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Colon tumor
Reviewers: Shilpa Jain, M.D., Charanjeet Singh, M.D. (see Reviewers page)
Revised: 23 October 2011, last major update August 2011
Copyright: (c) 2003-2011, PathologyOutlines.com, Inc.
Primary
references
Molecular pathways: general, chromosomal pathway, CpG island, microsatellite instability, MUTYH pathway
Polyps: general, biopsies, aberrant crypt foci, adenoma, carcinoma arising in adenoma, adenoma-carcinoma sequence, atheroemboli, cap polyposis, displaced glands, diverticular, fibroblastic, flat adenoma, hyperplastic, 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, 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, staging-neuroendocrine, 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
top
AJCC
Cancer Staging Manual (7th ed)
American Journal of Surgical Pathology
Archives of Pathology and Laboratory
Medicine
Human Pathology
Modern Pathology
Websites with images: PathoPic, PEIR digital library
Please refer to these primary references for more detailed discussions and photographs
Polyps of colon
Muciphages, without other abnormalities, have no clinical significance (Histopathology 2000;36:556)
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
Diagnosis requires (a) classic endoscopic (gross) appearance of mucosal elevation with flat/rounded surface and height less than half the diameter, (b) not resembling a hyperplastic polyp, and (c) dysplastic changes
Another study defined flat as thickness of 1.3 mm or less or thickness less than twice normal mucosal thickness
Controversial if associated with higher risk for high grade dysplasia (no-Clin Gastroenterol Hepatol 2004;2:905; yes-Dis Colon Rectum 1991;34:981); risk may be higher if central depression, individual history or family history of malignancy (Dis Colon Rectum 2000;43:782), or larger lesion (Dis Colon Rectum 1985;28:847)
Endoscopic images: flat adenoma
Case reports: with deep malignant component (Virchows Arch A Pathol Anat Histopathol 1993;422:415)
Gross: flat or slightly raised plaques, often with a central depression; usually height 2 mm or less; may be multiple
Micro: plaque-like, not polypoid or exophytic; up to twice the thickness of adjacent normal epithelium; usually tubular adenomas that show superficial adenomatous changes at periphery, and centrally may extend throughout the crypt
Also associated with aberrant crypt foci (Am J Gastroenterol 2005;100:1283)
Micro images: flat adenoma; A: flat adenoma; B: MUC2+; C: MUC1+ only focally; A: flat adenoma; B: MUC2+; C: MUC1+ at base of crypts; MUC2-left; MUC1-right
Molecular: some cases have multiple APC mutations (Eur J Hum Genet 1999;7:928)
References: Hum Path 1991;22:70, Am J Gastroenterol 2006;101:172
90% of all polyps
Usually patients age 50+ years, often in rectosigmoid
Present in 30-50% of normal individuals (85% of adults in Western world versus 2% in third world countries)
Due to delayed shedding of surface epithelial cells
Associated with cigarette smoking (Cancer Causes Control 2005;16:1021)
Previously considered to have no/minimal malignant potential (Arch Intern Med 2005;165:382), except for those in hyperplastic polyposis syndrome
Right sided hyperplastic polyps are molecularly more similar to serrated adenomas than to left sided hyperplastic polyps, and are associated with cancers that show microsatellite instability (but see J Clin Pathol 2004;57:1089)
Intermediate (6-9 mm) sized polyps are usually right sided, and are associated with synchronous colorectal carcinoma (J Gastroenterol Hepatol 2005;20:1572)
Case reports: with small invasive carcinoma (Endoscopy 2004;36:825)
Gross: small (< 5 mm), sessile, usually on top of mucosal folds, multiple, same color as surrounding mucosa; lesions up to several cm may occur in right colon but may be serrated adenomas
Gross images: hyperplastic polyp
Micro: well formed, elongated glands and crypts with serrated (saw tooth) or star-shaped appearance resembling secretory endometrium; mixture of goblet cells (with abundant mucin) and absorptive cells; bland cytology with eosinophilic cytoplasm, well defined brush borders, basal nuclei; thickened basement membrane; Paneth cells in 8%; may have multinucleated giant cells (AJSP 2005;29:912); cells at base of crypt may have nuclear elongation, crowding and increased mitotic rate, but this is not adenomatous change; may be splaying of muscularis mucosa fibers into submucosa; large hyperplastic polyps may have adenomatous foci
Micro images: serrated crypts #1; #2; #3; #4; #5; #6; right sided vs. left sided polyps
Virtual slides: hyperplastic polyp
Molecular: limited changes, no relation to changes in coexisting adenomas (J Clin Pathol 2004;57:1084)
Hyperplastic polyp of colon with misplaced epithelium
Also called “pseudoinvasion”
Some authorities consider it synonymous to inverted hyperplastic polyp, but others consider them different
Simulates adenoma with pseudoinvasion, but benign
Arises in left colon due to local trauma (torsion or twisting of polyp, vigorous peristalsis)
