Pathology Flashcards
Describe these types of non-neoplastic polyps:
- hyperplastic
- hamartomatous
- inflammatory
- lymphoid
Hyperplastic - hyperplasia of glands, most common
classically show a serrated/saw-tooth appearance, usually left-sided
Hamartomatous - sporadic or in Peutz-Jeghers syndrome or juvenile polyposis
Inflammatory - ulcerative colitis and Crohn disease; composed of regenerating intestinal mucosa
Lymphoid - found in children; intestinal mucosa infiltrated with lymphocytes
What are the criteria for determining the malignant potential of adenomatous polyps?
- degree of dysplasia
- villous adenomas more likely to be malignant than tubular
- larger size more likely to be malignant
(4. PATHOMA: sessile/grows against wall more likely to be malignant than pedunculated/grows on a stalk)
Nephrolithiasis in Crohn disease - what type of stones? Mechanism?
Calcium oxalate stones
Impaired bile acid absorption in the terminal ileum leads to loss of bile acids in the feces and subsequent fat malabsorption. Excess lipids in the lumen bind calcium ions and these soap complexes are then also excreted in feces. Oxalate normally binds calcium ions to form an unabsorbable complex for excretion, but with calcium bound to lipids, free oxalate is absorbed to form stones.
Thus oxalate normally is NOT absorbed much, but the inflammation associated with Crohn’s increases the uptake of oxalate, leading to stone formation.
IBD with:
- crypt abscesses filled with neutrophils?
- lymphoid aggregates with granulomas?
Location of each?
Extent of inflammation?
Which is associated with P-ANCA?
Ulcerative colitis = crypt abscesses filled with neutrophils
- begins in rectum and extends proximally up to cecum, continuous
- mucosal and submucosal ulcers
- associated with P-ANCA positivity
Crohn’s disease = lymphoid aggregates with granulomas
- most commonly in terminal ileum (anywhere from mouth to anus), skip lesions
- fill-thickness/wall inflammation with knife-like fissures
What are the layers of the intestinal wall? Where is the myenteric plexus? The submucosal plexus?
Mucosa
Submucosa
Muscularis propria (inner circular and outer longitudinal muscle layers)
Serosa
Myenteric/Auerbach’s plexus is between the inner circular and outer longitudinal muscle layers of the muscularis propria (regulates motility).
Submucosal/Meissner’s plexus is located in the submucosa (regulates blood flow, secretions, and absorption).
How to diagnose Hirschprung’s disease?
Absence of both myenteric and submucosal autonomic plexi.
Rectal suction biopsy (not just standard mucosal biopsy) needed to get a piece of the submucosa, the most superficial layer in which an absence of ganglion cells can be seen.
Want a biopsy from the narrowed area (where absence of ganglion cells will be found) rather than dilated/normal regions.
Alternating constipation and non-bloody diarrhea with fistula?
Crohn’s disease
lesions affect the entire thickness of the bowel wall, creating risk of fistula development (due to wall rupture)
Irritable bowel syndrome (IBS) is NOT associated with fistulas.
Longitudinal GE junction tears in an alcoholic vomiting?
Mallory-Weiss syndrome
due to increased intraabdominal and intraluminal gastric pressure due to abdominal straining (retching or vomiting).
What is a hiatal hernia and what are its associations?
herniation of the upper part of the stomach into the thorax
increased risk for GERD and for Mallory-Weiss syndrome
Celiac disease - what are the lab findings and how is it diagnosed?
Autoantibodies (very sensitive and specific):
- IgA against tissue transglutaminase
- IgA against endomysium
- IgA against gliadin
- IgG: in pts with IgA deficiency (associated with celiac disease), IgG levels useful
Confirmatory diagnosis:
Small intestinal biopsy
- flattening of the mucosa with loss of villi
- chronic inflammatory infiltration of the lamina propria
Most pronounced changes in duodenum and proximal jejunum because higher concentration of gluten in these regions.
What stain is used to identify Tropheryma whippelii in the lamina propria of the small bowel? What does this stain detect?
Period acid-Schiff (PAS) stain detects polysaccharides (glycogen) and mucosubstances (glycoproteins, glycolipids, mucins)
Glycoprotein in the cell walls of T. whippelii colors magenta with PAS.
