Pathology of The Liver - Practice

2017/2018 – 2. semester

Classification of Liver Diseases

Metabolic diseases

Congenital anomalies

Circulatory disorders

Hepatitis

Infectious

Toxic

Autoimmune

Diseases of bile ducts

Neoplastic

Epithelial

Non-epithelial (mesenchymal)

Focal tumor-like lesions (nodules)

Benign

Malignant

Primary

Metastatic

*

*

*

Non-neoplastic

Childhood

Adulthood*

Natural History of Chronic Liver Diseases (general features)

Chronic injury

Hepatocyte damage / degeneration

Activation of immune cells

Activation of Ito-cells (qHSC aHSC)

Fibrosis Cirrhosis

Activation of myofibroblasts

HCC

Alcoholic Liver Disease

http://alancam.com/study/path/Liver%20-%20Cirrhosis%20(Pathoma).html

STEATOSISFatty degenerationPerivenular fibrosis

NORMAL LIVERFIBROSISCIRRHOSIS

ALCOHOLIC HEPATITISLiver cell necrosisInflammationMallory bodiesFatty degeneration

90-100%

10-35%

10-20%

Ab

stin

ence

Not 'one' disease but a spectrum!

High mortality in fulminant cases!

Soft, yellow, greasy

Fragile

Enlarged

Empty vesicles in

hepatocytes, corresponding

to dissolved lipids

(centrolobular in an early

stage)

Perivenular fibrosis around central veins

pericellular fibrosis - 'chicken wire'

Mallory-Denk bodies

Tangled aggregates of intermedate filaments

Non-specific, present in other liver diseases: PBC, PSC, Wilson, HCC

Hepatocyte balooning

Swelling of hepatocytes

Alcoholic hepatitis

neutrophil granulocytes around liver cells showing hyalin necrosis

Alcoholic cirrhosis

Typically micronodular

NAFLD – Nonalcoholic fatty liver disease

NASH – Nonalcoholic steatohepatitis

Increasing incidency in developed countries

Mimics the entire spectrum of hepatic changes (macroscopy, microscopy) of alcoholic liver disease

Causes: Obesity (central), insulin-resistance, diabetes mellitus, dyslipidemia

Might lead to cirrhosis in the long run

Nonalcoholic Fatty Liver Disease – NAFLD, NASH

• Viral

• Hepatotropic: HAV, HBV, HCV, HDV, HEV

• Others: CMV, EBV, HSV, Adenovirus

• Autoimmune

• AH1, AH2, AH3

• Toxic, drug-induced

• Alcohol

• Paracetamol!, etc.

• NASH

• Other infections

• Idiopathic

• Other (medical herbs)

Hepatitis - causes

Viral hepatitis

ACUTE VS CHRONIC

• Centro-/panlobular inflammation

• Balloon cells

• one-cell/massive cell death

• Councilman bodies

• Fibrosis - not always

• Lobular disarray

• Regenerative nests

• 1% fulminant

Histological picture is usually not specific

• Portal inflammation

± lobular inflammation

• Balloon cells

• 'One-cell' cell death

(so called lytic necr.)

• Fibrosis! (stage)periportalbridgingcirrhosis

Grade –Histology activity index

}

Chronic hepatitis

https://commons.wikimedia.org/wiki/File:Interface_hepatitis_--_high_mag.jpg

Portal inflammation + Interface hepatitisBatts KP, Ludwig J. Chronic hepatitis: an update on terminology and reporting. Am J Surg Pathol. 1995;19:1409-1417.

https://clinicalgate.com/acute-and-chronic-infectious-hepatitis/#s0095

Chronic hepatitis

https://commons.wikimedia.org/wiki/File:Lobular_necro-inflammation_--_intermed_mag.jpg

Lobular inflammation

Chronic hepatitis Fibrosis

Clin Infect Dis. 2012;56(6):853-860. doi:10.1093/cid/cis957

Ishak0 2 4 6

Trichrome staining

Batts KP, Ludwig J. Chronic hepatitis: an update on terminology and reporting. Am J Surg Pathol.1995;19:1409-1417.

Chronic hepatitis – HBV specialities

ground-glass hepatocyte

HBsAg accumulation in the endoplasmic reticulum of liver cells

HBsAg: HBV surface antigenHBcAg: HBV core antigenHBeAg: HBV „e” antigen

Chronic hepatitis – HBV specialities

HBsAg HBcAg

citoplasmic, perinuclear 'lunar' positivity

IHC IHC

citoplasmic and nuclear positivity =Sign of active replication of viruses

Batts KP, Ludwig J. Chronic hepatitis: an update on terminology and reporting. Am J Surg Pathol.1995;19:1409-1417.

Chronic hepatitis – HCV specialities

Batts KP, Ludwig J. Chronic hepatitis: an update on terminology and reporting. Am J Surg Pathol.1995;19:1409-1417.