Micro: colonic epithelium in lamina propria with mixed pattern (lobules and irregularly distributed crypts) or lobular pattern; continuous with mucosal portion of polyp in deeper levels; defects are present in muscularis mucosa, and muscle fibers are splayed round misplaced epithelium; often lymphoid aggregates adjacent to misplaced epithelium, fresh hemorrhage, vascular congestion, hemosiderin deposits; usually no significant inflammation, no dysplasia
Micro images: misplaced epithelium #1; #2; #3; #4; Ki67/MIB1; collagen IV
Positive stains for misplaced epithelium: Ki-67, E-cadherin, collagen IV basement membrane
References: Mod Path 2001;14:869
Inverted hyperplastic polyp of colon
More frequent in right colon
May be more common in women
Case reports: associated with adenoma (Eur J Gastroenterol Hepatol 2004;16:107), inverted hyperplastic polyposis (J Clin Pathol 1993;46:56)
Gross images: inverted polyposis
Micro: endophytic growth pattern, penetrates muscularis mucosa (AJSP 1985;9:265)
Micro images - inverted polyps #1; #2 associated with submucosal adipose; #3-large submucosal mucin cyst; #4 with epithelial displacement to lymphoid follicle; CEA+ (normal colon at upper right is CEA neg)
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, although patients with inflammatory polyposis due to ulcerative colitis have an increased risk of dysplasia, usually in flat lesions
Case reports: with ischemia (Am Surg 1993;59:315), with schistosomiasis (J Clin Gastroenterol 1983;5:169), simulating carcinoma due to multiple fused polyps (Am J Gastroenterol 1980;73:441)
Endoscopic images: inflammatory polyps in ulcerative colitis
Treatment: treat underlying inflammatory condition
Gross: smooth hyperemic or hypervascular appearance; variable surface erosion
Gross images: inflammatory pseudopolyps in ulcerative colitis #1; #2
Micro: inflamed lamina propria and distorted colonic epithelium (branched, tortuous, elongated or cystic crypts); may have surface erosion, congestion/hemorrhage or crypt abscesses; may have bizarre stromal changes in reactive fibroblasts resembling sarcoma in a fibroblastic or granulation tissue stroma, particularly underneath areas of ulceration; no/few mitotic figures, no atypical mitotic figures, often zonation
Micro images: ulcerative colitis #1; #2; #3; annotated images; bizarre stromal cells
Positive stains: vimentin
Negative stains: S100, cytokeratin, CMV
DD: pyogenic granuloma (Ann Diagn Pathol 2005;9:106)
Giant inflammatory polyp / polyposis of colon
Definition: inflammation and polyps at least 1.5 cm
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: 40 year old man with rectal bleeding (Case of the Week #147), no history of colonic disease (Gastroenterol Clin Biol 2006;30:913, Neth J Surg 1987;39:95), with cystic fibrosis and Crohn’s disease (Pediatr Dev Pathol 2006;9:25), with Crohn’s disease (Pathol Int 2002;52:318), remission after topical budesonide (Anticancer Res 2005;25:2961)
Treatment: usually surgery (Z Gastroenterol 2000;38:845) since cannot clinically distinguish dysplastic and inflammatory polyps
Gross images: associated with protein losing enteropathy; various images
Case of the Week #147 - #1; #2
Micro images: various images; Case of the Week #147 - #1; #2; #3; #4; figure 6
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
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
Micro images: figure 3; staining for non-sulfated mucins
EM images: thick superficial layer of mucus
References: Am J Gastroenterol 2002;97:370, Histopathology 1993;23:63
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
Gross images: small bowel
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
Micro images: small bowel; figures 2-3; figure 2; figure 3
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
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)
Micro images: inflammatory granulation tissue and prominent smooth muscle
DD: inflammatory polyp (no abundant smooth muscle), Peutz-Jegher polyp (no prominent inflammation)
References: AJSP 1992;16:772
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
Gross images: prolapsing through rectum; multiple polyps; cross section
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
Micro images: cystically dilated glands and inflammation #1; #2; #3; #4; #5
Virtual slides: juvenile polyp
DD: inflammatory polyp
Carcinoma of colon
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
Micro images: various images (article in Korean but captions in English); rectal tumor
ampulla of Vater - H&E, chromogranin
cervix - trabecular pattern with mitotic activity
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
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), 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
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
Micro images: various images; figure 2; figure 4
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
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
Micro images: H&E, synaptophysin; left-H&E, right-synaptophysin; with overlying villous adenoma (D: synaptophysin+)
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
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
