MD4 Smorgasbord Flashcards
Pheochromocytoma Clinical Presentation
Severe or episodic HTN, palpitations, tachycardia, anxiety, and excessive sweating

Steatosis

Chronic Cholecystitis
What is the prognosis of hepatocellular carcinoma?
Poor
10% 5-year survival

Adenomatous Polyps
Progression of normal epithelium to adenocarcinoma


Hemochromatosis

Pancreatic Endocrine Neoplasm
(Islet Cell Tumor - cells are well-differentiated)

Acute Hemorrhagic Gastritis
What is acute cholecystitis and how is it characterized?
Acute onset of symptoms, 90% associated with gallstones
Gallbladder often enlarged, tense
Fibrinous serosal exudates
May be hemorrhagic, filled with pus, or health with calcification (porcelain GB)

Pheochromocytoma

Hypertrophic gastropathy

Chronic Pancreatitis Pancreatic pseudocyst

Medullary Carcinoma

Normal Stomach

Gastric Ulcer
MEN-1 vs. MEN-2


Ischemic Enteritis
What is the most common cause of chronic gastritis?
Helicobacter pylori. Spiral bacteria may be found in gastric biopsies

Cortex
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
Medulla

Metastatic Carcinoma
What are some complications of pancreatic adenocarcinoma?
Primary effects:
- Metastases (lung, liver, peritoneum)
- Pancreatic carcinoma
- Abdominal pain (peripheral lymphatic invasion)
Secondary effects:
- Trousseau syndrome: Migratory peripheral thrombophlebitis (10-25%)
- Courvosier gallbladder: painless jaundice, dilated gallbladder
- Weight loss
- Obstructive jaundice


Acute Pancreatitis
White foci= fat necrosis due to fat digestion by lipase, releasing fatty acids that bind to calcium forming soaps (saponification)

Grave’s Disease

Waterhouse-Friderichsen Syndrome purpura
Acute adrenal insufficiency due to DIC/hemorrhage caused by Neiserria meningititides infection.

Adrenal Cortical Carcinoma

Candida Esophagitis

Cirrhosis
What are predisposing factors for hepatocellular carcinoma (hepatoma)?
Cirrhosis
Hep B and C
Thorotrast (formerly used as radiographic contrast agent)
Alcohol
Radiation
Alpha-1 antitrypsin deficiency
Hemochromatosis
what is hereditary hemochromatosis?
Hereditary hemochromatosis (Bronze diabetes)
Autosomal recessive disorder of iron metabolism (HFE gene, chromosome 6p)
1-2/1,000 and M:F = 7:1 (men present earlier in life)
Prussian blue stain for iron shows granular staining in hepatocytes
What are some complications of acute pancreatitis?
Systemic organ failure, shock, ARDS, acute renal failure
DIC
Pancreatic abscess
Pancreatic pseudocyst

Adrenal Cortical Adenoma

Normal Thyroid

Carcinoid Tumor

Chronic Pancreatitis Pancreaticpseudocyst (no epithelial lining)

Parathyroid Hyperplasia
Sestamibi Scan
Layers of Adrenal Gland
Outer yellow cortex and red brown medulla (10:1)
Zona glomerulosa (10-15%): mineralocorticoids
Zona Fasciculata (60-70%): glucocorticoids
Zona Reticularis (20-30%): androgens

Gastric Lymphoma

Viral Hepatitis B
Ground glass change - cytoplasm turns into smooth ground glass appearance due to viral replication
Etiology of Hyperparathyroidism


Normal esophagus by endoscopy

Gastric Adenocarcinoma
Gross pathology of ischemic enteritis/colitis
Dusky discoloration of the bowel, blood in lumen

Squamous Cell Carcinoma of Esophagus

Reflux Esophagitis (increased eosinophils)

Metastatic Gastric Carcinoma
Virchow’s node
Two hereditary colon cancer syndromes
- Familial adenomatous polyposis
- Hereditary non-polyposis colorectal cancer (Lynch syndrome):
a. Germline mutations in mismatch repair genes result in defective DNA repair, which is manifest as microsattelite instability
b. Increased risk for cancer of the colon/rectum, stomach, endometrium, ovary, etc.
c. Diagnosis of HNPCC: MSI by PCR, immunohitochemistry for mismatch repair proteins (MLH1, MSH2, MSH6, PMS2)
d. Stage for tage, patients with HNPCC have a better prognosis than sporadic colon cancers

Acute Pancreatitis

Colon Carcinoma

Pituitary Adenoma
What is the stalk effect?
(in terms of excess prolactin)
Mildly elevated PRL is a common phenomenon, related to “stalk effect” rather than direct secretion by a pituitary adenoma. Any mass in the site can interfere mechanically with hypothalamic-hypophyseal connections and disrupt the steady-state inhibitory effect of the hypothalamus on PRL secretion by the AP gland. Does not justify a diagnosis of PRL-secreting pituitary adenoma.

Acute Pancreatitis

Hashimoto’s Thyroiditis
Lymphoid follicle with germinal center

Hepatocellular Carcinoma

Papillary Carcinoma
Calcification - Somoma body

Medullary Carcinoma

Pancreatic carcinoma

Papillary Carcinoma

Esophageal Varices
Local complications of ulcerative colitis


Cholelithiasis

Cirrhosis

Gastric Ulcer

Acute Pancreatitis

Insulinoma

Esophageal Varices

Tubular Adenoma

Left: Zona Fasciculata
Right: Zona Reticularis

Normal
Medullary carcinoma
How common is it
Associations
Produces ____
Due to ____
Histo
Metastasis
5-10% of thyroid carcinomas, some associated with MEN2A/2B
Derived from parafollicular cells (neuroendocrine tumor)
Produce calcitonin (hypocalcemia uncommon)
Due to activating mutations of RET proto-oncogene (familial and some sporadic tumors)
Histo: Marked variation in appearances
Commonly has neuroendocrine appearance with nests & trabeculae of uniform cells
Amyloid within stoma common (calcitonin deposition)
Tumor cells stain from chromogranin and synaptophysin (neuroendocrine markers)
Spreads via lymphatics/blood to lymph nodes, lungs, liver, bones

Follicular Adenoma

Herpes Esophagitis
Lymphomas of the stomach
What is the most common form?
Most common site of extranodal lymphomas
5% of gastric malignancies, 20% of all extranodal lymphomas
Most common form: low-grade B-cell lymphoma of MALT (mucosa-associated lymphoid tissue)
Associated with H. pylori infection
Composed of dense infiltrate of small lymphoid cells, often showing plasma cell differentiation and invasion of gastric glands (lymphoepithelial lesions)
What is alcoholic hepatitis?
Develops in 20-25% of heavy drinks
Characterized by:
Inflammation and hepatocyte degeneration
Neutrophilic infiltrate
Steatosis
Mallory bodies (eosinophilic PAS +, corkscrew shaped intracytoplasmic stuctures made of intermediate filaments (keratin)


Papillary Carcinoma
Nuclear clearing - pale “orphan annie” nuclei
Blood vessels & cuboidal tumor cells

