Esophagus, Stomach, and Small Bowel
Ulcerative Colitis (Slides)
-Inflammatory infiltrate in lamina propria -Crypt abscesses: Consist of aggregates of PMNs (neutrophils) and debris -In chronic UC: Crypt architecture have DISTORTION
Colon: Vascular Pathology
-Intestinal Iscehmia -Colonic Ischemia -Angiodysplasia -Hemorrhoids
Esophagus: Non-neoplastic entities
-Esophageal ring -Esophageal web -Esophageal Diverticulum -Achalasia -Infectious Esophagitis
Stomach Histology
-Foveolae (Pits) -Glands >Parietal Cells: HCl and Intrinsic Factor (IF) >Chief Cells: Pepsinogen
Stomach: Gastric neoplasms
-Gastric adenocarcinoma -Gastro Intestinal Stromal Tumors (GIST) -Gastric MALT lymphoma
Small intestinal obstruction
-Herniation: *Protrusion* of peritoneal cavity though a *weakness/defect of abdominal wall* (inguinal or femoral canal, umbilicus). >Most common cause of intestinal obstruction worldwide. >If bowel herniates through defect, compression of veins at narrow opening may cause ischemia and infarction (strangulation) -Adhesion >*Fibrous bridges that adhere* segments of bowel due to prior surgery, infection, inflammation. >Most common cause of obstruction in USA. >Segments of bowel may get entrapped WITHIN the adhesion, causing strangulation. -Volvulus >TWISTING of a loop of bowel that can cause ischemia/ infarction due to vascular compromise. Sigmoid > cecum > small bowel -Intussusception
Colon (Congenital anomalies)
-Hirschprung disease -Imperforate anus
Pedunculated tubular adenoma
-Hyperchromatic -Cigar-shaped nuclei -Nuclear stratification -All seen at the surface of the crypts, indicating LACK of cellular maturation
Non-Neoplastic Polyps
-Hyperplastic Polyps -Mucosal Prolapse Polyps -Inflammatory pseudopolyp -Juvenile Polyp
Celiac Disease
-Immune-mediated enteropathy triggered by foods containing *gluten* in genetically-susceptible individuals -Gluten = protein in wheat, rye, barley >Composed of *gliadin + glutenin* -*Gliadin digestion induces inflammation in celiac patients* >Induces inflammatory response >Over time: villous atrophy causes loss of brush border surface area-> malabsorption. GSE= Gluten Sensitivity Enteropathy
Esophageal candidiasis
-Immunosuppressed -Diabetics -Recent antibiotics Slide: -"Sticks n' stones" >Pseudohyphae= Sticks >Yeast= Stones -Adherent WHITE PLAQUES -See neutrophils on slide
HSV Esophagitis
-Immunosuppressed patients -ULCERS form: lateral margin of ulcer >Multiple ulcers that can become confluent; may have raised edges -*Cowdry A*: INTRAnuclear "groundglass" multinucleated inclusion -3 M's >Multinucleation >Margination of chromatin >Molding of nuclei -Slide see Cowdry bodies and ground glass appearance
Omphalocele
Defect in abdominal wall muscle allows herniation of contents ventrally into a *membranous peritoneal sac* *Sac or peritoneum prevents direct exposure to environment*
Medullary Carcinoma (slide 3)
PUSHING BORDER -As opposed to infiltrating
Tropical Sprue (Histomorphology)
Same as celiac disease, although thought to affect ENTIRE small bowel more often- Rather than just PROXIMAL bowel
Small bowel partial resection: Representative section of jejunal mass
"Arborizing" smooth muscle
Inflammatory pseudopolyp
"Island of regenerating mucosa in a sea of ulceration" -Common in ulcerative colitis
Pseudomyxoma peritonei (Clinical presentation)
#1) Abdominal girth #2) Men: *inguinal hernia (filled w/mucin)* -Women: ovarian mass (R sided) #3) Appendicitis (can occur years s/p appy)
Ménétrier's Disease (Gross)
* Hyperplastic gastropathy* -Marked thickening of fundic/body rugal folds
Reactive Gastropathy
*"Cork-screwing"* of glands due to foveolar HYPERPLASIA -LACK of significant inflammation in lamina propria
Neuroendocrine tumors (Histology zoomed)
*"Insular" architecture = like islands*
Neuroendocrine tumors (Histology)
*"Insular" architecture = like islands*
Pseudomyxoma peritonei (CT)
*"Scalloping" of liver and occasionally spleen*
Helocobacter Pylori Gastritis
*#1 cause of chronic gastritis* -Chronic *ANTRAL predominant gastritis* caused by H. pylori -Associated with peptic ulcer disease (stomach and duodenum), gastric lymphoma and carcinoma
FAP (Gross)
*100's-1000's colonic polyps*
Mucinous adenocarcinoma (slide 1)
*>50% EXTRACELLULAR mucin*
Mucinous adenocarcinoma
*>50% extracellular mucin* -Associated with HNPCC: Loss of DNA mismatch repair protein expression -R=L colon >Thus, greater proportion of R-sided tumors d/t L-sided predominance in adenocarcinoma NOS
Barrett's Esophagus
*A complication of CHRONIC GERD* Endoscopically recognizable *columnar metaplasia* of the esophageal mucosa that is confirmed pathologically to have intestinal metaplasia including *goblet cells* -Both the endoscopic and pathologic components should be present to establish BE -Normal pic: Smooth and no mix of cels -Barrett's Pic: Islands of squamous mucosa with columnar mucosa GOBLET CELLS + COLUMNAR METAPLASIA = INTESTINAL METAPLASIA = BARRETT'S ESOPHAGUS -Can develop in adenocarcinoma: Metaplasia-> Dysplasia-> Carcinoma
Gastritis
*A mucosal inflammatory process.* -Inflammatory cells are required -Abrupt onset of abdominal pain and bleeding with use of alcohol, NSAIDs, or low hemodynamic state following trauma -Acute vs. Chronic gastritis ≠ type of cell seen (neutrophil vs. lymphocyte), but rather *time course of disease* >Acute >Chronic ->H. pylori ->Autoimmune ->Eosinophilic ->Lymphocytic ->Granulomatous
Neonatal necrotizing enterocolitis (NEC)
*ACUTE vascular compromise* that results in *transmural necrosis* in neonates upon starting oral feeds (a form of ischemia) -Distention, bloody stools, perforation-> possible death. -Premature or low-birthweight neonates -Pathogenesis likely *bowel immaturity* -Occurs more in the colon -Slide shows lack of blue and purple= lack of nuclei due to *coagulative necrosis*
Mucosal prolapse polyps
*AKA Inflammatory polyp* Typically seen in RECTUM -Results from *impaired relaxation* of *anorectal sphincter* with recurrent ABRASION
Acute appendicitis
*Acute inflammation* of the appendix with *neutrophilic infiltration* of the appendiceal wall -Adolescents and young adults -Initial *periumbilical pain* that later localizes to the *RLQ* -McBurney sign: tenderness located 2/3rds of distance from umbilicus to right anterior superior iliac spine. -Intraluminal pressure (due to obstruction by a fecalith commonly)-> Stasis-> Bacterial proliferation-> Inflammatory response, edema, neutrophilic infiltration, all of which THICKEN muscular wall-> COMPROMISES venous outflow
Pseudomembranous colitis
*Antibiotic-associated colitis-> Clostridium difficile colitis* -Note: pseudomembranes are not specific to C. difficile -30% of hospitalized patients are carriers of C. difficile -Bacterial OVERGROWTH of C. difficile due to long-term antibiotic use->ELIMINATION of other beneficial colonic flora that normally keep C. difficile in check -C. difficile releases toxin-> loss of epithelial cell TIGHT-junctions -> sloughing of epithelium-> *pseudomembrane formation and watery diarrhea* -Typical clinical presentation is watery diarrhea in a hospitalized patient receiving long-course of antibiotics. -Treatment is with antibiotics (metronidazole or vancomycin) or fecal transplants
Familial adenomatous polyposis (FAP)
*Autosomal dominant* -Innumerable colorectal adenomas (at least 100 for diagnosis)->100% risk of *adenocarcinoma* often before 30 years old -Accounts for 1% of all colorectal cancer -Inheritance of mutated APC (germline mutation) >APC = adenomatous polyposis coli, a tumor suppressor gene -Adenomas result from LOSS of 2nd allele within colonic epithelium-> allows additional mutations in *KRAS, TP53* -Wide extracolonic manifestations >Periampullary adenomas and adenocarcinomas have become most common cause of morbidity/mortality in FAP patients who have undergone prophylactic colectomy -Screening during adolescence followed by postadolescent colectomy is treatment of choice Treatment: prophylactic totally colectomy. >Even after colectomy, patients at risk for adenomas at other GI tract sites, particularly Ampulla of Vater and stomach.
