mesenteric lymph nodes are frequently enlarged, firm, and matted together. The intestinal lumen is narrowed by edema in early cases and by a combination of edema and fibrosis in long-standing disease. Nodular swelling, fibrosis, and mucosal ulceration lead to a cobblestone appearance. In early cases, ulcers have either an aphthous or a serpiginous appearance; later they become deeper and appear as linear clefts or fissures.
  2. The Cut Surface Q of the bowel wall shows thickening, edema, and fibrosis of all layers. Involved loops of bowel are often adherent and fistulas between such segments are frequent. Most fistulas end blindly, forming abscess cavities in the peritoneal cavity, mesentery, or retroperitoneal structures.
  3. Microscopically, Q Crohn disease appears as a chronic inflammatory process. During early phases of the disease, the inflammation may be confined to the mucosa and submucosa. Small, superficial mucosal ulcerations (aphthous ulcers) are seen, together with mucosal and submucosal edema and an increase in the number of lymphocytes, plasma cells, and macrophages. Destruction of mucosal architecture, with regenerative changes in crypts and villous distortion, are frequent. The Microscopic Hallmark Of Crohn Disease is transmural nodular lymphoid aggregates. Discrete, noncaseating granulomas, mostly in the submucosa, may be present. These granulomas are like those of sarcoidosis and consist of focal aggregates of epithelioid cells, vaguely limited by a rim of lymphocytes. Multinucleated giant cells may be present. The centers of the granulomas usually display hyaline material and only very rarely necrosis.
Ulcerative Colitis
It is a Chronic Superficial Inflammation of the Colon and Rectum
It is characterized by chronic diarrhea and rectal bleeding, with a pattern of exacerbations and remissions and with the possibility of serious local and systemic complications. The disorder occurs principally, but not exclusively, in young adults. Q
It usually begins in early adult life, with peak incidence in the third decade. However, it also occurs in childhood and old age.
  1. Viruses or bacterial infection  
  2. Concordance in monozygotic twins.
  3. Abnormal immune response is involved. This disorder may have autoimmune-like concomitants, such as uveitis, erythema nodosum, and vasculitis. Q
  1. Increased circulating antibodies against antigens in colonic epithelial cells and against cross-reacting antigens in enterobacteria. Q
  2. Antineutrophil cytoplasmic antibodies (ANCAs) are found in 80% of patients with ulcerative colitis.
Three major pathologic features characterize ulcerative colitis and help to differentiate it from other inflammatory conditions:
  1. It extends from the most distal part of the rectum proximally. When it involves the rectum alone, it is called ulcerative proctitis. When the process extends toward the splenic flexure, the terms proctosigmoiditis and left-sided colitis are used.
  2. Inflammation in ulcerative colitis is generally limited to the colon and rectum. It rarely involves the small intestine, stomach, or esophagus. If the cecum is affected, the disease ends at the ileocecal valve, although minor inflammation of the adjacent ileum is sometimes noted (backwash ileitis).
  3. Ulcerative colitis is essentially a mucosal disease. Deeper layers are uncommonly involved, mainly in fulminant cases, usually in association with toxic megacolon.
The following morphologic sequence may develop rapidly or over a course of years.
  1. Early Colitis: Early in the evolution of the disease, the mucosal surface is raw, red, and granular. Later small, superficial erosions or ulcers may appear. These occasionally coalesce to form irregular, shallow, ulcerated areas that appear to surround islands of intact mucosa.
Microscopic Features include: (a) mucosal congestion, edema, and microscopic hemorrhages; (b) a diffuse chronic inflammatory infiltrate in the lamina propria; and (c) damage and distortion of the colorectal crypts, which are often surrounded and infiltrated by neutrophils. Suppurative necrosis of the crypt epithelium gives rise to the characteristic crypt abscess, which appears as a dilated crypt filled with neutrophils. Q
  1. Progressive Colitis: As the disease continues, mucosal folds are lost (atrophy). The strictures characteristic of Crohn disease are absent. Microscopically, colorectal crypts may appear tortuous, branched, and shortened in the late stages and the mucosa may be diffusely atrophic.