Esophageal Varices (ulceration + hemorrhage)

Cirrhosis

Celiac Disease

Normal Endocrine Pancreas
Antibody staining for insulin in beta-cells
Systemic complications of ulcerative colitis



Medullary Carcinoma
Dense secretory core granules
What are the associated metastases of stomach adenocarcinoma?
Left supraclavicular lymph node (Virchow’s node) or both ovaries (Krukenberg tumor)

Chronic Pancreatitis
Concretions and atrophy replaced by chronic scar tissue
What is the Rule of 2s of Meckel’s Diverticulum
- Affects 2% of the population
- Located within 2 ft of the ileocecal valve
- Approximately 2 inches long
- 2% are symptomatic

Acute cholecystitis
How do gallstones form
Secondary to supersaturation of bile


Adrenal Cortical Carcinoma

Multiple Endocrine Neoplasia 2B

Normal Stomach (Fundus)

Follicular Carcinoma

Adrenal Cortical Adenoma
Right: tumor, often with much lipid

Meckel’s Diverticulum
Presentation of Gastrinoma
75% located in pancreas, peripancreatic region, 23% in duodenum, and rare in stomach
70-90% are malignant
Usually solitary and malignant if not associated with other endocrine abnormalities
Usually multiple and benign in a component of MEN
Adrenal Cortical Adenoma gross and microscopic findings
Gross: Bright yellow or yellow-brown tumors, usually
Microscopic: Usually composed of clear-pale cells resembling adrenal cortical cells, may have pleomorphism of cells, mitotic activity is usually low

Appendicitis
Adenocarcinoma of GB
Pancreatic Endocrine Neoplasm:
Epidemiology
Area of pancreas that is affected
Functional?
Histology
Epi: much less common than tumor of exocrine pancreas; adults primarily affected; single or multiple; benign or malignant
Area: Usually body or tail of pancreas
Functional: 60% secrete one or several peptide hormones
Histo: uniform cells with round/oval nuclei, fine chromatin, and pale granular cytoplasm

Adenocarcinoma of Esophagus

Celiac Disease

Alcoholic Hepatitis
Arrow: Mallory body
Aggregate of inflammatory cells *largely neutrophils
What are the 2 main disorders of Hypertrophic Gastropathy?
Menetrier diseaes: hyperplasia of mucous neck cells due to elevated levels of TGF-alpha. Protein-losing enteropathy (diarrhea, edema). Associated with increased risk of gastric adenocarcinoma.
Zollinger Ellison Syndrome: Triad of gastrinoma (gastrin-secreting tumor usually in pancreas or duodenum due to hyperplasiz of oxyntic mucosa - parietal and chief cells), hypertrophic gastropathy and peptic ulcers due to hypersecretion of acid.

Hashimoto’s Thyroiditis
Oncocytic Herthle cells

Thyroid nodular hyperplasia
no capsule, benign

Parathyroid Adenoma

Gastrointestinal stromal tumor
Neuroblastoma Epi
7-10% of all childhood malignancies
2nd most common childhood solid malignancy
80% occur in children
Graves’ vs. Hashimoto’s Pathogenesis

What genetic alteration can be found in papillary thyroid carcinoma?
Rearragement of the tyrosine kinase portion of RET proto-oncogene (chromosome 10) to put the tyr kin portion under the promotor of a gene that is constitutively expressed by follicular cells. Normally, tyr kin receptor is not normally expressed by thyrocytes.
[Causes high-level expression of tyrosine kinsase portion of the receptor as an unregulated growth signal)

Meckel’s Diverticulum Complication
Intussusception
How do you distinguish hemochromatosis from secondary hemosiderosis?
Quantitative irone analysis
Secondary hemosiderosis = iron overload where iron accumulation typically affects Kupffer cells

Pituitary Adenoma

Ischemic Enteritis
RET Protooncogene mutations in MEN type 2


Acute Viral Hepatitis

Ulcerative Colitis

Villous Adenoma

Multiple Endocrine Neoplasia 2B
Mucosal neuromas
Have C cell hyperplasia nodules

Tubular Adenoma
S/Sx of thyroid hyperplasia


Barrett Esophagus

Squamous Cell Carcinoma of Esophagus
50% mid-esophagus, 30% distal, 20% proximal
What is hypertrophic gastropathy characterized by?
Giant, “cerebriform” enlargement of rugal folds of gastric mucosa due to hyperplasia of epithelial cells

Gastric Adenocarcinoma
Gross finidings in ulcerative colitis
- Extends proximally from the rectum in a continuous fashion (without skip lesions)
- Typically limited to the mucosa and submucosa, except in severe cases
- Ulceration of mucosa
- Pseudopolyps due to islands of mucosal regeneration
- May result in megacolon
What are some complications of cirrhosis?
Portal HTN
Esophageal varices
Ascites
Splenomegaly
Hepatic encephalopathy
Hepatocellular carcinoma

Epi of colorectal adenocarcinoma?
Second leading cause of cancer death in U.S.
Adenocarcinoma accounts for 98% of all cancers of large intestine

Crohn’s Disease

Normal Endocrine Pancreas
Antibody staining for glucagon in alpha-cells
Microscopic findings in DM pancreas (Types 1, 2)
Type 1: reduction in number and size of islets;
leukocytic infiltration of islets (“insulinitis”)
Type 2: hyalinization/fibrosis of islets;
amyloid deposition (compose of amylin - cosecreted with insulin)
What are the types of gallstones
Gallstones occur secondary to supersaturation of bile
only 10% of gallstones are pure
- cholesterol stones: pale, yellow, round/oval, single, radiolucent
- pigment stones (Ca2+ bilirubinate): black/brown, oval, multiple
Etiology of Hypercortisolism
Cushing’s Syndrome
Pituitary (Cushing’s Disease): 60-70%
Adrenal: 20-25%
Ectopic: 10-15%

What are some S/Sx of Cushing’s?


Herpes Esophagitis

Viral Hepatitis

Grave’s Disease
Resorption vacuoles; Hypertrophic columnar follicular cells

Candida Esophagitis
Pseudomembranes

Adrenal Cortical Carcinoma

Hemochromatosis
What are esophageal varices?
Collateral, dilated veins which develop in response to portal hypertension. Tortuous dilated veins within submucosa that may cause massive upper GI bleeding
10-30% of upper GI hemorrhage
25-35% of cirrhotic patients
30% of initial bleeds fatal

Neuroblastoma

Normal Small Intestine
What is the clinical significance of adenomatous polyps?
Patients are at increased risk of developing colorectal adenocarcinoma
Describe Gross/Histo of Follicular adenoma
Euthyroid
Gross: Usually solitary, encapsulated nodule
Histo: Macro/micro follicular, appearance of cells differs from surroudning normal thyroid gland
Neither capsular invasion nor vascular invasion present
What drug can be given for a prolactinoma?
Bromocriptine:
Dopamine agonist that inhibits PRL secretion and shrinks lactotrophs

Pseudomembranous Colitis
Immunology of Celiac Disease
Associated with HLA-DQ2 or HLA-DQ8