Gross images: top-flat lesion with slightly concaved surface
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
Micro images: invasion of submucosa; bottom-marked submucosal invasion #1; #2; minute focus of submucosal invasion (arrow)
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)
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
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)
Gross images: villous tumor with central ulceration
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)
Micro images: abrupt transition from benign to malignant mucosa #1; #2
Carcinoid tumors of colon
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
Micro images: submucosal tumor #1; #2; various images #1; #2; #3; #4; figures 2-3; chromogranin+ in a few cells
atypical carcinoid - H&E; angiolymphatic and perineural invasion; synaptophysin
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
Uncommon
Usually large, penetrate muscularis propria and involve regional lymph nodes
Not associated with carcinoid syndrome
Case reports: 58 year old man with tubulovillous adenoma and microcarcinoid tumors (Case of Week #189), with adenoma (Am J Surg Pathol 1988;12:607)
Gross: flat or depressed plaque or polypoid lesion; yellow-tan, particularly after formalin fixation
Gross images: large tumor
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
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
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
Micro images: not necessarily colon - various images; starry sky; touch prep; Ki-67
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
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)
Micro images: H&E #1; #2; CD20; bcl2; rectal tumor-left: H&E, upper right: CD20, lower right: bcl2
small bowel - H&E and stains
Positive stains: CD20, bcl2; also CD10
Negative stains: CD5, T cell markers (in tumor cells)
Molecular: bcl-2 - IgH translocation
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
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
Micro images: various images
Positive stains: CD15, CD30, EBER1, LMP1
Negative stains: CD45 (LCA)
MALT lymphoma of colon
Rare in colon
Usually adults
Often relapses, 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
Micro images: figures A-D; figures 2, 4, 5
Molecular: usually trisomy 3 or 18; less commonly t(1;14);(p22;q32) (Gut 2006;55:1581) or t(11;18)(q21;q21) in 15% (Mod Pathol 2003;16:1232); t(11;18) produces API2-MALT1 fusion gene; these tumors usually occur in males, are larger with more advanced stage; API2-MALT1 negative tumors usually occur in females
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
Gross images: lymphomatoid polyposis #1
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
Micro images: various images #1; #2; incidental tumor #1; #2; #3; figures 2, 3A-3D
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)
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
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)
Micro images: peripheral T cell lymphoma #1; #2; #3
Mesenchymal tumors of colon
Recommended that all stromal tumors be stained with CD117
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
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
Micro images: associated with prior surgery; metastases - A: FNA; B: AE1-3; C: H&E of liver primary; D: CD31
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)
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
Micro images: various images; metastatic tumor to colon; PgR+ tumor
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
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
Micro images: bland spindle cells #1; #2 with evenly spaced blood vessels
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)
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
Gross: polypoid; sessile or pedunculated
Gross images: ganglioneuromatous polyposis
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
Micro images: polypoid ganglioneuroma; ganglioneuromatous polyposis; diffuse ganglioneuromatosis #1; #2; #3; #4; #5 (ileum)
adult cases - spindled cells in lamina propria; ganglion cells (arrow); Schwann cells are S100+; ganglion cells are c-RET+
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
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
Micro images: spindle cell pattern
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
EM images: cellular processes and skenoid fibers; bulbous axon-like processes with empty vesicles and dense core granule
References: AJSP 2002;26:396
Gastrointestinal stromal tumors (GIST) of colon
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
Gross images: hepatic flexure; rectal GIST; various images; leiomyosarcoma vs. GIST
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)
Micro images: epithelioid cells and osteoclast-like giant cells; focal calcification; malignant tumor (figure 1)
site unspecified - cigar shaped cells with elongated nuclei; epithelioid GIST; prominent cytoplasmic vacuoles; pattern of interlacing fascicles; nuclear palisading; angiomatoid pattern; myxoid stroma; perivascular hyalinization; skenoid fibers; c-kit+
