Colon-tumor Printer Friendly Version

Last revised 20 December 2006

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Table of contents

Primary references, images needed

Polyps: general, biopsies, aberrant crypt foci, adenoma, carcinoma arising in adenoma, adenoma-carcinoma sequence, atheroemboli, 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)

 

Primary references

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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

 

Images needed for colon

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We welcome your contributions of digital images, which we will post in the appropriate section of this chapter, and which help pathologists worldwide.

To contribute, email your digital images (GIF or JPG, any size) to Dr. Pernick at info@PathologyOutlines.com.  We will list your name as a contributor unless you want to be anonymous.  Click here for more information

Gross, EM and immunohistochemistry images are needed for most disorders

Micro images are particularly needed for these lesions:

Polyps - atheroemboli associated, displaced glands, fibroblastic polyp, post-surgical polyp, transitional polyp
Familial polyposis syndromes - Cowden’s syndrome, Cronkhite-Canada syndrome, familial adenomatous polyposis (classic and attenuated), hereditary mixed syndrome, Lynch syndrome, Muir-Torre, MUTYH associated, Turcot’s syndrome

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

Polyps-general of colon

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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

 

Biopsies of colon

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Recommended to submit entire biopsy material and cut 3 levels

If clinically is a polyp but microscopically is normal, flipping specimen after melting paraffin block gives definitive diagnosis in 30% of cases (AJSP 2003;27:254)

Deeper levels may reveal polyps in negative biopsies (AJCP 2002;117:424)

Difficult to diagnose carcinoma (i.e. invasion into submucosa) if no submucosa is present

Can diagnose invasion if (a) marked desmoplasia, (b) infiltrative pattern, (c) ulceration or (d) clinical mass lesion

Muciphages, without other abnormalities, have no clinical significance (Histopathology 2000;36:556)

 

Aberrant crypt foci in colon

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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

References: Cancer Epidemiol Biomarkers Prev 1991;1:57. World J Gastroenterol 2003;9:2642, Anticancer Res 2006;26:107, summary

 

Adenoma-general of colon

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“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

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

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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

Can diagnose invasion without identification of submucosa if (a) marked desmoplasia, (b) infiltrative pattern, (c) ulceration or (d) clinical mass lesion

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

 

Adenoma-carcinoma sequence of colon

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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

References: H. Lee Moffitt Cancer Center, eMedicine (#413), National Cancer Centre-Singapore, BMJ 2000;321:886

 

Atheroemboli associated polyps of colon

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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

 

Displaced glands / pseudoinvasion of colon

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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

 

Diverticular polyp of colon

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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

References: AJSP 1991;15:871, Histopathology 1993;23:63

 

Fibroblastic polyp of colon

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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

 

Flat adenoma of colon

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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)

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)

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

 

Hyperplastic polyp of colon

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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

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

Molecular: limited changes, no relation to changes in coexisting adenomas (J Clin Pathol 2004;57:1084)

 

Hyperplastic polyp of colon with misplaced epithelium

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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

Positive stains for misplaced epithelium: Ki-67, E-cadherin, collagen IV basement membrane

References: Mod Path 2001;14:869

 

Inverted hyperplastic polyp of colon

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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)

Micro: endophytic growth pattern, penetrates muscularis mucosa (AJSP 1985;9:265)

 

Hyperplastic polyposis of colon

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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

Molecular: extensive methylation in adenomas and in normal mucosa (Gut 2006;55:1467)

 

Inflammatory polyp of colon

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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), 5 year old girl (Case Rep Clin Pract Rev 2006;7:212)

Treatment: treat underlying inflammatory condition

Gross: smooth hyperemic or hypervascular appearance; variable surface erosion

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

Positive stains: vimentin

Negative stains: S100, cytokeratin, CMV

DD: pyogenic granuloma (Ann Diagn Pathol 2005;9:106)

 

Giant inflammatory polyp / polyposis of colon

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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

EM: fibroblasts, myofibroblasts, mast cells and lymphocytes, collagen fibers, capillaries, venules and hypertrophic autonomous nerve plexuses; also remnants of original epithelium and smooth muscle cells (Dis Colon Rectum 1990;33:773)

References: AJSP 1986;10:420

 

Inflammatory polyp of colon secondary to mucosal prolapse

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Includes inflammatory cap polyposis and diverticular polyp (AJSP 1991;15:871)

Usually rectosigmoid

Associated with chronic straining

Median age 20 years in one study; associated with rectal bleeding and mucous diarrhea (Dis Colon Rectum 2004;47:1208)

Represented 1/3 of inflammatory polyps in children in one study (Arkh Patol 2003;65:29)

Different mucins are expressed than normal colon (Gut 1998;42:135)

Case reports: Japanese woman with polyps throughout colon (Gut 2005;54:1342), associated with protein losing enteropathy (Am J Gastroenterol 2000;95:2095)

Treatment: polypectomy; patients with multiple polyps or other pathology may require resection; infliximab (Gastroenterology 2004;126:1868) and Helicobacter treatment may be useful (Helicobacter 2004;9:651)

Gross: sessile polyp covered by cap of fibrinopurulent exudate

Micro: crypts are elongated, tortuous and distended with goblet cell hypertrophy and serrated tubules; eroded surface with fibrinopurulent inflammatory cap overlying acute and chronically inflamed stroma with fibromuscular obliteration of lamina propria and proliferation of muscularis mucosa

References: Am J Gastroenterol 2002;97:370, Histopathology 1993;23:63

 

Inflammatory fibroid polyp of colon

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Uncommon in colon

Any age, no clinical associations

Benign

Treatment: endoscopic excision if small (Intern Med 2000;39:25), resection if large

Case reports: 40 year old man with positive fecal occult blood test (Dig Liver Dis 2005;37:968), causing intussusception (Dis Colon Rectum 1979;22:575), with neurofibromatosis (Ann Acad Med Singapore 2004;33:797)

Gross: mean 3-4 cm, polypoid with broad base; tan-gray-yellow; overlying mucosa may be ulcerated

Micro: usually limited to submucosa; spindle cell lesion in fibrovascular stroma with chronic inflammatory infiltrate including eosinophils; may be sparsely cellular with myxoid stroma; cellular areas may have up to 2 mitotic figures/HPF; may have rarefaction (zone of loose connective tissue) around muscular-walled blood vessels

Positive stains: vimentin, muscle specific actin, smooth muscle actin, CD34; variable S100
Negative stains: desmin, CD117

DD: fibromatosis (invades bowel secondarily), arteriovenous malformation (J Gastroenter 2004;39:575)

 

Inflammatory myoglandular polyp of colon

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Mean age 53 years

Distal colon; rarely in ileum where it may cause intussusception

Associated with mucous diarrhea, tenesmus and hematochezia

Case reports: 80 year old man (Turk J Gastroenterol 2004;15:117), with rectal bleeding (Pathol Res Pract 2003;199:837)

Gross: solitary, pedunculated, red with smooth surface (Endoscopy 2003;35:363)

Micro: inflammatory granulation tissue in lamina propria, branching and dilated glands arising within proliferating smooth muscle (resembling Peutz-Jegher polyp)

DD: inflammatory polyp (no abundant smooth muscle), Peutz-Jegher polyp (no prominent inflammation)

References: AJSP 1992;16:772

 

Juvenile (retention) polyp of colon

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Most common childhood polyp

Usually children < 5 years, may occur in adults

80% in rectum

Commonly presents with rectal bleeding (Gastroenterol Jpn 1979;14:425); polyps may autoamputate (10%) due to torsion

Usually sporadic; rarely associated with juvenile polyposis syndrome (see below)

Not neoplastic by themselves, but may be associated with dysplasia (Archives 1996;120:1032)

Case reports: in esophageal colon interposition (J Pediatr Surg 1998;33:1418), with intramucosal carcinoma (Archives 1987;111:200), causing intussusception (Postgrad Med 1978;64:188)

Gross: hamartomatous, large (1-3 cm) lesions with long (1-2 cm) stalks, red granular or glistening surface; may see cystic cavities

Micro: granulation tissue and ulcer covering abundant cystically dilated glands filled with mucus in an edematous and inflamed stroma; 20% have hyperplastic changes; minimal epithelium or smooth muscle; no atypia; rarely osseous metaplasia, foreign-body giant cell reaction to ruptured glands

DD: inflammatory polyp

 

Lymphoid polyp of colon

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Also called lymphoid hyperplasia

All ages; may be associated with bleeding or prolapse

Usually solitary, sessile, in rectum

Case reports: 51 year old woman (J Clin Pathol 1997;50:1034), 8 year old boy with lymphoid hyperplasia throughout bowel (Z Gastroenterol 1997;35:271), causing massive bleeding in a transplant patient (Indian J Gastroenterol 1996;15:20)

Treatment: excision

Gross: soft, superficial polyp covered by intact, smooth, gray mucosa; single or multiple

Micro: mucosal or submucosal lymphoid follicles with germinal centers that may distort muscularis mucosa or involve muscularis propria

DD: lymphoma

 

Post-surgical polyp of colon

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Develops up to 40 years after uterosigmoidostomy

Features of retention and adenomatous polyp

Case reports: Prog Urol 1996;6:590, Dis Colon Rectum 1988;31:961, Eur Urol 1986;12:360, Am J Gastroenterol 1984;79:453, Cancer 1984;53:1006

 

Serrated polyp / adenoma of colon

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First described in 1990 (AJSP 1990;14:524)

The definition and significance of this entity is not well established

Neoplastic, 1-2% of all polyps

Combination of hyperplastic and adenomatous polyp

Usually in sigmoid colon and rectum (Anticancer Res 2000;20:1141)

Often have microsatellite-instability mutations and DNA methylation; right sided lesions may be precursor of sporadic microsatellite-unstable colorectal carcinoma, particularly if large, multiple and part of giant hyperplastic polyposis (J Natl Cancer Inst 2001;93:1282)

May be associated with attenuated (<100 polyps) familial adenomatous polyposis (Gut 2002;50:402)

Risk of subsequent carcinoma is 5-6% (AJCP 2005;123:349, World J Gastroenterol 2006;12:2770)

6% of colorectal carcinomas are associated with coexisting serrated adenomas (Pathol Int 2001;51:215)

Inhibition of apoptosis in upper and middle crypts of hyperplastic polyps and serrated adenomas may be due to reduced Fas expression and may cause serrated appearance (AJSP 2002;26:249)

Case report: developing into carcinoma within 2 years (J Gastroenterol 2002;37:467), polyp with intraepithelial carcinoma (Pathol Int 2001;51:215), associated with multiple “serrated adenocarcinomas” (J Pathol 2000;190:444)

Gross: mean 6-9 mm

Micro: variable, ranging from clearly adenomatous to resembling a hyperplastic polyp

Proposed definition: surface epithelial nuclear dysplasia (elongation, increased N/C ratio, nucleoli, atypia) and serration of 20%+ of lesional crypts (Mod Path 2003;16:417)

Left sided: have “normal proliferation” - less pronounced adenomatous features; may be vesicular cell type with prominent serration, irregular thickening of muscularis mucosa, decreased or dystrophic goblet cells, mucin in vesicular cells similar to hyperplastic polyp; also goblet cell type with less prominent serration but thick mucosa and thick basal membrane; also mucin poor type (rare) with prominent serration, no mucin

Right sided: usually large, with abundant mucin (intra/extracellular), abnormal proliferation (i.e. adenomatous changes), dilated and distorted crypts, often secondary papillae

Positive stains: CK7 and CK20 (Dig Dis Sci 2005;50:1741); similar mucin profiles as hyperplastic polyp and gastric antral mucosa (Pathol Int 2004;54:401), KI-67 (19%, intermediate between hyperplastic polyp and adenoma, proliferation in basal or intermediate [but not superficial] crypts, Pathol Int 2003;53:277); also p53 (29-50%) and hTERT (46-53%) (Scand J Gastroenterol 2002;37:1194), COX2 (Dis Colon Rectum 2001;44:1319)

Molecular: MLH1 and PMS2 is often lost in zones of dysplasia or early carcinoma (AJCP 2006;126:1); K-ras mutations in 40%, particularly in nodular and rectal lesions (Dis Colon Rectum 2003;46:327); more highly methylated than tubular adenomas (Am J Pathol 2003;162:815), often BRAF mutations (Virchows Arch 2005;447:597, Cancer Res 2003;63:4878)

DD: adenoma, hyperplastic polyp, colchicine effect (Archives 2002;126:615)

References: AJSP 2003;27:65, Batts: USCAP 2004

 

Serrated polyp of colon with abnormal proliferation

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Also called sessile serrated adenoma

Precedes microsatellite-unstable adenocarcinoma (AJCP 2003;119:778)

MIB staining not helpful in differentiating (AJCP 2006;125:407)

Cases with focal invasive adenocarcinoma or high grade dysplasia: most of polyp is nonmalignant, with abrupt transition to malignancy; hMLH1 negative (AJCP 2006;125:132)

Micro: expanded crypt proliferative zone, exaggerated serrated architectural outline in basilar crypt region, basilar crypt dilation, inverted crypts, and predominance of dysmaturational crypts (crypts with minimal cell maturation); also horizontal extension of the crypt base along the muscularis mucosa J Clin Pathol 2004;57:682)

Positive stains: Ki-67, Kras, BRAF and methylation present, but this does not distinguish these polyps from traditional hyperplastic polyps (AJCP 2006;125:407) or serrated adenomas (AJSP 2004;28:1452)