Metastatic Carcinoma

Pituitary Adenoma
Gross finidings in appendicitis
Swollen appendix with serosal exudates
Manifestations of Parathyroid Adenoma


Gastric Adenocarcinoma
Signet Ring Cell Morphology
With stain for cytokeratin (ensures that it’s carcinoma, not macrophage)
What is the traditional classification of cirrhosis (and its associated diseases)?
Macronodular (>3 mm)
- Viral hepatitis
- Alpha-1 antitrypisin deficiency
- Wilson’s Disease
Micronodular (
- Alcoholism
- Hemochromatosis
- Primary biliary cirrhosis
- Wilson’s Disease
Presentation of Waterhouse: Friderichsen Syndrome
Rapidly progressive hypotension leading to shock
DIC with purpura
Pathology: Bilateral adrenal hemorrhage and necrosis

Gastric Adenocarcinoma
What is diverticular disease?
Acquired outpouchings of the colonic mucosa and submucosa with an attenuated or absent muscularis propria.
Most common in the left colon, particularly sigmoid colon.
Most are asymptomatic; 20% have pain, constipation, abdominal distention, etc.
Types of necrosis in ischemic enteritis/colitis
- Mucosal necrosis: usually results from hypoperfusion
- Transmural necrosis: usually due to occlusion of a major mesenteric blood vessel (i.e. SMA or IMA)
Which is more common:
Primary tumors of the SI
Metastatic tumor involving SI
Metastatic.
Primary are relatively rare.

Gastric Carcinoma (Polyploid/ulcerated)
MEN-2B: Gorlin’s Syndrome
Mutation in RET oncogene
Medullary carcinoma of thyroid
Pheochromocytoma of adrenal gland
Mucosal neuromas (oral cavity, GI tract, etc.)
Marfanoid appearance

Diverticulosis
Microscopic findings in Crohn’s Disease
- Mucosal ulceration with acute inflammation
- Submucosal chronic inflammation with lymphoid aggregates and granulomas
- Epithelioid granulomas in muscularis propria and subserosal tissue
- Chronic mucosal damage (crypt architectural distortion)
What is the histology of gastritis?
Increased numbers of inflammatory cells within lamina propria, including lymphocytes, plasma cells, and neutrophils.
Neutrophils often infiltrate mucosal epithelium (“active” gastritis)

Parathyroid Adenoma

Carcinoid Tumor

Adrenal Cortical Carcinoma
What is the change that happens in Barrett’s esophagus?
Intestinal metaplasia (goblet cell metaplasia) of distal esophagus in response to acid-reflux

Follicular Adenoma
Contained by fibrous capsule (top left is adenoma)

Normal Stomach (Antrum)
Describe a normal Esophagus
Gross: Pale esophageal mucosa (as compared with tan-brown gastric mucosa) and discrete gastro-esophageal junction
Histo: Squamous-lined mucosa of esophagus with submucosal glands and muscularis propria

Hashimoto’s Thyroiditis

Cortex
Zona Glomerulosa
Zona Fasciculata
Zona Reticularis
Medulla
What is an erosion?
What is an ulcer?
Erosion: Partial thickness loss of mucosal tissue
Ulcer: Full-thickness loss of mucosa
What is ischemic enteritis/colitis?
Necrosis of the bowel due to insufficient blood supply

Ulcerative Colitis

Hemochromatosis

Adrenal Cortical Carcinoma
What form of hyperthyroidism shows exopthalmos?
Graves Disease. Only.
Treatment of graves focuses on reducing T4 secretion. This does not affect exophthalmos because it is an autoimmune problem (with TSI).
Adrenal Cortical Adenoma
Microscopic findings
Features of malignancy
Median survival
Microscopy: May be frankly anaplatic or resemble tumor cells of adrenal cortical adenoma
Malignancy: vascular invasion or metastasis
Survival: ~2 years

Candida Esophagitis

Gastric Adenocarcinoma

Normal Thyroid
Parafollicular cells only in lateral lobes (from neural crest)
Compare and contrast Menetrier Disease (adult) and Zollinger-Ellison Syndrome
Both are examples of Hypertrophic gastropathy


Gastric Ulcer

Waterhouse-Friderichsen Syndrome
Hemorrhagic necrosis of adrenal glands.

Celiac Disease
What are some complications of chronic pancreatitis?
Pseudocyst
Duct obstruction
Malabsorption, steatorrhea
Secondary diabetes

Normal Posterior Pituitary

Normal Endocrine Pancreas
What causes enlargement of the thyroid gland in Hashimoto’s thyroiditis?
Infiltration by lymphoid cells.
Do medullary carcinomas arise in the thyroid isthmus or thyroglossal duct remnants?
No. C cells migrate from neural crest to lateral thyroid lobes.

Adrenal Cortical Adenoma

Malignant Gastrointestinal stromal tumor
What are the different parts of the stomach?

What are some copmlications of ulcers?
Bledding, performation, obstruction

Medullary Carcinoma

Adrenal Tuberculosis
Caseous Necrosis

Gastritis

Diverticulosis
What are some features that favor GIST malignancy?
Tumor size (>5 cm)
Increased mitotic rate (>5 mitotic figures/50 high power fields)
Presence of tumor necrosis
Mucosal invasion
MEN-1: Wermer’s Syndrome
Mutation in MEN-1 gene (11q13)
Parathyroid hyperplasia/adenoma
Pituitary adenoma
Pancreatic (or duodenal) islet cell tumor (symptomatic tumors are commonly gastrinoma or insulinoma)

Gastrointestinal stromal tumor

Hashimoto’s Thyroiditis

Pseudomembranous Colitis
What are the gross and histologic patterns of adenocarcinoma of the stomach?
Gross: 1) Exophytic or polypoid, ulcerated mass
2) Diffuse thickening of stomach (linitis plastica “leather bottle” stomach)
Histologic: 1) “intestinal” type: cohesive, gland-forming tumor cells
2) “Diffuse” type: discohesive “signet” ring cells w/ intracytoplasmic mucin


Hypertrophic gastropathy
What is the definition of cirrhosis?
Scarring of entire liver with 1) diffuse fibrosis 2) loss of lobular architecture 3) nodular regeneration
It is the end-stage of many chronic disorders, so it is difficult to determine precise etiology by histology alone

Diverticulosis
Describe (macro and micro) the normal gall bladder
Macro: sac-like with thin wall and green mucosal lining
Micro: columnar epithelial lining, lamina propria, muscularis propria (no muscularis mucosae or submucosa)

Neuroblastoma

Parathyroid Carcinoma.
Bands of fibrous tissue.
What is Hashimoto’s thyroiditis?
Chronic lymphocytic thyroiditis
Predominantly affects women, usually middle aged-elderly
Anti-TSH receptor Ab (inhibitory), anti-thyroglobulin, anti-thyroid peroxidase Ab
Initially may be thyrotoxic, then become hypothyroid
Increased risk for malignancy, lymphoma, and possibly carcinoma

Multiple Endocrine Neoplasia
Are celiacs at increased risk for malignancy?
Yes: lymphoma and carcinoma

Gastric Lymphoma

Celiac Disease

Medullary Carcinoma
Amyloid composed of pro-calcitonin

Pancreatic Endocrine Neoplasm
(Islet Cell Tumor - arranged in groups)
Describe a normal stomach
Gross: Tan brown mucosa and gastric rugae (folds)
Microscopic: gastric pits lined by mucous neck cells with glands lined by parietal (red-pink) and chief (pale) cells. Little/no inflammatory cells normally present in gastric mucosa.

