Pathology of the Pathology of the Exocrine Exocrine PancreasPancreas

Tyler Verdun, PGY3 General Pathology

University of British ColumbiaNovember 5, 2013

ObjectivesObjectives Brief review of normal pancreatic anatomyBrief review of normal pancreatic anatomy Overview of acute and chronic pancreatitisOverview of acute and chronic pancreatitis Introduction to pancreatic adenocarcinomaIntroduction to pancreatic adenocarcinoma

This session will not cover: This session will not cover: Endocrine pancreas pathologyEndocrine pancreas pathology Congenital abnormalitiesCongenital abnormalities Cystic lesionsCystic lesions Benign tumors (SPPT, cystadenomas, etc.)Benign tumors (SPPT, cystadenomas, etc.) Neuroendocrine tumorsNeuroendocrine tumors

The Normal The Normal PancreasPancreas

Normal PancreasNormal Pancreas

http://upload.wikimedia.org/wikipedia/commons/f/fc/Pancreas_4.jpg

Normal PancreasNormal Pancreas

Wait! There’s something wrong with this Wait! There’s something wrong with this picture…picture… No islets: this is actually parotid salivary glandNo islets: this is actually parotid salivary gland Sourced from http://www.youtube.com/watch?v=1Kavxv3jHzASourced from http://www.youtube.com/watch?v=1Kavxv3jHzA

Dr. John Minarcik’s excellent “Shotgun Histology” seriesDr. John Minarcik’s excellent “Shotgun Histology” series

Normal PancreasNormal Pancreas

PancreatitisPancreatitis

Acute PancreatitisAcute Pancreatitis

1. The pancreas is (metaphorically) a box 1. The pancreas is (metaphorically) a box of corrosive chemicalsof corrosive chemicals

2. Damage to the pancreas by some 2. Damage to the pancreas by some etiologic factor releases these chemicals etiologic factor releases these chemicals from cellsfrom cells

3. Digestion, saponification, and 3. Digestion, saponification, and calcification of neighboring healthy calcification of neighboring healthy tissuetissue On gross examination/autopsy – greasy, On gross examination/autopsy – greasy,

chalk-white depositschalk-white deposits

Acute Pancreatitis - Acute Pancreatitis - EtiologiesEtiologies

I – IdiopathicI – Idiopathic

G – GallstonesG – Gallstones E – Ethanol abuseE – Ethanol abuse T – Trauma: anything that compromises the blood supplyT – Trauma: anything that compromises the blood supply

S – SteroidsS – Steroids M – Microbiological (bacterial, viral, or parasitic infections) M – Microbiological (bacterial, viral, or parasitic infections) A – Autoimmune diseasesA – Autoimmune diseases S – Scorpion bite: S – Scorpion bite: Tityus trinitatisTityus trinitatis in Trinidad and Tobago in Trinidad and Tobago H – Hypercalcemia or hyperlipidemiaH – Hypercalcemia or hyperlipidemia E – ERCP: endoscopic procedure; can cause pancreatitisE – ERCP: endoscopic procedure; can cause pancreatitis D – Drugs: too many to list…D – Drugs: too many to list…

FYI: in a pinch, never doubt the “The Big 3”© FYI: in a pinch, never doubt the “The Big 3”© Antibiotics, antiepileptics/antipsychotics, anti-Antibiotics, antiepileptics/antipsychotics, anti-

inflammatoriesinflammatories

II

G G EE TT

S S MM AA S S HH EE DD

Important

Not so much

Impress your staff!

Acute Pancreatitis – Acute Pancreatitis – DiagnosisDiagnosis

Clinical presentation:Clinical presentation: Moderate to severe epigastric pain radiating to Moderate to severe epigastric pain radiating to

backback Nausea and vomitingNausea and vomiting Fever, ↑HR, ↑RR, ↓BPFever, ↑HR, ↑RR, ↓BP Rarely: abdominal or flank bruising (Cullen & Rarely: abdominal or flank bruising (Cullen &

Grey-Turner)Grey-Turner) ImagingImaging

CT scan and abdominal ultrasound showing CT scan and abdominal ultrasound showing inflammation or cystic structures around pancreasinflammation or cystic structures around pancreas

LabsLabs Elevated amylase and lipaseElevated amylase and lipase Elevated glucoseElevated glucose May see elevated liver markersMay see elevated liver markers

Acute Pancreatitis – Acute Pancreatitis – Radiologic FindingsRadiologic Findings

http://upload.wikimedia.org/wikipedia/commons/9/97/Pankreatitis_exsudativ_CT_axial.jpg

Acute Pancreatitis – Acute Pancreatitis – HistologyHistology

Normal pancreas

Horror Show

Acute Pancreatitis – Acute Pancreatitis – HistologyHistology

Neutrophils

Necrosis

Background pancreas

Hemorrhage

Acute Pancreatitis - Acute Pancreatitis - PrognosisPrognosis

MildMild Resolves with minimal supportive care within daysResolves with minimal supportive care within days