Negative stains: p53 (usually); reduced expression of hMHL1 and hMSH2 (AJSP 2003;27:65)

References: Cesk Patol 2006;42:133

 

Transitional polyp of colon

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Only rarely described

Resemble transitional mucosa surrounding carcinoma and adenoma in the colon (Pathol Res Pract 1987;182:690)

Gross: small polypoid lesion

Micro: elongated and widened crypts, enlarged goblet cells, increased mucin

Positive stains: sialomucins

References: Endoscopy 1982;14:174

 

Tubular adenoma of colon

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90% of GI tubular adenomas occur in colon; also stomach and small intestine

50% are single

Prevalence of 30% in adults at autopsy, increasing with age

Risk of subsequent adenomas or colorectal carcinoma is related to size; higher risk if 6-10 mm or larger, multiple adenomas or family history (Ann Intern Med 1998;129:273, Gut 2002;51:424)

May bleed due to twisting; large polyps may cause change in bowel habits or intussusception

Associated with hypertriglyceridemia (World J Gastroenterol 2006;12:1261)

Case reports: osseous metaplasia (J Clin Pathol 2005;58:220), metastatic signet ring cell carcinoma in adenoma (Pathol Res Pract 2004;200:707, Archives 2003;127:1509), metastatic melanoma in adenoma (Dis Colon Rectum 2002;45:1681)

Gross: usually < 1 cm and pedunculated, but may be sessile; darker color than surrounding mucosa; multiple polyps tend to cluster

Micro: increased number of glands and cells per unit area compared to normal mucosa; cells are crowded with hyperchromatic nuclei, increased mitoses (some atypical); mucin production usually decreased; changes first affect superficial portion of glands; dysplasia from mild to severe (carcinoma in situ); rarely biotin-containing clear nuclei, squamous metaplasia (J Surg Oncol 1984;26:130), Paneth cells, cytoplasmic clear cells (Histopathology 1999;34:250), endocrine cells, malakoplakia

Positive stains: bcl2 (almost all cases), increased CEA (in atypical areas)

Negative stains: p53 (usually)

Molecular: 1/3 are aneuploid

 

Tubulovillous adenoma of colon

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At least 25% of each component; some define as approximately equal amounts of both components

May present with liver abscess (World J Gastroenterol 2006;12:990)

Case reports: causing intussusception (World J Gastroenterol 2006;12:146, Surg Today 2000;30:441), associated with malakoplakia (Ann Diagn Pathol 2004;8:364), with metastatic epithelioid angiosarcoma (Tumori 2005;91:210), overlying small cell carcinoma (Archives 2005;129:412), with gastric heterotopia (N J Med 1995;92:512)

 

Villous adenoma of colon

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Older adults, commonly in rectum or rectosigmoid

Less frequent than tubular adenoma

May invade directly into colon wall since no stalk is present to serve as buffer zone

Higher risk of malignancy than tubular adenoma; 40% risk if sessile and > 4 cm

Case reports: mimicking carcinoma (Turk J Gastroenterol 2004;15:270), associated with fluid and electrolyte imbalances (Ugeskr Laeger 2000;162:4272, Ann Surg 1964;159:604), associated with bowel perforation (Dis Colon Rectum 1997;40:244)

Treatment: local excision if small; may need larger surgery to completely excise, even if benign

Endoscopy: video

Gross: soft, usually large and sessile with papillary villous projections, large base and no stalk, may encircle the bowel

Micro: long fronds of papillary / villous projections arising directly from mucosal surface

References: eMedicine

 

 

Familial polyposis syndromes of colon

Adenomatous polyposis coli (APC) gene and colon

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Tumor suppressor gene with important role in familial adenomatous polyposis and Gardner syndromes

Mutated in most non-familial colon cancers; most colon tumors without APC mutations show mutations in beta-catenin

APC is a gatekeeper gene since it directs the downstream activity of different pathways

APC antagonizes the Wnt effector beta-catenin by promoting its proteosomal destruction, which directs beta-catenin away from the Tcf-Lef pathway (Dev Cell 2004;7:677)

Mutations in APC promote the Tcf-Lef pathway, and also inhibit the cellular adhesion complex; overall, this stimulates cell proliferation (Mol Cancer 2003;2:41)

References: Entrez Gene, University of Washington

 

Cowden's syndrome and colon

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Also known as multiple hamartoma syndrome and PTEN hamartoma-tumor syndrome

Bannayan-Riley-Ruvalcaba syndrome (OMIM 153480) is also associated with PTEN mutations

Autosomal dominant (with incomplete penetrance and variable expressivity) with facial tricholemmomas, acral keratoses, oral mucosal papillomas and colorectal polyps (Clin Genet 1986;29:222)

Patients have increased risk of malignancy (breast and thyroid cancer), but low rate of GI adenomatous polyps or GI malignancy (J Clin Gastroenterol 1986;8:576)

Micro: hamartomatous features with disorganization, proliferation and splaying of muscularis mucosa; polyps have same histology as mucosal prolapse syndromes (colitis cystica profunda)

Molecular: germline PTEN mutations in 70-80%

DD: Peutz-Jeghers

References: eMedicine, OMIM 158350, J Clin Oncol 2004;22:2954 (PTEN)

 

Cronkhite-Canada syndrome and colon

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Rare, non-hereditary disorder of multiple GI juvenile type polyps, usually colonic, associated with ectodermal changes (alopecia, nail atrophy, hyperpigmentation), protein losing enteropathy with associated diarrhea, weight loss, abdominal pain, weakness and anorexia

Polyps affect stomach, colorectum, small intestine

Usually age 50-60 years

Poor prognosis due to GI polyposis and nutritional complications; up to 50% may have remissions

15% develop colon carcinoma (Surg Today 1997;27:345)

Case reports: with adenoma containing focus of carcinoma (Indian J Gastroenterol 2003;22:189), with p53 but not APC or K-ras mutations (Z Gastroenterol 2001;39:365), use of nuclear medicine scan to locate areas of protein losing enteropathy (Dis Colon Rectum 2005;48:870), acute brain syndrome due to malabsorption (Psychiatr Danub 2005;17:90), 17 year old (Eur J Gastroenterol Hepatol 2005;17:1139)

Micro: multiple juvenile-type polyps with broad sessile base, cystically dilated glands filled with proteinaceous fluid or inspissated mucus, expanded edematous lamina propria (Am J Gastroenterol 1988;83:772); often are serrated adenomas (Digestion 2004;69:57); may have surface erosions and eosinophilic infiltrate; typically no dysplasia (AJSP 1989;13:940); mucosa between polyps also has dilated glands, edema, congestion and inflammation

References: eMedicine #1#2

 

Familial adenomatous polyposis of colon-classic

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Also known as familial polyposis coli

Due to defect in APC gene at 5q21

Autosomal dominant trait with high degree of penetrance

Polyposis patients without APC mutations often have mutations in MYH gene (see below)

Incidence of 1 per 8-30,000 individuals, 20% represent a new mutation

100% progress to colonic adenocarcinoma, often in teens, most by thirties

Patients have >100 colon polyps (usually thousands), beginning as teenagers; most are tubular adenomas

Polyps in children may have severe dysplasia (J Pediatr Surg 2006;41:658)

Polyps may also occur in stomach (fundic gland polyps) and small intestine, although most ileal lesions are lymphoid hyperplasia not adenomas

May also develop carcinoma of thyroid gland, gallbladder and adrenal gland; also desmoid tumors (10-25%)

APC mutations may cause expansion of crypt base cell population, including crypt stem cells; mutant crypt stem cells may clonally expand to form adenomas and carcinomas (Am J Pathol 2004;165:1489)

Diagnostic criteria: (a) 100+ colorectal polyps, (b) germ line mutation in APC gene, (c) family history of APC and (d) at least one of epidermoid cyst, osteoma or desmoid tumor

Case reports: cancer in 11 and 12 year old brothers (Eur J Pediatr 2005;164:306)

Treatment: prophylactic colectomy by age 20-25, must monitor rectal stump (if preserved) and possibly upper GI tract; screening of relatives

Gross: small to large adenomas involve entire bowel; may be flat or depressed (Int J Surg Pathol 2006;14:133)

Micro: tubular adenomas that progress to carcinoma; adenomatous epithelium may be present in only a single crypt taken from flat, endoscopically unremarkable mucosa

References: eMedicine #769, OMIM 175100, American Society of Colorectal Surgeons, Am J Gastroenterol 2006;101:385

 

Familial adenomatous polyposis of colon-attenuated FAP (AFAP)

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Previously called hereditary flat adenoma syndrome (Dis Colon Rectum 1992;35:411

Usually less than 100 polyps, but high risk for colorectal carcinoma (69% cumulative risk by age 80, Gastroenterology 2004;127:444)

Phenotypically and genetically heterogeneous (Gut 2006;55:1440)

Polyps usually more proximal (i.e. right sided) than in classic FAP; often rectal polyp sparing

Cancers usually develop at age 50-55 years, 15 years later than classic FAP

May develop stomach fundic gland polyps, gastric or small bowel flat adenomas and stomach / duodenal carcinomas (Cancer 1993;71:2709)

Diagnosis: genetic testing is important

Case reports: 60 flat adenomas in proximal colon (Int J Gastrointest Cancer 2003;33:117), 2 early cases (Cancer 1990;66:909), 42 year old presenting with ampullary adenoma

Gross: polyps are flat or slightly raised or plaque-like

Molecular: germline mutations in 5' and 3' end and exon 9 of APC gene (also biallelic MUTYH mutations, Int J Cancer 2006;119:807)

DD: hereditary nonpolyposis colon cancer (Am J Gastroenterol 2002;97:1822)

References: Fam Cancer 2003;2:43

 

Gardner’s syndrome and colon

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A variant of familial adenomatous polyposis

Incidence of 1 per million in US

Colonic adenomatous polyps plus extraintestinal features of multiple osteomas (skull, mandible, long bones), epidermal cysts, fibromatosis (10%, usually intraabdominal after surgery, aggressive, may cause death), fibromas, lipomas, impacted and supernumerary teeth, dental cysts, congenital hypertrophy of retinal pigment epithelium; also lymphoid polyps of terminal ileum

100% develop colon carcinomas

Due to mutations of APC gene, but with variable penetrance, so all extracolonic features may not be present

Case reports: 11 year old girl presenting with fibromatosis (World J Gastroenterol 2005;11:5408)

Treatment: similar to familial adenomatous polyposis

References: eMedicine #2712, eMedicine #163

 

Hereditary mixed polyposis syndrome and colon

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Uncommon

Autosomal dominant

May be a variant of juvenile polyposis syndrome

Micro: polyps of mixed histologic types (tubular adenomas, villous adenomas, flat adenomas, hyperplastic polyps and atypical juvenile polyps), totaling <15 per patient; most polyps are adenomas

Molecular: due to mutation in bone morphogenesis protein receptor 1A (OMIM 601299) in one family study (J Med Genet 2006;43:e13); 15q13-14 in Ashkenazi Jews (Am J Gastroenterol 2003;98:2317, Am J Hum Genet 2003;72:1261), different haplotype in Singapore (Zhonghua Wei Chang Wai Ke Za Zhi 2005;8:312)

References: OMIM 601228

 

Hyperplastic polyposis syndrome and colon

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See above

 

Juvenile polyposis syndrome and colon

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Also called juvenile polyposis coli

Autosomal dominant with incomplete penetrance

Associated with adenomatous polyps and adenocarcinoma of colon (30-40%), duodenum, stomach and pancreas

Diagnostic criteria: (a) 6 or more colorectal juvenile polyps, (b) juvenile polyps throughout entire GI tract, or (c) any number of polyps in a patient with a family history of juvenile polyposis (Histopathology 1988;13:619)

Rare lethal form occurs in infancy, associated with diarrhea, anemia, hypoalbuminemia

Rarely presents with GI hemorrhage (Am J Gastroenterol 2000;95:543)

Treatment: repeated endoscopic polypectomies and surgery; screening of family members

Micro: polyps have juvenile and adenomatous features; often complex glandular structures

Positive stains: often p53 and Ki-67 >50% (Arkh Patol 2004;66:28)

Molecular: often mutations in PTEN, SMAD4/DPC4/MADH4 (19%, J Mol Diagn 2006;8:84), BMPR1A (11%); also deletions in PTEN and BMPR1A (Am J Hum Genet 2006;78:1066); no loss of APC (Pediatr Res 2005;57:4)

References: GeneTests, OMIM 174900

 

Lynch syndrome and colon

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Also known as hereditary non-polyposis colon cancer (HNPCC), because patients have hereditary colon carcinoma but fewer polyps than familial adenomatous polyposis; “HNPCC” terminology has been criticized (World J Gastroenterol 2006;12:4943)

Hereditary disorder due to mutation in mismatch repair gene (see JAMA 2005;294:2195 for report on family tracked for 100 years)

Most common hereditary colorectal carcinoma syndrome (2-5% of all colorectal carcinomas)

Autosomal dominant

80% develop colorectal carcinoma; also increased risk of endometrial carcinoma (33%), ovarian carcinoma (5%), cancers of small bowel, stomach, urinary tract, and brain (Fam Cancer 2005;4:245)

Risk of endometrial carcinoma (33%) and ovarian carcinoma (5%) is reduced by prophylactic surgery (N Engl J Med 2006;354:261)