  2. Advanced Colitis: In long-standing cases, the large bowel is often shortened, especially in the left side. Mucosal folds are indistinct and are replaced by a granular or smooth mucosal pattern. MICROSCOPICALLY, advanced ulcerative colitis is characterized by mucosal atrophy and a chronic inflammatory infiltrate in the mucosa and superficial submucosa.
Mild Colitis: Their major symptom is rectal bleeding, sometimes accompanied by tenesmus (rectal pressure and discomfort). Extraintestinal complications are uncommon, and in most patients in this category, disease remains mild throughout their lives.
Moderate Colitis: They usually have recurrent episodes of loose bloody stools, crampy abdominal pain, and frequently low-grade fever, lasting days or weeks.
Severe Colitis: About 10% of patients have severe or fulminant ulcerative colitis, sometimes from its onset but often during a flare of activity. They may have more than 6 and sometimes more than 20, bloody bowel movements daily, often with fever and other systemic manifestations. Blood and fluid loss rapidly leads to anemia, dehydration, and electrolyte depletion. Massive hemorrhage may be life-threatening.
Extraintestinal Manifestations
  1. Eye inflammation (mostly uveitis) and skin lesions. Erythema nodosum and pyoderma gangrenosum. Q
  2. Liver disease, most commonly primary sclerosing cholangitis. Those with primary sclerosing cholangitis are at risk for the development of cholangiocarcinoma.
Ulcerative Colitis And Colorectal Cancer
  1. Persons with long-standing ulcerative colitis have a higher risk of colorectal cancer than the general population. The risk is related to the extent of colorectal involvement and the duration of the inflammatory disease.
  2. Young age at the onset of colitis is not an independent risk factor, but since patients in whom ulcerative colitis develops at a young age have a longer duration of disease, they also have a high cumulative incidence of cancer.
Comparison of the Pathologic Features in the Colon of Crohn Disease and Ulcerative Colitis
Lesion Crohn Disease Ulcerative Colitis
  Thickened bowel wall Typical Uncommon
  Luminal narrowing Typical Uncommon
  Skip lesions Common Absent
  Right colon predominance Typical Absent
  Fissures and fistulas Common Absent
  Circumscribed ulcers Common Absent
  Confluent linear ulcers Common Absent
  Pseudopolyps Absent Common
  Transmural inflammation Typical Uncommon
  Submucosal fibrosis Typical Absent
  Fissures Typical Rare
  Granulomas Common Absent
  Crypt abscesses Uncommon Typical

Colorectal Epithelial Dysplasia is a neoplastic epithelial proliferation and precursor to colorectal carcinoma in patients with long-term ulcerative colitis .
The Histopathologic Criteria include
  1. Alteration of mucosal architecture,
  2. Epithelial abnormalities (hypercellularity and stratification of nuclei), and epithelial dysplasia (variation in the size, shape, and staining qualities of nuclei). Dysplasia is divided into low-grade and high-grade dysplasia. High-grade epithelial dysplasia reflects a high risk for the development of colorectal cancer and when identified in a biopsy, it is a strong indication for colectomy. 

Polyps Of The Colon And Rectum

  1. Adenomatous Polyps Are Premalignant Lesions
    Adenomatous polyps (tubular adenomas) are neoplasms that arise from the mucosal epithelium.
    1. Epidemiology
      1. There is a modest male predominance (1.4:1).
  1. Pathology
  1. Located in the rectosigmoid region and can, therefore, be detected by digital examination or by sigmoidoscopy.
  2. The remaining half are evenly distributed throughout the rest of the colon.
  3. The macroscopic appearance of an adenoma varies from a barely visible nodule or small, pedunculated adenoma to a large, sessile (flat) adenoma.  Q
  4. Adenomas are classified by architecture into tubular, villous, and tubulovillous types. They are the usual precursor to colon carinoma, and their epithelium is often dysplastic.
  1. Tubular Adenomas:
  1. Tubular adenomas are usually less than 2 cm in diameter, which often have a stalk.
  2. Microscopically, tubular adenoma has closely packed epithelial tubules, which may be uniform or irregular. Tubules are embedded in a fibrovascular stroma similar to the normal lamina propria. Q Although most tubular adenomas show little epithelial dysplasia, one fifth (particularly larger tumors) may have dysplastic features, which vary from mild nuclear pleomorphism to frank invasive carcinoma. In high-grade dysplasia, glands become crowded and highly irregular in size and shape.
