1. Tumors/Polyps of Intestine
Non-neoplastic polyps of intestine
Adenomas
Colorectal carcinoma
Lecture 16

2. Polyp
• A polyp is a mass that
protrudes into the lumen of
the gut.
• Stalked or pedunculated polyp
• Sessile polyp

3. Tumors of the Small and Large Intestines
Non-neoplastic Polyps 90%
Hyperplastic polyps- most common
Hamartomatous polyps
Juvenile polyps
Peutz-Jeghers polyps
Inflammatory polyps
Lymphoid polyps

4. • Neoplastic Epithelial Lesions
• Benign polyps
• Adenomas
• Malignant lesions
Adenocarcinoma
Squamous cell carcinoma of the anus

5. • Other tumors
• Gastrointestinal stromal tumors
• Carcinoid tumors
• Lymphoma

6. Non-
neoplastic
polyps of
intestine

7. • The overwhelming majority of intestinal
polyps occur sporadically, particularly in the
colon, and increase in infrequency with age.
• Non-neoplastic polyps represent 90% of all
epithelial polyps in the large intestine and are
found in more than half of all persons age 60
years or older.

8. Hyperplastic Polyps
Colonic hyperplastic polyps are common
epithelial proliferations that are typically
discovered in the sixth and seventh decades of
life.

9. Pathogenesis
The pathogenesis of hyperplastic polyps is
incompletely understood, but they are thought to
result from decreased epithelial cell turnover and
delayed shedding of surface epithelial cells,
leading to a “piling up” of goblet cells and
absorptive cells.

10. • It is now appreciated that these lesions are
without malignant potential. Their chief
significance is that they must be
distinguished from sessile serrated
adenomas, histologically similar lesions that
have malignant potential.

11. • It is also important to remember that
epithelial hyperplasia can occur as a
nonspecific reaction adjacent to or overlying
any mass or inflammatory lesion and,
therefore, can be a clue to the presence of an
adjacent, clinically important lesion.

12. Hyperplastic Polyps cont.
• Most common non-neoplastic polyp in the colon
• Do not exhibit dysplasia
• Proliferation is mainly in the basal portion of the crypt
(used to distinguish from adenomas)
• Typically located in the rectosigmoid and are < 5mm
in
size
• Small left sided HP are not a significant marker of
colon cancer risk and finding them on sigmoidoscopy is
NOT a routine indication for colonoscopy

13. • When single, they do not have malignant
potential. Sessile serrated adenoma may have
malignant potential. They are small, nipple-
like, hemispherical, smooth protrusions of the
mucosa. They may occur singly but are more
often multiple. Although they may be
anywhere in the colon, well over half are
found in the rectosigmoid region.

14. Morphology
Hyperplastic polyps are most commonly found in the
left colon and are typically less than 5 mm in
diameter. They are smooth, nodular protrusions of
the mucosa, often on the crests of mucosal folds.
They may occur singly but are more frequently
multiple, particularly in the sigmoid colon and
rectum.

15. • Histologically, hyperplastic polyps are
composed of mature goblet and absorptive
cells. The delayed shedding of these cells
leads to crowding that creates the
serrated surface architecture
that is the morphologic hallmark of these
lesions.

16. • they contain
• abundant crypts
• lined by well-differentiated goblet or
absorptive epithelial cells,
• separated by a scant lamina propria.

17. Hyperplastic polyp. A, Polyp surface with irregular tufting of epithelial cells. B, Tufting
results from epithelial overcrowding. C, Epithelial crowding produces a serrated architecture
when glands are cut in cross-section.

19. Hamartomatous polyps
• Hamartomatous polyps occur sporadically and in
the context of various genetically determined or
acquired syndromes . Recall that hamartomas are
tumor-like growths composed of mature tissues
that are normally present at the site in which they
develop. Although Hamartomatous polyposis
syndromes are rare, they are important to
recognize because of associated intestinal and
extra-intestinal manifestations and the possibility
that other family members are affected.

