Pancreas

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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:[1]

  • 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.
  • Total pancreatectomy.
    • Specimen usually comes with the spleen.

Whipple procedure

  • AKA pancreaticoduodenectomy.

Indications:

  • Head of pancreas lesions, duodenal lesions.

Margins:[2]

  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);[3] usu. en face and in toto.[4]
  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:

Borderline epithelial:

Malignant epithelial:

Soft tissue tumours:

Ectopic pancreatic tissue

It comes in two flavours:[5]

  • Pancreatic ectopia.
  • Pancreatic (acinar) metaplasia.

Pancreatic acinar metaplasia

  • Abbreviated PAM.
  • AKA pancreatic metaplasia.[6]

General

  • Common in the GI tract.
  • Found in ~ 20% of eosphageal biopsies above the GEJ.[7]

Gross

  • May be a single lesion or a cluster of lesions.[6]

Microscopic

Features:

  • Pancreatic acini - only.
    • Intensely eosinophilic cytoplasm.

Negatives:

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

Images

IHC

Features:[8]

  • 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

Etiology

Mnemonic I GET SMASHED:

Acute pancreatitis

General

  • Rarely comes to pathology.
  • Usually diagnosed by abdominal CT, blood work (amylase, lipase).

Microscopic

Features:[9]

  • Loss of acini.
  • Neutrophils.
  • Hemorrhage.
  • +/-Loss of pancreatic islets.

Chronic pancreatitis

General

Complications:[10]

Autoimmune pancreatitis

Histologic subtypes of autoimmune pancreatitis:[11]

  1. Lymphoplasmacytic sclerosing pancreatitis (LPSP).
  2. Idiopathic duct-centric chronic pancreatitis (IDCP).
    • Typically IgG4 negative.
    • Approximately 20% of cases.
Lymphoplasmacytic sclerosing pancreatitis

General:

Microscopic:

  • Lymphoplasmacytic infiltrate.

IHC:

  • Plasma cells IgG4 +ve.

Radiology

Plain film findings:

  • Calcifications.

Microscopic

Features of chronic pancreatitis:[15]

  • Preservation of lobular architecture - evenly spaced ductal units.
  • Uniformly sized ductal elements.
  • Smooth ductal contours.
  • Ducts surrounded by acini or islets.
    • Islets usu. preserved better than acini.[16]
  • Intraluminal mucoprotein plugs.

Images:

Adenocarcinoma versus pancreatitis

This contrasts with the features of adenocarcinoma:[15]

  • Ductal architecture:
    • Random distribution of ductal structures.
    • Irregular ductal contours.
    • "Naked ducts in fat"; ducts without surrounding pancreatic elements or fibrous tissue.
    • Ducts adjacent to arterioles.
  • Nuclear atypia:
    • Enlargement (>3 times the size of a lymphocyte).
    • Pleomorphism.
    • Distinct nucleoli.
    • Hyperchromatic raisinoid nucleoli.
  • Generally assoc. with malignancy:

Notes:

  • Memory device: give 'em a fair chance at a benign diagnosis. Features suggestive of malignant:
    • Fat, adjacent to.
    • Arteriole, adjacent to.
    • Irregular ducts.
    • Random distribution of ducts/non-lobular arrangement.

IHC

  • IgG4 +ve plasma cells -- IgG4 sclerosing disease.

Positive in pancreatic carcinoma:[17]

  • p53.
  • Mesothelin.

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[18], (jhmi.edu)[19]
Intraductal papillary
mucinous tumour (IPMT)
male 62 head 4 (jhmi.edu)[19]
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

Note:

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

Serous cystadenoma of the pancreas

  • AKA serous microcystic adenoma,[20] AKA pancreatic serous cystadenoma.

General

  • 1-2% of all exocrine pancreatic tumours.
  • Female > male.
  • Mean age 66 years.
  • Truly benign with no malignant potenial.
  • May be part of von Hippel-Lindau syndrome.

Management:

  • Observe or resect.

Gross

Features:

  • Classically has a characteristic central scar.[22]
  • Bosulated surface.
  • Lobulated.
  • No (macroscopic) cysts apparent on gross.
  • Location: 50-70% occur in the body and tail.
  • Size: average size 11 cm.

Radiologic appearance:

  • Honey comb-like appearance.
  • Well demarcated border - may be described as a "coin lesion".

