Tumors of the small and large intestines

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Tumors of the small and large intestines

• Non-neoplastic polyps
• Neoplastic ( epithelial) polyps
• Mesenchymal lesions
• Lymphoma

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Tumors of the small and large intestine

• Epithelial tumors are a major cause of morbidity
  and mortality worldwide
• The colorectal cancer is the GIT segment most
  commonly affected by tumors
• It is the host to more primary tumors than any
  other tumor of the body.
• Colonic carcinoma is second to bronchogenic
  carcinoma as a cause of death in USA.
• Adenocarcinoma in colorectum represent 70 of all
  malignancy of GIT
• Benign tumors, primarily epithelial, are present
  in 25 to 50 of older adults.

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Terminology of Intestinal Tumors

• Polyps and Polyposis Syndromes
• Polyp is a mucosal growth that protrude into the
  lumen of gut. It could be sessile or pedunculated
• Polyps may be formed as the result of abnormal
  mucosal maturation, inflammation, or as
  epithelial proliferation with dysplasia

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Terminology of Intestinal Tumors

• Polypoid lesions is the inflammatory masses,
  hamartomas and tumors arising from the submucosa
  or muscle coat, but also protruding into the
  lumen.
• Polyposis is multiple polyps.
• Polyposis syndrome is hereditary, characterized
  by the presence of multiple pedunculated or
  sessile tumors of the mucosa

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Tumors of the small and large intestineClassifica
tion

• Non-neoplastic polyps
• Hyperplastic polyps
• Hamartomatous polyps (Juvenile Peutz-Jeghers
  polyps)
• Inflammatory polyps
• Lymphoid polyps
• Neoplastic ( epithelial) polyps
• Benign polyps (adenoma)
• Malignant lesions
• Adenocarcinoma
• Carcinoid
• Anal zone carcinoma
• Mesenchymal lesions
• GIT stromal tumors (benign malignant)
• Others ( lipoma, neuroma, angioma, Kaposi
  sarcoma)
• Lymphoma

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Intestinal Polyps

• Non-Neoplastic Polyps
• Represent 90 of all epithelial polypi found in
  large intestine.
• Found in more than half of all persons age 60
  years or older.
• Types 1. Hyperplastic polyp.
• 2. Hamartomatous polyp
  (Juvenile Peutz- Jeghers)
• 3. Inflammatory polyp
• 4. Lymphoid polyp

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Intestinal Polyps

• 1 Hyperplastic Polyp
• Asymtomatic
• gt 50 are located in the rectosigmoid, 20 in
  the ascending colon.
• Smooth, moist, round, small (0.5cm) sessile
  lesions.
• Multiple polyps are frequent.
• Composed of well-formed glands and crypts lined
  by differentiated goblet or absorptive cells.
• Pure hyperplastic polyps have no malignant
  potential.
• Larger hyperplastic polyps foci of adenomatous
  change.

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Non-Neoplastic Polyp

• 2 Hamartomatous polyp
• Juvenile Polyps (retention polyp)
• Developmental malformations affecting the glands
  and lamina propria, having no malignant
  potential.
• commonly occur in children under 5 years old in
  the rectum. In adult called retention polyp.
• Painless rectal bleeding after defecation.
• Large, rounded, smooth lesions with a stalk
• Histology mucus-filled, cystically dilated
  tubules lined by normal or inflamed mucosa.
• Juvenile polyposis syndrome. Occurrence of
  multiple hamartomatous polyps throughout the GI
  tract.

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Non-Neoplatic Polyps

• 2 Hamartomatous Polyps
• Peutz-Jehgers polyps
• Uncommon hamartomatous polyps accompanied by
  mucosal and cutaneous pigmentation around the
  lips, oral mucosa, face and genitalia.
• Rare, autosomal dominant.
• Caused by germ-line mutation in the LKB1 gene,
  which encodes a serine threonine kinase.
• Polyps tend to be large and pedunculated.
• May occur anywhere in the GI tract.
• Have an increased risk of developing carcinoma of
  the pancreas, breast, lung, ovary and uterus.

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hamartomatous polyp
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Non-Neoplastic Polyps

• 3 Inflammatory Polyps
• Occur in patients with longstanding IBD,
  especially in chronic ulcerative colitis.
• Usually multiple.
• Represent an exuberant reparative response to
  longstanding mucosal injury called pseudopolyps

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4 Lymphoid polyps
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Neoplastic Polyps (Adenomas)

• Adenomatous Polyp
• Occur mainly in large bowel.
• Prevalence 20 to 30 before age 40, 50 after
  age 60.
• Males and females are equally affected
• Spordic and familial
• Vary from small pedunculated to large sessile
• Epithelium proliferation and dysplastia with
  loss of basal orientation of nuclei
  (pseudostratified).
• Divided into
• Tubular adenoma has less than 25 villous
  architecture
• Villous adenoma villous architecture over 50
• Tubulovillous adenoma villous architecture
  between 25 and 50.