Achalasia: Barium swallow will show...
*Bird's Beak* -Massively dilated esophagus plus constricted LES= Bird beak NO RELAXATION of LES due to inhibitory neuron LOSS
Acute Gastritis (Mechanism)
*Breakdown of mucosal barrier* -Direct irritant action >Mucosal erosion, necrosis, hemorrhage >Irritation-> high salt concentrations -Drug mechanism of action -Hypoperfusion
Carcinoid syndrome only occurs if tumor has metastasized to...
*Carcinoid syndrome only occurs if tumor has metastasized to liver* -If still in GI, the serotonin will be inactivated by liver -Serotonin!!!
Small bowel mucosa
-Epithelium -Lamina propria: Contains BVs, lymphatics, and some lymphocytes -Crypts
Colonic ischemia
*Large intestines involved* Large intestine: -Superior mesenteric artery (up to ≈ splenic flexure). -Inferior mesenteric artery (splenic flexure to sigmoid) -*"Watershed" area by the splenic flexure, farthest from blood sources-> Most vulnerable to ischemic injury* ->SMA and IMA terminate -Causes: many, including atherosclerosis, hypercoagulable states, aortic aneurysm, heart failure, dehydration, vasoconstrictive drugs.
Neuroendocrine tumors (Biological entities)
*Carcinoid tumor is NOT a single biologic entity!* Different neuroendocrine cells= different tumor behavior -ECL cell (enterochromaffin-like) -ECC cell (enterochromaffin) -L cell (enteroglucogan) -G cell (gastrin) -D cell (somatostatin) (Know gen) -Explains why carcinoids of one site do better/worse than those of another -*Small bowel NETs are more AGGRESSIVE, in general, than those at other sites* -Potentially malignant >Usually metastasis will let you know -Better name for this= "Well-differentiated neuroendocrine tumor"
Small bowel: Neuroendocrine tumors
*Carcinoids* -A tumor derived from neuroendocrine cells -Can arise anywhere in the GI tract-> most commonly the *small intestine* -GI neuroendocrine system (GI-NES) largest single endocrine system in human body >30 hormones in 14 different cell types >Regulates motility, digestion, immune surveillance
Hirschprung disease
*Congenital aganglionic megacolon* -Failure of neural crest cells to fully migrate from cecum to rectum (all of colon affected) -Distal colon *WITHOUT innervation*->* failure of peristalsis* to travel full length of bowel= *functional obstruction* -Failure to pass meconium in the first few days of life followed by abdominal distention -Begins at anal sphincter, extends for variable distance PROXIMALLY -Associated with Down Syndrome
Ulcerative Colitis (Gross)
*Continuous involvement beginning at rectum* -*Pseudopolyps*: Nodules of regenerating mucosa with inflammation >Surrounded by denuded areas
IBD: Crohn disease vs. Ulcerative colitis
*Crohn Disease and Ulcerative colitis* -Ulcerative colitis: Located in colon and rectum-> CONTINUOUS involvement (distal to proximal) >RECTUM involved >No fissures >Mucosa and submucosa only >NO granulomas >Pseudopolyps >Ulcers -Crohn Disease: Skips lesions (segmental disease); ENTIRE GI is involved (mouth to anus) >Fissures and fistulae >Variable rectal involvement >Transmural inflammation >Granulomas can form >Ulcerations
GIST Spindle cell neoplasm
*Driven by mutations in C-kit (85%) or PDGFRalpha (<10%)* Prognostic indicators: -Site -Size -Mitotic index
Tropical Sprue
*Environmental enteropathy* *Malabsorptive disease* in regions with POOR sanitation -Likely bacterial infection on top of nutritional deficiencies that allow for an IMPAIRED gut mucosal barrier Treatment: antibiotics + folic acid + Vit B12
Condyloma acuminatum
*Exophytic, papillomatous lesion of squamous epithelium caused by HPV* -Most common tumor of the anal and perianal region -Mostly associated with *HPV 6 and 11* serotypes >Low risk of progression to malignancy -High-grade dysplasia in condyloma associated with *HPV 16 and 18* serotypes >High risk of progression to malignancy *HPV BLOCKS p53 and RB tumor supressor genes* LOOK LIKE Cauliflower!!! Genitoanal region- Buschke-Löwenstein
Diverticulum (Histological section)
*Gastric parietal and chief cells* in ileum= *gastric heterotopia* -Normally NOT in ileum but may see with diverticulum >Acid secretion can cause ulceration and bleeding (red currant jelly) >Heterotropia= Normal tissue in an abnormal area
GIST
*Gastro Intestinal Stromal Tumors*-> Mesenchymal tumor derived from *interstitial cells of Cajal* -Most common *mesenchymal tumor* of abdomen, derived from interstitial cells of Cajal-> the pacemakers cells of the GI tract *C-KIT positive* (typically) -Codes for receptor tyrosine kinase-> oncogenic mutation in C-kit WILL SEE A SUBMUCOSAL MASS -If mutated: *Imatinib (Gleevec)* therapy possible
GEJ Junction
*Gastroesophageal Junction* Junction between tubular esophagus and proximal stomach -Proximal stomach begins when see *rugal folds*
Juvenile Polyp (slide)
*Globoid Shape* -Dilated and branching crypts
Celiac Disease (Genetics)
*HLA typing for HLA DQ-2 or DQ8*-> optional test -If null for both, patient DOES NOT have celiac disease
Small bowel polyps
*Hamartomatous polyps= Peutz-Jeghers Syndrome* -Autosomal dominant syndrome that consists of multiple GI hamartomatous polyps (throughout GI tract) and mucocutaneous hyperpigmentation. -Hamartoma = benign disorganized overgrowth of cells normally found in that tissue. -These polyps are often the cause of *small bowel intussusception (telescoping)* as the initial presentation. -May find polypoid exophytic mass (LIMITED to mucosa) -intestinal polyposis, mucocutaneous pigmentation, and autosomal dominant inheritance -Small intestines>Colon>Stomach>Rectum
Peutz-Jeghers polyp is a _______ polyp
*Hamartomatous*
Ménétrier's Disease
*Hyperplastic gastropathy* -Body and fundus: Restricted hyperplasia of *foveolar (mucous cell) epithelium* with hypoproteinemia -Loss of plasma proteins (albumin) through gastric mucosa-> peripheral EDEMA >Due to loss of oncotic pressure from intravascular protein loss -*TGF-Alpha overexpression* -Marked THICKENING of body rugal folds in fundus and body (antrum spared) --- Patient may see: -Cessation of nausea and vomiting -INCREASED serum albumin -Elevated TGF-Alpha
IBS
*Inflammatory Bowel Syndrome* Abdominal pain 3 days/month over 3 months with IMPROVEMENT after defecation and a CHANGE in stool frequency or form -Other GI disease must be excluded -Biopsies of the GI tract are all NORMAL -Female predominance, 20-40's -Change in gut flora, psychological abnormalities, motility abnormalities, sensory abnormalities, CNS processing abnormalities-> PAIN -Abdominal pain + bloating, flatulence, and change in bowel habits (diarrhea or constipation)-> DEFECATION helps! -Dietary fiber may helps symptoms!
