
Colon-tumor
Last revised 28 May 2008
Last major update October 2006
Copyright (c) 2003-2008, PathologyOutlines.com, Inc.
See also Colon-nontumor, Anus and perianal area
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Primary references, images needed
Polyps: general, biopsies, aberrant crypt foci, adenoma, carcinoma arising in adenoma, adenoma-carcinoma sequence, atheroemboli, cap polyposis, displaced glands, diverticular, fibroblastic, flat adenoma, hyperplastic, hyperplastic polyposis, inflammatory, inflammatory fibroid, inflammatory myoglandular, juvenile, lymphoid, Peutz-Jegher, post-surgical, serrated, transitional, tubular adenoma, tubulovillous adenoma, villous adenoma
Familial polyposis syndromes: APC gene, Cowden’s, Cronkhite-Canada, familial adenomatous polyposis-classic, attenuated, Gardner’s, hereditary mixed polyposis, hyperplastic polyposis, juvenile polyposis, Lynch, Muir-Torre, MUTYH associated, Peutz-Jegher, Turcot’s
Carcinoma: general, molecular pathways, WHO classification, post-treatment changes, intramucosal, adenocarcinoma, adenosquamous, carcinosarcoma, clear cell, glassy cell, hepatoid, lymphoepithelioma-like, medullary, metastases to colon, mucinous, neuroendocrine, papillary, signet ring, small cell, small early flat, squamous cell, villous
Carcinoid tumors: rectum, not rectum
Lymphoma and hematopoietic lesions: general, Burkitt’s, follicular, HHV8, Hodgkin’s, MALT, mantle cell, mast cell sarcoma, T cell
Mesenchymal tumors: general, angiomyolipoma, angiosarcoma, endometrial stromal sarcoma, fibromatosis, ganglioneuromatosis, GANT, GIST, hemangioma, histiocytic sarcoma, idiopathic retractile mesenteritis, idiopathic retroperitoneal fibrosis, inflammatory myofibroblastic tumor, Kaposi’s sarcoma, leiomyoma, leiomyomatosis, leiomyomatosis-like lymphangioleiomyomatosis, leiomyosarcoma, lipoma, lipomatosis, liposarcoma, Mullerian adenosarcoma, perineurioma, perivascular epithelioid cell tumor, pyogenic granuloma, reactive nodular fibrous pseudotumor, schwannoma, solitary fibrous tumor
Other tumors: Langerhans cell histiocytosis, Rosai-Dorfman disease, teratoma
Other: grossing, staging, features to report
Go to Colon-nontumor (normal, congenital anomalies, diverticular disease, inflammatory bowel disease, colitis (non-infectious and infectious), non-neoplastic non-congenital lesions)
AJCC Cancer Staging Manual (6th Ed)
American Journal of Clinical Pathology (AJCP), Jan 1975 to October 2006
American Journal of Surgical Pathology (AJSP), March 1977 to September 2006
Archives of Pathology and Laboratory Medicine (Archives), January 1976 to September 2006
Human Pathology (Hum Path), March 1970 to September 2006
Journal of Clinical Pathology, January 1966 to September 2006
Modern Pathology (Mod Path), January 1988 to September 2006
Biomed Center, to 8 September 2006
Mills: Sternberg's Diagnostic Surgical Pathology (4th ed), 2004
Rosai: Rosai and Ackerman's Surgical Pathology (9th ed), 2004
Websites with images: PathoPic, PEIR digital library
Please refer to these primary references for more detailed discussions and photographs
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Gross, EM and immunohistochemistry images are needed for most disorders
Micro images are particularly needed for these lesions:
Carcinoma - post-treatment changes, intramucosal carcinoma, adenosquamous, glassy cell, hepatoid, metastases to colon, neuroendocrine, squamous cell
Carcinoid - not rectum
Mesenchymal tumors - leiomyomatosis, reactive nodular fibrous pseudotumor, solitary fibrous tumor
Other tumors - hemangioma, Langerhans cell histiocytosis, Rosai-Dorfman disease, teratoma
Polyps of colon
Definition: mass protruding into lumen of gut
Sessile: no stalk
Pedunculated: polyp with stalk, may be due to traction on the mass
Polyps that are due to abnormal mucosal maturation, inflammation or architecture are non-neoplastic
Polyps that are due to proliferation and dysplasia are neoplastic / adenomatous
Polypoid lesions may also be due to mucosal or submucosal tumors
