Nelson: Path Small Intestine, Colon cont. Flashcards
Where do inflammatory polyps occur?
ANYWHERE in GI tract
What is an inflammatory pseudopolyp?
When the area around the “polyp” is ulcerated so the remaining mucosa appears to be a polyp
Most common location for a juvenile (retention) polyp?
Rectum
What mutations may a patient with juvenile polyposis have?
What are they at increased risk of?
SMAD4-encodes a cytoplasmic intermediate of the TGF-Beta signaling pathway) or BMPRIA (a kinase)
Increased risk of adenocarcinoma
Multiple hamartomatous polyps and mucucutaneous hyperpigmentation makes you think of….?
Peutz-Jeghers syndrome (PJS)
Most common location for Peutz-Jeghers polyps?
Small bowel
What mutation may patients with PJS have?
Loss of function mutations of STK11 tumor suppressor
Patients with PJS are at increased risk for what?
GI adenocarcinomas as well as malignancies of other organs such as breast, lung, pancreas, gonads, uterus
*Note: GI tract adenocarcinomas can arise independently of the hamartomatous polyps
How may patients with PJS present in childhood?
GI bleeding
Intussusception
What are the Peutz-Jeghers polyps like?
Smooth muscle pattern, frequently pedunculated.
Most common type of adult colonic polyp?
Hyperplastic polyps
Where are most hyperplastic polyps?
Left colon (rectum)
____________ are neoplastic polyps that are more common in the colon but when they occure in the small bowel they are usually in the ________ of the duodenum.
Adenomas
Ampulla
What two types of proliferation can occur in adenomas?
Tubular
Villous
Adenomas are benign or malignant?
Can be precursors to what?
Benign
Adenocarcinoma
What should be done when an adenoma is discovered?
NEEDS TO BE COMPLETELY REMOVED
Primary location for sessile serrated polyps?
right colon
What chance occurs in a sessile serrated polyp for it to be considered to have low grade dysplasia?
Adenomatous type epithelial change! Dysplastic glandular proliferation
Describe the inheritance of Familial Adenomatosis Polyposis (FAP).
Autosomal dominant
Mutation in the APC tumor suppressor gene
Patients inherit a single APC mutation and then acquire a second –> resulting in adenomas
What is the risk of colorectal adenocarcinoma in patients with FAP?
100 % risk
How is FAP diagnosed?
Clinical presentation: >100 polyps, detection of germline mutations of the APC gene
What can be seen on the ophthalmic exam in many patients with FAP?
Congenital hypertrophy of the pigmented retinal epithelium
Gardner’s syndrome?
APC mutation ------- FAP Desmoid tumors Osteomas Epidermal cysts Dental abnormalities Thyroid tumors
Turcot syndrome?
Coexistence of a hereditary colon cancer syndrome along with CNS tumors. Some patients have FAP (w/ APC mutation) and develop medulloblastoma and other patients have a DNA mismatch repair gene mutation as in HNPCC and are prone to develop GBM.
HNPCC (Lynch Syndrome)?
Mutations in the genes that encode enzymatic mismatch repair proteins responsible for the detection, excision, and repair of errors that occur during DNA replication.
Patients with HNPCC inherit one defective allele and one normal allele. When the second allele is lost through an acquired mutation or epigenetic silencing, the defect in these mismatch repair enzymes (MLH1, MSH2, MSH6, PMS2) leads to the accumulation of mutations, mostly in the regions containing short repeating DNA sequences known as microsatellite DNA.
How does HNPPC affect the colon?
These patients do not have an increased number of adenomas but when adenomas do occur, they have a GREATLY INCREASED risk of MALIGNANT TRANSFORMATION
*risk of colon cancer is 80-90 %
Sx of colorectal adenocarcinoma?
May develop insidiously over a long period of time.
Left sided tumors: cramping, left lower quadrant discomfort, changes in bowel habits (constipation or diarrhea) and occult bleeding.
Right sided tumors: fatigue, weakness due to iron deficiency anemia as a result of occult bleeding)
Dx of colorectal adenocarcinoma?
Colonoscopy with tissue biopsy
Primary tx of colorectal adenocarcinoma?
surgical resection + resection of regional lymph nodes
Key factors that affect prognosis in colorectal adenocarcinoma?
Depth of invasion
Presence or absence of lymph nodes and hematogenous metastases
Poorly differentiated, mucinous, signet ring cells….poorer prognosis
What is the rationale for using KRAS mutation analysis?
Mutations are found in 40 % of CRC
KRAS mutations lead EGFR cascade signaling regardless of the monoclonal antibody that is present. Signaling cannot be prevented.
Most common location for small bowel adenocarcinoma?
Ampulla of Vater of duodenum
Risk factors for small bowel adenocarcinoma?
FAP
Crohn Disease
Celiac disease
Most common location for neuroendocrine tumors of GI tract?
Small bowel-Ileum
Clinical presentation of non-functioning small bowel neuroendocrine tumors?
Vague…crampy abdominal pain, nausea, vomiting, weight loss
How do patients with small bowel neuroendocrine tumors of the ileum or jejunum often present?
With transmural invasion and metastases at the time of dx…may have carcinoid syndrome
How do colonic neuroendocrine tumors present?
Bulky, right-sided high grade neuroendocrine carcinomas
Morphology similar to SCC of lung!
*rare
Location for a neuroendocrine tumor that is more common than colonic tumor, presents as polyps, and has a favorable prognosis?
Rectum!
Melanosis coli
Deposition of lipofuscin-like pigment in mucosal macrophages….can be associated with use of anthracene laxatives
What does a lymphomatous polyposis pattern of mantle cell lymphoma of the large bowel look like?
Nuclear contours show irregularity!
Definition of appendicitis
Acute inflammation involving at least the muscularis propria
Etiology of appendicitis?
Increased intraluminal pressure compromises venous outflow….ischemic injury and stasis of luminal contents…bacterial overgrowth…acute inflammation and neutrophil infiltration
Initiated by obstruction (fecalith) or lymphoid hyperplasia
What generally comes first in appendicitis? what follows?
Abdominal pain develops THEN nausea and vomiting occurs
What is pseudomyxoma peritonei?
Gross descriptive term for the presence of abundant mucinous material on the peritoneal surfaces. Almost all cases are due to appendiceal mucinous tumors.
Difference between low and high grade mucinous adenocarcinoma?
Low grade: pools of mucin are virtually acellular
High grade: pools of mucin have high cellularity
Anal hemorrhoids
Cause: persistently elevated venous pressure causes ectasia of the rectal venous plexus
What is dilated in external hemorrhoids?
Inferior rectal vessels
*Below pectinate line
What is dilated in internal hemorrhoids?
Superior rectal vessels
Common causes of hemorrhoids?
straining from consitapation, venous stasis of pregnancy
Anal fissure
Linear separation of tissues of anal canal extending through mucosa (most posteriorly located and caused by firm bowel movements)
Anal fistula
Usually due to an intersphincteric abscess arising in an anal duct…can be caused by trauma, Crohn’s disease or ulcerative colitis
Rectal prolapse
intussusception of rectum through anus due to weak rectal support
*associated with straining at stool
Condyloma accuminatum
anogenital polyploid wart
HPV associated
Anal intraepithelial neoplasia (AIN).
Various degrees of premalignant squamous dysplasia of the anal canal and similar to cervical intraepithelial neoplasia.
Associated with HPV infection…usually sexually transmitted
Most common type of anal carcinoma?
Squamous cell carcinoma
Most important risk factor for anal carcinoma?
HPV! Particularly HPV 16 or 18
