pancreas Flashcards
List 5 causes of acute pancreatitis
metabolic (alcohol, hypercalcemia) mechanical (gallstones, trauma) genetic (mutations in cationic trypsinogen PRSS1 and trypsin inhibitor SPINK1 genes vascular: vasculitis, shock infection: mumps
LIst 3 gross features of acute pancreatitis
- edema - hemorrhage - necrosis of pancreatic parenchyma and peripancreatic fat
List 3 mechanisms that can cause activation of pancreatic proenzymes
- Obstruction of pancreatic duct (gallstones, alcohol induced thick secretions) - Acinar injury; may be chemical (etoh), infection (cmv, mumps), mechanical (trauma) - Metabolic activation of proenzymes (hypercalcemia)
List pancreatic proenzyes activated by trypsin that contribute to damage in pancreatitis
- Phospholipase and lipase (fat necrosis) - Elastase: damages vessel walls (hemorrhage) - Proteinase: acinar damage - Kallikrein: activates Factor XII of clotting cascade and complement cascade (small vessel thrombosis)
Describe pathogenesis of autodigestion of pancreas by innappropriately activated pancreatic enzymes
pancreatic duct obstruction, primary acinar injury, defective intracellular transport–>activation of trypsin–>activation of prozenzymes: phospholipase/lipase, elastase, proteinase, kallikrein
List 5 complications of acute pancreatitis
- Chronic pancreatitis - Medical emergency: DIC, ARDS, shock, ATN - Diffuse fat necrosis, hypocalcemia - Pancreatic abcess or pseudocyst - Exocrine/endocrine insufficiency
List 3 histologic findings of autoimmune pancreatitis
- Duct centric lymphoplasmacytic infiltration and peridutal fibrosis - Perivenulitis and obliterative thrombophlebitis - Increased numbers of IgG4+ plasma cells
LIst 3 sequelae of chronic pancreatitis
- Pancreatic insufficiency and diabetes mellitus - chronic pain - pancreatic pseudocysts
List 3 gross findings in chronic pancreatitis
- Irregular scar - Dilated pancreatic duct with secretions and calcifications - Pseudocysts and autodigestive fat necrosis in adjacent fat
List 4 histologic features of chronic pancreatitis
- Acinar atrophy - Fibrosis - Irregular, distorted ducts - Pseudoincrease in islets (due to atrophy)
What features differentiate chronic pancreatitis from pancreatic carcinoma?
Chronic pancreatitis: - diffuse, segmental or focal; irregular scar w/secretions, pseudocytst and fat necrosis; partial preservation of lobular architecture, dilated ducts w/ calcifications, ductal epithelium with atrophy, metaplasia but no dysplasia, acinar atrophy with prominent islets, patchy fibrosis without glands, chronic inflammatory cells, no vascular or perineural invasion Ductal adenocarcinoma: - localized, usually head of pancreas; hard, solitary poorly demarcated mass without pseudocysts, fat necrosis and may have dilated duct; no lobular architecture, irregular neoplastic glands lined by dysplastic cells, necrotic cells, no acinar atrophy or prominent ilsets, desmoplastic stroma without inflammation, perineural/vascular invasion
Name the most common mutated oncogene and the most frequently inactivated tumor suppressor gene in pancreatic carcinoma
KRAS: most commonly mutated oncogene p16: more frequently inactivated tumor suppressor gene
Name the precursor lesion for pancreatic adenocarcinoma
- Pancreatic intraepithelial neoplasia (PanIN)
List 2 hereditary familial syndrome associated with pancreatic adenocarcinoma
- Hereditary pancreatitis - Peutz-Jeghers
List cystic neoplasms of pancreas and demographic associations
- Serous cystadenoma: F>M (2:1), 60-70yrs - Mucinous cystadenoma: F (95%) - Intraductal papillary mucinous neoplasm: M>F - Solid pseudopapillary neoplasm: young F
