Hepatopancreaticobiliary pathology

Jemimah Denson

EXOCRINE PANCREAS

Specimen cut-up

• Margins :– Transection:

• Pancreatic• Bile duct (cystic, CHD, CBD) • Gastric and duodenal

– Dissection:• SMV• SMA• Posterior• CRM around CBD stump

Specimen cut-up

From RCPath dataset copyright Paul Brown St James’s University Hospital, Leeds

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Chronic pancreatitis

• Causes:– ETOH + smoking (act synergistically)– Obstruction– hereditary

• Macro– Diffuse or focal – mimic tumour on imaging– Shrunken and very hard– Dilated ducts with concretions.

Chronic pancreatitis

• Micro:– Acinar atrophy– Fibrosis– Pancreatic duct changes– Inflammation often mild– Islets remain– Enlarged peripheral nerves– Perineural invasion!!

• Complicatons – DM, pseudocyst, vascular

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Autoimmune pancreatitis

• Two types:

• Type 1 – part of IgG4 disease spectrum

• Type 2 – don’t have raised IgG4 & rarely develop extrapancreatic IgG4 disease. Requires tissue for diagnosis.

Autoimmune pancreatitis

• Macro– Usually diffuse but can be focal & mass

forming– Main PD is diffusely or segmentally narrowed

(cf other forms of pancreatitis)– 60% pancreatic head involved with narrowing

of CBD – May involved peripancreatic fat & enlarge LNs

– mimics Ca

Autoimmune pancreatitis

• Micro– Common to both types:

• Periductal lymphoplasmacytic inflammation• Inflammation of acinar parenchyma• Patchy distribution

– Type I• Storiform fibrosis• Obliterative phlebitis• Involvement of peripancreatic fat

– Type II• Granulocytic epithelial lesion (GEL)

AIP

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IgG4

• What is positivity??• Depends on tissue and criteria• HISORt

– >10 positive cells per hpf– Better for biopsy material

• Boston– >50 positive cells per hpf AND IgG4:IgG >40%– Better for resection specimens

• Interpret with caution

Groove pancreatitis

• I have yet to see an example• Aka paraduodenal pancreatitis• Clinical history• Underlying cause is ectopic pancreatic tissue

within wall of duodenum – usually between ampulla of Vater and minor ampulla.

• Impaired drainage of pancreatic secretions leads to duct dilatation, cyst formation, rupture and inflammation.

• Worsened by ETOH

Groove pancreatitis

• Cysts in duodenal wall and pancratoduodenal groove

• Cystic spaces lined by flattened ductal epithelium or granulation tissue

• Acute and chronic inflammation

• Thickened duodenal MP with other foci of ectopic pancreas

• Brunner’s gland hyperplasia

Case history

• 25 year old female

• Abdominal and back pain, N&V, early satiety

• Imaging – large solid and cystic neoplasm in head of pancreas

Microscopy

Microscopy

Solid pseudopapillary neoplasm

• Characteristically young females

• Low grade malignant but usually excellent prognosis

• Usually solitary

• Anywhere in pancreas

• Solid or cystic and anything in between, cyst is degenerative

• Usually encapsulated

Solid pseudopapillary neoplasm

• Poorly cohesive monomorphic cells

• Pseudopapillae

• Degnerative changes

• Cells:– Eosinophilic, foamy or vacuolated– Nucleus often indented or grooved– Eosinophilic globules

SPN immunohistochemistry

• Positive• Vimentin, CD10, β-catenin (nuclear and

cytoplasmic), PR, ORA beta, CD56, NSE• A1AT/A1ACT highlight eos. globules

• +/-• Synaptophysin, epithelial markers

• Negative• CK 7 & 19, chromogranin A, ORA alpha

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Pancreatic cystsNeoplastic epithelial:Serous cystic neoplasm

Mucinous cystic neoplasm

IPMN

SPN

Acinar cell cystadenoma

Cystic teratoma

Cystic ductal adenocarcinoma

Cystic pancreatoblastoma

Cystic mets

Nonneoplastic epithelial:Congenital cyst

Duplication

Choledochal cyst

Cystic hamartoma

Lymphoepithelial cyst

Retention cyst

Groove pancreatitis

Endometrial cyst

Neoplastic non-epithlieal:Lymphangioma

Haemangioma

Cystic schwannoma

Cystic degeneration in LMS

Cystic degeneration in GIST

Cystic degeneration in MPNST

Cystic degeneration in paraganglioma

Nonneoplastic non-epithelial:Pseudocysts

Parasitic cysts

Serous cystic neoplasms

• Serous cystadenoma or cystadenocarcinoma (very rare)