SevereSevere Significant fluid depletion and electrolyte Significant fluid depletion and electrolyte

abnormalitiesabnormalities Systemic inflammatory response and disseminated Systemic inflammatory response and disseminated

coagulationcoagulation Pseudocyst formationPseudocyst formation Necrosis and hemorrhageNecrosis and hemorrhage Abscess formation and sepsisAbscess formation and sepsis May require ICU and surgical managementMay require ICU and surgical management

Chronic PancreatitisChronic Pancreatitis

Consequence of long-standing inflammationConsequence of long-standing inflammation Usually will have had recurring episodes of Usually will have had recurring episodes of

acute pancreatitisacute pancreatitis ~80% will have history of alcoholism~80% will have history of alcoholism

Clinical presentationClinical presentation Chronic epigastric painChronic epigastric pain Persistent nausea and vomitingPersistent nausea and vomiting Other common findings Other common findings

Weight lossWeight loss Fatty stoolsFatty stools Low or normal plasma amylase and lipase levelsLow or normal plasma amylase and lipase levels

Chronic Pancreatitis – Chronic Pancreatitis – Radiologic FindingsRadiologic Findings

http://upload.wikimedia.org/wikipedia/commons/7/7b/Chronische_Pankreatitis_mit_Verkalkungen_-_CT_axial.jpg

Chronic Pancreatitis – Chronic Pancreatitis – HistologyHistology

Residual pancreas

Fibrosis and lymphocytic inflammation

Chronic Pancreatitis Chronic Pancreatitis

Functional pancreatic tissue is Functional pancreatic tissue is destroyeddestroyed 1. Enzyme levels are decreased or 1. Enzyme levels are decreased or

misleadingly normalmisleadingly normal 2. Loss of enzymes 2. Loss of enzymes decreased food decreased food

digestion and nutrient absorption in digestion and nutrient absorption in small bowelsmall bowel Fatty stoolsFatty stools

3. Weight loss3. Weight loss

Pancreatic Pancreatic AdenocarcinomaAdenocarcinoma

Pancreatic Adenocarcinoma Pancreatic Adenocarcinoma – Diagnosis– Diagnosis

Risk factorsRisk factors Chronic pancreatitisChronic pancreatitis SmokingSmoking ObesityObesity

Signs and symptoms:Signs and symptoms: Painless jaundicePainless jaundice Pain that radiates to backPain that radiates to back Weight lossWeight loss

Physical examPhysical exam Sometimes no major findingsSometimes no major findings Ascites and hepatomegaly due to metastasesAscites and hepatomegaly due to metastases Abdominal and rectal nodules from metastasesAbdominal and rectal nodules from metastases

Approximately 75% will present at an advanced Approximately 75% will present at an advanced stagestage

Pancreatic Adenocarcinoma Pancreatic Adenocarcinoma – Radiologic Findings– Radiologic Findings

http://upload.wikimedia.org/wikipedia/commons/f/f6/MBq_cystic-carcinoma-pancreas.jpg

Pancreatic Adenocarcinoma Pancreatic Adenocarcinoma – Whipple Resection– Whipple Resection

http://upload.wikimedia.org/wikipedia/commons/1/17/Macroscopic_image_of_pancreas_adenocarcinoma_removed_by_Whipple_procedure.jpg

Duodenum(cut open) Common bile

duct

Head of pancreas(cut open)

Pancreatic Adenocarcinoma Pancreatic Adenocarcinoma – Histology– Histology

Cancerous glands with mucin production

Pancreatic Adenocarcinoma Pancreatic Adenocarcinoma – Histology– Histology

Residual pancreas

Tumor with mucin

Pancreatic Adenocarcinoma Pancreatic Adenocarcinoma – Histology– Histology

Pleomorphic (ugly) cells

Mitoses

Pancreatic Adenocarcinoma Pancreatic Adenocarcinoma - Prognosis- Prognosis

http://progressreport.cancer.gov/doc_detail.asp?pid=1&did=2009&chid=95&coid=927&mid

Pancreatic Adenocarcinoma Pancreatic Adenocarcinoma - Prognosis- Prognosis

Why so poor?Why so poor? Pancreatic anatomyPancreatic anatomy

Anatomically isolatedAnatomically isolated Lacks a capsule Lacks a capsule contiguous with contiguous with

surrounding fatsurrounding fat Rich vascular supplyRich vascular supply

Cancer cells respond poorly to Cancer cells respond poorly to chemotherapychemotherapy Thick connective tissue in tumor prevents Thick connective tissue in tumor prevents

diffusion of chemo drugs?diffusion of chemo drugs?

Thank You Thank You