Liver Carcinoma

  • Derek C. Allen


Liver Carcinoma: this chapter outlines the incidence, risk factors, clinical presentation, investigations, treatments and prognosis of cancer at this anatomical site. These features are correlated with the core data that are required to make the corresponding histopathology reports of a consistently high quality, available in an appropriate timeframe, and clinically relevant to patient management and prognosis. Summary details of the common cancers given at this site include: gross description, histological types, tumour grade/differentiation, extent of local tumour spread, lymphovascular invasion, lymph node involvement, and the status of excision margins. Current WHO Classifications of Malignant Tumours and TNM7 are referenced. Notes are provided on other associated pathology, contemporary use of immunohistochemistry, updates on the role of evolving molecular tests, and the use of these ancillary techniques as biomarkers in diagnosis, and prediction of prognosis and treatment response. A summary is given of the commoner non-carcinoma malignancies that are encountered at this site in diagnostic practice.


Hepatitis Adenoma Sarcoma Encapsulation Aflatoxin 

Primary liver cancer is the sixth commonest cause of cancer worldwide and second commonest cancer in Asia and the fourth in Africa. Hepatocellular carcinoma is the most frequent subtype (90 %). Risk factors are chronic viral infection (hepatitis B(HBV), hepatitis C(HCV)), alcohol, tobacco, aflatoxin ingestion, and in Western society cirrhosis due to various causes e.g. alcohol, alpha-1-antitrypsin deficiency, and haemochromatosis. There is a rising incidence of hepatocellular carcinoma in Europe and the USA due to the increasing prevalence of chronic liver disease e.g. HCV, non-alcoholic fatty liver disease. Some 50–90 % of cases arise in a background of cirrhosis, the presence of cirrhosis or advanced fibrosis being an indicator of an “unstable liver” and a contraindication to resection as it is a predictor of local recurrence.

Intrahepatic cholangiocarcinoma forms a minority of primary liver cancers and risk factors include long standing ulcerative colitis, particularly when associated with primary sclerosing cholangitis.

Liver disease can be asymptomatic until relatively late in the disease course. Otherwise presentation of hepatic malignancy may be with jaundice, weight loss, anaemia and anorexia. There can be right upper quadrant pain or a palpable mass and investigations include serum alpha-fetoprotein (AFP) and CA19-9, liver function tests and imaging studies. Diagnosis of hepatocellular carcinoma is usually based on a combination of elevated (>400 ng/ml) or continuously rising serum AFP levels and appropriate radiological features obviating the need for biopsy. Cholangiocarcinoma is diagnosed by demonstration of obstruction and distortion of the intrahepatic bile duct system usually by magnetic resonance cholangiography (MRC). Suspected metastatic colorectal or pancreatic cancer may have an appropriate past history and raised serum CEA and CA19-9 tumour markers. CT/PET scan is of use in distinguishing metabolically active tumour from benign or necrotic mass lesions. Where metastases or a primary hepatocellular carcinoma are potentially resectable, or transplant is considered, there is a reluctance to carry out fine needle aspiration (FNA)/needle biopsy for fear of upstaging the tumour e.g. needle tract implantation (1–2 % of cases). However in the absence of a significantly elevated serum AFP or other obvious primary site targeted needle biopsy (percutaneous or transjugular) under USS/CT scan guidance may be needed for a firm tissue diagnosis and to exclude other treatable tumours e.g. malignant lymphoma. Needle biopsy yields either a positive diagnosis or the changes adjacent to a mass lesion i.e. liver plate atrophy, prominent sinusoids and focal inflammation.

Transjugular cores are very fine and require careful handling in the laboratory. However they can produce useful morphological and immunohistochemical results if the tumour is in a suitably accessible location. Some of the potential upstaging risks are also obviated if a percutaneous route is avoided.

Hepatic resection in malignant disease is dependent on careful patient selection and is potentially considered for
  • Primary liver tumour involving a single lobe with no invasion of portal vein or inferior vena cava and no significant background cirrhosis. Also one lesion <5 cm or up to three lesions <3 cm.