low risk tumor has bland tumor cells and no mitotic activity; intermediate risk tumor is cellular with higher N/C ratio; high risk tumor is cellular with high N/C ratio and mitotic activity
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
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)
Micro images: cavernous hemangioma of colonic serosa; incidental finding in sigmoid colectomy
Histiocytic sarcoma of colon
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
Micro images: nuclear pleomorphism, mitotic activity and hemophagocytosis; prominent spindling
not necessarily colon - large epithelioid cells invading bone and exhibiting hemophagocytosis; immunostains
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
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
Micro images: dense collagen and chronic inflammatory cells; angiomatoid proliferation with microthrombi (figure 5); infiltration of mesentery by foamy macrophages
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
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
Micro images: diffuse fibrosis infiltrating adipose, also fat necrosis; involving ureters
DD: Whipple’s disease (lipogranulomatous inflammation with large, round, empty spaces containing PAS+ bacilli)
References: eMedicine #605, eMedicine #3664
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, 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
Micro images: figure 2
not necessarily colon - inflammatory cells and spindle cells #1; #2; mesenteric mass; pancreatic mass; ALK staining; CD117 negative
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
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
Endoscopic images: images #1; #2
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
Micro images: jejunum - low power; high power #1; #2; CD34; PAS+ hyaline globules (site unknown)
Positive stains: CD31, CD34; CD117 (focal in 15%)
Negative stains: S100, desmin, muscle specific actin, HMB45
DD: GIST, melanoma
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
Micro images: muscularis mucosa #1; #2; symplastic leiomyoma; smooth muscle actin and desmin; H&E, smooth muscle actin and CD117; figure 2
Positive stains: smooth muscle actin, desmin
Negative stains: CD34, CD117, S100
References: Mod Path 2001;14:950
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
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
Gross image: diffuse wall thickening
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
Micro images: spindle cells in bowel wall, and smooth muscle cells arising from vein; HMB45
Positive stains: HMB45 (epithelial cells only), smooth muscle actin, desmin, vimentin
Negative stains: CD117, CD34, S100, ER, PgR, bcl2
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
Gross images: leiomyosarcoma vs. GIST; rectal tumor
Micro: resembles smooth muscle but with high grade histology; rarely has osteoclast-like giant cells (Archives 2004;128:440)
Micro images: spindle cells in fascicles with mitotic figures (arrows); well differentiated tumor #1; #2; moderately differentiated; poorly differentiated; spindle and epithelioid tumors with osteoclast-like giant cells
Virtual slides: leiomyosarcoma
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
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
Gross images: submucosal tumor #1; #2
Micro: may have overlying mucosal ulceration, atypical stromal cells, florid vascular proliferation due to repeated intussusception (Pathol Int 2005;55:160)
Micro images: lipoma
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
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)
Gross images: tumor of pericolonic adipose tissue
Micro: various subtypes; dedifferentiated tumors resemble GIST, but usually have foci of well differentiated liposarcoma
Micro images: well differentiated liposarcoma of axilla
Negative stains: CD117
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
Micro images: adenosarcoma of uterus
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
Micro images: perineal tumor - H&E and EMA
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
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
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
Micro images: site unspecified
Positive stains: endothelial cells - CD34, Factor VIII (AJSP 1995;19:1054)
DD: inflammatory polyp, bacillary angiomatosis, Kaposi’s sarcoma
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)
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 with synchronous colonic adenocarcinoma (World J Surg Oncol 2005; 3:46)
Gross: well circumscribed but usually not encapsulated, polypoid intraluminal mass 0.5 to 5.5 cm with mucosal ulceration, usually in right colon
Gross images: rectal tumor #1; #2; sigmoid tumor
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
Micro images: spindle cells; plexiform tumor (figure 3); rectal tumor #1; #2 (stains); various images
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
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
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)
