Chapter 17: Small Intestine and Colon Flashcards
1
Q
Acquired hernias most typically occur anteriorly via which sites?
A
- Femoral and Inguinal canals
- Umbilicus
- Surgical scars
2
Q
Which type of hernia is most often associated with obstruction and why?
A
- Inguinal hernias
- Narrow orifices and large sacs
3
Q
What is the most common cause of intestinal obstruction in the US?
A
Adhesions
4
Q
What do adhesions between bowel segments create and what does this lead to?
A
Create closed loop segments, trapping other parts of small bowel —> internal hernias
5
Q
Although rare, where does Volvulus of the bowels most often occur?
A
Sigmoid colon > cecum > small bowel > stomach
6
Q
What is the most common cause of intestinal obstruction in children <2 yo?
If left untreated may progress to what?
A
- Intussusception
- Untreated = intestinal obst. –> compress mesenteric vessels –> infarction
7
Q
Although typically idiopathic, some cases of intussusception have been associated with what?
A
- Viral infections
- Rotavirus vaccine
- Intraluminal mass or tumor (adults)
8
Q
What is used both diagnostically and therapeutically for intussusception in infants and young children?
A
Contrast enemas
9
Q
What should be considered in the differential diagnosis of focal colitis of the splenic flexure or rectosigmoid colon?
Why?
A
- Ischemic disease
- These areas are watershed zonesi
10
Q
What are the 2 phases of intestinal response to ischemia?
Which phase does the greatest amt. of damage occur in?
A
1) Hypoxic injury: onset of vascular compromise; not much damage occurs in this phase; epithelial cells of gut resistant to injury
2) Reperfusion injury: time when the greatest amt. of damage occurs and in severe cases may trigger multiorgan failure
11
Q
Where are the watershed zones of the intestines and blood supply ending at each?
A
- Splenic flexure: SMA and IMA terminate
- Sigmoid and Colon: IMA, pudendal, and iliac as. end
12
Q
How does the route of intestinal capillaries running along glands from crypt to surface epithelium play a role in the pattern of atrophy and necrosis seen with ischemic intestinal disease?
A
- Surface epithelium is particularly vulnerable
- Morphological signature = surface epithelial atrophy or necrosis and sloughing w/ normal or hyperproliferative crypts
13
Q
What are the gross morphological characteristics of GI ischemia especially with transmural infarction?
How does it look after initial insult and then later on?
A
- Demarcation b/w normal and ischemic bowel is sharply defined
- Initially congested and dusky to purple-red
- Later –> bowel wall thickened and rubbery by edema
14
Q
Within 1-4 days following GI ischemia what type of necrosis is seen and of which layer?
A
Coagulative necrosis of muscularis propria
15
Q
In both acute and chronic ischemia of the GI, what does bacterial superinfection and entero toxin release induce?
Resembles?
A
- Induce pseudomembrane formation
- Resembles C. difficle-associated pseudomembranous colitis
16
Q
Ischemic disease of the colon is most common in what age group?
A
Age 70+
17
Q
Acute colonic ischemia typically presents clinically how?
A
- Sudden onset of cramping
- LLQ pain
- Desire to defecate
- Passage of blood or blood diarrhea
18
Q
Mortality from acute colonic ischemia is doubled in patients with what type of presentation?
Why?
A
- Right-sided colonic disease
- Since right side of colon is supplied by SMA, which also supplies much of the small intestine
19
Q
Other than right-sided involvment in acute colonic ischemia what are other poor prognostic indicators?
A
- Co-existing COPD
- Persistence of sx’s for >2 weeks
20
Q
Intermittent blood diarrhea + intestinal obstruction are most often seen in what type of GI infarction?
A
Mucosal and mural infarctions
21
Q
Which virus may cause ischemic GI disease due to viral tropism for endothelial cells?
A
CMV
22
Q
Beyond clinical hx, the presence of what may provide an important clue to the etiology of radiation enterocolitis?
A
Presence of highly atypical “radiation fibroblasts” within stroma
23
Q
What are the sx’s of acute radiation enteritis?
A
- Anorexia
- Abdominal cramps
- Malabsorptive diarrhea
24
Q
What is the most common acquired GI emergency of neonates, particularly premature or low-birth weight infants?
When does it typically manifest?
A
- Necrotizing enterocolitis (NEC) –> transmural necrosis
- Presents when oral feeding is initiated
25
Lesions characterized by **malformed submucosal and mucosal blood vessels**, occurring **most often in the cecum or right colon**, during the sixth decade of life is known as?
