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WHO Classification of Tumours
Secondary tumours of the liver and intrahepatic bile ducts


Definition
Malignant neoplasms that have metastasized to the liver from extrahepatic primary tumours.

Epidemiology
Metastases predominate over primary hepatic tumours in a ratio of 40 : 1 in Europe and North America 1
Berge T, Lundberg S (1977). Cancer in Malmo. Acta Pathol Microbiol Scand S250: 140-149.

2
Pickren JW, Tsukada Y, Lane WW (1982). Liver metastases: analysis of autopsy data. In: Liver Metastases. Weiss L, Gilbert HA, eds. Hall Medical Publishers: Boston, pp. 2-18.

and by 2.6 : 1 in Japan 3
Pickren JW, Tsukada Y, Lane WW (1982). Liver metastases: analysis of autopsy data. In: Liver Metastases. Weiss L, Gilbert HA, eds. Hall Medical Publishers: Boston, pp. 2-18.

. In contrast, primary hepatic tumours are more common than metastases in south-east Asia and sub-Saharan Africa

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Motola-Kuba D, Zamora-Valdés D, Uribe M, Méndez-Sánchez N (2006)
Hepatocellular carcinoma. An overview.
Ann Hepatol 5: 16-24



owing to the high incidence of hepatocellular carcinoma (HCC), shorter life expectancy (common extrahepatic carcinomas affect older age groups) and the low incidence of certain tumour types (e.g. carcinomas of the lung and colorectum). Autopsy studies in Japan and the USA have shown that up to 40% of patients with an extrahepatic primary tumour have hepatic metastases
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Craig JR, Peters RL, and Edmondson HA
Tumours of the Liver and Intrahepatic Bile Ducts
Armed Forces Institute of Pathology
Washington, DC. 1989




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Disibio G, French SW (2008)
Metastatic patterns of cancers: results from a large autopsy study.
Arch Pathol Lab Med 132: 931-9



4
Pickren JW, Tsukada Y, Lane WW (1982). Liver metastases: analysis of autopsy data. In: Liver Metastases. Weiss L, Gilbert HA, eds. Hall Medical Publishers: Boston, pp. 2-18.

.

Etiopathology
The liver has a rich systemic (arterial) and portal (venous) blood supply, providing a fertile environment for entrapping circulating neoplastic cells. The arrest of such cells is controlled by Kupffer cells in the sinusoids

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Bayón LG, Izquierdo MA, Sirovich I, van Rooijen N, Beelen RH, Meijer S (1996)
Role of Kupffer cells in arresting circulating tumor cells and controlling metastatic growth in the liver.
Hepatology 23: 1224-31




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Kan Z, Ivancev K, Lunderquist A, McCuskey PA, McCuskey RS, Wallace S (1995)
In vivo microscopy of hepatic metastases: dynamic observation of tumor cell invasion and interaction with Kupffer cells.
Hepatology 21: 487-94



and may be enhanced by growth factors such as transforming growth factor α (TGFα)
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Wang N, Thuraisingam T, Fallavollita L, Ding A, Radzioch D, Brodt P (2006)
The secretory leukocyte protease inhibitor is a type 1 insulin-like growth factor receptor-regulated protein that protects against liver metastasis by attenuating the host proinflammatory response.
Cancer Res 66: 3062-70



, tumour necrosis factor (TNF)
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Kitakata H, Nemoto-Sasaki Y, Takahashi Y, Kondo T, Mai M, Mukaida N (2002)
Essential roles of tumor necrosis factor receptor p55 in liver metastasis of intrasplenic administration of colon 26 cells.
Cancer Res 62: 6682-7



, or insulin-like growth factor-1 (IGF- 1)
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Nakamura M, Miyamoto S, Maeda H, Zhang SC, Sangai T, Ishii G, Hasebe T, Endoh Y, Saito N, Asaka M, Ochiai A (2004)
Low levels of insulin-like growth factor type 1 receptor expression at cancer cell membrane predict liver metastasis in Dukes' C human colorectal cancers.
Clin Cancer Res 10: 8434-41