Portal lymphoid aggregates

often with follicleMacrovesicular steatosis

End stage of liver diseases – CirrhosisDiffuse transformation of the liver into regenerative parenchymal nodules surroundedby fibrous bands, accompained by functional disorders

Etiology

• HBV, HCV

• Alcohol

• Autoimmune

• Postnecrotic

• PBC

• Wilson disease,haemochromatosis,Gaucher disease, α1-AT-deficiency

• Toxic

Decompensatio vascularis et parenchymatosa hepatis

Morphology

• Micronodular < 3 mm

• Macronodular > 3 mm

• Combined

CIRRHOSIS

„weeping”: ascites leaks through liver capsule, drop by drop into abdominal cavity

icterus/jaundiceasciteshepatorenal syndromecoagulopathy gynecomastia hypogonadismhairless skin spider angiomapalmar/plantar erythema portal hypertensionporto-caval anastomoses hepatic encephalopathy…

Cirrhosis – symptoms

Classification of primary liver tumors

Benign hepatocellular lesions (Ø cirrh.)

• Hepatic adenoma

• Focalis nodular hyperplasia (FNH)

• Others (pl. NRH, FFC, pseudolipoma)

Benign/Premalignt hepatocellular lesions (cirrh.)

• Large / macroregenerative nodule

• Low-grade dysplastic nodule

• High-grade dyplastic nodule

Malignant hepatocellular lesions

• HCC

• fibrolamellar HCC

Benign mesenchymal lesions

• Cavernosus haemangioma

• Infantile hemangioendothelioma

• Mesenchymalis hamartoma

• Angiomyolipoma

• Inflammatoric pseudotumor

Malignant mesenchymal lesions

• Angiosarcoma

• Epithelioid hemangioendothelioma

• Undifferentiated embryonal sarcoma

• Kaposi sarcoma

Benign biliary tumors

• Biliar hamartoma

• Bile duct adenoma

• Biliar cystadenoma

• Other

Precursor intraductal biliary lesions

• Biliar dysplasia

• Intraductal papillary neoplasia

Malignant biliary tumors

• Cholangiocarcinoma – intrahepatic

Fletcher: Diagnostic Histopathology of Tumors (3rd Edition)

Hematopoietic

• Primer hepatic lymphoma

• Lymphomas, leukaemias

Cavernous hemangioma

Most common primary tumor of the liver

Usually an incidental finding

Thought to be congenital, doesn't grow, doesn't cause symptoms

More frequent in women, might grow when taking hormonal contraceptives

circumscribed, reddish-brownish,spongy,size ≤ 5 cm

If > 5 cm giant hemangioma

Usually soliter - (can be multiplex in eg. von Hippel-Lindau syndrome)

Complication: Kasabach-Merritt syndrome, rarely: rupture

Treatment: surgical resection

Cavernous hemangioma http://peir.path.uab.edu/library/picture.php?/7968

https://www.omicsgroup.org/articles-admin/disease-images/liver-hemangioma-82710.jpg

https://emedicine.medscape.com/article/364860-overview#a2

http://www.patologia.cm.umk.pl/atlas/gastrointestinal/liver/hemangioma/

Wikimedia commons

https://www.easynotecards.com/notecard_set/72292#&image

Cavernous hemangioma

Epidemiology:

• 6. most common malignant tumor (female: 8., male: 5.)

• 2. most common tumorous cause of death (after lung tu.)

• 80% of cases occur in underdeveloped regions

Far-East, Africa

50% in China!

• Background: cirrhosis (70-90%), chronic liver disease:

hepatotropic viruses (HBV, HCV), alcohol, NAFLD, other

Hepatocellular carcinoma (HCC)

https://www.nature.com/articles/nrgastro.2010.100

Causes (every disease, that leads to cirrhosis):

Chronic HBV infection

Chronic HCV infection

Alcohol

Aflatoxin-B1

NAFLD - NASH

Hepatocellular carcinoma (HCC)

20160426_Gasztro_Fak_Maj_epeutak_daganatai_HritzI.pdf

• Diagnosis: • radiology• core biopsy /FNAB

• Prognosis: median survival 6-9 months, 5 year survival ~10-20%

• Therapy: • surgical (early stage, 15-35%)

• ablation (RFA, PEI, TACE, …)

• sorafenib

• Histological types: trabecular, pseudoglandular, solid, scirrhosus, --- Fibrolamellar (separate subtype)

Hepatocellular carcinoma (HCC)

https://www.hopkinsmedicine.org/liver_tumor_center/conditions/cancerous_liver_tumors/hepatocellular_carcinoma.html

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Metastasis of Adenocarcinoma In The Liver

• 20x more frequent, than primary liver tumor

• Most common 'source' GI tract ( portal circulation)

but can originate from any site

• One of the most common 'target organ' for metastasis formation is liver

METASTATIC LIVER TUMOR

MultiplexWell-circumscribed,expansive growth

Liver is not cirrhotic (usually)

PRIMARY LIVER TUMOR

SoliterInfiltrative growth

Liver is cirrhotic (usually)

VERSUS