Angiodysplasia
26
Angiodysplasia is a significant cause of what?
**Major episodes** of **lower intestinal bleeding**
27
Which 4 diseases are associated with a defect in **intraluminal digestion?**
1) Chronic pancreatitis
2) Cystic Fibrosis
3) Primary bile acid malabsorption
4) IBD
28
Painful, bloody, small-volume diarrhea is known as?
Dysentery
29
Differentiate the 4 categories of diarrhea: Secretory diarrhea, Osmotic diarrhea, Malabsorptive diarrhea, and Exudative diarrhea.
Which persist and are relieved by fasting?
1) **Secretory:** isotonic stool and **persists during fasting**
2) **Osmotic:** like which occurs w/ lactase deficiency; excess osmotic forces due to unabsorbed luminal solutes; **relieved** **w/ fasting**
3) **Malabsorptive:** follows gen. failure of nutrient absorption; assoc. w/ **steatorrhea** and is **relieved by fasting**
4) **Exudative:** due to inflammatory disease; characterized by purulent, blood stools that **continue during fasting**
30
What type of diarrhea is associated with CF?
**Malabsorptive** due to exocrine pancreatic insufficiency
31
Explain the pathogenesis of Celiac Disease starting with the undigested α-gliadin peptide until deposit of gliadin in the damaged epithelium.
- **Gliadn** induces epithlial cell expression of **IL-15** --\> triggers activation/proliferation of **CD8+** lymphocytes
- **CD8+ cells** express **NKG2D** (receptor for **MIC-A**)
- Stressed **e****nterocytes**express**MIC-A**and are attacked by**CD8+ cells**
- **Gliadin** deposits in damaged epithelium and are **deaminated** by **tissue transglutaminase (tTG)**
32
Deamidated gliadin peptides in the damaged epithelium interact with what on APC's?
Leads to?
- Interact w/ **HLA-DQ2** or **DQ-8** on APC's
- Stimulates **CD4+ T cells** to produce **cytokines** which contribute to **tissue damage**
33
What is the histopathology of celiac disease characterized by?
Which cells are seen in increased numbers?
- Increased CD8+ T cells (**intraepithelial lymphocytosis**)
- **Crypt hyperplasia** --\> high rate of epithelial turnover --\> lack of differentiation
- **Villous atrophy**
- Increased # of **plasma cells, eosinophils,** and **mast cells**
34
What is a sensitive marker for Celiac Disease even in the absence of villous atrophy and epithelial damage?
What combo is most specific for diagnosis?
- **Increased #** of **intraepithelial lymphocytes**, particularly within **villus**
- Combo of **histology + serology** is **most specific** for diagnosis
35
Between what ages does Celiac Disease most commonly present?
30-60 yo
36
Many cases of Celiac Disease are often asymptomatic and clinical symptoms don't become evident until the development of what?
**Anemia** due to **chronic iron** and **vitamin malabsorption**
37
Which sex is Celiac disease detected 2x as frequently in and what may be a contributing factor?
- Females
- Monthly menstrual bleeding --\> accentuating the effect of impaired absorption
38
Which characteristic rash is seen in some patients with Celiac Disease?
Cause?
- **Dermatitis Herpetiformis --\>** itchy, blistering skin lesion
- IgA deposition @ tips of dermal papillae --\> herpes-like blister
39
What are the 2 most sensitive serologic tests for Celiac disease?
- IgA **anti-tTG** Abs
- IgA **anti-endomysial** Abs
40
Which malignancies are most common in patients w/ Celiacs Disease?
- **Enteropathy associated T-cell lymphoma** (**most common**)
- Small intestinal adenocarcinoma
41
When a patient with Celiac disease is following a gluten-free diet but is still experiencing symptoms of weight-loss, abdominal pain, and diarrhea, what differential diagnoses must be considered?
- Cancer
- Refractory sprue
42
What is Enviornmental Enteropathy also known as?
Where is it most commonly seen?
- Tropical sprue
- Populations w/ **poor sanitation** and **hygiene**: sub-Saharan Africa, aboriginal populations, some groups of S. America and Asia, India, and Pakistan
43
What are some of the common signs and symptoms of pts with Tropical Sprue?
- Malabsorption/malnutrition
- Stunted growth
- Defective intestinal mucosal immune function
44
The cause of Tropical Sprue isn't known, but what are some of the likely involved factors?
