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LIVER PATHOLOGY(3)

Prof. Andras Kiss. M.D., Ph.D., D.Sc.

Semmelweis University

2nd Department of Pathology

Budapest

February 26. 2018

Vascular disorders

� Inflow – A.hepatica thromb., embolia – infarctus

– V.portae obstruction, thrombosis (pylethrombosis) –portal hypertension, causes

� Trough– congestion, hepar moschatum, peliosis hepatis

� Outflow– Budd-Chiari syndrome

– VOD

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Budd-Chiari syndrome(Extended hemorrhages in the liver parenchyma caused by thrombosis of hepatic veins)

Nemesánszky-Schaff-Szalay Hepatologia Oktató CD2004 Falk

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Liver alterations associated with pregnancy

� Acute steatosis in pregnancy– rare, from mild to severe (could be fatal), 3.trimester,

perinatal, microvesicular steatosis, pancreatitis (common)

� Intrahepatic cholestasis in pregnancy– 3. trimester, icterus, iching, cholestasis, ??

� Praeeclampsy, eclampsy– HELLP-syndrom (hemolysis, elevated liver enzymes,

low platelets), pale liver with red foci, fibrin deposits in sinusoids, hemorrhages

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LIVER PATHOLOGY (3)

• Focal liver lesions

– Benign tumors and tumor-like lesions

– Malignant tumors

• Liver transplantation

• Diseases of gallbladder and bile ducts

– Diseases of gall bladder

– Diseases of extrahepatic bile ducts

– Tumors

• (**)= important , (×), not for exam (extra)!!!

Focal liver lesions (**)

• Tumor-like lesions of the liver

– FNH, NRH, mesenchymal hamartoma, cysts,

inflammatory pseudotumor, abscessus, infarctus

• Benign liver tumors

– Non epithelial: haemangioma, fibroma,

angiomyolipoma etc

– Epithelial: adenoma (HCA, CCA)

• Malignant liver tumors

– Non epithelial: haemangiosarcoma, -endothelioma

embryonal sarcoma, lymphoma

– Epithelial: hepatocellular cc, cholangiocellular cc.,

mixed, hepatoblasoma

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Classification of liver cysts (1) (×)

I. Parasitic

II. Non parasitic

A. Soliter

B. Hereditary

1. Non-communitating ductal

2. DPM („ductal plate malformation”- communitating)

• CHF (cong. hepatic fibrosis)

• ARPKD

• syndromes (Meckel-Gruber, Ivemark)

3. Isolated hepatic

*Witzleben, G. L., Ruchelli, E.

II. Non parasitic

C. Systemic biliary dilatative

1. Without choledochus cyst

(„simple” Caroli disease)

2. With choledochus cyst

D. Other

1. Traumatic, infarction

2. Duodenal duplication

3. Tumors with cyst

• cystadenoma/-carcinoma

• mesenchymal hamartoma

• giant cavernous haemangioma

• teratoma

• other

4. Peliosis

*Witzleben, G. L., Ruchelli, E.

Classification of liver cysts (2) (×)

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Ecchinococcus cyst

1 cm

Hepar polycysticum

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1 cm

Mesenchymal hamartoma (children, benign)

Tumor-like focal liver lesions (**)

– Focal nodular hyperplasia (FNH)

– Inflammatoric pseudotumor

– Mesenchymal hamartoma

– Nodular regenerativ hyperplasia

– Infarct

– Granulomas (Boeck, tbc etc)

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Focal nodular hyperplasia (FNH)(**)- Female predominance,

- Well circumsized, - No capsule

- Central scar (fibrous septa radiate,

„focal cirrhosis”)

- Color (pale, fatty, haemorrhagic etc.)

- Bile ducts: numerous, tortuous

- Inflammatory cells

-important!!!

Focal NodularHyperplasia (FNH)(central scar!!!)

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1 cm

FNH

1 cm

4319-88

FNH

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Haemangiomahepatis(giant form)

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1 cm

1 cm

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Focal Nodular Hyperplasia(FNH)

FibroLamellar hepatocellularCarcinoma (FLC)

Focal Liver Lesions

FNH HCA (prev. FNH – teleang.)

Hemang.