Clinical impression correlates poorly with neoplasia (J Gastroenterol Hepatol 2006;21:563)
Appelman recommends calling “benign mucosal polyp” unless (a) diagnosis is adenoma [the only diagnosis that causes clinicians to do anything different] or (b) you can classify it within 30 seconds
Muciphages, without other abnormalities, have no clinical significance (Histopathology 2000;36:556)
Earliest neoplastic lesion of colon
May predict future adenoma or carcinoma (Am J Gastroenterol 2006;101:1362, Am J Gastroenterol 2005;100:1283)
May be useful to monitor effects of chemoprevention agents (Clin Gastroenterol Hepatol 2005;3:S42)
Micro: crypts are 2-3x larger than normal crypts, are microscopically elevated, have slit-like openings, and have thick epithelial lining that stains darker than normal crypts (particularly with Methylene blue), with large pericryptal zone
Micro images: aberrant crypt foci #1; #2 with dysplasia; #3 (methylene blue)
References: Cancer Epidemiol Biomarkers Prev 1991;1:57. World J Gastroenterol 2003;9:2642, Anticancer Res 2006;26:107, summary
“Adenoma” is an incorrect term - they are not benign neoplasms, but polypoid areas of epithelial dysplasia
Present in 20% (US) at age 40 years, 50% at age 60; in autopsy studies, almost all have tubular adenomas, <5% have tubulovillous or villous adenomas
Low incidence in developing countries
No gender predilection
Slow growing
Decreased risk of distal colon adenoma associated with dietary fiber intake (Lancet 2003;361:1491), fruit consumption in women (Cancer Res 2006;66:3942); folate intake (J Nutr 2005;135:2468); only weak association between fiber and adenoma recurrence (Am J Gastroenterol 2005;100:2789)
30% develop new polyps after mean 26 month follow up; higher risk if 3 or more adenomas and at least one in proximal colon (Dis Colon Rectum 2004;47:323)
Risk of invasive colorectal adenocarcinoma in the adenoma depends on size: <1% if < 1 cm vs. 10% if > 2 cm; higher risk if villous component
Risk of subsequent carcinoma is related to presence of 3 or more polyps, location at transverse colon or proximal, or [one study] presence of monotonous population of elongated cells (AJSP 2006;30:1120)
Vienna classification (1999) described at J Gastroenterol Hepatol 2006;21:1697.
Treatment: excision of a pedunculated adenoma, even with invasive carcinoma (see below), is considered adequate treatment if margin is negative, there is no vascular or lymphatic invasion and carcinoma is moderate or well differentiated; invasive adenocarcinoma in a sessile polyp requires more than polypectomy
Gross: classified as pedunculated (with stalk), sessile or flat; tubular are red (darker than surrounding mucosa); villous are shaggy with papillary fronds; true margin of resection should be inked when grossing, or can be determined by diathermy artifact
Gross images: peduculated adenoma #1; #2; #3; #4; #5; #6; sessile adenoma #1; #2
Micro: classify microscopically as tubular, tubulovillous (5%) or villous (1%) adenoma; all contain epithelial proliferative dysplasia; dysplasia can be classified as low grade or high grade, although some GI pathologists recommend not using high grade dysplasia terminology unless clinicians want to know
Low grade: nuclei are elongated and dysplastic, but don’t reach cell surface; apical mucin present
High grade: cytologic and architectural changes of dysplasia; nuclei are enlarged, hyperchromatic or vesicular with prominent nucleoli; nuclei are stratified and reach luminal border; cribriform or irregular budding/branching of crypts is present; prominent mitotic figures; reduced mucin; necrosis may be present; no invasion through muscularis mucosa into submucosa; high grade dysplasia present in 12% of adenomas
Intramucosal carcinoma: invasion of lamina propria only with desmoplastic response; no biologic potential for metastases
References: Am J Gastroenterol 2006;101:255 (prevalence)
Invasive carcinoma arising in a colonic adenoma
Present in 5% of adenomas (G Chir 2001;22:26)