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• All adenomatous lesions arise as the result of
  epithelial proliferation and dysplasia, which may
  range from mild to so severe as to represent
  transformation to carcinoma.

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Neoplastic Polyps

• 1 Tubular adenoma
• Represents 75 of all neoplastic polyps.
• Occurs sporadicaly and in well defined hereditary
  syndromes.
• Average age is 60 years
• 75 occur in the distal colon and rectum.
• More than 50 occur singly.
• Size few millimeters (sessile) to many
  centimeters (have stalk).
• Stalk has a central core of fibrovascular tissue,
  covered with dysplastic colonic mucosa.
• Severe dysplasia and invasive carcinoma may
  supervene.

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Tubular adenoma
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Neoplastic Polyps

• 2 Villous Adenoma
• The least common, largest and most ominous of
  epithelial polyps.
• Age 60 to 65 years, MF ratio roughly equal.
• Present with rectal bleeding or anemia, large
  ones may secrete copious amounts of mucoid
  material rich in protein.
• 75 located in rectosigmoid area.

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Neoplastic Polyps

• 2 Villous Adenoma
• Morphology
• Size 1 to 10 cm in diameter.
• Most are broad, sessile, velvety lesions
  projecting 1 to 3 cm.
• Frondlike papillary projections of adenomatous
  epithelium with a delicate fibrovascular core.
• All degree of dysplasia with frank invasive
  carcinoma in up to 40.

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Neoplastic Polyps

• 3 Tubulovillous adenoma
• Intermmediate in size, frequency of having a
  stalk, degree of dysplasia and malignant
  potential between tubular and villous adenomas.

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Neoplastic Polyps

• Clinical features
• The smaller adenomas are usually asymptomatic,
  occult bleeding.
• Villous adenomas are much more frequently
  symptomatic because of overt or occult rectal
  bleeding or mucoid material rich in protein and
  potassium to produce hypoproteinemia or
  hypokalemia.
• Adenomas in the immediate vicinity of the ampulla
  of Vater may produce biliary obstruction.

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Relationship of Neoplastic Polyps to Carcinoma

• Adenoma to carcinoma sequence is documented by
  several observations and genetic alterations.
• The probability of carcinoma occuring in a
  neoplastic polyp is related to
• 1. The size of the polyp.
• 2. The relative proportion of its villous
  features.
• 3. The presence of significant cytologic atypia
• (dysplasia) in the neoplastic cells.

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Familial Polyposis Syndrome

• Patients have genetic tendencies to develop
  neoplastic polyps, most often autosomal dominant.
• Familial polyposis coli (FPC)
• Genetic defect ch5 q21.
• Innumerable neoplastic polyps in the colon (500
  to 2500)
• Polyps are also found elsewhere in alimentary
  tract
• Most polyps are tubular adenomas
• The risk of colorectal cancer is 100 by midlife.
• Gardeners syndrome
• Polyposis coli, multiple osteomas, epidermal
  cysts, and fibromatosis.
• Turcot syndrome
• Polyposis coli, glioma and fibromatosis

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Malignant Tumors of Large IntestineAdenocarcinoma

• Constitutes 98 of all cancers in the large
  intestine.
• Worldwide distribution, highest incidence in
  west.
• Causes 15 of all cancer-related death in the
  USA.
• The mortality rate and incidence is higher in
  blacks.
• Peak incidence in the sixth to seventh decade.

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Malignant Tumors of Large IntestineAdenocarcinoma

• Predisposing factors IBD, polyposis syndrome.
• Malefemale ratio is 21 in rectal cancer,
  roughly equal in colon cancer, generally males
  are affected about 20 more than females.
• Diet appears to play an important role in the
  risk for colon cancer
• - Low content of unabsorpable vegetable fibre.
• - High content of refined carbohydrates.
• - High fat content.
• - ? Increased intake of nitrites, nitrates
  (nitrosamines).
• - Reduced intake of vit A, C E.
• The use of aspirin and NSAID (cyclooxygenase-2
  inhibitors) exerts a protective effect against
  colon cancer

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• When colorectal cancer is found in a young
  person, preexisting ulcerative colitis or one of
  the polyposis syndromes must be suspected.
• Individuals with hereditary nonpolyposis
  colorectal cancer syndrome (HNPCC, also known as
  Lynch syndrome), caused by germ-line mutations of
  DNA mismatch repair genes, are at a high risk of
  developing colorectal cancers.
• (HNPCC patients are also at risk of developing
  other tumors, such as cholangiocarcinomas.)

