Pancreas

The pancreas hangs-out in the upper abdomen. It occasionally is afflicited by cancers, the most common of which is very fatal.

Normal anatomy

Divided into three portions: head, body & tail:

• Head:
  • Includes unicate process.
  • Extend to superior mesenteric vein (by definition).
• Body:
  • Superior mesenteric vein to left edge of aorta (by definition).
• Tail:
  • Remainder of pancreas.

Pancreatic surgeries

Common pancreatic surgeries include:

• Whipple (includes duodenum).
• Distal pancreatectomy.
  • Removal of tail +/- body.
• Total pancreatectomy.
  • Often with splenectomy.

General classification of pancreatic tumours

• Metstatses.
  • Most common = renal cell carcinoma.
• Primary.
  • Endocrine.
    • Usually small as hormonally active.
  • Exocrine.

Pancreas neoplasms in a table

Type	Key feature	Subtypes	Image	IHC	Detailed microscopic	Usual location	Other	DDx
Serous tumours	cuboidal cells, clear cytoplasm	cystadenoma, borderline t., cystadenocarcinoma	[1], [2]	IHC?	cuboidal cells, clear cytoplasm, central nucleus	body or tail	-	clear cell RCC, oligomucinous mucinous tumours
Intraductal papillary mucinous tumour (IPMT)	mucin, no ovarian-like stroma	clear cell variant	[3]	IHC?	papillae, tall columnar mucin-producing cells	head	-	mucious neoplasms (other pancreatic, duodenal)
Mucinous tumour	mucin, ovarian-like stroma	cystadenoma, borderline t., cystadenocarcinoma	Image?	IHC?	tall columnar mucin-producing cells, ovarian-like stroma	body or tail	-	IPMT, metastatic mucinous tumours
Solid pseudopapillary tumour	eosinophilic intracytoplasmic globules	clear cell variant (cytoplasm clear)	[4]	IHC	sheets of cells, focally loosely cohesive, eosinophilic cytoplasm, uniform nuclei with grooves	none	-	ductal adenocarcinoma
Ductal adenocarcinoma	irregular shaped glands, cytologic atypia	mucinous, spindle cell, mixed ductal-endocrine	[5], [6]	IHC?	glands, sheets, single cells, nuc. atypia, +/-mitoses, +/-necrosis	head	arises from the precursor PanIN	ampullary carcinoma, chronic pancreatitis
Pancreatoblastoma	squamoid nests, whorling	-	Image?	IHC?	squamoid nests of cells, whorling, nested growth, +/-keratinization	none	-	acinar cell carcinoma
Acinar cell carcinoma	acinar arch.	-	[7]	IHC?	nests or trabeculae, nucleolus, mod. basophilic granular cytoplasm	head (slight predilection)	-	pancreatoblastoma
Undifferentiated carcinoma with osteoclast-like giant cells	giant cells	-	Image?	IHC?	giant cells, usu. with AIS or inv. ductal adenocarcinoma	head	-	anaplastic carcinoma
Chronic pancreatitis	fibrosis, loss of acinar tissue	-	[8]	IHC?	loss of acinar tissue with preservation of islets, fibrosis	?	not a neoplasm, included here as it is in the DDx	ductal adenocarcinoma

Most important cystic lesions

• Serous.
• Mucinous.
  • Ovarian-like stroma.
• Solid pseudopapillay tumours.
• Intraductal papillary mucinous tumour (IPMT).
  • No ovarian-like stroma.

Mnemonic SIMS: Serous, IPMT, Mucinous, Solid pseudopapillary tumour.

Mucinous vs. IMPT

IMPT:

• No ovarian-like stroma.
• Usually has total pancreatectomy.

Cystic tumors of pancreas

• Uncommon.
  • 10% of cystic lesion (90% pseudocyst).
• Diagnostic difficulties (hard to differentiate pseudocyst & cyst).

Note:

• Pseudocysts: not real cysts... as no lining epithelium.

Cystic tumours

General

• 50% incidental finding.
• Vague Sx.
• Abdo mass.
• Wt loss.
• Jaundice.

Note:

• Usually diagnosed by imaging (CT/MRI, ERCP, Endoscopic ultrasound).