Molecular: defect in mismatch repair genes (caretaker genes) MLH1 or MSH2 (90%), MSH6 (7-10%) or PMS2 (less common, Gastroenterology 2006;130:312), which proofread DNA replication; associated with microsatellite instability (MSI, microsatellites are dinucleotide repeat sequences, such as (CA)n, normally present in human genome), although MSI is not specific (World J Gastroenterol 2006;12:4745)

MSI is detected by instability at 2 or more of 5 microsatellite markers (MSH2, MLH1 are most common)

Defective mismatch repair genes can be reliably detected  (negative staining) by immunohistochemistry (AJCP 2004;122:389, N Engl J Med 2005;352:1851)

These adenocarcinomas have better survival, respond better to 5 FU chemotherapy

Amsterdam I screening criteria (all 4 must be met): 3 or more family members with a confirmed diagnosis of colorectal cancer, one of whom is a first degree (parent, child, sibling) relative of the other two; two successive affected generations; one or more colon cancers diagnosed before age 50; familial adenomatous polyposis has been excluded (Dis Colon Rectum 1991;34:424); these criteria are relatively sensitive but not specific for Lynch syndrome since these patients may lack mismatch repair gene mutations

Amsterdam II criteria (all 4 must be met): 3 or more family members with HNPCC-related cancers, one of whom is a first degree relative of the other two; two successive affected generations; one or more HNPCC-related cancers diagnosed before age 50; familial adenomatous polyposis has been excluded (Gastroenterology 1999;116:1453)

Table of Amsterdam I and II criteria

Revised Bethesda criteria (any criteria must be met): colorectal cancer diagnosed before age 50 years; presence of synchronous or metachronous colorectal cancers or other HNPCC-associated tumors, regardless of age; colorectal cancer with the MSI-H histology diagnosed before age 60 years; colorectal cancer diagnosed in one or more first degree relatives with an HNPCC-related tumor, with one of the cancers being diagnosed before age 50 years; or colorectal cancer diagnosed in 2 or more first or second degree relatives with HNPCC-related tumors, regardless of age, table (J Natl Cancer Inst 2004;96:261)

Screening: full colonoscopy every 1-2 years beginning at age 20-25 years, annual screening for endometrial cancer beginning at age 25-35, annual urinalysis and cytologic examination beginning at age 25, annual skin surveillance, and upper GI endoscopy beginning at age 35 when gastric cancer is part of the family spectrum (JAMA 2006;296:1507)

At colonscopic screening, have similar rate of adenomas as non syndrome patients, but much higher incidence of carcinoma (Gastroenterology 2006;130:1995)

Case reports: colorectal carcinoma and duodenal follicular lymphoma (Mod Path 2000;13:586), urothelial carcinoma of ureter (Archives 2003;127:E60)

Gross: usually proximal colon, 18% multiple, 40% metachronous (multiple separate occurrences)

Micro: tumors tend to be poorly differentiated with abundant mucin and marked lymphocytic infiltration

References: GeneReviews, OMIM 120435

 

Muir-Torre syndrome and colon

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Also called Torre-Muir syndrome

Clinical variant of Lynch syndrome

Rare autosomal dominant disorder with < 100 adenomas, usually in proximal colon

Multiple colorectal tumors associated with multiple sebaceous tumors, keratoacanthomas and basal cell carcinoma

15% of women develop endometrial cancer

Molecular: mutations in MSH2, MLH1 and MSH6

Negative stains: MSH2 and MSH6 in colonic polyps (Arch Dermatol 2006;142:1039), CK15 and MSH2 in sebaceous neoplasms (J Cutan Pathol 2006;33:634, Dermatol Online J 2006;12:4)

References: Hum Path 1995;26:422, eMedicine #275, OMIM 158320

 

MUTYH/MYH associated polyposis and colon

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Gene is at 1p; protein is base excision repair enzyme (Ned Tijdschr Geneeskd 2005;149:2970)

Autosomal recessive

Biallelic patients (mutations in both genes) have multiple adenomas (Hum Mutat 2006;27:1064), 93x excess risk of colorectal carcinoma compared to normal controls, but account for <1% of all cases (Am J Hum Genet 2005;77:112)

Overlaps with familial adenomatous polyposis, although MUTYH patients often had attenuated or atypical phenotype (Int J Cancer 2006;119:807)

Case reports: with duodenal carcinoma (J Clin Pathol 2006 Aug 30; [Epub ahead of print])

References: OMIM 604933

 

Peutz-Jeghers syndrome and colon

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Rare; autosomal dominant with variable penetrance, usually diagnosed in 20’s

Diagnostic criteria: (a) 3+ histologically confirmed Peutz-Jeghers polyps, (b) any Peutz-Jeghers polyp with a family history, (c) characteristic melanotic mucocutaneous pigmentation (lips, oral mucosa, genitalia, digits, palms, soles) with a family history or (d) Peutz-Jegher polyp and characteristic mucocutaneous pigmentation

Hamartomatous polyps are present throughout GI tract excluding esophagus

All patients have small intestinal polyps; 25% involve stomach and colon

Increased risk of cancer from adenomatous polyps other than classic Peutz-Jeghers polyps; however, no apparent increased risk from solitary polyps (Int J Colorectal Dis 2003;18:33)

Very high risk of cancer overall (Gastroenterology 2000;119:1447), with half dying of cancer by age 60

Almost all patients have sex-cord tumor / tumorlet with annular tubules in ovary or testis

Also associated with mucinous tumors, adenoma malignum of cervix and carcinomas of breast, pancreas, lung and uterus

Large polyps may cause intussusception and GI bleeding

Gross: large, lobulated, pedunculated polyps resembling adenomas

Micro: polyps have broad bands of muscularis mucosa smooth muscle fibers in superficial mucosa, thicker centrally than peripherally, with “Christmas tree” appearance at low power; disorganized glands resemble epithelium adjacent to polyp; also Paneth cells; epithelial structures may herniate into bowel wall (pseudoinvasion, more common in small intestine); no atypia

Molecular: mutation at 19p13.3 (STK11/LKB1 gene) in 60%

References: eMedicine #1807, GeneReviews, OMIM 175200

 

Turcot’s syndrome and colon

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Pronounced with silent second t (Turcot was French Canadian)

Rare; autosomal recessive variant of familial adenomatous polyposis

CNS tumors (gliomas or glioblastomas) and later familial adenomatous polyposis

May be 2 types - (a) gliomas plus nonpolyposis adenomas with mismatch repair gene mutations and (b) medulloblastomas plus adenomatous polyposis with APC mutations

Case reports: colon carcinoma and astrocytoma (Neurol Med Chir (Tokyo) 2004;44:124), colonic adenocarcinoma and astrocytoma (Neurol Med Chir (Tokyo) 1989;29:606).

Molecular: MLH1, MSH2 and PMS2 germline mutations; also APC (N Engl J Med 1995;332:839)

References: OMIM 276300

 

 

Carcinoma of colon

Carcinoma-general of colon

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98% of colonic cancers are adenocarcinomas

#2 cause of cancer deaths in US after lung cancer with 185,000 new cases and 55,000 deaths/year

Affects 5% of US population during their lifetime

Most common GI tumor in US; less common in Africa, Asia, parts of South America

Peak age 60-79 years; < 20% before age 50

Note: lymph nodes in rectal carcinoma patients may be involved by prostate cancer as an occult second primary

Risk factors: older age, obesity, physical inactivity, ulcerative colitis, Crohn’s disease, schistosomiasis, polyposis syndrome, family history of colorectal neoplasia, diet

Polyposis syndromes: familial adenomatous polyposis and variants (APC gene), juvenile polyposis (DPC4, PTEN genes), Peutz-Jeghers syndrome (STK11 gene), Lynch syndrome and variants (MSH2, MLH1, PMS1, PMS2, MSH3 and MSH6 genes)

Diet risk factors: low vegetable fiber, high refined carbohydrates, increased beef consumption, decreased Vitamins A, C, E

Low fiber prolongs transit time (toxic oxidative byproducts are in longer contact with colonic mucosa) and alters bacterial flora; beef consumption enhances synthesis of bile acids by liver, which may be converted into carcinogens by bile acid

Screening: endoscopy, guaiac stool examination; serum CEA (elevated levels associated with various carcinomas or liver disease, useful for monitoring recurrences but not sensitive for early tumors)

Symptoms: rectal bleeding, change in bowel habits (alternating diarrhea and constipation), anemia due to blood loss, vague abdominal pain; cecal tumors may mimic appendicitis

Metastases: most commonly to regional lymph nodes and liver; also peritoneum, lung, ovaries; metastases may simulate primary tumors of affected organs

Prognosis: 5 year survival 40-60%; most recurrences are within 2 years

Poor prognostic factors: high stage; high grade / poorly differentiated tumors, positive margins (particularly rectal carcinoma); small cell, mucinous, anaplastic or signet ring subtypes; flat or ulcerative carcinomas tend to invade deeper (and have higher stage) than polypoid carcinomas; also highly infiltrative growth pattern at margin, extensive tumor budding, undifferentiated cells; free tumor cells in peritoneal space (AJCP 2003;119:108), angiolymphatic invasion (particularly outside of bowel wall); perineurial invasion, very young or very old patients; male patients; perforation; elevated serum CEA > 5 ng/ml,  reduced claudin 1 expression in Stage II tumors (Mod Path 2005;18:511)

Treatment: resection with endoscopic follow up; local excision for small rectal carcinomas; surgical excision of isolated distant metastases; radiation therapy or chemotherapy

References: Wikipedia

 

Molecular pathways of colorectal carcinoma

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(1) Chromosome instability pathway

80% of carcinomas

Mutations in oncogenes and tumor suppressor genes, including APC, beta catenin, KRAS, BRAF, SMAD4, PTEN, P53 and bax

Have altered total DNA content, cytogenetics aneuploidy and numerous allelic gains and losses

Important in familial adenomatous polyposis and variants (APC gene) and juvenile polyposis (DPC4, PTEN genes)

Alterations in beta catenin pathway appear to be important in ulcerative colitis related and sporadic colon carcinomas (Mod Path 2001;14:29)

Diagram

 

(2) Microsatellite instability pathway

15% of carcinomas

Have high (MSI-H) or low levels of instability (MSI-L)

Includes alterations in mismatch repair genes MSH2, MSH6, MLH1, PMS2 and genes whose alterations cause gross chromosomal abnormalities (BUB1, BUBR1, CDC4, Cancer Metastasis Rev 2004;23:11)

Inactivation of both alleles of nucleotide mismatch repair, usually hMSH2 or hMLH1, promotes tumorigenesis

Tumors have numerous nucleotide substitutions and insertion/deletion mutations in repeated nucleotide sequences (microsatellites), normal total DNA content and relatively normal cytogenetics with only infrequent allelic gains/losses

Either germline mutations (Lynch syndrome and variants) or sporadic due to promotion methylation

Includes medullary, mucinous and signet ring carcinoma subtypes

Often present at earlier stage than other colon carcinomas (AJSP 2003;27:1393)

Frequent present in colon/stomach double primaries (Mod Path 2001;14:543

Gross: usually right sided, expansive growth

Micro: tumor infiltrating lymphocytes, peritumoral lymphocytes, no “dirty” necrosis; may be associated with serrated adenomas

 

(3) MYH pathway

Mutations in both copies of MUTYH / MYH repair gene; not well understood

Biallelic patients (mutations in both genes) have multiple adenomas (Hum Mutat 2006;27:1064), 93x excess risk of colorectal carcinoma compared to normal controls, but account for <1% of all cases (Am J Hum Genet 2005;77:112)

 

(4) CpG island methylation pathway

30% of carcinomas

Important mechanism of inactivating tumor suppressor genes in chromosomal instability pathway above (Curr Mol Med 2006;6:401, Cancer Metastasis Rev 2004;23:29)

CpG islands are 500 to 2000 base regions rich in cytosine-guanosine dinucleotide repeats present at 5’ region in 50% of human genes; methylation of cytosine residues in promoter regions and proximal exons of these islands represses transcription; may also have methylation of MLH1

 

References: Howard Hughes Medical Institute

 

World Health Organization (WHO) classification of colorectal carcinoma

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Adenocarcinoma

Adenosquamous carcinoma

Mucinous (colloid) adenocarcinoma

Signet ring cell carcinoma

Small cell carcinoma (oat cell)

Squamous cell carcinoma

Undifferentiated carcinoma

Medullary carcinoma

Other

References: Hamilton: Pathology and Genetics of Tumours of Digestive System; 2000

 

Post-treatment changes of colonic carcinoma

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Preoperative (neoadjuvant) radiation therapy, with or without chemotherapy, is often used to treat rectal adenocarcinoma

Presence of acellular mucin reflects pretreatment tumor

Gross: flat firm mass with central ulceration; may be no identifiable lesion

Micro: regenerated mucosa at edge of ulcer; tumor cells with variable tumor effects of fibrosis, mucin pools, inflammation, necrosis

Positive stains: cytokeratin to detect rare residual tumor cells

 

Intramucosal carcinoma of colon

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Stage Tis

Some of these lesions are also called small flat carcinomas

Controversial terminology - may reflect differing thresholds for malignancy between West (higher threshold) and Japan (lower threshold), as Japanese pathologists diagnose as malignant what West calls high grade dysplastic lesions

