Pancreas

A drawing of the pancreas. (WC/Gray's Anatomy)

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

Pancreatic cytopathology is dealt with in the gastrointestinal cytopathology article.

A general introduction to gastrointestinal pathology is in the gastrointestinal pathology article.

Introduction

Normal anatomy

Divided into three portions: head, body & tail:

• Head:
  • Includes unicate process.
  • Extends to the left edge of the superior mesenteric vein (SMV) - by definition.
    • All of the SMV is with the head.
• Body:
  • Right edge of the superior mesenteric vein to the left edge of aorta - by definition.
    • All of the aorta is with the body.
• Tail:
  • Remainder of pancreas.

Pancreatic surgeries

Common pancreatic surgeries include:

• Whipple procedure (AKA pancreaticoduodenal resection) - includes duodenum and usually the distal stomach (antrum).
• Distal pancreatectomy.
  • Removal of tail +/- body.
  • Specimen usually comes with the spleen.
  • Typically done form islet cell tumours.
• Total pancreatectomy.
  • Specimen usually comes with the spleen.

Whipple procedure

• AKA pancreaticoduodenectomy.

Indications:

• Head of pancreas lesions, duodenal lesions.

Margins:

1. Proximal mucosal margin (stomach or duodenum).
2. Distal mucosal margin (duodenum or jejunum).
3. Bile duct margin.
4. Pancreatic retroperitoneal (uncinate process) margin.
   • At SB done on edge (not en face).
5. Pancreatic neck transection margin (AKA distal pancreatic resection margin); usu. en face and in toto.
6. Sometimes superior mesenteric vein (SMV).
7. Rarely superior mesenteric artery (SMA) margin.

Opening:

1. Open the proximal (stomach) and distal (small bowel) stappled margins.
2. Open the duodenum along it length on the anterior aspect.
3. Open the stomach along the greater curvature.
4. Join the cuts that open the stomach and duodenum.

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], (WC), (WC)	IHC?	cuboidal cells, clear cytoplasm, central nucleus	body or tail	cystadenoma may be assoc. with von Hippel-Lindau syndrome	clear cell RCC, oligomucinous mucinous tumours
Intraductal papillary mucinous tumour (IPMT)	mucin, no ovarian-like stroma	clear cell variant	(wjso.com), (upmc.edu)	IHC?	papillae, tall columnar mucin-producing cells	head	-	mucious neoplasms (other pancreatic, duodenal), intra-ampullary papillary-tubular neoplasm (see ampullary carcinoma)
Mucinous tumour	mucin, ovarian-like stroma	cystadenoma, borderline t., cystadenocarcinoma	(WC), (WC)	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)	(WC), (bmj.com)	beta-catenin +ve, E-cadherin +ve, synaptophysin +ve, chromogranin -ve	sheets of cells, focally loosely cohesive, eosinophilic cytoplasm, uniform nuclei with grooves	none (head, body or tail)	usu. younger women	ductal adenocarcinoma, neuroendocrine tumours
Ductal adenocarcinoma	irregular shaped glands, cytologic atypia	mucinous, spindle cell, mixed ductal-endocrine	(WC), (WC)	IHC?	glands, sheets, single cells, nuc. atypia, +/-mitoses, +/-necrosis	head	arises from the precursor PanIN	ampullary carcinoma, chronic pancreatitis
Pancreatoblastoma	squamoid nests, whorling	-	(nature.com)	CK7 (acinar comp.), CK8, CK18, CK19	squamoid nests of cells, whorling, nested growth, +/-keratinization	none	usu. paediatric population	acinar cell carcinoma
Acinar cell carcinoma	acinar arch.	-	(WC), (histopathology-india.net)	trypsin, lipase	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, preservation of lobular arch.	-	[2]	IHC?	loss of acinar tissue with preservation of islets, fibrosis	?	not a neoplasm, included here as it is in the (clinical) DDx	ductal adenocarcinoma

WHO classification

Benign epithelial:

• Serous cystadenoma.
• Mucinous cystadenoma.
• Intraductal papillary mucinous adenoma.
• Mature teratoma.

