PANCREAS PATHOLOGY

EXOCRINE PANCREAS

NORMAL

-ventral -> head/uncinate

-dorsal -> tail/body

-intralobular ducts -> intercalated ducts -> acini

CONGENITAL ANOMALIES

-Ectopic (stomach, duodenum, Meckel’s -> any component permitted)

-Agenesis

-Duct abnormalities

-Pancreas divisum (incomplete fusion -> prone to pancreatitis)

-Annular pancreas (encircles duodenum -> duodenal obstruction)

-Cysts (duplication, AV malformation, bronchogenic)

 

TRANSPLANT

• -for Diabetes Mellitus, cytology for follow-up
• Microscopy
• -lymphocytes, eosinophils, plasma cells
• -loss of acini, fibrosis
• -vascular change (endotheliitis, fibrinoid necrosis, fibrointimal hyperplasia)

 

PANCREATITIS

ACUTE PANCREATITIS

• Cause: alcohol, gallstones, infections (mumps, coxsackie, HIV), ischemia (embolism, shock), drugs, hyperCa, hyperTG, pregnancy, hereditary
• Clinical: abdo pain, shock, ARDS
• Labs:
• ↑WBCs
• ↑amylase
• ↑lipase
• ↑CRP
• ↑glucose (hyperglycemia)
• ↓Ca
• Gross: chalky fat necrosis, severe: blue black hemorrhage
• Microscopy:
• Mild -> fat necrosis, edema
• Severe -> necrosis of acinar, ductules and islets
• Pathology
• Microscopyvascular leakage -> edema
• 2. release of lipolytic enzymes -> fat necrosis
• 3. acute inflammation
• 4. proteolytic destruction (pancreatic enzymes, trypsin) -> parenchyma, BV
• Mechanisms to acute pacreatitis:
• duct obstruction (gallstones)
• 2. acinar cell injury (alcohol, drugs) -> release of intracellular enzymes + activation of enzymes
• 3. defective intracellular transport (alcohol, drugs) -> intracellular activation of enzymes

Chronic pancreatitis

Clinical: repeated bouts of mild-moderate pancreatitis, pancreatic insufficiency (malabsorption, DM)

Gross: hard, dilated ducts, calcified concretions, -+/-pseudocysts, tumor or stones -> simulates cancer

Microscopy:

• -focal vs diffuse but uneven distribution
• -¯ acini but ducts preserved
• -sparing of islets -> become more concentrated

-periductal fibrosis and chronic inflammation

-lobular architecture preserved

-ductal metaplasia

-no atypia, no mitoses

Types of cysts in the pancreas

Congenital

▪ Enteric duplication cyst

▪ AV malformation

▪ Retroperitoneal bronchogenic cyst

Infectious

▪ Echinococcal cyst

Inflammatory

▪ Lymphoepithelial cyst

▪ Pseudocyst

Neoplastic

Epithelial

• Benign

▪ serous cystadenoma (microcystic adenoma)

▪ mucinous cystadenoma

▪ intraductal papillary mucinous adenoma

Uncertain Malignant Potential

▪ intraductal papillary mucinous with moderate dysplasia

Malignant

▪ Serous cystadenocarcinoma

▪ Mucinous cystadenocarcinoma

▪ Intraductal papillary mucinous carcinoma

-non-invasive

-invasive

▪ Acinar cell cystadenocarcinoma

 

PSEUDOCYST

• -secondary to acute or chronic pancreatitis

Gross: within or adjacent to pancreas

Microscopy: pancreatic secretions from damaged ducts

wall: fibrous tissue with histiocytes, GCs

 

EXOCRINE TUMOURS

What are the syndromes associated with pancreatic cancer:

▪ BRCA-2

▪ Peutz-Jeghers

▪ Familial pancreatitis

PREINVASIVE LESIONS

INTRADUCTAL PAPILLARY MUCINOUS NEOPLASMS (IPMNS)

Gross

-papillary projections in large ducts with abundant mucous production

Microscopy:

-papillae lined by tall columnar mucin-producing cells

• -may be assoc/ adenoca

Immunohistochemistry: CK7,8,18

 

PANCREATIC INTRAEPITHELIAL NEOPLASIA (PanIN)

-Microscopyscopic papillary lesions

-Grades 1A,1B, 2,3

 

ADENOCARCINOMA

Location: 2/3 head of pancreas

Risk Factors:

Smoking

Pancreatitis, familial relapsing, Peutz Jeghers

Alcohol

Male

Benzidine, BRAC-2

Obesity

Symptoms: obstruction-related (head), -progressive jaundice with pain, wt.loss, fatigue

-Trousseau’s sign mig. thrmbophlebitis

Gross: irreg, firm, yellow-gray

Microscopy:

Grade: well, mod, poorly dif.

