Small Intestine and Colon Pathology #3 - Nelson

Question 1

What are the features of Gardner’s syndrome?

Answer 1

• In addition to FAP (with the APC mutation), patients develop:
  
  • desmoid tumors
  • osteomas
  • epidermal cysts
  • dental abnormalities
  • thyroid tumors

Question 2

What are the features of Turcot syndrome?

Answer 2

• Coexistence of a hereditary colon cancer syndrome along with CNS tumors.
• Some patients have FAP (with the APC mutation) and develop medulloblastoma.
• Other patients have mutations associated with HNPCC (DNA mismatch repair gene mutation)
  
  • prone to develop glioblastoma multiforme.

Question 3

What is the pathogenesis of colorectal cancer?

Answer 3

• Loss of one normal copy of the tumor suppressor gene APC occurs early.
• Individuals born with one mutant allele (as in FAP) are therefore at increased risk of developing colon cancer.
• Alternatively, inactivation of APC in colonic epithelium may occur later in life (sporadic cases).
  
  • This is the “first hit”
• The loss of the intact second copy of APC follows (“second hit”).
• Other changes, including mutation of KRAS, losses at 18q21 involving SMAD2 and SMAD4, and inactivation of the tumor suppressor gene TP53, lead to the emergence of carcinoma, in which further mutations occur.

Question 4

What is the morphology behind colorectal cancer?

Answer 4

• variable gross morphology, such as:
  
  • a large fungating, exophytic mass, as a deeply penetrating, ulcerated tumor, or as an obstructive annular lesion.
  • Right sided tumors are rarely obstructive, as opposed to left sided tumors which can form “napkin ring” lesions that produce narrowing and obstruction.

Question 5

What is the clinical presentation of colorectal cancer?

Answer 5

• Symptoms may develop insidiously over a long period of time.
• Patients with left sided tumors may present with cramping, left lower quadrant discomfort, changes in bowel habits (constipation, diarrhea), and occult bleeding.
• Patients with cecal and right sided tumors may present with fatigue and weakness due to iron deficiency anemia as a result of the occult bleeding

Question 6

What is the rationale for mismatch repair protein testing and KRAS testing in colon cancer?

Answer 6

• Mutations in the downstream signaling cascade (such as mutated KRAS) leads to activation of the signaling pathway, regardless of the monoclonal antibody.
• KRAS mutations are found in 40% of CRC.
• to detect microsatellite instability or loss of MMR proteins in the tumor tissue

Question 7

What is the most common location of small bowel adenocarcinoma?

Answer 7

Approximately 50% occur in the duodenum, especially at the ampulla of Vater.

Question 8

What are the risk factors for small bowel adenocarcinoma?

Answer 8

• FAP
• Crohn’s disease (arising from dysplasia, often in the ileum)
• Celiac disease.

Question 9

What are the various typical presentations of GI tract neuroendocrine tumors (i.e. those arising in small bowel, appendix, colon, and rectum)?

Answer 9

• Stomach
  
  • gastritis, ulcer
  • histamine, somatostatin, serotonin
• Duodenum
  
  • peptic ulcer, biliary obstruction, abdominal pain
  • gastrin, somatostatin, CCK
• Jejunum and Ileum
  
  • asymptomatic, obstruction, metastatic disease
  • serotonin, substance P, polypeptide Y,
• Appendix
  
  • asymptomatic, incidental
  • serotonin, polypeptide Y
• Colorectum
  
  • abdominal pain, weight loss, incidental
  • serotonin, polypeptide Y

Question 10

What is melanosis coli (describe it)?

Answer 10

• mucosa exhibits brown mucosa
  
  • due to deposition of lipofuscin-like pigment in mucosal macrophages
• can be associated with the use of anthraceneline laxatives

Question 11

What is lymphomatosis polyposis (describe it)?

Answer 11

• tumor cells show irregularity of their nuclear contours
  
  • often seen in mantle cell lymphoma
• The lymphomatous polyposis pattern can be seen in other lymphomas such as follicular lymphoma.