Celiac Disease Histology
*Intraepithelial lymphocytes (IEL) with possible villous blunting*
Anal squamous cell carcinoma
*Invasive malignant neoplasm demonstrating squamous differentiation* -F:M 2:1 -More in young males, *especially HIV+* -More in urban populations, AA > Caucasians -Demographic shift occurring *from elderly females to young adult males*
Autoimmune gastritis (slide)
*Limited to body/fundus* Lymphoplasmacytic inflammation in DEEP, glandular lamina propria -Chronic inflammatory infiltrate centered DEEPR in the lamina propria around the *gastric glands*= causing their destruction -Not affect antrum as their are no parietal cells located there
Hereditary non-polyposis colon cancer (HNPCC)
*Lynch Syndrome* Most common cause of hereditary colon cancer (5% of all colon cancer) -*Autosomal dominant* >Inherited defects in one of the DNA mismatch repair enzymes *MLH1, MSH2*, MSH6, PMS2 >Additional mutations rapidly occur in sites known as microsatellites (short repeating sequences) -> this is known as microsatellite instability. -Leads to microsatellite instability-> rapid ACCUMULATION of somatic mutations in genes that control tumor progression -Risk of colorectal cancer 80-90% -Cancers occur at YOUNGER ages than sporadic colon cancer -More often *right sided* -Have risk of cancer in other organs as well: endometrium (MOST COMMON), ovary, small bowel, stomach, urinary tract, brain, etc. Morphology: remember these do NOT have a polyp as a precursor (NON-POLYPOSIS). >HOWEVER: The cancers do have typical morphologies
Colorectal Adenocarcinoma
*Malignant neoplasm of colorectal epithelium* -3rd most common cancer in US, males and females -3rd cause of cancer death in US, males & females -60s avg age at diagnosis (40s for HNPCC) Risk factors: -Family history of colorectal cancer -IBD -HNPCC, FAP, other genetic syndromes
Gastric Adenocarcinoma
*Malignant neoplasm of gastric epithelium* -2nd most common cancer worldwide -Incidence varies widely -Higher in developing countries -Lowest rates in N American, N Europe, Africa -Highest rates in Japan, Costa Rica, East Asia, E Europe -M>F Two histopathologic types: -Intestinal type -Diffuse (signet ring cell) type
Gastric Adenocarcinoma (Etiology)
*Malignant neoplasm of gastric epithelium* -Diet >INCREASED Risk: nitrites, nitrates, salt, salted foods, and smoked foods >DECREASED risk: fruits and vegetables -Smoking INCREASES risk -Chronic atrophic gastritis -Chronic H. pylori (longer than 10 years) -Epstein-Barr virus (EBV)
Small Bowel:Congenital Disorders
*Meckel Diverticulum*
Peutz-Jeghers syndrome: Finding around mouth
*Mucocutaneous pigmentation in >95% patients* -Pigments may also be seen on fingers and toes -Autosomal dominant inheritance pattern
What is the major histologic clue to distinguish an acute from a chronic colitis?
*Presence of crypt architectural distortion*
Entamoeba histolytica
*Protozoan that causes Amebiasis* -Fecal-oral transmission -Prevalent in developing countries with POOR sanitation -in US: migrants from and travelers to endemic countries, institutionalized patients, and homosexual patients -Cysts RESISTANT to gastric acid-> pass to colon where they RELEASE trophozoites-> if INVADE colon= BLOODY diarrhea -However: 90% of infections are asymptomatic! -Treat with metronidazole
Signet ring cells (diffuse type) are in what layer?
*Signet ring cells in the muscularis propria* = Stiff gastric walls
Gastric adenocarcinoma Diffuse type (Singlet Ring Cells)
*Signet ring cells* = *intracytoplasmic mucin droplet* displacing nucleus to the side = DIFFUSE type adenocarcinoma
Esophageal SCC
*Smoking and alcohol are additive effects to SCC of esophagus*
SCJ Junction
*Squamocolumnar Junction* -*Z-line* -Mucosal junction of *squamous and columnar tissue* -May NOT correspond to GEJ -Picture shows SCJ is just north of GEJ >See columnar metaplasia between the SCJ to GEJ due to acid reflux
Esophagus (Slide)
*Stratified nonkeratinizing squamous mucosa* rests on LOOSE lamina propria >Lamina Propria contains supporting vasculature and scattered inflammatory cells-> CT and BVs -Nonkeratinizing squamous mucosa= "Basket Weave Cells"
Acute erosive/hemorrhagic gastritis
*Stress Gastritis* Gross -Petechiae, erosions, ulcers Microscopic -*Limited to mucosa*: >Superficial lamina propria hemorrhage >Mucosal sloughing/necrosis >Neutrophils Therapy >Acid-supression: histamine blockers or proton-pump inhibitors
Acute self-limited (infectious) colitis
*Transient, presumably infectious colonic inflammation that presents with ACUTE-onset diarrhea* (sometimes bloody) -Ingestion of pre-formed toxins (Staphylococcus aureus, Vibrio cholera, Clostridium perfringens; cause symptoms within hours including explosive diarrhea) Infection by toxigenic organisms (toxigenic E. coli, incubation of hours to days) -Infection by enteroinvasive organisms which invade and DESTROY mucosal epithelium cells (enteroinvasive E. coli, Shigella) -Infection by viral organisms (CMV, HSV, HIV, etc.) -Differential diagnosis also includes drug effect -Resolves 2-4 weeks (usually)
Whipple Disease (Macrophages)
*Villi distended by foamy macrophages filled with organisms*
Whipple Disease (PAS stain)
*Villi distended by foamy macrophages filled with organisms* -Partially destroyed organisms are present in macrophage lysosomes (positive for PAS)
Esophageal Diverticulum
*Zenker diverticulum* -An OUTPOUCHING of esophageal wall ABOVE upper esophageal sphincter (UES) -Food may collect here, causing *halitosis* (bad breath), regurgitation, and possibly predispose to carcinoma (SCC). -Reflects underlying motor dysfunction -Not all 3 layers of esophagus are herniated
Esophagus Congenital Anomlies
-Esophageal atresia -Tracheoesophageal fistula
Two pathways to colon cancer
-*APC pathway* Chromosomal INSTABILITY pathway -*Microsatellite instability pathway* >Germline MSI pathway >*Acquired CpG island hypermethylation phenotype (CIMP)*
Acute Gastritis (Etiologies)
-*Aspirin/Acetylsalicylic Acid (ASA) and other NSAIDs* -*Steroids* -*Post operative state* --- Others: -ETOH -Cocaine, crack -Acid/Alkali ingestion -KCl -Iron pills -Radiation/ChemoRx -Sepsis -Major trauma -Severe burn
Secondary Achalasia
-*Chagas disease*: Trypanosoma cruzi infection DESTROYS myenteric plexus= Megaesophagus -Diabetic autonomic neuropathy -Malignancy -Amyloidosis -Sarcoidosis: infiltrative diseases -Associated with Down syndrome -Possible autoimmune association (Know gen)
Esophageal Web
-*Eccentric*, THIN membrane of tissue in the esophagus, most commonly PROXIMAL region -*Plummer-Vinson syndrome (PVS)* has 4 main symptoms: upper esophageal web + IRON-deficiency anemia + Glossitis (inflammation of tongue) + cheilosis (inflammation of corners of the mouth) *Responds to iron*
Celiac Pathogenesis
-*HLA: DQ2 and DQ8* >Genetic testing -Anti-gliadin, anti-endomysium, and anti-tTG >Do serology to test -More so in PROXIMAL bowel -Will have diarrhea, abdominal distention, failure to thrive, bloating, etc -Dermatitis herpetiformis -Gluten free diet helps
Entamoeba histolytica morphology
-4 Nuclei max -INGESTED RBC soft criterion for E. histolytica
Anal squamous cell carcinoma (Risk factors)
-Anal intercourse -Heavy smokers -History of STDs -HIV+ -Immunosuppression (organ transplant pts) -Cervical dysplasia/cancer in females -Low socioeconomic status *All predispose to infection with HPV, which is the driver of all these tumors*
Celiac Disease (Serology)
-Anti-tissue transglutaminase IgA -Anti-endomysial IgA -Total IgA -If patient is IgA deficient, get anti-TTG IgG) -Can be used to monitor adherence to gluten-free diet (compliance) *Most sensitive test is serology for anti-tissue transglutaminase IgA*
Granulomatous gastritis
-Any gastritis with *granulomas* -Differential diagnosis: >Crohn disease >Sarcoidosis >Infection (must exclude mycobacteria and fungi
Peutz-Jeghers syndrome (Summary)
-Autosomal DOMINANT syndrome that consists of *multiple GI hamartomatous polyps (throughout GI tract) and mucocutaneous hyperpigmentation* -These polyps are often the cause of *small bowel intussusception* as the initial presentation -PJS patients have a greatly *INCREASED risk of malignancy* throughout the body over the lifetime -Pathogenesis: associated with germline *STK11 mutation (also known as LKB1)*, a tumor SUPPRESSOR gene. -Acquisition of a "second hit" spurs cancer formation
Bethesda Criteria to Identify Those for Genetic Testing for Lynch Syndrome
-CRC in a patient less than 50 years of age -Presence of synchronous/metachronous HNPCC associated tumors, regardless of age (endometrial, colon, etc) -*Colorectal cancer with HIGH-frequency microsatellite instability histology diagnosed in a patient who is younger than 60 yr of age. >Presence of tumor-infiltrating lymphocytes, Crohn's-like lymphocytic reaction, mucinous/signet ring differentiation, or medullary growth pattern* ---- Clinical features -Asymptomatic (screening) -Change in bowel habits (L>R) -Obstruction -Perforation -Bleeding often microscopic -Anemia symptoms -Pain and tenesmus -Metastatic presentation
Infectious esophagitis
-Candidiasis -HSV -CMV
Colon Cancer
-Colorectal adenocarcinoma -Appendiceal adenocarcinoma and pseudomyxoma peritonei -Anal tumors
Stomach: Congenital Disorders
-Congenital diaphragmatic hernia -Omphalocele -Gastroschisis -Congenital hypertrophic pyloric stenosis
H. Pylori gastritis: Pathogenesis Pathway
-Contain Urease: Convert urea to ammonia NEUTRALIZING the gastric acid and allowing bacteria to survive -Mucinase is another enzyme causing mucosal damage >Inflammation occurs >Flagella helps move through the mucus Infection can result in either increased acid production OR multifocal atrophic gastritis with decreased acid production >Increased acid production= Duodenal ulcers (antral predominant gastritis) >Decreased acid production= an increased risk of intestinal metaplasia, dysplasia, and adenocarcinoma.
