GI Malignancies Flashcards
What are the two most common lymphomas seen in the gut? Which other one is associated with celiac disease?
Two most common lymphomas of the gut are MALToma (indolent and low grade) and
diffuse large B-cell lymphoma (high grade). Enteropathy-associated intestinal T-cell
lymphoma (EATL) is seen with increasing frequency in areas with a high prevalence of
celiac disease. The relative risk of EATL in the small intestine is increased
approximately 1020-fold in patients with protracted clinical celiac disease.
What are MALTomas? Where are they more common? What are they associated with? What are they like microscopically?
o Lymphomas of mucosa-associated lymphoid tissue (MALT)
o More common in stomach
o Associated with H. pylori infection, eradication of the infection induces durable remissions with low rates of recurrence
Dense lymphocytic infiltrate in the lamina propria
Lymphoepithelial lesions (neoplastic lymphocytes infiltrate the gastric glands)
Occasionally the tumor cells accumulate large amounts of pale cytoplasm, a feature referred to as “monocytoid” change
Positive for CD19 and CD20, negative for CD5 and CD10, positive for CD43 in 25%
Monoclonality can be demonstrated by either κ or λ light chain restriction or by molecular detection of clonal IgH rearrangements.
What is EATL? What is it associated with? Where does it occur most commonly? What is it like grossly? Microscopically?
Enteropathy-associated intestinal T-cell lymphoma
o Strong association with celiac disease
o Occurs most commonly in jejunum and proximal ileum
o Gross: multiple ulcerating raised or flat mucosal lesion
o Miroscopic: medium to large-sized lymphoid cells with roundish or angulated vesicular nuclei, prominent nucleoli and moderate to abundant pale staining cytoplasm.
What is a carcinoid tumor? What do the cells contain? Where are they located? How does this effect prognosis?
A. Malignant proliferation of neuroendocrine cells; low-grade malignancy
1 . Tumo r cells contain neurosecretory granule s that are positive for chromogranin.
B. Can arise anywhere along the gut; small bowel is the most commo n site,
1 . Grows as a submucosal polyp-like nodule (Fig. 10.20)
The most important prognostic factor for GI carcinoid tumors is location, *** midgut is generally bad*** o Forgut (esophagus, stomach and duodenum proximal to the ligament of Treitz) – rare metastasis, cure by resection o Midgut (jejunum and ileum) – multiple and more aggressive. Depth of o Hindgut (appendix and colorectum) – incidental findings, usually < 2 cm, invasion, size, necrosis, and mitosis are associated with poor outcome almost uniformly benign.
What does a carcinoid tumor look like grossly and microscopically?
Gross: intramural or submucosal masses that create small polypoid lesions, overlying mucosa may be intact or ulcerated, yellow or tan on cut surface, firm, may cause kinking of the bowel and obstruction.
Microscopic: islands, trabecullae, strands, glands, or sheets of uniform cells with scant pink granular cytoplasm and a round to oval stippled nucleus (often referred to as “pepper and salt” chromatin pattern), minimal pleomorphism, immunostain positive for synaptophysin and chromogranin A (two neuroendocrine markers), cytoplasmic dense core neurosecretory granules on EM.
How does a carcinoid tumor lead to carcinoid syndrome and carcinoid heart disease? How is carcinoid syndrome characterized? What triggers the symptoms? How is carcinoid heart disease characterized? Why is one part of the heart involved and the other not?
C. Ofte n secretes serotonin
1 , Serotonin is released into the portal circulation and metabolized by liver monoamin e oxidase (MAO ) into 5-HIAA.
2. 5-HIAA is excreted in the urine.
D. Metastasis of carcinoid tumo r to the liver allows serotonin to bypass liver metabolism.
1 , Serotonin is released into the hepatic vein and leaks into systemic circulation via hepato-systemic shunts, resulting in carcinoid syndrome and carcinoid heart
disease.
2. Carcinoid syndrome is characterized by bronchospasm, diarrhea, and Hushing of
skin; symptoms can be triggered by alcohol or emotional stress, which stimulate serotonin release trom the tumor,
3 . Carcinoid heart disease is characterized by right-sided valvular fibrosis (increased collagen) leading to tricuspid regurgitation and pulmonary valve stenosis; left-sided valvular lesions are not seen due to presence of monoamine oxidase (metabolizes serotonin) in the lung,
What is a GIST tumor? What do the cells arise from? What mutation do most of the cells have? What are they like grossly? Microscopically? What is the metastasis like? What is the treatment ?
Arise from interstitial cells of Cajal, pacemaker cells in the gut
Majority bares c-KIT or PDGFRA mutation
Gross: large, solitary, well-circumscribed, fleshy mass covered by ulcerated (like umbilicus) or intact mucosa
Microscopic: tumor composed of fascicles of spindle cells in majority, epitheloid can also be seen, positive c-KIT immunostain in 95% of gastric GIST
Metastases may take the form of multiple serosal nodules thoughout the peritoneal cavity or more nodules in liver; spread outside of abdomen uncommon
Treatment: surgical resection of localized disease, target therapy with Gleevac (imatinib, a tyrosine kinase inhibitor) can be effective in metastatic or non-
resectable cases.