22. Juvenile Polyps
• Juvenile polyps are focal malformations of
the mucosal epithelium and lamina propria.
These may be sporadic or syndromic, but the
morphology of the two forms may be
indistinguishable. The vast majority of
juvenile polyps occur in children less than 5
years of age. When present in adults, polyps
with identical morphology are sometimes
confusingly referred to as inflammatory
polyps.

23. • The majority of juvenile polyps are located in
the rectum and most present with rectal
bleeding. In some cases prolapse occurs and
the polyp protrudes through the anal
sphincter. Sporadic juvenile polyps are
usually solitary lesions and may be referred
to as retention polyps.

24. • In contrast, individuals with the autosomal
dominant syndrome of juvenile polyposis have
from 3 to as many as 100 hamartomatous polyps
and may require colectomy to limit the chronic
and sometimes severe hemorrhage associated
with polyp ulceration. A minority of patients also
have polyps in the stomach and small bowel.
Pulmonary arteriovenous malformations are a
recognized extra-intestinal manifestation of the
syndrome.

25. Morphology
Most juvenile polyps are less than 3 cm in diameter.
They are typically pedunculated, smooth-surfaced,
reddish lesions with characteristic cystic spaces
apparent after sectioning.
Microscopic examination shows these cysts to be
dilated glands filled with mucin and inflammatory
debris . The remainder of the polyp is composed of
lamina propria expanded by mixed inflammatory
infiltrates. The muscularis mucosa may be normal
or attenuated.

26. Juvenile polyposis. A, Juvenile polyp. Note the surface erosion and cystically
dilated crypts. B, Inspissated mucous, neutrophils, and inflammatory debris can
accumulate within dilated crypts.

27. • Although the morphogenesis of juvenile polyps is
incompletely understood, some have suggested
that mucosal hyperplasia is the initiating event.
This hypothesis is consistent with the discovery
that mutations in pathways that regulate cellular
growth cause autosomal dominant juvenile
polyposis. The most common mutation identified
is of SMAD4, which encodes a cytoplasmic
intermediate in the TGF-β signaling pathway.
BMPR1A, a kinase that is a member of the TGF-β
superfamily, may be mutated in other cases.

28. However, these mutations account for fewer
than half of patients, suggesting that changes
in other genes can also cause juvenile
polyposis. Dysplasia occurs in a small
proportion of juvenile polyps, and the
juvenile polyposis syndrome is associated
with an increased risk of colonic
adenocarcinoma.

29. Hamartomatous Juvenile polyps
• Hamartomatous proliferations, mainly of the
lamina propria, enclosing widely spaced,
dilated cystic glands. They occur most
frequently in children younger than 5 years
old but are also found in adults of any age; in
the latter group they may be called retention
polyps.

30. large in children (1-3 cm in diameter) but
smaller in adults;
they are rounded , smooth, or slightly lobulated
and sometimes have a stalk as long as 2 cm.

31. • In general, they occur singly and in the
rectum, and being Hamartomatous they have
no malignant potential.
• Juvenile polyps may be the source of rectal
bleeding and in some cases become twisted
on their stalks to undergo painful infarction.

32. Peutz-Jeghers Syndrome
• This rare autosomal dominant syndrome
presents at a median age of 11 years with
multiple GI hamartomatous polyps and
mucocutaneous hyperpigmentation. The
latter takes the form of dark blue to brown
macules around the mouth, eyes, nostrils,
buccal mucosa, palmar surfaces of the hands,
genitalia, and perianal region. These lesions
are similar to freckles but are distinguished
by their presence in the buccal mucosa.

33. • Peutz-Jeghers polyps can initiate
intussusception, which is occasionally fatal.
Of greater importance, Peutz-Jeghers
syndrome is associated with an increased risk
of several malignancies, including cancers of
the colon, pancreas, breast, lung, ovaries,
uterus, and testicles, as well as other unusual
neoplasms, such as sex cord tumors.

