LIVER TUMORS

Dr. Mohammad ZarinMBBS, FCPS, MRCS, FMASAssociate Professor,Surgical “E” ward,Khyber Teaching Hospital, Peshawar.

CLASSIFICATION OF LIVER TUMMORS

1.PRIMARY SOLID BENIGN TUMORS 2.Primary Solid Malignant

Neoplasms 3.CYSTIC NEOPLASMS 4.METASTATIC TUMORS

1.PRIMARY SOLID BENIGN TUMORS LIVER CELL ADENOMA FOCAL NODULAR HYPERPLASIA HEMANGIOMA ADENOMATOUS HYPERPLASIA NODULAR REGENERATIVE HYPERPLASIA MESENCHYMAL HAMARTOMAS FATTY TUMORS BENIGN FIBROUS TUMORS BILE DUCT ADENOMAS

2.Primary Solid Malignant Neoplasms HEPATOCELLULAR CARCINOMA INTRAHEPATIC CHOLANGIOCARCINOMA ANGIOSARCOMA NON-HODGKINS LYMPHOMA CARCINOID TUMORS MALIGNANT GERM CELL TUMORS EPITHELIOD HEMANGIOENDOTHELIOMA.

3.CYSTIC NEOPLASMS

SIMPLE CYST CYSTADENOMA & CYSTADENOCARCINOMA POLYCYSTIC LIVER DISEASE BILE DUCT CYSTS.

4.METASTATIC TUMORS.

COLORECTAL METASTASES NEUROENDOCRINE METASTASES NON- COLORECTAL NON- NEUROENDOCRINE METASTASES.

In Detail….

Liver Cell Adenoma

Liver Cell Adenoma

a relatively rare young women (aged 20-40 years) female-to-male ratio 11:1 associated with steroid hormone use such as

oral contraceptive pills usually single The presence of 10 or more adenomas is termed

adenomatosis.

CLINICAL PRESENTATION

50% to 75% patients are symptomatic Upper abdominal pain is common tumor markers are normal CT usually demonstrates a well-circumscribed heterogenous

mass that shows early enhancement during the arterial phase.

MRI scans of LCA have specific imaging characteristics, including a well-demarcated heterogenous mass containing fat or hemorrhage.

resection may be necessary to secure a diagnosis in difficult cases.

MANAGEMENT

Emergency Hepatic Artery embolization for Patients with acute hemorrhage

Once stabilized and resuscitated, RESECTION of the mass is required

Asymptomatic patients are watched for regression after stopping the OCPs

Focal Nodular Hyperplasia

Focal Nodular Hyperplasia

Second most common benign tumor of the liver Mostly in young women. Usually a small (<5 cm) nodular mass Characterized by a central fibrous scar with

radiating septa

CLINICAL PRESENTATION

Incidental finding at laparotomy or on imaging studies If symptomatic, most often vague abdominal pain Slightly deranged LFTs may be found Serum AFP levels are normal Diagnosed accurately by Contrast-enhanced CT and MRI a homogeneous mass with a central scar that rapidly

enhances during the arterial phase of contrast administration

Rupture, bleeding, and infarction are exceedingly rare, and malignant degeneration of FNH has never been reported.

MANAGEMENT

Asymptomatic patients with typical radiologic features do not require treatment

If diagnostic uncertainty exists, resection may be necessary for histologic confirmation

Persistent symptomatic FNH or an enlarging mass need to be considered for resection.

