GI Pathology - Colon Flashcards
What symptoms characterize IBS?
How is IBS diagnosed?
What is used to divide it into sub-types?
Chronic, relapsing abdominal pain, bloating and changed in bowel habits.
It is a clinical and functional diagnosis (the gross and microscopic eval. is normal).
The Rome criteria
What is the pathogenesis of IBS?
It is poorly defined, but there is clear interplay between psychologic stressors, diet, perturbation of gut biome, increased enteric response to gut stimuli and abnormal GI motility.
What is the prevalence of IBS?
What age/sex is most common?
5-10%
F>M; 20-40
Crohn disease vs. Ulcerative colitis macroscopic features
Location and distrubution
Strictures?
Wall appearance
CD - ileum and colon; skip lesions
- yes strictures
- thick wall
UC - colon only; diffuse
- rarely strictures
- thin wall
Crohn disease microscopic features
Inflammation Pseudopolyps Ulcers Lymphoid reaction Fibrosis Serositis Granulomas Fistulae/sinuses
Inflammation - transmural Pseudopolyps - moderate Ulcers - deep (knife-like) Lymphoid reaction - marked Fibrosis - marked Serositis - marked Granulomas - yes (approx. 35%) Fistulae/sinuses - yes
Ulcerative colitis microscopic features
Inflammation Pseudopolyps Ulcers Lymphoid reaction Fibrosis Serositis Granulomas Fistulae/sinuses
Inflammation - limited to mucosa Pseudopolyps - marked Ulcers - superficial, broad-based Lymphoid reaction - moderate Fibrosis - mild to none Serositis - mild to none Granulomas - none Fistulae/sinuses - none
Crohn disease
Perianal fistula Fat/vitamin malabsorption Malignant potential Recurrence after surgery Toxic megacolon
Perianal fistula - yes (in colonic dz) Fat/vitamin malabsorption - yes Malignant potential - yes (if colonic involvement) Recurrence after surgery - commonly Toxic megacolon - no
Ulcerative colitis
Perianal fistula Fat/vitamin malabsorption Malignant potential Recurrence after surgery Toxic megacolon
Perianal fistula - no Fat/vitamin malabsorption - no Malignant potential - yes Recurrence after surgery - no Toxic megacolon - yes
In which IBD is smoking protective vs. a risk factor?
Protective: UC
Risk factor: CD
In which IBD is perianal disease common?
In which IBD is rectal involvement common?
Perianal: CD
Rectal involvement: UC
What are the symptoms of Crohn disease?
Abdominal pain, diarrhea, nausea, vomiting and weight loss; rarely there are perforating/obstructive symptoms
What are the symptoms of Ulcerative colitis?
Abdominal pain, rectal bleeding, and bloody diarrhea. Can be relasping.
What age is most common to develop IBD? Which form is more common in females?
What race is most common?
What countries are most common?
Teens/early 20s; UC more common infemales, wit a second peak in 6-7th decade
Caucasians (3-5x more common in Ashkenazi Jews in US)
North America, Europe, Australia
Which systems/organs have some extra-intestinal manifestations of IBD? (8)
Eyes Kidneys Skin Mouth Liver Biliary tree Joints Circulation
What are the histologic features of colonic mucosa of UC?
Red and granular, or have broad-based ulcers.
What are pseudopolyps and mucosal bridges in UC?
Pseudopolyps are isolated islands of regenrating mucosa that bulge into the lumen. The tips of the pseudopolyps may fuse to create mucosal bridges.
As opposed to CD, what is the appearance of the mucosa in UC?
There is no mucosal thickening in UC; the serosal surface is normal and strictures don’t occur.
What is the most feared long-term complication of UC or colonic CD?
Development of neoplasia
What are 3 factors that increase the risk (in UC or colonic CD) of developing neoplasia?
Duration of disease: risk increases 8-10 years after disease onset.
Extent of disease: pts. with pancolitis are at greater risk than those with only left-sided disease.
Nature of the inflammatory response: presence of neutrophils increases risk.
What are 3 acquired conditions that predispose patients to cancer (in UC or colonic CD)?
Chronic inflammation
Precursor lesions
Immune defiency
What is the goal of surveillance of colitis-associated neoplasia?
To identify dysplastic epithelium, which is the precursor to colitis-associated carcinoma.
What is the clinical setting where you might see diversion colitis?
What is the most striking feature microscopically?
What cell-types might be abundant? (4)
What may promote mucosal recovery?
It may develop post-op due to diversion - most commonly in patients with UC.
Numerous mucosal lymphoid follicles
Increased numbers of:
- lamina propria lymphocytes
- monocytes
- macrophages
- plasma cells
Enemas containing SCFA can promote mucosal recovery
What 2 entities are included in microscopic colitis?
What is the cause?
What is the presentation?
What age/sex is most common?
What are the histological features? (3)
Collagenous colitis and lymphocytic colitis
Idiopathic
Chronic, non-bloody diarrhea without weight loss
Middle-aged to older women
Dense subepithelial collagen layer
Increased numbers of intraepithelial lymphocytes
Mixed inflammatory infiltrate within the lamina propria
Lymphocytic colitis shows a strong association with what other disease?
Celiac disease
AI dz - Graves dz, RA, autoimmune gastritis, etc.
When does graft vs. host disease colitis occur?
What is the most common histological finding?
What is the presentation?
Post hematopoeitc stem cell transplantation
Epithelial apoptosis of crypt cells
Watery diarrhea, which may become bloody in severe cases
Colonic diverticular disease is most common from what ages?
What is the prevalence vs. the percent that manifest symptoms?