34. Pathogenesis
Germline heterozygous loss-of-function
mutations in the gene LKB1/STK11 are
present in approximately half of individuals
with familial Peutz-Jeghers syndrome as well
as a subset of patients with sporadic
PeutzJeghers syndrome. LKB1/STK11 is a
kinase that regulates cell polarization,
growth, and metabolism.

35. The function of the second “normal” copy of
LKB1/STK11 is often lost through somatic
mutation in cancers occurring in Peutz-
Jeghers syndrome, consistent with the view
that LKB1/STK11 is a tumor suppressor gene
and providing an explanation for the high risk
of neoplasia in affected patients. The GI
adenocarcinomas arise independently of the
hamartomatous polyps, indicating that the
hamartomas are not preneoplastic precursor
lesions.

36. Morphology
The polyps of Peutz-Jeghers syndrome are most
common in the small intestine, although they
may occur in the stomach and colon, and, with
much lower frequecy, in the bladder and lungs.
Grossly, the polyps are large and pedunculated
with a lobulated contour. Histologic
examination demonstrates a characteristic
arborizing network of connective tissue, smooth
muscle, lamina propria, and glands lined by
normal-appearing intestinal epithelium .

37. The arborization and presence of smooth
muscle intermixed with lamina propria are
helpful in distinguishing polyps of Peutz-
Jeghers syndrome from juvenile polyps.

38. Peutz-Jeghers polyp. A, Polyp surface (top) overlies stroma composed of smooth
muscle bundles cutting through the lamina propria. B, Complex glandular architecture and the
presence of smooth muscle are features that distinguish Peutz-Jeghers polyps from juveni le
polyps.

39. Clinical Features
Because the morphology of Peutz-Jeghers
polyps can overlap with that of sporadic
hamartomatous polyps, the presence of
multiple polyps in the small intestine,
mucocutaneous hyperpigmentation, and a
positive family history are key to the
diagnosis. Detection of LKB1/STK11
mutations can be helpful diagnostically in
patients with polyps who lack
mucocutaneous hyperpigmentation.

40. However, the absence of LKB1/STK11
mutations does not exclude the diagnosis,
since mutations in other presently unknown
genes can also cause the syndrome. Because
of the increased risk of cancer, routine
surveillance of the GI tract, pelvis, and
gonads is typically recommended.

41. Cowden syndrome and Bannayan-Ruvalcaba-Riley syndrome
are autosomal dominant hamartomatous polyp
syndromes associated with loss-of-function
mutations in PTEN, a gene encoding a lipid
phosphatase that inhibits signaling through the
PI3K/AKT pathway. PTEN, a well-characterized
tumor suppressor, is also mutated in a small
number of patients presenting with juvenile
polyposis.

42. • The multiple syndromes associated with
PTEN mutations are sometimes grouped
together under the heading “PTEN
hamartoma syndrome.” The basis for the
differing presentations of these syndromes is
not understood; interaction of PTEN loss-of-
function mutations with other unknown
modifying genes is suspected.

43. • Cowden syndrome is characterized by
macrocephaly, intestinal hamartomatous polyps,
and benign skin tumors, typically trichilemmomas,
papillomatous papules, and acral keratoses. A
variety of other lesions derived from all three
embryologic layers, including subcutaneous
lipomas, leiomyomas, and hemangiomas, also
occur. While individuals with Cowden syndrome
do not have increased risk of GI malignancy, they
are predisposed to breast carcinoma, follicular
carcinoma of the thyroid, and endometrial
carcinoma.

44. • Bannayan-Ruvalcaba-Riley syndrome can be
distinguished from Cowden syndrome on clinical
grounds; for example, mental deficiencies and
developmental delays are only seen with the
Bannayan-Ruvalcaba-Riley syndrome, which also
seems to be associated with a lower incidence of
neoplasia than Cowden syndrome. Features
shared by these two syndromes include GI
hamartomatous polyps, lipomas, macrocephaly,
hemangiomas, and, in males, pigmented macules
on the glans penis.