Epigastric pain that worsens after meals leading to weight loss in pt with HTN, hyperlipidemia, and history or coronary artery disease?
Chronic mesenteric ischemia - generalized atherosclerosis that involves the intestinal arteries
Bowel suffers from diminished blood supply, particularly after meals when there is more demand.
Papulovesicular skin rash and periodic abdominal discomfort/diarrhea? Mechanism?
Dermatitis herpatiformis (small vesicles that occur symmetrically on extensor surfaces that are very pruritic) associated with celiac disease
Immunofluorescence reveals IgA deposits at the tips of the dermal papillae.
Features of colorectal carcinoma associated with ulcerative colitis? What factors increase risk in these pts?
unlike sporadic colorectal cancer, colitis-associated carcinomas:
- more likely to arise from NON-polypoid dysplastic lesions
- multifocal in nature
- develop early p53 mutations and late APC mutations
- higher histological grade
Increased risk with pt history of >10 years and greater extent of colonic involvement (pancolitis)
Carcinoid tumor diagnosis? Treatment?
Increased level of 5-HIAA in urine is diagnostic
Treatment:
- surgical excision of tumor
- for disseminated disease, octreotide (somatostatin analog)
Octreotide acts on somatostatin receptors and inhibits secretion of many hormones and hormone-like substances.
Where is the most common site in the GI for a carcinoid tumor? What tumor marker is used?
When do symptoms of serotonin syndrome begin to manifest?
What are the effects on the heart and why?
small bowel chromogranin positive (neurosecretory granules of tumor cells)
Metastasis of carcinoid tumor to the liver allows serotonin syndrome to manifest by bypassing liver metabolism. In GI, serotonin goes through portal circulation and MAO in liver degrades serotonin to 5-HIAA before getting systemic.
Right-heart valvular fibrosis (increased collagen) leading to tricuspid regurgitation and pulmonary valve stenosis.
Left-sided lesions not seen because MAO in the lung metabolizes serotonin before it reaches that side.
What does squamous cell carcinoma of the esophagus consist of? Where in the esophagus is it located? Major risk factors?
solid nests of neoplastic squamous cells with abundant eosinophilic cytoplasm and distinct borders (areas of keratinization may be seen = white blobs = well-differentiated)
Upper 2/3 of esophagus most common
most common causes/risk factors = alcohol and tobacco
but any irritation to the esophagus increases risk
Mechanism of H.pylori-induced duodenal ulcers vs. gastric ulcers?
duodenal ulcers:
decrease in somatostatin-secreting cells in gastric mucosa leading to unchecked gastrin production
gastric ulcers:
destruction of local mucosal layer from bacteria presence and inflammatory response (increased acid not required)
Describe Virchow’s node, Sister Mary Joseph nodule, and Krukenberg tumor. Associated with?
Virchow’s node: left supraclavicular node (drains stomach)
Sister Mary Joseph nodule: sucutaneous mass in the periumbilical region
Krukenberg tumor: mucin-producing, signet-ring neoplastic cells in ovarian stroma
All indicate metastasis of gastric cancer.
How does Shigella gain access to the GI mucosa?
invades the M cells in Peyer’s patches of the ileum through endocytosis
then lyses endosome, multiplies, and spreads laterally into epithelial cells
How do right-sided colon cancers present? Left-sided?
Right-sided: grows as exophytic/raised masses leading to blood loss; larger caliber than left so no obstruction
- iron deficiency anemia (fatigue and pallor) from blood loss
- anorexia, malaise, weight loss
Left-sided: infiltrate intestinal wall and encircle lumen; present with symptoms of partial obstruction
- decreased stool caliber, constipation
- cramping abdominal pain and distention
- nausea and vomiting
Curling ulcer? Cushing ulcer?
Curling ulcers - arise in proximal duodenum in association with severe trauma or burns
Cushing ulcers - arise in the esophagus, stomach, or duodenum in pts with high intracranial pressure
Increased intracranial pressure directly stimulates vagus nerve leading to hypersecretion of gastric acid.
Both are stress-induced acute gastric mucosal defects.
Obstructive jaundice with enlarged but nontender gallbladder? Risk factors?
