GI pathology Flashcards
Increased ALT and AST but AST is < ALT
Do viral serology
+ = hepatitis
- = autoimmune hepatitis (ASM, ANA) WIlson disease (ceruloplasmin) Hemochromatosis (Fe saturation) alpha-antitrypsin (serum level) drugs and toxins
ceruloplasmin
wilson disease
AST > ALT <500 IU/L
Hepatitic cause
Alcoholic liver disease
increased ALK phos and GGT
cholestatic –>get imaging diameter of common bile duct
1 cm = extrahepatic
cholestatic Intrahepatic cause of jaundice
AMA +
primary biliary cirrhosis
AMA - cholestatic intrahepatic cause of jaundice
Primary sclerosing cholangitis
pregnancy
cholangiocarcinoma
hereditary syndromes
GVH and HVG
extrahepatic cholestatic causes of jaundice
pancreatic CA
gallstones
what does the liver catabolize
estrogen
drugs
toxins
NH3
Zone 1
highest O2
affected first by viral hepatitis and toxins
Zone 3
lowest O2
closest to central vein
at risk for hypotension and congestion
increased drug metabolism
Dendritic cells in the liver
DCs in the liver are uniquely positioned to monitor the portal circulation. they are in the space of Disse and are part of innate immune response
stellate cells
inside space of disse
fat soluble vitamin storage
fibrosis production
can contract and push fluid along in the space of disse
kupffer cells
inside sinusoids
part of innate immune system
where does Detox/
Delivery of synthesized/
metabolized products
( like bilirubin) to hepatocytes//system go
bile canaliculi to canal of hering to bile duct
space of Disse
lymph fluid is in this space
The hepatic lymph primarily
comes from the hepatic sinusoids. Fluid filtered out
of the sinusoids into the space of Disse flows through
the channels traversing the limiting plate either independently
of blood vessels or along blood vessels and
enters the interstitial space of either the portal tract,
sublobular veins, or the hepatic capsule.
if there is blockage in space of disse or mall then ascites occurs
what special types of cells are in the canal of hering
Canal of hering- bile is delivered to canal of hering which is a very small bile duct delivered to bile ducts of portal tracts
-stem cells of liver may be located in the canal of hering – source of regeneration of the hepatocytes
what is the space of Mall
lymphatic fluid flows from space of Disse into the portal area filling the space of Mall and then flowing into the larger portal lymphatics to the thoracic duct
what is sythesized in the liver
albumin
clotting factors (VIII, XI)–> liver transplant cures hemophilia A
acute phase reactants
in terms of mechanisms of cell injury what is generally the stage of irreversibility
membrane damage
what is fetor hepatis
distinctive smell of breath “musty” “sweet and sour” from shunting and dimethyl sulfide made by gut bacteria
seen in chronic liver failure
macronodular cirrhosis
> 3mm viral causes
micronodular
<3mm ethanol
in cirrhosis, what activates stellate cells into myofibroblasts
PDGFR-Beta
TNF
Kupffer cells release cytokines and chemokines that stimulate fibrogenesis in stellate cells
what is the most common cause of isolated increase in AST and ALT in typical Americans
NASH
Nonalcoholic Steatohepatitis
in what types of liver disease will you find the highest levels of aminotransferases
acute viral or ischemic liver injury , or toxic liver injury
cirrhotic pt’s and chronic hepatitis pt’s may have aminotransferases at what level?
