GI path Flashcards
A 35 year old woman presents to her physician after a dentist appointment where the dentist discovered a mobile mass in her left parotid gland. The mass was excised and the following was discovered. What is the most likely diagnosis and treatment? What is the prognosis?
Pleomorphic adenoma of salivary gland
- MOST COMMON salivary glands neoplasm
- Most commonly in the PAROTID followed by minor salivary glands
- Wide age at presentation
- PAINLESS, slowly growing mass, mobile
- Paresthesia due to nerve compression - rare
Histo:
- Well-circumscribed, variably encapsulated mass
- Multinodular (esp. in recurrent disease)
- Composed of three cell types:
1. Epithelial glandular ductal structures
2. Myoepithelial cells
3. Mesenchymal stroma: myxoid, chondroid, hyalinized, osseous
Treatment:
- Surgical excision
Prognosis:
- Recurrence rate: 45% after simple enucleation (due to lack of encapsulation or incomplete removal)
- Recurrence rate: 2.5 % with superficial or total parotidectomy
- Malignant transformation – in 2-7%
The following histologic specimen was obtained from a parotid gland mass. There was a similar mass on both parotid glands (bilateral). Based on the appearance, what is the diagnosis, treament and prognosis?
Warthin’s tumor:
- Second most common benign salivary gland tumor
- Characteristically presents in the parotid
- Bilaterality or multifocality occurs more frequently than any other tumor, and it is synchronously identified with other tumors more than any other tumor type
Histo:
- Circumscribed, solid/cystic. Cysts may contain yellow-brown fluid.
- Papillary fronds and cystic spaces lined by double layered oncocytic epithelium
- Dense lymphoid node-like stroma intimately associated with the epithelial component
Treatment:
- Surgical excision
Prognosis:
- 4-25% recurrence due to multifocality or incomplete excision
Mucoepidermoid carcinoma
Most common malignant tumor
- Mucinous and squamous components
- Painful mass d/t common involvement of facial nerve
A 45 year old woman presents to her physician with increasing difficulty swallowing as well as trouble breathing at night. Upon barium swallow, the following is visible. What is her diagnosis and treatment?
Achalasia- esophageal dilation
Achalasia= Inability of the LES (lower esophageal sphincter) to relax after swallowing, resulting in periodic esophageal obstruction
Clinical: dysphagia, odynophagia, regurgitation, increased risk for squamous cell carcinoma
Histo: reduction/absence of myenteric ganglion cells
Barium swallow= see smoothly tapered distal end due to:
- Hypertensive LES (Most common cause)
- Incomplete LES relaxation
- Aperistalsis of esophageal body
Diagnosis: barium swallow, upper endoscopy, abdominal CT, endoscopic ultrasound to rule out secondary causes (carcinoma, etc.)
Treatment: Botulinum toxin, pneumatic dilatation, surgical myotomy (laproscopic)
A 55 year old obese man reports frequent chest pain, especially after eating spicy foods or drinking coffee. What is his diagnosis based on the endoscopic exam and what are the complications of this condition?
GERD: see hyperemia, vertical linear streaks due to mucosal erosions/ulcers
Pathogenesis:
- Defective/weak LES pressure barrier
- Abnormal/inappropriate transient LES relaxations
- Increased acid/pepsin secretion
- Esophageal clearing defects: peristalsis, gravity, salivary flow, hiatal hernia
Associated symptoms: Regurgitation, pulmonary symptoms (adult-onset asthma), cough (at night), hoarseness, laryngitis, chest pain, disturbed sleep
Lab tests:
1) 24-hour ambulatory esophageal pH monitoring= gold standard (measures proximal and distal esophagus, stomach pH)
2) Endoscopy (with biopsy)- rule out other pathology, look for Barrett’s
3) Bernstein test= reproduce patient’s symptoms by infusing acid into esophagus
Complications: Esophagitis–> peptic stricture, esophageal hemorrhage, ulcer, pulmonary symptoms, Barrett’s esophagus
- Biopsy findings are NOT specific: ANYTHING causing injury to esophageal tissue can cause histology ressembling GERD
A 56 year old man with a history of chronic liver disease comes to the ER with hematemesis. Based on the specimens below, what is his diagnosis, what caused this anomaly, and how should he be treated?
Esophageal varices= dilatation of submucosal esophageal veins, often due to portal hypertension secondary to cirrhosis
- *Treatment**
1) ABCs - Tranfuse hemoglobin
2) Pharmacological therapy - Somatostatin analogues: octreotide
- Prophylactic antibiotics
3) Endoscopic therapy – band ligation (put band at base of varice - If unsuccessful, then tamponade – Sengstaken-Blakemore or Minnesota tube
4) Shunt= transjugular intrahepatic porto-systemic shunt (moves flow from portal vein to hepatic vein)–> risk for HEPATIC ENCEPHALOPATHY, ischemia of liver (bypassing liver metabolic processes, depriving liver blood flow)
Below: Portal hypertensive gastropathy= increased vascularity of stomach mucosa (milder form of portal HTN pathology)
A 35 year old man complains of new onset pain with swallowing. He is sexually active and states that he recently engaged in unprotected oral sex with another man. Based on the endoscopic view below, what is his diagnosis?
Herpes esophagitis: pain with swallowing (odynophagia) due to severe inflammatory process disrupting esophageal mucosa
Histo: lateral margin of ulcer: see Cowdry A intranuclear inclusions
A 30 year old man with a history of asthma goes to see his physician because of chronic symptoms of heartburn. He tells his doctor he’s tried Tums and he just finished a 3-week trial of Prilosec but his symptoms have persisted. The physician decides to perform an endoscopy- the results of which are below. What is the patient’s diagnosis and treatment?
Primary eosinophilic esophagitis
Clinical features
Dysphagia, food impaction, mimics GERD
Many pts have allergic history (asthma, etc.)
By definition, pts have normal pH monitoring levels &/or fail antireflux therapy
Histo: > 15 eosinophils/high powered field in squamous epithelium in patients lacking response to PPIs/have normal pH (to rule out GERD which also causes eosinophilia)
Treatment: dietary modification +/- corticosteroids
A 67 year old alcoholic patient presented with profusely bloody vomit to the emergency room and later expired. The following was found at autopsy. What caused this pathology?
Mallory-weiss laceration
- at GE junction (usually on gastric side)
- Forceful vomiting/retching forces prox stomach through diaphragm
- Laceration may bleed profusely
- Acute esophageal rupture–> Boerhaave’s syndrome
A 40 year old woman comes to her doctor complaining of difficulty swallowing. Additionally, she has increased bruising and her periods have gotten heavier. Based on the endoscopic image below, what is her diagosis?
Esophageal web= eccentric, thin membrane of tissue in esophagus, most commonly proximal. Can cause dysphagia, aspiration
Plummer-Vinson syndrome= esophageal webs + iron deficiency anemia + glossitis; seen in women, responds to iron supplementation
An 85 year old man reports to his physician that he feels like he gets food stuck in his throat. He reports no problems swallowing (getting the food out of his mouth and down into his throat), but once in his throat it feels like it gets stuck. Based on his endoscopic exam, what is his diagnosis?
Esophageal diverticula= outpouchings of esophageal wall
True= all layers, including muscle
False= mucosa and submucosa only
Zenker’s diverticulum = false, seen in elderly, cervical esophagus
Epiphrenic diverticulum= true diverticulum, any age, just above diaphragm
A 55 year old man has had chronic heartburn for the last 20 years that he has “managed” with tums and decreasing ingestion of spicy foods. Upon endoscopic examination, you see the following. What is his diagnosis and what other concerns might you have?
Barrett’s esophagus= Endoscopically recognizable columnar metaplasia of the esophageal mucosa that is confirmed pathologically to have intestinal metaplasia, the latter defined by goblet cells. Complication of longstanding reflux
Both the endoscopic and pathologic components should be present to establish BE
See “salmon pink tongues” (columnar metaplasia) and goblet cells in luminal esophagus= intestinal metaplasia
Below: contrast with normal GE junction: Barrett’s squamocolumnar junction (Z-line) does not correspond to gastroesophageal junction
Development of adenocarcinoma in BE= metaplasia–> dysplasia–> carcinoma sequence (50-fold increase in adenocarcinoma- 5-8% 5-year survival)
* 2% risk in BE pts W/O dysplasia
* 20% risk in BE pts W/ high-grade dysplasia (~45% low-grade dysplasia progress to high grade)
35 year old male presents with colicky abdominal pain and diarrhea 4-5 times a day for the past 2 years. What is his differential and diagnosis based on the colonoscopy image below?
