BASIC SCIENCE

Pathology of liver tumours

Christopher Bellamy

Abstract
The liver is an important site for both primary and metastatic tumours. In non-cirrhotic patients, the commonest hepatic presentation of malignant disease is metastasis from other sites, most commonly colon, lung, stomach, pancreas and breast. In patients with cirrhosis, hepatocellular carcinoma is the most likely cause of hepatic malignancy, and is a major cause of cancer death worldwide. The malignant cells of hepatocellular carcinoma show differentiation resembling hepatocytes. There is a strong link with chronic viral hepatitis and cirrhosis of any cause, although an unusual slow growing variant of hepatocellular carcinoma called brolamellar carcinoma does not show these associations. Cholangiocarcinoma is adenocarcinoma arising in a bile duct, and is usually of unknown cause although some cases are linked with chronic biliary inammation or infection. Intrahepatic cholangiocarcinoma is increasingly often diagnosed, although denitive diagnosis requires clinical exclusion of a metastasis from elsewhere. There is a variety of benign liver tumours, often manifesting incidentally during investigations. Some have a risk of malignant progression (dysplastic nodules in cirrhotic liver, some hepatocellular adenomas), while others are notable mainly for mimicking more serious disease than for great intrinsic signicance.

Histologic diagnosis relies on examination of high-quality tissue sections stained with haematoxylin and eosin, supplemented with other histochemical stains as necessary, and with immunohistochemistry to demonstrate particular target proteins of diagnostic, therapeutic or prognostic signicance. Molecularcytogenetic testing is beginning to play a role in some situations, but is not yet routine. However the use and range of immunohistochemistry for diagnosis is increasing all the time. Proper xation of the tissue is essential to provide the highquality sections needed for diagnosis, and buffered formalin is the usual xative of choice. Formalin penetrates tissue relatively slowly (about 1 mm per hour), which is not a problem for needle biopsies. However, sizeable resection specimens must have formalin introduced into the specimen to allow timely xation before the tissue degrades, which requires the pathologist to perfuse or thinly slice the unxed specimen as soon as possible. Hence resection specimens are generally best submitted fresh direct to pathology at the end of the procedure, rather than placed in small amounts of formalin and left to the vagaries of the local specimen pickup. If the operation is completed late at night, the specimen can be placed in a bag on ice and left overnight in the fridge for prompt transport direct to pathology the next morning. This will give a better result than leaving it at room temperature unsliced in formalin.

Epithelial tumours and tumour-like lesions

Hepatocellular lesions Focal nodular hyperplasia: Denition e a hyperplastic tumour-like growth of hepatocytes, typically lobulated with radiating brous septae carrying abnormal arterial vessels, and often with a central scar (Figure 1). The lesion is characterized by abnormal arterial hyperperfusion and lack of portal venous perfusion of the affected liver parenchyma, thought to be the root cause of the localized hyperplasia (Table 1). Clinical features e these occur in non-cirrhotic liver, although similar lesions are described in cirrhosis. They most often affect adult women, who are usually asymptomatic or sometimes have abdominal discomfort. Pathology e most are under 5 cm diameter, although can be much larger. There may be multiple lesions in the affected liver,

Keywords Cholangiocarcinoma; dysplastic nodule; focal nodular hyperplasia; hepatocellular adenoma; hepatocellular carcinoma; liver pathology

This article describes the pathology and practical issues relating to diagnosis of tumours or tumour-like lesions arising in the liver. Metastases to the liver will not be covered. The presentation and management of liver tumours are dealt with elsewhere in this issue (see Benign conditions of the liver on pp. 627e631), so will not be fully repeated here. Nevertheless, it is important to emphasize that denitive evaluation and management of a primary liver tumour will usually need to be carried out in specialist hepatobiliary units with a multidisciplinary approach (hepatobiliary surgeon, hepatologist, interventional radiologist, medical oncologist, specialist pathologist) and a full range of diagnostic and therapeutic options.