Definition: malignant change confined to mucosa; for adenomas, no invasion into submucosal stalk, no undifferentiated carcinoma, no vascular invasion, no desmoplastic stroma

Rosai suggests calling these lesions polyps with severe atypia

Little metastatic potential as there are minimal lymphatic channels in colonic mucosa, so resection is not indicated

If tumor invades stalk of polyp, then bowel resection may be justified

Case reports: juvenile polyp with intramucosal carcinoma (Archives 1987;111:200)

 

Adenocarcinoma of colon

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98% of colonic cancers are adenocarcinomas

Rarely associated with endometriosis and unopposed estrogen therapy (AJSP 2000;24:513); these cases usually involve serosa and spare mucosa, have endometrioid histology and squamous differentiation; important to differentiate since staging and treatment may be different

Only rarely produces pseudomyxoma peritonei, even if mucinous

Right colon tumors: polypoid exophytic masses; anemia, weakness and fatigue are common, but obstruction is uncommon; iron deficiency anemia in older man is presumed to be a GI carcinoma unless proven otherwise

Left sided tumors: annular, encircling lesions (napkin ring [image] constrictions of bowel); diarrhea, obstructive symptoms

Rectosigmoid tumors: usually more advanced at presentation

Poor prognostic factors: high grade, possibly intramural venous invasion (identify with elastic stain, J Clin Pathol 2002;55:17)

Case reports: metastases - cervix in 17 year old girl (J Reprod Med 2005;50:793), ear (Ear Nose Throat J 2005;84:36), kidney (Int J Urol. 2005;12:93), larynx (Acta Otolaryngol 2006;126:661), mandible (Head Neck 2005;27:729), perianal fistula (Int Semin Surg Oncol 2006;3:25), skin (Ann Acad Med Singapore 2006;35:585, Int Semin Surg Oncol 2006;3:2), sphenoid sinus (Otolaryngol Pol 2005;59:429), thyroid gland (Tumori 2006;92:252, Endocr J 2006;53:339),

other - coexistent mantle cell lymphoma (Archives 2003;127:E64), coexisting GIST (Int J Colorectal Dis 2006 Apr 26 [Epub ahead of print]), with enteroliths (Actas Urol Esp 2006;30:206), with hypercalcemia (Surg Today 2005;35:692), with urinary diversion for exstrophy (World J Surg Oncol 2004;2:20)

Gross: usually single; polypoid or ulcerative; may have serosal puckering if muscularis propria involved

Micro: well to poorly differentiated tumor cells with marked desmoplasia, particularly at edge of tumor, often mucin producing; glands often filled with necrotic debris (“dirty necrosis”); inflammatory cells and scattered neuroendocrine cells common (Pol J Pathol 2005;56:89); rarely germ cell elements (Archives 2001;125:558)

Low grade (grade 1): well differentiated, 15-20% of all carcinomas; well formed glands or simple tubules with uniform, basally oriented nuclei, resembles adenomatous epithelium

Moderately differentiated (grade 2): 60-70% of all carcinomas; tubules may be simple, complex or slightly irregular; loss of nuclear polarity

High grade (grade 3): poorly differentiated in 50% or more of tumor (i.e. less than 50% gland formation), 15-20% all of carcinomas; majority of tumor (excluding advancing edge of tumor) is sheets of cells without gland formation; usually right sided (Hepatogastroenterology 2004;51:1698)

Note: preoperative histologic grading is not accurate (J Med Assoc Thai 2005;88:1535)

Positive stains: CK20, mucin (MUC1 and MUC3), CEA, B72.3, CDX2 (sensitive but not that specific, Hum Path 2006 Aug 10 [Epub ahead of print], AJSP 2003;27:303); also hCG (often), p53, P504S (AJSP 2002;26:926), CD10 (stromal cells), estrogen receptor (Hum Path 2001;32:940 but see AJCP 2000;113:364), villin; may have scattered endocrine cells

Negative stains: CK7, HepPar1, DPC4 (SMAD4), PR (AJCP 2000;113:364), MUC2, MUC5AC

EM: prominent microfilaments perpendicular to cell membrane and entering the brush border

References: Archives 2001;125:1074 (keratin stains), Mod Path 2000;13:962 (CK7, CK20), Hum Path 2002;33:806 (CD10), Clin Cancer Res 2005;11:3766 (algorithm for adenocarcinoma of unknown primary-figure 1C), eMedicine #413, eMedicine #182

 

Adenosquamous carcinoma of colon

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Rare ( 0.1 to 0.2% of colon carcinomas, AJSP 1978;2:47)

Associated with ulcerative colitis

Aggressive behavior (Dis Colon Rectum 1996;39:1265)

Poorer prognosis with advanced disease than adenocarcinoma (Dis Colon Rectum 1999;42:258)

Case reports: tumor of rectosigmoid junction (Am Surg 2006;72:754), with nodal metastases (J Exp Clin Cancer Res 2001;20:293), with hypercalcemia (Int J Clin Oncol 2005;10:144)

Micro: malignant glandular and squamous components

Positive stains: CD44 (squamous component, Archives 2000;124:212)

References: Dis Colon Rectum 2001;44:341

 

Carcinosarcoma of colon

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Also called sarcomatoid carcinoma

Very rare

Aggressive

Case reports: 81 year old man with ascending colon tumor and liver metastases (BMC Cancer 2006;6:185), invading mesentery and omentum (Clin Imaging 2005;29:259), 80 year old woman with recurrent tumor (Surg Today 2003;33:545)

Micro: typical adenocarcinoma plus malignant spindle cells with bony or cartilaginous differentiation

Positive stains: cytokeratin for both components

 

Clear cell carcinoma of colon

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A minor morphologic variant of adenocarcinoma with intracytoplasmic glycogen

Usually left colon

Usually elderly men

Case reports: associated with endometriosis (J Clin Pathol 2001;54:76), death due to liver metastases (J Clin Pathol 1995;48:1142), 89 year old woman (Int J Colorectal Dis 2004;19:264)

Positive stains: PAS, CEA

Negative stains: mucin

DD: metastatic renal cell carcinoma (CEA-)

 

Glassy cell carcinoma of colon

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Rare in colon; more common in cervix

Considered a poorly differentiated adenosquamous carcinoma

Case reports: hCG production (AJSP 1996;20:187)

Micro: moderate ground glass or finely granular cytoplasm; cell wall is PAS+ and distinct; enlarged nuclei with prominent nucleoli

DD: focal hCG producing adenocarcinoma (more common)

 

Hepatoid carcinoma of colon

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Rare

Elevated serum AFP

Metastases may mimic hepatocellular carcinoma (AJSP 2003;27:1302)

Case reports: tumor with adenocarcinoma and hepatoid areas (Dis Colon Rectum 2003;46:826), with ulcerative colitis (Dis Colon Rectum 2000;43:105), AFP producing tumor (Pathology 1995;27:277)

Micro: adenocarcinoma plus hepatocellular-like carcinoma composed of trabecular or solid pattern of large polygonal cells with abundant eosinophilic or clear cytoplasm; often vascular invasion

Positive stains: mucin, polyclonal CEA (cytoplasmic staining in adenocarcinoma and canalicular staining in hepatoid areas)

References: Histopathology 1997;31:47

 

Lymphoepithelioma-like carcinoma of colon

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Very rare in colon

Case reports: rectal tumor associated with EBV (Pathol Res Pract 2001;197:577), in Lynch syndrome with colonic mucinous and well-differentiated adenocarcinomas (Archives 1999;123:720), with tumors at other sites (Dis Colon Rectum 1998;41:925)

Micro: syncytial growth pattern of undifferentiated pleomorphic malignant epithelial cells with ill-defined borders, prominent nucleoli, brisk mitotic activity, prominent stromal and intratumoral lymphoid infiltrate; focal necrosis; infiltrative margins

Positive stains: cytokeratin (AE1/AE3, CAM 5.2), EBV (often), p53 (10% of tumor cells)

Negative stains: mucin (may be focal), neuroendocrine markers, S100

DD: medullary carcinoma (lymphocytic infiltrates are peritumoral, not intratumoral; pushing not infiltrative margins, monomorphic tumor cells)

 

Medullary carcinoma of colon

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Also called undifferentiated carcinoma; a subtype of poorly differentiated adenocarcinoma

<1% of colorectal neoplasms

Often elderly women, right sided tumors

Strongly associated with high degree of microsatellite instability (MSI), indicative of loss of normal DNA repair gene function

Often better clinical outcome independent of stage than microsatellite stable tumors or tumors with low levels of microsatellite instability; usually no/few nodal metastases; may be more sensitive to 5 FU chemotherapy; may have more metachronous colonic carcinomas

Case reports: 79 year old woman with ulcerated cecal tumor (Archives 2005;129:113)

Gross: large with invasion into adjacent organs

Micro: expansive growth pattern of well circumscribed sheets of tumor cells; also nested, organoid, or trabecular patterns, but no/minimal mucin production and no tubule formation; pushing border with prominent lymphocytic infiltration; cells are uniform, polygonal to round, small to medium sized with variable eosinophilic cytoplasm, small/medium nuclei with open chromatin and prominent nucleoli, frequent mitotic activity; neuroendocrine features but negative for neuroendocrine markers

Positive stains: keratin, CEA, EMA

Negative stains: neuroendocrine markers, MLH1 and MSH2 (Mod Path 2002;15:741), p53

Flow cytometry: diploid

DD: lymphoepithelioma-like carcinoma

References: AJCP 2005;123:56, Hum Path 1999;30:843

 

Metastases to colon

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Common primaries are lung (large cell), melanoma, prostate (by extension), breast, stomach, ovary

Gross: central ulceration extending towards mucosa, but often sparing it

Micro: no in situ or mucosal malignancy

 

Primary sites of metastases to colon

Bladder: case report of signet ring carcinoma (Dig Liver Dis 2006;38:609)

 

Breast: rare (Tech Coloproctol 2004;8 Suppl 1:s135)

 

Endometrial stromal sarcoma: may resemble GIST but plump spindle cells with invasive tongues at periphery and angiovascular invasion; also CD10+, CD117-

 

Endometrioid adenocarcinoma: associated with endometriosis

 

Leukemia: usually involves right colon and terminal ileum; polypoid or transmural infiltrates

 

Melanoma

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May have long time interval between primary and metastases

Case report: unknown primary site (The Internet Journal of Gastroenterology 2006;4: Number 2)

Micro: usually multiple submucosal metastases with normal overlying mucosa; undifferentiated epithelial neoplasm with discohesive cells with pink cytoplasm, large nucleoli

Positive stains: HMB45, MelanA/Mart1, S100

 

Prostate: infiltrative into submucosa; no in situ or intramucosal carcinoma; classic prostate histology; resections for rectal cancer rarely contain nodes with metastatic prostate carcinoma

 

Stomach: linitis plastica type metastases may resemble poorly differentiated carcinoma (Kaohsiung J Med Sci 2004;20:552)

 

Mucinous (colloid) carcinoma of colon

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Relatively common (10% of all colorectal carcinomas), usually in rectum

Note: this entity is defined as having mucin lakes comprising 50% or more of tumor mass

Associated with microsatellite instability (Cancer 2005;103:2023)

Associated with villous adenomas, ulcerative colitis or other colitis, prior pelvic radiation (Cancer 1976;37:1891)

Usually presents with more advanced stage (Dis Colon Rectum 1993;36:49), greater nodal involvement (Gastroenterol Hepatol 2002;25:534) than nonmucinous tumors, but see J Med Assoc Thai 2006;89:25

Similar prognosis by stage as other carcinomas

Case reports: with perianal fistula (Dig Surg 2003;20:69), 11 year old girl (J Postgrad Med 1993;39:218)

Gross: exophytic, gelatinous

Micro: bland tumor cells floating in large extracellular mucin lakes comprising 50%+ of tumor mass; may have signet ring cells (with intracellular mucin)

DD: signet ring carcinoma (no mucin lakes)

References: Dis Colon Rectum 2005;48:1161

 

Neuroendocrine carcinoma of colon

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Discussion excludes carcinoid tumors and small cell carcinoma (see below)

Rare; highly aggressive with nodal metastases (AJSP 1990;14:1010)

Often high stage at diagnosis (Dis Colon Rectum 2004;47:163)

Mixed neuroendocrine carcinoma-adenocarcinoma also occurs (Virchows Arch 2006;448:644)

Micro: organoid appearance, larger cells than small cell carcinoma, marked nuclear pleomorphism, large irregular hyperchromatic nuclei with prominent nucleoli, frequent mitotic activity, tumor necrosis

Positive stains: cytokeratin, usually EMA, NSE, chromogranin and synaptophysin; c-kit/CD117 in 23% but not associated with activating mutations (AJSP 2003;27:1551

DD: focal neuroendocrine cells in adenocarcinoma (more common)

References: Korean J Gastroenterol 2006;48:97

 

Papillary adenocarcinoma of colon

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Not in WHO classification; may not be a distinct histologic variant

7% incidence in recent study (Zhonghua Nei Ke Za Zhi 2006;45:9)

Case reports: with psammoma bodies (Jpn J Clin Oncol 1997;27:193, full text), with Paneth cells (Histopathology 1979;3:489)

Micro: arise in polyps, have distinct invasive papillary component

Negative stains: p53, p27 (limited number of cases)

References: Hum Path 2002;33:372

 

Signet ring carcinoma of colon

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Also known as linitis plastica type carcinoma

