1 - Pathology

Question 0

Describe Esophageal Cancer.

Answer 0

1) Squamous Cell Carcinoma and Adenocarcinoma dominate in the US
2) SCC: linked to smoking, EtOH, nitrites, radiation, lye -> upper 2/3 of esophagus; AA male –> less p53, p16/INK4a
3) Adeno: chronic GERD leading to Barrett’s Esophagus (intestinal metaplasia) and dysplasia -> lower 1/3 esophagus; white male –> less p53, Rb; more cERB-B2, cyclin D1/E
* * both spread locally as opposed hematogenously
4) Presentation: dysphagia and wt loss, odynophagia, emesis, aspiration
5) Dx: typically only symptomatic after significant development; dx via endoscopy or contrast imaging -> Barrett’s(red velvety from GEJ; goblet cells in columnar epi), strictures, ulcerations, ulcerations
6) Tx/Prognosis: esophagectomy, stricture ballooning, chemo -> 5yr @ 25%

Question 1

What is ileus?

Answer 1

• temporary absence of contraction within any of the intestinal segments caused by irritation of the intestine
• commonly seen after surgery
• mediated by VIP and NO release and enteric and sympathetic nervous stimulation
• symptoms: nausea, vomiting, no bowel sounds, constipation, and low appetite

Question 2

Describe Gastric Adenocarcinoma.

Answer 2

• *2nd most common cause of cancer related death
  1) Intestinal Type: metaplasia of gastric mucousal cells; typically in the antrum; can ulcerate (thick/rolled edges, NOT smooth bottom) -> Risk: H.pylori, chronic gastritis, high salt diet
  2) Diffuse Type (linitis plastica): cells lack normal cohesion resulting in diffuse, infiltrating mass; more common in younger patients –> Signet Ring neoplasm
  3) Presentation: frequently asymptomatic until very advanced; pain, post-prandial fullness, wt loss, nausea; Metastasis to Left Supraclavicular node (node of virchow); mets to ovaries; mets to umbilical node (Sister Mary Joseph sign)
  4) Tx: surgery, chemo, radiation -> 5yr @ 10-20%

Question 3

Describe Peptic Ulcer Disease.

Answer 3

1) results from a disruption in the balance between the acidic/neutralizing influences of the antrum/proximal duodenum
2) MOST commonly associated w/ H.pylori (gm -, curved rod) -> hyperchlohydric chronic gastritis (urease, VacA, CagA)
3) Presentation: pain that is relieved by eating, iron deficiency, pernicious anemia (intrinsic factor), hemorrage
4) Ulcers: solitary (unless Zollinger-Ellison) round to oval, “punched-out” appearance, edges are even w/ surrounding tissue, folds radiate from the rim of lesion, covered w/ necrotic debris and neuts; Base of the lesion -> smooth, granulation tissue and fibrous CT
5) Risk: H. pylori (gastric), NSAIDs, tobacco, corticosteroids (Cushing Syn)
6) Tx: triple/quadruple therapy (PPI + 2 antibiotics/PPI + 2antibiotics + bismuth sulfate)

Question 4

Describe Pleomorphic Adenoma.

Answer 4

1) most common neoplasm of the salivary glands
2) Benign tumor of mixed cell type (ductal, myoepithoid, myxoid, hyaline) frequently seen in the Parotid
3) Encapsulated, lobulated tumor w satellite extensions ; gray-white center
4) Distinguish from Warthin tumor: double-layered columnar cells, secretes mucin, cystic w/ lymphocytes in center; smokers at 8x risk

Question 5

Describe Celiac disease.

Answer 5

1) autoimmune entity w/ Ab to gliadin fraction of gluten
2) Symptoms: chronic diarrhea w/ steatorrhea and pale, foul-smelling stool; growth retardation/failure to thrive; associated w/ dermatitis herpetiformis (grouped, pus vesicles)
3) Histo: mucousal inflammation -> villus atrophy w/ crypt hyperplasia of duodenum and jejunum (mostly)
4) Dx: anti-gliadin, anti-endomysial, anti-TTG

Question 6

Describe Chron disease.