within reference range
what is the significance of the t 1/2 life of albumin of 20 days
Albumin binds conjugated bilirubin- if the conjugated bili is elevated for extended periods of time, the conjugated bili can strongly bind to albumin- delta bilirubin is this complex – the half life of albumin is about 20 days so this delta bilirubin is going to be present in the blood for long periods of time – important to understand this delta bili . If you allow bile to run through the duct again the pt’ stays yellow for a while b/c you have to wait for the albumin to clear before the deposition of conjugated bili can actually go away
Increase in IgA
alcoholic liver disease
Increase in IgM
primary biliary cirrhosis
increase in IgG
autoimmune hepatitis
mean incubation period of hep A
1 month
mean incubation period of Hep B
3 months
mean incubation period of Hep C
2 months
mean incubation period of Hep e
1 month
why is it hard to develop a vaccine for Hep C
- This genomic instability and antigenic variability have hampered development of a vaccine…no vaccine
- Elevated titers of anti-HCV antibody do not confer effective immunity
Hairy leukoplakia is caused by what
EBV
may be first sign of HIV
99mTc nuclear scan
meckel diverticulum–> will show gastric mucosa and symptomatic meckel’s diverticula have ectopic gastric or pancreatic cells within them
if you have a positive Tzanck test what will you see?
multinucleated giant cells within inclusions
inclusions represent the herpes virus particles inside the nucleus
when do you lose ameloblasts
loss of ameloblasts? You lose these before the tooth ruptures through the gum
failed involution of vitelline duct
meckel’s diverticulum
what causes double bubble sign
annular pancreas
duodenal atresia
where are the regional lymph nodes located for the colon ?
periocolonic adipose tissue attached to the bowel
where do colon cancer cells travel to if they migrate into a vascular space
travel via lymphatics
get to liver by tumor cells invading into veins–> goes to portal vein–> right to liver
brain? travels through liver sinusoids, central vein–> hepatic vein–> IVC–> through lungs–> left side heart–> brain
when malignant colonic cells mets to the liver, where will they most likely stop and begin to multiply and grow–> becoming metastatic nodule
sinusoidal lumen
space of disse
what paraneoplastic syndrome is most common with colonic adenocarcinoma
nephrotic syndrome- membranous glomerulopathy, immune complexes, autoAb’s against antiphospholipase A2 receptor
how do malignant colonic tumor cells get to the regional lymph nodes?
float invade into them diffuse pushed mechanically and probably sucked into
what are the genes involved with HPV associated squamous cell carcinoma
E6/E7 oncogenic proteins
what is the central dot sign
ciliopathy- congenital defect
these represent the portal veins and the empty space around the veins are the dilated cysts
what is a ground glass appearance of the liver indicative of
Hep B
Type I autoimmune hepatitis
female predominance
young to perimenopausal
elevated IgG
ANA, ASMA
negative AMA
Type 2 autoimmune hepatitis
Children and teenagers
AMA
rare but potentially fatal syndrome of mitochondrial dysfunction with massive microvesicular steatosis
occurs in children that receive aspirin for fevers
reye syndrome
cause of hepatocellular necrosis in zone 3
acetaminophen
what is vinyl chloride associated with?
Angiosarcoma
what is budd-chiari syndrome associated with
oral contraceptives
Budd-Chiari syndrome is an uncommon condition induced by thrombotic or nonthrombotic obstruction of hepatic venous outflow and characterized by hepatomegaly, ascites, and abdominal pain.
what are some substances or conditions that are associated with Zone 1
Fe overload
allyl alcohol
what are some substances that are associated with zone 3 hepatotoxicity
CCL4
Acetaminophen
Ethanol
what pattern of injury does oral contraceptives cause
cholestasis
Acetaminophen
Zone 3 necrosis
Toxicity is from a metabolic by-product –> NAPQI
Toxicity is greatly enhanced by concurrent ETOH consumption (upregulation of cytochrome P-450 system…CYP2E1)
Commonly used for suicide – commonest cause of acute liver failure
- In the US, 50% overdoses are unintentional
Antidote for Acetaminophen
N-acetyl cysteine
restores GSH
must be given within 8-12 hours
Isoniazid
First line anti-TB drug with toxic metabolite (Fibrosis and cirrhosis)
1% get hepatitic damage; 10-20% show increase in ALT
methotrexate and the liver
Used to treat immune diseases (psoriasis, rheumatoid arthritis..)