  • Isolated metastases (e.g. well differentiated neuroendocrine (carcinoid) tumour, colorectal carcinoma) localised to a single lobe with no metastatic spread elsewhere, and adequate excision of the primary lesion. More recently this criterion has been extended to include multiple hepatic metastases provided resection is technically feasible leaving sufficient functioning hepatic remnant. Use of neoadjuvant chemotherapy, intravascular chemoembolisation or radiofrequency ablation can facilitate operative resection or be used in a palliative setting by down sizing the tumour deposits. Patient fitness must also be taken into account, but in patients with colorectal cancer and low volume metastatic disease 40 % 5 year survival can be achieved by metastasectomy. Diagnostic and staging assessment of patients for liver resection of primary and metastatic cancer is performed by regional or network specialist teams.

Depending on the anatomical extent of disease as determined by MRI/CT/ultrasound scans the resection can be major (partial hepatectomy, lobectomy) or segmental, the latter excised with its supplying lymphovascular pedicle. Note that the surgical definition of lobes and their constituent segments differs from the classical anatomical lobes. Small subcapsular metastases of carcinoma can be removed by open or laparoscopic non-anatomical wedge resection, or erroneously diagnosed as such at frozen section during radical cancer surgery due to mimicry by a bile duct adenoma or Von Meyenberg complex (Fig. 10.1).
Fig. 10.1

Liver and regional lymph nodes (Reproduced, with permission, from Wittekind et al. (2005), © 2005)

10.1 Gross Description


  • FNAC (fine needle aspiration cytology)/core biopsy/wedge excision/segmentectomy/partial hepatectomy/R/L lobectomy.

  • Size (cm) and weight (g).



  • Subcapsular/parenchymal/ductocentric/vasculocentric/lobe/multifocal (particularly when cirrhosis is present).


  • Length × width × depth (cm) or maximum dimension (cm).

  • In a cirrhotic liver a solid irregular lesion >5 cm diameter is probably a hepatocellular carcinoma.

  • The diffuse, periductal pattern of cholangiocarcinoma often shows microscopic infiltration beyond its clinical macroscopic extent.


  • Hepatocellular carcinoma: solitary/nodular/diffuse/multifocal (particularly in cirrhosis)/bile stained/venous spread/pedunculated/encapsulated/background cirrhosis/haemochromatosis. The cancer often shows a mosaic of macroscopic patterns.

  • Cholangiocarcinoma: papillary/nodular/stenotic/scirrhous/ductocentric/multifocal.

  • Metastatic carcinoma:single/multiple/necrotic/umbilicated/calcification/diffuse/mucoid/subcapsular.


  • Circumscribed/irregular.

10.2 Histological Type

Hepatocellular Carcinoma

  • Trabecular, plate like or sinusoidal.

  • Pseudoglandular (acinar).

  • These are the usual types comprising hepatoid cells, bile cytoplasmic staining and canalicular plugging, eosinophilic intranuclear pseudoinclusions, and a sinusoidal vascular pattern with a CD34 positive endothelial lining (capillarisation).

  • Solid (compact): inconspicuous sinusoids.

  • Scirrhous: fibrotic. Distinguish from cholangiocarcinoma and post chemo-/radiotherapy changes.

  • Rarely: pleomorphic, clear cell, spindle cell, lymphoepithelial (EBV positive) or osteoclast like.

  • Variants with good prognosis: fibrolamellar carcinoma (90 % <25 years old); pedunculated carcinoma; minute, small or encapsulated carcinoma (see Sect. 10.8.).

Intrahepatic Cholangiocarcinoma

  • 515 % of primary liver cancers. Usually mass forming (single/multifocal/peripheral), periductal infiltrative (perihilar tumours/scirrhous) or intraductal (papillary: rare in the West).

  • Ductulo-acinar pattern of heterogeneous cuboidal to columnar mucin secreting cells in a fibrous stroma with a hyalinised sclerotic hypocellular centre and more cellular periphery. Sometimes papillary.

  • Portal expansion/periportal sleeve like and parenchymal sinusoidal distributions.

  • Few survive longer than 2–3 years due to late presentation and limited resectability.

  • Rarely: mucinous; signet ring cell; adenosquamous; clear cell; pleomorphic; osteoclast like; spindle cell (sarcomatoid). These are prognostically adverse variants.

Combined Hepatocellular/Cholangiocarcinoma

  • 1 % of cases. Mixed phenotypes of usual morphology and immunohistochemical expression, with foci of intermediate character.