45. Cronkhite-Canada Syndrome
• Cronkhite-Canada syndrome contrasts sharply
with other hamartomatous polyposis syndromes
in that it is nonhereditary and most often develops
in individuals over 50 years of age. The clinical
symptoms are nonspecific and include diarrhea,
weight loss, abdominal pain, and weakness. The
most characteristic feature is the presence of
hamartomatous polyps of the stomach, small
intestine, and colorectum that are histologically
indistinguishable from juvenile polyps.

46. • However, the nonpolypoid intervening
mucosa also shows cystic crypt dilatation and
lamina propria edema and inflammation.
Associated abnormalities include nail
atrophy and splitting, hair loss, and areas of
cutaneous hyperpigmentation and
hypopigmentation. The cause of Cronkhite-
Canada syndrome is unknown, and no
specific therapies are available. Supportive
nutritional therapy, which alleviates cachexia
and anemia, can occasionally induce
remission. Nonetheless, as many as 50% of
cases are fatal.

47. Inflammatory Pseudopolyps
• A projecting mass of hypertrophied mucous
membrane
• Irregularly shaped islands of residual intact
colonic mucosa that are the result of the
mucosal ulceration and regeneration that occurs
in IBD (benign with no malignant potential).
• Usually multiple, filiform and scattered
throughout the colitic region of the colon
(Ulcerative Colitis)

48. A projecting mass of hypertrophied mucous membrane (as in
the stomach or colon) resulting from local inflammation

49. • The polyp that forms as part of the solitary
rectal ulcer syndrome is an example of a
purely inflammatory lesion. Patients present
with a clinical triad of rectal bleeding, mucus
discharge, and an inflammatory lesion of the
anterior rectal wall.

50. • The underlying cause is impaired relaxation
of the anorectal sphincter that creates a
sharp angle at the anterior rectal shelf and
leads to recurrent abrasion and ulceration of
the overlying rectal mucosa. An
inflammatory polyp may ultimately form as a
result of chronic cycles of injury and healing.
Entrapment of this polyp in the fecal stream
leads to mucosal prolapse.

51. • Thus, the distinctive histologic features are
those of a typical inflammatory polyp with
superimposed mucosal prolapse and include
lamina propria fibromuscular hyperplasia,
mixed inflammatory infiltrates, erosion, and
epithelial hyperplasia

52. Solitary rectal ulcer syndrome. A, The dilated glands, proliferative epithelium,
superficial erosions, and inflammatory infiltrate are typical of an inflamatory polyp.
However, the smooth muscle hyperplasia within the lamina propria suggests
that mucosal prolapse has also occurred. B, Epithelial hyperplasia. C, Granulation
tissue-like capillary proliferation within the lamina propria caused by repeated
erosion and re-epithelialization.

53. Submucosal Polyps
• Lymphoid aggregates, lipomas, leiomyomas,
pneumatosis cystoid intestinalis, hemangiomas,
fibromas, carcinoids, and metastatic lesions
• Can be neoplastic or non-neoplastic
• Smooth overlying mucosa
• Lipoma can be diagnosed endoscopically because
of its yellow color and softness (pillow sign)
• EUS can be useful in defining the site of origin and
for biopsy of submucosal lesions if the diagnosis is
in doubt.

55. Neoplastic
Polyps

56. Adenomas

57. Adenomatous Polyps
2/3 of colonic polyps are adenomas
By definition they are dysplastic and have
malignant potential
Time for development of adenomas to cancer is
about 7 to 10 years.
Adenomas

58. Advanced adenoma
high grade dysplasia or
adenoma that is > 10 mm in size or
with villous component.

59. Synchronous adenoma
adenoma that is diagnosed at same time as
index colorectal neoplasm

60. Metachronous adenoma
diagnosed at least six months after diagnosis of
previous adenoma.

61. Epidemiology of Adenoma
Older age is a major risk factor
More common in men
Large adenomas (> 9mm) may be more
common in African Americans
African Americans have a higher risk of right-
sided colonic adenomas and may present with
cancer at a younger age (< 50 years) than
Caucasians.