  3. The risk of invasive carcinoma correlates with the size of the tubular adenoma. Only 1% of tubular adenomas under 1 cm display invasive cancer at the time of resection; among those between 1 and 2 cm, 10% harbor malignancy; and among those over 2 cm, 35% are cancerous. Small flat adenomas may be missed during conventional endoscopy and have a high malignant potential.
  1. Villous Adenomas:
  1. These polyps constitute one ten of colonic adenomas and are found predominantly in the rectosigmoid region.
  2. They are typically large, broad-based, elevated lesions with a shaggy, cauliflower-like surface but they can be small and pedunculated. Most are over 2 cm in diameter. On occasion, they reach 10 to 15 cm acrossQ
  3. Microscopically, villous adenomas are composed of thin, tall, fingerlike processes that superficially resemble the villi of the small intestine.
  4. They are lined externally by neoplastic epithelial cells and are supported by a core of fibrovascular connective tissue corresponding to the normal lamina propria.
Villous adenomas contain foci of carcinoma more often than tubular adenomas. In polyps less than 1 cm across, the risk is 10 times higher than that for comparably sized tubular adenomas. 50% of villous adenomas larger than 2 cm harbor invasive carcinoma.. Q
  1. Tubulovillous Adenomas:
  1. Many adenomatous polyps have both tubular and villous features. Polyps with more than 25% and less than 75% villous architecture are termed tubulovillous.
  2. These adenomas tend to be intermediate in distribution and size between the tubular and villous forms, one fourth to one third being larger than 2 cm across. Q
  3. Tubulovillous Polyps Are Also Intermediate Between Tubular And Villous Adenomas In The Risk Of Invasive Carcinoma.
  1. The precursor to colorectal carcinoma is dysplasia, usually in the form of an adenoma.
  2. The pathogenesis of adenomas of the colon and rectum involves neoplastic alteration of crypt epithelial homeostasis with (1) diminished apoptosis, (2) persistent cell replication, and (3) failure to mature and differentiate as the epithelial cells migrate toward the surface of the crypts.
  1. Hyperplastic Polyps
  1. Hyperplastic polyps are small, sessile mucosal excrescences that with exaggerated crypt architecture. Q
  2. They are the most common polypoid lesions of the colon and are particularly frequent in the rectum. Hyperplastic polyps are present in 40% of rectal specimens in persons younger than 40 and in 75% of older persons. Q
  3. They are more common than usual in colons with adenomatous polyps and in populations with higher rates of colorectal cancer.
  1. Pathogenesis
  1. Hyperplastic polyps are believed to arise due to a defect in proliferation and maturation of normal mucosal epithelium.
  2. In a hyperplastic polyp, proliferation occurs at the base of the crypt, and upward migration of the cells is slowed.
  3. Thus, epithelial cells differentiate and acquire absorptive characteristics lower in the crypts. Moreover, cells persist at the surface longer do than normal cells.
  1. Pathology
  1. Hyperplastic polyps are small, sessile, raised mucosal nodules, up to 0.5 cm in diameter but occasionally larger. Q
  2. They are almost always multiple and have even been mistaken for familial adenomatous polyposis (FAP). Q Histologically, the crypts of hyperplastic polyps are elongated and may show cystic dilation. The epithelium contains goblet cells and absorptive cells, with no dysplasia. The surface cells are elongated giving a tufted appearance; this accounts for the serrated contour of the glands near the surface.
  1. Familial Adenomatous Polyposis (FAP) is an Autosomal Dominant Trait
  1. Also termed adenomatous polyposis coli (APC), It is caused by a mutation of the APC gene on the long arm of chromosome 5 (5q21-22). Most cases are familial, but 30% to 50% reflect new mutations. Q
  2. FAP is characterized by hundreds to thousands of adenomas carpeting the colorectal mucosa, sometimes throughout its length, but particularly in the rectosigmoid area. Q
  3. The adenomas are mostly of the tubular variety, although tubulovillous and villous adenomas are also present.
  4. Carcinoma of the colon and rectum is inevitable, the mean age of onset being 40 years.
  5. Total colectomy before onset of cancer is curative.
Genetic testing for FAP is available, but mutations are found in only 75% of familial cases. Subtypes of FAP include:
  1. Attenuated FAP: In this condition adenomas in the colon number less than 100.
  2. Gardner syndrome: Q This variant features extracolonic lesions including osteomas of the skull, mandible, and long bones; epidermoid cysts; desmoid tumors; and congential hypertrophy of the retinal pigment epithelium. APC gene mutations do not predict this phenotype.