Celiac sprue:
- Antibodies to gliadin
- Distal duodenum, proximal jejunem
- Loss of villi on histology
Malabsorption of:
- Vitamin K–> hemorrhagic diathesis
- Iron deficiency
- associated with dermatitis herpetiformis
- Increased risk of malignancy (T-cell lymphoma)
Labs:
- Abnormal tissue transglutaminase
- IgA to gliadin
- Anti-endomysial, anti-reticulin antibodies
- HLA-DQ2/DQ8
- *Chronic diarrhea without blood**= Malabsorption due to:
- Pancreatic insufficiency
- Small intestinal bacterial overgrowth
- Celiac Sprue
- Lactose Intolerance
- Diabetes
- Infectious: HIV (microsporidia, isospora and cryptospora), Giardia
- Diabetes associated with nocturnal diarrhea
- Irritable bowel syndrome
- Microscopic colitis
Colonoscopy= celiac sprue; see small-bowel scalloping
Testing:
- Gluten-containing diet before biopsy, response to gluten-free diet
- Serology: Anti-tTG IgA (anti-tissue transglutaminase; high sensitivity, specificity), serum IgA (to rule out IgA deficiency= false negative), anti-endomysial, HLA testing of DQ2/DQ8
- Thyroid function tests
- Stool (WBCs, ova, parasites, culture)
- Colonoscopy for: colonic polyps, IBD, collagenous colitis, microscopic colitis
- Be careful with biopsies from duodenal bulb: subjected to physiologic peptic injury–> broader, shorter villi and increased PMNs in normal physiologic state
Fast patient for 48 hours: If malabsorption is suspected (steatorrhea), workup includes:
- 72 fecal fat collection (100gm fat diet) nl
- D-xylose test if abnormal suggest small bowel, if nl suggests pancreatic insufficiency
- Small bowel malabsorption celiac, Whipples, Crohn’s
- Bacterial overgrowth: Hydrogen breath test, trial of antibiotics
- Schilling test for B12 absorption
- *Below:** Increased intraepithelial and lamina propria lymphocytes, lamina propria plasma cells, severe villous blunting, crypt elongation- Marsh 3 classification. Other conditions with histologic pattern of increased IEL/ villous blunting:- Disorders of immune regulation (common variable immunodeficieny, HIV, enteropathy, autoimmune)
- Infections (H. pylori, tropical sprue, bacterial overgrowth, parasites)
- NSAID injury
A 34 year old woman was recently in a car accident where she sustained severe trauma. She underwent surgery and had to recieve 3 units of blood. A week later during her hospital stay she reports horrible abdominal pain and begins to vomit- the vomit contains threads of blood. Based on the histologic specimen below, what is her diagnosis and what caused this? What is the treatment?
Acute erosive/hemorrhagic gastritis= Abrupt onset of ab pain & bleeding a/w ETOH, NSAIDs, or low hemodynamic state following trauma
Mechanism: Breakdown of mucosal barrier due to:
- Direct irritant action
- Drug mechanism of action
- Hypoperfusion
- *Curling’s ulcer**= burn/uremia/EtOH–> decreased plasma volume–> sloughing of gastric mucosa (Curling irons burn)
- *Cushing’s ulcer**= brain injury–> increased vagal stimulation–> increased Ach–> increased H+ (lose Cushion in the brain)
Etiologies:
- ASA, NSAID, EtOH, Steroids, cocaine, crack, acid/alkali ingestion, KCl, iron pills, radiation/chemo
- Sepsis, major trauma, severe burn
- Post-operative state
- *Gross:** petechiae, erosions, ulcers
- *Histo**: limited to mucosa; superficial lamina propria hemorrhage, mucosal sloughing/necrosis, neutrophils
Treatment: Acid-suppression (H2 blockers, PPIs)
A 50-year-old man presents with recurrent GERD. He states that he has been avoiding spicy foods and doesn’t eat for at least 3 hours before going to bed, but he still has acid reflux. Based on the histologic sample below, what is his diagnosis and treatment?
H. pylori gastritis= spiral shaped organisms resting on surface of mucous layer–> secrete toxin (non-invasive organism)–> neutrophilic infiltrate in pits, crypts, and crypt lumens Seen in antrum (vs body/fundus in autoimmune gastritis)
Definition= Chronic antral-predominant gastritis caused by H. pylori (environmental atrophic gastritis- vs autoimmune)
Clinical= Associated with peptic ulcer disease (stomach & duodenum), gastric lymphoma & carcinoma
Histo: pititis, cryptitis, crypt abscesses (neutrophils= activity)
* Gastric MALT lymphoma due to H. pylori can regress after eradication of infection
A 55 year old man presented to his physician complaining of worsening nausea and vomiting over the past several days. On physical exam, the physician noted some ascites but no other symptoms of liver disease. The patients blood panels came back normal except for decreased albumin. An endoscopic exam was performed and a sample of gastric tissue was taken (below)- what is the patient’s diagnosis?
Menetrier’s disease: hyperplastic gastropathy
Definition= Body & fundus-restricted hyperplasia of foveolar (mucous cell) epithelium with hypoproteinemia
Clinical= decreased plasma proteins (albumin) from gastric mucosa, decreased acid production
Pathogenesis= TFG-alpha overexpression
Gross= Markedly thickened rugal folds in fundus & body (resembling brain)- looks grossly identical to Zollinger-Ellison
Microscopic= Foveolar (mucous cell) hyperplasia–> corkscrewing
A 35 year old man comes into your office complaining of recurrent symptoms of heartburn and right upper quadrant pain. Additionally, he has been having diarrhea that is seemingly unrelated to food intake (even after he stops eating for a day, he continues to have symptoms). He appears dehydrated and his blood labs reveal hyponatremia. Based on the histologic specimen of the antrum below, what is his diagnosis?
Zollinger-Ellison Syndrome=
Hypergastrinemia usually due to a gastrinoma (a gastrin-secreting neuroendocrine tumor) in either the pancreas, duodenum, or antrum
- Symptoms: GERD, secretory diarrhea (causing hyponatremia, dehydration)
Microscopic
Fundic expansion with increased parietal cells (in contrast to mucous cell hyperplasia in Ménétrier’s disease)
- Over half of gastrin-producing tumors are locally invasive or have already metastasized at the time of diagnosis
- In approximately 25% of patients, gastrinomas arise in conjunction with other endocrine tumors as part of the MEN-1 syndrome
17 year old male presents with lower right quadrant abdominal pain, arthralgias, uveitis, rash on his shins, and bloody diarrhea 6-8 times daily. What is his differential diagnosis, diagnosis based on colonoscopy, and treatment?
- *Chronic diarrhea with blood**: IBD (ulcerative or Crohn), Malignancy
- Pain in right lower quadrant: ileo-cecal area
Crohn disease: 3 types:
1. Inflammatory: fever, anorexia, weight loss, diarrhea +/- blood, abdominal pain, arthralgias, fatigue
- Fibrostenotic: obstruction, diarrhea (bacterial overgrowth)
- Fistulizing: perianal, rectovaginal, enterocutaneous, enteroenteric
Extra-intestinal manifestations: polyarticular arthropathy, uveitis, rashes
Colon involvement:
Patchy “skip” lesions, rectal sparing (not always)
- Mild: aphthoid ulcers, edema, hyperemic spots, loss of vascular pattern
- Moderate/severe: deep, linear, stellate, coalescing “bear claw” ulcers, cobblestoning
Rule of Thirds (approx. 30% each)
- Small bowel and colon
- Small bowel only
- Colon only
- Perianal
Much less common in esophagus or gastroduodenal (except in pediatric pts)
- *Features of chronicity** in IBD:
- Architectural distortion (“pant legs”)
- Paneth cell metaplasia (Left colon- only R colon normal)
- Hypertrophy/hyperplasia of muscularis mucosa
27 year-old male has a history of longstanding abdominal pain and diarrhea. What is the histologic finding below indicative of?
Crohn Disease non-caseating granuloma
- Lymphoid aggregates going all the way through bowel–> transmural inflammation (vs UC, only in mucosa)
Disordered immune response to intestinal bacteria:
- Th1 cells–> delayed hypersensitivity–> IL-2, IFN-gamma–> macrophages–> TNF-alpha (hence granuloma formation, treat with TNF-alpha monoclonals)
- NK-kappa-B activity increased–> increased cytokines (proper immune response blunted, microbes persist–> chronic inflammation
Extraintestinal manifestations:
- migratory polyarthritis, erythema nodosum, ankylosing spondylitis, uveitis, Oxalate kidney stones (low calcium reabsorption–> oxalate crystal formation)
Labs:
- HLA-DR1, NOD2 (epithelial cells, leukocytes oversecrete NF-kappaB)
A 32 year old woman presents to her physician with a history of chronic diarrhea. A colonscopy reveals chronic inflammation in different portions of her bowel, including her terminal ileum. Based on the gross specimen below, what is the differential diagnosis? Based on her symptoms, what is her likely diagnosis?
Strictures caused by: chronic ischemia, cancer or Crohn disease
Crohn stricture: transmural strictures, fissures, creeping fat, abscesses; seen in terminal ileum, skip lesions, rectum spared, can affect ANY part of columnar GI tract
Crohn disease: string sign
* Yersinia infection can mimic Crohn Disease
- See exudative diarrhea (contains blood, pus)
A 25 year old man comes to his physician with a history of alternating diarrhea and constipation as well as lower abdominal pain. The symptoms have resolved somewhat over the past few months, but there is still blood in his stool and the physician decides to perform a colonoscopy which reveals the following. What is his diagnosis?
Ulcerative Colitis: Lead pipe colon (loss of Haustral folds)- seen in quiescent disease)
Symptoms:
- Hematochezia (grossly bloddy stool)
- Diarrhea
- Constipation
- Tenesmus
- Urgency
- Incontinence
- Nocturnal awakening
- Lower abd pain
Associated with HLA-DR2 phenotype
- Pyoderma gangrenosum
- Primary sclerosing cholangitis (PSC)
- Ankylosing spondylitis, uveitis
- Continuous involvement of mucosa (only) beginning in rectum extending various distances. RARE to see patchy involvement (vs Crohn disease- transmural, may not involve rectum, patchy)
- *Histo: inflammatory polyps** (exaggerated regenerative response in non-ulcerated epithelium to surrounding inflammation/ulceration. Can regress or become filiform (finger-like) polyps of non-inflamed mucosa
- Crypt abscesses and ulcers, bleeding, NO granulomas (Th2 mediated reaction)
- Collection of neutrophils
- *Treatment**:
- ASA (sulfsalazine), 6-MP, infliximab, colectomy
*Increased risk of colon cancer: colectomy with signs of dysplasia on colon biopsy
- flat and non-polypoid
- mucinous
- displays p53 mutation BEFORE APC (vs other CRC)
- Higher histologic grade
- Proximal colon distribution (esp. with Crohn’s, UC)
- multifocal
Features of chronicity in IBD:
- Architectural distortion (“pant legs”)
- Paneth cell metaplasia (Left colon- only R colon normal)
- Hypertrophy/hyperplasia of muscularis mucosa
A 35 year old man with a 15 year history of ulcerative colitis comes to his physician complaining of a gradual onset of constipation. Every few days he will have large bowel movements and then nothing for several days, which is a large change from his usual frequency due to his UC. Based on the surgical findings below, what is his diagnosis?