Answer 6

1) Inflammatory Bowel Disease -> focal, transmural inflammation occurring throughout the GI tract (most common in terminal ileum and colon)
2) Symptoms: diarrhea w blood and mucous, crampy abdominal pain, fever, tenesmus, wt loss, blood loss
3) Gross: transmural inflammation, cobblestone-mucosa, bowel wall thickening, strings of ulcerations, fissures/fistulas due to transmural affect
4) Histo: noncaseating granulomas, lymphoid aggregates
5) Extraintestinal: migratory polyarthritis, erythema nodosum, ankylosing spondylitis, Uveitis, immunological disorders

Question 7

Describe ulcerative colitis.

Answer 7

1) Inflammatory Bowel Disorder -> continuous, ulcerative disease of the mucosa/submucosa that proceeds from anus through colon
2) Symptoms: diarrhea w blood and mucous, crampy abdominal pain, fever, tenesmus, wt loss, blood loss -> Complications: toxic megacolon, Colorectal Carcinoma
3) Gross: continuous, friable mucousal Psuedopolys with free hanging mesentery
4) Histo: Crypt abcesses and ulcers -> NO ganulomas
5) Extaintestinal: pyoderma granrenosum, Primary Sclerosing Cholangitis

Question 8

Describe diverticulitis.

Answer 8

1) Diverticulosis: typically asymptomatic out-pouchings of the colon (sigmoid more common)
2) Associated w/ low fiber diet which caused increased intraluminal pressure
3) Diverticulitis: most common complication of diverticulosis; fecal impaction can lead to lyphatic obstruction, localized ischemia, and bacterial overgrowth
4) Presentation: LLQ pain, rebound tenderness, leukocytosis, fever, bloody stool -> can lead to perforation and peritonitis
5) Barium Enema and Colonoscopy are CONTRAINDICATED

Question 9

Describe colon polyposis syndromes.

Answer 9

1) typically genetic disorders that present as polyps of the proximal/right colon in younger ages
2) Familial Adenomatous Polyposis -> autosomal dominant mutation of APC gene(5q21), present w/ 1000s of cancerous/pre-cancerous polyps -> ~100% develop colon cancer
3) Hereditary Nonpolyposis Colorectal Cancer (HNPCC) -> Autosomal dominant mutation in DNA repair gene (hMLH1/hMSH2); causes colorectal adenomas and cancer
4) Peutz-Jeghers Syndrome: Autosomal dominant mutation (LKB1/STK11) resulting in hamartomatous colon polyps AND mucocutaneous hyperpigmented lesions of the lips, oral mucosa, hands and genitals; increased risk of Colon Cancer

Question 10

Describe colorectal cancer.

Answer 10

1) Adenocarcinoma of the large intestine/rectum -> VERY common
2) Risk: age, family hx, low fiber diet, Villious Adenomas, IBD(UC), Familial Adenomatous Polyposis, Peutz-Jerhers, Jevenile polyposis, HNPCC
3) Thought to be primarily a progression from adenoma-to-carcinoma based on environmental and genetic factors -> APC, p53, K-RAS
4) Symptoms: Left -> obstruction of left colon (napkin-ring, apple-core constriction) presents as bowel habits; Right -> anemia, wt loss, abdominal pain, watery diarrhea; Either -> constitutional symptoms, melena, pencil-thin-stool
5) Dx: colonoscopy w/ biopsy, CT, Carcinoembryonic Antigen (CEA) for post-tx progress
6) Tx: surgical resection, chemo,

Question 11

Describe Hirschsprung’s disease.

Answer 11

1) complete functional obstruction of the large bowel due to absence of ganglion cells of both the myenteric and submucosal plexuses
2) ALWAYS involves the anus and progresses proximally -> dilation -> congenital megacolon (as opposed to toxic megacolon in UC)
3) Mutation in RET (oncogen) is also associated with Down syndrome, Waardenburg syndrome -> male more common
4) Presents: failure to pass meconium w/in 48hrs of birth; bilious vomiting, abdominal distention,

Question 12

Describe pancreatitis.