, chemokines such as CXCR4
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Gassmann P, Haier J, Schlüter K, Domikowsky B, Wendel C, Wiesner U, Kubitza R, Engers R, Schneider SW, Homey B, Müller A (2009)
CXCR4 regulates the early extravasation of metastatic tumor cells in vivo.
Neoplasia 11: 651-61



and adhesion molecules such as integrin αb6
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Yang GY, Xu KS, Pan ZQ, Zhang ZY, Mi YT, Wang JS, Chen R, Niu J (2008)
Integrin alpha v beta 6 mediates the potential for colon cancer cells to colonize in and metastasize to the liver.
Cancer Sci 99: 879-87



. As tumour deposits enlarge, they induce angiogenesis using native sinusoidal endothelium, thus enhancing their chances of survival
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Gervaz P, Scholl B, Mainguene C, Poitry S, Gillet M, Wexner S (2000)
Angiogenesis of liver metastases: role of sinusoidal endothelial cells.
Dis Colon Rectum 43: 980-6



. Most metastases from unpaired abdominal organs reach the liver via the portal vein, and from other sites via the systemic arterial circulation. Lymphatic spread is less common and extension to the liver via the peritoneal fluid is rare
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Craig JR, Peters RL, and Edmondson HA
Tumours of the Liver and Intrahepatic Bile Ducts
Armed Forces Institute of Pathology
Washington, DC. 1989



. Cirrhosis provides a measure of relative protection against seeding by secondary tumours
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Pereira-Lima JE, Lichtenfels E, Barbosa FS, Zettler CG, Kulczynski JM (2003)
Prevalence study of metastases in cirrhotic livers.
Hepatogastroenterology 50: 1490-5



. In contrast, experimental models suggest that steatohepatitis promotes metastatic formation
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VanSaun MN, Lee IK, Washington MK, Matrisian L, Gorden DL (2009)
High fat diet induced hepatic steatosis establishes a permissive microenvironment for colorectal metastases and promotes primary dysplasia in a murine model.
Am J Pathol 175: 355-64



, as does excess consumption of alcohol
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Maeda M, Nagawa H, Maeda T, Koike H, Kasai H (1998)
Alcohol consumption enhances liver metastasis in colorectal carcinoma patients.
Cancer 83: 1483-8



. In most patients, metastases to the liver are a manifestation of systemic, disseminated disease. Colorectal carcinoma, neuroendocrine neoplasms, and renal cell carcinoma are exceptions, as these neoplasms sometimes produce isolated, even solitary, deposits
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Alves A, Adam R, Majno P, Delvart V, Azoulay D, Castaing D, Bismuth H (2003)
Hepatic resection for metastatic renal tumors: is it worthwhile?
Ann Surg Oncol 10: 705-10




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Mayo SC, Pawlik TM (2009)
Current management of colorectal hepatic metastasis.
Expert Rev Gastroenterol Hepatol 3: 131-44



.

Origin of the metastases
The most frequent secondary neoplasms of the liver are carcinomas followed by melanomas

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Disibio G, French SW (2008)
Metastatic patterns of cancers: results from a large autopsy study.
Arch Pathol Lab Med 132: 931-9




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Singh AD, Bergman L, Seregard S (2005)
Uveal melanoma: epidemiologic aspects.
Ophthalmol Clin North Am 18: 75-84, viii



. Hepatic involvement by lymphomas or sarcomas is uncommon
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Jaffe ES (1987)
Malignant lymphomas: pathology of hepatic involvement.
Semin Liver Dis 7: 257-68




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Loddenkemper C, Longerich T, Hummel M, Ernestus K, Anagnostopoulos I, Dienes HP, Schirmacher P, Stein H (2007)
Frequency and diagnostic patterns of lymphomas in liver biopsies with respect to the WHO classification.
Virchows Arch 450: 493-502




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Stavrou GA, Flemming P, Oldhafer KJ (2006)
Liver resection for metastasis due to malignant mesenchymal tumours.
HPB (Oxford) 8: 110-3



