159. Pathology of Pancreas Disorders

Question 1

Acute Pancreatitis

• what is it
• pathogenesis/possible causes
• clinical features (men vs women, sx, labs)
• path: gross/histo
• natural history
• tx

Answer 1

Reversible inflammatory disorder varying in severity (focal edema/fat necrosis to widespread hemorrhagic necrosis)
PGen: autodigestion of pancreas by inappropriately activated pancreatic enzymes
causes: duct obstruction (cholelithiasis), acinar cell injury (alcohol, drugs, trauma), defective intracellular transport (alcohol, metabolic injury)
Premature trypsin activation causes 1. interstitial inflammation/edema, 2. proteolysis (protease), 3. fat necrosis (lipase), 4. hemorrhage (elastase)

CP: adults, men due to alcohol, women due to gallstones
Sx: upper abd pain, N/V, radiates to back
Labs: high amylase and lipase

Gross: swollen/edematous, fat necrosis as white/yellow patchy plaques, hemorrhagic = dark brown with cavitation
Histo: acute neutrophil inflammation/hemorrhage, dead adipocytes + cellular debris (fat necrosis)

Nat Hx: mild cases recover in 5-7 days, severe have more complications/mortality (pancreatic abscess/pseudocyst)

Tx: supportive care, infection prevention

Question 2

Pancreatic Pseudocyst

• epidemiology
• what is it
• histo

Answer 2

Most common pancreatic cyst lesion (>75% cysts)
Cyst with collection of fluid and cell debris (huge hemorrhagic cavity of cell debris)
Histo: cyst wall of fibrous tissue, inflammation, and NO EPITHELIAL LINING (key for pseudocyst)

Question 3

Chronic Pancreatitis

• what is it
• most common cause
• sx
• gross
• histo
• complications

Answer 3

Long-standing inflammation = irreversible destruction of exocrine pancreas, loss of islets of Langerhans
Most common cause: ALCOHOL
sx: abd pain, steatorrhea, DM, Weight Loss, N/V

Gross: pancreas shrunken and hard, fibrotic white surface, dilated ducts w/ calculi (stones)

Histo: fibrosis, chronic inflammation, loss of exocrine acini and endocrine tissue, dilated ducts with no acini, eosinophilic concretions in duct

Complications: maldigestion of carbs/proteins/fats, DM (loss of endocrine insulin), pseudocyst, CBD obstruction, slight increased risk of pancreatic cancer

Question 4

Pancreatic Ductal Adenocarcinoma (PDAC)

• epidemiology
• sx
• gross
• histo
• gene

Answer 4

Epi: 4th leading cause of cancer death, >85% tumors, unresectable at presentation due to late dx
ages: 60s-80s
sx: nonspecific - causing late dx
Gross: solid, infiltrative mass; if large - necrosis and secondary cystic changes
Histo: malignant glands infiltrating into fibrotic stroma, lack of lobularity - big glands and fibrosis, haphazard ductal elements on background of fibrosis (dif shapes and sizes), perineural invasion (gland development near nerve), ducts in vascular space/lumen

Genes: KRAS oncogene (90%), p16/CDK2NA tumor suppressor (95%), TP53 tumor suppressor (50-70%) SMAD4 tumor suppressor (55%)

Question 5

What are the three types of precursor lesions of PDAC? What is their pathophys? Who do they affect more? histo

Answer 5

1. Pancreatic Intraepithelial Neoplasm (PanIN)
   Normal - (KRAS mut) - low grade dysplasia (PanIN1) - (p16 mut) - PanIN2 - (mut) - PanIN3 (high grade dysplasia) - invasive carcinoma
2. Intraductal Papillary Mucinous Neoplasm (IPMN)
   M>W; involves HEAD of pancreas
   Cystic/nodular duct
   Histo: cystic lesion with papillae in lumen, varying dysplasia
3. Mucinous Cystic Neoplasm (MCN)
   Perimenopausal women; TAIL of pancreas
   thick-walled, multi-lobular cyst
   Histo: cyst lined by tall columnar, mucin-producing epithelium; OVERIAN TYPE STROMA (progesterone receptor immunostain)

Question 6

Well-differentiated Neuroendocrine Tumor

• age of pts
• etiology
• types
• gross
• histo
• prognosis

Answer 6

2-5% all pancreatic neoplasms
pts 30-60yo
Etiology: most sporadic, some syndromic (MEN1, von Hippel-Lindau, Tuberous Sclerosis)
types: functional vs. non-functional (insulinoma, glucagonoma, somatostatinoma)
Gross: well-circumscribed homogeneous rubbery mass
Histo: trabeculae, ribbons, nests of fibrosis and pseudorosettes
Cytology: monotonous cells with round nuclei and “SALT AND PEPPER” chromatin

Prognosis: worse if high mitosis/proliferation index, vascular invasion, tumor necrosis