Thyroid Nodular hyperplasia
Due to iodine deficiency, diet, meds/genetics
Colorectal adenocarcinoma malignant tumors

Gross findings in Crohn’s Disease
- Sharp demarcation with segmental intestinal involvement (skip lesions)
- Thickened bowel wall with luminal narrowing (string sign by imaging)
- Serpentine mucosal ulcers or a cobblestone appearance to the involved mucosa
- Tendency toward fistual formation or bowel perforation

Viral Hepatitis
Risk factors for cholesterol stones
Female, fat, >40, fertile
Drugs
GI disorders

Normal Pituitary Gland
What is the prognosis of stomach adenocarcinoma?
Depends on stage, overall 5 year survival about 30%

Hashimoto’s Thyroiditis
“Fish-flesh” and infiltrated by lymphocytes
4 major and 2 minor cells types of endocrine pancreas and their hormones
- Beta cell: insulin
- Alpha cell: glucagon
- delta cell: somatostain
- PP cell: pancreatic polypeptide
- D1 cell: vasoactive intestinal polypeptide
- Enterochromafiin cell: serotonin

Gastric Ulcer (Malignant)
What skin condition is associated with celiacs?
Dermatitis herpetiformis: blistering skin disorder with IgA deposits

Crohn’s Disease

Neuroblastoma
Left: area of necrosis

Hypertrophic gastropathy

Diverticulosis

Reflux Esophagitis
Microscopic findings in appendicitis
Acute inflammation (neutrophils) infiltrating muscularis propria, often with mucosal inflammation/ulceration

Diabetes Mellitus Type 1
Congo red stain of amyloid

Pseudomembranous Colitis

Adenocarcinoma of Esophagus

Carcinoid Tumor
Where do adenocarcinomas of the esophagus occur?
What are some other risk factors?
What are adenocarcinomas?
What is it associated with?
Prognosis?
Majortiy arise in distal esophagus in association with Barrett esophagus
Risk Factors: smoking tobacco, obesity
Adenocarcinoma = gland-forming malignancy
Associated with dysplasia of adjacent glandular epithelium
Prognosis: Varies depending on stage, but overall 5yr survival

Chronic Cholecystitis
Immunohistochemistry for mismatch repair proteins

Immunohistochemistry for mismatch repair proteins
How do you distinguish chronic from acute hepatitis?
Distinction from acute made clinically, not pathologically
Usually requires elevation of liver enzymes for >6 months (or persistently elevated viral load)
Complications of Meckel’s Diverticulum
- Peptic ulcer (if gastric mucosa present)
- Infection - may mimic acute appendicitis
- Volvulus
- Intussusception

Adrenal Tuberculosis
Acid Fast Bacilli

Ulcerative Colitis
What is acute hepatitis characterized by?
Inflammation (mostly lymphocytic, with some neutrophils and eosinophils)
Lobular disarray
Ballooning degeneration
Acidophil (Councilman) bodies
May see bridging necrosis (severe cases)
What is the grosss and microscopic pathology of Hashimoto’s thyroiditis?
Gross: diffuse firm enlargement of thyroid, well demarcated from adjacent tissue
Microscopic: lymphocytic infiltrate with germinal centers
Oncocytic (Hurthle cell) metaplasia of follicular epithelium
Destruction of follicles, leading to fibrosis in late stages
What is acute pancreatitis characterized by?
Diffuse edema, acute inflammation, hemorrhage, fat necrosis, fibrosis, calcification
20% mortality

Pancreatic carcinoma

Barrett Esophagus
What is the clinical relevance of Barrett’s esophagus?
Increased risk of adenocarcinoma (dysplasia –> carcinoma)


Adenocarcinoma of GB

Gastritis

Gastrointestinal stromal tumor

Thyroid nodular hyperplasia
Can compress trachea or recurrent laryngeal -> hoarse voice

Normal Adrenal Gland
Cortex is yellowish.
Medulla is reddish-brown.
What mutagenic agent increase the incidence of papillary thyroid carcinoma?
Radiation

Normal anterior pituitary
Red = acidophils
Purple = basophils
Clear = chromophobes

Medullary Carcinoma

Adenomatous Polyps
Distinctive Features of Crohn’s Disease and Ulcerative Colitis (table)


Squamous Cell Carcinoma of Esophagus
What is ulcerative colitis?
A form of idiopathic inflammatory bowel disease which is limited to the colon and rectum.

Necrolytic Migratory Erythema
(Glucagonoma)

Adrenal Cortical Carcinoma

Meckel’s Diverticulum
What cells give rise to medullary carcinoma of the thryoid?
C cells

Neuroblastoma
Tumor cells form rosettes around a central anucleated zone.

Waterhouse-Friderichsen Syndrome
Hemorrhage in adrenal glands.
Acute adrenal insufficiency due to DIC/hemorrhage caused by Neiserria meningititides infection.

Parathyroid Adenoma
Solid sheets of cells.
Adenomas have compressed non-neoplastic tissue at edges.

Normal Esophagus and stomach

Candida Esophagitis

Papillary Carcinoma

Metastatic Gastric Carcinoma in liver

Metastatic Carcinoma

Normal Pituitary gland

Porcelain gallbladder
MEN-2A: Sipple’s Syndrome
Mutation in RET oncogene (10q11)
Medullary carcinoma of thyroid
Pheochromocytoma of adrenal medulla
Parathyroid hyperplasia

Left: Follicular adenoma
Middle: Follicular carcinoma
Right: Papillary carcinoma
What HLA types are associated with Hashimoto’s?
HLA-DR5
HLA-DR3
Presentation of Conn’s Syndrome
Primary hyperaldosteronism due to adrenal cortical adenoma.
HTN, neuromuscular symptoms (weakness, paresthesias), potassium wasting, increased aldosterone with typically decreased renin levels.
Almost invariabley caused by an adrenocortical adenoma.
Gastrinoma Triangle


Herpes Esophagitis

Follicular Carcinoma
Widely invasive
Pathogenesis of acute pancreatitis


Adrenal Cortical Adenoma
Uniform, arranged in nests.