Hepatotoxic with fatty change and fibrosis –cirrhosis
macrovascular fatty change
tetracycline and the liver
microvesicular fatty change
where do the patterns of disease of alcohol toxicity occur and what are the 3 patterns
begin in zone 3
hepatic steatosis (fatty change)
alcoholic hepatitis
cirrhosis
mallory bodies and AST>ALT are seen in what
increased ALK phos and GGT
leukocytosis (mainly neutrophilic)
Malaise, fever, jaundice, RUQ pain
alcoholic hepatitis
Mallory bodies–> represent tangles of intermediate keratin filaments complexed with proteins like ubiquitin
copper overload
wilson disease
what are the 5 cancers associated with smoking
pancreas
lung
HNSCC (squamous cell carcinoma of head and neck)
bladder
esophagus
what happens to flow in the hepatic artery as portal vein undergoes occlusion
increases
this holds true in cirrhosis as well
if there is acute occlusion , then the hepatic artery can’t catch up, but if the occlusion is slow/chronic, the hepatic artery will adapt and deliver adequate blood flow
under conditions of reduced portal venous flow with induction of the hepatic arterial buffer response, preferential shunt perfusion leads to a disproportionally increased contribution of perfusion of sinusoids with hepatic artery-derived blood. This guarantees maintenance of oxygen supply despite an overall reduction of nutritive blood flow.
space of Mall. Chemicals in this space/ environment…we think adenosine and NO…control the flow in this shunt…making sure enough O2 is getting to the hepatocytes
in hypovolemic shock, which area of the liver is injured first (necrotic changes)
zone 3 (around central vein) necrosis (also seen in acetominophen poisoning)
what happens to the liver with CHF
Increased sinusoidal pressure in zone 3 leads to hepatocyte and sinusoidal endothelial cell damage in Zone 3–> this activates stellate cells and leads to fibrosis (beginning in zone 3) “cardiac cirrhosis”
nutmeg liver
can lead to cardiac cirrhosis
benign hepatocyte neoplasm in young women taking oral contraceptives
hepatic adenoma
what virus is associated with hepatocellular carcinoma
HBV
presents in the background of cirrhosis
elevated AFP
HCC
AFP is a major plasma protein produced by the yolk sac and the liver during fetal development. It is thought to be the fetal form of serum albumin.
occurs in young patients with normal livers
looks like focal nodular hyperplasia but is malignant
has no association with HBV, HCV or cirrhosis
single large hard mass
micro–> shows malignant hepatocytes with characteristic stromal fibrosis
Fibrolamellar carcinoma (5% of HCC’s)
Arises from bile duct epithelium and resembles other adenocarcinomas
60% are perihilar (Klatskin tumor)
Risk factors: primary sclerosing cholangitis, congenital biliary cystic diseases, thorotrast exposure, parasites (liver fluke)
Hematogenous route of metastasis in ~ 50%
Frequently difficult to differentiate from metastatic carcinoma from breast or pancreas
Lethal tumor (median survival 6 months)
cholangiosarcoma
Constitutional: fatigue, weakness, weight loss
Estrogenic: spider angiomata, palmer erythema, gynecomastia, testicular atrophy
seen in what?
chronic liver disease cirrhosis
HFE gene
cysteine-to-tyrosine substitution at amino acid 282 (called C282Y)
hereditary hemochromatosis
autosomal recessive
HFE
histadine-to-aspartate substitution at amino acid 63 (called H63D)…worldwide distribution…mild disease.