Handling of tissue specimens

Tissue sent for pathological diagnosis may take the form of a targeted needle biopsy (one or more passes into the lesion, sometimes with a pass into non-lesional tissue for comparison), an open biopsy (occasionally with tissue sent for provisional frozen section diagnosis), or may be the resection specimen itself (possibly after some form of ablative treatment or chemotherapy has already been administered). Each of these specimen types offers its own challenges to diagnosis.

Christopher Bellamy PhD FRCPath is a Reader in Pathology at Edinburgh University and an Honorary Consultant Pathologist at the Royal Inrmary of Edinburgh, Scotland, UK. Conicts of interest: none declared.

Figure 1 Resection specimen showing a focal nodular hyperplasia within non-cirrhotic liver. Note the slightly off-centre scar (arrowhead) with radiating white septae that delineate a vaguely lobular appearance to the lesion.

SURGERY 29:12

597

2011 Elsevier Ltd. All rights reserved.

BASIC SCIENCE

Major primary neoplasms and tumour-like lesions of the liver

Benign
C

Malignant
C

Hepatocellular Focal nodular hyperplasia Dysplastic nodule Hepatocellular adenoma

Biliary Solitary bile duct cyst Ciliated foregut cyst von Meyenburg complex Peribiliary gland hamartoma Biliary papillomatosis Biliary cystadenoma Vascular Haemangioma Infantile haemangioendothelioma Others Angiomyolipoma Inammatory pseudotumours Mesenchymal hamartoma

Hepatocellular Hepatocellular carcinoma Fibrolamellar hepatocellular carcinoma Combined hepatocellularcholangiocarcinoma Hepatoblastoma Biliary Cystadenocarcinoma Cholangiocarcinoma

Vascular Epithelioid haemangioendothelioma Angiosarcoma C Others Hepatic lymphoma Other sarcomas

C

Table 1

or the focal nodular hyperplasia may itself be incidental to another lesion such as liver cell adenoma. The histology on a needle biopsy can resemble a biliary cirrhosis unless the pathologist is alert to this being a focal lesion, but is generally distinctive enough, with thickened vessels in brous septa with marginal ductules, the septa delineating regions of blandappearing hepatocytes without portal tracts. Liver cell (hepatocellular) adenoma: Denition e a benign neoplasm of liver cells that arises in non-cirrhotic liver and can be solitary or multiple. Clinical features e hepatocellular adenomas most often affect women of reproductive age (about 90%) and are associated with oral contraceptive usage, but can also arise in particular disease settings where men are more often affected, including inherited glycogen storage diseases, familial diabetes mellitus, exposure to non-contraceptive oestrogens (e.g. Danazol) and anabolic steroids. Diagnosis is often by chance, but patients may present with abdominal discomfort, or sometimes acutely due to intraperitoneal haemorrhage. Small adenomas may remain stable after stopping the oral contraceptive, while a few may regress. Patients with an adenoma may also have a focal nodular hyperplasia or haemangioma elsewhere in the liver (possibly a greater than chance association), and so the nature of each additional lesion in the liver has to be considered independently. There is no particular clinical value in categorizing patients