Ulcerative colitis Toxic Megacolon: in severe cases of UC, there is a complete shutdown of NM function–> toxic megacolon
Ulcerative colitis: pseudopolyps
A 30 year old man comes into the office complaining of alterations in his bowel habits- he has abdominal pain relieved by defecation and constipation followed by diarrhea. Based on the examinaiton of his anus below as well as his symptoms, what might his diagnosis be?
Irritable bowel disease: can also see Elephant ears (below). Generally due to Crohn Disease
Also at risk for developing enteroenteric fistula
A 75 year-old woman presents with abdominal pain and chronic constipation. She has not had a colonoscopy in 10 years. You perform a colonoscopy and find the following. What is her diagnosis and treatment?
Diverticulitis
Symptoms: Abdominal pain (Left distal colon), constipation, fever
- Common cause of hematochezia (older person losing lots of blood per rectum!)
Etiology: Very common in elderly (incidence correlates with age)
- Poorly understood but is related to intestinal motility, colonic structure, diet and genetics
- Low residue/ low fiber diet
- May be related to muscular hypertrophy of the colon and increased intraluminal pressure (created by pulsion)
- Prolonged colonic transit, decreased fecal fiber
Progression:
- Symptomatic uncomplicated disease
- Recurrent symptomatic disease
- Complicated disease
- Hemorrhage, abscess, perforation, peritonitis, stricture, fistula
Natural history
80-85% asymptomatic
15-20% present with abdominal pain
1-2% will require hospitalization
0.5% will require surgery
Treatment
- Surgery
- IV antibiotics
- Oral antibiotics
- Low fiber diet
- 50-70% of patients with one event will not have another event
- Then high fiber diet in 6-8 weeks
Increased in:
- Family history of diverticulitis
- Complicated diverticulitis with retroperitoneal abscess
- More than 5cm of colon involved in the initial episode
Cirrhotic liver: trichrome stains fibrosis blue
- Chronic hepatitis/alcohol ingestion–> cirrhosis
- Only 3% of patients with cirrhosis decompensate each year
Diffuse microvesicular steatosis: rare, reflects hepatocellular injury and damage to mitochondria, beta-oxidation of fatty acids
- See small lipid vacuoles (multiple) in hepatocytes
- Can be seen in lysosomal storage diseases, toxicities to medications (Reye’s)
A 65 year-old man with a history of chronic Hepatitis C infection comes to his doctor for an annual physical. His LFTs are elevated and his doctor orders a biopsy. Based on the histologic sample below, what is his diagnosis and what put him at risk for developing this?
Hepatocellular carcinoma: See pseudoglanular architecture, thickened cords of atypical hepatocytes, fibrotic tissue (cirrhosis from chronic Hep B)
Seen in setting of cirrhosis- most common primary liver cancer
Risk factors;
- Cirrhosis (most important)
- Underlying etiology for cirrhosis plays role: ex: Hep C, hep B (without cirrhosis)
- Male > female
- 50% patients with HCC have markedly elevated alpha-fetoprotein
Histo: nuclear atypia, liver plates expanded (10 cells thick vs 1-2 cells)–> nested appearance (confirm with reticulin stain–> expansion)
The followng was recovered from a mass in the liver of a 40 year old woman with no history of hepatitis or alcohol use. What is her diagnosis?
Cavernous Hemangioma= benign neoplasm comprised of blood vessels. Most common benign liver tumor
Histo: Large, dilated vascular channels in fibrous tissue
A 35 year old sexually-active woman presents with sudden onset of abdominal swelling and a positive Gray-Turners sign (intra-abdominal bleeding). A CT is performed that reveals a mass in her liver that is bleeding and she is taken to surgery. The following histologic specimen is recovered from the tissue. What is her diagnosis and prognosis?
Hepatic adenoma: associated with OCP, anabolic steroid use
- Benign clonal proliferation of hepatocytes; arises in non-cirrhotic liver
- Risk factors: diabetes, obesity, females >males
Tumors often excised because: - May rupture/bleed (below)
- Reports of extremely rare malignant transformation
- Diagnostic purposes (can’t tell what it is in stiu)
Histo: Thick-walled intra-lobular arteries with no portal tract; steatosis; no marked expansion of hepatic plates
A 55 year old woman with a history of clotting problems presents to her physician for an annual physical. The physician notes hepatomegaly and her labs show elevated LFTs and bilirubin. A liver biopsy is taken and the following specimen is recovered. What is her diagnosis?
Venous outflow obstruction: Seen in:
- Right-sided heart failure
- Budd-Chiari= acute/chronic obstruction of major hepatic veins due to thrombosis. Seen in myeloproliferative disorders, disorders of coagulation (antithrombin deficiencies, protein-S, Protein C, mutation in factor V), antiphospholipid syndrome, HCC
- *Histo**: Venous outflow obstruction can lead to portal hypertension–> causes dilation of Zone 3 sinusoids, can also see ischemic necrosis.
- Red blood cells can be pushed into Space of Disse
Chronic outflow obstruction–> atrophy and fibrosis (Below)–> called “cardiac cirrhosis/sclerosis”
Chronic passive congestion–> nutmeg liver
A 35 year old woman presents to you with difficulty breathing. Auscultation of her lungs reveals prolonged exhalation with slight wheezing. Upon taking her history, she states she had neonatal jaundice and she admits to smoking a pack a day for the past 10 years. Based on her history, exam, and histologic specimen of her liver below, what is her diagnosis?
Alpha-1-antitrypsin deficiency: Alpha-1 antitrypsin is elastase inhibitor- autosomal co-dominant (PiZZ or PiMZ) defect causes misfolding–> deficiency. Proteins get stuck in liver and cause damage:
- Neonatal jaundice in 10% PiZZ
- Adult presentation: chronic hepatitis, cirrhosis
- Increased risk of HCC
- Seen in 10-15% of PiZZ genotypes (mostly Europeans, Scandinavians)
Emphysema: alpha-1 antitrypsin blocks elastase in lungs–> excess lung tissue breakdown
Treatment: Liver transplant cures disease
Histo: globules stained with PAS and diastase (to eliminate glycogen staining)
Dublin-Johnson Pigment: dark brown-black “melanin-like” pigment seen in hepatocytes in Dublin-Johnson syndrome (autosomal recessive disorder causing increased conjugated bilirubin, grossly black liver–> oral contraceptives and pregnancy can reveal underlying disorder due to jaundice)
*Rotor syndrome= similar to Dublin-Johnson without melanin-like dark pigment deposition in liver
A 20 year old college student presents to you for a physical before beginning the season. He states that he has some pain in his knees that an orthopedist diagnosed as arthritis, and he has been seeing a physical therapist. On physical exam, you palpate the lower margin of his liver 1 cm below the costal margin. Out of curiosity, you perform a slit lamp exam and notice the following abberation in his irises. Based on this, what should your next step be, what might the diagnosis be, and what is the treatment?
Wilson’s disease: Rare, autosomal recessive mutation in ATP7B (transmembrane copper-transporting ATPase) on chromosome 13
Disorder of copper excretion through bile canaliculus–> hamage liver through formation of ROS species in hepatocytes
- *Natural history:**
- Stage 1: Accumulation of copper in liver (latency)
- Stage 2: Hepatic capacity exceeded–> critical systemic illness (hemolysis at 6-50 years)–> hepatic encephalopathy (asterixis)
- Stage 3: Accumulation of copper in brain (basal ganglia= putamen, caudate, globus pallidus–> dementia, dyskinesia, dysarthria), eye (corneal deposition), other extrahepatic tissues
- Stage 4: Chelation therapy to acheive copper balance, chelation therapy in some cases
Symptoms:
- Kayser-Fleisher rings
- Neuropsychiatric disorders
- Cardiomyopathy
- Hepatitis, Cirrhosis
- Fanconi syndrome
- Hemolysis
- Osteopenia, arthropathy
Diagnosis:
Ceruloplasmin (low)- < 20 mg/dL
Slit lamp exam for Kayser-Fleisher rings
Urine copper > 100 ug/ 24hr
*If positive for any of three above, liver biopsy with quantitative copper (250 microgram copper/ 1 g dried liver); Genetic testing for ATP7B mutations
Treatment:
Chelation of excess circulating copper
- Trientine
- D-penicillamine
Zinc: diminishes copper absorption
Liver transplantation is curative
First degree relatives should be screened
- ceruloplasmin level, slit-lamp examination
A 35 year old man presents to his physician for a physical exam. Upon arriving at the office, it is noted that he appears somewhat tanned, even though it is February- he denies travel or using a tanning bed. His blood testing reveals an elevated fasting glucose (140) though he is not overweight. Additionally, his hematocrit seems unusually elevated. An MRI of his liver reveals the following. Based on his symptoms and test results, what further testing should be done to confirm his suspected diagnosis? If the diagnosis is correct, what is his treatment?