List the clinicopathological features used to differentiate IPMN, mucinous cystic neoplasm, serous cystadenoma
IPMN: 50-75 yrs, men, hx pancreatitis, bulging papillae into duodenum lumen, found at head of pancreas, duct epithelium involved, usually multiple cysts, extensive papilla formation, columnar mucin producing epithelium, no ovarian stroma, adjacent pancreas normal mucinous cystic neoplasm: 40-50yrs, female, no specific history, solitary multilocated cysts, body/tail, no connection to duct, single cyst, usually minimal papillae, columnar mucinous epithelium, ovarian stroma present, atrophic pancreas serous cystadenoma: 50+yrs, usually female, no specific hx, CT honeycomb cyst, anywhere in pancreas, no relationship to duct, honeycomb cut surface, no papillae, flattened cuboidal epithelium ++glycogen, no ovarian stroma, normal pancreas
Compare/contrast features of PanIN from IPMN
PanIN: size 1cm, mucin hypersecretion, dilated duct, tall papillae with stroma core, MUC1+ in pancreatobiliary/oncocytic, MUC2+ in intestinal type, NO KRAS mutations, DPC4+, associated with colloid carcinoma
Describe the handling of a whipple specimen
- Identifiy and orient anatomical structures including distal stomach, duodenum, CBD, pancreas. Ink the specimen @ parenchymal resection margins - Open stomach along greater curvature/across anterior wall of pylorus, down outer curvature of duodenum. Record dimensions of all structures. - Sample margins: distal pancreas margin, uncinate margin, CBD, duodenum, gastric margin - using probe, cut through CBD, pancreatic duct, ampulla of vater - Identify/describe lesion: size, colour, consistency, demarcation, relationship to duodenum, CBD, portal vein, distance to margins, ductal obstruction - Photograph - Describe non-neoplastic tissue - Fix overnight in 10% formalin - Prepare blocks: 6 blocks of tumor including relationship to pancreatic/cbd, ampulla, duodenum, surrounding pancreas, margins, non-neoplastic pancreas, ampulla, all lymph nodes
List 2 pancreatic cystic tumors that are PR positive
- Solid pseudopapillary neoplasm: neoplastic epithelial cells (they are ER negative!!!) - Ovarian stroma of mucinous cystic neoplasm (ER also +)
List the criteria for defining Ampulla of Vater tumors
- Epicenter of tumor: must be within ampulla - Pre-invasive neoplasia in the ampulla of Vater
Compare the IHC panel of intestinal type and pancreatobililary type tumors of ampulla
Intestinal type: MUC2+, CK20+, CDX2+, CK7-, MUC5AC-, MUC1- Pancreatobiliary type: CK7+, MUC5AC+, MUC1+, CK20-, CDX2-, MUC2-
Name the proenzymes of the pancreas
- trypsinogen, chymotripsinogen, procarboxypeptidase, proelastase, kallikreinogen, prophospholipase A/B
Describe how autodigestion of pancreas is prevented
- Proenzymes (except amylase, lipase) - sequestered in membrane-bound zymogen granules in acinar cells - activation required conversion of inactive trypsinogen to trypsin by duodenal enteropeptidase (which cleaves proenezymes) - inhibotors are SPINK1 - acinar cells are intrinsically resistant to trypsin chymotrypsin and phospholipase A2
Name 4 congenital anomalies of the pancreas
- pancretic agenesis - pancreas divisum - annular pancreas - ectopic pancreas
What is the gene mutation associated with agenesis of pancreas
- PDX1 (pancreatic and duodenual homeobox gene), chromosome 13
What is the abnormality in pancreas divisum and proposed clinical consequence?
- failure of fusion of fetal duct systems of dorsal/ventral pancreatic primordia - bulk of pancreas drains through small-caliber minor papilla - duct of wirsung is very short and drains small portion of head - may predispose to chronic pancreatitis
What is the abnormality in annular pancreas? clinical manifestations?