according to whether they have one or multiple adenomas, and it is the clinical setting, gender and lesion size that are important. Pathology e adenomas are circumscribed tumours in noncirrhotic liver. They may be as large as 20 cm or more, but are more typically several centimetres diameter. Where there is more than one adenoma (as many as one-third of patients), the additional lesions may range down to 1 cm or even smaller (called microadenomas). Adenomas larger than 4e5 cm often have areas of haemorrhage and sometimes necrosis. Those with haemorrhage identied on imaging at presentation may have arterial embolization/ligation as a temporary control measure in the months preceding resection. In such cases, the haematoma and sometimes the resected adenoma itself can have shrunk substantially from the size at presentation. On microscopy, there are sheets of bland-looking hepatocytes with mildly thickened liver plates and prominent small vessels, but no true portal tracts with bile ducts. Distinction from a welldifferentiated hepatocellular carcinoma on a needle biopsy can be very difcult or impossible. There has been considerable recent progress in identifying clinically relevant molecular subgroups of adenomas, although a minority remain unclassied. These subgroups tend to have characteristic appearances on routine histology which can usually be validated with immunohistochemistry, even if molecular analytic techniques are unavailable. Adenomas with extensive fatty change (detectable with imaging) are often HNF1a-mutated, seem to be stable with a low risk of malignant progression, and are more often associated with other microadenomas in the liver. Immunohistochemistry for loss of liver fatty acid binding protein expression from the tumour cells is diagnostic. Adenomas expressing inammatory proteins on immunohistochemistry (inammatory adenomas) often have characteristic inammation and vascular changes on histology (sometimes also called telangiectatic adenomas). The patients may also have a biochemical inammatory syndrome, and there are associations with high alcohol intake, obesity and fatty liver disease (Figure 2). Molecular analysis shows these adenomas to characteristically have mutations activating inammatory signal transduction pathways. A small minority show malignant progression.

Figure 2 Resection specimen showing a 91 mm adenoma arising in noncirrhotic liver in a morbidly obese patient. On microscopy, the adenoma was of telangiectatic (inammatory) type, and the surrounding liver showed steatohepatitis.

SURGERY 29:12

598

2011 Elsevier Ltd. All rights reserved.

BASIC SCIENCE

Complications e haemorrhage is the commonest complication. The risk of malignant progression within the adenoma to hepatocellular carcinoma is increased in larger adenomas (>5 cm) and adenomas showing b-catenin-activation, which can sometimes be detected with immunohistochemistry. However malignant progression is sufciently more likely in men that adenomas of any size in males may be considered at risk. Identication of the malignant areas is generally only possible in the resected specimen, so the clinical management of adenomas is dictated by risk factors rather than direct identication of malignancy with imaging or biopsy. Dysplastic nodule: Denition e a benign nodule of neoplastic hepatocytes in cirrhotic liver, with increased potential to develop hepatocellular carcinoma. Clinical features e on imaging, these can be impossible to discriminate from small well-differentiated hepatocellular carcinoma, both having an iso- or hypovascular appearance. Pathology e these are nodules usually around 1e1.5 cm diameter, but sometimes up to about 2 cm diameter, either incidental ndings on resection specimens or pre-detected on imaging. They may show areas of fatty change, and on histology are characterized by a mildly atypical population of compact hepatocytes, still with residual portal tracts present, but with the beginnings of neovascularization (new arterioles growing into the lesion) in more advanced lesions. The most abnormal (high grade) examples can be difcult to discriminate from malignancy. Occasionally, a subnodule showing progression to frank well-differentiated hepatocellular carcinoma is present, in which case it is obviously no longer appropriate to diagnose the lesion as benign. Large regenerative nodule: a regenerative macronodule of hepatocytes occurring in liver affected with severe venous disease (Budd-Chiari syndrome or portal vein thrombosis). The nodule contains abnormal arterialized feeding vessels (on which its growth depends) and retains scattered residual portal tract structures with bile ducts, although it does not receive signicant portal vein ow. Some examples closely resemble focal nodular hyperplasia, which shares the dependence on arterial hyperaemia. Hepatocellular carcinoma: this is the commonest primary liver malignancy and fth commonest malignancy worldwide, with a rising incidence in Western countries. Better imaging and screening protocols in high risk patients are capturing the disease at an earlier stage that is better susceptible to treatment (see Malignant Liver Tumours on pp. 632e639 of this issue). While hepatocellular carcinoma usually arises in patients with cirrhosis (who are regularly screened for liver cancer), a signicant minority do not have cirrhosis. Indeed, recent attention has been directed to hepatocellular carcinomas arising in elderly noncirrhotic patients with metabolic syndrome, possibly developing from pre-existing adenoma in some cases. Moreover, the brolamellar variant of hepatocellular carcinoma (see below) has no association with any chronic liver disease. Pathology e hepatocellular carcinoma most often develops in cirrhotic liver, in which the carcinoma may be single or multiple, and accompanied or not by dysplastic nodules elsewhere in the