Hemangioma

Hemangioma

Commonest benign tumor of the liver. Male to female (3:1 ratio) ,at a mean age of about 45 years Cavernous hemangiomas have been associated with FNH. Enlargement of hemangiomas are by ectasia rather than

neoplasia. Lesions >5 cm are arbitrarily called giant hemangiomas

Involution or thrombosis result in dense fibrotic masses which are symptomatic & difficult to differentiate from malignancy

CLINICAL PRESENTATION

Mostly asymptomatic and incidentally found on imaging studies

Large compressive masses may cause vague upper abdominal symptoms

An associated syndrome of thrombocytopenia and consumptive coagulopathy known as Kasabach-Merritt syndrome

INVESTIGATIONS

LFTs and tumor markers are usually normal CT and MRI show a typical peripheral nodular enhancement

pattern Labeled red blood cell scans Percutaneous biopsy of a suspected hemangioma is potentially

dangerous and inaccurate and is therefore not recommended

MANAGEMENT

Asymptomatic patients are simply observed In Symptomatic patients resection is done Rupture, change in size, and development

of the Kasabach-Merritt syndrome are indications for resection

The preferred approach to resection is enucleation with inflow control

Liver hemangiomas in children

Account for about 12% of all childhood hepatic tumors Usually multifocal and can involve other organs Can result in congestive heart failure secondary to

arteriovenous shunting, which are treated with Therapeutic Embolisation

Untreated symptomatic have a 70% mortality rate, but small capillary hemangiomas almost all resolve

Resection may be necessary for symptomatic lesions or for rupture

Macroregenerative nodules

previously known as adenomatous hyperplasia may be single or multiple Result from the hyperplastic response to chronic

liver injury Well-circumscribed, bile-stained, bulging surface

nodules that occur primarily in cirrhotic patients Have malignant potential and can be very difficult

to distinguish from hepatocellular carcinoma

Nodular regenerative hyperplasia (NRH) Benign, diffuse, micronodular (usually <2

cm) Associated with lymphoproliferative

disorders, collagen vascular diseases, and the use of steroids or chemotherapy.

No malignant potential Not associated with cirrhosis. Biopsy may be necessary to distinguish

from malignancy

Mesenchymal Hamartoma

Mesenchymal Hamartoma

75% are age 1 year or less (rarely adults), 60-70% male 8% of pediatric liver tumors Usually asymptomatic Serum AFP is usually normal or mildly elevated Rarely associated with undifferentiated sarcoma Adult cases are usually women with abdominal pain, more

prominent fibrosis and a lesser myxoid component than childhood cases, usually no extramedullary hematopoiesis

Treatment Excision liver transplantation

Cystic Tumors

Cystic Tumors

May be single or multiple May be part of polycystic kidney disease Often asymptomatic No specific management required

Cystic Tumors

Simple cysts:• Asymptomatic• Pathogenesis:

• Embryonal development of intrahepatic biliary duct

• Single layer columnar/cuboidal epitheliuam, straw-colored serous fluid

• Diagnosis: imaging• Treatment: Injection or

enucleation if symptomatic

Cystic Tumors

Multiple Cysts:• Asymptomatic• Polycystic liver disease – autosomal

dominant• Hepatic parenchyma and function

preserved• Pathogenesis:

• histo same as simple cysts• Diagnosis: Imaging• Treatment: resection or transplant if

symptomatic

Cystic TumorsCystadenomas• Presentation:

• Benign w malignant potential

• Slow growing,• Pathogenesis

• Multilocular, single layer cuboidal/columnar epithelium

• Dx: Imaging• Treatment: Resection

Cystic Tumors

Echinococcal/Hydatid Cysts• Presentation:

• Travel SW US, Scotland, Greece, Europe

• Asymptomatic, +/- fever, abdominal pain

• Pathogenesis• Echinococcus – humans

intermediary hosts• Diagnosis: Imaging• Treatment:

Albendezole, enucleation

Primary Solid Malignant Neoplasms

Hepatocellular Carcinoma

AETIOLOGY

Chronic alcohol abuse synergistic with HBV and HCV infection

Cigarette Aflatoxin, produced by Aspergillus Nitrites, hydrocarbons, solvents, pesticides, and

vinyl chloride & Thorotrast (colloidal thorium dioxide)

CLINICAL PRESENTATION Most commonly, men 50 to 60 years of age right upper quadrant abdominal pain and

weight loss and have a palpable mass anorexia, nausea, lethargy, and weight loss are

common Another common presentation of HCC is hepatic

decompensation in a patient with known mild cirrhosis or even in patients without previously recognized cirrhosis.