Invasive only if cancer has invaded through muscularis mucosa into submucosa
Recommended to NOT use “carcinoma in situ” terminology in colorectum; use either high grade dysplasia or invasive carcinoma
Report type of carcinoma, grade, presence of angiolymphatic invasion (tumor emboli in true endothelial lined channels away from tumor, not retraction artifact), status of resection margins (close to margin is within one high power field or 1-2 mm from diathermy or at diathermy), presence of dysplasia
Sample report #1: poorly differentiated carcinoma arising within an adenoma, extending to resection margin, no angiolymphatic invasion
Sample report #2: moderately differentiated carcinoma arising with an adenoma; tumor 2.5 cm from resection margin, no angiolymphatic invasion
Case reports: adenoma with carcinoma and mixed carcinoid-adenocarcinoma (Pathol Int 2003;53:457), with sarcoid reaction in regional lymph nodes (J Clin Gastroenterol 1999;28:377), squamous cell carcinoma arising in villous adenoma (Hum Path 1988;19:362), metastatic signet ring carcinoma in adenoma (Archives 2003;127:1509)
Treatment: polypectomy probably adequate unless margin involvement, poorly differentiated or angiolymphatic invasion (J Surg Oncol 1987;36:116)
Recurrent disease, nodal metastases or residual local disease: 20% incidence if cancer is near margin, is poorly differentiated or if angiolymphatic invasion is present
Gross images: adenocarcinoma arising in villous adenoma; focal carcinoma in adenoma
Micro images: adenocarcinoma arising in tubular adenoma; arising in villous adenoma; metastatic signet ring adenocarcinoma in adenoma
Well characterized series of histopathologic events associated with distinct molecular alterations
There are two general pathways - chromosomal instability (abnormal number of chromosomes, not diploid) and microsatellite instability (diploid but DNA mismatch repair gene alterations)
Chromosomal instability pathway
Carcinomas arise from accumulation of mutations in various genes that initially cause adenomatous polyps (usually), some of which then acquire addition mutations and become malignant (4-10 mutations required to produce malignant phenotype)
Molecular pathway may vary in each particular tumor
Earliest event often involves APC gene (mutated in familial polyposis)
Other early events are DNA methylation changes (Genes Chromosomes Cancer 2006;45:781), which may cause oncogene activation or tumor suppression gene repression
K-ras (10% of adenomas, 50% of adenomas with severe dysplasia, 50% of carcinomas) occurs in larger but not smaller polyps
DPC4 and DCC (18q21, reduced expression in 70% of carcinomas) occur later
p53 mutations (17p, losses in 70% of carcinomas) occur late
Removing adenomas via screening colonoscopy reduces incidence of colorectal cancer (N Engl J Med 1993;329:1977)
Polyposis syndrome patients have increased risk for carcinoma (nearly 100% for familial polyposis and Gardner’s syndrome)
Villous adenomas have higher malignant risk than tubular adenomas
Microsatellite instability pathway
Some carcinomas arise without a polypoid dysplastic stage (AJCP 2006;125:132); associated with DNA mismatch repair or microsatellite instability
BRAF mutations are also associated with the microsatellite instability pathway (Gut 2004;53:1137)
Polyps with no malignant risk: solitary hyperplastic polyps, juvenile polyps and Peutz-Jegher polyps
Diagrams: diagram #1; #2
References: H. Lee Moffitt Cancer Center, eMedicine (#413), BMJ 2000;321:886
Atheroemboli associated polyps of colon
May be associated with rectal bleeding (AJSP 1991;15:1078)
Case reports: 68 year old man with diabetes and 2 year history of bloody diarrhea (AJSP 1993;17:1054), polypoid mass without clinical evidence of ischemia (Archives 1994;118:308), cholesterol emboli in polyp (J Clin Gastroenterol 1994;19:231)
Micro: edematous submucosa with superficial ulceration and atheroemboli in arterioles of submucosal polyps
First described in 1985 (Br J Surg 1985; 72 (Suppl) S133)
Rare
Etiology unknown, but may be associated with mucosal prolapse (Gut 1993;34:562)