liver, or occasionally may be detected arising within a dysplastic nodule. Advanced hepatocellular carcinoma (>2 cm) can be grossly categorized as nodular, massive (occupying an entire lobe) or diffuse (myriad small nodules replacing a lobe or the entire liver, somewhat resembling cirrhotic nodules). The carcinomas often develop a brous outer capsule as they enlarge, while bile production by the carcinoma may colour the tumour. Vascular invasion, usually into portal vein branches draining the tumour, becomes common even in moderately progressed carcinomas, and can be large enough to show up on imaging as intravascular thrombi. Small hepatocellular carcinoma (<2 cm) can also be a distinct nodule (Figure 3), but is only classed as an early hepatocellular carcinoma if it manifests as an ill-dened (vaguely nodular) lesion that is also well-differentiated on microscopy. Early hepatocellular carcinomas have a better prognosis than other small carcinomas that are distinctly nodular or moderately differentiated, which are considered to be more progressed forms of the disease. On microscopy, the malignant cells generally resemble hepatocytes (and may make bile that can be seen under the microscope), but are arranged in aberrantly thick plates or other architectures that are not seen in non-neoplastic liver. There is no mucin secretion as in adenocarcinoma. Small carcinomas are usually well or moderately differentiated, but as the tumour enlarges such areas become replaced with less differentiated carcinoma. Early carcinomas generally contain very compact cells, while more advanced carcinomas contain larger and more atypical cells with a variety of appearances common within a single tumour. A few residual portal tracts can be seen in early hepatocellular carcinomas, which are not yet extensively neovascularized. Invasion by carcinoma cells into these residual portal tracts is a useful clue to diagnosis. However, portal tracts are no longer evident in more progressed carcinomas where extensive neovascularization by feeding arterioles makes the lesion hypervascular on imaging.

Figure 3 Resection specimen showing a small (17 mm) distinctly nodular hepatocellular carcinoma that on microscopy was moderately differentiated. The surrounding liver shows cirrhosis due to genetic haemochromatosis.

SURGERY 29:12

599

2011 Elsevier Ltd. All rights reserved.

BASIC SCIENCE

Immunohistochemistry can conrm hepatocellular differentiation and exclude cholangiocarcinoma with antibodies to CD13 (canalicular staining) or hepatocyte parafn-1 antigen, or in some poorly differentiated hepatocellular carcinomas with antibody to a-fetoprotein. A minority of hepatocellular carcinomas also express the biliary cytokeratin 19, suggesting a relationship with hepatic progenitor cells that can differentiate into both hepatocytes and cholangiocytes. Such CK19-positive hepatocellular carcinomas are more likely to recur. Fibrolamellar hepatocellular carcinoma e this is an uncommon but clinico-pathologically distinct form of slow growing hepatocellular carcinoma that has a better prognosis than conventional hepatocellular carcinoma, even after extrahepatic spread (>60% 5-year survival). Unlike conventional hepatocellular carcinoma:  most affected patients are young adults (mean age 23 years)  there is no gender difference  the tumour arises in non-cirrhotic liver: there are no predisposing factors e the cause is unknown. Macroscopically, the tumour is usually large, solitary and well dened, often with radiating brous septa lending it a lobulated appearance, and sometimes with central scarring rather like a focal nodular hyperplasia. Microscopically, there is more brosis than with conventional hepatocellular carcinomas, organized in characteristic bands of parallel lamellae of collagen (Figure 4). The carcinoma cells lie between the brous bands in groups of characteristically large polygonal cells with pinkstaining cytoplasm made granular by numerous mitochondria. Hepatoblastoma: it is the commonest primary liver tumour in children, nearly all (90%) occurring before 5 years of age. A majority are boys, typically presenting with abdominal enlargement and found to have raised serum a-fetoprotein. Liver biopsy is usually done to conrm the diagnosis. Cure requires complete excision, and preoperative chemotherapy is successful in rendering many otherwise incurable cases resectable. Risk factors e the risk is much increased in patients with familial adenomatous polyposis, or with BeckwitheWiedemann