Hemochromatosis: Autosomal recessive mutation in HFE (C282Y or H63D)–> defective hepcidin production in liver–> no feedback inhibition of iron absorption in intestines–> excess iron buildup
- **HLA-A3 type
- Total body iron may reach 50 g**
- Progressive deposition in Zone 1—> Zone 3
Clinical presentation:
- Cirrhosis
- Bronzing skin
- Diabetes
- Testicular atrophy
- Conduction abnormalities in heart
Diagnostic testing:
Genetic: GOLD standard
- Homozygous C282Y/C282Y (white Europeans)
- Compound heterozygous C282Y/H63D (worldwide)
Serum tests:
- iron (high > 175)
- iron binding capacity (low < 300)
- transferrin saturation (high > 50%)
- ferritin levels (high > 300)
Radiographs: T2 weighted MRI, lower than normal intensity signal in liver
Liver biopsy:
- Stainable iron (prussian blue)
- Hepatic iron index (> 5600 compared to 1800)
Treatment: Response to phlebotomy
** high risk of HCC (first degree relatives should be screened by transferrin saturation, ferritin)
A 50 year old woman presents to her physician with pruritis all over her body. Her blood tests reveal an elevated alkaline phosphatase. Besides this she is asymptomatic. Based on the histologic specimen below, what is her diagnosis?
PBC= Primary biliary cholangitis; serum anti-mitochondrial antibodies (autoimmune reaction–> lymphocytes and granulomas; destruction of intrahepatic ducts, cholestasis
- Associated with CREST, RA, celiac, Sjogren’s
Female
Early signs:
- Asymptomatic with elevated alkaline phosphatase (out of proportion to bilirubin)
- Pruritis without Jaundice
- Malabsorption of fat-soluble vitamin ( can lead to elevated INR in absence of end-stage liver disease due to decreased Vit K absorption)
Later signs:
- Xanthomas
- Osteoporosis (Vit D malabsorption)
- Jaundice, ascites, portal HTN (liver failure)
Treatment:
1, Ursodeoxycholic acid (Ursodiol)
- replaces hepatotoxic bile salts
- Symptomatic/biochemical improvement
- transplant-free survival advantage
2. Cholestyramine
- Binds bile acids, can relieve pruritis
- No effect on natural history of disease
3. Liver transplantation (curative but can RECUR)
Testing:
- Elevated Alkaline phosphatase
- Ultrasound of liver/gallbladder (look for obstruction)
- AMA blood test
- Liver biopsy
Labs:
- AMA (antimitochondrial antibodies)- 90%
- Elevated Alkaline phosphatase without liver failure
- *Histo**:
- Involves intrahepatic bile ducts (MICROscopic)
- See bile duct lesions (lymphocytic infiltration/granulomatous inflammation)
- Chronic non-suppurative destruction cholangitis
- Leads to ductopenia/fibrosis
a 50 year old man with a 20-year history of ucerative colitis presents to his physician with full-body itching and a low-grade fever. Upon physical exam, the physician notes mild jaundice. Labs indicate increased alkaline phosphatase and an atypical P-ANCA. Based on the liver sample below, what is the patient’s diagnosis and treatment?
- *Onion skin fibrosis**= intrahepatic duct involvement in primary sclerosing cholangitis.
- Strictures and dilation–> beading of intra- and extra-hepatic ducts on ERCP
Associated with hypergammaglobulinemia, Ulcerative colitis
- can lead to secondary biliary cirrhosis
below: fibrosis causing ductopenia
PSC features:
- Rule of 7s: 70% male, 70% associted with Ulcerative Colitis (rare Crohn association), 7% develop cholangiocarcinoma
- Pruritis
- Jaundice
- Fever due to ascending cholangitis
- Increased Alk Phos
- Atypical P-ANCA (reaction with nuclear envelope proteins of neutrophils)
- Involves extrahepatic/hilar (large) bile ducts; may involve intrahepatic ducts
- Histologic features: onion skin fibrosis (small duct involvement), ductopenia, fibrosis
- *- Beading on cholangiography**
An obese, 40 year old woman comes into your office complaining of upper right quadrant pain that worsens with food. Upon further questioning she remembers that it is more painful after greasier meals. She reports using oral contraceptive pills. On physical exam, she has a positive Murphy’s sign. Based on the gross specimen recovered below, what is her diagnosis and risk factors?
Cholesterol gallstones
Risk factors: (female, fat, fertile, forty)
- Reproductive age women (estrogen)
- Obesity
- Oral contraceptives
- Genetics (Pima indians)
- Diet/metabolic abnormalities (cholesterol)
- Drugs (fibrates)
Stones composed largely of cholesterol are radiolucent
Sufficient calcium carbonate is found in10-20% of cholesterol stones to render them radiopaque
A 30 year old Asian woman comes to your clinic. She has noticed tenderness in her right upper abdomen that has increased over the past few weeks. She also has a history of bruising easily and her skin and sclera appear slightly yellowed. You order some lab tests and see elevated Billirubin levels (3.8 mg/dl, 0.6mg/dl direct). Why might she have RUQ pain and what might the underlying cause be?
Black pigmented stones due to unconjugated hyperbilirubinemia. This patient exhibits signs of either hemolytic anemia or a thalassemia, which cause to an excess of bilirubin that the liver is unable to conjugate. This excess backs up in the gallbladder and forms black stones. Additionally she developed jaundice from the excess bilirubin levels.
* Brown pigmented stones= conjugated hyperbilirubinemia due to obstruction of duct
Causes of unconjugated hyperbilirubinemia:
(Diagnosed if more than 80% of an elevated total bilirubin is indirect)
Elevation results from either:
- Increased bilirubin production
- Hemolytic anemia (bilirubin rarely > 4 mg/dL)
- Hematoma
- Ineffective erythropoiesis (thalassemia, pernicious anemia)
- Neonatal (physiologic) jaundice - Reduced hepatic ability to conjugate bilirubin= Glucuronosyltransferase deficiency in:
- Gilbert’s syndrome (young men)= jaundice in times of stress/illness- not fatal
- Crigler-Najjar syndrome (rare)
- Neonatal (physiologic syndrome)
Imaging: black stones contain high levels of calcium carbonate and phosphate–> 50-75% radiopaque
A 30 year old man comes into your office. He recently was diagnosed with a salmonella infection which was resolving, but he has recently started feeling acute pain in his right upper quadrant. Besides the recent infection, he is in good health and has no chronic conditions. He has a positive Murphy’s sign and is taken to the hospital where he has his gallbladder removed. Based on his history and the gross specimen below, what is his diagnosis?
Acute cholecystitis: diffuse inflammation of the gallbladder. 90-95% of cases associated with gallstones.
- Acalculus cholecystitis occurs in sepsis, severe trauma, salomonella infections, polyarteritis nodosa
- *Gross pathology**:
- Usually enlarged and tense, may assume a bright red or blotchy, violaceous to green-black discoloration, imparted by subserosal hemorrhages
- The serosal covering is frequently layered by fibrin and, in severe cases, by suppurative exudate
- The gallbladder lumen may contain stones, is filled with a cloudy or turbid bile that may contain large amounts of fibrin, pus, and hemorrhage
- The gallbladder wall is thickened, edematous, and hyperemic.
- Complication: Perforation (bile peritonitis)
Below: cholecystitis with empyema
Histo: acute inflammation, edema, hemorrhage, mucosal ulceration/widespread necrosis (gangrenous)
A 50 year old woman with a history of cholecystitis presents to the emergency room with intense abdominal pain and nausea as well as a low grade fever. She says the pain radiates to her back. On exam there is mild abdominal distension and decreased bowel sounds. Based on the histology of her pancreas below, what is happening and what is the treatment?
Acute pancreatitis:
An inflammatory condition of the exocrine pancreas that results from injury to acinar cells and release of enzymes
Pancreatic pseudocyst= lined by granulation tissue (not epithelium)- can rupture and hemorrhage
Clinical presentation:
- Attacks typically mild, but 20% very severe
- An attack lasts for a short time and usually resolves completely
- Severe cases lead to hemorrhagic pancreatitis with massive necrosis
- Abdominal pain, nausea, low-grade fever, dehydration
Etiologies:
Metabolic: alcoholism, hyperlipoproteinemia, hypercalcemia, drugs
Mechanical: gallstones, trauma, operative injury, endoscopic procedures
Vascular: shock, atheroembolism, vasculitis
Infectious: mumps, coxsackievirus
Genetic: mutations in cationic trypsinogen (PRSS1) and trypsin inhibitor (SPINK1)
Labs: elevated amylase (also in saliva) and lipase (more specific to pancreas)
- Markers= CRP, TAP (trypsinogen activation peptide), MCP (monocyte chemotactic protein)
Complications:
- Lung: Phospholipase A2 released from pancreas–> breaks down surfactant (ARD), subdiaphragmatic irritation causes restricted breathing
- Kidney: vasoconstriction, hemorrhage–> kidney damage
- DIC: release of factors enhancing fibrinolysis and coagulation
Imaging:
- CT= imaging modality of choice. Wait 72 hours before administering with contrast (rehydrate patient or dye could damage kidneys).
- MRI= in pregnant patients
Prognosis: 80% mild, 20% severe attacks (9% mortality)
Treatment: supportive
- Replenish fluids
- Monitoring
- Antibiotics ONLY if sign of infection
- Feed the gut: insure gut immune functions continue
Histo: see fat saponification (think like vegetable cells), calcification
Morphology:
(1) Edema caused by microvascular leakage
(2) Fat necrosis by lipolytic enzymes (saponification)
(3) Acute inflammation
(4) Proteolytic destruction of pancreatic parenchyma
(5) Destruction of blood vessels and subsequent interstitial hemorrhage
Normal gastro-esophageal (squamocolumnar) junction: Mucosal junction (gastroesophageal) and squamocolumnar tissue line up at Z-line
* In metaplasia (Barrett’s)- Z line (mucosal junction) ABOVE columnar tissue
The following gross specimen was recovered from a 3 week old infant who died of renal dysplasia. Before passing away, the infant would projectile vomit after feeding. What is this congenital anomaly, and what other syndromes is it associated with?