Barrett’s esophagus
What are the functional classification of pituitary adenomas?
Classification of pituitary tumors based on serum hormone levels and/or immunohistochemical staining.
10% Corticotroph adenoma - secrete ACTH and POMC -> Cushing’s syndrome
20% Somatotroph adenoma - secrete GH -> Acromegaly, gigantism
1-3% Thyrotroph adenoma (rare) - secrete TSH -> thyrotoxicosis, usu. asymptomatic
10-15% Gonatotroph adenoma - secrete LH, FSH, & subunits -> usu. asymp.
25% Lactotroph adenoma (prolactinoma) most common - secrete PRL -> galactorrhea, hypogonadism, amenorrhea, infertility, loss of libido & impotence in men
20-30% Null cell adenomas - do not secrete hormones

Ischemic Enteritis

Pheochromocytoma
Secretory granules with catecholamines
Present with HTN intermittently
Can measure urinary metanephrines/VMA

Meckel’s Diverticulum

Pancreatic Endocrine Neoplasm
(Islet Cell Tumor - on the left)
Circumscribed/encapuslated.
In pancreas or region around pancreas.
What is celiac disease?
Gluten-sensitive enteropathy
A disorder resulting from hypersensitivity to gluten (protein component of wheat and other grains), which primarily affects the SI, leading to diarrhea and malabsorption (defective absorption of fats, vitamins, proteins, carbohydrates, and water).

Adrenal Cortical Adenoma

Parathyroid Hyperplasia

Alcoholic Liver Disease

Waterhouse-Friderichsen Syndrome
Acute adrenal insufficiency due to DIC/hemorrhage caused by Neiserria meningititides infection.

Gastrointestinal stromal tumor
Can arise anywhere in GI tract, thought to be due to Cajal cells

Appendicitis

Adrenal Cortical Adenoma
Normal Parathyroid Gland
Four glands (variable)
Mixture of chief cells (pale cytoplasm) and oxyphil cells (eosinophilic cytoplasm)
Variable amounts of adipose tissue (increases with age)

H. Pylori

Esophagitis (acute)
-Intercellular edema (spongiosis) and inflammatory cells in lamina propria

Hashimoto’s Thyroiditis
Metaplasia
What are the most common primary sites for metastatic carcinoma?
GI tract, breast, and lung
Papillary thyroid carcinoma
How common is it?
Who is affect?
How does it present? (Gross/Histo)
Prognosis?
Most common type of thyroid carcinoma (75-85% of thyroid carcinoma)
Women more commonly affects, presents with cold thyroid nodule
Gross: solid/cystic, firm, fibrous, often infiltrative appearance
Histo: Papillae lined by cuboidal to columnar cells
Nuclear features characteristic (intranuclear pseudoinclusions; nuclear clearing/grooves)
Psammoma bodies (laminated calcifications)
Prognosis: 95% 10 year survival, commonly metastasize to regional lymph nodes

Diabetes Mellitus Type 1
Deposits of extracellular amyloid composed of amylin, which is co-secreted with insulin

Gastric Lymphoma
Pathologic findings in familial adenomatous polyposis
By young adulthood, (mean age = 16 years), the entire colon is typicalliy covered in a carpet of adenomatous polyps. Adenocarcinoma develops after an average of 10-15 years.

Papillary Carcinoma
Finger-like projections
Celiac Disease Pathogenesis Diagram


Chronic Gastritis
Loss of glands + fibrosis
Comparison of Type 1 and Type 2 Diabetes Mellitus


Neuroblastoma
What is steatosis?
Increased storage of lipid in liver, resulting in yellow appearance (macroscopic) and cytoplasmic vacuoles (microscopic)
May be due to variety of causes (alcohol, DM, obesity, protein malnutrition, metabolic disorders)
What is Waterhouse-Friderichsen Syndrome?
Hemorrhagic destruction of adrenals related to severe bacterial infection: Meningococcus, pneumococci, Staphylococci, Pseudomonas, Haemophilus
Two growth patterns of colorectal adenocarcinoma
- Left colon: annular, apple-core lesions which often cause obstruction
- Right colon: polypoid, fungating mass often causing bleeding
Serology of Celiac Disease
Antibodies:
Anti-transglutaminase
Anti-gluten
Anti-endomysial

Metastatic Carcinoma

Chronic Pancreatitis

Colonic Adenocarcinoma
What is a GIST?
Gastrointestinal stromal tumor of stomach
Major of mesenchymal tumors of GI tract now classified as GISTs.
Thought to be dervied from interstitial cells of Cajal (pacemaker cells of GI tract).
Histo: Spindled (elongated) tumor cells

Villous Adenoma

Steatosis

Follicular Adenoma
Confined by capsule, no vascular invasion

Adenocarcinoma arising in Barrett Esophagus
What is appendicitis?
Inflammation of the appendix, usually associated with obstruction (i.e fecalith)
Patient has Hashimoto’s.
Patient takes oral contraceptives.
Patient has slightly elevated total T4 (with decreased free T4).
Why?
OCPs can increase the quantitiy of binding proteins and drive up the total T4 without changing the free fraction.

Papillary Carcinoma
Intra-nuclear pseudo-inclusions (invagination of cytoplasms)

Normal Small Intestine
Gross findings of DM pancreas
Pancreas may be small, atropic

Ischemic Enteritis
Presentation of Parathyroid Adenoma
Women > men, 3:1
Usually too small to be palpated
Presentation related to hypercalcemia due to PTH secretion (80% asymptomatic)
Encapsulated, cellular neoplasm
Usually chief cells predominate, other cell types may be present

Cirrhosis
Blue collagen bands in trichome stain

Acute cholecystitis
PMNs infiltrating mucosa
What is Crohn’s Disease?
A transmural granulomatous inflammatory disease that usually affects the terminal ileum or colon, but may involve any portion of the GI tract from mouth to anus.

Villous Adenoma

Gastric Ulcer

Appendicitis
-omas


Follicular Carcinoma
Vascular invasion

Pheochromocytoma
Adrenal medulla turns dark brown in a solution of chromium salts (oxidizes cathecholamines)

Alcoholic Hepatitis
Mallory Hyaline Body
What are the different causes of gastritis?
Alcohol, drugs (NSAIDS), bile reflux, stress, radiation, chemotherapy
What is Adenocarcinoma of the stomach associated with?
H. pylori infection

Normal Colon

Gastrointestinal stromal tumor
What is the most important screening test to determine functional status of the thyroid gland?
TSH assay: elevated in hypo, close to zero in hyperthroidism.

Gastric Adenocarcinoma
Microscopic findings in ulcerative colitis
- Ulceration with acute and chronic inflammation
- Crypt abscess formation
- Crypt architectural distortion with branched crypts
- Basal plasmacytosis
What are some differences between H. pylori and autoimmune gastritis?
Location, inflammatory infiltrate, acid production, gastrin, other lesions, serology, sequelae, and associations

Describe the anterior lobe of the pituitary gland
adenohypophysis: Origin from Rathke’s pouch. Produces GH, FSH, LH, ACTH, TSH
Somatotrophs (30%) and Lactotrophs (20%) - lateral regions
Corticotrophs (15%) and thyrotrophs (10%) - central regions
Gonadotrophs (20%) - diffusely distributed
Histology: Mixed population of epithelial cells arranged in acini
Portal blood supply from hypothalamus to anterior pit.

