L10- GIT Pathology V (cancer) Flashcards
In the SI, (benign/malignant) tumors are more common. Although it is the longest segment, it is only responsible for (2)% of GIT tumors.
1- benign
2- 3-6%
list the types of GIT polyps
Non-Neoplastic
- Inflammatory: IBD, granulation tissue
- Non-Inflammatory: hyperplastic, hamartomatous, pseudo-polyps
Neoplastic:
- benign
- malignant
Juvenile Polyp = (1):
- common in (2) age group
- (3) part of GIT affected
1- *Hamartomatous polyp, Retention polyp
2- children <5, but adults also affected
3- rectum
Juvenile Polyp:
- (1) most common form / syndrome with (high/low) risk for malignancy
- rarely (3) a (4) inherited disease with (high/low) risk for malignancy
- (6) is another associated syndrome
(Hamartomatous polyp)
1- Sporadic SINGLE polyp
2- no malignant potential
3- juvenile polyposis syndrome
4- AD
5- high
6- Cowden and Bannayan-Ruvacalba-Riley syndromes (PTEN mutations)
Juvenile Polyp:
- (1) size
- (with/with-out) stalk
- On histology: (3) is expanded, (4) and (5) are abundant,
(Hamartomatous polyp)
1- 1-3 cm, lobulated
2- with stalk
3- expanded lamina propria
4- cystically dilated glands
5- inflammatory cells (neutrophils)
PJ polyp:
- inherited in (1) fashion
- (single/multiple) polyps in (2) part of the GIT
- (4) is the critical other clinical feature
(Peutz Jegher Polyp- hamartomatous polyp)
1- AD
2- multiple
3- entire GIT
4- hyperpigmentation (melantotic pigmentation) in mucocutaneous areas: lips, peri-oral areas, face, genitalia, palms
PJ Syndrome:
- (1) forms
- (2) is the major GIT issue, surrounded by (3)
- high risk to develop (4)
(Peutz Jegher polyp)
1- sporadic, syndromic forms
2- arborizing SM network between glands
3- lined with non-dysplastic epithelium rich in goblet cells
4- cancer of: pancreas, breast, lung, ovary, uterus
PJ Polyp:
- polyp will overlie (1- include composition) which are cutting through (2)
- complex (3) architecture along with (1) distinguish it from a (4) polyp
1- stroma of smooth muscle bundles
2- lamina propria
3- glandular
4- juvenile polyp
Adenoma:
- mostly found in (1)
- (2) forms
- (3) appearing nuclei
- (4) location in GIT wall
- usually (high/low) grade dysplasia
1- colon (90%)
2- flat (sessile), pedunulated
3- tall, hyperchromatic, crowded
4- confined to pre-existing crypts, no invasion
5- low (some are high => premalignant)
Adenoma pathogenesis:
- (1) type mutations
- (2) is an alternate or contributing genetic change
1- APC initially, p53 last (adeno-carcinoma sequence)
2- loss of DNA mismatch repair proteins: MSI
Conventional adenoma refers to (1). (2) is the other type.
1- polyp via APC pathway
2- sessile (flat) via MSIs
Sessile adenomas become dysplastic via (1) process and get their name from (2) appearance. Its classifications are (3).
1- MSI (microsatellite instabilities from loss of DNA mismatch repair)
2- saw-tooth (serrated)
3:
- sessile serrated polyps w/o dysplasia
- sessile serrated adenoma w/ dysplasia
- traditional serrated adenoma w/ dysplasia
Adenoma architecture types
[Note- all are precursors for carcinomas]
Tubular
Villous (pure villous)
Tubulovillous (>20% villous)
list the characteristics (by ranking) of adenomas that indicate in chance of malignancy
1) (by far) polyp size, >10mm/1cm => 40% chance of malignancy
2) dysplasia severity
3) villous > tubulovillous > tubular
4) (number) 3 or more adenomas
tubular adenoma histology
- smooth surface, rounded glands
- active inflammation occasionally
- crypt dilation and rupture
villous adenoma histology
long, slender projections (appear like SI villi)
sessile serrated adenoma histology
- lined with goblet cells
- no features of dysplasia
- neoplastic extensions into crypts –> lateral growth
Colonic Adenomas:
- (1) classic Sxs
- (2) and (3) are possible complications
1- asymptomatic
2- anemia, occult blood loss due to polyp trauma, obstruction, stalk twisting, prolapse
3- intussusception (rarely) in polyps with slender, long stalks
FAP:
- (1) genetic defect
- affects (2) part of GIT
- (3) main characteristic, with (4) as another key identifying feature
- (5) Tx
(familial adenomatous polyposis)
1- APC gene, 5q21
2- colorectum (sometimes SI, stomach)
3- 500-2500 adenomas (termed attenuated if <100)
4- unicrypt adenoma + fundic gland polyp in stomach
5- colectomy to prevent cancer
describe the associated FAP syndromes
(familial adenomatous polyposis)
Garder Syndrome: tubular adenomas with osteomas, desmoid tumors, epidermal cysts
Turcot Syndrome: tubular adenomas with CNS gliomas
Colorectal Carcinomas:
- more common in (younger/older) individuals, where the other needs one of the following predispositions for development, (2)