- **Defective intestinal barrier function**
- **Chronic exposure** to **fecal pathogens**
- **Repeat** bouts of **diarrhea** within the **first 2 or 3 years of life**
45
What is the inheritance pattern of Autoimmune Enteropathy?
**X-linked**
46
Autoimmune enteropathy is chararcterized by what (sx's) and occurs at what age?
- **Severe** **persistent diarrhea** and **autoimmune disease**
- Occurs **most** often in **children**
47
A particularly severe familial form of Autoimmune Enteropathy is known as?
What is the underlying genetic defect?
- IPEX - **immune dysregulation Polyendocrinopathy, Enteropthy, and X-linkage**
- Germline mutation of ***FOXP3 gene*** expressed by CD4+ Treg cells
48
Autoantibodies to what are often seen in Autoimmune Enteropathy?
- Auto-abs to **enterocytes/goblet cells**
- Auto-abs to **parietal cells/islet cells**
49
What is the treatment for Autoimmune Enteropathy?
- Immunosuppressive drugs: **Cyclosporine**
- Rare cases: **HSC transplant**
50
What is the inheritance pattern of congenital lactase deficiency?
Autosomal Recessive
51
What are the sx's of congenital lactase deficiency?
- **Osmotic diarrhea:** explosive w/ watery, frothy stools
- Abdominal distention
- All upon milk ingestion
52
What is the cause of acquired lactase deficiency?
Particularly common in what populations?
Can develop after what?
- Down-regulation of lactase gene expression
- Common in Native Americans, Blacks, and Chinese
- Can develop following enteric viral or bacterial infections
53
What is the inheritance pattern of Abetalipoproteinemia?
Autosomal Recessive
54
Which mutation is seen in Abetalipoproteinemia?
Mutation in **microsomal triglyceride transfer protein (MTP)**
55
What is the defect caused by the mutation in Abetalipoproteinemia?
- Without MTP, enterocytes **cannot** assemble or export lipoproteins, especially **A****poB**
- Results in **intracellular accumulation** of lipids
56
What is seen histologically in Abetalipoproteinemia?
Stained how?
- **Vacuolization** of **small intestinal epithelial cells**
- Stains such as **oil red-O**, particularly after fatty meal
57
When is the onset of Abetalipoproteinemia and what are the signs/symptoms?
What is seen serologically?
- Presents in **infancy**
- Failure to thrive, diarrhea, and steatorrhea
- Complete absence of plasma ApoB (**serology**)
- Failure to absorb fat-soluble vitamins (**ADEK**)
58
Failure to absorb essential FA's in Abetalipoproteinemia leads to deficiencies of fat-soluble vitamins as well as lipid membrane defects that can be recognized by the presence of what in peripheral blood smears?
Acanthocytic red cells (**Burr cells**)
59
What age is the peak prevalance of IBS seen?
Which sex most affected?
- Peak prevalence **20-40 yo**
- **Females**
60
Once enteric infection or IBD is excluded, what are the current criteria used for diagnosis IBS
- Abdominal pain **at least 3 days/month** **over 3 months**
- **Improvement of sx's w/ defecation**
- Change in **stool frequency** or **form**
61
What has been identified as one cause of diarrhea-predominant IBS?
**Excess bile acid synthesis** or **bile acid malabsorption**
62
How does the location and morphological expression of Ulcerative Colitis differ from that of Chron Disease?
- **Ulcerative colitis:** limited to **colon** and **rectum;** extends only into the **mucosa** and **submucosa**
- **Chron disease:** may involve **any** area of **GI (Ileum** ± **colon)** and typically **transmural**
63
When does IBD (Chron and UC) typically present?
More prevalent in which population?
- **Teens** and **early 20's**
- **Eastern European Ashkenazi Jews (3-5x)**
64
Mutation of which gene is most strongly associated with Chron disease?
What are some of the other implicated genes?
- ***NOD2*** - encodes proteins that **bind** bacteria **peptidoglycan** and activate **NF-kB path**
- **ATG16L1** = part of autophagy path
- **IRGM** = part of autophagy path
\*All involved in recognition and response to intracellular pathogens
65
Which T helper cell response is polarized in Chron Disease?
**TH1**
66
AR mutations in which cytokine and receptor genes are linked to severe, early onset IBD?
**IL-10** and the **IL-10 receptor**
67
Which epithelial defect is associated with Chron Disease?
Defects in **intestinal epithelial TIGHT JUNCTION barrier**
68
Which polymorphisms associated with epithelial barrier defects have been implicated in ulcerative colitis?