HCC can present as a rupture, hepatic vein occlusion (Budd-Chiari syndrome), obstructive jaundice, hemobilia, or fever of unknown origin.

DIAGNOSIS

Ultrasound plays a significant role in screening and early detection of HCC

definitive diagnosis and treatment planning rely on CT and MRI

An AFP level greater than 20ng/mL is noted in about three fourths of documented cases of HCC

a hypervascular mass consistent with HCC combined with an AFP higher than 400ng/mL is diagnostic

AFP levels are particularly useful in monitoring treated patients for recurrence after normalization of levels

CONTD…..

Percutaneous needle biopsies of liver lesions suspected of being HCC are only necessary in patients who are being considered for nonoperative therapies

Contrast-enhanced CT and MRI protocols aimed at diagnosing HCC take advantage of the hypervascularity of these tumors, and arterial phase images are critical to adequately assess the extent of disease

CT and MRI also evaluate the extent of disease in terms of peritoneal metastases, nodal metastases, and extent of vascular and biliary involvement

STAGING A. assessing the extent of disease Extent of disease in the liver, including macrovascular invasion

and the presence of multiple liver masses the common sites of metastases must be considered A preoperative chest x-ray is mandatory Routine bone scans are not performed unless there are

suggestive symptoms or signs.

B. Assessment of liver function

absolutely critical in considering treatment options for a patient with HCC

the risk for postoperative liver failure and death must be considered.

clinical assessment schemes most commonly, Child's status (as modified by Pugh) is used.

significant portal hypertension regardless of biochemical assessments is highly predictive of postoperative liver failure and death

Chronic liver disease is classified into Child-Pugh class A to C, employing the added score from above.

ROLE OF STAGING LAPAROSCOPY

Staging laparoscopy has recently been employed as a staging tool in HCC

spares about one in five patients a nontherapeutic laparotomy Laparoscopy yields additional information about extent of

disease in the liver, extrahepatic disease, and cirrhosis

STAGING SYSTEMS

probably depend on the specific population being staged and the etiology of HCC in that particular population

The TNM staging system is not routinely used for HCC; it does not accurately predict survival because it does not take liver function into account

The Okuda staging system is an older but simple and effective system that takes into account liver function and tumor-related factors

The most well-validated staging system is the Cancer of the Liver Italian Program (CLIP).

T1 Single tumour without vascular invasionT2 Single tumour with vascular invasion or multiple nodules, none more than 5 cm in

greatest dimensionT3a Multiple tumours >5 cmT3b Single tumour or multiple tumours of any size involving a major branch of the portal or

hepatic veinT4 Tumour(s) with direct invasion of adjacent organ other than gallbladder or perforation of

visceral peritoneumNX Regional lymph nodes cannot be assessedN0 No regional lymph node metastasesN1 Regional lymph node metastases

Survival Rate of Liver Cancer

Stage I-III five year survival rate is 50% Stage IV five year survival rate is 10%

The Cancer of the Liver Italian Group Score (CLIP)

CLINICAL PARAMETERS CUTOFF VALUES POINTSChild-Pugh stage A 0  B 1  C 2Tumor morphology Uninodular, <50% extension 0  Multinodular, <50%

extension1

  Massive or extension >50% 2AFP (ng/dL) <400 0  >400 1Portal vein thrombosis No 0 Score ranges from 0 to 6; scores of 4 to 6 are generally considered advanced disease, whereas scores of 0 to 3 have the potential for long-term survival.