hereditary hemochromatosis
HAMP
HJV
mutations in juvenile hemochromatosis
chronic inflammation and IL-6 lead to increased activation of hepcidin transcription
what is the effect on Fe
Fe is not absorbed into the blood in sufficient amounts and the person becomes iron deficient…so called “iron deficiency of chronic disease” =
“anemia of chronic disease”
hepcidin is an acute phase reactant
So, if there is no hepcidin …Fe is constantly being absorbed into blood stream…and abnormally deposited in tissues like the liver, heart, pancreas
what is the presentation of hemochromatosis
most common symptoms now include fatigue, malaise, arthralgia, and loss of libido (endocrine
unexplained cirrhosis, bronze-colored skin, diabetes (and other endocrine diseases), joint inflammation, and heart disease in middle-aged white men
iron stains blue with prussian blue stain
transferrin saturation increased, normal TIBC , increased serum ferritin
HFE mutation (C282Y)
what is the classic triad of complications in hemochromatosis
skin pigmentation
cirrhosis- iron activates stellate cells to induce fibrosis
diabetes
auto recessive disorder
WD gene
impaired biliary excretion of copper
failure to incorporate copper into ceruloplasmin
kayser-fleischer rings
mutation in Cu-ATPase ATP7B
Wilson disease
copper accumulates in liver, brain and eye
Liver disease: acute fulminant hepatitis, chronic active or cirrhosis
CNS: behavioral and/or Parkinson-like, strange smile (dystonia of muscles of the face- risus sardonicus)- basal ganglia lesions
Eye: Kayser -Fleischer rings*** - by the time these are visible, there should already be neurological symptoms
what are the lab findings in wilson disease
low serum ceruloplasmin (screening)
increased urine copper (specific)
Increase liver copper content by biopsy (most sensitive, highest PPV+)
Serum copper is highly variable as it depends on ceruloplasmin level
lymphocytes are the main infiltrate in the liver without inflammation
rhodanine stain for copper is positive
autosomal recessive
very low serum levels of protease inhibitor –> deficiency leads to emphysema and hepatic disease
Alpha 1 antitrypsin deficiency
most common abnormal variants is PiZZ
Protease normally inhibits 1) neutrophil elastase 2) cathepsin G, 3) proteinase 3…all made by neutrophils at site of inflammation
Defect blocks release of α1-antitrypsin from hepatocytes
Mutant alpa1-antitrypsin is abnormally folded which leads to the “unfolded protein response”…accumulates in hepatocyte…activates caspases and induces apoptosis…cirrhosis
Lack of inhibitor to neutrophil proteases in lung allows alveolar damage →emphysema
how do you make the diagnosis of alpha 1 antitrypsin deficiency
Decreased serum α1- antitrypsin level
Phenotyping for PiZZ
Liver biopsy shows accumulated α1-antitrypsin (abnormal protein folding)…
round to oval PAS positive cytoplasmic inclusions in hepatocytes - begin around the periportal area first and then spread to central vein region
progressive destruction of the small to medium bile ducts
antimitochondrial antibodies (AMA) * directed against the E2 component of pyruvate dehydrogenase complex (PCD-E2) in small bile duct epithelial cells in Hering’s canal closest to the portal tract (periportal)
more common in women middle aged
pruitis
non- caseating granulomas , florid duct lesions (involves ductular epithelium)
Primary biliary cirrhosis (PBC)
You see massive leukocytic infiltration in the portal tracts (lymphocytes and plasma cells)
how is the AMA test in primary biliary cirrhosis done
This is an immunofluorescence study/picture. A drop of the patient’s serum (which pathologically contains AMAs) is placed on normal test tissue. The serum and tissue are incubated and the abnormally present AMAs in the patient’s serum bind to the PDC-E2 in the normal mitochondria of the tissue specimen. The test specimen (patient’s serum-normal tissue) is then washed and a drop of fluorescently tagged anti-anti-mitochondrial antibody is incubated on the tissue. This anti-anti- mitochondrial antibody binds to the AMAs binding to the tissue. This positive reaction can be seen with fluorescent light activation and is seen as bright green staining in the cytoplasm of the test cells. If there were no AMAs in the patient’s serum, no bright green reaction would be seen.
A progressive disease of liver characterized by cholestasis with obliterative fibrosis of intra and extrahepatic bile ducts (with dilation of preserved segments)
most present in Chronic inflammatory bowel disease
male, age 40
cholelithiasis
65% have pANCA, 50% have ANA (Antinuclear Ab)
and 50% have increased serum IgM
onion skinning appearance of bile duct!
primary sclerosing cholangitis
what confirms the diagnosis?