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Malignant Tumors of Large IntestineAdenocarcinoma

• Colorectal carcinogenesis
• Two pathogenetically distinct pathways for the
  development of colon cancer, both seem to result
  from accumulation of multiple mutations
• The APC/B-catenin pathway
• chromosomal instability that results in stepwise
  accumulation of mutations in a series of
  oncogenes and tumor suppressor genes.
• Localized colon epithelial proliferation followed
  by the formation of small adenomas, become more
  dysplastic, and ultimately develop into invasive
  cancers.

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Malignant Tumors of Large IntestineAdenocarcinoma
Colorectal carcinogenesis
This adenoma-carcinoma sequence accounts for
aboout 80 of sporadic colorectal cancers.
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Malignant Tumors of Large IntestineAdenocarcinoma

• The DNA mismatch repair genes pathway
• 10 to 15 of sporadic cases.
• There is accumulation of mutations (as in the
  APC/B-catenin schema) but the involved genes
  are different.
• Unlike in the adenoma-carcinoma sequence, there
  are no clearly identifiable morphologic
  correlates

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Malignant Tumors of Large IntestineAdenocarcinoma

• In DNA mismatch repair genes pathway defective
  DNA repair caused by inactivation of DNA mismatch
  repair genes is the fundamental and the most
  likely initiating event in colorectal cancers
• Inherited mutations in one of five DNA mismatch
  repair genes (MSH2, MSH6, MLH1, PMS1, AND PMS2)
  give rise to the hereditary non polyposis colon
  carcinoma (HNPCC)
• MLH1 gene is the one most commonly involved in
  sporadic colon carcinomas

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Malignant Tumors of Large IntestineAdenocarcinoma

• Microsatellite instability (MSI) is the molecular
  signature of defective DNA mismatch repair
• Most microsatellite sequences are in noncoding
  regions of the genes so mutations in these genes
  are probably harmless.
• However, some micorsatellite sequences are
  located in the coding or promoter region of genes
  involved in regulation of cell growth.

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HNPCC
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Colorectal Carcinoma

• Morphology
• Sixty to 70 of colorectal carcinomas are in the
  rectum, rectosigmoid and sigmoid colon.
• Left-sided carcinomas tend to be annular,
  encircling lesions with early symptoms of
  obstruction.
• Neoplasms start superficially, slowly invading
  the deeper layers with ulceration and eventually
  metastasis.

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Colorectal Carcinoma

• Morphology
• Right-sided carcinomas tend to grow as polypoid,
  fungating masses, obstruction is uncommon.
• Invasion of the wall and extend to the mesentery,
  regional lymph nodes and more distal sites.
• Mucinous adenocarcinoma secret abundant mucin
  that may dissect through cleavage planes in the
  wall.
• Small cell undifferentiated carcinomas are rare
  (arising from neuroendocrine cells)
• In UC, poorly differentiated infiltrative
  adenocarcinoma without an exophytic growth.

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Colorectal Carcinoma

• Clinical features
• The condition tends to be present for a
  considerable time before producing symptoms.
• Left-sided lesions tend to present earlier but
• also have a more infiltrative growth pattern
  and a poorer prognosis.
• Right-sided lesions tend to present with
  weakness, malaise, weight loss, unexplained
  anemia (secondary to early bleeding).

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Colorectal Carcinoma

• Spread - direct extension.
• - metastasis through
• - lymphatic
• - blood vessels
• - favored sites are regional lymph node,
  liver, lungs, bones.
• Serum levels of carcinoembryonic antigen (CEA)
  are related to tumor size and extent of spread.
  They are helpful in monitoring for recurrence of
  tumor after resection.
• Overall 5-year survival is 35 to 49 in the
  United States.

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Colorectal Neoplasm

• Other Tumors
• Malignant spindle cell (mesenchymal) tumors and
  lymphomas.
• Grossly and microscopically resemble those
  arising elsewhere in the GI tract.
• Carcinoid tumors may arise anywhere in the colon,
  especially the rectum.
• Squamous cell carcinomas are largely limited to
  the rectal canal. Initially present as
  plaque-like lesions, later becoming ulcerated or
  fungating.
• Malignant melanoma at the anal verge.