- band-like ring of normal pancreas encircling 2nd portion of duodenum - association with other congenital anomalies, duodenal obstruction
List 4 common sites where ectopic pancreatic tissue are found
- stomach/duodenum - jejunum - meckel’s diverticulum - ileum
What are biochemical markers of pancreatitis
- plasma amylase, lipase
What is the clinical presentation of acute pancreatitis?
- abdominal pain, possible back/left shoulder pain, anorexia, N/V, acute abdomen
How is acute pancreatitis managed
- total restriction of oral intake, supportive therapy with IV fluids, analgesia, +/- abx
What distinguishes acute from chronic pancreatitis clinically?
- irreversible impairment of pancreatic function in chronic pancreatitis
Describe the 2 types of non-neoplastic pancreatic cysts
- Congenital cysts: unilocular, thin-walled, small; lined by glistening cuboidal epithelium/flattened, contain serous fluid. May be sporadic or seen in autosomal dominant polycystic kidney disease or von Hippel-Lindau - Pseudocysts are collections of necrotic/hemorrhagic material containing pancreatic enzyme and have no cyst lining. Arise after acute pancreatitis. Solitary, either within pancreas or lesser omental sac, can be upto 30 cm
What is the treatment of mucinous cystic neoplasms? What is the rate of associated malignancy?
- Complete surgical resection (distal pancreatectomy) - 1/3 of MCN harbour associated invasive adenocarcinoma
Diagnosis?
Serous cystadenoma
Diagnosis?
serous cystadenoma
Diagnosis?
pancreatic pseudocyst
Diagnosis?
mucinous cystic neoplasm
Diagnosis?
IPMN
What are features of solid-pseudopapillary neoplasms?
- Seen mostly in young women
- Large, well-circumscribed masses with solid/cystic component
- Cysts with hemorrhagic debris
- Neoplastic ells in solid sheets or pappialle
- B-catenin/APC gene utation alteraions
- Surgical resection because locally aggressive
Name 5 most common molecular alterations in pancreatic adenocarcinomas
- KRAS (90%)
- p16 (95%)
- p53 (50-70%)
- SMAD4 (55%)
- AKT2 (20%)
- MYB (10%)
What are risk factors for pancreatic adenocarcinoma?
- Smoking, etoh
- age
- high-fat diet
- chronic pancreatitis
- DM
What inherited syndromes pre-dispose to pancretic carcinoma?
BRCA2 (hereditary breast/ovarian) 4-10x
p16/CKDN2a (familial atypical mole/melanom) 20-35x
LKB1 (Peutz-Jeghers) 130x
Hereditary pancreatitis (SPINK1/PRSS1) 50-80x
any strong family history 14-30x
Name histologic variants of pancreatic ductal carcinoma
- adenosquamous, colloid, hepatoid, medullary, signet-ring, undifferentiated, undif with osteoclast-like giant cells
What pancreatic malignancy occurs in childhood?
- Pancreatoblastoma, rare
- age 1-15 yrs
- squamous islands admixed with acinar cells
- somewhat better survival than ductal adenocarcinoma
What are 2 types of autoimmune pancreatitis and how do they differ?
- TYpe 1 and Type 2 autoimmune pancreatitis
- Type 1 is pancreatic manifestation of systemic IgG4 disease, shows higher serum level IgG4, shows more interlobular inflammation and fibrosis with obliterative phlebitis; higher nuber of IgG4 plasma cells (>50/HPF)
- Type 2 is confined to pancreas; shows periductal inflammation, ductular/lobular abcesses and ductal ulceration, less elevation in serum IgG4, fewer IgG4+ cells
List cystic lesions and tumors of the pancreas
- Non-neoplastic: pesudocyst, lymphoepithelial cyst, ductal retention cyst, mucinous non-neoplastic cyst, paraampullary duodenal wall cyst (groove pancreatitis)
- Neoplastic: serous cystic neoplasm, MCN, IPMN, intraductal tubulopapillary neoplasm, solid pseudopapillary neoplasm, cystic acinar neoplasm ** some pancreatic neuroendocrine tumors can also be cystic)
Non-neoplastic cystic lesions of pancreas: describe pseudocyst, ductal retention cyst, lymphoepithelial cyst, paraampullary duodenal wall cyst
Pseudocyst: most comon cystic lesion of pancreas, results from pancreatitis/trauma. Usually in tail. Cyst lined by granulation/fibrous tissue without epithelial lining.