  • 50–60 % of childhood liver cancers, 90 % are <5 years of age.

  • Usually a large solitary mass and raised serum AFP. Epithelial component of two cell types (fetal/embryonal hepatocytes or small cell anaplastic) and fibrous mesenchyme (25 % of cases: osteoid or undifferentiated spindle cells). Treatment is neoadjuvant chemotherapy to shrink the tumour and then surgery with a 50–70 % long term survival. Age <1 year, large size and a significant small cell component are adverse factors.

Metastatic Carcinoma

  • In order of frequency: secondary carcinoma (breast, colorectum, pancreas, stomach, lung), neuroendocrine tumour (pancreas) and malignant melanoma. Malignant lymphoma and sarcoma (except metastatic GIST) are uncommon although diffuse large B cell malignant lymphoma and granulocytic sarcoma (myeloid leukaemia) can form single or multiple mass lesions mimicking metastatic carcinoma.

  • Direct spread: stomach, colorectum, pancreas, gall bladder and biliary tree.

  • Distant spread: stomach, oesophagus, colorectum, lung, breast, malignant melanoma, kidney, urinary bladder, ovary, teratoma.

The tumour distribution and appearance may reflect its origin e.g.
  • Colorectum: multiple, large nodules with central necrosis and umbilication, ± mucin, ± calcification. As in renal cell carcinoma can be solitary and massive.

  • Gall bladder: the bulk of disease is centred on the gall bladder bed.

  • Lung: medium sized nodules and fleshy appearance (small cell carcinoma).

  • Breast, stomach: medium sized nodules or diffuse cirrhotic like pattern of sinusoidal infiltration.

  • Malignant melanoma: pigmented.

  • Angiosarcoma, choriocarcinoma, leiomyosarcoma, renal/thyroid carcinoma, gastrointestinal neuroendocrine tumours, GIST: haemorrhagic/cystic.

Note that carcinoma rarely metastasises to a cirrhotic liver, i.e. the tumour is more likely to be a primary liver cancer. Histologically there can be considerable difficulty distinguishing hepatocellular carcinoma and its variants from other metastases e.g. neuroendocrine tumour, renal cell carcinoma, adrenal cortical carcinoma and malignant melanoma. Similarly cholangiocarcinoma (look for adjacent BilIN/mucosal dysplasia) from gastrointestinal secondaries. Morphology allied to a panel of antibodies should be used including:
  • Hepatocellular – Hep Par 1, AFP, canalicular polyclonal CEA/CD 10.

  • Adrenal – inhibin, melan-A, vimentin, synaptophysin.

  • Renal – EMA, vimentin, RCCab, CD10, pax8.

  • Colorectum – CK20, CDX-2.

  • Lung adenocarcinoma – CK7, TTF-1, napsin A.

  • Malignant melanoma – S100, HMB-45, melan-A.

  • GIST – DOG-1, CD117.

  • Neuroendocrine tumours – chromogranin A, synaptophysin, CD56(±), Ki-67, CDX-2 (from gastrointestinal tract), TTF-1 (from lung).

Resection of hepatic metastases: can be done to good effect e.g. well differentiated endocrine (carcinoid) tumour, colorectal carcinoma. Tumour macroscopic and microscopic appearances may be altered by preoperative ablative or neoadjuvant therapy. Extensive sampling is required to establish response which can be assessed as complete, incomplete or absent. Tumour regression is often accompanied by a histiocytic and fibrous reaction with mucin lakes. The number of metastatic deposits and clearance of metastasectomy surgical margins are prognostically significant although equivocal margins are often obliterated by operative diathermy and haemostasis techniques.

Hepatic mass lesions at clinical follow up: a common issue at specialty multidisciplinary team meetings is the finding of a solitary (or several) liver lesion(s) on CT scan staging or post treatment follow up of a cancer originating from various primary sites. A circumscribed hypodense, or, characteristic appearance may allow the radiologist to designate simple cysts or specific entities such as haemangioma with confidence. Indeterminate lesions can be monitored for size and contour change with time. Irregularity of edge or content signal is more worrying for a metastatic deposit and further characterisation can be sought with MRI and CT/PET scans. This is correlated with serum tumour marker levels e.g. CEA, CA125, CA19-9. Ultimately, if radiologically accessible, a tissue diagnosis may be desirable either by FNAC or core biopsy, as a basis for proceeding to further surgical or medical oncological treatment. Importantly new pathology can also be excluded e.g. a patient with previously treated colorectal cancer developing metastatic pancreatic neuroendocrine tumour rather than colorectal metastases, or a mass forming diffuse large B cell malignant lymphoma.

