Chapter 17 part 8 Flashcards
Crohn Disease Morphology–areas involved
- involves small intestine alone in 40% of cases
- small intestine and colon in 30%
- other areas uncommon
Crohns disease–Gross Morphology
- Skip lesions
- Punched out mucosal aphthous ulcers
- cobblestone appearance
Skip lesions in Crohns Disease
-separate, sharply delineated disease areas with granular and inflamed serosa and adherent “creeping” mesenteric fat; the bowel wall is thick and rubbery and often strictured
Punched out mucosal pathos ulcers in Crohn’s disease
-coalescing into axially oriented serpentine ulcers
Cobblestone appearance in Crohn’s disease
- Sparing of interspersed mucosa gives a cobblestone appearance with diseased tissue depressed relative to normal mucosa
- fissures and fistula tracts are also common
Microscopic morphology of Crohn’s Disease
- Mucosal inflammation and ulceration with intraepithelial neutrophils and crypt abscesses
- Chronic mucosal damage with villus blunting, atrophy, pseudopyloric or Paneth cell metaplasia and architectural disarray
- Transmural inflammation with lymphoid aggregates in submucosa, muscle wall, and subserosal fat
- Noncaseating granulomas throughout the gut, even in uninvolved segments (but only seen in 35% of patients)
S/S of CD
- intermittent attacks of diarrhea, fever, and abdominal pain
- asymptomatic periods last for weeks to months
Extensive CD can lead to?
-malabsorption and malnutrition, loss of albumin (protein-losing enteropathy), iron-losing enteropathy, iron deficiency anemia and/or vitamin B12 deficiency
Tx for Crohn’s Disease
- Fibrotic strictures or fistulas to adjacent viscera, abdominal and perineal skin, bladder or vagina require surgical resection
- disease often recurs at the anastomosis with 40% of patients requiring additional surgery within a decade
Extra intestinal manifestation for Crohn’s Disease
- migratory polyarthritis
- sacroilitis
- ankylosing spondylitis
- erythema nodosum
- uveitis
- cholangitis
- amyloidosis
Crohn’s disease increases the risk for?
-colonic adenocarcinoma in patients with long-standing colon involvement
Potent therapeutic option for Crohn’s disease
-Anti-TNF Abs!!
Ulcerative Colitis
- disease of continuity with no skip lesions
- involves rectum and extending proximally in retrograde fashion to involve the entire colon (pan colitis)
- distal ileum may also show some inflammation (backwash ileitis)
Gross morphology of Ulcerative colitis
- Mucosa is reddened, granular, and friable with inflammatory pseudo polyps and easy bleeding
- can be extensive ulceration or atrophic and flattened mucosa
Microscopic morphology of Ulcerative colitis
- Mucosal inflammation is similar to CD but generally limited to mucosa
- crypt abscesses, ulceration, chronic mucosal damage, glandular architectural distortion, and atrophy but no fissures, aphthous ulcers, or granulomas
Clinical features of Ulcerative colitis
- present with intermittent attacks of blood mucoid diarrhea and abdominal pain that can persist for days to months before subsiding
- half have mild disease, but most will relapse within 10 years and up to 30% require colectomy within 3 years to control symptoms
Extra intestinal manifestations of Ulcerative colitis
- migratory polyarthritis
- sacroiliitis
- ankylosing spondylitis
- uveitis
- cholangitis (up to 7.5% of patients) and skin lesions
UC increases the risk for?
-colonic adenocarcinoma
Colitis associated Neoplasia–risk of malignancy in IBD
- Increases sharply 8-10 yrs after disease onset
- greater with pan colitis vs. left sided only disease
- Increases with severity and duration of active inflammation
Patients with long standing disease of UC are followed by
- biopsy surveillance
- dysplasia is classified histologically as low or high grade and can be multifocal
Other causes of chronic colitis
- Diversion colitis
- Microscopic colitis
Diversion colitis
- occurs in blind distal colonic segment created after surgery diverts fecal stream to an ostomy site
- lack of short-chain fatty acids and other nutrients, and changes in the flora
- mucosal erythema and friability with lymphoplasmacytic inflammation and a characteristic lymphoid follicular hyperplasia
Microscopic Colitis
- middle aged women
- present as chronic watery diarrhea with abdominal pain
- Endoscopic findings are grossly normal (“microscopic”)
- 2 forms: Collagenous colitis and Lymphocytic colitis
Microscopic Colitis–Collagenous colitis
-dense submucosal bandlike collagen with mixed inflammation in lamina propria
Microscopic Colitis–Lymphocytic colitis
- prominent intraepithelial infiltrate of lymphocytes without the sandlike collagen
- associated with autoimmune diseases and sprue
Graft vs. Host Disease
-occurs following hematopoietic stem cell transplantation due to donor T cells targeting Ags on the recipient’s GI epithelial cells
GVHD presentation and hits
- watery diarrhea but may become bloody in severe cases
- small bowel and colon are involved in most cases
- most common histo finding: Epithelial apoptosis, particularly of crypt cells!!!