. In autopsy studies in North America and Europe, the frequency of hepatic metastases per primary site is greatest for testicular, ocular (uveal melanoma) and pancreaticobiliary cancers. Breast, lung and colorectal carcinomas also frequently metastasize to the liver
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Disibio G, French SW (2008)
Metastatic patterns of cancers: results from a large autopsy study.
Arch Pathol Lab Med 132: 931-9



. In terms of absolute numbers, the most common metastases to the liver are derived from breast, colorectal and gastric carcinomas
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Disibio G, French SW (2008)
Metastatic patterns of cancers: results from a large autopsy study.
Arch Pathol Lab Med 132: 931-9



. Hodgkin and non-Hodgkin lymphomas may involve the liver in up to 20% of patients at presentation and 55% at autopsy
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Jaffe ES (1987)
Malignant lymphomas: pathology of hepatic involvement.
Semin Liver Dis 7: 257-68



. Only 6% of patients with sarcoma may have hepatic metastases at presentation, but 34% have hepatic metastases at autopsy
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Jaques DP, Coit DG, Casper ES, Brennan MF (1995)
Hepatic metastases from soft-tissue sarcoma.
Ann Surg 221: 392-7



.

Clinical features
Signs and symptoms
In many patients, the presence of a hepatic metastasis is asymptomatic. Patients with symptomatic hepatic metastases often present with ascites, hepatomegaly or abdominal fullness, hepatic pain, jaundice, anorexia, and weight loss. There may be constitutional symptoms, such as malaise, fatigue and fever

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Shafqat A, Merchant M, Malik IA (1996)
Clinico-pathological features and survival of patients presenting with hepatic metastases: a retrospective analysis.
J Pak Med Assoc 46: 99-102



. On examination, nodules or a mass are felt in up to 50% of cases, and a friction bruit may be heard on auscultation. Symptomatic presentation is associated with bulky, rapidly progressing tumours with a poor prognosis
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Shafqat A, Merchant M, Malik IA (1996)
Clinico-pathological features and survival of patients presenting with hepatic metastases: a retrospective analysis.
J Pak Med Assoc 46: 99-102



. Rarely, patients present with fulminant hepatic failure
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Rajvanshi P, Kowdley KV, Hirota WK, Meyers JB, Keeffe EB (2005)
Fulminant hepatic failure secondary to neoplastic infiltration of the liver.
J Clin Gastroenterol 39: 339-43



caused by diffuse infiltration of the liver, most often seen in association with metastatic small cell carcinoma. Patients with functioning neuroendocrine carcinomas that metastasize to the liver may present with carcinoid syndrome
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Bendelow J, Apps E, Jones LE, Poston GJ (2008)
Carcinoid syndrome.
Eur J Surg Oncol 34: 289-96



. "Carcinomatous cirrhosis" with jaundice, ascites, and bleeding varices due to diffuse infiltration of the liver has also been described
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Sass DA, Clark K, Grzybicki D, Rabinovitz M, Shaw-Stiffel TA (2007)
Diffuse desmoplastic metastatic breast cancer simulating cirrhosis with severe portal hypertension: a case of "pseudocirrhosis".
Dig Dis Sci 52: 749-52



.

Laboratory studies
Levels of alkaline phosphatase and serum transaminase, although nonspecific, are elevated in about 80% and 67% of patients respectively, and probably represent the effects of hepatic parenchymal infiltration by the tumour and of generalized wasting. Elevated levels of lactic dehydrogenase are relatively specific for the presence of metastatic melanoma. Tests of synthetic function, e.g. prothrombin time and levels of serum albumin, may be normal despite extensive metastatic involvement. Levels of α-fetoprotein (AFP) may be slightly to moderately elevated, but very high concentrations are more consistent with a diagnosis of HCC

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Zhou L, Liu J, Luo F (2006)
Serum tumor markers for detection of hepatocellular carcinoma.
World J Gastroenterol 12: 1175-81



. Levels of carcinoembryonic antigen (CEA), which are raised in as many as 90% of patients with metastases from colorectal carcinoma, can be useful in monitoring patients after resection of the primary tumour, together with routine clinical and imaging follow-up studies
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Tan E, Gouvas N, Nicholls RJ, Ziprin P, Xynos E, Tekkis PP (2009)
Diagnostic precision of carcinoembryonic antigen in the detection of recurrence of colorectal cancer.
Surg Oncol 18: 15-24



.