What are complications of hereditary hemochromatosis?
Cirrhosis
Hepatocellular carcinoma
Hypopituitarism, skin pigmentation, cardiac failure, DM, arthropathy, testicular atrophy


PancreaticCarcinoma

Metastatic Carcinoma

Normal Stomach (fundus)
Chief cells - purple (Pepsinogen)
Parietal cells - pink (HCl, IF)

Acute Pancreatitis
How common are ductal adenocarcinomas?
Where in the pancreas do most of these malignancies occur?
Pretty common
85% of all pancreatic malignancies
2/3 occur in head of pancreas
Describe metastatic carcinoma
Usually multiple circumscribed nodules
Microscopic findings in pseudomembranous colitis?
Necrotic debris on mucosal surface consisting of necrotic epithelial cells, degenerating inflammatory cells, mucus, and fibrinous material

Adrenal Tuberculosis
Histiocytes or macrophages

Follicular Carcinoma

Diverticulosis

Acute Pancreatitis

Hashimoto’s Thyroiditis

Acute Pancreatitis
Adenomatou Polyps diagram


Herpes Esophagitis
(sharply demarcated lesions)

Pancreatic carcinoma
What is the gross and microscopic pathology of a pituitary adenoma?
Gross: Enlarged pituitary gland with mass effect (macroadenoma >1cm) or circumscribed nodule within pituitary gland (micro
Microscopic: Disruption of normal pituitary architecture (sheets, expanded nests, trabeculae), monomorphous population of cells
Gross pathology of Celiac Disease
Flattening or loss (atrophy) of villi of the SI mucosa
Histology of ischemic enteritis/colitis
Necrosis and hemorrhage within affected regions

Pancreatic Carcinoma
What is the difference between a malignant and benign ulcer?
Can’t absolutely distinguish between benign and malignant ulcers by macroscopic exam alone.
Benign: small, regular smooth edges
Malginant: large, irregular with “rolled” or “heaped up” borders
Crohn’s Disease vs. Ulcerative Colitis (picture)


Steatosis

Parathyroid Adenoma

Choledocholithiasis

Normal Stomach
What is Meckel’s Diverticulum
Persistence (failure of involution) of the intestinal end of the omphalomesenteric duct (connects the lumen of the lumen of the developing gut to the yolk sac)
True diverticulum having all 3 layers of the normal bowel
Located on anti-mesenteric side of the SI
May have gastric or pancreatic heterotopia

Ulcerative Colitis

Pituitary Adenoma
Expansion of gland into sella turcica

Pancreatic carcinoma

Viral Hepatitis
Balloon hepatocytes that are degrading
Pathogenesis of Hashimoto’s Thyroiditis

Pheochromoctyoma Rule of 10
10% extra-adrenal (paraganglioma)
10% multiple (sporadic cases)
10% malignant
10% occur in children
10% familial (MEN2A/2B, NF-1, VHL)

Pancreatic Carcinoma

Steatosis
Describe the normal thyroid gland
15-25 gm in adults, but variable
Right & left lobes connected by isthmus, may have pyramidal lobe
Follicles lined by follicular epithelial cells (cuboidal/low columnar)
Colloid (stored thyroid hormone, thyroglobulin) appears eosinophilic, acellular material
Parafollicular “C” cells located between follicles

Crohn’s Disease

Gastrinoma Triangle

Viral Hepatitis

Acini of cheif cells; granular cells = oxyphil cells
Gross findings in pseudomembranous colitis?
Pseudomembrane formation appearing as dirty green-yellow plaques

Gastric Lymphoma
What is chronic cholecystitis and how is it characterized?
Recurrent biliary colic or absence of prior acute cholecystitis, virtually always associated with gallstones
Wall thickened and fibrotic
Chronic inflammation
Entrapped epithelial crypts (Rokitansky-Aschoff sinuses)

Hepatocellular Carcinoma

Gastric Adenocarcinoma
Diabetes Complications (Picture 2)

What are some S/sx of Acromegaly?


Ischemic Enteritis
What is metaplasia?
Reversible change from one mature cell type into another. May represent adaptive (protective) change in response to injury

Herpes Esophagitis
Ground glass appearance
What are some of the mutations associated wth pancreatico adenocarcinoma?
K-Ras, p16, p53, BRCA2, DPC4/SMAD4

What is the most common malignant tumor of the liver?
Metastatic carcinoma

Gastrointestinal stromal tumor

Ischemic Enteritis
Multiple Endocrine Neoplasia (MEN) Syndromes


Metastatic Carcinoma

Viral Hepatitis (Hemorrhagic)
What explains visual defecits in AP adenomas?
Compression of the optic chiasm causes bitemporal loss of peripheral vision.

Diabetes Mellitus Type 1
Autoimmune destruction of islets.
Inflammation and infiltration by T lymphocytes (dark cells) = insulinitis

Barrett Esophagus
Low grade dsyplasia
What is the most common malignancy of th esophagus?
What are risk factors?
Where does it occur?
What is the prognosis?
What is the histology?
Squamous cell carcinoma
Risk factors: Alcohol, tobacco, consumption of hot beverages, dietary foods
Location: Upper 1/3 - 20%, Middle 1/3 - 50%, Lower 1/3 - 30%
Prognosis: usually advanced stage at time of Dx, poor prognosis, overall 5yr survival 20%
Histo: polygonal tumor cells with prominent intercellular bridges and foci and keratinization (Squamous pearls)
What are the common causes of hypoadrenalism?
Autoimmune adrenalitis
Granulomatous infections of the adrenal gland
Anterior Pituitary failure
How is Barrett’s esophagus diagnosed?
Combination of clinical & pathologic criteria
Clinical: Endoscopic presence of salmon-colored mucosa above GE junction
Pathologic: Histologic evidence of intestinal metaplasia (presence of goblet cells) within columnar epithelium biopsied

Barrett Esophagus
High grade dysplasia

Gastric Ulcer

Esophageal Varices

Gastric Carcinoma
Signet Ring Cell Morphology

Gastric Adenocarcinoma
Signet ring cell morphology

Gastric Adenocarcinoma
What serum marker may be elevated in hepatocellular carcinoma?
Alpha feto-protein
What is a goiter?
Enlargement of the thyroid gland
Nodular vs. diffuse
Hyper vs. hypofunctioning
What is reflux esophagitis?
What is it characterized by?
Due to acid reflux; characterized by intra-epithelial inflammatory cells (esp. eosinophils), basal layer hyperplasia, spongiosis, and elongation of papillae of lamina propria

Alcoholic Hepatitis
Typically involves neutrophils that infiltrate lobules

Normal anterior pituitary
GH Antibody staining

Barrett Esophagus

Adrenal Tuberculosis

Appendicitis
What is the macroscopic and microscopic description of hepatocellular carcinoma?
Macro: single/multiple, may have bile staining
Micro: Atypical hepatocytes with nuclear pleomorphisms, thickened trabeculae (several layers thick), absent portal tracts

Cholelithiasis
What is dysplasia?
Pre-malignant change involving abnormalities in nuclear size, shape, and (lack of) maturation

Follicular Carcinoma
Capsule invasion

Ulcerative Colitis

Cholelithiasis
What hormone does medullary thyroid carcinoma most commonly secrete?
Calcitonin
(ACTH also possible)

Squamous Cell Carcinoma of Esophagus with keratin pearls
Describe Carcinoid Syndrome
- Only seen in the presence of hepatic metastasis (liver normally inactivates 5-HT secreted by tumor)
- Sx include abdominal cramps, diarrhea, bronchospasm, episodic facial flushing (due to vasodilation), cardiac valve fibrosis
Carcinoid tumors have roughly equal incidence as carcinomas.
Carcinoid tumors (neuroendocrine tumors) may produce bioactive substances (ie. serotonin or 5-HT).
All carcinoid tumors are potentially malignant (although appendicieal and rectal carcinoids rarely metastasize).