• Microcystic (more♀) or macrocystic (more ♂) • Solid serous adenoma• Often asymptomatic – incidentally detected• Characteristic imaging for microcystic with

‘starburst’ pattern• Associations – minority vHL & NETs

Serous cystadenoma• Macro

– Microcystic mostly body/tail. Sponge like with stellate scar

– Macrocystic mostly head. Few thin walled cysts with watery fluid

– Don’t usually communicate with duct system.

• Micro– Single layer cuboidal cells with clear cystoplasm

• ICC and ∆∆• Malignancy diagnosed on clinical behaviour

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Mucinous cystic neoplasms

• Classification– Premalignant

• Low-grade, intermediate & high-grade dysplasia.

– Malignant i.e. invasive carcinoma

• Mostly female• Mean age 45• Most in body or tail• Solitary – uni or multilocular• Don’t communicate with duct system• Lined by tall, columnar, mucin-producing cells

with characteristic ovarian-type stroma

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Intraduct papillary mucinous neoplasia

• Grossly and radiologically visible papillary mucin forming lesion arising from main PD or its branches

• Classification:– Premalignant

• Low to high grade dysplasia

– Malignant

• Mean 65 yrs, ♂:♀ = 1.5:1• Associations ??P-J & FAP. Synchronous &

metachronous extrapancratic malignancies in 10-40%

IPMN

• Further subtyped into:– Main duct type, branch duct type or mixed– Epithelial subtype:

• Gastric (BD > MD)• Intestinal (MD > BD)• Pancreaticobiliary (BD > MD)• Oncocytic (BD > MD)

• Gastric type most likely to be LG, rest more likely to be HG

PanIN

• Precursor lesion for pancreatic ca• Classification

– PanIN 1A = mucinous (pyloric) metaplasia, flat lesion

– PanIN 1B = papillary architecture– PanIN 2 = atypical hyperplasia (LG dysplasia)– PanIN 3 = HG dysplasia

• Microscopic diagnosis• ∆∆• Show 29021/13

Ductal adenocarcinoma

• Risk factors– Age– Sex– Race– Chronic pancreatitis– Smoking– Familial/inheritied (10%)

• FAMMM• BRCA2• Peutz-Jeghers• HNPCC & FAP

Ductal Adenocarcinoma

• Site– Distal BD, ampulla, pancreas

• Epithelial subtypes– Pancreaticobiliary, intestinal, clear cell, foamy cell

etc..

• Mixed tumours/variants– Adenosquamous (squame at least 30%)– Colloid (mucin pools at least 80%)– Signet ring, Medullary, hepatoid, undifferentiated etc– MANEC (both at least 30%)

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Acinar cell carcinoma

• Mostly adults, mean 60 yrs, but account for 15% of paediatric exocrine pancreatic neoplasms.

• May get lipase hypersecretion syndrome

• 50% present with mets

• Macro – large, well circumscribed or encapsulated tumours. Pushing border. Occur anywhere in pancreas.

Acinar cell carcinoma

• Lobules of cellular tumour sep’d by fibrous bands.

• Acinar pattern, solid or trabecular• Granular eosinophilic cytoplasm• Prominent nucleoli• Zymogen granules PAS/D positive• ICC:

– Trypsin, chymotrypsin, lipase, (amylase)– Bcl10, A1AT, AE1/AE3

http://www.surgicalpathologyatlas.com/glfusion/mediagallery/media.php?f=0&s=200911130910313&i=0&p=0

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Other pancreatic tumours

• Non-epithelial– Very rare <1% of pancreatic neoplasms– More often spread from extrapancreatic

primary

• Paediatric

• Mets– Lung, kidney, breast, colon and MM most

common

LIVER

Classification

• Hepatocellular

• Biliary

• Other

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Focal nodular hyperplasia• Young women• Aetiology ?abnormal blood flow• Can have more than 1 lesion• Characteristic macroscopic appearance

with central scar• Large, thick walled vessels within fibrous

septae• Bile ductules at periphery• Features of cholestasis• Bland, normal appearing hepatocytes

Sounds like FNH??