-beading of bile ducts (ERCP or MRI)
Causes in Adults
Obstruction by gallstones
Malignant neoplasms of biliary tree/head of pancreas
Strictures from previous surgery in the bile duct tree
PBC,PSC
Causes in Children
Biliary atresia
Choledochal cysts
Cystic fibrosis
see nodular formation with regeneration ductular proliferation, bile lakes
secondary biliary cirrhosis
-results from prolonged obstruction of the biliary tree
cholestasis, then escape of bile, then inflammatory reaction to bile, then fibrosis (biliary cirrhosis)….may be complicated by ascending cholangitis
bile duct hamartomas
small clusters of dilated ducts or cysts within fibrous stroma
the portal area gets a disorganized bile duct proliferation but those ducts do NOT drain or connect to normal biliary system
von meyenburg complex
hundreds of biliary epithelium lined lesions
PKD1 associated
common fatal association with this disease is subarachnoid hemorrhage from rupture of berry aneurysm in circle of willis
polycystic liver disease
autosomal dominant polycystic kidney disease clinical extrarenal manifestations
bile duct cysts only
cyst + hepatic fibrosis
caroli disease
PC1 and PC2 abnormalites
altered mechanosensation by tubular cilia
altered calcium flux
associated with cysts- abnormal bile ducts
don’t know what the fuck he’d ask about this
what is the most common congenital dilatation of the bile duct
choledochal cysts
fat female fertile forty flatulent
cholelithiasis
cholesterol stones
radiolucent
at 20% CaCO3 become radiopaque
due to increased hepatic cholesterol and/or decrease bile salts/lecithin
abnormal bile flow
↓GB motility: fasting; weight loss, progesterone
heredity (25%): Pima Indians (have ↑cholesterol secretion & ↓bile salts )
Crohn disease: ?disrupted enterohepatic bile salt circulation
cholesterol stones
what are the 4 steps of stone formation
- Increased production/saturation
2. Crystallization (nidus) - Flow (volume, turbulence)
- Accretion (matrix/sludge)
what is the cause of strawberry gallbladder?
cholesterolosis
supersaturated bile and ↑mucosal uptake…can present clinically like acute/chronic cholecystitis …usually with stones (mechanism unknown if stone absent)
- formed from polymers of unconjugated bilirubin (bilirubin calcium salts)
- small (
BLACK PIGMENT STONES
- formed from unconjugated bilirubin + cholesterol
- soft, “soapy” to feel, laminated, may not be picked up on X-ray
- commoner in bile ducts than gallbladder; radiolucent
- associated with E. coli infection (bacterial cholangitis)
- common in Asia because of liver flukes (C. sinensis)
BROWN PIGMENT STONES
what is the evolution of the disease of acute cholecystitis
- Acute obstruction: stone blocks cystic duct→ CCK causes GB contraction → mid-epigastric, colicky pain, N & V
- Stone impaction: ↑mucous behind obstruction → chemical irritation and bacterial overgrowth (E. coli, gut flora) → acute inflammation → pain shifts to RUQ, continuous aching pain, ± radiation
- Bacterial infection: invasion of GB wall → peritonitis → + rebound, Murphy’s sign, neutrophilia, 90% resolve < 1 month
- Gangrenous necrosis: compression of wall vessels → full thickness necrosis → perforation → peritonitis
most common cause of acute cholecystitis is gallstones
what is the HIDA scan
radioactive dye (given IV) is excreted by the liver (GB not seen in acute cholecystitis …even up to 3 hrs…stone blocks duct)
dye normally fills the gallbladder and will later be seen in the small bowel
Helpful b/c if the gallbladder doesn’t appear then it is obstructed! – surgical reason/cause to remove the gallbladder
Caused by stasis/obstruction in biliary tract…stone…tumor
- There is secondary bacterial infection…organism is typically from duodenum - E. coli, Klebsiella, enterobacter ….