Yes 1

PATHOLOGY

Histologically, HCC is graded as well, moderately, or poorly differentiated

The grade of HCC, however, has never been shown to accurately predict outcome

A.HANGING TYPE B.PUSHING TYPE C.INFILTRTIVE TYPE. Small tumors less than 5 cm in size usually do not fall into any

of these groups and are often discussed as a separate entity

Treatment Options for Hepatocellular CarcinomaSurgical

SurgicalResectionOrthotopic liver transplantationAblativeEtOH injectionAcetic acid injectionThermal ablation (cryotherapy, radiofrequency ablation, microwave)TransarterialEmbolizationChemoembolizationRadiotherapyCombination Transarterial and AblativeExternal-beam Radiation TherapySystemicChemotherapyHormonalImmunotherapy

Complete excision of HCC either by partial hepatectomy or by total hepatectomy and transplantation is the treatment of choice when possible because it has the highest chance of long-term survival.

only 10% to 20% of patients are considered to have resectable disease. mortality rate less than 5% for partial hepatectomy Patients with Child's B or C cirrhosis or portal hypertension do not tolerate

resection. The volume of the future liver remnant (FLR) is also an important

consideration Preoperative portal vein embolization is an effective strategy to increase the

volume and function of the FLR

Optimal CriteriaSolitary tumor < 5 cmNo vascular invasionNo portal hypertensionWell-preserved hepatic function (Child-Pugh Class A

Negative prognostic factors tumor size, cirrhosis infiltrative growth pattern vascular invasion intrahepatic metastases, multifocal tumors lymph node metastases margin less than 1 cm lack of a capsule.

Resection Liver Transplantation

83, 57, 50 % 84, 74, 62 % 1, 3, 5-year Survival

70, 44, 31 % 83, 72, 60 % 1, 3, 5-year Disease free

ROLE OF LIVER TRANSPLANTATION

liver transplantation is the ideal treatment for HCC because it addresses both the liver dysfunction and the HCC

The limitations of transplantation are the need for chronic immunosuppression as well as the lack of organ donors

patients with single tumors less than 5 cm or multiple tumors no more than three in number and 3 cm in size have resulted in improved outcomes

Patients with advanced cirrhosis (Child's B and C) and early-stage HCC are considered for transplantation, whereas those with Child's A cirrhosis have similar results with transplantation and resection and should probably undergo resection

Optimal CriteriaSolitary tumor < 5 cmUp to three nodules <3 cmNo vascular invasionNo regional nodal or distant metasteses

Percutaneous ethanol injection (PEI)

useful technique for ablating small tumors The tumor is killed by a combination of cellular dehydration,

coagulative necrosis, and vascular thrombosis. Most tumors less than 2 cm in size can be ablated with a single

application of PEI, but larger tumors may require multiple injections.

Long-term survival after PEI for tumors less than 5 cm has been reported to range from 24% to 40.

Optimal CriteriaEarly stage HCCNot resectableSolitary tumors <3cm

Thermal ablative techniques

Thermal ablative techniques that freeze or heat tumors to destroy them have become very popular in recent years.

Cryotherapy uses a specialized cryoprobe to freeze and thaw tumor and surrounding liver tissue with resulting necrosis.

Cryotherapy is usually performed at laparotomy or laparoscopically but has recently been performed with percutaneous techniques

Radiofrequency ablation (RFA) uses high-frequency alternating current to create heat around an inserted probe, resulting in temperatures greater than 60°C and immediate cell death.

RFA can easily be performed percutaneously with low complication rates.

Transarterial therapy

based on the fact that most of the tumor's blood supply is from the hepatic artery

Hepatic arterial infusion (HAI) chemotherapy using 5-fluorouracil (5-FU)-based compounds, cisplatin, and doxorubicin has been studied

requirement of a laparotomy to place the pump and associated hepatic toxicity limits the applicability of this approach

patients with preserved liver function and asymptomatic multinodular tumors without vascular invasion ARE appropriate candidates .