• Nodular regenerative hyperplasia– Hyperplastic hepatocytes form small nodules,

without fibrous tissue. More diffuse, part of a process of disorder blood flow in liver

• Partial nodular transformation– Very rare, nodule at the hilum, similar to NRH

• Macroregenerative nodule– At least 8mm diam. Usually a large nodule of

cirrhosis. May be pre-neoplastic (see later)

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Hepatocellular adenoma

• Steatotic– HNF1α mutated – usually somatic but can be inherited –

association with hereditary DM, multiple colonic adenomas– Least associated with malignancy

• Inflammatory (telangiectatic)– OCP association and obesity, fatty liver, ETOH excess– Present with inflammatory syndrome

• Β-catenin activated– More often male– More malignancy risk, may be precursor lesion– ??FAP association

• Other

Hepatocellular adenoma

• General features– Occur in non-cirrhotic liver– Often unencapsulated– Bland hepatocytes, 2-3 cell thick plates, retained retic

network.– No bile ducts although ductules may be seen.

• Specific features– Steatotic– Β-cat mutated may show mild atypia & rosettes– Inflammatory – inflamed portal tracts with no

veins/BDs, thick walled vessels, ductular reaction, sinusoidal dilatation & peliosis

Hepatocellular adenoma

• Special stains– No specific marker– Reticulin– Steatotic

• LFABP negative (cf normal liver and other HCA types)

– β-catenin activated• Nuclear β-cat & GS positive

– CD34– Serum amyloid A

Premalignant/early malignant lesions

• Macroscopic lesions– Large regenerative nodule = MRN– Dysplastic nodule – low and high grade– Early HCC <2cm

• Microscopic features– Large cell change - ?if premalignant or not– Small cell change - premalignant– Dysplastic foci = <1mm diameter

• Definition of HCC = stromal invasion

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HCC

• Liver disease

• Environment

• Geographical

• Unless patient is being screened it often presents late

• Pt may have raised serum AFP

HCC

• Macroscopic– Classic appearance = ……– Usually soft tumour

• Microscopic– Varied but classically:

• pseudoglandular/trabecular growth• cells look like hepatocytes• Bile production• Various inclusions esp eosinophilic globules

Diagnosing HCC

• Hopefully characteristic macro and microscopic appearances

• On biopsy can be very difficult to ∆∆ low-grade HCC from dysplastic nodule or even adenoma.

• Histochemistry– Reticulin, DPAS

• ICC

HCC ICC

• Malignant or not?– CD34, glypican 3, HSP70, glutamine

synthetase all more +ve in HCC– CK7/19 can help differentiate between true or

pseudo invasion (+ve ductular reaction in pseudo)

• HCC vs non-hepatic– HepPar 1, AFP, TTF-1, CD10, pCEA

Show ICC & 21521/13

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Fibrolamellar HCC

• Younger patients

• Not associated with chronic liver disease/cirrhosis

• Better prognosis

• Polygonal eosinophilic cells within abundant fibrous stroma

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Benign biliary tumours

• Von Myenburg complex

• Bile duct adenoma

• Bile duct cyst

• Ciliated hepatic foregut cyst

• Intraductal papillary neoplasms & biliary papillomatosis

• Mucinous cystic neoplasm (hepatobiliary cystadenoma)

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Cholangiocarcinoma

• Intrahepatic vs hilar vs extrahepatic• Aetiology less clear than HCC• Increased risk in chronic biliary dx,

cirrhosis, parasitic infections (SE Asia), mucinous cystic neoplasm, biliary papillomatosis

• Diagnostic difficulties:– Intrahepatic CC vs met adenocarcinoma– HCC vs CC or mixed tumour

Mixed HCC-CC

• Peripheral mass forming intrahepatic CC thought likely to have a hepatic progenitor cell origin which may explain mixed tumours (which tend to behave like CC)

Non-epithelial liver lesions

• Vascular– Haemangiomas, epithelioid

haemangioendothelioma

• Other mesenchymal– Inflammatory pseudotumour– angiomyolipoma

• Leukaemias & lymphomas