Imaging studies
Ultrasound can identify tumours measuring 1–2 cm in size, differentiate solid from cystic lesions, and provide guidance for percutaneous needle biopsy. However, it provides poor anatomical definition and frequently misses smaller lesions. Computed tomography (CT), using contrasted and non-contrasted images, can also serve as a screening tool. The administration of intravenous contrast permits the detection of tumours as small as 0.5 cm in diameter

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Sitzmann JV, Coleman J, Pitt HA, Zerhouni E, Fishman E, Kaufman SL, Order S, Grochow LB, Cameron JL (1990)
Preoperative assessment of malignant hepatic tumors.
Am J Surg 159: 137-42; discussion 142-3



. Most metastases display decreased vascularity in comparison to the surrounding hepatic parenchyma and thus appear as hypodense defects. Tumours that are hypervascular (e.g. melanoma, carcinoids and some breast cancers) or calcified (e.g. colorectal carcinoma) are better delineated by noncontrast views. Magnetic resonance imaging (MRI) is more sensitive than CT in the detection of hepatic tumours and can detect additional lesions, too small to be seen via CT. Positron emission tomography (PET) can detect metastatic disease in the liver and elsewhere. The radiolabelled glucose analogue 2-(18)fluoro- 2-deoxy-D-glucose (F-18 FDG) can be used with PET to highlight metabolically active tissues. Through co-registration with anatomical studies like CT or MRI, viable malignant tumours can be differentiated from benign or necrotic lesions
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Andersson JL, Sundin A, Valind S (1995)
A method for coregistration of PET and MR brain images.
J Nucl Med 36: 1307-15



. However, a high rate of false-negatives has been shown for PET when evaluating mucinous carcinomas
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Berger KL, Nicholson SA, Dehdashti F, Siegel BA (2000)
FDG PET evaluation of mucinous neoplasms: correlation of FDG uptake with histopathologic features.
AJR Am J Roentgenol 174: 1005-8



.
Preoperative CT arterial portography or intraoperative ultrasound is associated with the highest sensitivities

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Soyer P, Levesque M, Elias D, Zeitoun G, Roche A (1992)
Detection of liver metastases from colorectal cancer: comparison of intraoperative US and CT during arterial portography.
Radiology 183: 541-4



. The former is capable of detecting lesions of 15 mm, although a false-positive rate of 17% has been reported
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Soyer P, Bluemke DA, Hruban RH, Sitzmann JV, Fishman EK (1994)
Hepatic metastases from colorectal cancer: detection and false-positive findings with helical CT during arterial portography.
Radiology 193: 71-4



. Its success relies on the fact that tumours are not fed by portal-vein blood, so that metastases appear as filling defects. Intraoperative ultrasound, capable of detecting lesions of 2–4 mm in diameter, delineates the anatomical location of tumours in relationship to major vascular and biliary structures and provides guidance for intraoperative needle biopsies. It is the definitive step for determining resectability at the time of exploratory laparotomy or laparoscopy. Although the use of angiography has declined in recent years, it is helpful in defining vascular anatomy for planned hepatic resections, selective chemotherapy, chemo-embolization, or devascularization procedures, for assessing whether there is metastatic involvement of the portal venous system and/or hepatic veins, or for differentiating between benign and malignant vascular lesions when other imaging studies have yielded equivocal results.