Esophageal atresia and tracheoesophageal fistula= Embryologic failure of tubal esophagus to connect mouth to stomach, ending in a blind pouch; fistula may connect segment to trachea (In 85% of cases, proximal esophagus is blind end, trachea attaches to distal esophagus)
Clinical picture:
- 1/3000 live births
- * 50% have congenital anomalies: VATER syndrome (vertebral defects, anal atresia, trachoesophageal fistula, renal dysplasia)
- See respiratory symptoms (aspiration pneumonia)
Pathogenesis: most likely due to abnormal hedgehog signaling pathway
Esophageal biopsy: what types of changes have occured?
Histo: dysplasia in Barrett’s esophagus
BE without dysplasia= 2% cancer risk
BE with dysplasia= 20% risk of cancer (high grade dysplasia)
- 45% of low-grade dysplasias will progress to high grade
A 4 week-old infant is brought to the pediatrician by his mother because of recent, frequent episodes of projectile vomiting following feeding. She is especially concerned because he is losing weight. On phyical exam, the baby appears thinner and somewhat dehydrated. Additionally there is a palpable mass on his upper abdomen just to the right of the midline. What is his diagnosis and treatment?
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; rare in blacks & Asians
Possible genetic as well as environmental (drugs, infection in utero) pathogenesis
Symptoms:
- Emesis (non-bilious, projectile) in 3-6 weeks
- Poor weight gain, dehydration (hypochloremic alkalosis)
Diagnosis: palpate “olive”, pyloric sonograms, UGI series
Treatment: surgical: pyloromyotomy (open up pyloris muscle)
baby: see palpable epigastric mass (olive)
gross path: concentric hypertrophy, hyperplasia of pyloric muscularis propria
A 50 year old woman has an annual physical- her physician notices small bruises on different parts of her body and the woman states that she noticed that she bruises more easily recently. A blood draw is performed that demonstrates low RBC with large cell formation (megaloblastic anemia). Additionally she states she has been avoiding eating red meat because it gives her indigestion, as do most larger meals. She also has some diarrhea and stomach upset after eating. Based on the histologic sample below, what is her diagnosis?
Autoimmune gastritis: Immune-mediated form of chronic gastritis–> loss of parietal cells–> hypo/achlorhydria, Vit B12 deficiency
Autosomal dominant, seen in < 5% chronic gastritis, F > M, accompanied by pernicious anemia (megaloblastic anemia due to decreased B12
Labs: increased gastrin, decreased B12, positive Anti-parietal cell Ab, anti-intrinsic factor Ab
Histo: only seen in body/fundus of stomach: lymphoplastic inflammation in deep, glandular lamina propria–> loss of glands–> atrophy–> achlorhydria.
Also see intestinal metaplasia of goblet cells, ECL hyperplasia (both are precursors to tumor formation: Intestinal metaplasia–> 13-fold increased risk of gastric carcinoma; ECL cell hyperplasia–> neuroendocrine tumors- 13-fold increase)
Colonic strictures:
Caused by: chronic ischemia (fibrosis) Crohn Disease (increased muscle, propria hypertrophy, hyperplasia), malignancy, recurrent bouts of diverticulitis; NOT seen in UC
A woman who recently completed a course of antibiotics to treat a UTI comes to your office complaining of difficulty swallowing. Based on the endoscopic exam, what is your diagnosis?
Candida esophagitis: pain with swallowing (odynophagia) due to severe inflammatory process disrupting esophageal mucosa
Seen in: immunosuppressed, diabetics, recent antibiotic usage
Histo: pseudohyphae
CMV esophagitis: pain with swallowing (odynophagia) due to severe inflammatory process disrupting esophageal mucosa
Histo: Base of ulcer: see large intranuclear inclusion with granular cytoplasmic inclusions
A man presents to his physician reporting difficulty with swallowing. He states that he used to have recurrent episodes of heart burn but he adjusted his diet and has been taking Prilosec for the past two months. Upon endoscopic examination, you find the following. What is his diagnosis and what caused this?
Peptic stricture: due to recurrent damage from GERD can form scar tissue in esophagus–> leads to achalasia (difficulty swallowing)
- long history of heartburn and antacid use–> symptoms remit as stricture develops
Below: GERD-induced esophagitis leading to stricture formation
A 68 year old man with a history of recurrent GERD has been monitored by his physician for the past 10 years due to the development of Barrett’s Esophagus. This past 3 months he has reported an increased difficulty with swallowing, and the physician finds the following on endoscopic exam. What is his diagnosis?
Esophageal adenocarcinoma
- Hx of recent, but, progressive dysphagia, older pts
- Irregular narrowing on barium swallow
- Endoscopic biopsy and/or cytology required for diagnosis
- Adenocarcinoma – arises in Barrett’s Esophagus
*Adenocarcinoma accounts for ~70% of esophageal cancers in USA
Patient presents with intermittent difficulty swallowing food (she says the last time this happened a piece of chicken got stuck in her throat and she felt like it didn’t move for a long time). You perform a barium swallow and the following is revealed. What is her diagnosis and treatment?
Schatzki’s ring:
- Thin mucosal invagination in distal esophagus at Gastro-esophageal junction
- Asymptomatic ring in about 10% of normals
- Intermittent dysphagia solids, persistent if <1.2 cm.
- Can be missed on barium swallow, so include solid bolus (marshmellow?) or endoscopy (EGD)
Diagnosis: intermittent dysphagia for solids (lumen 1.2 cm- 2.0 cm). persistant dysphagia with lumen < 1.2 cm
A 50-year old African American woman presents to your clinic with frequent episodes of heartburn. Additionally the dkin on her face feels rougher and appears hardened on her cheeks. Based on the barium swallow below, what is her diagnosis?
Scleroderma causing dysphagia: (80% of scleroderma pts)
- Weak LES, low amplitude/nonexistant contractions of esophageal body
Symptoms= heartburn, regurgitation; often associated with Raynaud’s syndrome
- Skin changes (Scleroderma skin): hardened, thickened skin on face, telangiectasia, sclerodactyly, calcinosis cutis (CREST syndrome)
A 68 year old man reports to the Emergency room with chest pain right over his sternum. An EKG reveals a normal conduction throughout his myocardium, and an MI is ruled out, though the nitroglycerin administered on admission has addressed his pain. He reports issues with swallowing any water administered to him in the ER and eventually a barium swallow is performed to evaluate his esophageal function. The following anomaly is discovered- what is his diagnosis?
Diffuse esophageal spasm
- Intermittent dysphagia to solid and liquids
- May cause severe chest pain (50% of non-MI chest pain cases in ER)- releved by nitroglycerin
- Simultaneous (non-peristaltic) contractions, usually mixed with peristaltic contractions
- Corkscew, step ladder, “rosary bead esophagus”
Diagnosis= symptoms of dysphagia +/- chest pain plus esophageal manometric anomalies
A 60 year old man with a history of seasonal allergies and peanut allergies (causing anaphylaxis) complains of issues swallowing solid foods. A endoscopic exam is performed and the following is discovered. What is the etiology of this condition and what is his treatment?
Eosinophilic esophagitis
Dysphagia for solid > liquid foods
More common in males, see history of allergen sensitivity
- “Ringed” or “feline” esophagus on endoscopy
- Dense eosinophilic infiltration (> 20 /hpf on mucosal biopsy
* leading cause of solid food bolus impaction in general GI practice (>50% of cases)
* Eosinophilic esophagitis patients are highly susceptible to mucosal tearing (laceration) and transmural perforation during endoscopy, dilation procedures, bolus impaction and vomiting.
Boerhaave’s syndrome= Spontaneous rupture (seen with transmural infiltrate)
Treatment:
- Elimination diets: Milk, eggs, soy, corn, wheat, beef, chicken
- Oral Fluticasone: Flonase, Flovent
- Steroids (Budesonide, Pednisone)
- Singulair?
- Chromalyn?
- Gentle Esophageal Dilatation only After Medical Trial
A 74-year old woman with a history of alcohol abuse and smoking a pack a day reports to her physician with severe problems with swallowing. An endoscopic exam is performed and the following is found. What is her diagnosis and what were her risk factors?
- Esophageal Squamous cell carcinoma: Risk factors are heavy smoking and alcohol
- See progressive dysphagia (initially only issues swallowing solid food)
- May see: extreme weight loss, irregular esophageal narrowing on Barium swallow (below)
A 22-year old woman presents with chronic diarrhea. What type of histologic changes have occured in her colon and what is suggestive of chronicity (vs acute inflammation)
Branched crypts in colon: Early/non-specific IBD
- Acute inflammatory cells, cryptitis/ crypt abscess
- Chronic IBD: paneth cell metaplasia, crypt distortion, basal lymphoid aggregation, chronic inflammatory cells
65 year old female presents with acute onset of crampy left lower quadrant abdominal pain followed by bloody diarrhea. She has medical history of atrial fibrillation, diabetes and coronary heart disease.
Splenic flexure ischemia: only 1 blood source
65 year old male presents with change in bowel habits (initially constipated and now with diarrhea), weight loss, anemia and blood in the bowel movements. What is his diagnosis?
Colon cancer
65 year old women presents to the office with 15-20 voluminous foul smelling watery bowel movements per day. She has abdominal pain, cramps, and fever. She was recently hospitalized for sinus surgery. You perform a colonoscopy which reveals the following. What is her diagnosis and treatment?