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
Gross/micro images: large pale histiocytes with emperipolesis
Positive stains: histiocytes - S100, lysozyme, CD68
Negative stains: histiocytes - CD1a
DD: Langerhans cell histiocytosis (grooved nuclei, CD1a+)
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
Gross/micro images: dermoid cyst
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
Polyps
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
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
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
Previous staging systems are 1932 Dukes staging system for rectal carcinomas applied to colon carcinomas or 1954 Astler-Coller modification of Dukes staging
Appendiceal adenocarcinomas or anal carcinomas are classified differently
Examination of all mesentery may be necessary to ensure correct pN status in pN1 cases (Mod Path 2004;17:402)
Note: many changes were made from AJCC 6th to 7th edition
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)
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 pericolorectal tissues
T4a: Tumor penetrates to the surface of the visceral peritoneum
T4b: Tumor directly invades or is adherent to other organs or structures
Note: tumor that is adherent to other organs or structures macroscopically is classified as cT4b; if no tumor is present in the adhesion, the classification should be pT1 to pT4a
Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in 1-3 regional lymph nodes
N1a: Metastasis in one regional lymph node
N1b: Metastasis in 2-3 regional lymph nodes
N1c: Tumor deposit(s) in the subserosa, mesentery or nonperitonealized pericolic or perirectal tissues without regional nodal metastasis
N2: Metastasis in 4 or more regional lymph nodes
N2a: Metastasis in 4-6 regional lymph nodes
N2b: Metastasis in 7 or more regional lymph nodes
Note: a satellite peritumoral nodule in the pericolorectal adipose tissue of a primary carcinoma without histologic evidence of residual lymph node in the nodule may represent discontinuous spread, venous invasion with extravascular spread (V1/2) or a totally replaced lymph node (N1/2). Replaced nodes should be counted separately as positive nodes in the N category, whereas discontinuous spread or venous invasion should be classified and counted in the Site-Specific Factor category Tumor Deposits.
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, gross image #1; #2; micro image; single CK+ cells
(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)
M0: No distant metastasis
M1: Distant metastasis
M1a: Metastasis confined to one organ or site (e.g. liver, lung, ovary, nonregional node)
M1b: Metastases in more than one organ/site or the peritoneum
Stage grouping Dukes staging Astler-Coller 5 year survival (JNCI 2004;96:1420)
top [based on AJCC 6th classification]
Stage 0: Tis N0 M0 - - 100%
Stage I: T1-T2 N0 M0 A A, B1 93%
Stage IIA: T3 N0 M0 B B2 85%
Stage IIB: T4a N0 M0 B B2 72%
Stage IIC: T4b N0 M0 B B3 72%
Stage IIIA: T1-T2 N1/N1c M0 C C1 83%
and T1 N2a M0
Stage IIIB: T3-T4a N1/N1c M0 C C1/C2 64%
and T2-T3 N2a M0
and T1-T2 N2b M0
Stage IIIC: T4a N2a M0 C C2/C3 44%
and T3-T4a N2b M0
and T4b N1-N2 M0
Stage IVA: Any T, any N, M1a - - 8%
Stage IVB: Any T, any N, M1b - - 8%
Residual tumor (R factor)
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)
Staging – neuroendocrine tumors
Primary tumor (T)
TX: Primary tumor cannot be assessed
T0: No evidence of primary tumor
T1: Tumor invades lamina propria or submucosa and size 2 cm or less
T1a: Tumor size less than 1 cm in greatest dimension
T1b: Tumor size 1-2 cm in greatest dimension
T2: Tumor invades muscularis propria or size more than 2 cm with invasion of lamina propria or submucosa
T3: Tumor invades through the muscularis propria into the subserosa, or into non-peritonealized pericolic or perirectal tissues
T4: Tumor invades peritoneum or other organs
For any T, add (m) for multiple tumors
Regional lymph nodes (N)
NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Regional lymph node metastasis
Distant Metastasis (M)
M0: No distant metastasis
M1: Distant metastasis
Anatomic stage / prognostic groups
Stage I: T1 N0 M0
Stage IIA: T2 N0 M0
Stage IIB: T3 N0 M0
Stage IIIA: T4 N0 M0
Stage IIIB: Any T N1 M0
Stage IV: M1 (any T, any N)
Features to report for colonic carcinoma or other tumors
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
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
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
Large vessel invasion
Type of polyp in which invasive carcinoma arose
Additional findings
Rectal tumor: local excision-mandatory to report
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
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
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
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)
Intra or peritumoral lymphocytic response
Pattern of tumor at periphery (pushing, infiltrative)
Intactness of mesorectum (incomplete, nearly complete or complete)
Checklists: Michigan Cancer Consortium
References: Archives 2000;124:1016
End of Colon-tumor chapter