- ***ECM1*** protein polymorphism ---\> typically inhibits **MM9**
- ***HNFA*** transcription factor polymorphisms
69
What type of lesions are characteristic of Chron Disease and can help differentiate it from UC?
**Skip lesions** --\> multiple, separate, sharply delineated areas of dz
70
Which inflammatory infiltrate is abundant in Chron Disease, where does it infiltrate, and causes?
- **Neutrophils**
- Infiltrate and damage **crypts --\> Crypt abscesses**
71
What is one of the morphologic hallmarks of Chron Disease?
**Non-caseating granlomas** of the intestinal wall
72
What are some of the characteristic clinical signs and symptoms of Chron Disease?
- Intermittent attacks of mild diarrhea, fever, abd. pain
- RLQ pain, fever, bloody diarrhea --\> mimicing acute appedicitis/ perf. bowel
- Periods of **active disease** + **asymptomatic periods**
- Iron-deficiency anemia, Hypoalbuminemia, and Malabsorption (B12 and Bile salts)
73
Relapsing blood diarrhea, Fistula, Fibrosing Strictures, and Perforations are all common findings in which IBD?
Chron Disease
74
What is a strong exogenous risk factor for the development of Chron Disease and in some cases disease onset is associated with the introduction of this factor?
Initiation of **smoking** sometimes associated w/ disease onset
75
What are the ulcers like in Chron Disease vs. UC?
- **Chron** = DEEP and **knife-like - elongated, serpentine**
- **UC** = SUPERFICIAL and **BROAD****-based**
76
Which 5 extraintestial manifestations are associated with both Chron and UC?
- Migratory polyarthritis
- Sacroiliitis
- **Primary sclerosis cholangitis**
- Ankylosing spondylitis
- Uveitis
- **Skin lesions**
77
Erythema nodosum and clubbing of the finger nails are associated with what form of IBD and may develop before intestinal disease is recognized?
Chron disease
78
How is UC different from Chron disease grossly when viewing the gut wall, serosal surface, and appearance of strictures?
- Mural thickening is **NOT present,** are **thin** instead
- Serosal surface = **normal**
- **Strictures** do NOT occur
79
Toxic megacolon can result from damage to the muscularis propria in which form of IBD?
Ulcerative Colitis
80
What are the clinical features (signs and symptoms) of Ulcerative Colitis?
- **Relapsing disorder**
- Attacks of **blood diarrhea** w/ **stringy, mucoid material**
- Lower abd. pain and cramps --\> **temporarily** relieved w/ pooping
81
Grossly, ulcerative colitis always involves which part of the colon?
Rectum
82
Isolating islands of regenerating mucosa bulging into the intestinal lumen, creating **pseudopolyps**, is characterisitc of which form of IBD?
Ulcerative Colitis
83
Does surgery (colectomy) cure UC?
Yes, but extraintestinal manifestations may persist
84
In contrast to Chron, what is the effect of smoking cessation and smoking on UC?
- Initial onset of sx's of UC may occur shortly after **smoking cessation**
- Smoking may **partially relieve symptoms!**
**\***In Chron disease, smoking is linked to the onset of disease and quiting smoking does not produce remission!
85
What is the location of Indeterminate Colitis?
**Colon only** (does **not** involve small bowel) and in **continous pattern**
86
Cobblestone mucosa, creeping fat, and strictures are associated w/ what form of IBD?
Chron disease
87
Which factors are associated with dysplasia and possible development of neoplasia in patients with Ulcerative Colitis and Colonic Chron Disease?
1. **Duration of disease:** risk increases sharply **8-10 y after dz onset**
2. **Extent of disease**: pts w/ **pancolitis** are at greater risk
3. **Nature of inflammatory response:** greater frequency and severity of active inflammatio (presence of **neutrophils**) = increased risk
88
Patients with IBD and which extraintestinal manifestation of the disease have a greatly increased risk of developing cancer and are generally enrolled for surveillance at the time of diagnosis?
Primary sclerosing cholangitis
89
What is the most striking feature of Diversion Colitis?
Development of **numerous mucosal lymphoid follicles**
90
What is the most common histological finding in GVHD affecting the small bowel and colon?
**Epithelial apoptosis** paticularly of **crypt cells**
91
Creation of a temporary or permanent ostomy and blind distal segment of colon, from which normal fecal flow is diverted may lead to development of what type of colitis?
Diversion Colitis
92
Acquired pseudo-diverticular outpouchings of the colonic mucosa and submucosa is known as?