1% of colonic carcinoma

May affect younger patients than classic colorectal carcinoma (Am J Gastroenterol 1996;91:2195)

Metastases to lymph nodes, peritoneal surface (malignant ascites) and ovary; liver less commonly (ANZ J Surg 2001;71:703)

Usually high stage/poor prognosis (Dis Colon Rectum 2005;48:1161, Dis Colon Rectum 1999;42:1176)

Case reports: foci within adenoma #1 (Archives 1999;123:957), #2 (Archives 2003;127:1509); with metastases to stomach (Mod Path 1989;2:265), early stage (World J Gastroenterol 2006;12:3446), mimicking inflammatory bowel disease (Dig Liver Dis 2005;37:537), incidentally detected with ulcerative colitis (Hepatogastroenterology 1999;46:236), with peritoneal dissemination (J Gastroenterol 2002;37:550), with multiple skin metastases (Kaohsiung J Med Sci 2002;18:359)

Gross: diffuse infiltration of bowel wall; rarely presents as polyp

Micro: diffuse growth of signet ring cells  (>50% of tumor cells) with little glandular formation; cells have intracellular mucin that displaces nucleus to side; often linitis plastica appearance

Positive stains: CK20, MUC2, villin, CDX2, MUC5AC; variable MUC1 and HepPar1

Negative stains: CK7, ER

DD: metastatic gastric, breast  or bladder carcinoma (Dig Liver Dis 2006;38:609), metastatic mucinous carcinoma (Pathol Res Pract 2004;200:707), benign signet ring change with pseudomembranous colitis (Pathol Res Pract 1998;194:197, AJSP 1996;20:599)

References: AJCP 2004;121:884 (immunostains), Appl Immunohistochem Mol Morphol 2000;8:183 (immunostains), Rev Gastroenterol Peru 2004;24:234

 

Small cell carcinoma of colon

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Usually in right colon or cecum

30% arise from villous or other adenoma

Mean age 63 years

<1% of colorectal carcinomas

Poor prognosis due to early metastases to lymph nodes and liver, poor response to therapy

FNA may identify metastatic disease before known primary (Diagn Cytopathol 1996;15:54)

2/3 dead at 5 months historically (AJCP 1991;95:315)

Case reports: with overlying villous adenoma (Archives 2005;129:412), with coexisting adenocarcinoma (Chirurg 2002;73:859), rapid growth after resection (Tohoku J Exp Med 2006;209:361), cecal tumor (Ann Diagn Pathol 2006;10:162), with ulcerative colitis (South Med J 1996;89:921)

Micro: resembles pulmonary tumor; sheets and nests of small round/ovoid cells with minimal cytoplasm, hyperchromatic nuclei with stippled chromatin, nuclear molding with peripheral palisading, usually brisk mitotic activity, apoptotic cells, necrosis and vascular invasion, may have Azzopardi effect (encrustation of nuclear material around blood vessels); adenoma present in 30-40%; may have foci of glandular differentiation with variable mucin production or squamous differentiation; no prominent nucleoli, no pleomorphism

Positive stains: neuron-specific enolase (84%), synaptophysin (50%), chromogranin (37%), Leu7 (CD57, 18%)

EM: few dense-core secretory granules

References: Archives 2001;125:1251

 

Small early flat carcinoma of colon

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Controversial entity

In Japan, represents 6-10% of colonic cancers

In US, small flat tumors are usually hyperplastic polyps (AJR Am J Roentgenol 2000;175:747), although adenocarcinomas do occur (Gut 2002;51:550)

May develop from flat adenomas

May be an important precursor of advanced malignancies (Ann Acad Med Singapore 2003;32:263)

Tend to invade submucosa at a smaller size than polypoid lesions (Ann Pathol 2002;22:18)

Tumors with central depression tend to rapidly invade submucosa (Société Internationale de Chirurgie 2000)

Case reports: submucosal tumor (Int J Gastrointest Cancer 2005;36:177), with extensive nodal metastases (Int J Colorectal Dis 2001;16:262)

Gross: flat, plaque like, often with central depression; 1 cm or less; easier to detect with dye spraying of mucosa

Micro: limited to mucosa or invasive only to submucosa, by definition; height is usually less than twice the height of adjacent normal mucosa; has cytologic features of high grade dysplasia with mild architectural changes

Molecular: frequently early multiple loss of heterozygosity of 17p, 18p, 18q and 22q, coupled with LOH of other loci either simultaneously or in the early clonal progression phase (Ann Oncol 2006;17:43)

 

Squamous cell carcinoma of colon

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Extremely rare

Diagnosis of primary colonic tumor requires no involvement of cloacogenic or squamous lined mucosa, no squamous cell carcinoma elsewhere in body, and generous sampling to exclude adenosquamous carcinoma (Surg Today 1994;24:75)

Associated with ulcerative colitis (J Surg Oncol 1995;59:48), radiation therapy, schistosomiasis

Aggressive (Saudi Med J 2006;27:874); often metastatic to liver, peritoneum or lung

Favorable survival if node negative at presentation (Dis Colon Rectum 2001;44:341

May cause hypercalcemia (Dig Surg 2005;22:371)

Case reports: in villous adenoma (Hum Path 1988;19:362), from colocutaneous fistula (World J Gastroenterol 2005;11:5251), in colon duplication (Cancer 1981;47:602), with elevated serum squamous cell carcinoma antigen (Clin Colorectal Cancer 2001;1:55)

Negative stains: HPV (Eur J Surg Oncol 2002;28:657)

DD: extension or metastasis from anal or other carcinomas (Eur J Cardiothorac Surg 2001;19:719)

 

Villous adenocarcinoma of colon

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5% incidence in one study (World J Gastroenterol 1998;4:527)

Pre-resection biopsies may not be diagnosed as carcinoma

Appear to have a good prognosis

Associated with profound electrolyte disturbance (Ann Surg 1962;156:318)

Micro: villous architecture in 50% or more; presence of epithelial islands in desmoplastic stroma is specific and 67% sensitive for carcinoma vs. adenoma (AJSP 2004;28:1460)

 

 

Carcinoid tumors of colon

Carcinoid-rectum

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Most common site of colonic carcinoid is rectum

Annual incidence in USA: 10 per million vs. 500 for adenocarcinoma (Int J Colorectal Dis 2006 Jul 15 [Epub ahead of print])

Rarely is familial (Tech Coloproctol 2006;10:143)

5 year survival is 90% (Cancer 2003;97:934)

Poor prognosis (malignant potential): 2 cm or larger (associated with nodal metastases), invasion of muscularis propria, 2+ mitotic figures/HPF, angiolymphatic invasion, anaplasia

Case reports: liver metastases from tumor less than 5 mm (Hepatogastroenterology 2004;51:1330), atypical carcinoid associated with ulcerative colitis (J Clin Path 1986;39:913)

Treatment: local excision (J Laparoendosc Adv Surg Tech A 2006;16:435); partial colectomy if malignant potential (see above)

Gross: usually 5 mm or less, round, no ulceration

Micro: islands, trabeculae, glands or sheets of monotonous cells with scant, pink granular cytoplasm and round-oval stippled nuclei, small nucleoli, minimal pleomorphism, minimal mitotic activity; rarely mucin secretion or anaplasia; no necrosis

Positive stains: chromogranin, synaptophysin, neuron specific enolase; also PAP (80%), CEA, hCG

Negative stains: PSA

EM: cytoplasmic, well formed membrane bound secretory granules with dense (osmophilic) cores

Molecular: diploid if nonmetastasizing, aneuploid if metastatic

DD: prostate carcinoma (PSA+, neuroendocrine markers-)

References: eMedicine #271

 

Carcinoid-colon but not rectum

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Uncommon

Usually large, penetrate muscularis propria and involve regional lymph nodes

Not associated with carcinoid syndrome

Case reports: with adenoma (AJSP 1988;12:607)

Gross: flat or depressed plaque or polypoid lesion; yellow-tan, particularly after formalin fixation

Micro: islands, trabeculae, glands or sheets of monotonous cells with scant, pink granular cytoplasm and round-oval stippled nuclei, small nucleoli, minimal pleomorphism, minimal mitotic activity, no necrosis; rarely mucin secretion and anaplasia

Positive stains: chromogranin, synaptophysin, neuron specific enolase

EM: cytoplasmic, well formed membrane bound secretory granules with dense (osmophilic) cores

References: eMedicine #126

 

 

Lymphoma and hematopoietic lesions of colon
Lymphoma-general of colon

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Less common in colon than small bowel or stomach

Usually B cell lineage in Western countries; 18-30% are T cell lineage in Korea (Dig Dis Sci 2005;50:2243) and China (Zhonghua Bing Li Xue Za Zhi 2004;33:445); T cell patients are younger, associated with perforation and poorer prognosis

Risk factors: transplants, ulcerative colitis, AIDS

Regional lymph nodes involved in 50% of cases

Advanced lesions may impair gut motility by destroying muscle wall

10 year survival is 85% if localized to submucosa

Gross: plaque like expansion of mucosa/submucosa, bowel wall thickening, polyps (“multiple lymphomatoid polyposis” if multiple polyps throughout colon) or ulceration

 

Burkitt’s lymphoma of colon

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See also Lymphoma-B cell chapter

Sporadic cases in Western world and Middle East may present with ileocecal involvement and pain or obstruction

Endemic cases in Africa usually don’t present with GI involvement

Case reports: with Crohn’s colitis (J Clin Gastroenterol 2003;36:332), presenting as wide-based polyp (Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi 1996;37:373)

Micro: small, noncleaved, monomorphic cells with basophilic cytoplasm, round nuclei, prominent multiple nucleoli; starry sky appearance on low power

Cytology: vacuoles

Positive stains: CD20, CD10; Ki-67 staining in >90% of cells

Negative stains: CD5, CD23

Molecular: c-myc translocations [t(8;14) and others]

References: Pathologist’s perspective

 

Follicular lymphoma of colon

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See also Lymphoma-B cell chapter

Rare in colon; more common in small intestine (Am J Pathol 1992;140:1327)

Resemble mucosal polyps

Case reports: rectal tumor with FISH (World J Gastroenterol 2004;10:2602), 10 cm tumor of splenic flexure (J Clin Oncol 1999;17:3684)

Positive stains: CD20, bcl2; also CD10

Negative stains: CD5, T cell markers (in tumor cells)

Molecular: bcl-2 - IgH translocation

 

HHV8 positive lymphoma of colon

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Case reports: HIV negative patient with Kaposi’s sarcoma (J Surg Oncol 2001;76:197); 2 HIV+ men with EBV+ tumors but no primary effusion lymphoma (Hum Path 2002;33:846), primary tumors with secondary effusions (AJSP 1997;21:719)

Micro: markedly pleomorphic cells resembling immunoblasts, somewhat similar to anaplastic large lymphoma

 

Hodgkin’s lymphoma of colon

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Rare in colon

Associated with inflammatory bowel disease (Leuk Lymphoma 2001;42:521), chronic inflammation or chronic immunosuppression; all may cause EBV mediated lymphoproliferation (AJSP 2000;24:66)

Stringent diagnostic criteria necessary due to rarity of primary disease and possible confusion with secondary spread

Case reports: 42 year old woman with inflammatory bowel disease (Archives 2000;124:1824), 62 year old man with acute appendicitis (Clin Transl Oncol 2006;8:450), presenting as polyp (Clin Colorectal Cancer 2001;1:185), with diverticular disease (Archives 1997;121:528), causing splenic vein obstruction (Indian J Gastroenterol 1994;13:70)

Treatment: discontinuation of immunosuppressive therapy may be helpful

Gross: transmural involvement of bowel wall, often multifocal, associated with fissuring ulcers, diverticula with abscesses

Micro: Reed-Sternberg cells in background of lymphoid hyperplasia, occasional granulomas

Positive stains: CD15, CD30, EBER1, LMP1

Negative stains: CD45 (LCA)

 

MALT lymphoma of colon

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Rare in colon

Usually adults

Often relapse, but usually only in GI tract

Case reports: 75 year old woman (World J Gastroenterol 2006;12:5573), with lymphomatoid polyposis (Am J Gastroenterol 1999;94:2540)

Treatment: early tumors are focal and curable by surgery; antibiotics may cause regression (J Gastroenterol 2005;40:843, Endoscopy 2002;34:343)

Micro: small atypical lymphocytes with irregular nuclei, lymphoepithelial lesions; reactive germinal centers and plasmacytic cells are common

Molecular: usually trisomy 3 or 18; less commonly t(1;14);(p22;q32) (Gut 2006;55:1581); t(11;18)(q21;q21) in 15% (Mod Path 2003;16:1232)

 

Mantle cell lymphoma of colon

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Uncommon in colon

Often presents as multiple lymphomatoid polyposis

Often present in benign appearing mucosa (Curr Opin Gastroenterol 2005;21:80)

88% males, mean age 61 years

Also involves stomach and small intestine

Mean survival historically less than 3 years; may be improving with newer treatments

Rarely coexists as incidental finding with adenocarcinoma (Archives 2003;127:E64, Mod Path 2001;14:811, free full text)

Case reports: diffuse involvement of GI tract without polyposis (J Gastroenterol 2004;39:995), associated with ulcerative colitis (AJSP 1996;20:1024), rectal tumor (Hepatogastroenterology 2001;48:675), University of Pittsburgh Case #441