Courvoisier sign
indicates adenocarcinoma at head of pancreas compressing bile duct
(tumors at body and tail do not obstruct common bile duct and do not produce symptoms until they invade the splanchnic plexus)
Pancreatic cancer risk factors:
- smoking (most important environmental)
- age
- diabetes
- chronic pancreatitis
- genetic predisposition (hereditary pancreatitis, MEN syndromes, FAP, HNCC, etc.)
Obstructive jaundice signs?
dark urine, pale stools, pruritis
Abdominal pain with white chalky lesions in mesentery (fat cell destruction and calcium deposition)? What is the process responsible for these findings?
Acute pancreatitis
pancreas is edematous with focal areas of fat necrosis, calcium deposition, and interstitial edema
- duct obstruction leads to stasis of pancreatic secretions
- lipase (does not need activation) digests adipose cells
- free fatty acids bind calcium ions to precipitates as insoluble calcium salts (white, chalky deposits)
- focal necrosis and Ca2+ precipitation induce inflammatory rxn
(acute interstitial pancreatitis) - if inflammatory process continues, blood flow will be compromised by edema leading to ischemic damage of acinar cells and trypsin release leads to activation of other proteolytic enzymes and autodigestion of pancreatic tissue (acute necrotic pancreatitis)
- destruction of blood vessels can cause hemorrhage into necrotic areas
Where are parietal cells found in the gastric glands? Where are chief cells found?
Parietal cells (HCl, IF) superficial region of gastric glands (oxyniti/pale pink)
Chief cells (pepsinogen) deeper region of the gastric glands (small, basophlic, granular)
Describe chronic gastritis type A vs. type B.
Location? Mechanism? Associations?
Type A:
- located in fundus/body (first part of stomach)
- Autoimmune disorder with Autoantibodies against parietal cells, leading to loss of HCl and IF production (Achlorhydria, Anemia)
- Associated with other Autoimmune disorders
Type B:
- located in antrum (second part of stomach after fundus/body)
- due to H.pylori infection
- associated with increased risk of gastric adenocarcinoma and MALT lymphoma
Both are NONerosive (vs. acute gastritis, which is erosive)
Problems night driving with generalized pruritis and dry skin?
Vitamin A deficiency
from biliary obstruction leading to chronic cholestasis and fat soluble vitamin malabsorption
What does urease convert urea into? What is used to conduct a rapid urease test?
carbon dioxide and ammonia (causes a pH increase)
rapid urease test: sample from gastric mucosa of pt is added to solution containing urea and pH indicator
Pt with antacid-resistant heartburn has fingertip ulceration and telangiectasias? Mechanism of heartburn development?
CREST syndrome Calcinosis Raynaud syndrome Esophageal dysmotility Sclerodactyly Telangiectasia
Mech unk, but CD4 accumulation and stimulation of fibroblasts, which produce collagen leading to excessive tissue fibrosis.
Esophageal dysmotility due to atrophy and fibrous replacement of esophageal muscles – esophageal body and LES become atonic and dilated, resulting in severe reflux.
What marker is used in colon cancer? What is it used for?
Carcinoembryonic antigen (CEA)
used to detect disease recurrence
cannot be used to screen or diagnose
Esophageal tumor with moderately differentiated tumor cells, keratin nests and pearls, and intracellular bridging?
Squamous cell carcinoma of the esophagus
Pathogenesis of acute appendicitis?
- Obstruction of lumen (fecaliths, hyperplastic lymphoid follicles, foreign bodies, tumor, nematodes) distends appendicular wall as mucus is retained and accumulates.
- Venous outflow obstructed resulting in ischemia and bacterial invasion
- Inflammation and edema of the wall occurs to further distend and put at risk for rupture
How does the inflammatory infiltrate differ in acute vs. chronic gastritis? How to differentiate between the two types of chronic gastritis?
acute - neutrophil-predominant
chronic - lymphocyte and plasma cell predominant
Chronic:
Type A - autoimmune against parietal cells/IF in body and fundus
Type B - H.pylori in the antrum
On what side does sporadic colon adenocarcinoma usually occur? HNPCC-associated colon adenocarcinoma? Associated cancers?