When diverticular are multiple is known as?
- Diverticular disease
- Diverticulosis = multiple
93
What are some of the factors contributing to the pathogenesis of Colonic diverticula?
- **Increased intraluminal pressure** in sigmoid colon + **unique** structure of muscularis propria in colon
- **Exaggerated peristaltic contractions** w/ spasmodic sequestration of bowel segments
- **Diets low in fiber --\> reduce stool volume, especially in sigmoid = enhances these risk factors**
94
Small, **flask-like outpouchings**, that occur in regular distribution alongside the taeniae coli and most often in the **sigmoid colon** are characteristic of?
Colonic diverticula
95
Which layer is totally absent in colonic diverticula?
Muscularis propria
96
Often times asymptomatic, but in subset of pts diverticular disease can producie what symptoms and clinical manifestations?
- Intermittent cramps, lower abd. discomfort, constipation, distention, or **sensation of never being able to fully empty rectum**
- Alternating constipation + diarrhea = mimics IBS
- Occasionally **minimal chronic** or **intermittent blood loss** --\> visible in **stool**
97
What is a sessile polyp vs. pedunculated polyp?
- **Sessile** = small elevation of mucosa (first stage)
- **Pedunculated** = polyp **w/ a stalk**
98
What is the mean age of presentation for Juvenile Polyposis?
**\<5 years old**
99
What are the most common mutated genes/pathways in Juvenile Polyposis?
Which gene mutation is most common?
- ***SMAD4*** *=* **most common mutation!**
- ***BMPR1A***
- **TGF-**β signaling pathway
100
Syndromic Juvenile Polyps have which inheritance pattern?
Autosomal **Dominant**
101
Where are most juvenile polyps located and associated symptoms?
Associated complications?
- In the **rectum** --\> present w/ **rectal bleeding**
- Complications = **intussusception, intestinal obstruction,** or **polyp prolapse** (through anal sphincter)
102
What are some of the recognized extraintestinal manifestations of juvenile polyps?
- Pulmonary arteriovenois malformations
- Digital clubbing
- Congenital malformation (i.e., **polydactyly)**
103
What are the risks of dysplasia in the sporadic vs. syndromic-type of juvenile polyps?
Which cancer may be manifested later in life?
- **Sporadic** = extremely rare
- **Syndromic** = high risk for dysplasia --\> **Colonic adenocarcinoma by age 45**
104
What is the inheritance pattern of Peutz-Jeghers Syndrome?
Autosomal **Dominant**
105
What is the median age of presentation for Peutz-Jeghers Syndrome?
How does it present?
- **Age 11**
- **Multiple GI hamartomatous polyps** + **M****ucocutaneous hyperpigmentation** (i.e., freckles)
106
The mucocutaneous hyperpigmentation associated w/ Peutz-Jeghers syndrome is similar to freckles, but **how** is it distinguised?
Presence on the **buccal mucosa**
107
Pts with Peutz-Jeghers Syndrome have a markedly increased risk of several malignancies, which malignancies are most common at birth, late childhood, and 2nd-3rd decades of life?
- **Birth** = sex cord tumors of testes
- **Late childhood** = gastric and small intestinal cancers
- **2nd-3rd decades** = colon, pancreatic, breast, lung, ovarian, and uterine cancers
108
Which gene mutation/pathways is most often present in patients w/ Peutz-Jeghers Syndrome?
- Loss-of-function (both alleles) of ***STK11 (tumor suppressor)***
- Causes **loss of AMP kinase-related pathways** regulating cell polarization and acting as a brake on growth/anabolic metabolism
109
Where do polyps of Peutz-Jeghers syndrome typically occur?
Small intestine
110
What is the distinguishing morphological characteristics of Peutz-Jeghers polyps, which can be helpful in differentiating from those of Juvenile Polyps?
**ARBORIZING** network of CT and **SMOOTH muscle** intermixed w/ **lamina propria**
111
What are the morphological characteristics of Juvenile Polyps?
- **Pedunculated**, smooth-surfaced, reddish lesions w/ **dilated** **cystic spaces**
- Remainder composed of **lamina propria** expanded by mixed **inflammatory infiltrates**
112
Which 3 factors/findings are critical for the diagnosis of Peutz-Jeghers syndrome?
- **Multiple polyps** in the **small intestine**
- **Mucocutaneous hyperpigmentation**
- **Postive family hx**
113
What are the most common **neoplastic polyps**?
Precursors to the majority of which type of cancer?