• -irreg. shaped glds, variable atypia and mitoses

-desmoplasia

-perineural invasion and lymphatic invasion

-20% carcinoma in situ (PanIN)

Variants:

-adenosquamous

-mucinous

-anaplastic

-w/ osteoclast GCs

-sarcomatoid

-acinar cell ca

Genetics: k-ras, p53, SMAD4 mutations

IHC: CK7+, 8/18+,  “loss of SMAD4 in 55%”

 

ACINAR CELL CARCINOMA

Gross & location: well cirm, solid

Microscopy:

• -small acinii
• -granular cytoplasm and single prominent nucleoli
• IHC: trypsin, chymotrypsin, lipase, CK8/18
• -occ syn, chrA
• EM: dense core zymogen type granules

 

MUCINOUS CYSTADENOMA CARCINOMA

• -women

Gross & location:

-cystic and mucinous

-90% in tail

Microscopy:

-columnar cells with mucin

• -ovarian-type stroma

Variants:

-can have sarcomatoid diff.

-can have osteoclast GC

-can have occasional endocine cells

• IHC: CK

SEROUS CYSTADENOMA CARCINOMA

-women

(only 1 carcinoma reported in the literature)

Gross: Microscopycysts

-central stellate scar

Microscopy:

• -mulitple cysts lined w cells “honeycomb pattern”
• -small central nuclei w/ clear cytoplasm

 

SOLID PSEUDOPAPILLARY NEOPLASM

Clinical: women

Gross: solid

Microscopy:

-sheets of cells with eosinophilic cytoplasm

-nuclei with grooves

-intracytoplasmic eosinophilic globules

• IHC: B-catenin (nuclear vs membranous in normal), A1AT, CD10

 

PANCREATOBLASTOMA

Clinical: infants, FTT, mass

Gross: lg, mass w/ fleshy cut surface

Microscopy:

-cellular with uniform cells

-acinar formation

-squamoid nests

IHC:

• ductal (if present) -> CEA
• endocrine -> syn, chrA
• acinar -> trypsin
• Other tumours seen in childhood:
• -endocrine tumours
• -ductal adenoca
• -acinar cell ca

ENDOCRINE PANCREAS

DIABETES MELLITUS

Classification:

Type I

Type II

MODY (maturity-onset diabetes of the young)

Pancreas

▪ ↓number and size islets

▪  infiltration of the islets with lymphocytes

 

Kidney

Diffuse basement membrane thickening:

- in bv and tubules

Diffuse glomerulosclerosis

-increase in mesangial matrix

-PAS+

-still leaky though, so nephrotic synd.

Nodular glomerulosclerois:

-so-called Kimmelsteil Wilson nodules

-nodules are PAS+ and surrounded by dilated capillary loops

-other glomeruli will have diffuse glomerulosclerosis

Advanved glomerulosclerosis

-tubule atrophy and interstitial fibrosis

Vascular lesions:

Atherosclerosis

Arteriolosclerosis (afferent and efferent glomerular arterioles)

Pyelonephritis

-acute or chronic inflm spreads from interstitium to tubules (glomeruli usu spared)

 

ENDOCRINE TUMOURS

• Clinical:
• -adults in body/tail
• -80% associated with MEN I (multiple endocrine tumors)
• -usually functional (larger -> less functional)
• -unpredictable behavior
• Gross: Well Definsed
• Microscopy:

-carcinoid like -> uniform, nuclear ┴ trabecular axis

-trabecular, glandular, solid

-variable fibrosis

-highly organized, relationship with numerous small BV

• -No necrosis, minimal mitoses
• -nucleoli from none to prominent
• -pale to eosinophilic or even clear cytoplasm
• -amyloid, psammoma
• IHC: syn, chr, insulin, glucagon, somatostatin, pancreatic polypeptide, gastrin, VIP
• Note: stains do NOT correlate with secretion; immunostains NOT necessary for diagnosis

* gastrinoma usually in duodenum, peripancreatic soft tissue, gastric antrum, along CBD

• Ddx: localized endocrine hyperplasia
• Approach to endocrine tumors
• -thorough sampling
• -silver stain for argyrophilic granules
• -IHC (CEA, NE markers, specific hormones)
• -EM
• Cytology: extremely cellular, clumping, eccentric nuclei
• Prognosis: size, mitoses, necrosis, grade, insulinoma only good one -> brief unpredictable

TUMORS WITH OVARIAN-LIKE STROMA

• MCN of pancreas
• Biliary cystadenoma
• Cystic nephroma