Often presents with mucoid or bloody diarrhea and hypoproteinemia
Endoscopy: multiple sessile rectosigmoid polyps with adherent white flecks, with normal intervening mucosa (Endoscopy 2001;33:262)
Case reports: Case of the Week #102
Treatment: traditionally polypectomy or partial colectomy (Dis Colon Rectum 2004;47:1208); recent case reports of dramatic results from medical treatment in patients with H. pylori gastritis (Helicobacter 2004;9:651) and using infliximab, an antibody to tumor necrosis alpha (Gastroenterology 2004;126:1868)
Gross: multiple, distinctive, inflammatory rectosigmoid polyps
Gross images: multiple colonic polyps
Micro: inflamed mucosa with tortuous, elongated crypts, attenuated towards the mucosal surface, with granulation tissue ”cap” on the mucosal surface
Micro images: image #1; #2; #3; #4
DD: amebic colitis, antibiotic associated colitis, inflammatory bowel disease
Also called epithelial misplacement
Presence of dysplastic glands from an adenoma beneath the muscularis mucosa due to biopsy related torsion or other trauma
A low power diagnosis
Occurs in 3% of adenomas, usually with well-defined stalks
Resembles intramucosal carcinoma, but cytologic features resemble adenoma
See also below (hyperplastic polyp with misplaced epithelium)
Micro: submucosal glands surrounded by loose inflamed stroma and granulation tissue, but not desmoplastic stroma; glands may have atypia associated with adenoma but not carcinoma
Negative stains: p53, E-cadherin, type IV collagen (AJSP 2002;26:206)
References: AJSP 1993;17:1262, Cancer 1974;33:206
Arises in background of diverticular disease
Usually in sigmoid colon
Part of the “mucosal prolapse” syndrome (Am J Gastroenterol 2002;97:370)
Treatment: high fiber diet is usually effective (Endoscopy 1986;18:84)
Gross: redundant or polypoid mucosal folds
Micro: mucosal hemorrhage and congestion, epithelial hyperplasia with dilated and serrated crypts and bizarre nuclei in stroma, mucosal edema, fibromuscular replacement of lamina propria with thickened and splayed muscularis mucosa; no dysplastic changes
Micro images: elongated crypts without dysplasia; figure 3: epithelial hyperplasia, inflammation, congestion and fibromuscular stroma; figure 4: smooth muscle actin staining
References: AJSP 1991;15:871, Histopathology 1993;23:63
Initially described in 2004 (AJSP 2004;28:374)
May be due to exuberant response to tissue injury (J Clin Gastroenterol 2005;39:778)
May be early stage of inflammatory fibrous polyp (AJSP 2004;28:1397-letter)
Solitary, usually in sigmoid colon
Treatment: excision (benign behavior)
Gross: 2-4 mm
Micro: mucosal polyp composed of bland, plump spindle cells in lamina propria with fibroblastic features; spindle cells are associated with muscularis mucosa, cause separation and disorganization of colonic crypts; often associated with serrated / hyperplastic crypts; no atypia, no mitotic activity, no necrosis
Positive stains: vimentin; occasional weak/focal CD34 or smooth muscle actin
Negative stains: desmin, CD31, CD68, bcl2, c-kit, S100, EMA
EM: sparse cytoplasmic organelles, many intermediate filaments
References: Histopathology 2006;48:431
Also called depressed adenoma
Present in asymptomatic populations (Gut 1998;43:229)
More difficult to detect during endoscopy, but targeted indigo carmine chromoscopy or other methods are useful (article and images)
Diagnosis requires (a) classic endoscopic (gross) appearance of mucosal elevation with flat/rounded surface and height less than half the diameter, (b) not resembling a hyperplastic polyp, and (c) dysplastic changes
Another study defined flat as thickness of 1.3 mm or less or thickness less than twice normal mucosal thickness
Controversial if associated with higher risk for high grade dysplasia (no-Clin Gastroenterol Hepatol 2004;2:905; yes-Dis Colon Rectum 1991;34:981); risk may be higher if central depression, individual history or family history of malignancy (Dis Colon Rectum 2000;43:782), or larger lesion (Dis Colon Rectum 1985;28:847)