Infection moves up the biliary tree into the liver bile duct system…sometimes resulting in multiple small liver abscesses
acute/ascending cholangitis
what is the presentation of a pt with acute ascending cholangitis
Charcot’s triad:
- fever
- jaundice
- abd pain
bile duct is filled with neutrophils/pus
Rokitanski-Aschoff sinuses
porcelain gallbladder
chronic cholecystitis
these are inflammation with occasional mucosal outpouchings -areas where the gallbladder is constricting due to long-standing inflammation
surface mucosa is pulled down into the wall of the mucosa
porcelain- due to dystrophic calcification of gallbladder– high risk for adenocarcinoma ***
most common gallbladder carcinoma
adenocarcinoma
2x more common in women
native americans and hispanics
no symptoms til advanced stge
ERBB2 (Her2-neu) overexpressed in 2/3
poor survival
what are the main causes of cholangiocarcinomas
primary sclerosing cholangitis
choledochal cysts
flukes
painless jaundice
Villous blunting and flattening
increase in intraepithelial lymphocytes
celiac disease
chronic diarrhea with steathorrhea
10% have dermatitis herpetiformis = subepidermal blistering skin lesions
most common cause of chronic gastritis
H. pylori
what do parietal cells secrete
Gastric acid (HCl)
intrinsic factor (Vitamin B12 absorption)
polyhydraminos
child unable to feed
atresia of esophagus
hamartomatous polyps
autosomal dominant
entire GI tract
splayed smooth muscle in the polyp
age 10-15
mutated STK11, AMP kinase-related pathways
mucocutaneous hyperpigmentation (think lips)
increased risk of thyroid, breast, lung, pancreatic and bladder cancers
Peutz-Jeghers syndrome
MLH1, MSH2 microsatellite instability (DNA mismatch repair defect)
10-15 % of sporadic cases of colon carcinoma (adenocarcinoma)
right sided
sessile/serrated
APC/beta catenin multiple hits
classic adenoma (colon adenocarcinoma)
left sided
typical tubular/villous
also seen in familial adenomatous polyposis syndrome
syndrome with esophageal tears from severe vomiting. Most cases occur in the
context of alcohol abuse.
mallory weiss
M>F
FAP related (APC/WNT pathway) , HNPCC related
P53
occurs in gastric antrum and pylorus
forms bulky tumors and masses that ulcerate
heaped up borders and central ulceration
demonstrates malignant gland formation invading the muscular wall of stomach
associated with h, pylori
Intestinal (non-signet ring) or usual type of gastric adenocarcinoma
M=F
no association with h. pylori
CDH1/E - cadherin mutations
p53
Germline loss-of-function mutation in tumor suppressor gene CDH1 (encodes E-cadherin)
very poor survival rates
do not tend to ulcerate but infiltrate diffusefly in to the wall of the stomach- thick , hard like a wine flask
linitis plastica –> gastric walls is markedly thik and rugal folds are lost
diffuse-type signet ring gastric adenocarcinoma
see signet rings
t11;18
t1;14
t14;18
h. pylroi related
constitutive activation of NF-kB- promotes b cell growth and survival
arises at sites of previous inflammation
50% disappear with Ab Tx
CD19+ and CD20 +
diagnosis:
lymphoepithelial lesions in the gastric epithelium with neoplastic lymphocytes surrounding and infiltrating gastric glands
MALTOMA
arises from interstitial cells of Cajal (pacemaker cells)
M>F, age 60
80% have tyrosine kinase c-KIT (CD117)
15% have PDGFA mutations
arises from mesenchyme NOT epithelial
Responds to Imatinib
Mesenchymal (gastro-intestinal stromal tumor) GIST
punched out lesions in the esophagus in immunocompromised
herpes simplex
well differentiated neuroendocrine carcinoma
salt and pepper in the nuclei of tumors
serotonin release:
- skin flushing
- diarrhea, abd pain,
- asthma, bronchoconstriciton
- strongly associated with mets
carcinoid tumors
pANCA found in what
75 % of UC
occurrence of a liver abscess after an episode of
diarrhea most likely results from infection with
Entamoeba histolytica
Infection with Tropheryma whippelii
causes Whipple disease,
which may involve any organ, but most often affects intestines, central nervous system, and joints
A 35-year-old woman has had increasing lower back pain for 5 years. At various times during the past year, she also
has had arthritic pain involving the knees, hips, and wrists. A stool sample is positive for occult blood. A pelvic radiograph
shows changes consistent with sacroiliitis. A colonoscopy is performed, and she undergoes a total colectomy. The figure
shows the gross appearance of the colectomy specimen. What is the most likely diagnosis?