Sporadic colon adenocarcinoma (adenoma-to-carcinoma sequence):
- predominantly left-sided
- uncommon to have other associated cancers
HNPCC-associated (microsallelite instability):
- predominantly right-sided
- increased risk for ovarian and endometrial cancers as well
NO polyps – macroscopically normal areas of dysplastic mucosa
What is the most common place for intussusception? What population is it most common in? Presentation?
Ileocolic junction / ileocecal valve
Most common in children under 2yo.
In older pts, a lead point (Meckel diverticulum, foreign body, tumor) should be sought.
- Intermittent, severe, colicky abdominal pain
- Currant jelly stools
- Palpable mass may be present in lower abdominal quadrant
Immune mediators and histology in Crohn’s disease? In ulcerative colitis?
Crohn’s disease:
- Th1-mediated
- non-caseating granuloma formation (Th1, delayed hypersensitivity)
Ulcerative colitis:
- Th2-mediated damage of mucosal cells
Where is H.pylori found in the greatest concentration in a colonized stomach?
antrum (prepyloric area)
What region is always involved in ulcerative colitis? Inflammation seen in which layers? Continuous or discontinuous?
rectum always involved
inflammation limited to mucosa and submucosa ONLY
continuous mucosal damage
Pt with low-grade fever, periodic diarrhea, fatiguability, abdominal pain with strictures and fistula development?
Crohn’s disease
strictures and fistulas due to transmural inflammation across entire wall
2nd step of the adenoma-carcinoma sequence: growth in size of polyp – what mutated? Last step?
K-ras leads to uncontrolled cell proliferation
p53 and DCC
p53 allows cells with genomic errors to enter cell cycle - leads to malignant transformation of preexisting large adenomatous polyps
Broad causes of malabsorption? How to assess for impaired nutrient absorption/malabsorption?
1) Pancreatic exocrine insufficiency (impaired hydrolysis of nutrients)
2) Intestinal mucosal defects (impaired nutrient transport)
3) Bacterial proliferation (competition for nutrients)
Stool stain (Sudan III) identifies presence of fat in sample.
What does a carcinoid tumor look like?
Uniformity is key to easy ID - minimal to no variation in shape and size of tumor cells!!
- eosinophilic cytoplasm
- oval-to-round stippled nuclei
- nests or sheets of uniform cells
Describe findings in diffuse vs. intestinal gastric carcinoma.
Diffuse:
- infiltration of signet rings throughout stomach wall
- desmoplasia results in linitis plastica (leather-bottle stomach)
Intestinal:
- nodular, polypoid, well-demarcated masses that resemble colon cancers
- well-formed glands that consist of columnar or cuboidal cells
- associated with metaplasia (chronic gastritis from H.pylori or autoimmune), nitrosamines)
BOTH associated with Virchow node and with potential acanthosis nigricans or Leser-Trelat sign
What adenomatous polyp type is associated with secretory diarrhea?
Villous adenomas
secrete large amounts of mucus, leading to secretory diarrhea
Where do most duodenal ulcers occur? What does a duodenal ulcer distal to that region suggest? Origin?
Most duodenal ulcers occur in the duodenal bulb (first portion of the duodenum).
Ulcers in distal duodenum or other atypical places suggest Zollinger-Ellison syndrome (gastrinoma).
Majority of gastrinomas are located in the pancreas.
What pathway of cancer are adenomatous polyps a stage in?
Adenoma-carcinoma sequence
APC-Kras-p53/DCC
Causes of acute pancreatitis? Most common causes?
Most cases caused by gallstones and chronic alcoholism.
GET SMASHED Gallstones Ethanol Trauma Steroids Mumps Autoimmune disease Scorpion sting Hypertriglyceridemia Hypercalcemia ERCP (endoscopic retrograde cholangiopancreatography) Drugs (e.g., sulfa drugs)
Signs of toxic megacolon? Mechanism? Diagnosis?
Abdominal pain, distention, fever, diarrhea, signs of shock typical.
Complete cessation of neuromuscular activity in intestinal wall leads to rapid distention and thinning of intestinal wall, leading to risk of rupture.
X-ray used to diagnosis (invasive methods increase risk of perforation)
What is NF-kB and what does it do?
transcription factor responsible for cytokine production in immune response to infectious pathogens
How does Kaposi’s sarcoma present in the GI tract?