Papillary Carcinoma
Calcification
Zollinger-Ellison syndrome
Gastrinoma, acid hypersecretion, peptic ulcers
Associated with gastrinoma

Pituitary Adenoma

Adrenal Cortical Carcinoma
Vascular invasion, metastasis = malignancy
Function of calcitonin?
Help lower serum calcium

Pheochromocytoma
Etiology of Hypoadrenalism
Adrenocortical Insufficiency
Primary: chronic (Addison’s) or acute (Waterhouse-Friderichsen)
Secondary: Pituitary insufficiency or exogenous corticosteroids
Diabetes Complications (Picture 1)


Celiac Disease

Colonic Adenocarcinoma

Radionuclide scan
Top left: Normal, moderate homogeneous uptake
Top right: Grave’s, diffuse increased uptake
Bottom Left: Multi-nodular goiter, heterogeneous uptake
Bottom right: Thyroid neoplasm/cyst; Cold nodule

Gastric Ulcer
What is chronic pancreatitis?
Usually not associated with acute pancreatitis
Chronic inflammation, ductal ectasia, squamous metaplasia of ducts, calcification, fibrosis, stone formation, pseudocysts


Adenocarcinoma of Esophagus

Alcoholic Hepatitis Mallory Body
Eosinophilic inclusion, composed mostly of filaments caused by damage to filaments to form cytokeratin
*EXAM*
Pheochromocytoma Gross and Microscopic findings
Indicator of malignancy
Gross: well demarcated, very vascular, pale grey to light brown tumors; tumor turns dark brown in chromium salt solution (Zenker’s solution); “pheochrome” refers to affinity for chromium salts
Microscopy: Large cells with basophilic granular cytoplasm, arranged in small nests separated by capillaries; may have nuclear pleomorphism and mitotic activty
Malignancy: metastatis

Adenocarcinoma of Esophagus

Gastric Lymphoma

Papillary Carcinoma
Nuclear groove “Coffee beans”

Crohn’s Disease
What HLA types are strongly associated with Graves disease?
HLA-B8
HLA-DR3

Familial Adenomatous Polyposis
What are some associated findings of gastritis?
Erosion/ulceration
Intestinal metaplasia
Atrophy & fibrosis

Esophageal Varices

Gastric Adenocarcinoma
Genetics of familial adenomatous polyposis
Mutation in the adenomatous polyposis coli tumor-suppressor gene on Ch 5q21

Hypertrophic Gastropathy

Pituitary MacroAdenoma

Pseudomembranous Colitis

Adrenal Tuberculosis
Activated T cells
Langhans nucleated cells
Presentation of Insulinoma
Most common functioning islet cell tumor.
Presents with episodic hypoglycemic attacks, low blood glucose, symptoms precipitated by fasting or exercise, symptoms relieved by glucose.
High plasma insulin levels, increased insulin:glucose.
90% are solitary tumors, may be small and require special imaging.
Only 10% are malignant.
Neuroblastoma Gross and Microscopic Findings
Gross: Large tumors (6-8cm avg.), sof, white, with areas of hemorrhage, necrosis, or calcification
Microscopic: Small blue cell tumor arranged in diffuse sheets (may see Homer Wright rosettes)
90% produce catecholamines (urinary metanephrines/VMA elevated)

Cholelithiasis

Diverticulosis

Villous Adenoma

Tubular Adenoma

Gastric Ulcer

Malignant Gastrointestinal stromal tumor

Normal Parathyroid Gland

Ulcerative Colitis
What is familial adenomatous polyposis?
An inhertied, autosomal dominant condition in which affected patients develop innumerable adenomatous polyps of the colon and subsequently, invasive adenocarcinoma.

Colon Carcinoma
What is the Whipple triad?
- Sx of hypoglycemia are present (esp. confusion, stupor, loss of consciousness)
- Hypoglycemia is present, typically glucose less than 50 mg/dL
- Attacks are precipitated by fasting or exercise and are promptly relieved by administration of glucose

Pancreatic Endocrine Neoplasm
(Islet Cell Tumor)
Circumscribed/encapuslated.
In pancreas or region around pancreas.

Gastric Adenocarcinoma

Gastric Ulcer
How is GIST treated?
Majority of GIST express CD117 (“c-kit”) which is the molecular target of tyrosine kinase inhibitor (Imatinib)

Colon Carcinoma
Crohn’s Disease diagram


Viral Hepatitis

Cholelithiasis (Pigment Gallstones)
Indicative of chronic hemolysis

Hepatocellular Carcinoma
Small tumors at periphery

Viral Hepatitis
Acidophilic (Councilman) body (arrow)
A hepatocyte undergoing apoptosis

Chronic cholecystitis

Diabetes Mellitus Type 1
Amyloid deposits
What is the origin of amyloid in medullary thyroid carcinoma?
Excess procalcitonin deposition

Normal Thyroid

PT Hyperplasia
Follicular carcinoma
Who does this affect?
Gross/Histo
Metastasizes to ___
Prognosis
15-20% of thyroid carcinomas
Women predominantly affected, older age group
Gross: Widely invasive or encapsulated nodule
Histo: Widely invasive-extensive infiltration of normal thyroid or vascular invasion
“Minimally invasive”-capsuclar or vascular invasion present
Hematogenous metastasis to lungs/bones
Prognosis: Widely invasive (50% 10yr survival); minimally invasive (90% 10yr survival)

Hepatocellular Carcinoma

Gastric Ulcer
Diffuse Hyperplasia
Who, Pathogenesis, Gross/Histo
Grave’s Disease Classic triad: hyperthyroidism, ophthalmopathy (exophthalmos), pretibial myxedema
Who: Young women (20-40 y.o)
Pathogenesis: TSI, anti-TSH Ab, Thyroid growth-stimulating immunoglobulins
Gross: symmetric enlargement of thyroid gland
Histo: Follicular hyperplasia with papillary infoldings, tall/columnar cells, scallping of margins of colloid within follicles

Grave’s Disease
Resorption vacuoles
Describe a pancreatic adenocarinoma (macro/microscopically)
Macro: Infiltrative, firm, tan-white tumor
Micro: irregular ducts/glands lined by atypical cuboidal to columnar cells, desmoplastic stromal response
What are adenomatous polyps?
Common, benign neoplasms of the colorectal mucosa which are associated with increased risk of developing carcinoma, either within the polyp or at other colorectal sites.
What is autoimmune gastritis?
What are some symptoms?
Autoantibodies against parietal cells, H/K ATPase, or IF
Chronic inflammation leads to mucosal injury and eventual atrophy.
Achlorhydria (low acid production) and hypergastrinemia
Pernicious anemia (B12 deficiency)
Increased risk for gastric cancer

Metastatic Gastric Carcinoma in Lung

Herpes Esophagitis
Loss of mucosa + exudate forming

Crohn’s Disease

Medullary Carcinoma
Apple-green birefringence

Pituitary Adenoma
Monomorphic & arranged in sheets, not acini

Adrenal Cortical Carcinoma
More mitotically active.