Endoscopic images: flat adenoma
Case reports: with deep malignant component (Virchows Arch A Pathol Anat Histopathol 1993;422:415)
Gross: flat or slightly raised plaques, often with a central depression; usually height 2 mm or less; may be multiple
Micro: plaque-like, not polypoid or exophytic; up to twice the thickness of adjacent normal epithelium; usually tubular adenomas that show superficial adenomatous changes at periphery, and centrally may extend throughout the crypt
Also associated with aberrant crypt foci (Am J Gastroenterol 2005;100:1283)
Micro images: flat adenoma with subtle merging of normal and adenomatous epithelium; flat adenoma; A: flat adenoma; B: MUC2+; C: MUC1+ only focally; A: flat adenoma; B: MUC2+; C: MUC1+ at base of crypts; MUC2-left; MUC1-right
Molecular: some cases have multiple APC mutations (Eur J Hum Genet 1999;7:928)
References: Hum Path 1991;22:70, Am J Gastroenterol 2006;101:172
90% of all polyps
Usually patients age 50+ years, often in rectosigmoid
Present in 30-50% of normal individuals (85% of adults in Western world versus 2% in third world countries)
Due to delayed shedding of surface epithelial cells
Associated with cigarette smoking (Cancer Causes Control 2005;16:1021)
Previously considered to have no/minimal malignant potential (Arch Intern Med 2005;165:382), except for those in hyperplastic polyposis syndrome
Right sided hyperplastic polyps are molecularly more similar to serrated adenomas than to left sided hyperplastic polyps, and are associated with cancers that show microsatellite instability (but see J Clin Pathol 2004;57:1089)
Intermediate (6-9 mm) sized polyps are usually right sided, and are associated with synchronous colorectal carcinoma (J Gastroenterol Hepatol 2005;20:1572)
Case reports: with small invasive carcinoma (Endoscopy 2004;36:825)
Gross: small (< 5 mm), sessile, usually on top of mucosal folds, multiple, same color as surrounding mucosa; lesions up to several cm may occur in right colon but may be serrated adenomas
Gross images: hyperplastic polyp
Micro: well formed, elongated glands and crypts with serrated (saw tooth) or star-shaped appearance resembling secretory endometrium; mixture of goblet cells (with abundant mucin) and absorptive cells; bland cytology with eosinophilic cytoplasm, well defined brush borders, basal nuclei; thickened basement membrane; Paneth cells in 8%; may have multinucleated giant cells (AJSP 2005;29:912); cells at base of crypt may have nuclear elongation, crowding and increased mitotic rate, but this is not adenomatous change; may be splaying of muscularis mucosa fibers into submucosa; large hyperplastic polyps may have adenomatous foci
Micro images: serrated crypts #1; #2; #3; #4; #5; #6; right sided vs. left sided polyps
Virtual slides: hyperplastic polyp
Molecular: limited changes, no relation to changes in coexisting adenomas (J Clin Pathol 2004;57:1084)
Hyperplastic polyp of colon with misplaced epithelium
Also called “pseudoinvasion”
Some authorities consider it synonymous to inverted hyperplastic polyp, but others consider them different
Simulates adenoma with pseudoinvasion, but benign
Arises in left colon due to local trauma (torsion or twisting of polyp, vigorous peristalsis)
Micro: colonic epithelium in lamina propria with mixed pattern (lobules and irregularly distributed crypts) or lobular pattern; continuous with mucosal portion of polyp in deeper levels; defects are present in muscularis mucosa, and muscle fibers are splayed round misplaced epithelium; often lymphoid aggregates adjacent to misplaced epithelium, fresh hemorrhage, vascular congestion, hemosiderin deposits; usually no significant inflammation, no dysplasia
Micro images: misplaced epithelium #1; #2; #3; #4; Ki67/MIB1; collagen IV
Positive stains for misplaced epithelium: Ki-67, E-cadherin, collagen IV basement membrane
References: Mod Path 2001;14:869
Inverted hyperplastic polyp of colon
More frequent in right colon
May be more common in women