Borderline epithelial:

• Mucinous cystic neoplasm with moderate dysplasia.
• Intraductal papillary mucinous neoplasm with moderate dysplasia.
• Solid pseudopapillary neoplasm

Malignant epithelial:

• Ductal adenocarcinoma.
  • Mucinous noncystic carcinoma.
  • Signet ring cell carcinoma.
  • Adenosquamous carcinoma.
  • Undifferentiated carcinoma.
  • Undifferentiated carcinoma with osteoclast-like giant cells.
  • Mixed ductal-endocrine carcinoma.
• Serous cystadenocarcinoma.
• Mucinous cystadenocarcinoma.
  • Invasive.
  • Noninvasive.
• Intraductal papillary mucinous carcinoma.
  • Invasive.
  • Noninvasive.
• Acinar cell carcinoma.
• Pancreatoblastoma.
• Solid pseudopapillary carcinoma.

Soft tissue tumours:

• See soft tissue lesions.

Ectopic pancreatic tissue

It comes in two flavours:

• Pancreatic ectopia.
• Pancreatic (acinar) metaplasia.

Pancreatic acinar metaplasia

• Abbreviated PAM.
• AKA pancreatic metaplasia.

General

• Common in the GI tract.
• Found in ~ 17-19% of gastroesophageal junction biopsies.
• Associated with intestinal metaplasia.
  • Not associated with changes of GERD, or Helicobacter gastritis.

Gross

• May be a single lesion or a cluster of lesions.

Note:

• Not associated with the endoscopic diagnosis of esophagitis or Barrett's esophagus.

Microscopic

Features:

• Pancreatic acini - only.
  • Intensely eosinophilic cytoplasm.

Negatives:

• No pancreatic ducts.
• No islets of Langerhans (pancreatic islets).

Images

• 

  PAM - high mag. (WC/Nephron)

• 

  PAM - low mag. (WC/Nephron)

IHC

Features:

• Trypase +ve.
• Lipase +ve.

Sign out

It can be debated whether it is worth reporting.

ESOPHAGUS (DISTAL), BIOPSY:
- COLUMNAR EPITHELIUM WITH MODERATE CHRONIC, FOCALLY ACTIVE, INFLAMMATION, AND
  PANCREATIC ACINAR METAPLASIA.
- REACTIVE SQUAMOUS EPITHELIUM.
- NEGATIVE FOR INTESTINAL METAPLASIA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Pancreatic ectopia

General

• May be confused with something pathologic.

Microscopic

Features:

• Consists of pancreatic acini and pancreatic ducts.
• +/-Islets of Langerhans.

Inflammatory

Pancreatitis

Classification

• Acute pancreatitis.
• Chronic pancreatitis.

Etiology

Mnemonic I GET SMASHED:

• Idiopathic.
• Gallstones ~45%.
• Ethanol ~35%.
• Tumours (pancreas, ampulla).
• Scorpion bites, snake bites.
• Microbial - mumps (paramyxovirus), Epstein-Barr virus (EBV), cytomegalovirus (CMV), mycoplasma.
• Autoimmune - Crohn's disease, polyarteritis nodosa (PAN), systemic lupus erythematosus (SLE).
• Surgery/trauma, e.g. ERCP, motor vehicle collision.
• Hypercalcemia, hyperlipidemia/hypertriglyceridemia, hypothermia.
• Emboli, e.g. post-CABG.
• Drugs - SAND = steroids & sulfonamides, azathioprine, NSAIDs, diuretics, such as furosemide.

Acute pancreatitis

Main article: Acute pancreatitis

Chronic pancreatitis

Main article: Chronic pancreatitis

Cystic lesions - overview

General

• True cystic lesions are uncommon.
  • A true cystic lesion: must have an epithelial lining.
    • Only 10% of cystic lesions are true cystic lesions, i.e. 90% of cystic lesions are really pseudocysts.
• It is hard to differentiate pseudocysts & cysts.

Cystic tumours - clinical

General:

• Usually diagnosed by imaging (CT/MRI, ERCP, Endoscopic ultrasound).
  • 50% incidental finding.
• Vague symptoms
• Abdominal mass.
• Weight loss.
• Jaundice.
• Usually favourable prognosis - mostly benign.

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.

Useful stains

• PAS-D.