Answer 12

1) Pancreatitis: inappropriate activation of pancreatic enzymes leading to pancreatic autodigestion with hemorrhagic fat necrosis
2) Presentation: sudden “burrowing” epigastric pain radiating to the back/flanks, anorexia, nausea -> following large meal/drinking
3) Dx: leukocytosis and elevated serum amylase/LIPASE, Fat Necrosis w/ pale basophilic calcium soaps, hemorrhage, necrotic debris and inflammatory response
4) Tx: supportive, pain control (opoids); surgical ONLY in trauma, stones/obstructive lesions
5) Complications: DIC, ARDS, diffuse fat necrosis, hypoglycemia, psuedocyst, hemorrhage and infection
6) Chronic Pancreatitis: typically presents as repeated episodes of acute pancreatitis; Pancreatic calcifications, steatorreah and diabetes mellitus
7) Risk: I GET SMASHED: Idiopathic, Gallstones, ETHANOL, Trauma, Steroids, Mumps, Scorpian, Hypercalcemia/lipidemia, ERCP, Drugs -> CF is common for child chronic pancreatitis

Question 13

Describe pancreatic adenocarcinoma.

Answer 13

1) Adenocarcinoma of exocrine pancrease w/ Trouseau Sign: migratory phlebitis
4) Lab: elevated bilirubin (conjugated) and AlkPhos; CA19-9 (non-dx)
5) Imaging: CT, ERCP, MRI, endoscopic ultrasound
6) Tx: surgical removal ->Whipple operation

Question 14

Describe pancreatic cysts.

Answer 14

1) Benign Cysts: Serous Cystadenoma, congenital cysts, psuedocysts
2) Invasive Cysts: Mucinous Cyst Carcinoma, intraductal pappillary mucinous neoplasms, solid pseudopapillary neoplasm
3) Serous -> small cysts lined w/ small, cuboidal cells filled w/ clear fluid
4) Mucinous -> large, shiny cysts lined w/ columnar mucinous epithelium

Question 15

Describe alcoholic hepatitis.

Answer 15

1) Reversible inflammatory disease caused by EtOH and is the most common precursor of cirrhosis in US
2) Presentation: many asymptomatic; nausea, malaise, Tachycardia, low fever -> can develop Cirrhosis and/or Portal HPTN -> ascitis, esophageal/umbilical varices, hepatic encephalopathy, hepato/splenomegaly
3) Labs: elevated AST, ALT (AST/ALT > 2), AlkPhos, and prolonged PT
4) Histo: fatty change, neutrophil infiltrate (not viral), ballooning necrosis, Mallory Bodies (eosinophilic inclusion bodies) –> fibrosis
5) Gross: yellow/brown non-glistening, Diffuse Nodular surface
6) Tx: abstinence, Vit K (coagulation), supportive
* *A Scotch and Tonic: AST»ALT = EtOH; ALT»AST = viral hepatitis

Question 16

Describe Cholelethiasis and Cholecystitis.

Answer 16

1) Cholelithiasis: stones precipitate in the gallbladder (duco - duct) due to disruption in cholesterol/bilirubin:bile acid ratio
2) Increased cholesterol/bilirubin load or decreased bile resorption
3) Symptoms: RUQ pain that radiates to right shoulder, worse after meals, nausea, vomiting
4) Risk: Cholesterol -> Chron’s, CF, estrogen, rapid wt loss; Pigment -> chronic RBC hemolysis, EtOH cirrhosis, biliary infection
5) Cholecystitis/Cholangitis: infection following stone obstruction; fever, leukcytosis, jaundice, Murphy Sign, wall thickening and edema help distinguish -cystitis from -lethiasis

Question 17

Describe hemochromatosis.

Answer 17

1) Hemochromatosis (inherited): autosomal recessive of HFE (most), transferrin receptor 2 or hepcidin
2) Presentation: typically subclinical until >40yrs; men present earlier than women due to menstration; early signs -> fatigue, wt loss, abdominal pain, lost libido; Late -> cirrhosis w/ Fe, hepatomegaly, DM type I (Fe in Islet cells), hyperpigmentation of skin (increased melanin production), heart failure (Fe in myocardium)
3) Hemosiderosis (acquired): Fe overload from repeated blood transfusion or in thalassemia
4) Tx: phlebotomy, chelating agents, NO EtOH, supportive

Question 18

Describe Hepatocellular Carcinoma.

