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.

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

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

Whipple

Margins:

  • Common bile duct (CBD).
  • Uncinate process.
    • At SB done on edge (not en face).
  • Pancreatic neck transection margin.[1]
  • Sometimes superior mesenteric vein (SMV).
  • Rarely SMA margin.

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], [3] 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 [4] IHC? papillae, tall columnar mucin-producing cells head - mucious neoplasms (other pancreatic, duodenal)
Mucinous tumour mucin, ovarian-like stroma cystadenoma, borderline t., cystadenocarcinoma [5], [6] 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) [7], [8] beta-catenin +ve, E-cadherin +ve,
synaptophysin +ve, chromogranin -ve 		sheets of cells, focally loosely cohesive, eosinophilic cytoplasm, uniform nuclei with grooves none usu. younger women, tail of pancreas ductal adenocarcinoma, neuroendocrine tumours
Ductal adenocarcinoma irregular shaped glands, cytologic atypia mucinous, spindle cell, mixed ductal-endocrine [9], [10] 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 usu. paediatric population acinar cell carcinoma
Acinar cell carcinoma acinar arch. - [11] 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, preservation of lobular arch. - [12] 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:

  • Ductal adenocarcinoma.
    • Mucinous noncystic carcinoma.
    • Signet ring cell carcinoma.
    • Adenosquamous carcinoma.
    • Undifferentiated carcinoma.
    • Undifferentiated carcinoma with osteoclast-like giant cells.
    • Mixed ductal-endocrine carcinoma.

Cystic lesions of the pancreas

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:

Usual sex Age (years) Usual site Typical
size (cm)
Serous microcystic
adenoma 		female 66 body & tail 11
Intraductal papillary
mucinous tumour (IPMT) 		male 62 head 4
Mucinous tumour female 49 body & tail 10
Solid pseudopapillary
tumour 		female 35 any 7.5

Serous cystic tumours

General

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

Subclassication

  • Serous microcystic adenoma (AKA serous cystadenoma[2]).
    • Many small cysts.
  • Serous oligocystic adenoma.
    • Large cysts.
  • Serous cystadenocarcinoma - very rare.[3]

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 syndrome.
  • 50-70% occur in the body and tail.
  • Average size 11 cm.

Radiology

  • Honey comb appearance.
  • "Coin lesion" - well demarcated border.
  • May have characteristic central scar.[4]

Gross

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

Microscopic

Features:

  • Cuboidal cells.
    • Glycogen rich.
    • Cilia. (???)

Images:

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

  • 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:[5]

  • 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.

Images:

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 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

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.[6]

Another paper: [7]

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

  • AKA solid pseudopapillary neoplasm.

General

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

Epidemiology

Features:[8]

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

Management

May be followed radiologically.

Microscopic

Features:[9]

  • Solid sheets of cells, focally dyscohesive.
  • Eosinophilic cytoplasm.
    • Occasionally clear cytoplasm.[10]
    • Focal eosinophilic (intracytoplasmic) globules - key feature.
  • Uniform nuclei with occasional nuclear grooves.
  • +/-Necrosis - creating spaces/cavities.

Images:

DDx

IHC

Features:[10]

  • 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).

Pancreatic intraepithelial neoplasia

  • Abbreviated PanIN.

General

  • PanIN is thought to be the precursor lesion for pancreatic carcinoma.[11]

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.

Microscopic

Features:[11]

  • 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).

Ductal adenocarcinoma

General

  • Usually in the head ~60%.
    • 15% in the body, 5% tail, 20% diffuse (head, body & tail).[12]
  • Abysmal prognosis.

Microscopic

Features:[13]

  • 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:

DDx:

  • Chronic pancreatitis.[14]

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:[15]

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

Chronic pancreatitis

General

  • May be confused with ductal adenocarcinoma radiologically... and pathologically.

Plain film findings:

  • Calcifications.

Microscopic

Features of chronic pancreatitis:[14]

  • 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.

This contrasts with the features of adenocarcinoma:[14]

  • 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:
    • Perineural and vascular invasion (rare).
    • Mitosis.
    • Necrotic cellular debris (intraluminal).

Notes:

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

Ectopic pancreatic tissue

It comes in two flavours:[17]

  • Pancreatic ectopia.
  • Pancreatic (acinar) metaplasia.

Pancreatic acinar metaplasia

  • AKA pancreatic metaplasia.