Image:

Microscopic

Features:

  • Cystic spaces lined by cuboidal cells.
    • Glycogen rich.
    • Cilia. (???)

DDx:

Notes:

  • Serous adenoma may coexist with aggressive tumours.

Images

Stains

  • PAS +ve.
  • PASD -ve.

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:[24]

  • 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

www:

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.

General

  • Morphologically and biologically distinct from ductal adenocarcinoma, mucinous cystic tumour and ductal papillary hyperplasia.
  • Prognosis:
    • Favourable if caught early; not much different than ductal adenocarcinoma if caught late.[25]
    • Dependent what is involved:[26]
      • Main duct (bad prognosis).
      • Branch (good prognosis).

Clinical:

  • Patient usually not jaundiced... as no obstruction.
  • Often diabetes... as pancreas is destroyed.
  • Patients may get a total pancreatectomy - as the disease is often multifocal.

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.

Gross

  • May be patchy/multifocal.
  • Multiple cystic spaces.

Microscopic

Features:

  • Pancreatic duct lining cells jut into the duct lumen - papillomatous growth pattern.
  • Cytology:
    • Cell enlargement.
      • Increased mucin production.
    • Nuclear changes:
    • Mitotic activity.

Note:

  • No ovarian type stroma underneath (as seen in mucinous tumours).

DDx:

Classification of IMPT

Commonly classified by the duct involvement:[27]

  1. Main duct type.
    • Commonly associated with invasive carcinoma.
  2. Branch duct type.
    • Less commonly associated with invasive carcinoma.
Behaviour - Khalifa
  • Adenoma.
  • Borderline mucinous tumour.
  • Carcinoma.

Notes:

  • Borderline tumours are rare.
  • If intralobular dilated ducts... carcinoma.
  • Any margin with mucin cells in thought to be badness!

Solid pseudopapillary tumour

  • AKA solid pseudopapillary neoplasm, abbreviation SPN.
  • AKA solid and papillary epithelial neoplasm, abbreviated SPEN.[28]

General

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

Epidemiology

Features:[29]

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

Management

May be followed radiologically.

Microscopic

Features:[30]

  • Solid sheets of cells, focally dyscohesive.
  • Eosinophilic cytoplasm.
    • Occasionally clear cytoplasm.[31]
    • Focal eosinophilic (intracytoplasmic) globules - key feature.
  • Uniform nuclei with occasional nuclear grooves.
  • +/-Necrosis - creating spaces/cavities.
  • +/-Cholesterol clefts.[32]

Images

www:

DDx

IHC

Features:[31]

  • Beta-catenin +ve ~100% (cytoplasmic & nuclear).
  • E-cadherin +ve ~100% (cytoplasmic), -ve (membrane); antibody dependent.
  • CD10 +ve ~ 80% (cytoplasmic + dot-like) key.
  • Synaptophysin +ve (weak cytoplasmic) ~70%.
  • Progesterone receptor +ve (nuclear) key.

Others:

  • CD56 +ve.
  • Chromogranin -ve.

Memory device PCB: PR (nuclear), CD10 (cytoplasmic), beta-catenin (cytoplasmic & nuclear).

Pre-malignant lesions

Pancreatic intraepithelial neoplasia

  • Abbreviated PanIN.

General

  • PanIN is thought to be the precursor lesion for pancreatic carcinoma.[33]

Overview

Putative preneoplasm-neoplasm-carcinoma sequence:

  • PanIN1a.
    • Not neoplastic, i.e. clonal.
  • PanIN1b.
    • Not neoplastic, i.e. clonal.
  • 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.
    • May be referred to as carcinoma in situ.[34]

Microscopic

Features:[33]

  • 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.

Images

www:

Solid tumours

Invasive ductal carcinoma of the pancreas

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

General

  • Most common type of pancreatic cancer.[35]
  • Location: usually in the head ~60%.
    • 15% in the body, 5% tail, 20% diffuse (head, body & tail).[36]
  • Abysmal prognosis.

Risk factors:[37]

  • Smoking (RR ~ 2).
  • Pancreatitis.
  • Family history, esp. BRCA2.
  • Diabetes mellitus - modest risk increase.