Serous cystic tumours

General

• Cell of origin: intralobular duct cells (ductular cells).
• Glycogen rich - but do not produce mucin.

Subclassication

• Serous microcystic adenoma.
  • Many small cysts.
• Serous oligocystic adenoma.
  • Large cysts.
• Serous adenocarcinoma - rare.

Note:

• If one mucin +ve cell, tumour = a mucinous tumour.

Characteristics of serous microcystic adenoma

• 1-2% of all exocrine pancratic tumours.
• Female>Male.
• Mean age 66 years.
• Truly benign with no malignant potenial.
• May not require surgical resection.
• May be part of von Hippel-Lindau.
• 50-70% occur in the body and tail.
• Average size 11 cm.

Radiology

• Honey comb appearance.
• "Coin lesion" - well demarcated border.
• May have central scar.

Gross

• Bosulated surface.
  • Lobulated.
• No (macroscopic) cysts apparent on gross.

Microscopic

Features:

• Cuboidal cells.
  • Glycogen rich.

DDx

• Renal cell carcinoma.
• Lympangioma.
• Hemangiomas.
• Oligocystic mucinous cystic tumors and pseudocysts.
  • Have mucin; PAS-D could be used to demonstrate its presence.

Notes:

• Serous adenoma my coexist with aggressive tumours.

Mucinous cystic tumours

• Gastro-entero-pancreatic cell differentiation with hypercellular ovarian-type stroma.
  • Stroma --> cellular.
• 2-2.5% of all exocrine pancreatic tumours.
• Almost exclusively in women.
• Mean age - 49 years.
• >80% in body and tail.
• Average size ~10 cm.

Note:

• Looks different than serous tumour.

Subclassification

• Sucinous cystadenoma.
• Borderline mucinous cystic tumour.
• Mucinous cystadenocarcinoma.

Borderline vs. Carcinoma

• Few mitoses in borderline.

Radiology

• Mucinous tumours: multilocular.
• Generally larger than serous.
• Often partially solid and cystic.
• Often calcified.
  • Calcification rare in serous.
• Usually tail & body.

Microscopic

Mucinous cystadenoma

Features:

• Simple tall columnar epithelium with large mucin vacuole on apical aspect.
• "Ovarian-type stroma" under epithelium.
  • Ovarin-type stroma: high density of small (non-wavy) spindle cells with eosinophilic cytoplasm.

Image: Mucinous cystadenoma - ovary (uchc.edu).

Notes:

• Appearance similar to mucinous cystadenoma in the ovary.
• Mucin stains +ve (intracytoplasmic).

Borderline mucinous cystic tumour

Features:

• May have finger like projections.
• Pseudostratification of epithelium.

Notes:

• Surgery does not change based on diagnosis on frozen section.
  • Only question is "Is the margin clear?".
• Borderline tumours are rare.

Carcinoma

• Cells floating in mucin.

Mucinous tumour vs. pseudocyst

mucinous t pseudocyst amylase & lipase low high viscosity high low CEA, CA124 high low

Prognosis:

• Benign looking tumours have the potential to transform into carcinoma.
• No report of assoc. pseudomyxoma peritonei.
  • US boards question -- it is an exception ... others one cause it.
• Prognosis of m. cystadenocarcinoma is slightly better than that of ductal adenocarcinoma.

Intraductal papillary mucinous tumour

General

• Often abbreviated IPMT.
• Papillomatous growth pattern.
• Morphologically and biologically distinct from ductal adenocarcinoma, mucinous cystic tumour and ductal papillary hyperplasia.
• Prognosis: favourable, if caught earlier; not much different than ductal adenocarcinoma if caught later.

Another paper:

Epidemiology

• 1% of all exocrine pancreatic tumours.
• More common in males.
• Mean age at presentation 62 years.
• 60-80% occur in the head of the pancreas.
• Average size 4 cm.

Khalifa's theory:

• Nothing but dilation of pancreatic duct + hypersecretion.

Gross

• May be patchy/multifocal.

Microscopic

Features

• Cell enlargement.
• Incr. NC ratio.
• Nuclear crowding and pleomorphism.
• Papillary tufting.
• Mitotic activity.
• Increased mucin production.

Classification IMPT

• Adenoma.
• Borderline mucinous tumour.
• Carcinoma.