  3. Turcot syndrome: Q This rare disorder combines FAP with malignant tumors of the central nervous system. Many cases, especially those with medulloblastoma, are due to germline mutation of the APC gene. Some cases, especially those with glioblastoma multiforme, are part of the spectrum of the HNPCC syndrome (see below). 
Non-Neoplastic Polyps Are Acquired Lesions
Non-neoplastic polyps are entirely different entities and are grouped together solely because of their gross appearance as raised lesions of the colonic mucosa.
  1. Juvenile Polyps (Retention Polyps)
    Juvenile polyps are hamartomatous proliferations of the colonic mucosa. They are most common in children younger than 10 years, although one third occur in adults. 
  1. Juvenile polyps are single or (rarely) multiple. They mostly occur in the rectum, but may be seen anywhere in the small or large bowel.
  2. Grossly, most are pedunculated lesions up to 2 cm in diameter. They have smooth, rounded surfaces, unlike fissured surfaces of adenomatous polyps.
  3. Microscopically, dilated and cystic epithelial tubules filled with mucus and are embedded in a fibrovascular lamina propria.
  1. Inflammatory Polyps
    Inflammatory polyps are not neoplasms but are elevated nodules of inflamed, regenerating epithelium. They are commonly found in association with ulcerative colitis and Crohn disease; they are also encountered in cases of amebic colitis and bacterial dysentery. Microscopically, inflammatory polyps are composed of a variable component of distorted and inflamed mucosal glands, often intermixed with granulation tissue. Q
    As healing proceeds, epithelial regeneration characterized by large, basophilic epithelial cells restores mucosal

Malignant Tumors

Adenocarcinoma Of The Colon And Rectum Is an Example of Multistep Carcinogenesis
  1. Colon cancer shows a slight female preponderance, whereas rectal cancer is somewhat more common in men.
  2. The proportion of cancers in the distal colorectum has been declining in recent decades.
  1. Most cancers of the colon and rectum arise in adenomatous polyps and so factors associated with the development of such polyps are relevant to the genesis of colorectal cancer.
  2. DIETARY FIBER: A diet low in indigestible fiber and high in animal fat has been implicated in the etiology of other colonic diseases, including diverticulosis and appendicitis. Q Such a diet is associated with slower transit of fecal contents through the colon, and some suggest that this permits longer exposure of the mucosa to possibly toxic substances in the stools. on such an explanation.
  3. DIETARY FAT: Consumption of animal fats is paralleled by increased colorectal cancer. Ingestion of fat elicits bile secretion into the intestine, and some bile acids may augment the tumorigenicity of experimental intestinal carcinogens.
  4. ANAEROBIC BACTERIA: The feces of persons in high-risk populations have a higher content of anaerobic bacteria than do those in low-risk populations. Q
  5. OTHER DIETARY FACTORS: Selenium, glutathione peroxidase, vit. E protective effect have ascorbic acid. Also diets rich in cruciferous vegetables (e.g., cauliflower, Brussels sprouts, and cabbage) and those that provide vitamin A may be associated with a lower incidence of colorectal cancer. Q
Molecular Genetics Of Colorectal Cancer
In 85% of cases of colorectal carcinoma, it has been estimated that at least 8 to 10 mutational events must accumulate before an invasive cancer with metastatic potential develops. This process is initiated in histologically normal mucosa, proceeds through an adenomatous precursor stage, and ends as invasive adenocarcinoma.
  1. APC Gene: As noted above, germline mutations in APC (adenomatous polyposis coli), a putative tumor-suppressor gene, lead to familial adenomatous polyposis.  Some tumors with normal APC have mutations in the b-catenin gene,Q whose product binds to the APC protein. APC mutations are seen in normal colonic mucosa preceding development of sporadic adenomas. Q
  2. Ras Oncogene: Activating mutations of the ras protooncogene occur early in tubular adenomas of the colon.
  3. DCC Gene: A putative tumor-suppressor gene, DCC (deleted in colon cancer) is located on chromosome 18 and is often missing in colorectal cancers.