C. Difficile infection following hospitalizations/antibiotic course (must rule out ischemia, which has similar pseudomembrane)
Cause= Antibiotics: Oral > IV; Cephalosporins, PCNs, Clindamycin; Up to 8 wks after abx course
Treatment
PO metronidazole 500mg TID x 10 days
PO vancomycin 125mg QID x 10 days
Expect response in 3 – 4 days, recurs in 12-24%
Probiotics (florastar 250mg 2tabs PO BID)
Handwashing
*Do NOT use anti-diarrheal (anti-motility) drugs- this can exacerbate the condition as it leaves bacteria in colon longer to cause more toxin damage
Histo: Pseudomembranes composed of fibrin, mucin, neutrophils. Glands lose epithelial cells (C. diff effects cells adhesion, while ischemia has hemosiderin laden macrophages)
Pancreatic acinar cells
Below: Islet of Langerhaans
Acute hemorrhagic pancreatitis:
- Abrupt onset following heavy meal/alcohol
- Extensive tissue destruction with circulatory collapse and shock
- Elevated serum amylase and lipase levels
- 50% mortality
- May develop pseudocyst (if survive)
A 50 year old man with a 20 year history of alcohol abuse presents to his physician with recent worsening pain in his abdomen and back. He says the pain worsens with food intake. Additionally he has been losing weight. His blood work shows an elevated fasting glucose (130). Based on the histologic specimen from his pancreas below, what is happening, how would this be diagnosed and what are the complications?
Chronic pancreatitis
- Recurrent, progressive pancreatic tissue destruction
- *- Alcohol abuse** is a major cause
- Chronic inflammation, fibrosis, calcification
- Pancreatic insufficiency with malabsorption and/or diabetes
- 3-4% mortality/year
- *Clinical presentation:**
- 50% of attacks are recurrent
- Symptoms of Acute pancreatitis
- Chronic pain / nausea: Constant, dull, radiates to back, worse with food
- Malabsorption: Diarrhea, steatorrhea
- Diabetes
- Weight loss
- *Alcholic pancreatitis:**
- Direct acinar cell toxicity
- Alters membrane infrastructure–> increased permeability
- Increased basal protein secretion
- Decreases trypsin inhibitor
- Alters lithostatin–> precipitation of Ca
- Decreased endocrine function
- *Diagnosis:
1. MRI/MRCP= GOLD standard** - Shows parenchymal fibrosis, ductal abnormalities
2. CT: irregular contour, calcifications, dilated duct, cysts
3. Endoscopic ultrasound
4. Plain X-ray film: shows calcifications - *Complications**:
- Narcotic addiiction
- Malnutrition
- Pseudocyst formation
- Common bile duct obstruction
- Duodenal obstruction
- Splenic vein thrombosis–> gastric varices (bleeding complications)
Autoimmune pancreatitis, lymphoplastic clerosing type
- Seen in 4th to 6th decade
- Associate with autoimmune conditions (primary sclerosing cholangitis, Sjogren, etc.)
- Some with “multifocal inflammatory fibrosclerosis” (Riedel thyroiditis, orbital pseudotumor, mediastinal and retroperitoneal fibrosis, etc.)
- Mimicks pancreatic carcinoma both clinically (obstructive jaundice) and radiologically (mass-like lesion); “sausage-like” appearance on imaging
- Some with elevated serum IgG4 levels (usually >135 mg/dl)
- Respond well to steroid administration
Histo:
- See duct-centric inflammation (lymphoplasmacytic cells), periductal fibrosis, periphlebitis, venule obliteration, interstitial fibroblast proliferation
- IgG4-positive plasma cells
A 50 year old alcoholic passes away from aspiration. His pancreas is removed- what changes occured?
Pseudocysts
complications of chronic pancreatitis, not true cyst (no epithelial lining)
A 65 year old man with a 40-year history of smoking a pack a day comes to the physician due to new onset jaundice. Additionally he states he has lost 15 pounds without trying and he has some persistant pain in the middle of his back. Based on the sample of his pancreas below, what is his diagnosis and what other histologic features accompany it? What is his prognosis?
Pancreatic ductal carcinoma: 85% of pancreatic cancers
Symptoms:
- Anorexia
- Weight loss
- Abdominal/back pain
- Jaundice
- Migratory thrombophlebitis (Trousseau’s sign) hypercoagulability and tendency to venous thrombosis
- *Ductal adenocarcinoma**:
- Derived from ductal cells–> Spreads by direct extension along nerves and lymphatic spread
- Significant cause of cancer deaths: 4th in men, 5th in women
- *- Only 20% of PDA patients are surgical candidates; of these only 5% will survive 5 years
- Overall 5 year survival is 5%**
Most lethal of all of the solid malignancies
Highest incidence after age 60
Risk factors:
- Smoking
- Chemical exposure
- High meat/fat diet
- Diabetes
- Chronic pancreatitis
* Approximately 10% familial
Somatic genetic changes in pancreatic carcinoma:
- 90% KRAS activating mutations
- 95% P16 deletion
- 70% TP53 mutation
- 55% SMAD4 mutation/deletion
Below: See perineural invasion
Serous cystadenoma
3:1 female predominance, and Von Hippel Lindau patients are at increased risk for its development
Symptoms are often nonspecific
Almost always benign, and surgical resection is curative in the vast majority of patients
Composed of glycogen-rich cuboidal cells surrounding small (1 to 3 mm) cysts containing clear, thin, straw-colored fluid
A 45 year old woman is in a car accident and has a CT performed on her abdomen to rule out any internal bleeding. On the scan, the physician notes a mass on the tail of her pancreas. She has no symptoms of pancreatic dysfunction (digestive issues, endocrine problems), no pain, and no history of pancreatitis. Based on the mass that was removed (below), what is her diagnosis and prognosis?
Mucinous cystic neoplasm
95% arise in women
1/3 associated with invasive cancer
Body or tail of the pancreas
Painless, slow-growing mass
The cysts are lined by columnar mucinous epithelium, and a dense ovarian-type stroma
Not involving the major pancreatic duct
Intraductal papillary mucinous neoplasm (IPMN)
- Precursor lesion to Pancreatic ductal adenocarcinoma
- More common in men
- Can be multifocal
- Involving the main pancreatic duct or its major branches
- Lack of ovarian type stroma
- 5 year survival:
IPMN: 90-100%
IPMN with associated invasive carcinoma: 40%
A 26 year-old woman comes into the office complaining of a feeling of fullness that persists long after eating and recently she has had some right upper quadrant pain after eating. On physical exam, you feel an intra-abdominal mass. Based on the histologic specimen from her pancreas below, what is your diagnosis?
Solid pseudopapillary neoplasm:
- Low grade malignant neoplasm
- Affects young women
- Symptoms of intra-abdominal mass, often palpable on clinical exam
- 30% discovered incidentally
- 10-15% of patients will develop metastasis or recurrence; most of these are resectable and patients survive long time
- Mutation of beta catenin gene- can see on histo stain
Pancreatoblastoma
Most common pancreatic tumor in children
Adults have mean survival of 18 months
Microscopically shows acini and squamoid corpuscle
A 45 year old patient comes to your office for recurrent episodes of dizziness, palpitations and fainting. He reports these issues seem to be worse when he hasn’t eaten in a while so he’s been trying to continuously have good on him to prevent these spells of hypoglycemia. Blood tests reveal elevated pro-insulin, c-peptide, insulin and lowered beta-hydroxylase. What is his diagnosis?
Pancreatic neuroendocrine tumor- insulinoma
- Derived from islet cells
- May be non-functional or functional (symptoms relate to hormone produced)
- 5% of clinically detected pancreatic neoplasms
- Males and females are equally affected
- Most occur between 30 and 60 yrs; those arising in patients with multiple endocrine neoplasia 1 (MEN1) syndrome occur at a younger age
Insulinoma: Derived from beta cells, most common pancreatic islet cell tumor (75%)
- Excess secretion of insulin (hypoglycemia, sweating, nervousness, hunger, confusion, lethargy)
- Most are benign, solitary, small (75% < 2 cm)
- Histo: stain for insulin: Uniform nests of cells, richly vascular, amyloid deposition
Normal gallbladder histo:
- Notice only ONE layer of smooth muscle (vs remainder of GI tract, with two layers: muscularis mucosae and muscularis externa
Below is a histologic specimen of a woman with a history of gallstones. What type of pathologic changes have occured and what is her diagnosis?
Chronic cholecystitis
Persistent inflammation of gallbladder
>90% associated with gallstones
Gallbladder has thickened and fibrotic wall
Histo: Rokitansky-Aschoff sinuses
Below: X-ray image showing porcelain gallbladder: calcification of the gallbladder resulting from chronic cholecystitis. Note: patients with porcelain gallbladder are at increased risk of cancer of the gallbladder*
* Brown stones in intra-hepatic/extra-hepatic bile ducts can be due to ascending infection–> bacteria unconjugates bilirubin
Below is a histologic specimen of a gallbladder of a man with familial hyperlipidemia. What has happened to the mucosa and what is the diagnosis?
A 65 year old woman with a recurrent history of gallstones comes to her physician with a new onset of RUQ pain and no appetite. Her physician does a physical and she has a positive murphy’s sign. However, the physician notes some nodal enlargement in the abdomen around the umbilicus. Her gallbladder is removed and the following histologic specimen is found. What is her diagnosis and prognosis?