Presents in skin but spread to lungs and GI also common.
Tumor cells are spindle-shaped with small vessel proliferation.
Characteristic lesions range from reddish/violet flat maculopapular lesions to raised hemorrhagic nodules or polypoid masses.
Biopsy shows spindle cells, neovascularization, and extravasated red blood cells.
What drug may help prevent development of progression in the adenoma-to-carcinoma sequence?
COX inhibitors (aspirin)
increased COX-2 activation seen in some forms of colon adenocarcinoma
What AST:ALT ratio is indicative of alcoholic hepatitis?
AST:ALT >2 indicative of alcoholic hepatitis
AST»_space; ALT since AST is in mitochondria and alcohol is a mitochondrial poison!
What is abetalipoproteinemia? Presentation and findings on histology?
mutation in MTP (chaperone protein involved in proper folding of apoB)
Chylomicrons and VLDL particles synthesized on the ER as lipids accumulate around a single apoB molecule.
ApoB-100 found in VLDL
ApoB-48 (truncated version without LDL receptor ligand) found in chylomicrons
Presents early in life with symptoms of malabsorption (distention, fatty stool) with lab studies showing very low plasma triglyceride and cholesterol levels. Fat-soluble vitamin deficiency.
Histology shows enterocytes with clear or foamy cytoplasm due to accumulation of lipids in absorptive cells of the intestinal epithelium.
What is the most common GI malignancy? What is the most frequent location of this malignancy? What are the symptoms?
colon adenocarcinoma
most frequently located in the rectosigmoid colon
left-sided presentation with obstructing symptoms (altered bowel habits, constipation, abd. distension, nausea and vomiting)
Nonbilious vomiting with olive-sized mass in abdomen? What is the mass? Treatment?
Pyloric stenosis
Mass develops due to hypertrophy of the pyloric muscularis mucosae.
Treatment is myotomy/surgical splitting.
What is an anal fissure and where does it most often occur/why?
tear in the lining of the anal canal below/distal to the dentate line
occurs most often on the posterior midline (this region is relatively poorly perfused, making its mucosa sensitive to trauma)
Mechanism of cystic fibrosis?
CFTR gene non-functional
(membrane protein that normally transports Cl- ions across mucosal epithelial cell membranes)
Mutation leads to suppressed transport of Cl- and water from cells, leading to secretion of viscous mucus.
Most pronounced changes in respiratory tract and pancreas – mucus plugging leads to duct/tract obstruction.
String sign and noncaseating granulomas?
Crohn’s disease
What is the difference between a gastric erosion and a gastric ulcer?
Gastric erosion – mucosal defects that do not fully extend through the muscularis mucosa and thus are limited to the mucosal layer
Gastric ulcer – penetrate through the mucosal layer and extend into the submucosal layer
LAYERS: mucosa [muscularis mucosa] submucosa muscularis propria serosa
Carcinoid tumor in intestine with serotonin syndrome?
Metastasis to the liver has occurred!
Why are pts with Crohn’s disease at risk for gallstones?
terminal ileum typically affected in Crohn’s disease
mucosa of terminal ileum plays critical role in “recycling”/reabsorbing bile acids necessary for fat absorption
- inflammation of mucosa inhibits reabsorption, leading to bile acid loss in the feces
- less bile acid present in bile, increasing ratio of cholesterol:bile acids
- precipitation of cholesterol forming gallstones
What regions of the intestine are most susceptible to ischemic damage during hypotension/low perfusion states (ischemic colitis)?
Splenic flexure (between SMA and IMA arteries) Distal sigmoid colon (between IMA and hypogastric arteries)
“watershed” areas that lie in between areas of perfusion of major arteries
Epigastric calcifications?
Pancreatitis
What is a pancreatic pseudocyst? Mechanism of formation? Why is it a pseudocyst?
complication of acute pancreatitis
- enzymes disrupt walls of pancreatic ducts to cause leakage of pancreatic secretions into peripancreatic space
- inflammatory reaction in walls of surrounding organs induced
- granulation tissue forms to encapsulate the fluid collection, forming a pseduocyst
Pseudocyst because the wall consists of granulation tissue and NO epithelial lining. (True cyst has walls lined by epithelial cells.)