Notes:

• No ovarian like stroma.
• Tumour in duct.
• Patient usually not jaundiced... as no obstruction.
• Often diabetes... as pancreas is destroyed.

Gross

• Multiple cystic spaces.

Microscopic

Features:

• Some places -- fronds of benign looking mucin producing epithelium.
• No ovarian type stroma underneath.

Notes:

• If no viable cells in the mucin then not cancer.
  • Mucin under pressure can disect through the tissue.
• Borderline tumours are rare.

Pitfalls

• Since it is multifocal may involve large segment of the ductal system.
  • Patients often get a total pancreatectomy.
  • If intralobular dilated ducts... carcinoma.
• Hard to get a negative margin.

NB - any margin with mucin cells -- badness!!!

• Dilated = mucin producing ducts (???).
  • DDx: PAN-IN1.
    • Needs a totally pancreatectomy.

Solid pseudopapillary tumour

General

• Obscure cell of origin.
• Considered low grade, i.e. prognosis is usually good.

Epidemiology

Features:

• Usually females (M:F=1:9).
• Mean age of presentation third decade (20s).

Management

May be followed radiologically.

Microscopic

Features:

• Solid sheets of cells, focally dyscohesive.
• Eosinophilic cytoplasm.
  • Occasionally clear cytoplasm.
  • Focal eosinophilic (intracytoplasmic) globules - key feature.
• Uniform nuclei with occasional nuclear grooves.
• +/-Necrosis - creating spaces/cavities.

Image: Solid pseudopapillary tumour (bmj.com).

DDx

• Pseudocyst.
• Cystadenoma.
• Cystadenocarcinoma.

Pancreatic intraepithelial neoplasia (PanIN)

• PanIN is thought to be the precursor lesion for pancreatic carcinoma.

Overview

Putative preneoplasm-neoplasm-carcinoma sequence:

• PanIN1a.
  • Not neoplastic, i.e. colonal.
• PanIN1b.
  • Not neoplastic, i.e. colonal.
• PanIN2.
  • Can be thought of as low-grade dysplasia, e.g. a (colonic) tubular adenoma without high-grade dysplasia.
• PanIN3.
  • Can be thought of as high-grade dysplasia, e.g. (colonic) villous adenoma.

Histomorphology

Features:

• PanIN1a - increased amount of cytoplasm.
  • Nuclear size & stratification perserved, arch. perserved.
• PanIN1b - increased amount of cytoplasm, folding of epithelium/moderated arch. distortion.
  • Nuclear size & stratification perserved.
• PanIN2 - increased cell size, and nuclear enlargement (increased NC ratio), moderate nuclear atypia with loss of (basal) nuclear polarization.
• PanIN3 - marked nuclear atypia with increased NC ratio.
  • No invasion identified.
• Pancreatic carcinoma - cytologic features of PanIN3 with definite invasion.

Image: Normal pancreas, pancreatic intraepithelial neoplasia and pancreatic carcinoma (WC).

Ductual adenoarcinomas

General

• Usually in the head ~60%.
  • 15% in the body, 5% tail, 20% diffuse (head, body & tail).
• Abysmal prognosis.

Microscopic

Features:

• Often glandular, may be solid.
• Nuclei.
  • May be bland - little pleomorphism.
  • Often small nuclei.
  • Sometimes coffee-bean appearance.
• Cytoplasm - granular, abundant.
• Quasi endocrine look.
  • May stain positive for endocrine markers.

Other features:

• +/-Necrosis.
• +/-Myxoid degeneration.
• +/-Cells around vessels.

Images:

• Pancreatic adenocarcinoma (WC).
• Pancreatic adenocarcinoma (WC).
• Normal pancreas, pancreatic intraepithelial neoplasia and pancreatic carcinoma (WC).

Cystic tumours

• Diagnosed by imaging/with help of images.

Stains

• PAS-D

Prognosis: very favourable (mostly benign).

Cystic tumours of the pancreas

Khalifa's table of cystic tumours:

	Sex	Age (years)	Usual site	Typical size (cm)
Microcystic	female	66	B&T	11
Mucinous	female	49	B&T	10
IPMT	male	62	H	4
Pseudopapillary	female	35	any	7.5

External links

• Pancreatic cancer - PanINs - pancreaticcancer2000.com.