- Colonic adenomas
- Precursors to the **majority** of **colorectal adenocarcinomas**
114
What is the frequency of colonic adenomas in the Western World and by what age?
**30%** of adults by **age 60**
115
In regards to colonic adenomas, what is the most important characteristic that correlates with malignancy?
Size
I.e., cancer extremely rare in adenomas \<1 cm, but 40% lesions \>4 cm contain foci of cancer
116
Familial adenomatous polyposis (FAP) is caused by what gene mutation and this gene is a key negative regulator of which signaling pathway?
- ***APC***
- **Wnt signaling pathway**
117
If FAP is left untreated there is a 100% chance of developing what?
Often by what age?
- Colorectal adenocarcinoma
- Often before age **30** and nearly **always** by age **50**
118
Which extraintestinal manifestation associated with FAP can generally be detected at birth and therefore may be an adjunct to early screening?
**Congenital hypertrophy** of the **retinal pigment epithelium**
**\***Can also be seen in attenuated FAP but won't present until age 40-50
119
Some FAP patients **without *APC* loss** may have **bi-allelic mutations** of which gene and the what is the function of this gene normally?
When present this disorder is called?
- ***MYH*** --\> **base-excision repair gene**
- ***MYH-associated*** polyposis
120
What is the inheritance pattern of *MYH-associated (aka MUTYH-associated)* polyposis?
Autosomal **recessive**
121
How is *MYH-associated* polyposis (aka *MUTYH-associated)* different from FAP?
- Similar to the **attenuated** version
- **Polyps develop LATER (age 30-50)** w/ **FEWER than 100 adenomas** and **delayed** appearance of colon cancer, often at ages 50 or older
\*FAP must have **at least 100 polyps** and can often have **1000's**i
122
Which other mutation and type of polyp is also frequently present in the *MYH-associated (aka MUTYH-associated)* polyposis?
**Serrated polyps**, often w/ ***KRAS* mutations**
123
What is the inheritance pattern of Hereditary Non-Polyposis Colorectal Cancer (aka Lynch Syndrome)?
Autosomal **Dominant**
124
Which genes are most frequently mutated and lead to HNPCC (aka Lynch syndrome)?
Normal function of these genes?
- ***MSH2*** *or **MLH1***
- Encode proteins responsible for **detection, excision, and repair of errors** that occur during **DNA replication**
125
***MYH-associated*** **polyposis** characteristically has what type of adenomas?
Which type of adenocarcinoma is common (typical or mucinous)?
- **Sessile serrated adenoma**
- **Mucinous** adenocarcinoma
126
With loss of both copies of the gene associated with HNPCC mutations accumulate at rates up to 1000x higher than normal, most often in **what regions = most frequent sites of mutations**?
Microsatellites ---\> **Microsatellite instability**
127
What age range is typical for the **classic**-type FAP?
10-15 yo
128
What age range is typical for the **attenuated**-type FAP?
40-50 yo
129
Which subtype of FAP is associated w/ **Osteomas,** Thyroid and **Desmoid Tumors,** and **Skin Cysts**?
Normally presents between what ages?
- **Gardner syndrome**
- Presents between **10-15 yo**
130
Which subtype of FAP is associated w/ Medulloblastoma and Glioblastomas?
Typically presents during which ages?
- **Turcot syndrome**
- Ages 10-15 yo
131
Which disease is associated w/ **hamartomatous polyps** of the stomach, small intestine, or colon and has extraintestinal manifestations including **nail atrophy, hair loss, abnormal skin pigmentation, cachexia and anemia**?
What is the mean age of presentation?
- Cronkhite-Canada syndrome
- Age = **\>50 yo**
132
What are some of the main differences between the colon cancers seen in HNPCC vs. sporadic colon cancers?
- **HNPCC** tends to occur at a **younger age**; located in **right side of colon**
- **Majority** of sporadic CC arises on the **left side**, but some variants can arise on right
133
What is the **morphology** of typical adenomas?
- **Pedunculated** or **sessile**
- Surface resembling **velvet** or **raspberry texture**
134
What are the distinguishing characteristics of epithelial dysplasia most easily appreciated at the surface of an adenoma?
- **Prominent nucleoli**
- **Eosinophilic** cytoplasm
- **Reduction** in # of **goblet cells**
135
What type of adenoma is this; what are the distinguishing features?
- **Sessile serrated adenoma**
- Serrated architecture, cyrpt dilation, and **lateral growth**
136
What is the normal histo features of the adenoma that arises from FAP?