  4. P53 Tumor-Suppressor Gene: In the most common type of adenocarcinoma of the colon, mutation of p53 participates in the transition from adenoma to carcinoma and is a late event in the carcinogenic pathway.
  5. In 15% of colorectal cancers, DNA mismatch repair (MMR) is impaired, leading to a deficient repair of spontaneous replication errors, particularly in simple repetitive sequences (microsatellites).
  6. MMR deficiencies can occur through two mechanisms in a hereditary form (HNPCC, Lynch syndrome), a germline mutation in one of the MMR genes is followed by a somatic mutation of the other allele. Q
  7. In a sporadic form, hypermethylation of the MMR promoter, MLH1, inactivates transcription of the gene.
Genes involved in development of colorectal cancer
Oncogenes / Protooncogene
Tumor suppressor
Mismatch Repair Genes
K-ras APC
DCC (Deleated in colon Cancer)
h MLH – 1
h MLH – 2
h MLH – 3
h MLH – 6
h MLH – 1
h MLH – 2
Extra Edge:
Beta-catenin is signal transducing protein which acts on proto-oncogene, c-myc causing cell proliferation. APC is a tumour suppressor gene & has an inhibitory control on the action of beta-catenin. The proteins from K-ras gene along with GTP-GDP act as important signal transducing pathway.
Important Points
  1. β Catenin is the main downstream target of APC actin.
  2. APC functions to modulate extracellular signals that are transmitted to the nucleus through a cytokeletal protein b -catenin' which then regulates transcription and other target genes.
  3. APC is a tumor suppressor gene that bind to b- catenin and causes its degradation unopposed stimulation of various pathways that lead to tumor genesis
  4. Besides inactivating mutations of APC gene, tumor genesis can also occur directly though dominant stimulatory mutations of the b- catenin gene. Such mutation are found in 15-20% of Microsatellite Instability colon cancers.
Risk Factors
  1. Age: Increasing age is probably the single most important risk factor for colorectal cancer in the general population.
  2. Prior Colorectal Cancer: Patients with a prior colorectal cancer are at increased risk for a subsequent tumor.
  3. Ulcerative Colitis And Crohn Disease: Q
    These chronic inflammatory diseases increase the risk of colorectal cancer in proportion to their duration and extent of involvement within the large bowel.
  4. Genetic Factors: Colorectal cancer is increased in frequency among relatives of patients with the disease.
  5. Diet: The daily consumption of red meat and animal fat leads to a higher risk of colorectal cancer than that in persons who eat little or no meat.
Pathology Q
  1. Grossly colorectal cancers resemble adenocarcinomas elsewhere in the gut.
  2. They tend to be polypoid and ulcerating or infiltrative and may be annular and constrictive. 
  3. Polypoid cancers are more common in the right colon, particularly in the cecum, where the large caliber of the colon allows unimpeded intraluminal growth.
  4. Annular constricting tumors are more common in the distal colon. Ulceration of tumors, irrespective of growth pattern, is common.
  5. Current staging of colorectal carcinomas uses TNM classification (tumor, lymph nodes, and metastasis). In this system T1 tumor invades the submucosa; T2 tumor infiltrates into, but not through, the muscularis propria; T3 tumor invades into the subserosal tissue; and T4 tumors penetrate the serosa or involve adjacent organs. N refers to presence or absence of nodal metastases, and M to the presence or absence of extranodal metastases.
Clinical Features
  1. Initially, colorectal cancer is clinically silent.
  2. As the tumor grows, the most common sign is occult blood in the feces when the tumor is in the proximal portions of the colon.
  3. Both occult blood and bright red blood in the feces may occur if a lesion is in the distal colorectum.
  4. Cancers on the left side of the colon, where the caliber of the lumen is small and the fecal contents more solid, often constrict the lumen, producing obstructive symptoms. These are manifested as changes in bowel habits and abdominal pain.
On the right side of the colon, particularly in the cecum, the colon lumen is large and fecal contents are liquid, tumors can grow to large size without causing symptoms of obstruction. 