□ (A) Dysregulated CD4+ T-cell responses
□ (B) Cross-reaction of antibodies against gut bacteria
□ (C) Auto-antibodies directed against tropomyosin
□ (D) Mutations in the NOD2 gene
□ (E) Germline inheritance of the APC gene mutation
The segment of the colon shows the diffuse and severe ulceration characteristic of ulcerative colitis. The
inflammation shown is so severe that areas of mucosal ulceration have produced pseudopolyps or islands of residual
mucosa. Ulcerative colitis is a systemic disease; in some patients, it is associated with migratory polyarthritis, ankylosing
spondylitis, and primary sclerosing cholangitis. The pathogenesis of ulcerative colitis is unclear, but is most likely mediated
by a T-cell response to an unknown antigen (but not a gut infection), leading to an imbalance between T-cell activation
and regulation. The CD4+ T cells present in the lesions secrete damaging substances.
NOD2
crohn’s
protein losing enteropathy
excessive secretion of TGF-alpha
Metetrier disease - type of hypertrophic gastropathy
enlarged rugal folds
this is diffuse hyperplasia of foveolar epithelium of body and fundus
pt’ presents with multiple peptic ulcers b/c of this gastrin secreting tumor
zollinger-ellison
F>M
sporadic and in pt’s with FAP
proton pump inhibitor related
Upper GI endoscopy reveals 3 circumscribed, round, smooth lesions in
the gastric body from 1 to 2 cm in diameter. Biopsies are taken and microscopically show the lesions to consist of irregular
glands that are cystically dilated and lined by flattened parietal and chief cells
fundic gland polyp
most common in the antrum, have intestinal metaplasia with dysplasia, and are
precursors to adenocarcinoma; they may occur with FAP
M>F
arise in chronic gastritis
epithelial dysplasia
gastric adenoma
most common bacteria in biofilm in mouth
streptococcus mutans
LL37
produced by neutrophils and made in the salivary glands.
produces Kostmann Disease- with horbbile peridontitis
mutlinucleated giant cell inclusions
establishes latency in trigeminal ganglion and recurs on lip or lower face
Tzanck test for Herpes Simplex Virus
what are the 2 types of initial HSV-1 infections
90% age 2 to 4 yr; asymptomatic or mild, transient orofacial blisters
10% Acute Herpetic Gingivostomatitis numerous variable-size mucosal ulcers
Pseudo-hyphae…budding blastoconidia
white - easy to scrape off
oral candidiasis
candida albicans
associated with immune suppression and EBV
lateral tongue
doesn’t scrape off
balloon cells
hairy leukoplakia
hypertrophy of filiform papillae on the dorsal surface of the tongue, usually due to a lack of mechanical stimulation and debridement. This condition often occurs in individuals with poor oral hygiene (eg, lack of tooth brushing, eating a soft diet with no roughage that would otherwise mechanically debride the dorsal surface of the tongue).