Mucinous vs. IMPT

IMPT:

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

Cystic tumours of the pancreas

Khalifa's table of cystic tumours:

Tumour	Usual sex	Age (years)	Usual site	Typical size (cm)	Gross pathology
Serous microcystic adenoma	female	66	body & tail	11	(joplink.net, (jhmi.edu)
Intraductal papillary mucinous tumour (IPMT)	male	62	head	4	(jhmi.edu)
Mucinous tumour	female	49	body & tail	10	(rsna.org)
Solid pseudopapillary tumour	female	35	any	7.5	(ajronline.org), (flickr.com/humpath)

Cystic lesions

Serous tumours - overview

General

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

Subclassication

• Serous microcystic adenoma (AKA serous cystadenoma).
  • Many small cysts.
• Serous oligocystic adenoma.
  • Large cysts.
• Serous cystadenocarcinoma - very rare.

Note:

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

Serous cystadenoma of the pancreas

• AKA serous microcystic adenoma, AKA pancreatic serous cystadenoma.

Main article: Serous cystadenoma of the pancreas

Mucinous cystic neoplasms of the pancreas

• 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

• Mucinous 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.

Notes:

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

Images

• 

  Benign mucinous cystic neoplasm - very low mag. (WC)

• 

  Benign mucinous cystic neoplasm - low mag.(WC)

• 

  Benign mucinous cystic neoplasm - intermed. mag. (WC)

• 

  Benign mucinous cystic neoplasm - showing stroma - high mag. (WC)

www:

• Mucinous cystadenoma - ovary (uchc.edu).

Benign mucinous cystic neoplasm of pancreas in a 62 year old woman. A. CT scan showed a peripherally calcified spheroidal mass at the tail of the pancreas. Cytology only showed debris and inflammatory cells, but CEA of the fluid was 2875.2 ng/mL. B. Almost all sections of the cyst showed acellular debris topping a fibrous, often calcified wall, consistent with a pseudocyst. C. Extensive sampling, undertaken because of the high CEA, revealed rare sections with a lining. D. Lining nuclei are bland, with even chromatin. Shape and size variation, as well as darkening when shrunken, are all explicable by degeneration. E. Within distal pancreas, a focus of changes of chronic pancreatitis is seen upper left, while a pancreatic duct in lower right shows an intraductal proliferation. F. Tumor cells show mucinous vacuoles, with better preserved nuclei.  Nuclear appearances remain bland. G. Cellular ovarian stroma appeared beneath epithelium of a separate focus of the cystic neoplasm.

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 versus pseudocyst

Finding	Mucinous tumour	Pseudocyst
Amylase & lipase	low	high
Viscosity	high	low
CEA, CA125	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

• Abbreviated IPMT.
• AKA intraductal papillary mucinous neoplasm, abbreviated IPMN.

Main article: Intraductal papillary mucinous tumour

Solid pseudopapillary tumour

• AKA solid pseudopapillary neoplasm, abbreviation SPN.
• AKA solid and papillary epithelial neoplasm, abbreviated SPEN.

Main article: Solid pseudopapillary tumour

Pre-malignant lesions

Pancreatic intraepithelial neoplasia

• Abbreviated PanIN.

Main article: Pancreatic intraepithelial neoplasia

Solid tumours

Invasive ductal carcinoma of the pancreas

• AKA ductal adenocarcinoma.
• AKA pancreatic ductal adenocarcinoma.
• AKA pancreatic adenocarcinoma.

Main article: Invasive ductal carcinoma of the pancreas

Pancreatic neuroendocrine tumour

• Abbreviated PanNET.
• AKA pancreatic islet cell tumour - considered to be an outdated term.
• AKA islet cell tumour - considered to be an outdated term.

Main article: Neuroendocrine tumour of the pancreas

Acinar cell carcinoma of the pancreas

Not to be confused with acinic cell carcinoma.

• AKA acinar cell carcinoma.
• AKA pancreatic acinar cell carcinoma.

Main article: Acinar cell carcinoma of the pancreas

Pancreatoblastoma

Main article: Pancreatoblastoma

See also

• Duodenum.
• Gallbladder.
• Gastrointestinal pathology.
• Von Hippel-Lindau syndrome.
• IgG4-related systemic disease.

References

Further reading

Klimstra, DS.; Pitman, MB.; Hruban, RH. (Mar 2009). "An algorithmic approach to the diagnosis of pancreatic neoplasms.". Arch Pathol Lab Med 133 (3): 454-64. doi:10.1043/1543-2165-133.3.454. PMID 19260750.

External links

• Pancreatic cancer - PanINs - pancreaticcancer2000.com.