Case reports: associated with adenoma (Eur J Gastroenterol Hepatol 2004;16:107), inverted hyperplastic polyposis (J Clin Pathol 1993;46:56)
Gross images: inverted polyposis
Micro: endophytic growth pattern, penetrates muscularis mucosa (AJSP 1985;9:265)
Micro images - inverted polyps #1; #2 associated with submucosal adipose; #3-large submucosal mucin cyst; #4 with epithelial displacement to lymphoid follicle; CEA+ (normal colon at upper right is CEA neg)
Uncommon
Also called serrated adenomatous polyposis because polyps appear to be serrated adenomas
WHO definition: (a) at least 5 histologically diagnosed hyperplastic polyps proximal to sigmoid colon, two of which are larger than 1 cm; or (b) any number of hyperplastic polyps proximal to sigmoid colon in patients with a first-degree relative with hyperplastic polyposis; or (c) more than 30 hyperplastic polyps of any size distributed throughout colorectum (Hyperplastic polyposis. Lyon: IARC Press; 2000)
High risk for colorectal carcinoma (Dis Colon Rectum 2004;47:2101, AJSP 2001;25:177); regular surveillance is recommended (Am J Gastroenterol 2004;99:2012), including family members
Case reports: associated with two synchronous carcinomas (Am J Pathol 2000;157:385), inverted hyperplastic polyposis (J Clin Pathol. 1993;46:56)
Gross: polyps are usually sessile
Gross images: inverted polyposis
Micro images: serrated adenoma in hyperplastic polyposis #1; #2; #3; associated with synchronous carcinoma
inverted hyperplastic polyps - #1; #2 associated with submucosal adipose; #3-large submucosal mucin cyst; #4 with epithelial displacement to lymphoid follicle; CEA+ (normal colon at upper right is CEA negative)
Molecular: extensive methylation in adenomas and in normal mucosa (Gut 2006;55:1467)
Inflamed regenerating mucosa surrounded by ulcerated tissue; also granulation tissue overlying epithelium
Associated with Crohn’s disease or ulcerative colitis; also amebiasis, schistosomiasis, ulcer, anastomotic sites
Usually asymptomatic but may cause obstruction or hemorrhage
Benign; no increased risk of dysplasia compared to surrounding mucosa
Case reports: with ischemia (Am Surg 1993;59:315), with schistosomiasis (J Clin Gastroenterol 1983;5:169), simulating carcinoma due to multiple fused polyps (Am J Gastroenterol 1980;73:441)
Endoscopic images: inflammatory polyps in ulcerative colitis
Treatment: treat underlying inflammatory condition
Gross: smooth hyperemic or hypervascular appearance; variable surface erosion
Gross images: inflammatory pseudopolyps in ulcerative colitis #1; #2; #3
Micro: inflamed lamina propria and distorted colonic epithelium (branched, tortuous, elongated or cystic crypts); may have surface erosion, congestion/hemorrhage or crypt abscesses; may have bizarre stromal changes in reactive fibroblasts resembling sarcoma in a fibroblastic or granulation tissue stroma, particularly underneath areas of ulceration; no/few mitotic figures, no atypical mitotic figures, often zonation
Micro images: ulcerative colitis #1; #2; #3; annotated images; bizarre stromal cells
Positive stains: vimentin
Negative stains: S100, cytokeratin, CMV
DD: pyogenic granuloma (Ann Diagn Pathol 2005;9:106)
Giant inflammatory polyp / polyposis of colon
Also called filiform polyposis if have long finger-like projections
Uncommon, benign
Usually associated with inflammatory bowel disease
May be diffuse (Archives 2004;128:1286)
May cause obstruction (J Gastroenterol 2005;40:536, Intern Med 1996;35:24) or intussusception (Inflamm Bowel Dis 2004;10:41),
Case reports: no history of colonic disease (Gastroenterol Clin Biol 2006;30:913, Neth J Surg 1987;39:95), with cystic fibrosis and Crohn’s disease (Pediatr Dev Pathol 2006;9:25), with Crohn’s disease (Pathol Int 2002;52:318), remission after topical budesonide (Anticancer Res 2005;25:2961)
Treatment: usually surgery (Z Gastroenterol 2000;38:845) since cannot clinically distinguish dysplastic and inflammatory polyps
Gross images: associated with protein losing enteropathy; various images
Micro images: various images; figu