IndicationsLarge unresectable HCCPrior to resection or RFAPalliative purposes

Radiofrequency AblationOptimal Criteria

Child-Pugh Class A/BSolitary tumors <4cm

Radio Frequency Ablation

Ethanol Injection

HCC: Chemoembolization Inject chemotherapy selectively in hepatic artery Then inject an embolic agent Only in pt with early cirrhosis No role for systemic chemotherapy

Chemoembolization

OTHER MODALITIES

Systemic chemotherapy with a variety of agents has been ineffective for the treatment of HCC and has a minimal role in the treatment of HCC

External-beam radiation therapy (EBRT) has a limited role in the treatment of HCC, although occasional dramatic responses are seen

IndicationsLarge unresectable HCCSymptomatic portal vein thrombosisSymptomatic jaundicePart of combined modality treatment

Fibrolamellar HCC

This tumor generally occurs in younger patients without a history of cirrhosis. The tumor is usually well demarcated and encapsulated and may have a

central fibrotic area. The central scar can make distinguishing this tumor from FNH difficult. FHCC does not produce AFP, but is associated with elevated neurotensin

levels. In general, FHCC has a better prognosis than HCC. This is likely related to high resectability rates, lack of chronic liver disease,

and a more indolent course. Long-term survival can be expected in about 50% to 75% of patients after

complete resection, but recurrence is common and occurs in at least 80% of patients.

Comparison of Standard Hepatocellular Carcinoma (HCC) and Fibrolamellar Hepatocellular Carcinoma (FHCC)

CHARACTERISTIC HCC FHCCMale-to-female ratio 2:1-8:1 1 : 1

Median age (yr) 55 25

Tumor Invasive Well circumscribed

Resectability <25% 50%-75%

Cirrhosis 90% 5%

α-fetoprotein positive 80% 5%

Hepatitis B positive 65% 5%

Fibrolamellar Variant of Hepatocellular Carcinoma Young adults 20-40 years, but 30-40% in patients are less than 20 years

old, no gender preference 1-5% of all hepatocellular carcinoma Not associated with hepatitis B virus, cirrhosis or metabolic

abnormalities; pathogenesis unknown Better prognosis than classic HCC; 5 years survival is 60% Metastasizes to abdominal lymph nodes, peritoneum, lung Xray: central scar (similar to focal nodular hyperplasia); often calcified

(uncommon with FNH) Laboratory: serum alpha fetoprotein elevated in only 10% vs. 60% of

classic HCC Gross: single (75%), large (mean 13 cm), hard, scirrhous, well-

circumscribed, bulging, white-brown tumor with fibrous bands throughout and central stellate scar; most cases involve left lobe, but may involve both lobes; variable bile staining, hemorrhage and necrosis

Hepatoblastoma Most common primary liver tumor in children (50% of liver

malignancies in children) 90% occur by age 5 years, 70% by age 2 years 2/3 male Associated with hemihypertrophy (Beckwith-Wiedemann

syndrome), Wilm’s tumor, glycogen storage disease, familial colonic polyposis); not associated with cirrhosis

Symptoms: variable virilization due to hCG production by multinucleated giant cells

Laboratory: elevated serum AFP in 75% Metastases to regional lymph nodes, lung, brain, adrenal glands,

bone marrow Treatment: preoperative chemotherapy and surgery; resect lung

metastases; liver transplant if unresectable Long term survival now 60-70% Prognostic factors: stage, age, sex; increase mitotic activity may

confer poorer prognosis; presence of osteoid may confer favorable prognosis

Hepatoblastoma

Gross: tan-green, 70% solitary, well circumscribed, variable hemorrhage and cysts; mean 10 cm (range 3-20 cm), often partially encapsulated; may be calcified in prominent mesenchymal component

Angiosarcoma

Rare (10-30 annual cases in US), but most common hepatic primary sarcoma in adults (2% of all primary liver tumors)

75% men, usually age 50+ years; rare in children Causes: 25-42% associated with exposure to vinyl chloride,

arsenic, Thorotrast (thorium dioxide) or androgen steroids; rarely associated with copper sulfate, estrogenic steroids, phenelzine, radiotherapy, chemotherapy, hereditary hemochromatosis