Gross: nodular, sessile or polypoid lesions, widely spaced, confluent studded or cobblestone appearance; each polyp 2 mm to 2 cm; may be dominant tumor mass in ileocecum; endoscopically normal mucosa may have small tumor infiltrates also

Micro: mantle cells (small lymphocytes with pale cytoplasm and cleaved nuclei), often invasion of submucosa, proliferation around germinal centers, sparing of mucosa; late - epithelial invasion and ulceration

Note: may also be minute lymphoid infiltrates in known mantle cell patients

Positive stains: CD20, CD5, cyclin D1/bcl1; immunohistochemistry for cyclin D1 may be more sensitive than FISH for t(11;14) or PCR for IgH (AJSP 2006;30:1274)

Negative stains: CD3, CD10, CD23

DD: nodular lymphoid hyperplasia (benign, associated with common variable immunodeficiency syndrome), multiple lymphoid polyps (benign germinal centers in children, patients with Gardner’s syndrome), MALT lymphoma (may present as multiple lymphomatoid polyposis, but has lymphoepithelial lesions, is negative for CD5 and cyclin D1), inflammatory bowel disease (may need immunostains to differentiate, Dig Dis Sci 1992;37:934)

 

Mast cell sarcoma of colon

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Rare

Case reports: 32 year old woman with ascending colon tumor (Mod Path 1999;12:739)

Micro: cells have abundant granular or clear cytoplasm; oval, lobulated or indented nuclei; numerous eosinophils

Positive stains: CD68, tryptase, CD45RB

 

T cell lymphoma of colon

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Rare in West, but 18% of colorectal lymphomas in Korea (Dig Dis Sci 2005;50:2243)

Usually EBV+ in China (Chin Med J (Engl) 2005;118:1542)

Often multifocal ulcerative lesions in relatively young patients; may resemble Crohn’s disease (Hepatogastroenterology 2002;49:950)

Poor prognosis, even if localized

Case reports: adult T cell leukemia/lymphoma (J Gastroenterol 2004;39:788), cytotoxic/suppressor phenotype #1 (AJSP 2000;24:296), #2 (Int J Hematol 2000;71:379), #3 with ulcerative colitis (J Gastroenterol 2003;38:376), gamma-delta phenotype causing lymphomatoid polyposis (Dig Liver Dis 2004;36:218), intravascular T cell lymphoma involving colonic vessels (Am J Hematol 2005;78:207), peripheral T cell lymphoma #1 in AIDS patient (Oncologist 2005;10:292), #2 with colonic adenocarcinoma (Pathol Oncol Res 2003;9:188), #3 with Crohn’s disease (Korean J Gastroenterol 2006;47:233), #4 with Crohn’s disease (Korean J Intern Med 1997;12:238), post-transplant tumor in child (AJSP 2004;28:967), T/NK cell lymphoma (J Gastroenterol 2002;37:939), lymphoma causing colojejunal fistula (Dis Colon Rectum 2005;48:158), with diffuse GI tract involvement (Korean J Intern Med 2000;15:245)

 

 

Mesenchymal tumors of colon

General

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Recommended that all stromal tumors be stained with CD117

 

Angiomyolipoma of colon

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Case reports: usually no association with tuberous sclerosis (Mod Path 1999;12:1132, Z Gastroenterol 2003;41:715, Dis Colon Rectum 2003;46:547, Gastroenterol Jpn 1989;24:407); may be HMB45 negative (Am J Gastroenterol 1996;91:1852), monotypic (J Clin Path 2005;58:1107) or pleomorphic (also called PEComa, Int J Surg Pathol 2000;8:67)

Positive stains: HMB45, CD68, vimentin, desmin, smooth muscle actin

Negative stains: CD34

 

Angiosarcoma of colon

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Very rare in GI tract as primary or metastasis

In GI series, median age 57 years (range 25-85 years, AJSP 2004;28:298)

Often death due to disease

Case reports: associated with retained surgical sponge (AJCP 1992;97:416), associated with prior surgery (World J Surg Oncol 2005;3:60), with rectal bleeding and obstruction (Dis Colon Rectum 2004;47:2202), in teenage boy (Acta Chir Belg 2004;104:465), cecal tumor (Indian J Gastroenterol 1995;14:31), metastatic from liver (Archives 2001;125:968), metastatic into tubular adenoma (Tumori 2005;91:210)

Micro: sheets of malignant appearing epithelioid cells with subtle areas of cleft-like spaces suggestive of vascular differentiation

Positive stains: CD31, CD34, Factor VIII, AE1-AE3; variable Cam 5.2/CK8, CK19, CK7

Negative stains: CK20, S100, EMA (usually)

DD: primary or metastatic carcinoma, melanoma, florid vascular proliferation due to prolapse or intussusception (Mod Path 2001;14:1114)

 

Endometrial stromal sarcoma of colon

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Rare complication of endometriosis and unopposed estrogen therapy (AJSP 2000;24:513)

Uterine primary tumors may also recur in colon (World J Gastroenterol 2005;11:2367, Eur J Gynaecol Oncol 2006;27:297)

Typically no death from disease (J Korean Med Sci 2002;17:412)

Case reports: with portal vein thrombosis (Archives 2001;125:1088), in bowel wall and mesentery (Eur J Gynaecol Oncol 2005;26:113), in mesentery (Ginekol Pol 2004;75:150)

Gross: tumor often arises in serosa or bowel wall

Micro: tongue like growth of tumor nodules composed of densely packed, plump spindle cells in short fascicles, interspersed with prominent small arterioles; tumor cells resemble proliferative endometrium with scanty ill-defined cytoplasm and round or ovoid nuclei with dispersed chromatin; often angiolymphatic invasion and perineural invasion despite low grade features; no/minimal pleomorphism or mitotic figures

Note - must see normal endometrial tissue to document malignant transformation of endometriosis

Positive stains: vimentin, ER, PgR, CD10; variable NKI/C3 and weak CD68

Negative stains: cytokeratin, EMA, S100, CD34, CD117, desmin, actin (muscle markers may be positive in epithelioid areas, Int J Gynecol Pathol 2002;21:48)

DD: GIST

 

Fibromatosis of colon

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Also called intraabdominal desmoid tumor

Uncommon, usually in mesentery or retroperitoneum; rarely adheres to or penetrates colonic wall

Mean age 34 years (younger than GIST patients)

May be associated with trauma, familial adenomatous polyposis, Gardner’s syndrome, Lynch syndrome (Cancer 1992;69:2049), hormonal stimulation

Locally aggressive (benign, but may recur)

Case reports: intraabdominal tumor with invasion of colonic wall (Eur J Pediatr Surg 2005;15:196); colonic mesenteric tumor causing acute abdomen (Indian J Gastroenterol 2002;21:199), inoperable recurrence causing death (Vojnosanit Pregl 2006;63:839), solitary colonic tumor in neonate (Eur J Pediatr Surg 2002;12:337), with Turner’s syndrome (Kurume Med J 1999;46:181)

Treatment: surgical excision, radiation therapy, possibly chemotherapy

Gross: firm, tan, homogenous; usually large (6 to 25 cm) with infiltrative margins

Micro: broad, sweeping fascicles of bland spindle cells with overall minimal mitotic activity (mean 4 mitoses/50 HPF), bland nuclear features, finely collagenous stroma; infiltrative borders, evenly spaced blood vessels; may involve muscularis propria but no necrosis, no hemorrhage, no myxoid degeneration, no epithelioid cells, no pleomorphism, no foam cells, no inflammatory cells

Positive stains:  vimentin, CD117 (some antibodies), smooth muscle actin, desmin (50%)

Negative stains: CD34, S100

EM: myofibroblastic/fibroblastic differentiation

DD: GIST (CD117+ with all antibodies, often malignant histologic features, AJSP 2000;24:947)

 

Ganglioneuromatosis of colon

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Either polypoid ganglioneuromas, ganglioneuromatous polyposis or diffuse ganglioneuromatosis

Usually arises from nerves within bowel wall

Polypoid ganglioneuromas: small, solitary/few; ganglion cells in nests in submucosa or mucosa, usually relatively normal surrounding tissue

Ganglioneuromatous polyposis: more than 20 lesions, each with greater variability in ganglionic, neural and stromal content

Diffuse ganglioneuromatosis: proliferation of neural elements involving entire enteric plexus (Ann Pathol 2004;24:129); large lesions up to 17 cm, poorly demarcated, can distort surrounding tissue; may cause diarrhea; associated with neurofibromatosis type 1 (NF-1 mutation), MEN 2b/3 (RET mutation, AJSP 1994;18:250, Gut 1999;45:143) or Cowden’s disease (PTEN mutation)

Adults - may have polyps, but usually a microscopic diagnosis (Gastroenterol Clin Biol 2003;27:219)

Low malignant potential

Case reports: causing chronic diarrhea (Ugeskr Laeger 1998;160:7139), with mucinous adenocarcinoma and hyperparathyroidism (Eur J Gastroenterol Hepatol 1999;11:447), with cutaneous lipomatosis (Archives 2006;130;1561)

Gross: polypoid; sessile or pedunculated

Micro: proliferation of ganglion cells and spindled Schwann cells in lamina propria and deeper layers; may see accentuation of submucosal and myenteric plexus in MEN 2b/3

Positive stains: Schwann cells - S100; nerve fibers - NSE, synaptophysin, neurofilament; ganglion cells - c-Ret

Molecular: c-RET mutations, even without MEN2b syndrome (J Clin Endocrinol Metab 1998;83:4191)

DD: Crohn’s disease (AJR Am J Roentgenol 2004;182:1166), intestinal neuronal dysplasia

 

Gastrointestinal autonomic tumor (GANT) of colon

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Variant of gastrointestinal stromal tumors with ultrastructural neural differentiation

Requires EM for diagnosis

Mean age 55 years, usually men

Rare in colon, more common in small bowel, mesentery, retroperitoneum

Recommended to consider as same entity as GIST

Case reports: colonic tumor (Int J Surg Path 1998;6:171), sigmoid tumor with relapse (Tumori 2001;87:349)

Gross: >10 cm, well circumscribed, transmural involvement of bowel wall, tan-pink, lobulated, hemorrhagic with necrosis and cystic degeneration

Micro: interlacing spindle cells with minimal pleomorphism, 1-2 mitoses/10 HPF

Positive stains: CD117, vimentin, NSE; variable CD34

Negative stains: muscle markers (usually)

Molecular: c-KIT mutations and loss of 22q13-qter region (Mod Path 2002;15:692)

EM: neuron like cells with axonal cytoplasmic processes; synapse like structures; dense core neurosecretory granules

References: AJSP 2002;26:396

 

Gastrointestinal stromal tumors (GIST) of colon

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Tumors that differentiate along lines of interstitial cells of Cajal, the gut’s pacemaker cells

5-10% of GISTs occur in colon, often in rectum

Median age 67 years, usually > 50 years

30-50% are malignant with 5 year survival of 50%

Don’t call GIST without expert concurrence if CD117 is negative

Case reports: prostatic stromal sarcoma with rectal GIST (Urology 2006;68:672.e11), malignant tumor

·  NIH criteria for assessing risk (Int J Surg Pathol 2002;10:81, Hum Path 2002;33:459)

·  High risk: > 1 cm and > 5 MF/50 HPF; also infiltrative border within muscularis propria; most colorectal tumors are high risk; 2/3 develop metastases (Dis Colon Rectum 2006;49:609)

·  Intermediate risk: 1-5 MF/50 HPF and > 1 cm

·  Low risk: < 1 cm (often are serosal)

Treatment: Gleevec (imatinib, STI571), which inhibits tyrosine kinases including CD117/c-kit and Abl protein in CML

Gross: often large, bulky, intramural masses; fish-flesh or tan-brown appearance, hemorrhage, necrosis, cystic softening

Micro: often histologically malignant, transmural, usually plump spindle cells with eosinophilic cytoplasm within variably hyalinized or edematous stroma; skenoid fibers (extracellular collagen globules) common; muscle infiltration is common but not predictive of behavior; may have epithelioid morphology; rarely has osteoclast-like giant cells (Archives 2004;128:440)

Positive stains: CD117, CD34, vimentin; alpha smooth muscle actin (30-40%), S100 (5%); variable keratin (weak)

Negative stains: desmin

Molecular: 36% have c-kit mutations in codon 11

EM: long interdigitating cytoplasmic processes, intercellular junctions, dense core granules

DD: leiomyosarcoma (atypical histology, positive for smooth muscle actin or desmin, CD117-, CD34-, no c-kit mutations), uterine type leiomyomas (attached to colon without wall involvement, resemble benign leiomyoma, actin+, desmin+, CD117-, Int J Colorectal Dis 2006;21:84, Int J Gynecol Cancer 2006;16:927), fibromatosis (may be CD117+ depending on antibody used, AJSP 2000;24:947, AJSP 2001;25:549)

References: AJSP 2000;24:1339, Mod Path 2003;16:366, Radiographics 2003;23:283

 

Hemangioma of colon

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Usually associated with systemic syndromes

Causes melena, anemia, rarely intussusception or obstruction

Capillary and cavernous subtypes

Capillary: small, closely packed capillaries, rarely multiple (Dtsch Med Wochenschr 2004;129:1970)

Cavernous: localized or diffuse; blood-filled sinus-like spaces with scant connective tissue, variable smooth muscle; often in rectum and associated with mass or bleeding; may be infiltrative (Rev Gastroenterol Mex 2004;69:94, Rev Esp Enferm Dig 2004;96:346)