10.3 Differentiation/Grade

For hepatocellular carcinoma well/moderate/poor, or, Edmonson/Steiner Grade I/II/III/IV.

This is based on the degree of resemblance to hepatic tissue. Well differentiated (GI/II) hepatocellular carcinomas resemble a dysplastic nodule in cirrhosis, or an adenoma in non-cirrhotics. Poorly differentiated (GIV) cancers are not recognisably hepatic in character, requiring more usual foci, appropriate immunophenotype and raised serum AFP. Well to moderately differentiated lesions show trabecular (plate like) or pseudoglandular patterns seen in tumours <2–3 cm diameter. Larger lesions (>3 cm) usually only have a well differentiated periphery, with a less differentiated centre characterised by greater cytoarchitectural atypia and no discernable sinusoids. This nodule within nodule appearance is diagnostically useful and highlights the heterogeneity and active evolution of hepatocellular carcinoma. Tumour grade in a preoperative biopsy can predict patient survival.

For cholangiocarcinoma based on the percentage tumour gland formation: well/G1 >95 %: moderate/G2 50–95 %: poor/G3 <50 %: undifferentiated/G4 no glands.

It is recognised that hepatocellular carcinoma and cholangiocarcinoma form a morphological spectrum with origin from a common progenitor stem cell. Mixed cancers can therefore occur.

10.4 Extent of Local Tumour Spread

Border: pushing/infiltrative.

Lymphocytic reaction: prominent/sparse.

Invasion through the hepatic (Glisson’s) capsule.

The TNM7 classification distinguishes between hepatocellular carcinoma and intrahepatic cholangiocarcinoma.

Hepatocellular Carcinoma


Solitary tumour with no vascular invasion


Solitary tumour with vascular invasion or multiple tumours, none >5 cm


Multiple tumours >5 cm (pT3a) or tumour involving a major branch of the portal or hepatic vein(s) (pT3b)


Tumour with direct invasion of adjacent organs other than the gall bladder or with perforation of visceral peritoneum

Vascular invasion is diagnosed by clinical imaging. The pathological classification includes gross and histological involvement. Criteria are: location within a portal tract appropriate to the site of a portal vein, an identifiable lumen and endothelial lining.

Multiple tumours includes multiple independent primaries or intrahepatic metastases from a single hepatic carcinoma. A multicentric distribution is associated with a poor prognosis (Figs. 10.2, 10.3, 10.4, 10.5 and 10.6).
Fig. 10.2

Hepatocellular carcinoma (Reproduced, with permission, from Wittekind et al. (2005), © 2005)

Fig. 10.3

Hepatocellular carcinoma (Reproduced, with permission, from Wittekind et al. (2005), © 2005)

Fig. 10.4

Hepatocellular carcinoma (Reproduced, with permission, from Wittekind et al. (2005), © 2005)

Fig. 10.5

Hepatocellular carcinoma (Reproduced, with permission, from Wittekind et al. (2005), © 2005)

Fig. 10.6

Hepatocellular carcinoma (Reproduced, with permission, from Wittekind et al. (2005), © 2005)

Intrahepatic Cholangiocarcinoma


Solitary tumour without vascular invasion


Solitary tumour with vascular invasion (pT2a) or multiple tumour deposits with or without vascular invasion (pT2b)


Tumour perforates the visceral peritoneum or directly invades adjacent extrahepatic structures


Tumour with periductal invasion (periductal growth pattern).

Cholangiocarcinoma can be mass forming directly invading the adjacent liver parenchyma, periductal infiltrating along portal pedicles, or, rarely shows ductal intraluminal spread.

10.5 Lymphovascular Invasion


Intra-/ extratumoural.

Note the particular propensity for vascular invasion by hepatocellular carcinoma to involve portal tract veins, major branches of portal and hepatic veins and inferior vena cava, ultimately with metastases to lung (47 %), adrenal gland (12 %) and bone (37 %).