Molecular characteristics:[38][39]

  1. KRAS (oncogene) mutation in ~ 90% of cases.
  2. CDKN2A[40] (AKA p16) inactivation ~ 95% of cases.
  3. TP53 (AKA p53).
  4. SMAD4.

Microscopic

Features:[41]

  • 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.

DDx:

Images

www:

IHC

Features:[42]

  • CD7 +ve.
  • CD20 +ve.
  • SMAD4 -ve ~55% of cases -- stomach usually +ve.
  • CDX2 -ve/+ve.
  • CEA +ve.[43]

Sign out

MASS, PANCREAS, CORE BIOPSY:
- ADENOCARCINOMA, MODERATELY DIFFERENTIATED.

Note:

  • On biopsy, it isn't easy to separate from cholangiocarcinoma. Thus, it is better to stay vague.

Pancreatic neuroendocrine tumour

  • Abbreviated PanNET.[44]
  • AKA pancreatic islet cell tumour[44] - considered to be an outdated term.
  • AKA islet cell tumour - considered to be an outdated term.

General

Classification

Based on peptide produced in the pancreatic islets:

  1. Glucagon from alpha cells (glucagonoma).
  2. Insulin from beta cells (insulinoma) - most common ~ 50% of islet cell tumours.
  3. Somatostatin from D cells (somatostatinoma).
  4. Pancreatic polypeptide from PP cells.

Others:

  1. Vasoactive intestinal peptide (VIPoma).
  2. Gastrin (gastrinoma).

Gross

  • Usually in the head of the pancreas - 68% in one series,[48] and 50% in another series.[48]

Microscopic

Features:

  • Nests of cells.
  • Stippled chromatin.
  • +/-Hyaline globules.

DDx:

Images:

IHC

  • CK19 +ve -- should be done as a routine in pancreatic NETs; poor prognostic factor.[49]

Note:

  • CK19 should not be confused with CA19-9.

Acinar cell carcinoma of the pancreas

Not to be confused with acinic cell carcinoma.
  • AKA acinar cell carcinoma.
  • AKA pancreatic acinar cell carcinoma.[50]

General

  • Rare.
  • Solid epithelial exocrine tumour.[51]
  • Poor prognosis; mean survival of 18 months in one series.[52]

Clinical:[52]

  • Increased serum lipase.
    • Associated with arthralgias (joint pain).
  • Classic presentation - Schmid triad:[53]
    1. Subcutaneous fat necrosis.
    2. Polyarthritis.
    3. Eosinophilia.

Gross

  • Usually head of pancreas.

Microscopic

Features:[52]

  • Cells reminiscent of pancreatic acinus cells:
    • Granular, basophilic cytoplasm - usu. abundant.
    • Round/oval nucleus.
      • Nucleolus prominent.
  • Architecture:
    • Nests, sheets, trabecular, glandular.

DDx:

Images

www:

Stains

Features:[52]

  • PAS +ve (granular).
  • PASD +ve.

IHC

  • Trypsin +ve -- key stain.
  • Lipase +ve.
  • Chromogranin +ve (scattered, focal).
  • CD56 -ve. (?)

Pancreatoblastoma

General

  • Very rare.
  • Tumour of childhood - age of diagnosis ~5 years old.[55]
  • Prognosis ~80% year survival in children[56] more aggressive in adults.
  • May be seen in adults.[57]

Associations:[58]

Microscopic

Features:[58][59]

  • Acinar-like structures.
  • Squamoid corpuscles.
  • Undifferentiated component.

Image:

IHC

Features:[59]

  • CK7 +ve -- acinar, undifferentiated component.
  • CK8 +ve -- squamous component.
  • CK18 +ve -- squamous component.
  • CK19 +ve -- squamous component.

See also

References

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  2. URL: http://www.cap.org/apps/docs/committees/cancer/cancer_protocols/2011/SmallbowelNET_11protocol.pdf. Accessed on: 29 March 2012.
  3. Jamieson, NB.; Foulis, AK.; Oien, KA.; Going, JJ.; Glen, P.; Dickson, EJ.; Imrie, CW.; McKay, CJ. et al. (Jun 2010). "Positive mobilization margins alone do not influence survival following pancreatico-duodenectomy for pancreatic ductal adenocarcinoma.". Ann Surg 251 (6): 1003-10. doi:10.1097/SLA.0b013e3181d77369. PMID 20485150.
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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