Arteriovenous malformation / hemangioma: composed of abnormal arteries and veins; see Vascular Ectasia in Colon-NonTumor chapter

Hemangiomas are associated with Klippel-Trenaunay-Weber syndrome (Ann Univ Mariae Curie Sklodowska [Med] 2004;59:356, somatic and bony hypertrophy, port wine stain, bladder hemangiomas) and blue rubber bleb nevus syndrome (Eur J Pediatr Surg 2003;13:137, skin and visceral hemangiomas)

Telangiectasias are associated with hereditary hemorrhagic telangiectasia (telangiectasias of skin, mucosa, internal organs), Turner’s syndrome (XO, short stature, webbed neck, streak ovaries, shield chest) and progressive systemic sclerosis

Cecum hemangiomas are associated with cardiac or vascular disease (Gastroenterology 1976;71:1079)

 

Histiocytic sarcoma of colon

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Rare

Many cases diagnosed without immunohistochemistry are actually lymphomas

Mean age 55 years (range 15-89 years)

Gross: solitary mass, often involving regional lymph nodes; infiltrative margins

Micro: sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin and prominent nucleoli; often binucleated or tumor giant cells; prominent inflammatory infiltrate; often mitotic activity and necrosis

Positive stains: CD45/LCA, CD45RO, CD68, CD4, lysozyme, CD31; CD163 (Mod Path 2005;18:693, free full text); variable S100, CD1a and CD30 (weak)

Negative stains: ALK1, CD21, CD35, CD3, CD20, CD34, myeloperoxidase, HMB45, keratin, c-kit, desmin

References: AJSP 2004;28:1133

 

Idiopathic retractile mesenteritis of colon

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Also called mesenteric panniculitis

Common in rural areas of Peru (Rev Gastroenterol Peru 1998;18 Suppl 1:114), otherwise rare

Nonneoplastic idiopathic condition usually affecting small bowel, which can also cause thickening and shortening of colonic mesentery

Usually men age 40+ years; associated with intestinal obstruction but no other systemic symptoms

Case reports: 12 year old girl (Pediatr Radiol 1997;27:342), 40 year old man with large mesenteric mass (Archives 2001;125:443)

Gross: markedly thickened and rubbery mesentery with twist of bowel

Micro: fibrosis with massive accumulation of dense collagen, fat necrosis, chronic inflammation, variable focal calcification; minimal atypia, no/minimal mitotic figures

DD: inflammatory pseudotumor, fibromatosis, idiopathic retroperitoneal fibrosis, sclerosing malignant lymphoma, liposarcoma (Chirurg 2001;72:742)

References: Surg Today 1996;26:435, Dis Colon Rectum 1987;30:962

 

Idiopathic retroperitoneal fibrosis of colon

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Also called Ormond’s disease

Fibrosis develops in retroperitoneum, often at aortic bifurcation

Associated with methylsergine, lymphoma, other fibrotic lesions (sclerosis of major bile ducts, Riedel’s thyroiditis, inflammatory pseudotumor of orbit), tumors as a paraneoplastic process (Acta Med Austriaca 2000;27:168)

Case reports: causing obstruction (Ann Surg 1972;176:199)

Gross: not well circumscribed

Micro: widely scattered germinal centers and plasma cells in background of dense fibrosis; may have fat necrosis

DD: Whipple’s disease (lipogranulomatous inflammation with large, round, empty spaces containing PAS+ bacilli)

References: eMedicine #605, eMedicine #3664

 

Inflammatory myofibroblastic tumor of colon

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Also called inflammatory pseudotumor, inflammatory fibrosarcoma, plasma cell granuloma

Often a pediatric tumor, usually multifocal, associated with fever, weight loss, anemia, leukocytosis, thrombocytosis, high sedimentation rate, hypergammaglobulinemia (J Pediatr Surg 2001;36:169)

Benign, but may recur

Case reports: 7 year old (Croat Med J 1999;40:550), 11 year old boy, 16 year old girl, 35 year old woman with clinical appendicitis (Scott Med J 2004;49:157), 69 year old man with incidental adenocarcinoma (Ann Ital Chir 1997;68:245); 71 year old woman with colonic obstruction (Surg Today 1998;28:416)

Gross: circumscribed

Micro: spindle cells with abundant amphophilic cytoplasm; variably prominent nucleoli, lymphoplasmacytic infiltration with polyclonal plasma cells; laminated or whorled fibrosis; may contain psammoma bodies if present in peritoneum

Positive stains: desmin, actin, ALK

Negative stains: S100, CD117, CD34

EM: myofibroblasts

DD: Schistosomiasis (J Natl Med Assoc 2006;98:1365) or other inflammatory masses

 

Kaposi’s sarcoma of colon

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GI involvement in 50-80% with visceral involvement due to AIDS or in endemic areas of Africa

GI symptoms are rare (diarrhea, protein-losing enteropathy, abdominal pain)

Case reports: HIV negative man #1 (J Surg Oncol 2001;76:197), #2 with ulcerative colitis (Dis Colon Rectum 1989;32:73), HIV negative woman with Crohn’s disease (Dig Dis Sci 1991;36:528)

Gross: red-brown to purple macules or nodules 5-15 mm

Micro: submucosal lesions similar to skin lesions; expansion of lamina propria by spindle cells with mild/moderate atypia that obliterate muscularis mucosa; extravasated red blood cells common

Positive stains: CD31, CD34; CD117 (focal in 15%)

Negative stains: S100, desmin, muscle specific actin, HMB45

DD: GIST, melanoma

 

Leiomyoma of colon

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Benign, commonly presents as incidental tumor of muscularis mucosa of colorectum

3% of GI leiomyomas occur in colon

2/3 male, median age 62 years (range 38 to 85 years)

Benign, total excision is adequate treatment

Case reports: 10 month old girl (Pediatr Surg Int 2003;19:104), producing giant retroperitoneal mass (Obstet Gynecol 2003;101:1132)

Gross: 4 mm, usually rectosigmoid, firm, white, well delineated polypoid lesion

Micro: well differentiated smooth muscle cells beneath mucosa that obliterates and merges with muscularis mucosa; may have significant atypia (symplastic leiomyoma); usually no mitotic activity, no necrosis

Positive stains: smooth muscle actin, desmin

Negative stains: CD34, CD117, S100

References: Mod Path 2001;14:950

 

Leiomyomatosis

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Case reports: involving small intestine and colon (Archives 1992;116(3):281), involving colon and mesentery (Am J Gastroenterol 1986;81:385), along 35 cm of colon (Cancer 1977;39:263), with severe combined immunodeficiency (Pediatr Dev Pathol 2003;6:449)

Gross: multifocal tumor masses in muscular layer

Micro: proliferating smooth muscle cells surrounded by prominent blood vessels; no atypia; no/rare mitotic figures

 

Leiomyomatosis-like lymphangioleiomyomatosis of colon

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Extremely rare  (one case report)

Case reports: 30 year old Chinese woman with tuberous sclerosis (Mod Path 2001;14:1141)

Treatment: excision

Gross: diffuse nodular thickening of colonic wall

Micro: smooth muscle proliferation within colonic wall and also arising from thin walled vessels; focal extension into pericolic fat; no pleomorphism, no atypia, no mitotic figures

Positive stains: HMB45 (epithelial cells only), smooth muscle actin, desmin, vimentin

Negative stains: CD117, CD34, S100, ER, PgR, bcl2

 

Leiomyosarcoma of colon

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Rare in colon; less common than GIST

Infantile tumors have favorable prognosis (J Pediatr Surg 2004;39:1257); adult patients often die of disease

May be a rare late effect of pelvic radiation (Hepatogastroenterology 2003;50:1933, Am Surg 1999;65:6)

Gross: intraluminal, bulging, polypoid mass

Micro: resembles smooth muscle but with high grade histology; rarely has osteoclast-like giant cells (Archives 2004;128:440)

Positive stains: smooth muscle actin, desmin

Negative stains: CD117, CD34, S100

Molecular: no c-kit mutations

DD: metastatic leiomyosarcoma (South Med J 1997;90:1238)

References: AJSP 2000;24:1339

 

Lipoma of colon

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Rare, usually submucosal in right colon

Second most common benign tumor of colon after adenoma

Easily discernible by CT or MRI (Ned Tijdschr Geneeskd 2006;150:1990)

May be associated with intussusception (Am Surg 2006;72:83, Rom J Gastroenterol 2005;14:393)

Case reports: 83 year old woman (World J Gastroenterol 2005;11:3167), with bloody stools

Micro: may have overlying mucosal ulceration, atypical stromal cells, florid vascular proliferation due to repeated intussusception (Pathol Int 2005;55:160)

 

Lipomatosis of colon

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Also called lipohyperplasia

Clinically may resemble tumor

Uncommon

Localized - usually asymptomatic

Diffuse - may cause obstruction, hemorrhage or diarrhea

Case reports: involving all intrapelvic organs (Urologe A 2003;42:1244), causing intussusception (Indian J Gastroenterol 2003;22:151), with diverticulosis (Dis Colon Rectum 2000;43:1767, Dis Colon Rectum 1995;38:769), with hyperplasia of epiploic appendages (Ann Ital Med Int 1995;10:55), with well differentiated liposarcoma (Hepatogastroenterology 1998;45:2151), with neurofibromatosis (Leber Magen Darm 1988;18:265)

Gross: polypoid masses of fat covered by normal mucosa

Micro: infiltration of fat into submucosa

References: Minerva Gastroenterol Dietol 1998;44:207

 

Liposarcoma of colon

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Frequently in retroperitoneum; tumors adherent to colon may involve colonic wall

Case reports: 12 cm subserosal tumor (J Gastrointest Surg 2006;10:652), well differentiated tumor #1 (Int t J Surg Pathol 2004;12:281); #2 of sigmoid mesocolon (Hepatogastroenterology 1998;45:2151)

Micro: various subtypes; dedifferentiated tumors resemble GIST, but usually have foci of well differentiated liposarcoma

Negative stains: CD117

 

Mullerian adenosarcoma of colon

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Associated with endometriosis and unopposed estrogen therapy (AJSP 2000;24:513)

Case reports: with tubulovillous adenoma (Int J Gynecol Cancer 2005;15:361)

Micro: proliferation of endometrioid glands and stroma with stromal condensation around glands, mild to moderate cytologic atypia of stromal, stromal mitoses; may have stromal pseudodecidualization, focal epithelial atypia; no definite malignant epithelial features

 

Perineurioma of colon

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Uncommon in GI tract

Usually women, mean age 51 years (range 35-72 years)

Benign, does not recur

Gross: small sessile polyp detected during colonoscopy, usually mucosal or submucosal in distal colon; median 0.4 cm

Micro: bland spindle cells with pale indistinct cytoplasm, ovoid nuclei, fine collagenous stroma; no atypia, no pleomorphism, no mitotic figures; adjacent mucosa may have hyperplastic changes

Positive stains: EMA, variable claudin1 and CD34

Negative stains: S100, GFAP, neurofilament, smooth muscle actin, desmin, KIT, keratin

EM: spindle cells with long bipolar cytoplasmic processes, prominent pinocytotic vesicles, discontinuous basal lamina

DD: neurofibroma, solitary fibrous tumor

References: AJSP 2005;29:859

 

Perivascular epithelioid cell tumor of colon

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Rare

May overlap with angiomyolipoma

Case reports: 43 year old Japanese woman with malignant tumor attached to colonic serosa (Pathol Int 2006;56:46), cecal tumor in young woman (Dis Colon Rectum 2004;47:1734), 40 year old British woman (J Clin Pathol 2005;58:1107)

Micro: sheets of epithelioid cells with clear or eosinophilic cytoplasm

Positive stains: HMB45, smooth muscle actin, desmin

Negative stains: S100, cytokeratin

 

Pyogenic granuloma of colon

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Also called lobular capillary hemangioma

Very rare

Case reports: 62 year old woman with rectal bleeding (Ann Diagn Pathol 2005;9:106)

Micro: lobular arrangement of capillaries within edematous stroma; endothelial cells often swollen; often surface ulceration; occasionally mitotic figures

Positive stains: endothelial cells - CD34, Factor VIII (AJSP 1995;19:1054)

DD: inflammatory polyp, bacillary angiomatosis, Kaposi’s sarcoma

 

Reactive nodular fibrous pseudotumor of colon

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First described in 2003 in 5 patients (AJSP 2003;27:532)

Mean age 56 years, range 48 to 71 years

Associated with prior abdominal surgery

At other sites, associated with endometriosis and ergotamine derivatives (Virchows Arch 2005;447:879)

May be related to a proliferation of multipotential subserosal cells (Int J Surg Pathol 2004;12:365)

Symptoms: acute abdominal pain, abdominal mass or incidental lesion

Treatment: complete resection appears curative

Gross: multiple or solitary tumors, usually involving outer wall of small intestine or colon; firm, tan-white, 3-10 cm, well circumscribed

Micro: low to moderately cellular, composed of stellate or spindled fibroblasts arranged haphazardly or in intersecting fascicles; may have infiltrative borders; stroma rich in collagen (wire-like, keloidal or hyalinized); peripheral lymphoid aggregates present

Positive stains: CD117 (80%), muscle specific actin or desmin (60%), vimentin, cytokeratin AE1-AE3