- (3) other risk factors
1- elderly
2- UC (40%), polyposis syndromes, HNPCC (Lynch syndrome)
3- obesity, low fiber diet, high animal fat diet, low antioxidant intake
list the symptoms of Colon Adenocarcinomas
-mostly asymptomatic
R-sided features (proximal colon): fatigue, weakness, IDA (chronic blood loss) [non-obstructive, several years]
L-sided features (distal colon): altered bowel habits (obstructive- napkin ring constriction]`
Colon Adenocarcinoma diagnosis:
- (1) gold standard
- (2) alternate
- (3) serum marker
1- colonoscopy
2- fecal immunohistochemistry (FIT, colo-guard)
3- carcinoembryonic antigen (CEA)
describe chromosomal instability pathway for colon cancer
(85-90% cases)
- adeno-carcinoma sequence
- APC gene mutations
- FAP, Gardner, Turcot
describe the MSI pathway for colon cancer
(microsatellite instability, 10-15% cases)
- arises from adenoma or other lesions (SSA)
- defect in DNA repair mechanism: MLH1, MSH2, MSH6, PMS2)
-85% sporadic, 15% familial (HNPCC/Lynch)
Sporadic MSI cancers:
- (1) main acquired genetic factor
- (2) histology characteristics with inc in (3) cells
1- hypermethylation of MLH1 promoter: loss of MLH1, PMS2
2- mucinous + poorly differentiated histology
3- inc lymphocytes
Colorectal adenocarcinoma:
- usually (solitary/multiple), it will be the other in (2) situations
- (3) distal / L colon tumor features
- (4) proximal / R colon tumor features
1- solitary
2- UC, FAP (multiple)
3- annular, encircling napkin ring constrictions
4- polypoidal, non-obstructive, presents with non-specific anemia (Fe deficiency, weight loss)
Colon adenocarinoma:
- invades (1) layers of the wall
- 10-15% tumors are termed (2) based on what they produce
- spread to (3) is more frequent than (4) spread that also occurs
- (5) general prognosis
1- mucosa, submucosa (possibly beyond)
2- mucinous, colloid (excess mucin)
3- regional LNs
4- *liver, peritoneum, lung, bones
5- no metastasis 97% survival, w/ metastasis 4%
list the locations neuroendocrine tumors can occur in the GIT
Esophagus- rare
Stomach- 3 settings
SI, Appendix- most common
Rectum
describe esophageal and rectal carcinoids
Esophageal are rare to occur
Rectal are usually small and benign
describe the types of stomach carcinomas
Type I: autoimmune gastritis
- glandular atrophy, achlorhydria
- hypergastrinemia => enterochromograffin cell-like (ECL) hyperplasia
Type II: Gastrinoma (Zollinger-Ellison syndrome):
-MEN1 syndrome, hypergastrinemia
Type III: sporadic
-more aggressive and multiple sites
describe carcinoid tumors in the SI / appendix
(most common site in GIT)
- often small, occult primary tumors
- mestastizes widely => carcinoid syndrome when LIVER is involved
Carcinoid Syndrome:
- (1) Sxs
- (2) special test
- (3) unique complication
1- wheezing, flushing, diarrhea (via 5-HT / serotonin release)
2- 5-HIAA urine test
3- R heart fibrosis (because liver and lungs breakdown serotonin, it never reaches L heart)
GI Neuroendocrine Tumors:
- tumor cells are embedded in (1)
- it can be seen on histology spreading to (2)
- high magnification has (3) appearance
1- dense fibrous material
2- mucosal lymphatic channels
3- ‘salt-n-pepper’ appearance: chromatin with fine, course clumps
GI Lymphomas:
- (1) primary tumor
- (2) secondary tumor
1- arises from MALT (mucosal associated lymphoid tissue) = extranodal lymphomas (NO liver, spleen, bone marrow involvment at Dx)
2- arises due to systemic involvement of GIT from nodal lymphomas (Hodgkin’s lymphomas)
GI Lymphomas:
-list the sites involved
(Note- most common site for extranodal lymphomas)
Stomach, 50%
SI, 37%
Colon/Rectum
list the types of Primary GI Lymphomas
low-grade NHL (B-cell)
- MALToma
- Mantle cell (lymphomatous polyposis)
- Follicular Lymphoma
- CLL/SLL
Diffuse large B-cell lymphoma
Burkitt lymphoma
Note- many, many T-cell lymphomas
primary GI lymphomas are often seen in ______ patients
- post-transplant
- AIDS
- congenital immunodeficiency
- IBD associated
- MTX therapy
MALToma:
- (1) main associated disease
- (2) age and gender demographics
- (3) earliest / hallmark feature
- (4) Sxs
1- H. pylori infection (chronic gastritis)
2- adult men (~60, 1.6:1 M:F)
3- lympho-epithelial lesions (lymphocytes effacing gastric pit epithelium)
4- dyspepsia 80% / abdominal pain, n/v, weight loss 45%
GI Lymphoma:
- (1) Tx
- (2) general prognosis
- (3) typical growth progression
- (4) are agents used for high stage / unresponsive cases
1- H. pylori eradication via antibiotics
2- 70-90% remission, 10% relapse (90% 5Y survival, 65-75% 10Y)
3- slow, remains localized
4- chemotherapy: Rituximab (anti-CD-20 agent)