syndrome. Congenital malformations (renal, cardiac etc) are present in some patients. Pathology e the resected tumour is usually large and solitary, with lobulations and discolouration depending on the differentiation and composition. There may be extensive necrosis in tumours resected after chemotherapy. Histologically, the composition can be purely epithelial cells or mixed epithelial-mesenchymal cells (each with subtypes), or sheets of undifferentiated small cells. The histological pattern or subtype does not independently affect prognosis except for the undifferentiated small cell subtype that has a very poor prognosis. Biliary lesions Bile duct adenoma (peribiliary gland hamartoma): this is a circumscribed mass of small bland tubules and glands in a brous stroma, often noticed just under the liver capsule as a white nodule. There may be a single or multiple such lesions, usually smaller than 1 cm and found incidentally at laparotomy. They have no intrinsic signicance but can cause concern to the surgeon for metastasis, and may therefore provoke an intraoperative frozen section to clarify their nature. Hepatobiliary cystadenoma: this solitary cystic neoplasm is very similar to the mucinous cystadenoma of pancreas. Nearly all patients are women, presenting with vague abdominal symptoms. The cystadenoma may recur if incompletely excised, and has the potential to progress to malignancy (cystadenocarcinoma), so complete excision is always recommended if possible. Pathology e cystadenoma is a solitary but multilocular tumour (unlike solitary bile duct cysts, which are unilocular), which is usually intrahepatic and varies in size from a few to over 25 cm diameter. The cyst wall is smooth and the contents gelatinous. Microscopically, the cyst is lined with cytologically benign columnar or cuboidal epithelium with mucin (few cases are serous). The epithelial lining may show metaplasia or low grade dysplasia. In women, the underlying cyst wall may have smooth muscle bundles, and often has characteristic areas of cellular brous stroma (so-called ovarian-like), similar to that of a pancreatic mucinous cystadenoma. The cyst can show secondary features such as haemorrhage, brosis, calcication (which may show up on imaging) or xanthogranulomatous inammation. Hepatobiliary cystadenocarcinoma: it is a rare form of adenocarcinoma, which in women has often arisen in a pre-existing hepatobiliary cystadenoma (still with its ovarian-like stroma in the wall). Others, including those in men, probably do not share this pathogenesis. Intrahepatic cholangiocarcinoma: cholangiocarcinoma is an adenocarcinoma arising from a bile duct. The site of origin has clinical implications, although the histology is similar: those arising within intrahepatic ducts tend to present later than either those around the conuence of the hepatic ducts (hilar cholangiocarcinomas) e which are often particularly small e or extrahepatic cholangiocarcinomas.

Figure 4 Microscopic image of a brolamellar hepatocellular carcinoma, showing the malignant cells in groups separated by bands of lamellar collagen bres (arrowheads).

