Tumours of the Lower GI Tract Flashcards
What proportion of all GI tumors are in the small intestine ?
3-6%
Identify the main benign tumors of the small intestine.
• Adenomas (25%) • Mesenchymal tumours – Leiomyoma – Lipoma – Angioma
Identify the main malignant tumors of the small intestine.
- Adenocarcinoma
- Carcinoid
- Lymphoma
- Sarcomas
Identify the main benign tumors of the large intestine and rectum.
- Non-neoplastic polyps
- Neoplastic (adenomas)
Identify the main malignant tumors of the large intestine and rectum.
- Adenocarcinoma (98%)
- Carcinoid
- Lymphoma
- Anal zone carcinoma
- Leiomyosarcoma
Which structure of the GI do small intestine adenomas often affect ?
Affects often ampulla of Vater
• enlarged and exhibits a velvety surface
Do small intestine adenomas have malignant potential ?
Yes, they do, can turn into adenocarcinoma
ADENOCARCINOMA OF SMALL INTESTINE
- Where in small intestine
- Epidemiology
- Macroscopic appearance
ADENOCARCINOMA OF SMALL INTESTINE
- Where in small intestine: Duodenum
- Epidemiology: 40 to 70 year old patients
- Macroscopic appearance: napkin-ringencircling pattern + polypoid exophytic masses
Identify the main symptoms, and 5-year survival rate of adenocarcinoma of the small intestine.
– intestinal obstruction
– cramping pain, nausea, vomiting, and weight loss
– may cause obstructive jaundice
– 70% five-year survival rate
Identify the main types of neoplastic, and non-neoplastic (both benign) tumors of the large intestine and colon.
• Non-neoplastic polyps:
– Hyperplastic(90%)
– Hamartomatous
• Neoplastic (AKA Adenoma):
– Tubular
– Villous
– Tubulovillous
HYPERPLASTIC POLYPS
- Epidemiology
- Size
- Macroscopic appearance
- Location in colon
- Histology
HYPERPLASTIC POLYPS
- Epidemiology: >age 60
- Size: <5mm
-Macroscopic appearance:
Nipple-like, hemispheric, smooth, moist protrusions of the mucosa
-Location in colon: 1/2 are found in the rectosigmoid colon
-Histology:
– well-formed glands and crypts
– lined by non-neoplastic epithelial cells
– most of which show differentiation into mature goblet or absorptive cells
What are the main kinds of Hamartomatous Polyps ?
1) Juvenile polyps
2) Peutz-Jeghers polyps
Distinguish between juvenile polyps and Peutz-Jeghers (both non-neoplastic) polyps based on:
- Cause
- Epidemiology
- Location in colon/rectum
- Histology
- Malignant potential
JUVENILE POLYPS
-Cause: malformations of the mucosal epithelium and lamina propria
- Epidemiology: children younger <5
- Location in colon/rectum: 80% in the rectum
-Histology: – abundant cystically dilated glands – Inflammation is common – Surface may be congested or ulcerated
-Malignant potential: None
PEUTZ-JEGHERS POLYPS
-Cause: Peutz-Jeghers autosomal dominant syndrome, mutation of the gene STK11 (LKB1) located on chromosome 19
-Location in colon/rectum: Stomach 25% colon 30% and small bowel
-Histology:
• Involve the mucosal epithelium, lamina propria, and muscularis mucosa
• Tend to be large and pedunculated
-Malignant potential: None, but increased risk of the pancreas, breast, lung, ovary, and uterus carcinoma
Which of the main kinds of adenomas are the most common ?
• Tubular adenomas (75%) > Tubulovillous adenoma (5-15%) > Villous adenomas (1-10%)
Distinguish between the structure of Tubular adenomas and Villous adenomas. How do they arise ?
They are all intra-epithelial lesions.
Tubular: Small pedunculated
lesions
Villous: Large neoplasms that are usually sessile
Arise as the result of epithelial proliferative dysplasia
Describe the epidemiology of adenomas.
Male = Female ratio
20% to 30% before age 40, rising to 40% to 50% after age 60
Why features of adenomas is the risk of malignancy correlated with ?