FLC

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Hepatocellular adenoma (HCA) (**)

- Female predominance

- Associated with oral contraceptives,

anabolic steroids

- Sharply demarcated, - Encapsulated

- Homogenous structure, but hemorrhage,

necrosis common,

- Steatosis, no bile ducts in the tumor

adenoma hepatocellulare (HCA)(yellow, steatosis, capsule)

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HCA: Variant 3

„teleangiectatic”

• Monoclonal

• Dilated vessels

• Haemorrhagies

• Less or no steatosis

• Biliary vessels (less in number)

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10 cm

HCA Variant 3

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CK7

Zucman-Rossi et al., Hepatology 2006;43;515

Classification of hepatocellular adenomas:

association with HCC or borderline lesion

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1 cm

Adenoma hepatocellulare (extended bleeding,rupture might occur)

Hepatocellular carcinoma (**)

- Cirrhosis (70%)

- Association with HBV/HCV/alkohol etc

- Gross: uneven border, usually no capsule,

haemorrhage, necrosis

- Hist: trabecular, pseudoglandular (acinar),

clear cell, scirrhous, fibrolamellar (grades

I-IV)

- Progression: infiltration of capsule (if exists),

venous invasion

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HCC

extracapsular

cirrhosis

HCC

necrosis

HCC

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1 cm

Fibrolamellar HCC

SCIENCE 2014 343:1010

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HCC

cirrhosis

cirrhosis

HCC HCC, trabecular form

Different histological types of HCC

HCC, trabecular HCC, pseudoglandular

HCC, anaplastic

HCC, venousinvasion

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Staging of HCC

TNM-Classification

T1 solitary tumor without vascular invasion

T2 solitary tumor with vascular invasion or

multiple tumors < 5 cm diameter

T3 multiple tumors > 5 cm diameter or

tumor invasion of major veins

T4 tumor(s) with invasion of adjacent organs

or perforation of visceral peritoneum

Stage Grouping

Stage I T1 N0 M0

Stage II T2 N0 M0

Stage IIIA T3 N0 M0

Stage IIIB T4 N0 M0

Stage IIIC any T N1 M0

Stage IV any T any N M1

Therapeutic (surgery) relevance

Llovet J.M., Bruix J. Hepatology 2008.48:1312-27

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Llovet J.M., Bruix J. Hepatology 2008.48:1312-27

Llovet J.M., Bruix J.

Hepatology 2008.48:1312-27

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• Proangiogenic factors overexpressed in HCC:

–Vascular endothelial growth factor (VEGF)

–Platelet-derived growth factor (PDGF)

–Placental growth factor

–Transforming growth factor α and β

–Basic fibroblast growth factor

–Epidermal growth factor (EGF)

–Hepatocyte growth factor

–Angiopoietinek

–Interleukin (IL)-4, IL-8

Angiogenesis and HCC

Semela D, Dufour J-F. J Hepatol 2004;41:864–80

Characteristics of HCC

• 5% of malignant tumors

• 564 000 new cases annually

• (in 2000) and similar death

• Incidence is dubbled in the past

20 yrs (Japan, USA, Sweden,

France)

• 7. in males

• 9. in femels

• Characteristic geography

• Etiological factors: HBV, HCV,

AFB1 (80%), alkohol etc

• 5% of malignant tumors

• 564 000 new cases annually

• (in 2000) and similar death

• Incidence is dubbled in the past

20 yrs (Japan, USA, Sweden,

France)

• 7. in males

• 9. in femels

• Characteristic geography

• Etiological factors: HBV, HCV,

AFB1 (80%), alkohol etc

Unknown

35%

HBV/HDV

5%HBV

15%

HCV

45%

Koff RS, et al. Viral Hepatitis. 2nd ed. 1994.

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HBV, HCV

HCC

Mutagen effects

Cirrhosis !

Aflatoxin

Fusarium toxin

Hepatocarcinogenesis

Etiological

factorsAlcohol

Androgens

Metabolic diseases

Schistosoma

Classification of tumors of bile ducts

Cholangiocarcinoma (CC)intrahepatic CCperihilar CC (previously Klatskin tumor)

distal (CC)

•

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Cholangiocarcinoma.

Perihilar CC

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Cholangiocarcinoma.

Ductus choledocus

Tumor, protruding from theLiver

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2014:1-12

Biliary hamartoma (von Meyenburg complex)

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Biliary hamartoma (von Meyenburg complex)

Gallbladder (**)

1. Tumorlike lesions- Inflammatory origin

(polyp, xanthogranulomatous

cholecystitis etc)

- Hyperplasia

(papillary, adenomyomatous)

- Heterotopic tissue (pancreas,

stomach, endocrin)

- Other

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Gallbladder (**)

2. Tumors

Benign

- adenoma

- cystadenoma

- papillomatosis

- mesenchymal

Malignant

- epithelial

- adenocarcinoma

- adenosquamosus cc.

- squamosus cc.

- differenciálatlan

- cystadenocarcinoma

- mesenchymal

- endocrin - carcinoid

Gallbladder carcinoma (**)

Gross

- infiltrating

- exophytic

Histology

- adenocarcinoma

Immunohistochem

- CEA

- CA 19-9

Other

- TNM

- occult carcinoma

- in situ carcinoma

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Gallbladder cc

Adenocarcinoma

Ductus choledochus carcinoma(CC, distal type)

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Most common metastatic liver tumors (**)

• Gastrointestinal tract, gallbladder,

bile ducts , pancreas

• Lung

• Kidney

• Breast

• Melanoma

• Neuroendocrin

Metastatic liver tumors