Small bowel: Diseases of malabsorption
-Cystic Fibrosis -Celiac Disease -Tropical Spure -Lactose intolerance -Abetalipoproteinemia -Whipple disease
Collagenous colitis
-DENSE subepithelial *collagen band* with INCREASED intraepithelial lymphocytes -THICKENED subepithelial collagen layer -MOSTLY females
Diverticulosis (Pathology)
-Diverticula = False diverticula, as only *mucosa + muscularis mucosae* herniate through muscularis propria -Grossly: sigmoid usually always involved, but any segment of colon may be affected -Histologically: FLASK shaped protrusion of mucosa + muscularis mucosae through muscularis propria
Lymphocytic gastritis
-ELEVATED *intraepithelial lymphocytes (IEL)* in SURFACE foveolar epithelium -Associated with *celiac disease*-> gluten free diet!
Presenting complains of Peutz-Jeghers patients...
-Intestinal obstruction (43%) -Abdominal pain (23%) -Blood in stool (14%) -Mucocutaneous pigmentation (13%) -Prolapse of polyp through anus (7%) --- Up to 69% of patients experience an *intussusception* during their lifetime, most often in the small intestine.
Abetalipoproteinemia (Slides)
-Lipids CANNOT get assembled into CHYLOMICRONS and out of enterocyte-> *Steatorrhea* >Vaculoated enterocytes -RBC Burr cells (acanthocytes) form due to LOSS of membrane lipids
Condyloma acuminatum (Slide)
-Marked acanthuses -Surface parakeratosis -Orderly maturation -*Koliocytes*
Juvenile polyps
-Most occur <5y old, in rectosigmoid -May be sporadic or syndromic -*Juvenile polyposis syndrome* >Autosomal dominant >Up to 100 *hamartomatous colonic polyps* >*SMAD4 or BMPR1alpha* mutation -*Risk of cancer* throughout GI tract >Frequent endoscopic surveillance -Gross: The resected colon harbors numerous sessile and pedunculated, reddish polyps (mostly in rectosigmoid)
Subtypes of colon adenocarcinoma
-Mucinous adenocarcinoma -Medullary carcinoma
Colon: Infectious pathology
-Pseudomembranous colitis -Entamoeba histolytica -Acute self-limited colitis
Normal Colon
-See layers: Mucosa, muscularis mucosae, submucosa, muscularis propria, serosa -Crypts -Find ganglion cells >Muscularis propria contains the *myenteric plexus (ganglion cells)* -The colon has NO VILI! -Glands are linear >straight and perpendicular to the surface -Lamina propria has FEW CELLS -Gland are close together -Normally: all mitotic (generative) activity occurs in the LOWER 1/3 (±) of colonic glands
PJS Syndrome: Cancer Risk
-Small Intestine (Most common) -Gastric -Pancreatic -Colorectal -Ovarian -Lung -Endometrial -Breast
Small Bowel (Various non-neoplastic entities)
-Small intestinal obstruction >Herniation >Adhesion >Volvulus >Intussusception -Neonatal necrotizing enterocolitis (NEC)
Diverticulitis (Gross)
-Stricturing fibrosis >THICKENED wall >Fecal shown getting stuck -Perforation and *fistula formation* -Adhesions Diverticulitis: Shows plugging up!
Gastric adenocarcinoma Diffuse type (Layers)
-Submucosa -Muscularis propria -Serosa
tracheoesophageal fistula (Slide)
-T= Tongue -Blind proximal esophagus -Distal esophagus with FISTULA to distal trachea
Anal squamous cell carcinoma and precursors
-Upper zone of anal canal is lined by columnar epithelium-> can get adenocarcinoma. -Lower zone of anal canal is lined by squamous epithelium-> can get squamous cell carcinoma >Associated with human papillomavirus infection. ->precursor for dysplasia-> subsequent squamous cell carcinoma.
Squamous Cell Carcinoma (Anal region slide)
-Well-defined cell borders -"Basket-weave" pattern -Dyskeratotic cells (very hard, pink cytoplasm) -+/- Keratin production
Ulcerative Colitis (Summary)
1.) *Continuous disease*: Distal to proximal-> *limited to colorectum* 2.) *Mucosal and submucosal inflammation ONLY (not transmural inflammation) 3.) Crypt architectural distortion and active cryptitis 4.) NO granulomas
Crohn Disease (Summary)
1.) SKIPS lesions 2.) Any segment of the GI tract 3.) Transmural INFLAMMATION: From mucosa all the way down through muscularis propria and serosa 4.) NON-NECROTIZING GRANULOMAS
IBD and risk for adenocarcinoma
3 factors determine risk: -Duration of disease: Risk starts at ≥ 10y disease -Extent: HOW much surface of the GI tract is affected -Severity: more severe inflammation = more risk -IBD patients get frequent colonoscopic biopsies to detect DYSPLASIA= the PREmalignant lesion Normal: Bland cells and nuclei are small Adenocarcinoma: Pleomorphism and back-to-back cells Dysplasia: Jumbled nuclei
Meckel Diverticulum: Case
A 3 year-old boy complains to his mother of abdominal pain. -It appears unrelated to eating or bowel movements and he describes it as "crampy" and "burning" and points to his *umbilicus* when asked where it hurts the most. -His past medical history and family history are unremarkable. -His mother notices *blood* in his diaper. -Used medical scan called a *technetium-99m pertechnetate scintiscan*: the pertechnetate is taken up by gastric mucosa >Stomach and bowel is okay to see absorption but the diverticlulum (arrow) shows it getting stuck there -The patient undergoes a partial small bowel resection of the ileum, approximately 20 cm proximal to the ileocecal valve.
Meckel Diverticulum
A TRUE diverticulum of the ileum: Outpouching of all three layers of the bowel wall -Failure of *vitelline duct to involute* >Vitelline duct connects developing gut to yolk sac *Rules of 2* -2% of population -*Symptomatic by age 2* -*Within 2 ft of ileocecal valve* -2 inches long -2x more common in males -Asymptomatic or may have bleeding
Sessile serrated adenoma
A type of polyp that most commonly occurs in the *RIGHT colon* and resembles a hyperplastic polyp but possesses malignant potential (Hyperplastic polyp occurs in the LEFT colon) -These polyps often harbor mutations in MLH1, a DNA mismatch repair gene, and are precursors of *right-sided colon cancer* -Even though there is no cytologic dysplasia, there is *architectural dysplasia*-> this is why the term adenoma is still used
Esophageal Ring
AKA Schatzki's ring Concentric, THIN diaphragm of tissue in the DISTAL esophagus, most commonly at GE junction -Includes ALL 3 LAYERS: Mucosa, submucosa, and lamina propria -Dyshphagia occurs --- Picture shows smooth mucosa, raised rim of tissue CONCENTRIC
Congenital diaphragmatic hernia
Abdominal organs HERNIATE upward through *defect in diaphragm*
Intestinal ischemia
Abrupt PAIN, bloody diarrhea, vomiting, distention, death Pathogenesis: Adults, occlusion of major blood vessels from atherosclerosis, tumor, other masses, volvulus, or shock (hypotension) -Children: volvulus from malrotation Histomorphology: -Mucosa most susceptible to ischemic injury, with musculature LEAST susceptible. >If cause is addressed: mucosa MAY regenerate. -If ischemia is longstanding: Full-THICKNESS necrosis may lead to perforation -Small or large bowel may be affected!