• Polypsize
– Rare in tubular adenomas < 1 cm
– High risk (40%) in sessile villous adenomas > 4 cm
• Histological architecture
• Severity of epithelial dysplasia
– Severe dysplasia, when present, is often found in villous areas
Is it possible to determine clinical significance of a polyp from its appearance ?
No, impossible from gross inspection of a polyp to determine its clinical significance
Describe the macroscopic morphology of Tubular Adenomas. Where in the GI tract do these occur ?
- Usually < 2.5cm
- Small tubular adenomas are smooth-contoured and sessile
- Larger ones tend to be coarsely lobulated and have slender stalks raspberry - like
(90%) in the colon (rest in the stomach and small intestine)
Describe the histological morphology of Tubular Adenomas.
– Stalk is composed of fibromuscular tissue and prominent blood vessels
– Presence of dysplastic epithelium, which lines glands as a tall, hyperchromatic, disordered epithelium that may show mucin vacuoles
– Degree of dysplasia is low- grade
– High-grade dysplasia may be present
– Carcinomatous invasion into the submucosal stalk of the polyp constitutes invasive adenocarcinoma
Describe the macroscopic morphology of Villous Adenomas. Where in the GI tract do these occur ?
– Sessile, up to 10 cm
– Velvety or cauliflower- like masses projecting 1 to 3 cm above the surrounding normal mucosa
Commonly in the rectum and rectosigmoid
Which kind of adenoma affects the older people ?
Villous adenomas affect older people
Describe the histological morphology of Villous Adenomas.
– Frond like villi form extensions of the mucosa
– Covered by dysplastic, sometimes very disorderly columnar epithelium
– All degrees of dysplasia may be encountered
– When invasive carcinoma occurs (40%), there is no stalk as a buffer zone, and invasion is directly into the wall of the colon
Describe the main clinical features of adenomas.
- Colorectal tubular and tubulovillous adenomas may be asymptomatic. Many are discovered during evaluation of anaemia or occult bleeding.
- Villous adenomas more symptomatic, and often discovered because of overt rectal bleeding
What is the metastatic potential of an intramucosal carcinoma with lamina propria invasion ?
Intramucosal carcinoma with lamina propria invasion only is regarded also as having little or no metastatic potential
What is the management for
a) an adenocarcinoma arising from a pedunculated adenoma
b) an invasive adenocarcinoma arising in a sessile polyp
Endoscopic removal of a pedunculated adenoma is regarded as an adequate if:
(1) the adenocarcinoma is superficial and does not approach the margin of excision across the base of the stalk
(2) there is no vascular or lymphatic invasion
(3) the carcinoma is not poorly differentiated
Invasive adenocarcinoma arising in a sessile polyp cannot be adequately resected by polypectomy
– further surgery may be required
FAMILIAL ADENOMATOUS POLYPOSIS (FAP) SYNDROME
- Cause
- Macroscopic morphology
- Histological morphology
- Risk of developing adenocarcinoma before age 30
FAMILIAL ADENOMATOUS POLYPOSIS (FAP) SYNDROME
- Cause: Mutations of the adenomatous polyposis coli (APC) gene on chromosome 5q21-22
- Macroscopic morphology: Patients typically develop 500 to 2500 colonic adenomas that carpet the mucosal surface
- Histological morphology: Histologically, the vast majority of polyps are tubular adenomas
- 100% risk of developing adenocarcinoma before age 30 = total colectomy indicated
ADENOCARCINOMA OF LARGE INTESTINE
- What proportion of all large intestine cancers are adenocarcinomas ?
- Epidemiology
- Countries with highest date rates
ADENOCARCINOMA OF LARGE INTESTINE
-What proportion of all large intestine cancers are adenocarcinomas ? 98%
-Epidemiology: peak incidence between ages 60 and 79
– in the rectum, the male>female ratio is 1.2:1
– for more proximal tumors, male=female ratio
-Countries with highest date rates: US, Australia, New Zealand
How does colorectal cancer rank in terms of mortality, amongst all other cancers ? Is the mortality rate from it increasing or decreasing ?
3rd
Mortality rate from colorectal cancer decreasing
What is the aetiology of colorectal adenocarcinomas ?