62. • The prevalence of colonic adenoma is 20% to
30% before age 40, rising to 40 to 60 % after
age 60. Males and females are affected
equally???.

63. • There is a well-defined familial predisposition
to sporadic adenomas, accounting for about a
fourfold greater risk for adenomas among first
degree relatives, and also a fourfold greater
risk of colorectal carcinoma in any person with
adenomas.

64. • All adenomatous lesions arise as the result of
epithelial proliferation and dysplasia, which
may range from mild to severe as to represent
transformation to carcinoma. Furthermore,
there is strong evidence that most sporadic
invasive colorectal adenocarcinomas arise in
preexisting adenomatous lesions.

65. Types of adenomas on the basis of the epithelial architecture
• 1. Tubular adenomas
• 2. Villous adenomas
• 3. Tubulovillous adenomas
• 4. Sessile Serrated adenomas

66. Endoscopic Classification
1. Sessile – base is attached to colon wall usually
large
2. Pedunculated – mucosal stalk is interposed
between the polyp and the wall
3. Flat – height less than one-half the diameter of
the lesion.
Depressed lesions appear to be particularly likely
to harbor high-grade dysplasia or be malignant
even if small.

67. Pathologic Classification
I. Low grade dysplasia: characterized by
branching crypts
lined by cells with long, thin nuclei that begin to
stratify, resulting in
increased nucleus-to-cytoplasm ratio and
a loss of normal goblet cells.

68. II. High grade dysplasia: do not contain invasive
malignancy, which is defined by breach of the
muscularis mucosa by neoplastic cells.
Represents an intermediate step in the
evolution from low grade adenomatous polyp
to cancer
Not associated with metastasis since there are
no lymphatic vessels in the lamina propria..

69. Tubular Adenoma
The most common, account for more than 80
percent of colonic adenomas.
Characterized by a complex network of branching
adenomatous glands.
Most TA are small and pedunculated.

70. Morphology of TA
May arise anywhere in the colon, but about half
are found in the rectosigmoid, the
proportion increasing with age.
In about half of the instances they occur singly,
but in the remainder two or more lesions are
distributed at random.

71. • The smallest adenomas are sessile; lesions
0.3 cm in size can be identified at endoscopy.
Among the larger tubular adenomas up to 2.5
cm in diameter, most have slender stalks 1 to
2 cm long and raspberry –like heads.

72. • Histologically the stalk is covered by normal
colonic mucosa, but the head is composed of
neoplastic epithelium, forming branching
glands lined by tall, hyperchromatic,
somewhat disorderly cell, which may or may
not show mucin secretion.

73. • In some instances there are small foci of
villous architecture.
• In the clearly benign lesion, the branching
glands are well separated by lamina propria,
and the level of dysplasia or cytologic atypia is
slight.

74. • However all degrees of dysplasia may be
encountered, ranging up to cancer confined to
the mucosa (intramucosal carcinoma) or
invasive carcinoma extending into the mucosa
of the stalk.
• A frequent finding in any adenoma is
superficial erosion of the epithelium, the
result of mechanical trauma.

75. Villous adenomas
Villous: account for 5 to 15 percent of
adenomas. They are characterized by glands
that are long and extend straight down from
the surface to the center of the polyp,
creating finger-like projections. Villous
adenomas tend to be large and sessile.

76. • Morphology of VA: Villous adenomas are the
larger and more ominous of the epithelial
polyps. They tend to occur in older persons,
most commonly in the rectum and
rectosigmoid, but they may be located
elsewhere. They generally are sessile, up to 10
cm in diameter, velvety or cauliflower-like
masses projecting 1 to 3 cm above the
surrounding mucosa.

77. • The histology is that of frondlike villiform
extensions of the mucosa covered by
dysplastic, sometimes very disorderly,
sometimes piled-up, columnar epithelium. All
degrees of dysplasia may be encountered, and
invasive carcinoma is found in as many as 40%
of these lesions, the frequency being
correlated with the size of the polyp.