Gallbladder adenocarcinoma:
- More common in females (females:males 3–4:1)
- >90% aged ≥50 years at diagnosis
- Right upper quadrant abdominal pain, anorexia
- *- Metastatic disease in ≈50% at surgery**
- Gross pathology: diffuse wall thickening or polypoid growth
- Histology: adenocarcinoma showing varying degree of differentiation
- *- 5-year survival rate: >90% for stages I and II, 11% for stages III and IV**
Risk factors: cholelithiasis, chronic cholecystitis
Prussian blue stain of hepatocytes: stains for iron (predominantly in zone 1)
- Chunky, golden-brown cytoplasmic pigment
Excessive iron= toxic to host tissues. Causes lipid peroxidation, stimulation of collagen (activates hepatic stellate cells), disrupts DNA–> apoptosis, hepatocellular carcinoma (HCC). No significant inflammation due to direct toxicity
Iron accumulation in:
- Hepatocytes= hereditary hemochromatosis
- Kupffer cells= secondary to blood transfusions, ineffective erythropoiesis (thalassemia)
- Mild accumulation in both hepatocytes and Kupffer cells= chronic liver disease (steatohepatitis, cirrhosis, HCV)
- Bile ducts
Accumulation can also be due to low levels of hepcidin (main regulator of iron absorption- decreases intestinal absorption)
Bile pigment (bilirubin): seen in canalicular space between hepatocytes (can also accumulate within hepatocytes/ Kupffer cells). Located primarily in Zone 3
- Heme breakdown–> billirubin–> bile pigment
- Accumulation= cholestasis, bilirubinostasis
Lipofuscin= finely granular, light yellow-brown cytoplasmic pigment. Zone 3
- “Wear and tear” pigment associated with aging and drugs
- NOT injurious to cell/functions, but demonstrates previous injury due to free radicals and lipid peroxidation
Macrovascular steatosis= abnormal accumulation of triglycerides in hepatocytes. Most common in alcohol abuse and non-alcoholic fatty liver disease (food abuse)
*Reversible cell damage
Below: Liver diffusely yellow due to fat accumulation. Due to alcohol abuse, non-alcoholic fatty liver disease, viral hepatitis C, drugs
VS: steatohepatitis= fatty liver with lobular inflammation and injury (due to ASH, NASH). See neutrophilic/lymphocytic inflammation, cellular swelling (ballooning), Mallory bodies
Hepatocellular swelling: liver cells unable to maintain homeostasis due to:
- Acute hepatitis, severe flare of chronic hepatitis
- Cholate stasis (feathery degeneration due to bile salt accumulation)
- Steatohepatitis “balloon cells” (fatty and fibrotic changes)
Histo: swelling, vacuolization/lightening of cytoplasm, clumping intermediate filaments, cell membrane blebbing (unlike vacuolization of fat in steatosis)
*Reversible cell damage
Apoptotic hepatocytes: spotty necrosis, councilman body (only in the context of yellow fever), acidophilic body= eosinophilic globule in liver
- SINGLE acidophilic cells= apoptosis (vs clusters= necrosis)
Hepatic necrosis= clusters of dead hepatocytes due to ischemia, drug-dependent injury
Kupffer Cells= hepatic macrophages, clean up damage (any type) in hepatocytes.
Grayish tinge (ceroid)= pigment accumulating in macrophages similar to lipofuscin (“wear and tear”) due to peroxidation of lipids
A 40 year old woman is found dead in an alleyway from a heroin overdose. At autopsy, the following changes in the histology of her liver are noted. What is her diagnosis?
Portal tract inflammation= typical of chronic hepatitis
- Mildly active (low levels of interface inflammation- as opposed to interface inflammation in image below)
Due to Hepatitis B (+/- Hep D), hepatitis C, or autoimmune hepatitis
- Other causes= drug reaction, Wilson’s disease, alpha-1-antitrypsin deficiency
Chronic hepatitis: lymphocytic inflammation (+/- plasma cells) found in portal tract
Activity determined by:
- Inflammation movement from portal tract into lobule
- Degree of hepatocellular damage (apoptotic hepatocytes, cellular swelling- more severe)
Interface hepatitis: lymphocytes rosette around hepatocytes at the limiting plate (sleeve of hepatocytes around portal tract)- this example shows moderate hepatitis due to prominence of interface inflammation
Chronic hepatitis lobular inflammation: with or without hepatocellular damage (apoptotic hepatocytes with cellular swelling) only seen in severely active cases. Can see lymphocytes in Zone 1, 2, 3 and apoptotic hepatocytes (councilman body)
Below: Chronic hepatitis severely active: HBV with HDV superinfection
- See interface AND lobular inflammation
* Remember: grading is based on activity/location of lymphocytes/ amount of inflammation (portal tract—> lobular) while staging is based on amount of fibrosis
A 42-year old man recently had unprotected intercourse and developed jaundice and hepatomegaly. Below is the appearance of his liver on biopsy. What is his diagnosis, prognosis and what other tests could confirm this?
Hepatitis B “ground glass”
Enveloped, dsDNA virus
- Progresses to chronic disease in 90% of infants infected (enveloped), only 5% in adults
- Acute illness in 35% (0.5% fulminant hepatitis–> necrosis, mortality)
* Increases risk for hepatocellular carcinoma (even outside of cirrhosis)
- Labs: serum HBsAg
- Histo: “ground glass” appearance
A 35 year old woman with a history of IV drug use is admitted to the hospital after being brought into the ER with severe confusion, fever, and apparent jaundice. She has a prior history of HBV infection. What might be causing these new symptoms?
HBV with HDV superinfection
Envelope (from HBV infection), ssRNA virus
- Can ONLY Infect HBV-infected cells
- Co-infection: aggressive (2-20% mortality)
- *- Superinfection: Chronic HBV with worsened condition (due to HDV)= 30% mortality**
- Higher risk of acute liver failure, cirrhosis, no clear association with HCC
- Associated with drugs, dependent on B
A 45 year old man with a 5-year history of IV drug use is seen in a community clinic. His blood labs return with elevated LFTs and no other symptoms. Based on the liver biopsy below, what type of other tests should be run?
Hepatitis C infection: tightly formed lymphoid aggregate in portal tract
Enveloped, ssRNA virus
- *Labs: anti-HCV+, RT-PCR for viral HCV RNA**
- Seldom seen in acute phase
- 85% chronically infected (enveloped)–> 20% develop cirrhosis
- 10% cirrhotic individuals develop hepatocellular carcinoma
A 50 year old woman with elevated AST and ALT (600 and 750) has a liver biopsy (below). She is not taking any medications or herbal remedies. What is her diagnosis?
Autoimmune hepatitis closely ressembles chronic viral hepatitis- MUST correlate with clinical and serologic findings.
- numerous plasma cells= histological clue
- more active than hepatitis
Features:
- More common in women (70%)
- Histology “perals: chronic pattern of injury, plasma cells, moderate to severe activity on biopsy
- Exclude viral causes/drug reactions
- ANA+ (60%), ASMA + (70%)= type 1
- Anti-LKA (type 2- pediatric)
- Anti-SLA (type 3- rare)
- Hypergammaglobulinemia
- Brisk response to steroids (bridging necrosis= bad–> completely resolved by steroids)
ANA= anti-nuclear antibody, ASMA= anti-smooth muscle antibody, LKM= anti-liver kidney microsomal, SLA= anti-soluble liver antigen
A 50 year old woman recenty returned to her physician after having her gallbladder removed. She has now developed some slight jaundice and itching that has been getting worse over the past few days. Based on the liver biopsy sample below, what is happening to her liver?
Bile duct obstruction–> Biliary injury to portal tract
Mixed infiltrate in portal tract:
- neutrophils= acute peri-cholangitis: acute inflammation around bile ducts; reaction to bile salts (destruction of tissue) * Not seen IN bile duct (within duct indicates ascending infection= acute cholangitis)
- lymphocytes: metaplasia of bile ducts in response to bile salt exposure (to protect hepatocytes) can cuase leakage into portal connective tissue–> lymphocytic infiltration
- eosinophils
below: bile ductular proliferation (small ducts at limiting plate= metaplastic process, reaction to bile salts). May be bypass mechanism to help drain bile–> ductular cells can absorb bile salts to protect hepatocytes (reabsorption will then cause leakage into portal connective tissue–> marked lymphocyte response)
A 40 year old woman presents with pruritis without jaundice. The following histologic sample is recovered from her liver biopsy. What is the diagnosis?
- *Cholate stasis**= damage from bile salts causes cellular swelling of hepatocytes (“feathery degeneration”)
- Seen in zone 1
Woman has Primary biliary cholangitis
- *Below**: Cholestasis: increasing inability to excrete bile–> bile pigment from bilirubin accumulates within lobule
- seen in zone 3
A 50 year old man presents with jaundice, itching, and light colored stools with darker urine. The following histologic sample is obtained from his liver. What is his diagnosis?
Bile infarct= sign of extrahepatic biliary obstruction (for example, primary sclerosing cholangitis)
Below: biliary sludge due to PSC
A 45 year old woman presents with itching and no jaundice. Blood tests reveal elevated INR and positive AMA- what is her diagnosis (based on histologic sample below) and what changes are noted because of her disease? How can she be treated?
Primary biliary cirrhosis/cholangitis: causes bile duct lesions due to lymphocytic infiltration (from excess bile salt)–> leads to ductopenia (bile duct loss).
- Differentiate from chronic hepatitis: prominent duct damage, mixed infiltrate (neutrophils and eosinophils) and granuloma
Granuloma (below)= not speciifc for PBC (can also be seen in hepatic sarcoidosis, drug reaction, infectious etiologies
Clinical features of PBC:
Female
Early signs:
- Asymptomatic with elevated alkaline phosphatase (out of proportion to bilirubin)
- Pruritis without Jaundice
- Malabsorption of fat-soluble vitamin ( can lead to elevated INR in absence of end-stage liver disease due to decreased Vit K absorption)
Later signs:
- Xanthomas
- Osteoporosis (Vit D malabsorption)
- Jaundice, ascites, portal HTN (liver failure)
Histo:
- Involves intrahepatic bile ducts (MICROscopic)
- See bile duct lesions (lymphocytic infiltration/granulomatous inflammation)
- Chronic non-suppurative destruction cholangitis
- Leads to ductopenia/fibrosis
Treatment of PBC:
- Urosodeoxycholic acid (UDCA)
- Cholestyramine= relieves pruritis
- Liver transplantation in advanced cases
What type of changes are noted on the gallbladder sample below and what might it be indicative of?