General

  • Common in the GI tract.
  • Found in ~ 20% of eosphageal biopsies above the GEJ.[18]

Microscopic

Features:

  • Pancreatic acini - only.
    • Intensely eosinophilic cytoplasm.

Negatives:

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

Images:

Pancreatic ectopia

Microscopic

Features:

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

See also

References

  1. ↑ 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.
  2. ↑ Mills, Stacey E; Carter, Darryl; Greenson, Joel K; Oberman, Harold A; Reuter, Victor E (2004). Sternberg's Diagnostic Surgical Pathology (4th ed.). Lippincott Williams & Wilkins. pp. 1630. ISBN 978-0781740517.
  3. ↑ Bano, S.; Upreti, L.; Puri, SK.; Chaudhary, V.; Sakuja, P. (Dec 2011). "Imaging of pancreatic serous cystadenocarcinoma.". Jpn J Radiol 29 (10): 730-4. doi:10.1007/s11604-011-0617-3. PMID 22009426.
  4. ↑ Kim YH, Saini S, Sahani D, Hahn PF, Mueller PR, Auh YH (2005). "Imaging diagnosis of cystic pancreatic lesions: pseudocyst versus nonpseudocyst". Radiographics 25 (3): 671–85. doi:10.1148/rg.253045104. PMID 15888617. http://radiographics.rsna.org/content/25/3/671.abstract.
  5. ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 489. ISBN 978-0443066573.
  6. ↑ Maire F, Hammel P, Terris B, et al. (November 2002). "Prognosis of malignant intraductal papillary mucinous tumours of the pancreas after surgical resection. Comparison with pancreatic ductal adenocarcinoma". Gut 51 (5): 717–22. PMC 1773420. PMID 12377813. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pubmed&pubmedid=12377813.
  7. ↑ Baiocchi GL, Portolani N, Missale G, et al. (2010). "Intraductal papillary mucinous neoplasm of the pancreas (IPMN): clinico-pathological correlations and surgical indications". World J Surg Oncol 8: 25. doi:10.1186/1477-7819-8-25. PMC 2858722. PMID 20374620. http://wjso.com/content/8/1/25.
  8. ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 493. ISBN 978-0443066573.
  9. ↑ Iacobuzio-Donahue, Christine A.; Montgomery, Elizabeth A. (2005). Gastrointestinal and Liver Pathology: A Volume in the Foundations in Diagnostic Pathology Series (1st ed.). Churchill Livingstone. pp. 493-5. ISBN 978-0443066573.
  10. ↑ 10.0 10.1 10.2 Serra S, Chetty R (November 2008). "Revision 2: an immunohistochemical approach and evaluation of solid pseudopapillary tumour of the pancreas". J. Clin. Pathol. 61 (11): 1153–9. doi:10.1136/jcp.2008.057828. PMID 18708424. http://jcp.bmj.com/content/61/11/1153.
  11. ↑ 11.0 11.1 Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 949. ISBN 0-7216-0187-1.
  12. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 950. ISBN 0-7216-0187-1.
  13. ↑ Cotran, Ramzi S.; Kumar, Vinay; Fausto, Nelson; Nelso Fausto; Robbins, Stanley L.; Abbas, Abul K. (2005). Robbins and Cotran pathologic basis of disease (7th ed.). St. Louis, Mo: Elsevier Saunders. pp. 951. ISBN 0-7216-0187-1.
  14. ↑ 14.0 14.1 14.2 Adsay, NV.; Bandyopadhyay, S.; Basturk, O.; Othman, M.; Cheng, JD.; Klöppel, G.; Klimstra, DS. (Nov 2004). "Chronic pancreatitis or pancreatic ductal adenocarcinoma?". Semin Diagn Pathol 21 (4): 268-76. PMID 16273946.
  15. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 223. ISBN 978-1416002741.
  16. ↑ Klatt, Edward C. (2006). Robbins and Cotran Atlas of Pathology (1st ed.). Saunders. pp. 225. ISBN 978-1416002741.
  17. ↑ URL: http://test.pathologyportal.org/newindex.htm?92nd/specgasth2.htm. Accessed on: 14 March 2011.
  18. ↑ Johansson J, Håkansson HO, Mellblom L, et al. (March 2010). "Pancreatic acinar metaplasia in the distal oesophagus and the gastric cardia: prevalence, predictors and relation to GORD". J. Gastroenterol. 45 (3): 291–9. doi:10.1007/s00535-009-0161-4. PMID 20012917.

External links

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