78. Tubulovillous adenomas
TVA: having 26 to 75 percent villous component
account for 5 to 15 percent of adenomas;
combination of above. Tubulovillous adenomas are
composed of a broad mix of tubular and villous
areas. They are intermediate between the tubular
and the villous lesions in their frequency of having a
stalk or being sessile, their size, the degree of
dysplasia, and the risk of harboring intramucosal or
invasive carcinoma.

79. Serrated Polyps
Display features of both hyperplastic and
adenoma Were classified in past as HP and
benign but new evidence shows that they may
behave as adenomas
No guidelines for management; it is generally
recommended that surveillance intervals should
follow that of other adenomas

80. Two types
Sessile serrated adenoma – precursors to large
HP in proximal colon of patients with
hyperplastic polyposis
Traditional serrated adenoma – look and behave
as conventional adenomas; often
pedunculated found more often in distal colon

81. Clinical features of adenomas
• The smaller adenomas are usually
asymptomatic, until such time that occult
bleeding leads to clinically significant anemia.
• Villous adenomas are much more frequently
symptomatic because of overt or occult rectal
bleeding. The most distal villous adenomas
may secrete sufficient amounts of mucosal
material rich in protein and potassium to
produce hypoproteinemia or hypokalemia.

82. • On discovery, all adenomas, regardless of
their location in the alimentary tract, are to be
considered potentially malignant; thus, in
practical terms, prompt and adequate excision
is mandated.

83. • Familial Polyposis Syndromes

84. • Familial polyposis syndromes are uncommon
• Autosomal dominant disorders. Their
importance lies in the propensity for
malignant transformation and in the insights
that such transformation has provided in
unraveling the molecular basis of colorectal
cancer.

85. • Individuals with familial adenomatous
polyposis (FAP) typically develop 500 to 2500
colonic adenomas that carpet the mucosal
surface; a minimum number of 100 is required
for the diagnosis.

86. • Multiple adenomas may also be present
elsewhere in the alimentary tract, including
almost a 100 % lifetime incidence of duodenal
adenomas.

87. • Most polyps are tubular adenomas; occasional
polyps have villous features.

88. • Polyps usually become evident in adolescence
or early adulthood. The risk of colonic cancer
is virtually 100% by midlife, unless a
prophylactic colectomy is performed.

89. Risk Factors for High grade dysplasia and cancer
Adenomatous polyps > 1 cm in diameter are risk
factor for containing CRC
Villous histology – adenomatous polyps with > 25
percent villous histology are a risk factor for
developing CRC
High-grade dysplasia – adenomas with high-grade
dysplasia often coexist with areas of invasive cancer
in the polyp.
Number of polyps: three or more is a risk factor for
development of metachronous adenomas with
advanced pathologic features.

92. Colorectal
Carcinoma
Adenocarcinoma 98%

94. Intestinal tumors
Non-neoplastic Polyps
Hyperplastic polyps
Hamartomatous polyps
Juvenile polyps
Peutz-Jeghers polyps
Inflammatory polyps
Lymphoid polyps
Neoplastic Epithelial Lesions
Benign polyps
Adenomas
Malignant lesions
Adenocarcinoma
Squamous cell carcinoma of the anus
Other Tumors
Gastrointestinal stromal tumors
Carcinoid tumor
Lymphoma
Epithelial tumors of the intestines:
major cause of morbidity and mortality worldwide
Colon, including rectum:
host to more primary neoplasms than any other
organ in the body

95. Adenocarcinoma
Adenocarcinoma is a cancer of an epithelium that
originates in glandular tissue, adeno means gland.
• 98% of all cancers in large intestine almost always
arise in adenomatous polyps, generally
curable by resection

96. Epidemiology
• peak incidence: 60 to 70 years of age
• < 20% cases before age of 50
• adenomas – presumed precursor lesions
for most tumors
• males affected ≈ 20% more often than
females

97. Epidemiology
• worldwide distribution
• highest incidence rates in United States,
Canada, Australia, New Zealand, Denmark,
Sweden, and other developed countries