SURGERY 29:12

600

2011 Elsevier Ltd. All rights reserved.

BASIC SCIENCE

Over one-third of cholangiocarcinomas are intrahepatic, and the incidence of diagnosis is increasing. Patients tend to be over 45 years old with advanced disease and short survival (median 6 months). Five-year survival improves from 5% to about 30% if resection with clear margins is feasible. Risk factors e many cases have no obvious risk factor. However, in others chronic biliary inammation is a clear-cut predisposing factor, including primary sclerosing cholangitis, hepatolithiasis and chronic parasitic infections of the biliary tree (Clonorchis sinensis, Opisthorchis viverrini in Thailand and Southeast Asia). Other risk factors for intrahepatic cholangiocarcinoma include chronic viral hepatitis (B or C) and heavy alcohol consumption. Pathology e typically, there is a hard white tumour with brous processes extending outwards, arising in non-cirrhotic liver (although there is an increased risk in cirrhosis related to chronic viral hepatitis C (Figure 5)). Histologically, there is usually well or moderately differentiated adenocarcinoma within a brous tumour-associated stroma. The carcinoma spreads avidly along neurovascular bundles, and intra or perineural invasion is common, as is spread along portal tracts. Unlike hepatocellular carcinoma, there can be mucin secretion but there is no bile secretion. Immunohistochemistry can conrm the lack of hepatocellular markers but is normally unable to discriminate cholangiocarcinoma from metastatic adenocarcinoma, a distinction that depends on clinical/radiological correlation for evidence of an extrahepatic primary cancer. Combined hepatocellular-cholangiocarcinoma: an uncommon carcinoma with intimately admixed elements of clear-cut hepatocellular carcinoma and cholangiocarcinoma; this is by contrast with a rare collision of two adjacent but separately arising hepatocellular and cholangiocarcinomas. The clinical behaviour may more closely align with hepatocellular carcinoma than cholangiocarcinoma, possibly with a poorer prognosis. It has been suggested that these bi-differentiated lesions reect origin from bipotential liver progenitor cells. Other liver carcinomas may also have a mixed phenotype, including the uncommonly diagnosed cholangiocarcinoma,

considered to be a variant of intrahepatic cholangiocarcinoma in which the malignant structures resemble cholangioles (canals of Hering), but which can have small areas with hepatocellular carcinoma differentiation. Conversely, some otherwise conventional hepatocellular carcinomas co-express the biliary cytokeratin 19 (see hepatocellular carcinoma, above).

Vascular tumours
Haemangioma: the commonest benign lesion of liver. Larger lesions may cause discomfort or rarely rupture, but most are clinically silent. They are more often diagnosed in women. Imaging is diagnostic and needle biopsy is contraindicated due to risk of haemorrhage. Pathology e most are solitary, with a dark red spongy appearance on cut section (Figure 6), becoming partly or completely white as they age and scar over (sclerosed haemangioma). Microscopically, there is a network of closely approximated and variably sized blood-lled channels that are lined with endothelium, supported by a brous stroma. Small thrombi are common. Large feeding arterial vessels may be apparent in the haemangioma and may show old thrombosis, associated with focal scarring, sometimes with calcication. Epithelioid haemangioendothelioma: a usually low grade and slow growing vascular (endothelial) malignancy, which may arise in lung, soft tissue or other sites, including liver. Patients are adults who usually present with abdominal discomfort or mass. There are no known causative factors. Five-year survival is over 50% and unresectable cases may be treated with liver transplantation. Pathology e there are often multiple white tumours within the liver (unresectable), from microscopic to several centimetres size, looking like metastases. Microscopically, the centre of a tumour may be very brous with few identiable malignant cells, while the periphery shows a subtle seeping inltration of the malignant cells along the sinusoids between the surrounding liver cell plates, which can appear remarkably undisturbed. Deeper in, the malignant endothelial cells grow in small groups

Figure 5 Resection specimen showing a segment VIII 32 mm peripheral cholangiocarcinoma, here arising in cirrhotic liver.

Figure 6 Resection specimen showing a partially sclerosed haemangioma adjacent to the left hepatic duct. Note the characteristic dark red spongy appearance which gives way to grey-white scarred areas (arrowhead) that are probably related to old intralesional thrombosis.

