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1

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%

2

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

3

Mucoepidermoid carcinoma

Most common malignant tumor

- Mucinous and squamous components
- Painful mass d/t common involvement of facial nerve

4

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)

5

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

6

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)

7

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

8

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

9

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

10

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

11

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

12

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)

13

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

14

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)

15

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

16

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

17

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

18

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

2. Fibrostenotic: obstruction, diarrhea (bacterial overgrowth)

3. 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

19

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)

 

20

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

21

Crohn disease: string sign

* Yersinia infection can mimic Crohn Disease

- See exudative diarrhea (contains blood, pus)

22

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

23

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

24

Ulcerative colitis: pseudopolyps

25

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

26

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

27

Cirrhotic liver: trichrome stains fibrosis blue

- Chronic hepatitis/alcohol ingestion--> cirrhosis

- Only 3% of patients with cirrhosis decompensate each year

28

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)

29

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)
 

30

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