Answer 18

1) Very common tumor w/ strong association to hepatitis B/C infection and a 4x male prevalence
2) Presentation: similar to other chronic liver dx; pain/mass in RUQ, bruit/rub over liver; elevated Alpha Ferroprotein (AFP) and AlkPhos -> can also present as acute exacerbation of underlying liver disease
3) Dx: Imaging, AFP>500-1000,
4) Tx/Prognosis: surgical resection, chemo and radiation; mets common to lung, brain, bone and adrenal; medial life exp = 6-20mo
5) Fibrolamellar Carcinoma: eospinophilic inclusions, collagen bands -> seen in younger (20-40) pt w/ no chronic live dx -> has better prognosis

Question 19

Describe Primary Biliary Sclerosis and Primary Sclerosing Chonlangitis.

Answer 19

1) PBC: autoimmune rxn (AMA+) of women (90%) to biliary duct epithelium leading to destruction of small-medium INTRAhepatic bile ducts
2) Presentation: early -> pruritis, fatigue, abdominal discomfort, skin pigmentation, xanthlasmas, steotorrhea; late -> jaundice, hepatic decompensation, portal hypertension, esophageal varices –> HCC
3) Associated -> collagen/vascular dx, Sjogren, systemic sclerosis
4) Histo: periportal mononuclear infiltrate, intrahepatic ductile prolipheration, granulomas, hepatic necrosis (ballooning degeneration), foamy xanthomas/inclusions
5) PSC: chronic cholestatic liver dx due to fibrosis and narrowing of INTRA and EXTRAhepatic bile ducts; more common to men (66%) and AMA(-)
6) Associated -> Ulcerative Colitis (70%), Cholangiocarcinoma

Question 20

Describe acetaminophen toxicity.

Answer 20

Stage 1) hours after ingestion - nausea, vomiting
Stage 2) recover for next 1-2d
Stage 3) return of nausea, vomiting w/ RUQ pain; progresses to jaundice, hypoglycemia, prolonged PT -> hepatic encephalopathy, hepatorenal syndrome, hemorrhage -> death?
Stage 4) recovery
1) Overdose causes the release of huge amounts of hepato-toxins that cause cell death –> HUGE increases in AST, ALT, bilirubin and PT
2) AST and ALT may fall as hepatocytes dropout, but PT and Albumin will still be abnormal (function vs damage enzymes)
3) Gross: submassive hepatic necrosis causes the liver to shrink and appear smooth/wrinkled surface; deep tan-brown or even green appearance
4) Histo: centri/mid-zonal coagulative necrosis leaving “islands” of viable hepatocytes; micro-steatorreah may be seen in viable cells
5) Tx: N-Acetylcystein (NAC) is the anecdote -> competes for CYP2E1 pathway
6) EtOH can potentiate toxic pathway

Question 21

Describe Gaucher Disease.

Answer 21

1) Gaucher Disease: autosomal recessive, lysosomal storage disorder due to deficiency of glucocerebrosidases
2) Glucocerebrosides accumulate in phagocytic cells throughout the body (Gaucher cells) -> large, pale stainging cells w/ fibrillary cytoplasms and elongated lysosomes
3) Accumulate in SPLEEN and LIVER as well as bone marrow, lungs, lymph nodes, etc.
4) Symptoms: Type I -> frequently presents as splenomegaly, anemia, leukopenia, thrombocytopenia; Type II -> neuropathic variant is characterized by progressive CNS deterioration at young age and death
5) Tx: splenectomy, liver transplant, transfusions, and Enzyme Transplant

Question 22

Describe Neonatal Cholestasis.

Answer 22

Causes:

1) Idiopathic neonatal hepatitis (40%)
2) Extrahepatic biliary atresia (30%)
3) alpha-1 antitrypsin deficiency (10%)
6) Hepatitis (TORCH infections) (5%)

1) Early ( EBA initially presents as cholestasis and ductal proliferation w/ expanded loose CT
2) Late (>6mo) -> Biliary Cirrhosis causes nodular, bile-stain liver -> bile lakes and necrosis
3) Tx: surgical repair