Pathology of the Pancreas

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Pathology of the Pancreas

• Alyssa Krasinskas, MD
• krasinskasam_at_upmc.edu
• January 6, 2003

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Normal Pancreas- Gross Micro
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Congenital Anomalies

• Agenesis
• Pancreatic Divisum
• Annular pancreas
• Heterotopic pancreas
• Cysts
• True Congenital
• Acquired (pseudocysts)
• Neoplastic

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Congenital Anomalies -Heterotopic Pancreas (in
stomach)
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Congenital Anomalies -Heterotopic Pancreas (in
stomach)
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Congenital Anomalies - Cysts

• Simple Cyst
• Ductal derived
• Microscopic to 3-5 cm
• Lined by flat cuboidal duct-type epithelium
• Filled with fluid
• Usually solitary and asymptomatic
• Cysts associated with other diseases
• Polycystic kidney disease
• Cysts in kidney, liver, pancreas
• Von Hippel-Lindau disease
• Cysts in pancreas, liver, kidney
• CNS angiomas

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Congenital Anomalies -Pancreatic Cyst - Gross
Micro
Modern Pathology 15154-158 (2002)
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Acute Pancreatitis

• Autodigestion and inflammation of the pancreas
• Most common causes
• Alcoholism
• Obstruction
• Gallstones
• Tumor, scar, congenital abnormality
• Possible mechanisms
• Duct obstruction
• Acinar cell injury
• Defective intracellular transport

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Acute Pancreatitis - Pathology

• Edema (microvascular leakage)
• Fat necrosis and saponification (release of
  lipolytic enzymes)
• Interstitial hemorrhage (destruction of blood
  vessel walls)
• Parenchymal necrosis (release of proteolytic
  enzymes)
• Acute inflammation
• Mild cases
• Edema, fat necrosis and saponification
• Severe cases (necrotizing pancreatitis)
• Necrosis of acinar cells, ducts, islets
• Fat necrosis (within and outside of abdomen)
• Necrosis of blood vessels - hemorrhage

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Acute Pancreatitis - Pathology

• Edema (microvascular leakage)
• Fat necrosis and saponification (release of
• lipolytic enzymes)
• Interstitial hemorrhage (destruction of blood
• vessel walls)
• Parenchymal necrosis (release of proteolytic
• enzymes)
• Acute inflammation

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Acute Pancreatitis - Pathology

• Mild cases
• Edema, fat necrosis and saponification
• Severe cases (necrotizing pancreatitis)
• Necrosis of acinar cells, ducts, islets
• Fat necrosis (within and outside of abdomen)
• Necrosis of blood vessels - hemorrhage

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Acute Pancreatitis - Gross
Parenchymal necrosis
Acute pancreatitis
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Acute Pancreatitis Micro(autodigestion)
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Acute Pancreatitis Micro (fat necrosis)
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Acute Necrotizing Pancreatitis - Gross
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Chronic Pancreatitis

• Recurrent bouts of inflammation leads to loss of
  pancreatic parenchyma and replacement by fibrosis
• Primary causes
• Alcohol abuse
• Hypercalcemia / hyperlipoproteinemia
• Pancreas divisum
• Hereditary pancreatitis

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Chronic Pancreatitis - Pathology

• Loss of lobular appearance of pancreas
• Loss of exocrine tissue (typically not islets)
• Irregularly distributed fibrosis
• Reduced size of pancreas
• Inflammation
• Destruction of ducts ductal dilatation
• Pseudocysts (25 of cases)

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Chronic Pancreatitis - Gross
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Chronic Pancreatitis- Micro
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Sequelae - Acute Pancreatitis

• Systemic complications
• Shock
• Organ failure
• DIC
• Pancreatic abscesses
• Pseudocysts
• Duodenal obstruction

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Sequelae - Chronic Pancreatitis

• Duct obstruction
• Pseudocysts
• Malabsorption
• Secondary diabetes

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Pancreatic Pseudocysts

• Localized collections of pancreatic
• secretions (within or adjacent to pancreas)
• Virtually all arise after a bout of acute
• or chronic pancreatitis
• Lack a true epithelial lining
• Lined by macrophages, fibrosis
• Different from sterile pancreatic abscesses
• Collections of neutrophils following liquefactive
  necrosis of pancreatic parenchyma

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Pancreatic Pseudocyst - Gross
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Pancreatic Pseudocyst - Micro
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Pancreatic Pseudocyst
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NeoplasiaTumors of the Exocrine Pancreas
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Ductal Adenocarcinoma

• Most common neoplasm of the pancreas
• 5th leading cause of cancer death in the US
• 28,000 new cases (and nearly as many deaths) per
  year
• Most common between 60 80 years of age
• Slight male predominance (1.61)

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Ductal Adenocarcinoma Risk Factors

• Cigarette smoking
• High fat diets
• Chronic pancreatitis
• Diabetes mellitus
• Chemical (carcinogen) exposure

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Ductal Adenocarcinoma Genetic Risk Factors

