Small Intestine and Colon Pathology 3

Question 1

Describe the features of FAP.

Answer 1

Autosomal dominent mutation in APC tumor suppressor gene

once second APC mutation is required, you get development of hundreds of adenomas - usually starting in late adolescence and early adulthoos

100% risk CRC adenocarcinoma - prophylactic colectomy undertaken

are at risk for adenocarcinoma trhoughout the rest of the GI tract

Question 2

Describe the features of Lynch syndrome (HNPCC)

Answer 2

Mutation in enzymatic mismatch repair proteins - MLH1, MSH2, MSH6, PMS2

end up with microsatellite instability with increasing number of DNA mutations - including in genes that regulate cell growth

adenomas that occur in the colon hav ea greatly increased risk of malignant transformation - lifetime risk for CRC is 80%

get extra=colonic tumors too

Question 3

Describe the features of Gardner’s syndrome.

Answer 3

In addition to FAP with the APC mutation, patients develop desmoid tumors, osteomas, epidermal cysts, dental abnormalities and thyroid tumors

Question 4

Describe the features of Turcot Syndrome.

Answer 4

defined as a coexistence of a hereditary colon cancer syndrome along with CNS tumors

some have FAP with medulloblastoma
others have HNPCC with glioblastoma multiforme

Question 5

Describe in detail the pathogenesis of colorectal cancer.

Answer 5

start with an adenomatous polymp

this progresses through the adenoma-carcinoma sequence with two main genetic pathways - APC/beta catenin and microsatellite instaiblity

additional mutations arise as cancer progresses

Question 6

Describe the morphology of colorectal cancer.

Answer 6

Can occur anywhere in the colon.

vary by morphology: can be a large fungating exophytic mass or a deeply penetrating, ulcerated tumor, or an obstructive annular lesions

those associated with MIN are usually on the right side

Question 7

Describe the clinical presentaiton of colon cancer.

Answer 7

Usually presents in the elderly with peak ages at 60-70

often insidious onset - can present with cramping, LLQ pain, changes in bowel habits and occult bleeding

some with fatigue and weakness from iron deficiency anemia

Question 8

Describe screening and prevention strategies for colorectal cancer.

Answer 8

colonoscopy every 10 years is gold standard

if polyps are found on screening, rescreening interval may be shortened to 3-5 years

other options are stool DNA tests to check fo rmethylation markers on promoter genes, KRAS mutations and beta-actin (a reference gene for DNA quantity)

Also Fecal immunochemical test for hemoglobin

Question 9

Describe the rationale for mismatch repair protein testing in CRC.

Answer 9

Using the revised bethesda criteria in selecting which patients to screen may miss up to 25% of patients with HNPCC, so it makes sense to just test every CRC patient for it

Question 10

Describe the rationale for KRAS testine in colon cancer.

Answer 10

EGFR monoclonal antibodies can be used to blocked growth factor binding to inhibit downstream signaling

mutations in KRAS lead to activation of the signalling pathway regalrdess of whether EGFR is binding or not - so the monoconal antibodies wouldn’t work

Question 11

Describe the most common location for small bowel adenocarcinoma.

Answer 11

50% occur in the duodenum - espeically at the ampulla of vater

Question 12

What are the risk factors for small bowel adenocarcinoma?

Answer 12

FAP, Crohn’s disease and celiac disease

Question 13

Describe presentaions of GI tract neuroendocrine tumors arising in the small bowel.

Answer 13

small bowel is the most common location! Especially the ileum

can be functional with zollinger-ellison syndrome

otherwise if they’re non-functional, presentation is usually fague with crampy abdominal pian, nausea, vomiting and weight loss

those in the ileum and jejunum are often over 2 cm in size and already show transmural invasion with metastases at the time of diagnosis. Thus, many patients present with caricnoid syndrome

Question 14

Describe the presentation of a GI tract neuroendocrine tumor arising in the colon.

Answer 14

rare - often present as bulky, right sided high grade neuroendocrine carcinomas with similar morphology to that of small cell carcinoma of the lung

Question 15

Describe the presentation of a GI tract neuroendocrine tumor arising in the rectum

Answer 15

more common than colonic

typically present as polyps usually less than 1 cm. favorable prognosis

Question 16

Describe melanosis coli

Answer 16

when the colon mucosa exhibits a brown mucosa due to deposition of lipofuscin-like pigemtns in mucosal macrophages

can be associated with use of anthraceneline laxatives

Question 17

Describe lymphomatosis polyposis

Answer 17

It’s mantle cell lymphoma of the bowel

Question 18

Describe the pathogenesis of acute appendicitis

Answer 18

acute inflammation of at least the muscularis propria of the appendix

advanced cases with suppurative inflammation and gangrenous necrosis

Question 19

Describe the morphologic findings of acute appendicitis

Answer 19

outer aspects growwly with thick purulent coating and marked hyperemia of the serosa

increased diameter of the appendix

you get massive inflammation with neutrophilia

Question 20

Describe the clinical presentation of acute appendiciis

Answer 20

periumbilical pain that ultimately localizes to the right lower quadrant, with adbdominal tenderness on examination over McBurney’s Point

Nausea and vomiting follow the development of the abdominal pain

often with elevated WBC with neutrophlia

Question 21

What are some helpful diagnostic tests for acute appendicitis

Answer 21

imagine with US or CT

Question 22

What are the potential complications of acute appendicitis

Answer 22

perforation with periappendiceal abscess, pyelophlebitis, portal venous thrombosis, liver abscess, bacteremia, sepsis and death

Question 23

Describe the typical morphology of appendiceal carcinoma

Answer 23

they are mucinous - typically called appendiceal mucinous tumors - can range from low to high grade

Question 24

Describe the typical morphology of pseudomyxoma peritonei

Answer 24

it’s a gross descriptive term for the presence of abdunant mucinous material on the peritoneal surface

Question 25

Define and describe anal hemorrhoids

Answer 25

ectasia of the hemorrhoidal venous plexus due to persistently elevated venous pressure

external = below pectinate line and due to dilation of the inferior rectal vessles
internal = above the pectinate line due to dilation of the superior rectal vessels

causes: straining, venous stasis of pregnancy

Question 26

Define and describe anal fissures

Answer 26

linear separation of the tissues of the anal canal extending through the mucosa

most are posterirly located - typically caused by firm bowel movements

Question 27

Define and describe an anal fistula

Answer 27

when a fistula tract goesf rom the anus to the skin, or soft tissue

most due to intersphincteric abscess arising in the anal duct, but can be caused by trauma, crohn’s disease and straining

Question 28

Define and describe rectal prolapse

Answer 28

intussusception of the rectum through the anus due to weak rectal support

associated with straining

Question 29

Define and describe a condyloma accuminatum.

Answer 29

it’s an anogenital wart - polypoid, HPV-associated

Question 30

What is an anal intraepithelial neoplasia (AIN)?

Answer 30

This describes various degress of premalignant squamous dysplasia of the anal canal

similar in concept to cervical intraepithelial neoplasia on PAPs.

all associated with HPV as a sexually transmitted disease

Question 31

Describe the most common type of anal carcinoma

Answer 31

most common type is squamous cell (either keratinixing or non-kearatinizing of basaloid type)

Question 32

What’s the most important risk factor for anal carcinoma?

Answer 32

HPV 16 or HPV 18

Question 33

What is the most common tumor of the appendix?

Answer 33

appendiceal neuroendocrine tumor (carcinoid tumor)

small non-functioning tumor measure less than 1 cm in the tip of the appendix. considered benign and simple appendectomt is ucrvative. Some can be higher grade and may results in metastasis and carcinoid syndrome.