Esophageal Cancer: Adenocarcinoma vs. Squamous Cell Carcinoma
Adenocarcinoma= -Demographic: White males in 60s -Incidence: HIGH in the US-> 80% of all esophageal tumors -Etiology: *GERD* >Barett's esophagus >Obesity >Alcohol -Location: Distal 1/3 --- SCC= -Demographic: African American Males in 60s -Incidence: LESS in the US (Predominates worldwide) -Etiology: CHRONIC IRRITATION >Alcohol + smoking >Achalasia >Zenker's diverticulum -Location: Middle 1/3
Colonic adenomas
Adenoma = usually cytologic dysplasia= premalignant precursor -This is why adults >50 years undergo screening colonoscopy >Remove the precursor = prevent colon cancer >Patients at HIGH risk start screening 10 years before youngest age at which a relative was diagnosed with colon cancer -SIZE MATTERS: Risk of malignancy within polyp correlates with polyp size most (not so much the type; tubular vs. villous) -1-2 cm, 5% risk > 2 cm, 10-20% risk tubular adenoma, villous adenoma, or tubulovillous adenoma
Neoplastic (pre-malignant) polyps
Adenomas Sessile Serrated Adenoma
Hirschprung disease (Barium enema study)
Aganglionic segment is shown on a barium enema study with patient that has Hirschprung disease
Primary Eosinophilic Esophagitis
An allergic disease (NOT related to acid reflux) in which the esophageal mucosa has significantly INCREASED eosinophils and the patient fails a trial of anti-reflux medication (typically, proton-pump inhibitors). -Dysphagia -Food impaction -Mimics GERD -Many patient have *allergic history* (asthma, etc.) -Patients have normal pH monitoring levels and/or fail antireflux therapy -Treatment includes dietary modification (ie. cow milk elimination) and corticosteroids -Usually seen in children --- Slide: The *eosinophilic microabscess* causes *RINGED esophagus* which is not normally seen >See RED granules
Esophageal Varices
Anything that cause IMPAIRMENT of blood flow from *portal vein* through liver (typically cirrhosis) -Results in portal HTN and possibly *esophageal varices*= DILATION of esophageal submucosal veinous plexus). -About half of cirrhotic patients have esophageal varices. >These varices can rupture and bleed, a medical emergency. -Can use banding (ligation of vein) TORTUROUS dilated veins in the esophagus
Appendiceal cancer vs. colorectal cancers
Appendiceal cancers IS NOT colorectal cancers
Peutz-Jeghers type polyp (Slide)
Arborizing smooth muscle + lobulated glands WITHOUT dysplasia (*pinwheel*)
Hyperplastic Polyp
BENIGN epithelial proliferations, with NO malignant potential -Hyperplasia of glands -Commonly occurs in the LEFT colon -Must be distinguished from *sessile serrated adenomas* (which look similar but have MALIGNANT potential) -So why are they removed? >To distinguish them from other polyps that do have MALIGNANT potential (tubular adenomas, sessile serrated adenoma, etc.) What's the phrase to remember to distinguish from this from a sessile serrated adenoma? HP's = "Normal cytology + normal architecture"
The epigenetic microsatellite instability pathway
BRAF mutations are associated with this pathway -Normally gene upstream will express and cause methylation of downstream genes -Mutation: Mutated gene (*MMR gene*) can be hypermethylated-> cannot methylate downstream genes and allow for their expression-> cancer risk
Intestinal Metaplasia (Gross)
Barett's Esophagus
Esophageal Ring vs. Esophageal Web
Both may cause DYSPHAGIA (Difficulty swallowing) and aspiration -Left= Esophageal Ring >*Schatzki's ring* >Concentric >Distal Esophagus -Right= Esophageal Web >Eccentric >Proximal Esophagus >*Plummer-Vinson syndrome (PVS)*
Mucosal prolapse polyps (General histology)
Broad strands of *muscularis mucosae* pushing UPWARD into lamina propria >Accompanying *inflammatory cells* and possible epithelial HYPERPLASIA
Cystic Fibrosis (Malabsorption)
CFTR gene encodes protein involved in Cl- transport across epithelia=> H2O follows In pancreas: -Defective hydration of pancreatic ducts-> pancreatic intraductal mucus and concretions with obstruction-> pancreatic autodigestion with *insufficiency of pancreatic enzyme secretion* >Thick, salty mucus BLOCKS pancreatic and bile ducts
Hyperplastic Polyp (Shapes)
CROWDING of epithelial cells -SERRATIONS -STAR SHAPED glands
H. Pylori gastritis: Patterns of involvement
Can develop from antral-predominant gastritis-> ulcer->duodenal ulcer-> carcinoma
Invasive Adenocarcinoma (slide 1)
Cellular material seen in the submucosa
Inflammatory Bowel Disease
Chronic inflammatory condition resulting from *dysfunctional MUCOSAL immune activation* -Early teens-20's, Caucasians, and Ashkenazi Jews-> suggests GENETIC component Pathogenesis -Idiopathic= NOT SURE -Research suggests epithelial DEFECTS in tight junctions allow microbial components to activate an ALTERED immune response to the gut microbiome -An ALTERED gut microbiome may have a role -Parts of bacteria get into lamina propria through a LEAKY gut-> set off *inflammatory reaction*
Invasive Adenocarcinoma (slide 2)
Circular structures GLANDULAR DIFFERENTIATION -Glands with nuclear hyperchromasia and ENLARGEMENT growing back-to-back with a desmoplastic (fibrotic) stromal response -Possibly signet ring cells
Diversion colitis
Colitis that occurs in portion of colon EXCLUDED from the normal fecal stream -A blind pouch created by surgery= *Hartmann's pouch* -Diversion of fecal flow deprives the diverted segment of *short-chain fatty acids* produced by bacterial digestion of fecal material-> these short-chain fatty acids are essential to colonic epithelial health-> without them= colitis Treatment: SCFA enema to the BLIND SEGMENT
In the esophagus, if the Z-line does NOT correspond to the gastroesophageal junction, what has occurred between the two points?
Columnar metaplasia
Congenital hypertrophic pyloric stenosis
Concentric enlargement of the pyloric sphincter and NARROWING of the pyloric canal that OBSTRUCTS the gastric outlet -M:F 4:1 -Mostly Caucasian and rare in blacks/Asians -Possible genetic as well as environmental (drugs, infection in utero) pathogenesis -Palpable epigastric mass= OLIVE -PROJECTILE, nonbilious vomiting -Hypertrophy and hyperplasia of pyloric muscularis propia
Lactose Deficiency
Congenital (rare) or acquired (adult) deficiency of lactase, and thus *inability to digest lactose (primary sugar in milk)* -Congenital: mutation in gene encoding lactase (rare) -Acquired: *down-regulation* of lactase gene expression -NORMALLY: Brush border enzymes (e.g., lactase) digest disaccharides (e.g., lactose) to simple sugars (glucose and galactose) -No lactase-> lactose broken down by bacteria in large intestine >Lactase deficiency is extremely common. >Diseases that affect brush border (celiac disease) may cause secondary loss of lactase. -Fermentation of lactose = GAS!
Sarcoid Mycobacteria
Crohn Disease
Sessile serrated adenoma (Slide)
Crypt basal dilatation (inverted "T") serration extending into crypt base -Crypts growing HORIZONTALLY >Basal dilatation of the crypts: like a flask *NO CYTOLOGIC DYSPLASIA*
Chronic Colitis (Slide)
Crypts *not oriented perpendicular to m. mucosa* -This is crypt architectural distortion: a sign of chronicity (long-standing inflammation), NOT a finding in ACUTE colitis
Normal Colon (Slide)
Crypts= TEST TUBES in a rack
Zollinger-Ellison Syndrome
DIFFUSE hyperplasia of fundic/body parietal cells in response to *hypergastrinemia* -Usually due to a *gastrinoma*: A gastrin-secreting neuroendocrine tumor in either the pancreas, duodenum, or antrum -Mimics Ménétrier's Disease grossly
Hemorrhoids (Slide)
DILATED thin-walled submucosal vessels with overlying normal squamous or columnar epithelium
Colon adenocarcinoma (Stages)
DONT need to know the stages "T" stage * Depth of invasion matters, size doesn't*
Familial adenomatous polyposis and variants
Derive from different APC mutations
Primary Achalasia
Due to DEGENERATION of DISTAL inhibitory ganglion cells -The cause is UNKNOWN
Normal small bowel
Duodenum Jejunum Ileum Layers: -Mucosa -Muscularis mucosae -Submucosa: Will see Brunner glands in duodenum -Muscularis propria
Lymphocytic colitis
ELEVATED intraepithelial lymphocytes WITHOUT a dense subepithelial collagen band. >Water will not enter cells -> watery diarrhea -Associated with celiac disease and other autoimmune diseases
Pedunculated tubular adenoma (Tubules)
ENLARGED, CIGAR-shaped hyperchromatic nuclei, pseudostratified = DYSPLASIA
Medullary Carcinoma
F>M, R>L colon -Often possess defects in DNA mismatch repair -More favorable prognosis Slide shows normal vs tumor
Colon Cancer Syndromes include...