98. Etiology
• genetic influences:
– preexisting ulcerative colitis or polyposis
syndrome
– hereditary nonpolyposis colorectal cancer
syndrome (HNPCC, Lynch syndrome) → germ-line
mutations of DNA mismatch repair genes

99. Etiology
• environmental influences:
– dietary practices
• low content of unabsorbable vegetable fiber
• corresponding high content of refined carbohydrates
• high fat content
• decreased intake of protective micronutrients (vitamins
A, C, and E)
– use of Aspirin®
and other NSAIDs: protective effect
against colon cancer?
• cyclooxygenase-2 & prostaglandin E2

100. Morphology
• 25% of colorectal carcinomas: in cecum or
ascending colon
• similar proportion: in rectum and distal
sigmoid
• 25%: in descending colon and proximal
sigmoid
• remainder scattered elsewhere
• multiple carcinomas present → often at
widely disparate sites in the colon

101. Morphology
• all colorectal carcinomas begin as in situ lesions
• tumors in the proximal colon: polypoid, exophytic
masses that extend along one wall of the cecum and
ascending colon

102. Morphology
• in the distal colon: annular, encircling lesions that
produce “napkin-ring” constrictions of the bowel and
narrowing of the lumen
• both forms of neoplasm eventually penetrate the bowel
wall and may appear as firm masses on the serosal
surface

103. Morphology
• all colon carcinomas - microscopically similar
• almost all - adenocarcinomas
• range from well-differentiated to undifferentiated,
frankly anaplastic masses
• many tumors produce mucin
• secretions dissect through the gut wall, facilitate
extension of the cancer and worsen the prognosis
• cancers of the anal zone are predominantly squamous
cell in origin

104. Clinical Features
• may remain asymptomatic for years
• symptoms develop insidiously
• cecal and right colonic cancers:
– fatigue
– weakness
– iron deficiency anemia
• left-sided lesions:
– occult bleeding
– changes in bowel habit
– crampy left lower quadrant discomfort
• anemia in females may arise from gynecologic causes, but it is a
clinical maxim that iron deficiency anemia in an older man means
gastrointestinal cancer until proved otherwise

105. Clinical Features
• spread by direct extension into
adjacent structures and by
metastasis through lymphatics and
blood vessels
• favored sites for metastasis:
– regional lymph nodes
– liver
– lungs
– bones
– other sites including serosal
membrane of the peritoneal
cavity
• carcinomas of the anal region →
locally invasive, metastasize to
regional lymph nodes and distant
sites
TNM Staging of Colon Cancer
Tumor (T)
T0 = none evident
Tis = in situ (limited to mucosa)
T1 = invasion of lamina propria or submucosa
T2 = invasion of muscularis propria
T3 = invasion through muscularis propria into
subserosa or nonperitonealized perimuscular
tissue
T4 = invasion of other organs or structures
Lymph Nodes (N)
0 = none evident
1 = 1 to 3 positive pericolic nodes
2 = 4 or more positive pericolic nodes
3 = any positive node along a named blood vessel
Distant Metastases (M)
0 = none evident
1 = any distant metastasis
5-Year Survival Rates
T1 = 97%
T2 = 90%
T3 = 78%
T4 = 63%
Any T; N1; M0 = 66%
Any T; N2; M0 = 37%
Any T; N3; M0 = data not available
Any M1 = 4%

106. Clinical Features
• detection and diagnosis:
– digital rectal examination
– fecal testing for occult blood loss
– barium enema, sigmoidoscopy and
colonoscopy
– confirmatory biopsy
– computed tomography and other
radiographic studies
– serum markers (elevated blood
levels of carcinoembryonic
antigen)
– molecular detection of APC
mutations in epithelial cells,
isolated from stools
– tests under development:
detection of abnormal patterns of
methylation in DNA isolated from
stool cells

107. Therapy
• chemotherapy
• radiotherapy
• photodynamic therapy
• radical surgery
• gene therapy