What are the symptoms?
30-60 y/o
50% prevalence, but only 20% of those manifest symptoms
Intermittent cramping, lower abdominal discomfort, constipation, distension or sensation of being unable to clear rectum.
What type of polyp is most common?
Where are they found?
At what age?
What must be ruled-out?
Hyperplastic polyps
Left colon
6-7th decade
R/O sessile serrated adenoma
Inflammatory polyps are part of what syndrome?
This syndrome has what triad?
Solitary rectal ulcer syndrome (SRUS)
Rectal bleeding, mucus discharge and naterior rectal wall location
Hamartomatous polyps occur how?
What are the 2 types/syndromes?
Germline mutations in what kinds of genes may be associated?
These polyps are associated with an increased risk for…
What may suggest presence of these polyps?
Sporadically or as components of various genetically determined or acquired syndromes.
Juvenile polyps and Peutz-Jeghers syndrome
TSGs or proto-oncogenes
Cancer - either within the polyps or at other sites
Extra-intestinal manifestations or family members also affected
Juvenile polyps occur how?
What age?
What is the location they appear?
Is dysplasia common?
What cancers may ensue as a result?
What are prominent extra-GI manifestations?
Sporadically (retention polyps) or syndromic (AD - 1/100K)
Under 5 y/o (infantile form is severe)
Rectum (SI and stomach in syndromic)
It is rare in sporadic, but common in syndromic
Gastric, SI, colonic, pancreatic adenocarcinoma
Congenital anomalies, digital clubbing
Peutz-Jeghers syndrome is what kind of inheritance?
At what age does it present?
What GI lesions may ensue?
What are extra-GI manifestations?
What gene pathway is mutated?
AD (rare - 1/25-100K)
10-15 y/o (approx 11 y/o)
Multiple hamartomatous polyps (intussusception)
Pigmented macules: increase risk for cancer in colon, breast, lung, pancreas and thyroid
LOF mutations in STK11 (in 50% of pts.)
Adenomatous polyps definition:
How many people have them? Which sex is more common?
What are the 3 morphologic types?
Adenomas that are intraepithelial neoplasms that range from small (ofte pedunculated) polyps to large sessile lesions.
30% of pts. by age 60 y/o; M>F
Tubular
Tubulovillous
Villous
Familial adenomatous polyposis is associated with which gene?
How many polyps exist as a teen?
What is the risk of cancer?
What is detected at birth that may cue a diagnosis?
APC gene
100-1000 polyps by teenage
Colorectal adenocarcinoma develops in 100% of cases that are untreated, often prior to 30 y/o, but always by age 50 y/o
Congenital hypertrophy of retinal pigment epithelium
What is the peak age associated with colonic adenocarcinoma? In what case would diagnosis at a younger age be possible?
60-70 y/o. It is rare under 50 y/o unless HNPCC.
What diet is associated with an increased rick for colon adenocarcinoma?
Low fiber
High refined carbs
High fat
What has a protective effect in the development of colon adenocarcinoma?
NSAIDs or aspirin
What are the 2 major pathways of colon adenocarcinoma development and how common is each?
Adenoma-carcinoma pathway (70-80%)
Microsatellite instability pathway - MSI (10-15%)
What variant of FAP/polyposis syndrome is associated with congenital RPE hypertrophy?
Which variant is associated with osteomas, thyroid and desmoid tumors, skin cysts?
Which variant is associated with medulloblastoma and glioblastoma?
Congenital RPE hypertrophy - classic FAP
Osteomas, thyroid and desmoid tumors, skin cysts - Gardner syndrome
Medulloblastoma and glioblastoma - Turcot syndrome
What are the age of presentation of the following:
Classic FAP Attenuated FAP Gardner syndrome Turcot syndrome MYH-associated
Classic FAP: 10-15 y/o Attenuated FAP: 40-50 y/o Gardner syndrome: 10-15 y/o Turcot syndrome: 10-15 y/o MYH-associated: 30-50 y/o
Familial adenomatous polyposis
Molecular defect Target gene Transmission (heredity) Predominant sites Histology
Molecular defect: APC/Wnt pathway Target gene: APC Transmission (heredity): AD Predominant sites: none Histology: tubular and villous; typical adenocarcinoma
Hereditary non-polyposis colorectal cancer (HNPCC)
Molecular defect Target gene Transmission (heredity) Predominant sites Histology
Molecular defect; DNA mismatch repair Target gene: MSH2, MSH1 Transmission (heredity): AD Predominant sites: right side Histology: sessile serrated; mucinous adenocarcinoma
Sporadic colon cancer (70-80%)
Molecular defect Target gene Transmission (heredity) Predominant sites Histology
Molecular defect: APC/Wnt pathway Target gene: APC Transmission (heredity): none Predominant sites: left side Histology: tubular, villous; typical adenocarcinoma
What is = to Lynch syndrome?
It is the most common…
When do patients present?
HNPCC
Most common syndromic form of colorectal cancer (2-4% of all colorectal cancers)
Earlier than other forms
What is the morphology of tumors in the proximal colon?
What is the morphology in the distal colon?
Proximal colon - polypoid, exophytic masses
Distal colon - tend to annular lesions
What are symptoms of right-sided vs. left-sided colon cancers?
Right-sided: fatigue and weakness due to iron deficiency anemia
Left-sided: occult bleeding, changes in bowel habits, cramping, LLQ discomfort
Is a screening colonoscopy useful for staging?
What are the 2 most important factors of colorectal cancers?
What is the survival rate at 5 years?
No
Depth of invasion and presence of LN mets
65% at 5 yrs