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Small Intestinal Neoplasms

• 3-6 of GIT neoplasm, slight preponderance to
  benign tumors.
• BENIGN
• Discovered incidentally, leiomyoma, adenoma and
  lipoma
• Large lesions may cause obstruction, bleeding,
  intussusception, volvulus.
• ADENOMAS
• Single or multiple polyps, most often in the
  duodenum and ileum.
• There is a risk of malignancy with larger
  adenomatous polyps.
• MALIGNANT
• In descending order of frequency carcinoid,
  adenocarcinomas, lymphomas and leiomyosarcomas.
• Leiomyosarcomas have tyrosine kinase receptors,
  can be treated by STI-571

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Small Intestinal Neoplasms

• Adenocarcinoma of small intestine
• Tumors grow as polypoid fungating ulcerating mass
  or encircling pattern
• Site duodenum ( ampulla of Vater)
• Presentation abdominal cramping pain, vomiting
  and weight loss
• Patients present late
• 5 years survival is 70 after en bloc resection
  

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Small Intestinal Neoplasms

• Carcinoid Tumors
• Neoplasms arising from endocrine cells Kulchitsky
  or enterochromaffin cells found along the length
  of GIT mucosa. Cells have an affinity for silver
  salts.
• 60 to 80 appendix and terminal ileum 10 to 20
  rectum, the remainder in the stomach, duodenum or
  esophagus.
• Other Location Lungs, pancreas, biliary tract,
  ovaries and liver.
• Peak age 6th decade, comprise 2 of colorectal
  carcinoma and 50 of small intestinal carcinoma.
• Tumors in the appendix and rectum, although
  spreading locally, seldom metastasize.
• Ileal, gastric, and colonic carcinoids are
  frequently malignant.

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Carcinoid Tumors

• Morphology
• Round submucosal elevations that are bright
  yellow or yellow-gray, may be deeply
  infiltrative and penetrate muscle to the serosa.
• Gastric and ileal carcinoids are frequently
  multiple.
• Tumor cells arranged in trabecular, insular,
  glandular or undifferentiated patterns are
  monotonously similar to each other with regular
  round nuclei
• Ultrastructral features neurosecretory
  electron dense bodies in the cytoplasm

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Small Intestinal Neoplasms

• Carcinoid Tumor
• Clinical features
• Asymptomatic
• May cause obstruction, intussusception or
  bleeding.
• May elaborate hormones Zollinger-Ellison,
  Cushings carcinoid or other syndromes.
• 5 years survival rate is 90, small bowel
  Carcinoid with liver metastasis the 5 years
  survival rate is better than 50

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Small Intestinal Neoplasms

• Carcinoid tumor
• Carcinoid syndrome
• Syndrome occur in 1 of all pt. with carcinoid
  in 20 of those of widespread metastasis
• Paroxymal flushing, episodes of asthma-like
  wheezing, right-sided heart failure, attacks of
  watery diarrhea, abdominal pain, edema and
  pellagra-like lesions of the skin and oral
  mucosa.
• The principal chemical mediator is serotonin
  (5-hydroxy-tryptamine-5HT).
• 5-HT is decarboxylated in the liver and lungs to
• 5-hydroxy-indoleacetic acid (5HIAA)
• The syndrome is classically associated with ileal
  carcinoids with hepatic metastases.

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Small Intestinal Neoplasms

• Lymphoma
• Up to 40 of lymphomas arise in sites other than
  lymph nodes, gut is the most.
• 1 to 4 of all gastrointestinal malignancies are
  lymphomas.
• Primary GIT lymphomas exhibit no evidence of
  liver, spleen, or bone marrow involvement at the
  time of diagnosis.

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Small Intestinal Neoplasms

• Lymphoma
• Sporadic lymphoma arise from the B cells of
  mucosa-associated lymphoid tissue (MALT).
• This usually affects adults, lacks a sex
  predilection, and may arise anywhere in the gut
  stomach - 55 to 60 -
• small intestine - 25 to 30 -
• proximal colon - 10 to 15 -
• distal colon - up to 10 -

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Small Intestinal Neoplasms

• Lymphoma
• Gastric MALT lymphomas arise in the setting of
  mucosal lymphoid activation, as a result of
  Helicobacter associated chronic gastritis.
• Celiac disease is associated with a higher than
  normal risk of T-cell lymphomas.

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Small Intestinal Neoplasms

• Lymphoma
• Primary GIT lymphomas have a better prognosis
  than do those arising in other sites.
• Treatment combined surgery, chemotherapy, and
  radiation therapy.

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