Lymphoplasmacytic cholecystitis: lymphoplasmacytic infiltrate in gallbladder. Occurs in distal bile duct obstruction in the absence of gallstones- seen in PSC
A 65 year old man presents to his physician for his annual physical. His blood panels come back with an AST= 5.1 and ALT= 2.3, elevated GGT. A liver biopsy is performed and the following abnormalities are found. What is his diagnosis?
Alcoholic Steatohepatitis: can see steatosis and lobular inflammation and injury (cellular swelling/ballooning- below), lymphocytic inflammation of lobules, presence of Mallory bodies (bottom). Indicative of steatohepatitis due to macrovesicular steatosis and cellular swelling/ swollen mitochondria
Mallory bodies= ubiquinated cytokeratins 8, 18.
It is likely this man has been drinking at least 100-150 g of alcohol a day
* AST/GGT synthesis enhanced by alcohol metabolism—> AST/ALT ratio >1 (2), GGT elevations
“Chicken-wire” fibrosis seen in steatohepatitis (predominantly in zone 3)
Below: ASH- alcoholic steatohepatitis–> Glycogenated Nuclei and megamitochondria. More commonly seen in ASH than NASH.
A 28 year old man with a 5 year history of ulcerative colitis goes for his annual physical. His metabolic panel indicates an elevated alkaline phosphatase. Based on the imaging below, what type of diagnostic procedure did he have, what is his condition, and what is the treatment?
Endoscopic retrograde cholangiopancreatography (ERCP)= diagnostic gold standard for primary sclerosing cholangitis, potential to apply therapy (opening strictures)
Treatment:
- NONE
- treat for cholangitis
- open strictures, monitor for cancer
- Liver transplant curative, can recur
A woman undergoing therapy for breast cancer is called back to her physician’s office for abnormal LFTs. The physician wants to determine if the medications she is taking are causing liver damage. A CT scan if performed, and findings correlate with the gross specimen below. What is her diagnosis?
Metastatic liver malignancy: Most common malignancy of liver
Seen in non-cirrhotic liver- metastases don’t like cirrhotic liver. Come from colon, pancreas, breast, lung
A 52-year old man with a history of Hepatitis C infection. A laboratory abnormality likely to be encountered in this patient is a marked elevation of what serum biological marker?
Alpha fetoprotein (seen in 50% of people with HCC- in this case due to chronic Hep C infection)
Histo: Expansion of liver plates visible
A 30 year old woman is in a car accident where she suffers abdominal trauma. At the hospital, a CT scan of her abdomen is performed and the radiologist notes a mass in her liver. A biopsy is performed to rule out a malignancy. Based on the histology below, what is her diagnosis and prognosis?
- *Focal nodular hyperplasia**:
- Benign non-neoplastic mass; arises in non-cirrhotic liver
- Asymptomatic- rarely grows or bleeds, no malignant potential
- Occasionally resected to differentiate from hepatic adenoma, tumors
- More common in Women, age 20-50
- *Histo**:
- Comes from malformation of arteries in center of nodules– central “stellate scar” (below)
- Fibrous bridges with dysplastic (malformed) arteries, without accompanying bile duct/vein. At edges of fibrosis, see ducts/veins
- Non-neoplastic: arises from alternating hepatocyte hyperplasia and atrophy due to malformed arteries
A 35 year old woman with a history of SLE presents to the emergency room with hematemesis. Endoscopic exam reveals esophageal varices. The woman denies a history of hepatitis or chronic alcohol consumption, but her blood panels reveal elevated bilirubin and LFTs. A liver biopsy is taken and the following is revealed. What is her diagnosis based on her symptoms and history?
- *Nodular regenerative hyperplasia**= non-cirrhotic portal hypertension; occurs in:
- Autoimmune disease, hypercoagulability disorders, hematologic disorders, portal vein thrombosis, drugs
- Zone 3 deprived of nutritionally rich blood from portal tract–> sinusoidal dilation, nodular appearance
Histo: See zone 3 nutritional atrophy–> sinusoidal dilation and NO fibrosis
- May also see portal tract venopathy (venous obliteration/narrowing)
* NOT regenerative or hyperplastic!
A 50 year old chronic alcoholic is brought to the ER for a 2 day history of vomiting and diarrhea accompanied by a recent onset of jaundice. Blood panels come back with the following: Elevated LFTs, elevated bilirubin, (-) for IgM Anti-HAV, IgM anti-HBc, IgM anti-HbE. A liver biopsy is obtained (below). What does it show and how should the patient be treated to prevent further illness?
Zone 3 necrosis caused by acetaminophen toxicity. Also seen in carbon tetrachloride exposure, severe hypoperfusion from shock or left sided heart failure. Infarcts are uncommon as liver has 2 blood supplies- portal venous and hepatic arterial system (therefore entire system needs to lose blood, not just infarct of hepatic artery)
- Seen in Zone 3= furthest from blood supply (last dibs- most vulnerable to ischemia)
- *Treatment**:
1. Rehydration (vomiting/diarrhea)
2. Acetaminophen overdose needs STAT administration of N-acetylcysteine (mimics function of glutathione which is depleted by alcohol ingestion–> breaks down toxic ethanol metabolites)- best if administered within 16 hours of ingestion
3. Liver transplant- most of the damage has already occured- will need a new liver
* 40% of acute liver failure (ALF) due to acetaminophen toxicity (occurs in anyone receiving sufficient dose)
60% ALF due to idiosyncratic drug reactions
A 25 year old woman comes to the emergency room after several days of vomiting, diarrhea, and new onset jaundice. She has no history of alcohol abuse and no chronic medical conditions or medications. She says she returned from a trip to Thailand with her boyfriend a month ago and felt fine until about 4 days ago. What tests should be ordered and what is her diagnosis based on the liver biopsy below? Are there any long-term complications?
Acute hepatitis. Acute viral hepatitis are NOT cytopathic–> injury due to T-cells eliminating infection by killing infected hepatocytes.
- *Diagnostics**:
1. Serology (NOT biopsy- despite example) to discover cause of hepatitis: - Hep A: Anti-HAV IgM (patient likely had immunization before leaving for Asia- test positive for Anti-HAV IgG)
- Hep B: Anti-HBc IgM (likely immunized, would test positive for Anti-HBs)
- Hep C: HCV RNA (unlikely to have acute infection- chronicity more common. history of IVD use?)
- Hep D: Would need concomittant HBV infection
- Hep E: anti-HEV IgM- no vaccine, no long-term risks unless pregnant)- Most likely diagnosis based on history of travel and adequate vaccination history.
- Biopsy ONLY if acute hepatitis source indeterminate or trying to assess amount of injury/fibrosis
Below: hepatocellular dropout in acute advanced hepatitis–> parenchymal collapse–> mimics fibrosis (“bridging necrosis”). Can also see cholestasis (hepatocytes fail to move bile out of liver)
Histo: lymphocytic infiltrate, lobular hepatitis- see cellular swelling, architectual disarray. Cellular swelling and apoptotic hepatocytes (councilman bodies) visible.
* Can also see “flare” of chronic hepatitis- resembles lobular changes, BUT there would also be portal inflammation
Histologic specimen of normal small intestine
Below: plica circulares
Normal small bowel mucosa
A villous height-‐to-‐crypt depth ratio of 3:1 to 5:1.
Less than 20 intraepithelial lymphocytes per 100 enterocytes, distributed in a decrescendo pattern (i.e. less concentrated at the tips)
The lamina propria contains a mild physiologic mix of plasma cells, lymphocytes, and occasional eosinophils.
Brunner’s glands within duodenum
Terminal ileum: see peyer’s patches (lympoid aggregates), villi with crypts of Lieberkuhn.
Absorptive cells blend and are lined by thin ribbon (brush border) with interspersed goblet cells
Normal Colonic Histo: “test tubes in a rack”
Below: Haustral folds
A 65 year old woman presents to her physician with complaints of chronic watery diarrhea. She denies any blood in the stool and had a clear colonoscopy 1 month ago. A colonoscopic sample is taken and the following is found. What is her diagnosis and treatment?
Lymphocytic colitis= form of microscopic colitis
- F: M ratio 3:1
- Increased intraepithelial lymphocytes
- No increased subepithelial collagen
- Lamina propria: increased lymphocytes, plasma cells, eosinophils
Microscopic colitis= chronic watery (non-bloody) diarrhea, normal endoscopy), typically seen in middle-aged and elderly patients, idiopathic, sometimes associated with long-term NSAIDs, celiac disease
Therapy: dietary, drug modification. Budesonide (glucocorticoid with mucosal activity and little systemic activity)
Below: unremarkable changes in colon surface on gross examination
A 65 year old woman presents to her physician with complaints of chronic watery diarrhea. She denies any blood in the stool and had a clear colonoscopy 1 month ago. A colonoscopic sample is taken and the following is found. What is her diagnosis and treatment?
Collagenous colitis= form of microscopic colitis
- F:M ratio 8:1
- Increased intraepithelial lymphcytes
- Thickened subepithelial collagen (pink)
- Increased lymphocytes, plasma cells, eosinophilas in lamina propria
- No architectural changes (no crypt distortion unlike UC/Crohn disease)
Microscopic colitis= chronic watery (non-bloody) diarrhea, normal endoscopy), typically seen in middle-aged and elderly patients, idiopathic, sometimes associated with long-term NSAIDs, celiac disease
Therapy: dietary, drug modification. Budesonide (glucocorticoid with mucosal activity and little systemic activity)
Below: no changes in colonic surface on colonoscopic exam
