The Liver

Dr. I Made Naris Pujawan, M.Biomed, Sp.PA

• Hepatic masses may come to attention for a variety of
reasons. They may generate epigastric fullness and
discomfort or be detected by routine physical examination or
radiographic studies for other indications

• Nodular hyperplasias are not neoplasms; the remaining

lesions discussed in this section are true neoplasms
• NODULAR HYPERPLASIAS
• BENIGN NEOPLASMS
• MALIGNANT TUMORS
NODULAR HYPERPLASIAS
• Solitary or multiple hyperplastic hepatocellular
nodules may develop in the noncirrhotic liver
• Two such conditions, having confusingly
overlapping names, are focal nodular
hyperplasia and nodular regenerative
hyperplasia
• Focal nodular hyperplasia appears as a well-
demarcated but poorly encapsulated nodule,
ranging up to many centimeters in diameter
• It presents as a spontaneous mass lesion in an
otherwise normal liver, most frequently in
young to middle-aged adults
• The lesion is generally lighter than the
surrounding liver and is sometimes yellow
Typically, there is a central gray-white,
depressed stellate scar from which fibrous
septa radiate to the periphery
• The central scar contains large vessels,
usually arterial, that typically show
fibromuscular hyperplasia with eccentric or
concentric narrowing of the lumen
• The radiating septa show foci of intense
lymphocytic infiltrates and exuberant bile
duct proliferation along septal margins
• The parenchyma between the septa shows
essentially normal hepatocytes but with a
thickened plate architecture characteristic
of regeneration
• Long-term use of anabolic hormones or of
contraceptives have been implicated in the
development of focal nodular hyperplasia
• Nodular regenerative hyperplasia denotes a
liver entirely transformed into roughly
spherical nodules, in the absence of
fibrosis. Microscopically, plump
hepatocytes are surrounded by rims of
atrophic hepatocytes
BENIGN NEOPLASMS
• Cavernous hemangiomas, blood vessel
tumors identical to those occurring
elsewhere are the most common benign
liver tumors
• They appear as discrete red-blue, soft
nodules, usually less than 2 cm in
diameter, generally located directly
beneath the capsule
• Histologically, the tumor consists of
vascular channels in a bed of fibrous
connective tissue
• Their chief clinical significance is that
they should not be mistaken for
metastatic tumors, and that blind
percutaneous biopsies not be performed
on them
Hepatic Adenoma
• Hepatic adenomas have clinical significance for three reasons:
• when they present as an intrahepatic mass they may be mistaken for the more ominous
hepatocellular carcinomas;
• subcapsular adenomas have a tendency to rupture, particularly during pregnancy (under
estrogen stimulation), causing life-threatening intraperitoneal hemorrhage;
• rarely, they may transform into carcinomas, particularly, when the adenoma arises in an
individual with glycogen storage disease, and adenomas in which mutations of the β-catenin
gene are present
• Although hormonal stimulation is clearly associated with the development of
solitary hepatic adenoma, the causal events are unknown
• Mutations in the genes encoding the transcription factor HNF1α and β-catenin
have been identified in 50% and 15% of the hepatic adenomas, respectively
• Multiple hepatic adenoma (adenomatosis) syndromes can occur in individuals
with maturity-onset diabetes of young (MODY3), with HNF1 mutation
• Liver cell adenomas are pale, yellowtan, and frequently bile-stained nodules, found anywhere in
the hepatic substance but often beneath the capsule
• Usually well demarcated, encapsulation might not be present
• The tumor commonly presents as a solitary lesion, but multiple lesions (adenomatosis) can occur
• Histologically, liver cell adenomas are composed of sheets and cords of cells that may resemble
normal hepatocytes or have some variation in cell and nuclear size
• Abundant glycogen may generate large hepatocytes with a clear cytoplasm. Steatosis is
commonly present
• Portal tracts are absent; instead, prominent solitary arterial vessels and draining veins are
distributed through the substance of the tumor
MALIGNANT TUMORS
• Malignant tumors occurring in the liver can be primary or metastatic
• Most primary liver cancers arise from hepatocytes and are termed
hepatocellular carcinoma (HCC). Much less common are carcinomas
of bile duct origin, cholangiocarcinomas
• Angiosarcoma of the liver resembles those occurring elsewhere, its
association with exposure to vinyl chloride, arsenic, or Thorotrast
• Hepatoblastoma is the most common liver tumor of young childhood.
Its incidence, which is increasing, is approximately 1 to 2 in 1 million
births
Hepatoblastoma
• The epithelial type, composed of small
polygonal fetal cells or smaller
embryonal cells forming acini, tubules,
or papillary structures vaguely
recapitulating liver development
• The mixed epithelial and mesenchymal
type, which contains foci of
mesenchymal differentiation that may
consist of primitive mesenchyme,
osteoid, cartilage, or striated muscle
• A characteristic feature of
hepatoblastomas is the frequent
activation of the WNT/β-catenin
signaling pathway
Hepatocellular Carcinoma (HCC)
• Four major etiologic factors associated with HCC have been established:
chronic viral infection (HBV, HCV), chronic alcoholism, non-alcoholic
steatohepatitis (NASH), and food contaminants (primarily aflatoxins)
• The pathogenesis of HCC may be different in high-incidence, HBV-prevalent
populations versus low-incidence Western populations, in which other
chronic liver diseases such as alcoholism, non-alcoholic steatohepatitis,
chronic HCV infection, and hemochromatosis are more common
• Repeated cycles of cell death and regeneration, as occurs in chronic