Cholangiocarcinoma typically shows lymphovascular and perineural invasion with spread to regional lymph nodes, lungs, bone, adrenal gland, kidney, pancreas and peritoneum.

10.6 Lymph Nodes

Site/number/size/number involved/limit node/extracapsular spread.

Regional nodes: hilar (hepatoduodenal ligament), hepatic (along the hepatic artery), periportal (along portal vein) and those along the inferior vena cava above the renal veins. For cholangiocarcinoma also the periduodenal, peripancreatic and gastrohepatic lymph nodes whereas periaortic, pericaval, superior mesenteric and coeliac lymph nodes are distant metastases (pM1). For primary liver cancers a regional lymphadenectomy will ordinarily include three or more lymph nodes. In cholangiocarcinoma lymph node metastases are often microscopic and subcapsular requiring careful scrutiny of serial slices of the lymph nodes.


No regional lymph node metastasis


Metastasis in regional lymph node(s).

10.7 Excision Margins

Distances (mm) to the limits of excision of parenchyma, bile ducts and veins. Microscopic involvement (R1) is generally regarded as tumour clearance <1 mm.

Mucosal dysplasia (BilIN) at the bile duct excision limits.

10.8 Other Pathology

Budd Chiari Syndrome

Veno-occlusion or small/large calibre hepatic venular obstruction secondary to malignant infiltration and thrombosis. It leads to hepatic ischaemia.

Hepatocellular Carcinoma

Risk factors: Hepatitis B and C: in 50–70 and 20–30 % of cases respectively, world-wide. Seropositive hepatitis B patients have ×100 risk of developing hepatocellular carcinoma.

Cirrhosis: its extent is assessed clinically by the Child-Pugh score and it is present in 6080 % of cases in the West secondary to viral hepatitis, alcohol, congenital bile duct atresia, alpha-1-antitrypsin deficiency or haemochromatosis.

Small/large cell liver cell change or dysplasia: a microscopic finding and usually <1 mm, there is a strong association between large cell change and hepatitis B surface antigen. Small cell change (enlarged nucleus, decreased volume of cytoplasm, nuclear crowding) is regarded as being premalignant and a more important risk factor for the development of carcinoma. Liver nodules can be macroregenerative, focal nodular hyperplasia like, or dysplastic.

Dysplastic nodules: arise in a background of cirrhosis and range from 1 mm to 2–3 cm diameter (usually 5–15 mm), ± a fibrous rim, and variable cytoarchitectural atypia (plates 3 cells thick, irregular edges, loss of reticulin, ± cellular dysplasia, arterialisation, increased Ki-67 proliferation index). They show a spectrum of changes towards hepatocellular carcinoma with type 2 (high-grade dysplastic) nodules particularly significant. Increasingly sophisticated radiological imaging is leading to greater detection of these premalignant dysplastic nodules and small, early hepatocellular carcinomas. Nodules <1 cm require reassessment by 3–6 month interval ultrasound. Nodules 1–2 cm in size are treated as hepatocellular carcinoma if there is typical hypervascularity and portal venous phase wash out on dynamic imaging (CT/MRI scan or contrast enhanced US). If the radiological investigations are inconsistent biopsy may be required. Nodules >2 cm in size with characteristic imaging findings do not require biopsy as a presumptive diagnosis of malignancy can be made.

Immunophenotype: hepatocellular carcinoma is positive for Hep Par 1 (86 %), AFP (37 %: high specificity but low sensitivity) and polyclonal CEA/CD 10 in bile canaliculi. Also CAM 5.2 (but not AE1/AE3), cytokeratins 8, 18 (but not 7,19), ER/PR. PAS positive cytoplasmic glycogen, intracellular PAS positive globular inclusions, loss of pericellular reticulin. EMA, Ber EP4 negative. Also positive for glypican 3, HSP70, glutamine synthetase one protein and nuclear Ki-67.


Risk factors: hepatolithiasis/primary sclerosing cholangitis/ulcerative colitis/liver fluke/biliary tree anomaly. Arises from flat mucosal dysplasia or BilIN – rarely from an intraductal papillary neoplasm (previously designated as biliary papillomatosis). Treatment is surgical (partial/total hepatic resection ± liver transplantation) but often palliative with stenting to relieve obstructive jaundice as prognosis is poor and overall mean survival is <2 years.