What type of adenocarcinoma (typical or mucinous)?
- **Tubular** or **Villous** appearing adenoma
- **Typical** adenocarcinoma
**\***Image on left = **tubular**, image on right = **villous**
137
Which type of adenocarcinoma arises in HNPCC (typical or mucinous)?
Typical adenoma seen?
- **Mucinous** adenocarcinoma on **right side**
- Sessile **Serrated adenoma**
138
Colorectal adenocarcinomas have the highest incidence in which geographical location?
North America
139
Colorectal cancer incidence peaks at which age?
**60-70** years old
140
Several epidemiologic studies have shown that which pharmacologic agent may have a protective effect against colorectal carcinomas?
- **NSAIDs,** which **inhibit** COX-2
- COX-2 is **highly expressed** in these cancers
141
Which gene/pathway mutation accounts for the **majority** of sporadic colonic adenocarcinoma?
Describe the normal role of this gene and the pathway it regulates.
- ***APC/ β-catenin*** (BOTH copies of APC must be inactivated)
- APC is **key** **negative regulator** of **β-catenin**, a component of the ***Wnt signaling pathway***
142
What is the most common **epigenetic** event associated w/ colonic adenocarcinoma?
**Methylation-induced gene silencing**
143
As neoplastic progression of colonic adenocarcinomas continues what additional mutations may be acquired along the way?
- Activating mutations of ***KRAS***
* -* Mutations in **SMAD2** and **SMAD4 --\> TGF-**β signaling
- Loss of function of***TP53***
144
In colonic adenocarcinomas, tumor suppressor genes may be silenced by methylation of which 2 regions?
- **CpG-rich zone**
- **CpG island**
145
Which chromosome is *APC, KRAS,* and *TP53* located on?
- ***APC*** ---\> Cr. **5**
- ***KRAS*** --\> Cr. **12**
- ***TP53*** --\> Cr. **17**
146
In the sporadic-type of colonic adenocarcinoma involving the APC/WNT pathway, what type of adenoma is seen?
What type of adenocarcinoma (typical or mucinous) and is seen usually on what side of colon?
- **Tubular**, **villous** adenomas
- **Typical adenocarcinoma** on the **LEFT** side
147
Other than the APC/WNT mutations some sporadic colonic adenocarcinomas are associated with defects in what?
This accumulation of mutations is referred to as?
- Defects in DNA mismatch repair
- **Microsatellite instability**
148
In cases of microsatellite instability-associated colonic adenocarcinomas, genes that encode what components are often mutated?
- **type II TGF-**β **receptor --\>** uncontrolled cell growth
- **pro-apoptotic protein BAX --\>** enhanced survival
149
A subset of microsatellite unstable colon cancers **without** mutations in DNA mismatch repair enzymes demonstrates which **CpG island hypermethylated phenotype**?
What is the signature of this pathway of carcinogenesis?
- ***MLH1*** **promoter** is hypermethylated
- Activating mutations in ***BRAF***
- **Signature of this pathway** = microsatellite instability + *BRAF* mutation + methylation of *MLH1*
150
Colonic adenocarcinomas with **mutations in DNA mismatch repair** (*MSH2, MLH1)* or with **microsatellite instabilities** are commonly associated with what type of adenoma?
Produce what type of adenocarcinoma (typical or mucinous)?
On what side?
- Sessile **serrated adenomas**
- **Mucionous adenocarcinoma**
- **RIGHT side**
151
Polypoid, exophytic masses that extend along one wall of the large-caliber cecum and ascending colon, rarely causing obstruction, describes what type of adenocarcinoma (i.e., location)?
Adenocarcinoma of the **proximal colon**
152
In contrast to tumors of the proximal colon, what are the characteristic morphologies of adenocarinomas in the **distal colon**?
i.e., type of lesions, constriction or not, narrowing/thickening, obstructions?
- **Annular** lesions
- Produce **"napkin ring" constrictions**
- **Luminal narrowing --\>** sometimes **obstruction**
153
Microscopically, what cells and morphology of these cells is seen in colonic adenocarcinomas?
**Tall columnar cells** that resemble **dysplastic epithelium**
154
Colonic adenocarcinomas that produce which substance are associated with poor prognosis?
Mucin
155
Which symptoms are generally what call clinical attention to the presence of **cecal** and other **right-sided colon cancers?**
Fatigue and weakness due to **iron deficiency anemia**
156
Which symptoms are generally what call clinical attention to the presence of **left-sided colon cancers**?