SURGERY 29:12

601

2011 Elsevier Ltd. All rights reserved.

BASIC SCIENCE

and cords, sometimes widely separated by matrix. Some of the malignant cells show early intracytoplasmic formation of a vascular-type lumen that may even contain red cells. Others are less distinctive, but demonstrate vascular endothelial markers with immunohistochemistry, such as CD31. There is little proliferation. Angiosarcoma: a highly malignant neoplasm of vascular endothelium that is the commonest sarcoma of liver, but still rare. Most patients are elderly, presenting with abdominal discomfort or a mass, or weight loss and anorexia. Imaging studies may suggest the diagnosis directly. A minority of cases are linked to anabolic steroid usage, vinyl chloride occupational exposure, inorganic arsenic (pesticides, historical medicinal), or thorotrast administration (a historical radiographic contrast). Pathology e there are typically multiple tumours within the liver, ranging from microscopic to several centimetres. Individual tumour deposits are reddish and haemorrhagic. Microscopically, there is little stroma. The malignant cells may seep between, disrupt and replace the liver cell plates, or they may grow in solid balls or in looser aggregates, the cells lining blood-lled lacunae. Identication of vascular endothelial markers with immunohistochemistry may be patchy because the cells can be very poorly differentiated, but conrms the diagnosis.

can occur at many different sites, including occasionally the liver. In liver, many of these lesions are an exuberant reaction to infection or occasionally some other immune trigger, but some (inammatory myobroblastic tumours) are believed to be benign neoplasms. Patients may present with hepatic pain and have systemic inammatory signs such as fever, weight loss and leucocytosis. There may be a history of sepsis. Pathologically, there is one or more well circumscribed grey or yellowish tumour masses. Microscopically, there are spindle shaped myobroblasts/broblasts with varying degrees of collagen, permeated with a dense inammatory cell inltrate of plasma cells, lymphocytes and some eosinophils. Microscopy can give a clue as to the nature of the lesion: in cases related to infection there may be numerous macrophages or abscess-like collections of neutrophils. Culture studies or histochemical stains may indicate infection directly. Immunohistochemistry to show ALK gene product overexpression can suggest a neoplastic diagnosis of inammatory myobroblastic tumour. A relative abundance of IgG4-positive plasma cells may suggest a diagnosis of systemic IgG4-related disease (which can also present with autoimmune pancreatitis or sclerosing cholangitis) e which is highly responsive to corticosteroids. A

Miscellaneous
Simple cyst (solitary bile duct cyst): a non-neoplastic and unilocular cyst comprising a thin brous wall lined with a single layer of bland columnar epithelium that encloses a volume of clear uid. Very occasionally they may become complicated with rupture, haemorrhage or infection. Angiomyolipoma: an unusual benign lesion that generally presents in middle-aged women and unlike its counterpart in kidney is only infrequently associated with tuberous sclerosis. The lesion comprises a characteristic admixture of adipose, smooth muscle and thick-walled vessels, aggregated together in varying proportions into a solid tumour-like mass which may become complicated with haemorrhage. Inammatory pseudotumours: a non-specic name that encompasses a confusingly heterogeneous group of lesions that
FURTHER READING Bioulac-Sage P, Cubel G, Balabaud C, Zucman-Rossi J. Revisiting the pathology of resected benign hepatocellular nodules using new immunohistochemical markers. Semin Liver Dis 2011; 31: 91e103. Goodman ZD, Terracciano L. Tumours and tumour-like lesions of the liver. In: Burt AD, Portmann BC, Ferrell LB, eds. MacSweens pathology of the liver. 5th edn. London: Elsevier, 2006; 761e814. Hamilton SR, Aaltonen LA. WHO classication of tumours: pathology and genetics of tumours of the digestive system. Lyon: IARC Press, 2000. International consensus group for hepatocellular neoplasia. Pathologic diagnosis of early hepatocellular carcinoma: report of the international consensus group for hepatocellular neoplasia. Hepatology 2009; 49: 658e64. Ishak KG, Goodman ZD, Stocker JT. Tumors of the liver and intrahepatic bile ducts. In: AFIP atlas of tumor pathology, 3rd series, fascicle 31. Washington DC: Armed Forces Institute of Pathology, 2001.

SURGERY 29:12

602

2011 Elsevier Ltd. All rights reserved.