Immunophenotype: cytokeratins (7,19), EMA, CEA, CA19-9, mucin positive. Also CAM 5.2 (low molecular weight cytokeratins, as for hepatocellular carcinoma) and AE1/AE3 (including high molecular weight cytokeratins, negative in hepatocellular carcinoma).

Differential Diagnosis of Hepatic Mass Lesions

Focal nodular hyperplasia: the commonest benign liver nodule after cavernous haemangioma. It occurs in young to middle aged women, is usually solitary, <5 cm diameter and asymptomatic. It has a radiological and gross central scar devoid of bile ducts with thick walled vessels, marginal ductular proliferation, plates 2 or 3 cells thick, and is a cirrhosis like nodule with adjacent normal parenchyma. It is a vascular anomaly representing an area of hyperplastic liver due to hyperperfusion by an anomalous artery.

Hepatocellular adenoma: 5–15 cm diameter in middle aged women sometimes with an acute haemorrhagic abdominal presentation and history of oral contraception (60 %), obesity or diabetes mellitus (both 30 %). It has no portal tracts or central veins, shows unaccompanied arteries, liver cell plates ≥2 cells thick with retention of reticulin pattern and sinusoidal Kupffer cells (CD 68 positive). It comprises steatotic, inflammatory and unclassified variants.

Hepatocellular carcinoma: there is often evidence of risk factors e.g. cirrhosis. Plates are >2–3 cells thick, show loss of reticulin pattern and Kupffer cells, sinusoid capillarisation (CD34), cellular atypia, and look for stromal, capsular and vascular invasion. Serum AFP is markedly elevated in 40 % of cases. CT/MRI scan shows the location of the lesion, its extent of invasion and multicentric distribution.

Poorly differentiated metastatic carcinoma: specific histological appearance (e.g. small cell carcinoma lung), immunogenicity (e.g. PSA positive) or histochemical feature (e.g. mucin positive – this cannot distinguish secondary adenocarcinoma from primary cholangiocarcinoma).

Problematic cases: sometimes the distinction between a regenerative nodule, adenoma and well differentiated hepatocellular carcinoma is not possible and the subsequent clinical course establishes the diagnosis. FNAC of hepatic mass lesions is useful for simple cysts, abscesses and some metastatic cancers (e.g. small cell lung carcinoma). Secondary adenocarcinoma cannot always be distinguished from cholangiocarcinoma and previous history is important e.g. resection for colorectal carcinoma. Differential cytokeratin expression may help: colorectal cancer (CK20+/CK7−), cholangiocarcinoma (CK7, 19+/CK20 ±). FNAC is reasonably robust for moderately differentiated hepatocellular carcinoma but needs to be supplemented by core/open biopsy in poorly differentiated carcinomas (to exclude metastatic cancers) and well differentiated lesions (to exclude adenoma, focal nodular hyperplasia, cirrhosis).

Diagnostic features for hepatocellular carcinoma: hepatoid cells (polygonal with central nucleus), nuclear/nucleolar enlargement, a trabecular pattern with sinusoidal capillarisation, nuclear pseudoinclusions, bile secretion and an absence of bile duct epithelial and inflammatory cells. Immunostaining may also be helpful e.g. AFP/polyclonal CEA/CD10/CD34/glypican 3 positive and CK7/19 negative for hepatocellular carcinoma.


Treatment of hepatocellular carcinoma depends on surgical resection ± liver transplantation the latter treating the underlying causative disease. Local resection of carefully selected patients has a 50 % 5 year survival rate but a 70 % recurrence rate. Small tumours may also be successfully treated by high radiofrequency ablation (RFA). Chemotherapy is used for recurrent or inoperable tumours with new agents emerging combined with adjuvant radiotherapy. Prognosis relates to tumour size (>5 cm), cell type or differentiation, encapsulation, multifocality, high serum AFP levels (>100 ng/ml at diagnosis), vascular invasion and the presence or absence of a background cirrhosis (an adverse indicator). Five year survival is at most 1015 % and more usually about 3 %. The majority die within several months of presentation with liver failure, haemorrhage and infection. Small tumours (<3–5 cm) and variants such as fibrolamellar and pedunculated carcinoma are potentially curable (see below). In cases that are resected tumour stage and resection margin status are important prognostic indicators. Hepatic arterial chemoembolisation, percutaneous alcohol injection and radiofrequency ablation also have roles to play with potential survival benefit and easing of pain in non-operable disease. These modalities can also be applicable to metastatic deposits in the liver e.g. colorectal carcinoma. Cholangiocarcinoma is an aggressive disease with early invasion, widespread metastases, late presentation and ineffectual treatment modalities. A mass forming tumour has a more favourable outlook (39 % 5 year survivial) than a periductal infiltrating type lesion with few patients surviving beyond 2–3 years.