black hairy tongue
white patch/plaque that cannot be scraped off and is due to increased keratin
Leukoplakia
hyperplasia/hyperkeratosis
Hyperkeratosis alone is NOT a premalignant change
But, 5 - 25% leukoplakia do contain premalignant findings
Biopsy is needed to evaluate if premalignant changes present
what is the prognosis of erythroplakia
less common than leukoplakia, but more ominous … represents highly vascular eroded mucosa …” ~ 90% have dysplasia or CIS, some have invasive SCC
oral pharynx squamous cell carcinoma is most likely caused by what
HPV type 16 (tonsils, base of tongue, oral pharynx) and have p16, E6 and E7 mutations
these have better prognosis usually
whereas SCC of the oral cavity are usually due to chronic alcohol/tobacco use, mutaitons in p53, NOTCH1
parotid gland acinar epithelial cell type
serous
Acute onset of bilateral (~90% cases) tender, self-limited swelling of parotid or other salivary glands lasting 2+ days
Major complication: Testicular inflammation (orchitis) occurs ~40% of postpubertal males. Sequela may be sterility.
mumps!
SS-A (Ro) and SS-B(La) antibodies
angular chelitis -corners of mouth
dry eyes and mouth
commonly associated with RA
women
Sjogren’s
immunologically mediated destruction of the lacrimal and salivary glands
Biopsy of the lip (to examine minor salivary glands) is essential for the diagnosis of Sjögren syndrome.
50% all salivary gland tumors and 70% of benign neoplasms
Location: 60% - parotid, 40% - submandibular/sublingual; rare - in minor salivary glands.
Termed “Mixed Tumor” because both epithelial and mesenchymal (myxoid - cartilage) elements - neoplasm arises from multipotential basal myoepithelial cells
Carcinoma in this disease develops In 5-yrs , 2% develop carcinoma. In 15-yrs period, 10% of those unresected will develop cancer.
white glistening tumors
pleomorphic adenoma (mixed tumor) benign
arises almost exclusively in the parotid gland (the only tumor virtually restricted to the parotid) and occurs more commonly in males than in females, usually in the fifth to seventh decades of life
more common in smokers
On microscopic examination these spaces are lined by a double layer of neoplastic epithelial cells resting on a dense lymphoid stroma (lymphocyte follicles) sometimes bearing germinal centers
Double layer of tall eosinophilic epithelial cells over a lymphoid stroma
Warthin Tumor (Papillary Cystadenoma Lymphomatosum)
Parotid is the predominant site
[Parotid contains ~75% salivary tissue mass]
Slow-growing, but relentless:
difficult to excise and treat
Grade most important prognostically
Low-grade: locally aggressive, rarely metastasizes
>95% 5-yr and 10 year survival
High-grade: Invasive, frequent metastasis
mucoepidermoid carcinoma
Difficult to Treat
“Perineural invasion”
Tumor spreads via peripheral nerves with numerous “skip” or non-contiguous tumor extensions
“swiss cheese” appearance
adenoid cystic carcinoma
receptor tyrosine kinase RET
associated w/ down syndrome
hirschsprung disease
, presents as a triad of postcricoid dysphagia, esophageal webs, and iron deficiency anemia.[1] It most usually occurs in postmenopausal women.
often complain of a burning sensation with the tongue and oral mucosa, and atrophy of lingual papillae produces a smooth, shiny, red dorsum of the tongue.
Symptoms include: Dysphagia (difficulty in swallowing) Pain Weakness Odynophagia (Painful swallowing, also called Algiaphagia) Atrophic glossitis Angular stomatitis increased risk of carcinoma
Plummer–Vinson syndrome (PVS
CREST
calcinosis - calcium deposits in skin
Raynaud’s phenomenon
Esophageal dysfunction- acid reflux and decrease in motiliyt of esophagus- rubber hose like tube
Sclerodactyly - thickening and tightening of the skin on the fingers and hands
Telangiectasis - dilation of capillaries causing red marks on surface of skin
10% of pt’s with primary biliary cirrhosis have CREST
anti-DNA topoisomerase (anti-Scl 70)
bacterial enterocolitis infection associated with guillan barre sydnrome
campylobacter