• Dietary factors:
– (1) Excess dietary caloric intake relative to requirements
– (2) Low content of vegetable fibre
– (3) High content of refined carbohydrates
– (4) Intake of red meat
– (5) Decreased intake of protective micronutrients
Describe the pathogenesis of colorectal adenocarcinomas.
Germline or somatic (acquired) mutations of cancer suppressor genes ↓ MUCOSA AT RISK ↓ Methylation abnormalities + Inactivation of second allele ↓ ADENOMA ↓ Protooncogene mutations ↓ Homozygous loss of additional cancer suppressor genes + Over-expression of COX-2 ↓ CARCINOMA ↓ Additional mutations
What are the most common sites of colorectal adenocarcinoma ?
- Rectosigmoid colon, 55%
- Caecum/Ascending colon, 22%
- Transverse colon, 11%
- Descending colon, 6%
- Other sites, 6%
BUT
• All begin as carcinoma in situ lesions
Describe the macroscopic morphology of colorectal adenocarcinomas in the proximal colon.
– Polypoid, exophytic masses
– Obstruction is uncommon
– Penetrate the bowel wall as subserosal and serosal white, firm masses
Describe the macroscopic morphology of colorectal adenocarcinomas in the distal colon.
– Annular, encircling lesions - napkin-ring constrictions
– The margins are classically heaped up, beaded, and firm, and the mid-region is ulcerated
– The lumen is markedly narrowed, and the proximal bowel may be distended
– Penetrate the bowel wall as subserosal and serosal white, firm masses
Identify investigation techniques for colon cancer.
Colonoscopy
X-ray (barium enema technique)
Describe appearance of X-ray (barium enema technique) of adenocarcinoma in the colon.
“Constriction of the lumen of the colon”, i.e. classic “apple core” lesion.
Describe the histological morphology of colorectal adenocarcinoma.
- May range from tall, columnar cells resembling their counterparts in adenomatous lesions to
- Undifferentiated, frankly anaplastic masses
- Many produce mucin
- Invasive tumour incites a strong desmoplastic (“desmoplasia is the growth of fibrous or connective tissue”) stromal response
Identify the main clinical features of colorectal adenocarcinoma.
• Asymptomatic for years
• Caecum and right colonic:
– fatigue, weakness, and iron-deficiency anaemia (consequences of anemia)
• Left-sided lesions:
– occult bleeding, changes in bowel habit, or crampy left lower quadrant discomfort
• Systemic manifestations such as weakness, malaise, and weight loss signify more extensive disease (i.e. metastasis of adenocarcinoma)
What does iron deficiency in an older male mean, unless proven otherwise ? What about systemic manifestations, in this same context ?
- Iron-deficiency anaemia in an older male means gastrointestinal cancer until proven otherwise
- Systemic manifestations such as weakness, malaise, and weight loss signify more extensive disease (i.e. metastasis of adenocarcinoma)
How often do colorectal cancers spread ? How do colorectal adenocarcinomas spread ?
• All colorectal tumors spread
Adenocarcinomas spread:
1) Directly (through wall of large bowel) extension into adjacent structures (e.g. uterus, bladder)
2) Metastasis through lymphatics, or blood vessels (e.g. via portal vein into liver, then potentially via IVC into R heart, and then lungs via pulmonary artery)
3) Regional lymph nodes, liver, lungs, and bones, serosal membrane of the peritoneal cavity, brain, and others
Describe Duke’s stages of colorectal adenocarcinomas ?
A) confined to the submucosa or muscle layer (90+%)
B) spread through the muscle layer, but does not yet involve the lymph nodes (70%)
C) involvinglymph nodes (35%)
CARCINOID TUMORS
- Site
- Cells involved
- Epidemiology
CARCINOID TUMORS
- Site: Appendix is the most common site, but small intestine (primarily ileum), rectum, stomach, and colon.
- Cells involved: Derived from endocrine cells
- Epidemiology: Age >60
What proportion of all colorectal malignancies are carcinoid tumors ?
What proportion of small intestine malignancies are carcinoid tumors ?