Fibrolamellar Carcinoma

  • Large eosinophilic cells in a fibrous stroma, potentially resectable.

  • 50 % cure rate.

  • Serum AFP is not raised, and there is no cirrhosis. May also have areas of usual liver cell carcinoma and cholangiocarcinoma.

  • Can express CK7,19.

Pedunculated Carcinoma

  • Inferoanterior aspect right lobe, up to 1 kg weight.

Minute, Small Encapsulated Carcinoma

  • 2–5 cm, encapsulated by fibrous tissue.

  • 90–100 % 5 year survival if no angio-invasion.

10.9 Other Malignancy

Malignant Lymphoma/Leukaemia

  • Secondary involvement by Hodgkins/non-Hodgkins malignant lymphoma (50–60 % of cases) or leukaemia (80 % of CLL cases). Malignant lymphoma is mainly portal and leukaemia sinusoidal but mixed patterns of distribution are common.

  • Primary malignant lymphoma is rare but of more favourable prognosis. Solitary/multiple masses or diffuse and high-grade large B cell in type. Associated with hepatitis C infection, HIV and primary biliary cirrhosis.


  • Cirrhosis, PVC, thorotrast exposure, the commonest liver sarcoma.

  • Exclude peliosis (well-differentiated angiosarcoma) and primary and secondary carcinoma (poorly differentiated angiosarcoma).

  • Growth is typically along vascular structures (sinusoids, vessels) and the liver cell plates. The endothelial cells are atypical and CD31/34 positive.

Epithelioid Haemangioendothelioma

  • Multinodular fibrous masses with a zoned periphery of cords and tube like structures of spindle and epithelioid cells in myxoid stroma and a central hyalinised scar. Paranuclear cytoplasmic vacuoles, CD31 positive.

  • Associated with Budd Chiari syndrome.

  • Of low to intermediate-grade malignancy: also seen in skin, lung and bone.

Kaposi’s Sarcoma

  • AIDS (15–20 % of fatal cases).

Embryonal Sarcoma

  • 15 % 5 year survival in patients of 6–10 years of age.

  • Spindle/stellate/pleomorphic/rounded cells.

Embryonal Rhabdomyosarcoma

  • <5 years of age, poor prognosis although changing with emerging neoadjuvant therapies and aggressive surgery. Desmin/myo D1/myogenin positive small cells in a cellular subepithelial cambium layer.

  • Arises from major bile ducts near the porta hepatis.

Leiomyosarcoma, Fibrosarcoma

  • Rare. More often represents spread from a retroperitoneal primary.

  • Exclude sarcomatoid liver carcinoma, and, more commonly secondary sarcoma e.g. GIST.

Well Differentiated Neuroendocrine (Carcinoid) Tumour

  • Usually represents metastases from gastrointestinal tract or pancreas. Associated with carcinoid syndrome. Detected clinically by octreotide or CT scans.

Mimics of Malignancy

  • Abscess secondary to ascending cholangitis, portal pyaemia or septicaemia, cavernous haemangioma, sclerosed haemangioma, inflammatory myofibroblastic or pseudotumour (spindle cells in a storiform pattern, plasma cells), PEComa/angiomyolipoma (fat, dystrophic vessels, HMB 45 positive spindle cells, coexisting renal lesion(s)), solitary fibrous tumour (storiform spindle cells, CD34 positive).


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Copyright information

© Springer-Verlag London 2013

Authors and Affiliations

  • Derek C. Allen
    • 1
  1. 1.Histopathology LaboratoryBelfast City HospitalBelfastUK

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