• Hereditary breast and ovarian cancer
• BRCA2 families
• Hereditary pancreatitis (50X!)
• Peutz-Jeghers Syndrome
• HNPCC

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Ductal Adenocarcinoma- Clinical Features

• Painless jaundice
• Abdominal pain
• Weight loss
• Migratory thrombophlebitis

TROUSSEAU SIGN
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Ductal Adenocarcinoma- Molecular Genetics

• K-RAS point mutations
• (present in gt90 of pancreatic cancers)
• Tumor suppressor gene mutations
• P53 (present in 60-80)
• p16
• HER/2-neu overexpression
• (present in 70)

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Ductal Adenocarcinoma- Gross Pathology

• Most occur in the head of the pancreas (60)
• 15 in the body
• 5 in the tail
• 20 diffuse
• Poorly circumscribed, grey-white, firm masses
• Can infiltrate outside the pancreas into other
  organs

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Ductal Adenocarcinoma- Histopathology

• Arise from ductal (glandular) epithelium
• Typically moderately to poorly differentiated
  adenocarcinoma
• Perineural and angiolymphatic invasion common
• Almost always associated with chronic
  pancreatitis
• Histologic variants
• Adenosquamous Carcinoma
• Anaplastic Carcinoma
• Undifferentiated carcinoma with osteoclast-like
  giant cells

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Ductal Adenocarcinoma - Gross
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Ductal Adenocarcinoma - Micro
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Ductal Adenocarcinoma - Micro
Moderately differentiated
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Ductal Adenocarcinoma - Micro
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Ductal Adenocarcinoma - Micro
Perineural invasion
NERVE
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Ductal Adenocarcinoma- Treatment

• Surgical resection
• Pancreaticoduodenectomy (Whipple procedure) for
  tumors in the head
• Distal pancreatectomy for tumors in the body and
  tail
• Prognosis
• 3 months without treatment
• 10-20 months with Whipple
• Medical
• Combined 5-FU-based chemotherapy and radiation
  therapy
• Palliative (supportive) therapy

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Other Exocrine Tumors

• Intraductal Papillary Mucinous Neoplasm (IPMN)
• Mucinous Cystic Neoplasm
• Microcystic Adenoma
• Solid-pseudopapillary Neoplasm
• Acinar Cell Carcinoma
• Pancreatoblastoma
• Not covered in Robbins

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Intraductal Papillary Mucinous Neoplasm (IPMN)

• Mucinous neoplasm that arises in and causes
  cystic dilatation of the main (large) pancreatic
  ducts
• Can progress to invasive adenocarcinoma

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IPMN
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Mucinous Cystic Neoplasm

• Form unilocular or multilocular cysts
• Often within the tail of the pancreas
• No connection to the ductal system
• Usually occurs in women
• Can progress to invasive adenocarcinoma

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Mucinous Cystic Neoplasm
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Acinar Cell Carcinoma

• Tumor of the pancreatic acinar cells
• Not ductal-derived

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Pancreatoblastoma

• Really Really Really Really Really Rare.
• Occurs in children (lt10y)

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NeoplasiaTumors of the Endocrine Pancreas
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Islet Cell Tumors

• Rare (1-6 of pancreatic neoplasms)
• Mean age 58 years
• MF
• Risk factors
• Not many
• MEN I

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Islet Cell Tumors- Clinical Features

• Depends on functionality
• Functional (elaborate hormones into the blood)
• Insulinoma
• Gastrinoma
• Glucagonoma
• Somatostatinoma
• VIPoma
• Non-functional
• Often found incidentally

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Islet Cell Tumors - Pathology

• Gross Features
• Occur throughout pancreas
• Solid, soft, often well-circumscribed
• Cystic degeneration can occur

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Islet Cell Tumors - Pathology

• Microscopic features
• Small to medium uniform cells with round nuclei
• Even salt-and-pepper chromatin distribution
• Arranged in cords, acini, or solid sheets
• Insulinomas can have amyloid
• Somatostatinomas can have psammoma bodies

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Islet Cell Tumors - Pathology

• Immunohistochemistry
• Synaptophysin, chromogranin, NSE
• Hormones

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Islet Cell Tumors - Pathology

• Benign versus Malignant Yikes!
• All islet cell tumors should be considered
  potentially malignant, but
• Insulinomas tend to be benign
• Other hormone secreting tumors are more likely
  malignant
• Size lt2.0cm good prognosis gt3.0cm poor
  prognosis
• Also mitotic activity, vascular invasion,
  necrosis.
• Metastatic malignant

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Islet Cell Tumors - Management

• Surgical resection is the only curative treatment
• In patients with non-resectable tumors and/or
  metastatic disease
• Conservative Observation, medical management of
  symptoms (since the course is usually long and
  indolent)
• In rapidly progressive disease octreotide
  (somatostatin analogue), obliterative treatment
  of hepatic mets

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Islet CellTumor- Gross
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Islet Cell Tumor- Micro
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Islet Cell Tumor - Micro
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Islet Cell Tumor - Micro