What are colonic polyps? What are the two most common types? What are they like grossly and micro? Are they benign? Malignant potential? How is screening/diagnosis performed? What are 3 characteristics that make progression to carcinoma more likely?
A. Raised protrusions of colonic mucosa
B . Most c o m m o n types are hyperplastic and adenomatous polyps.
L Hyperplastic polyps are due to hyperplasia of glands; classically show a ‘serrated*
appearanc e on microscopy
i. Most commo n type of polyp; usually arise in the left colon (rectosigmoid)
ii. Benign, with no malignant potential
- Adenomatous polyps are due to neoplastic proliferation of glands (Pig. 10.25);
2nd most commo n type of colonic polyp
i. Benign, but premalignant; may progress to adenocarcinoma via the
adenoma-carcinoma sequence
ii.• Size: 0.3 cm – 10 cm
• Gross: pedunculated or sessile
• Characterized by epithelial dysplasia
– nuclear hyperchromasia, elongation and stratification
C. Screening for polyps is performed by colonoscopy and testing for tecal occult blood; polyps are usually clinically silent, but can bleed.
1 . Goal is to remove adenomatous polyps before progression to carcinoma.
D. On colonoscopy, hyperplastic and adenomatous polyps look identical. Hence, all polyps are removed and examined microscopically.
1 . Greatest risk for progression from adenoma to carcinoma is related to size > 2 cm, sessile growth, and villous (opposed to tubular and tubulovillous) histology.
Describe the adenoma-carcinoma sequence.
3 . Adenoma-carcinoma sequence describes the molecular progression fro m normal
colonic mucosa to adenomatous polyp to carcinoma.
i. APC (adenomatous polyposis coli gene) mutations (sporadic or germline) increase risk for formation of polyp.
ii. K-ras mutation leads to formation of polyp.
iii. p53 mutation and increased expression of COX allow for progression to carcinoma; aspirin impedes progression fro m adenoma to carcinoma.
What is FAP? What causes it? How is it treated? What is Gardner syndrome? Turcot syndrome?
A. Autosomal dominant disorder characterized by 100s to 1000s of adenomatous colonic polyps (Fig. 10.26)
B. Due to inherited APC mutation (chromosome 5); increases propensity to develop adenomatous polyps throughout colon and rectum
C. Colon and rectum are removed prophylactic ally; otherwise, almost all patients develop carcinoma by 40 years of age.
D. Gardne r syndrome is FAP with fibromatosis and osteomas.
1 . Fibromatosis is a non-neoplastic proliferation of fibroblasts; arises in retroperitoneum (desmoid) and locally destroys tissue
2. Osteoma is a benign tumo r of bone that usually arises in the skull.
E. Turcot syndrome is FAP with CNS tumors (medulloblastoma and glial tumors)
What is a Sessile serrated adenoma/polyp? Where is it more common? What does it lack? What is its hallmark?
- Serrated like hyperplastic polyp
- More common in right colon
- Larger
- lack cytologic atypia or
conventional dysplasia
• Hallmark: **architectural
atypia**
– full thickness serration
– Lateral/horizonal growth and crypt dilation
What is a hamartomatous polyp? Give 5 examples.
• Tumor-like growths composed of mature tissue normally present
– Juvenile Polyps
– Peutz-Jeghers syndrome
– Cowden syndrome
– Cronkhite-Canada syndrome
– Tuberous sclerosis
What is a juvenile polyp? How does it present? What is juvenile polyposis? What is its significance? What are they like?
A. Sporadic, hamartomatous (benign) polyp lhat arises in children (< 5 years)
1 . Usually presents as a solitary rectal polyp that prolapses and bleeds
B, Juvenile polyposis is characterized by multiple juvenile polyps in the stomach and colon; large numbers of juvenile polyps increase the risk Of progression to
carcinoma.
• Dilated glands filled with inflammation and mucin
What is Peutz-Jeghers Syndrome? What are the polyps like? Where are the polyps located? What are pts. at increased risk for?
A. Hamartomatous (benign) polyps throughout GI tract and mucocutaneous hyper pigmentation (freckle-like spots) on lips, oral mucosa, and genital skin;
B. Increased risk for colorectal, breast, and gynecologic cancer
• Polyps: small bowel>colon> stomach
• Branching bands of smooth muscle surrounded by
glandular tissue
What is HNPCC? What causes it? What are people at increased risk for? What do pts. develop? When? Where? What is the histology of the polyps like?
Hereditary non polyposis colorectal carcinoma (HNPCC ) is due to inherited
mutations in DNA mismatch repair enzymes.
i. Increased risk for colorectal, ovarian, and endometrial carcinoma
ii. Colorectal carcinoma arises de novo (not from adenomatous polyps) at a relatively early age; usually right-sided
• AKA: Lynch syndrome
• Associated with mismatch repair deficiency and
microsatellite instability
• Histology: Sessile serrated adenoma, mucinous
adenocarcinoma