Sigmoid Diverticular Disease
-acquired colonic pseudodiverticular outpouchings (diverticulosis)=uncommon in pts younger than age 30 but occur in 50% of Western population older than 60
Pathogenesis of Sigmoid Diverticular Disease
-Focal bowel wall weakness (at sites of penetrating blood vessels) allows mucosal out pouching when there is increased intraluminal pressure (e.g., with constipation and exaggerated peristaltic contractions)
Morphology of Sigmoid Diverticular disease
- Multiple flashlike outpouchings, 0.5 to 1 cm in diameter=more common in distal colon
- occur where vasculature penetrates the inner circular layer of muscular propria at taeniae coli
- diverticulum wall is lined by mucosa and submucosa without significant muscular propria, although muscular bw diverticula is hypertrophic
- Obstruction of diverticula leads to inflammation producing DIVERTICULITIS–can perforate with tissue damage and increased pressure
Clinical features of Sigmoid Diverticular Disease
- Usually asymptomatic but associated with cramping, abdominal discomfort, and constipation
- can result in pericolic abscesses, sinus tracts and peritonitis
- Even without perforation, can cause fibrotic thickening and stricture formation
Polyps
-Masses that protrude into the gut lumen can be pedunculated or sessile and can be non-neoplastic or neoplastic
Types of polyps
- Hyperplastic polyps
- Inflammatory Polyps
- Hamartomatous polyps
- Neoplastic polyps
- Adenomatous polyposis
Hyperplastic polyps
- result from decreased epithelial turnover with delayed shedding
- have no malignant potential
- usually less than 5mm and are composed of well-formed mature, albeit crowded, glands
Inflammatory polyps
- result from recurrent cycles of injury and healing
- see lamina propria fibromuscular hyperplasia, mixed inflammatory cell infiltrates, and mucosal erosion and/or hyperplasia
Hamartomatous polyps
- tumorlike growths of tissues normally present at the site
- occur in setting of many genetic or acquired syndromes:
- Juvenile polyps
- Juvenile polyposis syndrome
- Peutz-Jeghers syndrome
Juvenile polyps
- focal hamartomatous malformations of small intestine and colon mucosa
- most occur in children<5 years and involve rectum
- SINGLE, large (1-3 cm) rounded and pedunculated with mystically dilated glands and abundant lamina propria
Mutations associated with juvenile polyps
-SMAD4 and BMPR1A genes involved in TGF-B signaling
Juvenile polyposis syndrome
- rare autosomal dominant disorder–up to 100 hamartomatous polyps
- may require colectomy to limit bleeding due to polyp ulceration and pulmonary arteriovenous malformations are known extra intestinal manifestations
- also an increased risk o bowel malignancy–30% to 50% will develop adenocarcinoma by age 45
Peutz-Jeghers syndrome
- rare autosomal dominant syndrome
- median age of onset=11
- associated with multiple GI hamartomatous polyps and mucocutaneous hyperpigmentation
Peutz-Jeghers syndrome–genetic associations
-In half of patients, there is a heterozygous LoF mutation in the LKB1/STK11 gene encoding a kinase that regulates cell polarization and growth
What are the polyps like in Peutz-Jeghers syndrome?
- order=small bowel>colon and stomach
- large, pedunculated and lobulated with arborizing smooth muscle surrounding normal abundant glands
- can initiate intussusception
- Hyperpigmentation takes the form of molecules around mouth, eyes, nostrils, buccal mucosa, palms, and genital and perianal regions
Peutz-Jeghers syndrome–pt has increased risk for what?
-several cancers including colon, pancreas, breast, lung, gonads, and uterus
Neoplastic polyps–colonic adenomas
- benign polyp precursors to majority of colorectal carcinomas
- Epithelial dysplasia!!
- 50% incidence by age 50 but majority do NOT progress to malignancy
- Most are clinically silent but large ones can cause anemia and potassium loss causes hypoproteinemic hypokalemia
Neoplastic lesions–risk of malignancy
- correlated to size
- polyps >4cm have 40% risk harboring cancer and severity of dysplasia
Morphology of adenomas
- range from 0.3 to 10 cm
- can be pedunculated or sessile
- Dysplastic changes include hyperplasia, nuclear hyperchromasia and loss of polarity
Adenomas–classification
- classified based on architecture
- tubular, tubulovillous and villous
- have little clinical significance though
Sessile serrated adenomas
- full gland length exhibits serrated architecture; despite malignant potential
- do not have typical dysplastic changes seen in other adenomas
Intramucosal carcinoma
- occurs when dysplastic cells invade lamina propria or muscluaris mucosa
- little metastatic potential because colonic mucosa lacks lymphatic channels
Polyps with invasive adenocarcinoma
-malignant with metastatic potential bc have crossed into submucosa and can access lymphatics