- Occult bleeding
- Changes in bowel habits
- Cramping
- LLQ discomfort
157
What are the 2 most important prognostic factors for colonic adenocarcinomas?
1. Depth of invasion
2. Presence of LN metastases
158
What is the most common site and other sites of metastases by colonic adenocarcinomas?
- **Liver** = MOST common
- **Regional LNs**
- **Bone**
- **Lungs**
159
The anal canal is divided into thirds, what type of cells are found in the upper, middle, and lower 1/3?
**Upper** = columnar rectal epithelium
**Middle** = transitional epithelium
**Lower** = stratified squamous epithelium
\*From top to bottom; 'C' comes before 'S'
160
In the anal canal, when the entire tumor displays a basaloid pattern, which term is used to describe the tumor?
Cloacogenic carcinoma
161
Pure squamous cell carcinoma of the anal canal is frequently assoicated with what type of viral infection?
Which characteristic precursor lesions may this infection produce?
- **HPV** infections
- Precursor lesions = **condyloma acuminatum**
162
Hemorrhoids are associated with what predisposing influences?
- Straining at defecation
- Constipation
- Venous stasis of pregnancy
- Portal HTN
163
What is the initiating event in the development of appendicitis?
**Progressive increases in intraluminal pressure** that **compromise venous outfow**
164
Diagnosis of acute appendicitis requires what morphological finding?
**Neutrophilic** **infiltration** of the **muscularis propria**
165
What is the most common tumor of the appendix?\
Benign or malignant?
- Well-differentiated **neuroendocrine** (**carcinoid**) tumor
- Typically **benign**
166
What type of adenoma and tumor may be seen in the appendix and can enlarge/cause obstruction that mimics appendicitis?
**Conventional adenomas** or **typical adenocarcinomas**
167
A dilated appendix filled with mucin is called what?
May also be a consequence of what type of adenoma or tumor?
- Mucocele
- **Mucinous cystadenoma** or **Mucinous cystadenocarcinoma**
168
**Mucinous** cystadenocarcinomas of the appendix **can invade the wall** and lead to i**ntraperitoneal seeding and spread**, and in some advanced cases the abdomen fills with what?
This condition is called?
- Abdomen fills with **tenacious**, **semisolid mucin**
- **Pseudomyxoma peritonei** = disseminated intraperitoneal disease
169
What is **sterile peritonitis** due to?
Leakage of **bile** or **pancreatic enzymes**
170
Perforation or rupture of the biliary system evokes what type of peritonitis; may lead to?
- Highly irritating peritonitis
- Bacterial superinfection
171
Which cause of peritonitis is associated with **leakage of pancreatic enzymes** and **fat necrosis**?
**Acute hemorrhagic pancreatitis**
172
What is released into the peritoneum with a rupture dermoid cyst and what type of rxn ensues?
- **Keratin** is released
- **Intense granulomatous rxn**
173
What are the 5 most common organisms associated with bacterial peritonitis?
- *E. coli*
- Streptococci
- *S. aureus*
- Enterococci
- *C. perfingens*
174
Which 2 underlying conditions are most commonly associated with spontaneous bacterial peritonitis?
- Cirrhosis
- Ascites
175
Sclerosis retroperitonitis (aka **idiopathic retroperitoneal fibrosis** or **Ormond disease**) is characterized by what findings?
Thought to be related to what?
What is frequently compressed in this disorder?
- **Dense fibrosis** that may extend to involve the **mesentery**
- Spectrum of **IgG4-related sclerosis disease**, an **autoinflammatory disorder**
- **Ureters** are frequently compressed!
176
Primary malignant tumors of the peritoneal cavity arise from the peritoneal lining and are called?
Almost always associated with what risk factor?
- **Mesotheliomas** (similar to tumors of the pleura and pericardium)
- Asbestos exposure
177
Although rare, what is the **most common** malignant **soft-tissue** tumors of the peritoneum and retroperitoneum?
Usually seen in whom?
- Desmoplastic small round cell tumor
- Children and young adults (resembles **Ewing Sarcoma**)
178
What type of **translocation and fusion gene product** is associated with desmoplastic small round cell tumors of the peritoneum?
- **t(11;12)**
- Fusion of ***EWS*** and ***WT1*** genes
179
Mucinous carcinomas, particularly of the appendix may cause what in the peritoneum?
Pseudomyxoma peritonei
180
Secondary tumors of the peritoneum from direct spread or metastatic seeding are called what?
Peritoneal carcinomatosis