Question 12

What is the pathogenesis of of acute appendicitis?

Answer 12

• Etiology is thought to be related to increased intraluminal pressure that compromises venous outflow.
• Ischemic injury and stasis of luminal contents
  
  • which lead to bacterial overgrowth
  • triggers an acute inflammatory response with edema and neutrophilic infiltration
• These sequences of events can be initiated by obstruction, either by a fecalith, which is a stone-like mass of hard stool, or by lymphoid hyperplasia (following viral infection in children).

Question 13

What are the morphologic findings in of acute appendicitis?

Answer 13

• acute inflammation involving at least the muscularis propria
• thick purulent coating is often seen together with marked hyperemia of the serosa
• increased diameter
• massive inflammatory infiltrate, extensive ulceration, and hemorrhage

Question 14

What is the clinical presentation of acute appendicitis?

Answer 14

• Periumbilical pain that ultimately localizes in the right lower quadrant
• Abdominal tenderness on examination over “McBurney’s Point” (located two thirds of the distance from the umbilicus to the right anterior superior iliac spine)
• Nausea and vomiting follows the development of abdominal pain.
• Elevated white count with neutrophilia is seen in 80% of patients.

Question 15

What are the helpful diagnostic tests for acute appendicitis?

Answer 15

• Elevated white count with neutrophilia
• Imaging studies
  
  • US
  • CT scan

Question 16

What are the potential complications of acute appendicitis?

Answer 16

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

Question 17

What is the typical morphology of appendiceal carcinoma?

Answer 17

• small non-functioning tumor
  
  • measuring less than 1 cm
  • often located in the tip of the appendix
  • when measuring <1 cm and confined to the appendix without invasion into the mesoappendix,→ benign
    
    • simple appendectomy is almost always curative

Question 18

What is the typical morphology of pseudomyxoma peritonei?

Answer 18

• abundant mucinous material on the peritoneal surfaces
• well-differentiated glandular epithelium in pools of mucin

Question 19

What malignancy typically causes pseudomyxoma peritonei?

Answer 19

almost all cases are due to appendiceal mucinous tumors

Question 20

Define and describe anal hemorrhoids.

Answer 20

• ectasia (dilation) of the hemorrhoidal (rectal) venous plexus, due to persistently elevated venous pressure
  
  • external → located below the pectinate line and are due to dilation of the inferior rectal vessels
  • internal → located above the pectinate line and are due to dilation of the superior rectal vessels
• present with pain and rectal bleeding, particularly bright red blood seen on toilet paper

Question 21

Define and describe anal fissure.

Answer 21

• Linear separation of the tissues of the anal canal extending through the mucosa
  
  • Most (90%) are posteriorly located, typically caused by firm bowel movements

Question 22

Define and describe anal and fistula?

Answer 22

• Fistula tract in anus:
  
  • may lead to the skin, or end blindly in perianal soft tissue
• Most cases are due to an intersphincteric abscess arising in an anal duct.
  
  • Can be caused by trauma, Crohn’s disease, or ulcerative colitis.

Question 23

Define and describe rectal prolapse.

Answer 23

• Intussusception of the rectum through the anus
  
  • due to weak rectal support.
• Common in the elderly, associated with straining at stool.

Question 24

Define and describe condyloma accuminatum.

Answer 24

• Anogenital wart
  
  • polypoid wart
• HPV associated

Question 25

Define and describe anal intraepithelial neoplasia (AIN).

Answer 25

• various degrees of premalignant squamous dysplasia of the anal canal
  
  • similar to cervical intraepithelial neoplasia
  • lesions are graded based on the microscopic and cytologic atypia present
    
    • grades correspond to mild squamous dysplasia, moderate squamous dysplasia, and severe squamous dysplasia/carcinoma in situ

Question 26

What is the most common type and most important risk factor for anal carcinoma?

Answer 26

Most common type is squamous cell carcinoma (either keratinizing, non-keratinizing, or basaloid type)

Most of the squamous cell carcinomas are associated with HPV, particularly HPV type 16 or 18.