Hereditary Nonpolyposis Colorectal Cancer Syndrome

  1. HNPCC, or Warthin-Lynch syndrome is an autosomal dominant inherited disease that accounts for 3% to 5% of all colorectal cancers.
  2. It is characterized by (1) onset of colorectal cancer at a young age (2) few adenomas (3) a high frequency of carcinomas proximal to the splenic flexure (70%); (4) multiple synchronous or metachronous colorectal cancers; and (5) extracolonic cancers, including endometrial and ovarian cancers, adenocarcinomas of the stomach, small intestine, and hepatobiliary tract, as well as transitional cell carcinomas of the renal pelvis and ureter. Q
  3. Patients with HNPCC may also have sebaceous adenomas and carcinomas and multiple keratoacanthomas.
  4. HNPCC-related colorectal cancers are characterized by a high frequency of mucinous, signet ring cell and solid (medullary) carcinomas, and frequent intratumoral lymphocytes.
  1. HNPCC is caused by germline mutations in a DNA mismatch repair gene.
  2. In most cases, hMSH2 (human MutS homolog 2) on chromosome 2p and hMLH1 (human MutL homolog 1) on chromosome 3p are affected. A smaller number of cases are caused by mutations in hMSH6 (human MutS homolog 6) and hPMS2 (human postmeiotic segregation 2) on chromosomes 2p and 7p, respectively. Q
  3. In patients with HNPCC there is a germline mutation in one allele of one of the mismatch repair genes, and the second allele is deleted in a somatic second hit. The result is that spontaneous replication errors are not repaired effectively. This leads to widespread genomic instability, particularly in simple repetitive sequences (microsatellites), which are particularly prone to replication errors. Thus, genes that regulate growth and differentiation, and other mismatch repair genes, are disabled by unrepaired mutations. Q
  4. Mismatch repair deficiency can be assessed by testing for microsatellite instability and loss of immunohistochemical expression of mismatch repair proteins in a tumor. If suspicion of HNPCC persists, mutation analysis of mismatch repair genes is available.
Carcinoid Tumors (Neuroendocrine Tumors)
  1. Colorectal carcinoid tumors behave like similar tumors of the small intestine.
  2. Half of carcinoid tumors of the colorectum have metastasized at the time they are discovered.
Large Bowel Lymphoma is Usually B-cell Lymphoma
  1. Primary lymphoma of the colorectum is uncommon.
  2. It may be seen as (1) segmental involvement of the mucosa, (2) diffuse polypoid lesions, or (3) a mass extending beyond the confines of the colorectum.
  3. Presenting symptoms are similar to those of other primary intestinal cancers, but the diffuse polypoid form may resemble inflammatory polyps or adenomatous polyps.
  4. Most large bowel lymphomas are derived from B cells.

Cancers Of The Anal Canal Are Epidermoid Carcinomas

  1. Carcinomas of the anal canal, may arise at or above the dentate line.  Q
  2. These tumors more common in women.
  1. Anal cancers have various histologic patterns, such as squamous, basaloid (cloacogenic) or mucoepidermoid, but the different tumor types exhibit similar clinical behavior and so are all classed as epidermoid carcinomas.
  2. Bowen disease of the anus is squamous carcinoma in situ, while extramammary Paget disease at this site reflects intraepithelial adenocarcinoma (either primary of the mucosa or metastatic).
  3. Carcinoma of the anus penetrates directly into surrounding tissues, including internal and external sphincters, perianal soft tissues, prostate, and vagina.
Clinical Features:
  1. Infection with human papilloma virus (HPV) and chronic inflammatory disease of the anus (e.g., venereal disease), fissures, and trauma predispose to anal cancer.
  2. Factors associated with genital carcinoma (cancer of the penis, scrotum, cervix or vulva), poor hygiene, indiscriminate sexual practices, and genital warts also contribute to the development of anal cancer. Q
  3. The usual symptoms of anal cancers include bleeding, pain, and an anal or rectal mass. Often a tumor is not clinically recognized as a malignant lesion and may be discovered only in a hemorrhoidectomy specimen. Q
  4. Combined chemotherapy and radiation therapy is the customary treatment, although abdominal perineal resection is sometimes carried out. More than half of patients survive for at least 5 years.

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