Familial adenomatous polyposis (FAP) Hereditary non-polyposis colon cancer (HNPCC)
FAP and variants (Table)
Familial adenomatous polyposis: 100s-1000s of polyps >Dudodenal adenomas, gastric fundic gland polyps, hypertrophy of the retinal pigment epithelium-> 100% risk of carcinoma Attenuated familial adenomatous polyposis <100 adenomatous polyps Gardner's syndrome -Osteomas, skin cysts, dental abnormalities, fibromas, demoed tumors Turcot's syndrome -CNS tumors (medulloblastomas)
Gastroschisis
Herniation through ALL LAYERS of abdominal wall -Thus abdominal contents are completely OUTSIDE body >NOT contained within a sac like in omphalocele
Autoimmune gastritis (gland slide)
Fundic gland damaged by patchy lymphocytic infiltrates -Loss of glands over time-> atrophy (*atrophic gastritis*)
Stomach Histology in different layers
Fundus and body: >Surface fovelar cells (Pits) >Deep glands -> Parietal Cells ->Chief Cells Cardia and antrum: >Surface foveolar (mucus) cells >Deeper mucus glands
Malabsorption: mechanistic overview
GENERAL -Chronic malabsorption may reflect a defect in lumenal or intestinal phases of digestion. -*Lumenal defects* mostly affect digestion and processing of food in the small intestinal lumen-> within the TUBE of the gut -*Intestinal phase* defects often reflect altered *villous cells or structures that absorb and transport nutrients*-> the gut lining cells
GIST (Spindle cells)
GIST is a spindle cell neoplasm -Gastrointestinal STROMAL tumor Stroma = *spindle cells*(commonly)
Small bowel: infectious organisms (parasites)
Giardia lamblia Cryptosporidium parvum
The germline microsatellite instability pathway (Lynch Syndrome)
HNPCC Mismatch repair enzymes affected -MSH2 gets hit twice= micro satellite instability
GERD (Endoscopy)
HYPEREMIA, vertical linear streaks represent superficial mucosa erosion/ulcers -Acid is moving up causing the erosion/ulceration
Gastric Adenocarcinoma (Intestinal dysplasia slide)
High Grade Dysplasia
Achalasia
INABILITY of the LES (lower esophageal sphincter) to RELAX after swallowing -Results in *periodic esophageal obstruction* -Dysphagia, odynophagia, and regurgitation >Risk for *squamous cell carcinoma (SCC)* -Reduction or absence of *myenteric INHIBITORY neurons* >Normally sphincters are tonically contracted but inhibition will allow muscle to relax and let food pass through-> in achalasia the peristaltic wave cannot move through *LES DOES NOT RELAX= HARD TO SWALLOW*
Abetalipoproteinemia
INABILITY to secrete triglyceride-rich lipoproteins due to genetic mutation in a transporter (autosomal recessive) -Lipids (free fatty acids) accumulate within enterocyte cytoplasm -Presents in infancy -*Diarrhea, steatorrhea, deficiency of FAT-soluble vitamins* -Lipid membrane defects= *RBC burr cells= acanthocytes*
Microscopic Colitis
Idiopathic disease that is associated with *celiac disease, autoimmune disease, and drugs (NSAIDs)* -Presents with watery diarrhea and NORMAL findings on colonoscopy *Include Lymphocytic colitis and collagenous colitis*
How microsatellite instability happens
If loop of mismatched DNA from slippage occurs and there is DNA mismatch repair deficiency-> incorporation of mismatch occurs
Normal Ileum
Ileum resembles jejunum but has MORE *lymphoid tissue in submucosa= Peyer patches* Also has plicae circularis, villi, and microvilli NORMAL
Autoimmune gastritis
Immune-mediated form of chronic gastritis, results in LOSS of parietal cells >*Hypo- or achlorhydria* (DECREASED acid) >*Pernicious anemia/ Megaloblastic Anemia* (vitamin B12 deficiency due to DECREASED intrinsic factor) -Associated with anti-parietal cell and anti-intrinsic factor antibodies Parietal cells destroyed -Women associated with other autoimmune diseases (Hashimoto's, diabetes, graves, MG, etc) *Corpus fundus restricted atrophic gastritis*
Cytomegalovirus esophagitis
Immunosuppressed -Ulcers: Base of ulcer -LARGE (cytomegalo) cell with single large INTRANUCLEAR inclusion with smaller intracytoplasmic inclusions Slide: See big cells NOT multinucleated
Normal GEJ (Slide)
In this case GEJ corresponds with the change of cell type (Squamocolumnar Junction) -Esophagus has stratified squamous cells -Gastric cardia has simple columnar
Whipple Disease
Infectious disease by gram + bacteria *Tropheryma whiplelii* -Macrophages filled with organism accumulate in small intestine lamina propria, mesenteric lymph nodes, joints >FOAMY macrophages *Whipple's triad*: -Diarrhea -Weight loss -Arthralgia -Treatment: Antibiotics
Colon: Inflammatory Diseases
Inflammatory Bowel Disease (IBD): Crohn Disease and Ulcerative colitis Irritable Bowel Syndrome (IBS) Diversion colitis Microscopic Colitis: Lymphocytic colitis and collagenous colitis Diverticulosis/Diverticulitis Acute appendicitis
Gastric Adenocarcinoma (Intestinal metaplasia slide)
Intestinal metaplasia = Goblet cells = Chronic ATROPHIC gastritis -Intestinal metaplasia of the stomach is a precursor to DYSPLASIA (like Barrett's esophagus)
Autoimmune Gastritic (Intestinal metaplasia)
Intestinal metaplasia occurs-> see GOBLET CELLS
Gastric adenocarcinoma (Intestinal type slide)
Into the ulcer = Gastric adenocarcinoma, Intestinal type -Intestinal type= GLAND FORMING
Colonic ischemia (Slide 2)
Ischemia= Superficial mucosal necrosis "Withering" atrophy of surface epithelium that may progress to ulceration, but submucosa and muscularis propria are usually PRESERVED
Esophageal SCC (Histology)
KERATIN PEARLS: Keratin production -Squamous epithelium, recognized due to intercellular bridges, with nuclear hyperchromasia, enlarged nuclei, and architectural disorganization
Ulcerative Colitis
LIMITED to *colon and rectum* in a CONTINUOUS fashion, distal to proximal, *without skip regions* -Relapsing attacks of BLOODY diarrhea and abdominal pain that is relieved by DEFECATION -Associated with primary sclerosing cholangitis (7.5% of pts) -*INCREASED Risk of adenocarcinoma* -Smoking can protect from UC
Zenker's Diverticulum (Photos)
Left shows Barium swallowing test -Late phase shows entrance to diverticulum -Significance: Regurgitation and aspiration -Food can get caught in diverticulum-> predispose to SCC
Normal vs autoimune gastritis (slide)
Left: No inflammation and see clear borders Right: Lymphoplasmacytic inflammation in DEEP, glandular lamina propria
Normal Gastric Body vs. Ménétrier's Disease
Left: Normal Right: Hyperplastic gastropathy >Foveolar (mucous cell) hyperplasia *Foveolar hyperplasia with corkscrewing*
Autoimmune gastritis: Pathogenesis of achlorhydria and hypergastrinemia
Less HCl present-> G cells will produce more gastrin in response to increase HCl levels BUT due to anti-parietal Abs the HCl cannot change= HYPERGASTRINEMIA
Gastric adenocarcinoma Diffuse type (Gross)
Linitis plastica -Lesion is EVERYWHERE -HARD and crunchy feel on biopsy with obvious LACK of distension of gastric walls despite continous air insufflation
Mallory-Weiss laceration