hepatitis from any cause, are important in the pathogenesis of HCCs
• Universal vaccination of children against HBV in endemic areas can
dramatically decrease the incidence of HBV infection, and most likely, the
incidence of HCC
Morphology
• HCC may appear grossly as (1) a unifocal (usually
large) mass ( Fig. 18-47A ); (2) multifocal, widely
distributed nodules of variable size; or (3) a
diffusely infiltrative cancer, permeating widely
and sometimes involving the entire liver
• cause liver enlargement, particularly the large
unifocal and multinodular patterns
• The diffusely infiltrative tumor may blend
imperceptibly into a cirrhotic liver background
• All patterns of HCCs have a strong propensity for
invasion of vascular structures
• HCCs range from well-differentiated to
highly anaplastic undifferentiated lesions
• In well-differentiated and moderately
differentiated tumors, cells that are
recognizable as hepatocytic in origin are
disposed either in a trabecular pattern
(recapitulating liver cell plates) or in an
acinar, pseudoglandular pattern
• In poorly differentiated forms, tumor
cells can take on a pleomorphic
appearance with numerous anaplastic
giant cells, can be small and completely
undifferentiated, or may even resemble
a spindle cell sarcoma
• A distinctive variant of HCC is the fibrolamellar carcinoma, which was first described in 1956
• This variant constitutes 5% of HCCs
• It occurs in young male and female adults (20 to 40 years of age) with equal incidence
• Patients usually do not have underlying chronic liver diseases, and so the prognosis is better than the
conventional HCC
• The etiology of fibrolamellar carcinoma is unknown. It usually presents as single large, hard “scirrhous”
tumor with fibrous bands coursing through it
• On microscopic examination it is composed of well-differentiated polygonal cells growing in nests or cords,
and separated by parallel lamellae of dense collagen bundles
• The tumor cells have abundant eosinophilic cytoplasm and prominent nucleoli
Clinical Features
• most patients have ill-defined upper abdominal pain, malaise, fatigue, weight
loss, and sometimes awareness of an abdominal mass or abdominal fullness
• In many cases the enlarged liver can be felt on palpation, with sufficient
irregularity or nodularity to permit differentiation from cirrhosis. Jaundice, fever,
and gastrointestinal or esophageal variceal bleeding are inconstant findings
• Elevated levels of serum α-fetoprotein are found in 50% of persons with HCC
• The natural course of HCC involves the progressive enlargement of the primary
mass until it seriously disturbs hepatic function, or metastasizes, generally first to
the lungs and then to other sites
• With implementation of screening procedures and advances in imaging, the
detection of HCCs less than 2 cm in diameter has increased in countries where
such facilities are available and can be removed surgically with good prognostic
outcomes
Cholangiocarcinoma (CCA)
• Cholangiocarcinoma, the second most common hepatic malignant tumor
after HCC, is a malignancy of the biliary tree, arising from bile ducts within
and outside of the liver
• The risk factors for development of CCA include primary sclerosing
cholangitis (PSC), congenital fibropolycystic diseases of the biliary system
(particularly Caroli disease and choledochal cysts that will be discussed
later), HCV infection, and previous exposure to Thorotrast (formerly used in
radiography of the biliary tract
• According to their localization, CCAs are classified into intrahepatic and
extrahepatic forms
• Klatskin tumors, which are located at the junction of the right and left
hepatic ducts forming the common hepatic duct, and distal bile duct
tumors
Morphology
• Extrahepatic CCAs are generally small lesions at the time of diagnosis
• Most tumors appear as firm, gray nodules within the bile duct wall;
some may be diffusely infiltrative lesions; others are papillary, polypoid
lesions
• Most are adenocarcinomas that may or may not secrete mucin
• Uncommonly, squamous features are present
• For the most part, an abundant fibrous stroma accompanies the
epithelial proliferation
• Klatskin tumors generally have slower growth than other CCAs, show
prominent fibrosis, and infrequently involve distal metastases
Intrahepatic CCAs
• Occur in the noncirrhotic liver and may track along the intrahepatic portal tract
• CCAs resemble adenocarcinomas arising in other parts of the body
• These neoplasms are usually markedly desmoplastic, with dense collagenous stroma separating
the glandular elements
• Mixed variants occur, in which elements of both HCC and CCA are present.
• Three forms are recognized:
• (1) separate tumor masses of HCC and CCA within the same liver
• (2) “collision tumors,” in which tumorous masses of HCC and CCA commingle at an identifiable interface; and
• (3) tumors in which elements of HCC and CCA are intimately mixed at the microscopic level. These “mixed
tumors” are infrequent, but careful microscopic examination of CCAs can often reveal small foci of
hepatocellular differentiation
METASTATIC TUMORS
• The liver and lungs share the dubious distinction of being the visceral
organs that are most often involved in the metastatic spread of cancer
• primary sources producing hepatic metastases are those of the colon,
breast, lung, and pancreas, any cancer in any site of the body may spread
to the liver, including leukemias, melanomas, and lymphomas
• Typically, multiple nodular metastases are found that often cause striking
hepatomegaly and may replace over 80% of existent hepatic parenchyma
• The liver weight can exceed several kilograms
• massive destruction of liver substance or direct obstruction of major bile
ducts, jaundice and abnormal elevations of liver enzymes may appear
 MATUR
SUKSMA