Adrenal Cortical Adeonoma
Left: tumor
Right: Residual normal adrenal tissue

Familial Adenomatous Polyposis

Colonic Adenocarcinoma
What are the damaging and defensive forces of the stomach?
What causes each?
Damaging: gastric acid, peptic enzymes
Caused by: H. pylori, NSAIDS, aspirin, cigarettes, alcohol, gastric hyperacidity, duodenal gastric reflux
Defensive: surface mucus secretion, HCO3 secretion into mucus, mucosal blood flow, apical surface membrane transport, epithelial regenerative capacity, elaboration of prostaglandins
Caused by: Ischemia, shock, delayed gastric emptying, and host factors

Pheochromocytoma
Diagnosis of Adrenal Cortical Carcinoma
May have hemorrhage and necrosis
May appear encapsulated or circumscribed

Parathyroid Adenoma
Molecular pathogenesis of familial adenomatous polyposis
APC protine has normal functions within the cytoskeleton and in the intercellular adhesion. APC binds to the cytoskeletal protein beta-catenin in a complex with the cell adhesion molecule E-cadherin. When not bount to E-cadherin, beta-catenin also binds T-cell factor/lymphoid enhancer factor, which is a transcriptional activator of various genes involved in cell proliferation and inhibition of apoptosis. By binding to beta-catenin, APC promotes beta-catenin degradation. A mutation in the APC gene leads to decreased affinity for beta-catenin, thereby leading to a state of increased cell proliferation that predisposes to the development of carcinoma.

Crohn’s Disease Pathogenesis

What is acute pancreatitis associated with?
80% of cases associated with gallstones or alcoholism

Squamous Cell Carcinoma of Esophagus

Gastric Adenocarcinoma
Signet ring cell morphology

Cirrhosis

Gastric Ulcer

Pheochromocytoma
Islets of Langerhans
Clusters of uniform cells scattred within exorine pancreas
Presentation of Glucagonoma
Mainly adult females (perimenopausal or postmenopausal).
Associated with glucagonoma synrome: mild glucose intolerance, anemia, skin rash “necrolytic migratory erythema”, weight loss, glossitis/stomatitis
High plasma glucagon levels
Overall 60-70% malignant
Usually malignant if associated with glucagonoma syndrome, otherwise benign

Hemochromatosis
Excessive hemosiderin stores

Adenocarcinoma of Esophagus

Waterhouse-Friderichsen Syndrome
Hemorrhagic necrosis of adrenal glands.
Acute adrenal insufficiency due to DIC/hemorrhage caused by Neiserria meningititides infection.

Meckel’s Diverticulum Complication
Volvulus
How can you differentiate between hypoglycemia caused by beta-cell tumors and self-induction by insulin/sulfonylureas?
Beta-cell tumors are accompanied by high serum levels of C peptide.

Ischemic Enteritis
Nodular hyperplasia
Multinodular goiter
Idiopathic, usually clinicaly euthyroid
Mutliple nodules, often with one dominant nodule
Variable appearances: large/cellular/hyperplastic nodules, hemorrhage, cystic degeneration

Ulcerative Colitis
Pheochromocytoma Diagnosis
Elevated urine metanephrines and vanillylmandelic acid (VMA), which are metabolites of cathecholamines

Follicular Adenoma
Presentation of Adrenal Tuberculosis
Infection of adrenal glands by Mycobacterium tuberculosis
Formely the most comon cause of chronic adrenal insufficiency
Granulomatous inflammation: epitheliod histiocytes, giant cells, and acid-fast bacilli
S/Sx of Hashimoto’s Thyroiditis


Gastric Lymphoma

Pseudomembranous Colitis

Parathyroid Carcinoma
Very uncommon.
Tend to have higher Ca++ levels because they’re larger.
Invasive to soft tissues of the neck.

Cirrhosis
Adenomatous Polyps:
Two main Growth patterns
Three histologic subtypes
- Pedunculated
- sessile
- Tubular adenoma (>90%): exhibit more than 75% tubular pattern
- Tubulovillous adenoma (5-10%): exhibit 25-50% villous pattern
- Villous adenoma (1%): exhibit more than 50% villous pattern
Histology of Celiac Disease
Diffuse inflammation within lamina propria and epithelium, along with partial or complete loss of villi (villous:crypt ratio is reversed)

Acute Pancreatitis

Adenocarcinoma of GB

Gastric Adenocarcinoma
What is pseudomembranous colitis?
Iatrogenic disease due to antibiotic therapy (classically clindamycin), which alters the normal intestinal flora and allows overgrowth of Clostridium difficile. Certain strains of C. difficile produce a cytotoxin (toxin A and/or B), which results in epithelial necrosis.

Pituitary Adenoma
Salt & Pepper chromatin

Hemochromatosis

Porcelain Gallbladder

Normal Appendix
What are 2 types of infectious esophagitis?
Describe them.
Herpes esophagitis: Sharply “punched out” ulcers with multinucleated giant cells and intranuclear “ground glass” inclusions
Candida esophagitis: Gray-yellow exudates with yeast/pseudohyphae

Hypertrophic gastropathy
Hyperplasia of mucus-secreting cells
Describe the posterior lobe of the pituitary gland
Neurohypophysis: origin-floor of 3rd ventricle
Releases vasopressin (ADH) and oxytocin - hormones produced in hypothalamus and travel in axons to posterior lobe)

Gastric Polyploid Carcinoma
What are some risk factors for pigment stones?
Chronic hemolysis
Certain infections (Bacteria - E. coli; Parasites - Clonorchis)
GI disorders

Barrett Esophagus
Left side replaced by columnar glandular mucosa

Esophageal Varices (ulceration that became thrombosed)
What is an adenocarcinoma of the Gallbladder?
- How often does it occur?
- Who does it occur in most?
- Association with gallstones?
Rare malignancy that is more common in females
80-90% associated with gallstones
Most have invaded liver by time of diagnosis
Uniformly fatal

Crohn’s Disease

Cirrhosis
Shrunken, atrophic liver (scarring then liver tries to regenerate, forming nodules)
Pathogenesis of various carcinomas

Presentation of Cushing’s Syndrome


Gastritis with erosions
What is the prognosis of pancreatic adenocarcinoma?
Overall poor prognosis: 10% 1-year survival; 2% 5-year survival

Squamous Cell Carcinoma of Esophagus

Crohn’s Disease

Adrenal Gland