Longitudinal mucosal tear near/across gastroesophageal (GE) junction -At GE junction-> usually on GASTRIC side -Forceful vomiting/ retching forces PROXIMAL stomach through diaphragm (alcoholics, bulimics, etc) - Laceration may bleed PROFUSELY -Hematemesis -Acute esophageal rupture can lead to *Boerhaave's syndrome* >Rupture of esophagus leading to air into the mediastinum >Chest pain >Medical emergency
Vilious Adenoma
Looks like SMALL BOWEL VILLI
Gastric MALT lymphoma (Slide)
Lymphoepithelial lesion= glands with INTRAepithelial lymphocytes and DESTRUCTION
Gastric MALT Lymphoma
Lymphoma of mucosa-associated lymphoid tissue (MALT) is most common *primary gastric B-cell lymphoma* -Most commonly arises from chronic *H. pylori gastritis* -Treatment of H. pylori can lead to lymphoma remission -However, if tumor undergoes genetic translocations (t(11;18)), treatment of H. pylori INEFFECTIVE
H. pylori gastritis (Slide 1)
Lymphoplasmacytic inflammation admixed with *neutrophils* in SUPERFICIAL mucosa ---- -Marked chronic active inflammation in the superficial lamina propria of the gastric antrum (usually) with pit abscesses and marked lymphoplasmacytic infiltrate
Esophageal atresia and tracheoesophageal fistula
MOST COMMONLY occurs as an *UPPER esophageal atresia (blind pouch) with the DISTAL esophageal segment forming a fistula (connection) with the trachea* -Causes aspiration, pneumonia, fluid, and electrolyte imalances -50% have associated congenital anomalies *VATER syndrome* >Vertebral defects >Anal atresia >TrachEoesophageal fistula >Renal dysplasia -Pathogenesis: exact embryologic defect is UNKNOWN
Whipple disease and lymphatics
Macrophages distend villi and cause *lymphatic obstruction*-> LACTEALS
Crohn Disease (Pathology)
May affect ALL layers of gut wall -EDEMA and EXPANSION of submucosa with abundant lymphoid aggregates, including in subserosal soft tissues -Thickened wall in involved area -Granulomas can be present due to lymphoid aggregates
Crohn Disease
May affect ANY segment of GI tract from mouth to anus -Tends to begin in *terminal ileum* -NON-bloody diarrhea, fever, abdominal pain, and possibly malabsorption with nutritional deficiencies -Fistulae (abnormal connections) may develop >Perianal fistal (anus+skin) >Enterocutaneous fistula (small bowel+skin) -Colovesical fistula (colon+bladder) -Extraintestinal manifestations: Uveitis (inflammation of uvea of the eye) and Arthritis -INCREASED risk for *adenocarcinoma* -Disease reactivation may be due to stress, diet, and cigarette smoking
Progression of Barrett's esophagus to carcinoma (Slides)
Metaplasia -> Dysplasia-> carcinoma sequence (adenocarcinoma) -Dysplasia: Nuclei are enlarged and move up the cell -Carcinoma: Gland forming carcinoma-> back to back circles-> adenocarcinoma
Neuroendocrine tumors (Cytology)
Monophormic bland cytology -*"Salt & pepper" chromatin* FINE chromatin is the salt Coarse granules are the pepper
Imperforate anus
Most common form of *congenital intestinal atresia* Failure of *cloacal diaphragm* to INVOLUTE -Failure to pass meconium with *abdominal distension*
Giardia lamblia
Most common parasite in humans -Fecal-oral transmission through *fecally-contaminated water* -Rural streams-> Campers -Cause microvillus damage and APOPTOSIS of intestinal epithelial cells -Symptoms range from *asymptomatic to diarrhea* -Most commonly seen in duodenal biopsies from infected patients -Most common human parasites
Appendix and cancer
Mucinous adenocarcinoma and pseudomyxoma peritonei When adenocarcinoma invades through the wall of the appendix -> Appendiceal perforation -> Seeding and spread of tumor cells throughout abdomen -> Continued production of mucus by tumor cells -> Mucin fills abdomen -> PSEUDOMYXOMA PERITONEI
Esophagus
Muscular tube connecting pharynx to stomach; -Upper (cricopharyngeal) and lower (gastroesophageal) muscular sphincter -Stop passage of food via muscle CONTRACTION -Passage of food via RELAXATION
Mucosal prolapse polyps (herniation slide 1)
Muscularis mucosa HERNIATION UPWARD into mucosa ->Enveloping crypts
Mucosal prolapse polyps (herniation slide 2)
Muscularis mucosa herniation upward into mucosa-> enveloping crypts
Celiac Disease (Biopsy)
Must be on a gluten-containing diet for histology to show INFLAMMATION -May be normal on gluten-free diet
Ménétrier's disease vs. Zollinger-Ellison syndrome
Ménétrier's disease: -Foveolar (mucous cell) hyperplasia -TGF-Alpha overexpression Zollinger-Ellison syndrome: Fundic (parietal cell) hyperplasia -Hypergastrinemia from tumor -*Parietal cell hyperplasia (NOT foveolar hyperplasia)*
Neuroendocrine tumor (Secretions)
NETs are part of MEN1 -*Carcinoid Syndrome* (Serotonin) >Flushing, diarrhea, wheezing, etc -Zollinger-Ellison syndrome (Gastrinoma) >Pain, ulcers, diarrhea -Insulinoma Syndrome >Hypoglycemic, besity, sympathetic overdrive, neuroglycopenia -Glucagonoma >Hyperglycemia, anemia, weight loss, thromboembolism, etc -VIPoma >Watery diarrhea, hypokalemia, hyperglycemia, flushing, etc
Hyperplastic Polyp (cytology)
NO CYTOLOGIC ATYPIA-> Small nuclei, NO hyperchromasia= NO DYSPLASIA -Crowding of epithelial cells-> serrations -NO malignant potential
Crohn Disease (Granuloma)
NON-necrotizing (Noncaseating) granulomas can form -Active cryptitis and crypt abscesses: Neutrophils within crypt epithelium and lumen
Invasive colorectal adenocarcinoma (NOS)
NOS= Not otherwise specified
GERD Biopsy findings are...
NOT SPECIFIC Without clinical info, a diagnosis of reflux esophagitis cannot be established by biopsy alone Histology can be various differentials: -Infectious esophagitis -Pill esophagitis -Ingestion of corrosive substances (Lye) -Chemotherapy/radiation -Primary eosinophilic esophagitis -Collagen vascular disease -Crohn's disease -Stevens-Johnson syndrome -Bullous disease -Lichen planus -Graft-versus-host Disease Trauma
H. pylori gastritis (Slide 2)
Neutrophils = "activity," thus chronic active gastritis
Acute self-limited (infectious) colitis (Slide)
No signs of crypt architectural distortion (branching) = process hasn't been going on a long time (*no chronicity*) -Active cryptitis: *intraepithelial neutrophils* -Crypt abscesses: neutrophils in crypt lumens NO CRYPT ARCHITECTURAL DISTORTION
Entamoeba histolytica: Pathogenesis
Noninvasive or invasive disease -Can go to liver and form liver abscesses
Acute appendicitis: Histology
Normal Acute Appendicitis: PMNs are found in wall -Mucosal ulceration *Neutrophilic infiltration of the muscularis propria* -Can be due to lymphoid hyperplasia or fecalith
Normal GE junction vs. Barrett's Esophagus (Gross and slide)
Normal GE Junction: See clear separation and rural folds Barrett's Esophagus: Rugal folds seen but also see "salmon pink tongues" -Goblet cells seen on slide= Mucin inside (should not bee seen in esophagus)
Hirschprung Disease (Slide)
Normal: See ganglion cells Hirschprung Disease: Ganglion cells are ABSENT *Absence of ganglion cells in affected segment*
Colorectal Cancer Types
Not one disease process!
Intussusception
One bowel segment "telescopes" into an adjacent segment >COMPRESSION of mesenteric vessels-> infarction >Most COMMON cause of obstruction in children <2y old.