Negative stains: CD34, S100, ALK1

EM: myofibroblasts

DD: retroperitoneal fibrosis (disease of retroperitoneum, associated with Reidel’s sclerosing thyroiditis, methylsergine), sclerosing mesenteritis (involves mesentery or mesocolon, mean 10 cm but up to 40 cm, usually no prior trauma, thick collagen bands dissecting lobules of mesenteric fat with fat necrosis)

 

Schwannoma of colon

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Rare; less common than colonic GIST

Median age 65 years, range 18-87 years; affects men and women equally

Benign behavior; not associated with neurofibromatosis

Case reports: 2 cases (Surg Today 2001;31:833), sigmoid tumor (Kurume Med J 2000;47:165), plexiform schwannoma #1 (Mod Path 1997;10:1075); #2 causing intussusception (Thomas Jefferson University 2006); rectal tumor #1 with synchronous colonic adenocarcinoma (World J Surg Oncol 2005; 3:46), #2 misdiagnosed as sarcoma (Med Sci Monit 2000;6:779),

Gross: well circumscribed but usually not encapsulated, polypoid intraluminal mass 0.5 to 5.5 cm with mucosal ulceration, usually in right colon

Micro: spindle cells surrounded by lymphoid cuff; usually trabecular pattern with indistinct/no Verocay bodies; often focal nuclear atypia; 0-4 mitotic figures/50 HPF; usually not encapsulated, no vascular hyalinization, no xanthoma cells, no prominent nuclear palisading; may have epithelioid or plexiform features

Positive stains: S100, GFAP; may have PAS+ needle-shaped crystalloids (AJSP 1999;23:431); also type 4 collagen, low affinity nerve growth factor receptor (p75)

Negative stains: CD117/kit, smooth muscle actin, desmin, CD34 (usually), Ki-67 (less than 3%)

DD: GIST (CD117+, CD34+, S100-, no prominent lymphoid infiltration, no microtrabecular pattern), leiomyomas (rare, usually small polyps, positive for smooth muscle markers), inflammatory myofibroblastic tumors (spindle cells with abundant amphophilic cytoplasm)

References: AJSP 2001;25:846

 

Solitary fibrous tumor of colon

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Occasionally occurs in peritoneal cavity and adheres to bowel

Case reports: malignant tumor growing into adipose tissue surrounding colon (Hinyokika Kiyo 2002;48:637)

Micro: patternless pattern of spindle cells and collagen

Positive stains: CD34

Negative stains: CD117

 

 

Other tumors of colon

Langerhans cell histiocytosis of colon

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Uncommon; present in ~10% of children with multisystemic disease, J Pediatr Gastroenterol Nutr 1999;29:462)

Diagnose by rectal biopsy

Case reports: 5 month old baby with GI bleeding (J Pediatr Gastroenterol Nutr 1985;4:286)

 

Rosai-Dorfman disease of colon

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Extranodal form of sinus histiocytosis with massive lymphadenopathy

Rare in colon, <15 cases reported thru Aug03, usually incidental or at autopsy

Polyclonal / reactive; usually has protracted clinical course

Case reports: 51 year old woman with intermittent hematochezia (Archives 2003;127:E74)

Gross: round mass with intact overlying mucosa

Micro: sheets of large foamy histiocytes without nuclear grooves, mixed with lymphocytes and plasma cells; infiltrates submucosa and muscularis propria but not mucosa; histiocytes demonstrate emperipolesis (ingestion of red blood cells); lymph nodes have similar findings

Positive stains: histiocytes - S100, lysozyme, CD68

Negative stains: histiocytes - CD1a

DD: Langerhans cell histiocytosis (grooved nuclei, CD1a+)

 

Teratoma of colon

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Rare (<25 cases reported through Aug03)

Usually mature; excision is curative in all colonic cases of mature cystic teratoma reported to date

Case reports: mature cystic teratoma (dermoid cyst) in cecum of 30 year old man (Archives 2002;126:97), presenting as hairy polyp (Endoscopy 1989;21:148), malignant teratoma associated with ulcerative colitis (Virchows Arch A Pathol Anat Histopathol 1987;411:61)

Gross (dermoid cyst): unilocular cyst with thin uniform wall and smooth lining, contains tan/white cheesy material that flakes away in layers; may contain hair or teeth

Micro (dermoid cyst): cyst lined by keratinizing stratified squamous epithelium with granular tissue; cyst wall may contain sebaceous glands and other adnexal structures; variable fibrosis and smooth muscle; no endodermal or mesodermal elements; no immature elements or atypia

 

 

Other

Grossing of colonic lesions

Polyps

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Fix first for proper sectioning

Take section through surgical margin of stalk (may want to ink first)

Embed entirely to detect high grade dysplasia or invasive carcinoma (AJCP 2001;116:336)

 

Colectomy - no tumor

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Remove mesentery and sample lymph nodes while fresh

Either open bowel and pin overnight to fix, or inject specimen with formalin to fix

Take these sections:

Abnormal areas by taking sections perpendicular to mucosal folds (through bowel wall)

Resection margins

Appendix, terminal ileum, cecum, ileocecal value, if present

 

Colectomy - tumor

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Remove mesentery and dissect lymph nodes while fresh

May use clearing agent to obtain sufficient number of lymph nodes (see staging)

Either open bowel (don’t cut through tumor) and pin overnight to fix, or inject specimen with formalin to fix

Take these sections:

Tumor (entire tumor if 5 sections or less or 1 section per cm diameter)

Serosa at point of deepest penetration of tumor (may want to ink serosal first)

Full thickness of bowel wall (may need to split to fit into a cassette)

Resection margins

Appendix, terminal ileum, cecum, ileocecal value, if present

Any abnormalities

Normal appearing bowel

 

Staging of colonic carcinoma

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Previous staging systems are 1932 Dukes staging system for rectal carcinomas applied to colon carcinomas or 1954 Astler-Coller modification of Dukes staging

TNM staging excludes anal canal tumors

Appendiceal adenocarcinomas are recorded separately

Examination of all mesentery may be necessary to ensure correct pN status in pN1 cases (Mod Path 2004;17:402)

 

Dukes (designed for rectum, often applied to entire colon)

A - growth limited to wall of rectum

B - extension of growth to extra rectal tissues, no metastasis to regional lymph nodes

C - metastases in regional lymph nodes, modified in 1935 to C1 and C2 stages

     C1 - metastases to regional lymph nodes

     C2 - metastases to lymph nodes at point of mesenteric blood vessel ligature

D - distant metastases (not part of original classification)

 

Astler-Coller classification

A - lesion limited to mucosa

B1- lesion involves muscularis propria but does not penetrate through it

B2- lesion penetrates through the muscularis propria

C1- metastatic tumor in lymph nodes but the tumor itself is still confined to the bowel wall

C2- metastatic tumor in lymph nodes and tumor itself has penetrated through the entire bowel wall

 

Note: per Rosai, call stage B if no identifiable muscularis propria layer between tumor and serosal surface

 

TNM staging of colorectal carcinoma

Primary tumor (T)

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TX: primary tumor cannot be assessed

T0: no evidence of primary tumor

Tis: carcinoma in situ (i.e. intraepithelial or invasion of lamina propria but not through muscularis mucosa into submucosa)

T1: tumor invades submucosa

T2: tumor invades muscularis propria

T3: tumor invades through the muscularis propria into the subserosa, or into non-peritonealized periappendiceal tissues

T4: tumor directly invades other organs or structures (T4a) or perforates visceral peritoneum (T4b)

 

Note: tumor that is adherent to other organs or structures macroscopically is classified as T4; if no tumor is present in the adhesion, the classification should be pT3

Note: pT4 (serosal involvement) includes (a) tumor close to, but not at, serosal surface due to mesothelial inflammatory or hyperplastic reaction, (b) tumor at serosal surface with inflammatory reaction, mesothelial hyperplasia or erosion, or (c) free tumor cells on the serosal surface with underlying ulceration.  All of these, particularly (b), are associated with decreased survival.  The presence of tumor well clear of the serosa has no independent adverse effect.  Touch preps may be helpful.

 

Regional lymph nodes (N)

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NX: regional lymph nodes cannot be assessed

N0: no regional lymph node metastases

N1: metastasis in 1-3 regional lymph nodes

N2: metastasis in 4 or more regional lymph nodes

 

Note: a tumor nodule in the periappendiceal adipose tissue of a primary carcinoma without histologic evidence of residual lymph node in the nodule is classified in the pN category as a regional lymph node metastasis if the nodule has the form and smooth contour of a lymph node.  If the nodule has an irregular contour, it should be classified in the T category and also coded as microscopic (V1) or macroscopic venous invasion (V2), because there is a strong likelihood that it represents venous invasion

 

Notes:

(a) 10-15 lymph nodes are required for accurate staging (Eur J Cancer 2005;41:2071)

(b) increasing number of negative nodes in Stage IIIB/C disease has favorable prognostic value (Am J Gastroenterol 1998;93:1949)

(c) sentinel node staging with cytokeratin is highly accurate for clusters of tumor cells; isolated cytokeratin+ cells may not represent tumor, Archives 2003;127:673, Archives 2000;124:1759

(c) most lymph nodes with metastases are 5 mm or less

(d) nodal metastases often have involvement of surrounding veins

(e) presence of micrometastases currently has no definitive value

 

Distant Metastasis (M)

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MX: distant metastasis cannot be assessed

M0: no distant metastasis

M1: distant metastasis; includes seeding of abdominal organs and metastases to external iliac or common iliac lymph nodes

 

Stage grouping           Dukes staging   Astler-Coller             5 year survival (JNCI 2004;96:1420)

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Stage 0: Tis N0 M0                  -                -                                     100%

Stage 1: T1-T2 N0 M0              A           A, B1                                 93%

Stage 2A: T3 N0 M0                B             B2                                     85% 

Stage 2B: T4 N0 M0                B             B3                                     72%                 

Stage 3A: T1-T2 N1 M0           C            C1                                     83%

Stage 3B: T3-T4 N1 M0           C            C2/C3                                64%      

Stage 3C: Any T N2 M0           C            C1/C2/C3                          44%

Stage 4: Any T, any N, M1       -              D                                         8%

 

Staging diagrams: UCSF, Stonybrook

 

Residual tumor (R factor)

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Tumor remaining in patient after surgical resection

 

RX: presence of residual tumor cannot be assessed

R0: no residual tumor; margins histologically negative

R1: microscopic residual tumor (corresponds to positive resection margin)

R2: macroscopic residual tumor (either positive margins or gross disease remains after resection)

 

References: Archives 2006;130:318 (staging problems)

 

Features to report for colonic carcinoma or other tumors

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Note: “mandatory” means for accreditation purposes by the American College of Surgeons Committee on Cancer

“recommended” means suggested by the literature

 

Colonic biopsy-recommended features to report

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Histologic type

Histologic grade (low grade: 50%+ gland formation; otherwise high grade)

Depth of invasion (if identifiable)

Angiolymphatic invasion (including extramural venous invasion)

 

Polypectomy-mandatory to report

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Tumor site

Polyp size

Polyp configuration (pedunculated with or without stalk, sessile, fragmented)

Histologic type

Histologic grade (low grade: 50%+ gland formation; otherwise high grade)

Depth of invasion

Involvement of deep (stalk) margin by invasive carcinoma or distance of invasive carcinoma from margin

Involvement of mucosal/lateral margin by invasive or in situ carcinoma

Lymphatic invasion

 

Polypectomy-recommended but not required to report

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Large vessel invasion

Type of polyp in which invasive carcinoma arose

Additional findings

 

Rectal tumor: local excision-mandatory to report

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Specimen intact or fragmented

Tumor size

Histologic type

Histologic grade (low grade: 50%+ gland formation; otherwise high grade)

pT and pN staging

Lateral margin involvement by invasive carcinoma or distance to margin

Deep margin involvement by invasive carcinoma or distance to margin

Focal or multifocal involvement of deep margin by invasive carcinoma

Lymphatic invasion

Large vessel invasion

 

Rectal tumor: local excision-recommended but not required to report

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Distance of tumor from anal verge

Lateral margin involvement by adenoma

Perineural invasion

Dysplasia present (high grade, low grade)

Depth of invasion (part of staging)

Additional findings

 

Colorectal resection for tumor-mandatory to report

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Specimen type

Tumor site

Tumor size

Histologic type

Histologic grade (low grade: 50%+ gland formation; otherwise high grade)

pT, pN and pM staging

Proximal margin involvement by invasive carcinoma or adenoma or distance to margin

Distal margin involvement by invasive carcinoma or adenoma or distance to margin

Radial margin involvement by invasive carcinoma or adenoma or distance to margin

If all margins are negative, specify closest margin and distance of invasive carcinoma from this margin

Lymphatic invasion

Large vessel invasion

 

Colorectal resection for tumor-recommended but not required to report

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Specimen length

Gross tumor configuration (exophytic, infiltrative, ulcerative, other)

Peritoneal (mesenteric) margin involvement by invasive carcinoma or adenoma or distance to margin

Perineural invasion

Depth of invasion (part of staging)

Additional findings

 

Possible features to report (suggested by some authors)

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Intra or peritumoral lymphocytic response

Pattern of tumor at periphery (pushing, infiltrative)

Intactness of mesorectum (incomplete, nearly complete or complete)

 

Link to College of American Pathologist protocols

Checklists: Michigan Cancer Consortium, University of Texas

References: Archives 2000;124:1016

 

End of Colon-tumor chapter

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