Ductal retention cyst: aka simple cyst, caused by obstruction. Unilocular cyst lined by simple epithelium. If mucinous=mucinous non-neoplastic
Lymphoepithelial cyst: lined by squamous epithelium (keratinized), with abundant lymphocytes +/- germinal centres.
Paraampullary duodenal wall cyst: in groove beween head of pancreas, duodenum and CBD. Caused by obstruction of minor papillaa. Causes Segmental chronic pancreatitis. Dilated ducts within duodenal wall, lining may have mucinous epithelium and wall has fibrous tiussue with mixed inflammation.
Neoplastic cystic lesions of pancreas: give features of serous cystadenoma, intraductal tubulopapillary neoplasm, intraductal tubular adenoma, cystic acinar cell cystademona, cystic pancreatic neuroendocrine tumors
Serous cystadenoma: benign, cystic, body/tail in elderly. Sporadic or VHL. Multilocular, spongy gross appearance with stellate central scar. Micro: cysts lined by flat/cuboidal cells, pale cytoplasm. IHC: cytokeratins, MUC6.
ITPN: solid nodule obstructing duct system, tubulopapillary structures with little mucin. Cells have HGD, some invasive CA. NO KRAS OR BRAF
Intraductal tubular adenoma: pyloric type glandular structures (not sure why considered cystic!!!)
Cystic acinar cell cystadenoma: VERY RARE, unilocular, lined by acinar cells, if really dysplastic=acinar cell cystadenocarcinoma
Cystic pancreatic neuroendocrine tumors: partially cystic, otherwise like any other neuroendocrine tumor
Mucinous cystic neoplasm pancreas: give relevant clinicpathologic featurs
MCN: tail/body of pancreas, females>>>males, middle age, solitary, multilocular cystic mass with mucin
- no communication with duct system
- cyst lining with tall columnar mucinous cells, underlying OVARIAN type stroma (positive for ER, PR, inhibin)
- Classified by cytologic and architectural features of lining epithelium into: MCN with LGD, MCN with moderate/intermediate dysplasia, MCN with HGD
- Severe dysplasia; papillary, branching, cribriform, budding growth patterns, marked nuclear stratification and atypia, mucin depletion, frequent mitosis
1/3 have associated invasive component (usually ductal type), but also adenosquamous, undiff, etc.
- Mangement: resection, prognosis determined by presence of invasive carcinoma, stage and resectability
Describe the features of IPMN in the pancreas
- Grossly visible (>1cm) epithelial tumor arising in main pancreatic duct or its branches
- Branch-duct type involves uncinate, often incidentally detected whereas main branch are symptomatic
- Neopastic epithelium forms papillary fronds lined by mucin producing columnar cells
- Categories: IPMN w LGD, IPMN w intermediate dysplasia, IMPN HGD and IPMN with invasive
- Four types of mucinous epitheium: gastric, intestinal, pancreatobiliary, oncocytic, with their specific IHC
- IHC: gastric: MUC1/MUC6/ neg MUC2. Intestinal: MUC2/neg MUC1 and MUC6, pancreatobiliary: MUC1/MUC6 neg MUC2, oncocytic only MUC6
- associated invasive carcinoma determines prognosis, seen in 1/3
- submit entire lesion for examination
Pancreas. Dx?
Acute pancreatitis