Whipple Disease (Pathogenesis)
Organism-LADEN macrophages ACCUMULATE in small intestinal lamina propria and mesenteric lymph nodes, leading to *lymphatic obstruction* -> Malabsorption due to impaired lymphatic transport -> Malabsorption and diarrhea -> Macrophages also accumulate in other organs -> Joints (arthritis), heart (carditis), CNS problems
Diverticulosis/diverticulitis
Outpouchings of the colonic mucosa/submucosa-> typically *sigmoid colon* >50% of people over 70 year old have diverticula in Western countries (LOW-fiber diet; also tend not to squat during defecation) -10-25% will become symptomatic >LLQ cramping, constipation/ diarrhea, sensation of never being able to empty rectum -Obstruction of diverticula by stool/mucus-> stasis-> bacterial overgrowth-> INFLAMMATION (-itis) -Multiple diverticula = diverticulosis -INFLAMED diverticulosis = diverticulitis.
Cryptosporidium parvum
Parasite acquired from fecally-contaminated water -Especially prevalent in *AIDs patients with diarrhea* -Parasite resides in an endocytic vacuole within APICAL enterocyte cytoplasm (the microvillus), although it appears to be sitting just on TOP of the cell (INSIDE though) -Causes sodium malabsorption-> Chloride secretion-> Watery diarrhea
Colonic adenoma shapes
Pedunculated Polyp Sessile Polyp
Medullary Carcinoma (Slide 1)
Peritumoral lymphocytic response = "Crohn's-like reaction"
Autoimmune gastritis Labs
Pertinent Labs -α-parietal cell abs -α-intrinsic factor abs -ELEVATED gastrin -ELEVATED/nl gastric pH (should be LOW) -DECREASED vitamin B12
Pseudomembranous colitis (Slide 1)
Pseudomembrane "Volcano" lesion of DISTENDED crypts by mucopurulent exudate that forms the pseudomembrane.
GERD
REFLUX of gastric acid into the esophagus with mucosal damage Symptoms: heartburn, acid regurgitation, dysphagia, globus sensation, chronic sore throat, etc. Risk Factors: Age, alcohol, tobacco (LES relaxation) Contributing factors: hiatal hernia (Stomach rolls), weak LES, impaired esophageal peristalsis, DELAYED gastric emptying *RELAXATION of esophageal sphincter allows for reflux*
Stomach Anatomy
RUGAE are present
Gastropathy
Reactive changes -Little or NO inflammation -When mucosal epithelial cells show reactive changes, but inflammatory cells are absent. -Causal factors include: NSAIDs, alcohol, bile reflux from duodenum, and stress.
Hyperplastic Polyp (Slide)
SERRATIONS: Like teeth on a saw blade STAR SHAPED
Crohn disease (Gross)
SKIP LESIONS= *Discontinuous involvement* -Various ulcerated areas >Will see surrounding normal and ulcerated areas -Longitudinal ulcers and cobblestoning >Fissures: knife-like cuts into the mucosa that may extend DEEP into wall and possibly cause fistulas and perforation -Creeping fat *FULL thickness inflammation*
Juvenile Polyp (Stroma)
STROMAL INFLAMMATION -Dilated and MUCIN-FILLED crypts >Filled with inflammatory cells
Hemorrhoids
SWELLING of internal or external perianal tissue due to persistently ELEVATED venous pressure within hemorrhoidal plexus -Causes include straining at defecation, pregnancy, portal hypertension, a sedentary lifestyle of prolonged sitting
Angiodysplasia
Second-leading cause of lower GI bleeding (after diverticulitis) -INCREASE incidence with age -*Tortuous focus of mucosal and submucosal vessels*, usually located in *cecum/right colon* -Vessels may lie directly underneath surface epithelium, leading to EASY bleeding typically in older adults.
Esophageal Varices: Gross vs slide
See dilated vein with hemorrhages Slide shows massively dilated veins (filled with blood)
Normal vs Celiac Disease Histology
See lymphocytes at villous tips
Mucinous adenocarcinoma and pseudomyxoma peritonei (slide)
See omental mucin deposits
Sessile serrated adenoma vs. Hyperplastic Polyp
Sessile serrated adenoma: Right Colon; Inverted T Hyperplastic adenoma: Left colon; V shaped
Eosinophilic Gastritis
Significantly INCREASED eosinophils in gastric lamina propria -Think allergy or parasitic infection
Intestinal ischemia (Small intestine)
Small intestine: superior mesenteric artery + anastomosing arcuate arteries. -Blood supply most vulnerable to interruption at or near source-> pancreas swelling (pancreatitis), tumor, lymphadenopathy, atherosclerotic plaque, thrombus, or embolus. -Ascending and transverse colon also affected.
GIST (Slide)
Spindle cells commonly -Need immunohistochemical stains (for C-kit) to definitively diagnose.
Which portion of the colon is most likely to be affected in a patient with systemic hypotension?
Splenic Flexure
Gastric cancer (pathogenesis)
Sporadic (non-hereditary) -*Chronic gastritis*-> intestinal metaplasia (due to atrophic gastritis) ->Dysplasia-> adenocarcinoma -*Familial (hereditary)* >Germline E-cadherin/CDH1 gene mutations >Increased risk lobular breast carcinoma >70-80% penetrant, average age 37 at diagnosis >Prophylactic gastrectomy should be considered Two histopathologic types: -Intestinal type: gland-forming mass lesion -Diffuse (signet ring cell) type: Infiltrates as single discohesive cells throughout stomach without forming a discrete mass
Mucinous adenocarcinoma (Slide 2)
Strips of neoplastic epithelium floating in *abundant mucin*= mucinous carcinoma
Colonic ischemia (Slide 1)
Submucosa and muscularis propria are INTACT Mucosa ulcerated and LOSS of crypts
Diversion colitis (Slide)
Submucosa with INCREASED lymphoid follicles-> *lymphoid hyperplasia* -Lymphoid aggregates with germinal centers-> fill in submucosa -NORMAL mucosa
Esophageal cancer Metastasis
TNM= Tumor node metastasis T is DEPTH of invasion Maters HOW DEEP it goes not the size
GERD (Slide)
TOP: Normal squamous mucosa showing basal and suprabasal cells that involve <15% of the thickness of the epithelium. -The lamina propria papillae involve approximately 50% of the THICKNESS of the epithelium. BOTTOM: There is *basal and suprabasal cell hyperplasia*, ELONGATION of the lamina propria papillae, LACK of surface maturation with the presence of NUCLEATED squamous cells at the surface of the epithelium, and INCREASED inflammation in the *lamina propria*. -Overall more cells are "born due to stress" >Elongation of papillae and decreased maturation
Malabsorption
The small bowel is beautifully constructed to maximize surface area for absorption
Entamoeba histolytica colitis (Slide)
This *entamebic ulcer is DEEP and flask-shaped*,undermining adjacent normal mucosa. -Intamoeba histolytica in the inflammatory exudates, containing ingested erythrocytes.
Pseudomembranous colitis (Slide 2)
Toxin causes LOSS of cell adhesion -Sloughing of cells, PMNs, and mucus into pseudomembrane
Medullary Carcinoma (slide 2)
Tumor-infiltrating lymphocytes = "TILs" "Medullary" growth pattern = islands of polygonal cells with *prominent nucleoli, syncytial growth*
Invasive colorectal adenocarcinoma (NOS) (Slide)
Typical colorectal adenocarcinoma -A proliferation of complex glandular structures is noted, with infolding and bridging of the epithelium. -The cells have cylindrical to ovoid nuclei. -The lumen contains abundant *eosinophilic and nuclear debris ("dirty" necrosis)*. >This pattern of necrosis is characteristic of colorectal adenocarcinoma. -In addition to glandular cells, a variable amount of Paneth cells, neuro-endocrine cells, squamous cells, melanocytes, and trophoblasts can be found in "usual" adenocarcinoma. >Typically, the presence of these other cell types has no prognostic significance. -No SCC in colon!!!
Giardia (Slide)
Typically in duodenal biopsies -Pear-shaped trophozoites with TWO nuclei of equal size found right about brush border WITHOUT invasion; flagella present -Nuclei look like eyes
Inflammatory pseudopolyp (Slide)
Ulcerations and pseudopolyp
GSE Pathology
Vary with disease SEVERITY: -Chronic inflammation -Villous blunting -Intraepithelial lymphocytes (IEL) -LOSS of brush border
Clinical Features of gastric cancers
Virchow's node = Supraclavicular Sister Mary Joseph's node = periumbilical Blumer Shelf: Pouch of Douglas (cavity between rectum and uterus) Krukenberg tumor = BILATERAL ovarian drop metastases
Whipple Disease (Slide)
Whipple Disease: Villi DISTENDED by *foamy macrophages*