2% of colorectal malignancies but almost 1/2 of small intestinal malignant tumours
Describe the histological differences between seemingly benign and obviously malignant carcinoid tumours.
No reliable histological difference between seemingly benign and obviously malignant carcinoid tumours
What factors does aggressive behavior of a carcinoid tumor correlate with ?
• Aggressive behaviour correlates with: – site of origin, – depth of local penetration – size of the tumour – histological features of necrosis and mitosis
Describe the macroscopic morphology of a carcinoid tumor.
• Usually solitary lesion
– except ileum and stomach (multicentric)
• Intramural or submucosal masses that create small polypoid or plateau-like elevations < 3 cm.
• Solid, yellow-tan appearance on transection
Describe the histological morphology of a carcinoid tumor.
- Neoplastic cells may form discrete islands, trabeculae, stands, glands, or undifferentiated sheets
- Tumour cells are monotonously similar, having a scant, pink granular cytoplasm and a round to oval stippled nucleus
- By electron microscopy tumour cells contain membrane-bound secretory granules with dense-core granules in the cytoplasm
Identify the clinical features of carcinoid tumors.
• Rarely produce local symptoms:
– caused by angulation or obstruction of the small intestine
– Some neoplasms are associated with a distinctive carcinoid syndrome (from excess of serotonin (5-hydroxytryptamine, 5-HT)):
- Cutaneous flushes and apparent cyanosis
- Diarrhoea, Cramps, nausea, vomiting
- Cough, wheezing, dyspnoea
Describe the spread of carcinoid tumors. What is the 5-year survival rate for carcinoids ?
- Appendiceal and rectal carcinoids do not metastasize
- 90% of ileal, gastric, and colonic carcinoids that have penetrated halfway through the muscle wall have spread to lymph nodes and distant sites such as the liver at the time of diagnosis
The overall five-year survival rate for carcinoids is 90%
Define a primary GI lymphoma.
Primary gastro-intestinal lymphomas exhibit no evidence of liver, spleen, mediastinal lymph node, or bone marrow involvement at the time of diagnosis
What are the main types of GI lymphomas ? What is the prognosis for each of these ?
- B-cell lymphomas (much better prognosis, Ten-year survival for patients with localized mucosal or submucosal disease ≈85%
- T-cell lymphomas (prognosis is poor, 11% five-year survival rate), associated with a long-standing malabsorption syndrome
What are the main types of B cell lymphomas ?
- MALT (mucosa-associated lymphoid tissue)
- Immunoproliferative small-intestinal disease (IPSID) tissue (i.e. Mediterranean lymphoma)
- Burkitt lymphoma
What are the main sites for MALT (type of B cell lymphoma) ?
Stomach (55% to 60%) Small intestine (25% to 30%) Proximal colon (10% to 15%) Distal colon (up to 10%)
Identify the main types of mesenchymal tumors (both benign and malignant). Where are these located ?
- Lipomas (small intestine)
- Leiomyomas (small intestine)
- Leiomyosarcomas (large intestine/rectum)
Describe the histological morphology of lipomas.
Well-demarcated, firm nodules <4 cm arising within the submucosa or muscularis propria
Describe the histological morphology of leiomyosarcomas.
Large, bulky, intramural masses that eventually fungate and ulcerate into the lumen or project subserosally into the abdominal space
What is the five-year survival rate of leiomyosarcomas ?
Five-year survival rate 50% to 60%
Identify the main regions of the anal canal. What tissue makes up each ?
– Anal canal divided into three zones
• the upper (covered with rectal mucosa)
• the middle (partially covered with a transitional mucosa)
• lower (covered by stratified squamous mucosa)
Identify the main benign tumors of the anal canal. What is this caused by ?
Warts (condyloma acuminata) are the commonest benign neoplasm of the anus
-Caused by HPV infection
Identify the main malignant tumors of the anal canal, giving the main feature of each.
1) Carcinoma with Basaloid pattern
- immature proliferative cells derived from the basal layer of a stratified squamous epithelium
2) Squamous cell carcinoma
- closely associated with chronic HPV infection
3) Adenocarcinoma
- extension of rectal adenocarcinoma
4) Malignant Melanoma (very rare)