Patients with exposure to vinyl chloride or Thorotrast may have synchronous cholangiocarcinoma or hepatocellular carcinoma

Most patients die within 6 months from hepatic failure, intraabdominal bleeding; metastasizes widely, often to lung

Undifferentiated Sarcoma

Also called embryonal sarcoma, malignant mesenchymoma, mesenchymal sarcoma

Usually ages 6-10 years, rare in adults, 10% of pediatric hepatic tumors (#3 after hepatoblastoma and hepatocellular carcinoma)

Often aneuploid Appears to be a primitive mesenchymal neoplasm with

possible foci of differentiated sarcoma Presents with abdominal mass, fever, pain, normal serum

AFP Most patients die within 2 years due to direct extension;

often metastasizes to lung, pleura, peritoneum Treatment: complete resection

Undifferentiated sarcoma

Gross: 10-30 cm, solitary, well-demarcated, soft tumor with cystic, gelatinous, hemorrhagic and necrotic foci

Micro: variably cellular tumor with anaplastic, spindled / oval cells with hyaline globules and ill-defined borders within pseudocapsule; nuclei have stippled chromatin, inconspicuous nucleoli; variably myxoid stroma with numerous thin-walled veins

Cholangiocarcinoma (intrahepatic)

Also called bile duct carcinoma 10% of primary liver cancers High prevalence in southeast and eastern Asia 10-20% are associated with cholangitis due to autosomal dominant

polycystic disease, congenitally dilated hepatic ducts (Caroli’s disease), congenital hepatic fibrosis, infection by liver flukes, Thorotrast, anabolic steroids, intrahepatic lithiasis (5-10% of these patients), primary sclerosing cholangitis (7-42% of these patients)

Diagnosis of exclusion (must rule out metastatic adenocarcinoma) Usually age 60+ years; no gender preference Laboratory: normal AFP Poor prognosis; death usually within 6 months 50-75% metastasize to regional lymph nodes, lungs, vertebrae,

adrenals, brain, elsewhere at autopsy

Intra Hepatic Cholangiocarcinoma

15%of primary liver cancers Primary sclerosing cholangitis a predisposing

condition Widespread infection with liver flukes

(Clonorchissinensis) is at least partly responsible for the higher incidence of these tumors in some parts of Asia

There is evidence to suggest that chronic hepatitis C infection is associated with the rising worldwide incidence of intrahepatic cholangiocarcinoma

Cholangiocarcinoma (intrahepatic)

Gross: solitary, 7-10 cm, multinodular or diffuse small nodules < 1 cm; gray-white and firm; often hepatomegaly and satellite nodules; rarely cirrhosis; rarely bile stained; may invade portal vein

Cholangiocarcinoma (intrahepatic) Patterns signet ring adenosquamous osteoclast giant cell sarcomatous colloid, mucoepidermoid, rhabdoid, clear cell, lymphoepithelioma-like

The appearance of intrahepatic CCA is suggestive of a secondary tumor

Diagnosis of intrahepatic CCA usually requires a biopsy

which reveals an adenocarcinoma that is indistinguishable from a hepatic metastasis arising from a primary adenocarcinoma

An elevated CA 19-9 concentration is strongly suggestive of this diagnosis

Epithelioid Hemangioendothelioma

Malignant endothelium derived neoplasm with intermediate clinical course between hemangioma and angiosarcoma

Hepatic EH is considered a neoplasm of unpredictable malignant potential: the metastatic rate of hepatic EH was 27%, and 43% of the patients ultimately died of their disease.

Mean age 47 years, but occurs at any age, 60% women

No predisposing factors FNA not recommended as even small

biopsies can be misleading

Secondary Liver Tumors (Metastatic)

Secondary Liver Metastases The most common site for blood born

metastases Common primaries : colon, breast, lung,

stomach, pancreases, and melanoma Mild cholestatic picture (ALP, LDH) with

preserved liver function Dx imaging or FNA Treatment depends on the primary cancer In some cases resection or

chemoembolization is possible

Thanks