Macroscopy
Some studies suggest that right-sided colon cancers predominantly metastasize to the right lobe of the liver, while leftsided colon cancers metastasize to both lobes, supporting the existence of the "streaming" effect in the portal vein

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Konopke R, Distler M, Ludwig S, Kersting S (2008)
Location of liver metastases reflects the site of the primary colorectal carcinoma.
Scand J Gastroenterol 43: 192-5



. Metastases may be multinodular, diffusely infiltrative, or solitary. Very large solitary metastases are most often seen in association with metastatic colorectal or renal cell carcinoma. Umbilication (a central depression on the surface of a metastatic deposit) is caused by necrosis or scarring and is typical of metastatic adenocarcinomas from the stomach, pancreas or colorectum. A vascular rim around the periphery of the metastatic lesion is often seen. Mucin-secreting adenocarcinomas appear as glistening, gelatinous masses, while well-differentiated keratinizing squamous cell carcinomas are granular. Metastatic carcinoid tumours are typically solid but can form pseudocysts
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Dent GA, Feldman JM (1984)
Pseudocystic liver metastases in patients with carcinoid tumors: report of three cases.
Am J Clin Pathol 82: 275-9



. Extensive haemorrhage is more frequently seen in metastatic choriocarcinoma, carcinomas of the thyroid or kidney, neuroendocrine neoplasms, or vascular leiomyosarcomas. Diffusely infiltrating neoplasms, such as small cell carcinoma, lymphoma and sarcoma may have a soft, opaque, fleshy appearance. Rarely, metastatic breast carcinoma can produce extensive fibrosis simulating cirrhosis. Calcification of hepatic metastases may be seen in association with a variety of primary neoplasms. In colon cancer, calcifications within hepatic metastases are associated with a better prognosis
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Easson AM, Barron PT, Cripps C, Hill G, Guindi M, Michaud C (1996)
Calcification in colorectal hepatic metastases correlates with longer survival.
J Surg Oncol 63: 221-5



.

Histopathology and differential diagnosis
Metastatic neoplasms to the liver are usually histologically similar to their primary tumour of origin and to related metastases at other organ sites.
Metastases arising from renal cell carcinoma, adrenocortical carcinoma or melanoma may mimic HCC, which can usually be distinguished by its trabecular structure and presence of sinusoids, absence of mucin secretion or desmoplastic stroma, bile production, and the demonstration of bile canaliculi by polyclonal CEA antisera (specific for a liver-cell origin). Other useful immunophenotypic features are the presence of liver export proteins (albumin, fibrinogen, α-1-antitrypsin) and expression of hepatocyte- paraffin-1 (HepPar1), AFP and the oncofetal protein glypican-3

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Kakar S, Gown AM, Goodman ZD, Ferrell LD (2007)
Best practices in diagnostic immunohistochemistry: hepatocellular carcinoma versus metastatic neoplasms.
Arch Pathol Lab Med 131: 1648-54



. Of note, AFP and glypican-3 also stain germ cell tumours, and glypican-3 can also be positive in melanoma. Moreover, AFP is expressed in only a minority of HCCs, and glypican-3 is often not positive in well-differentiated HCCs
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Ligato S, Mandich D, Cartun RW (2008)
Utility of glypican-3 in differentiating hepatocellular carcinoma from other primary and metastatic lesions in FNA of the liver: an immunocytochemical study.
Mod Pathol 21: 626-31




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Shafizadeh N, Ferrell LD, Kakar S (2008)
Utility and limitations of glypican-3 expression for the diagnosis of hepatocellular carcinoma at both ends of the differentiation spectrum.
Mod Pathol 21: 1011-8



. Adrenocortical carcinomas are typically positive for inhibin and melanA
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Murakata LA, Ishak KG, Nzeako UC (2000)
Clear cell carcinoma of the liver: a comparative immunohistochemical study with renal clear cell carcinoma.
Mod Pathol 13: 874-81




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Renshaw AA, Granter SR (1998)
A comparison of A103 and inhibin reactivity in adrenal cortical tumors: distinction from hepatocellular carcinoma and renal tumors.
Mod Pathol 11: 1160-4



, and renal cell carcinomas are typically positive for paired box gene 8/PAX8
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Tong GX, Yu WM, Beaubier NT, Weeden EM, Hamele-Bena D, Mansukhani MM, O'Toole KM (2009)
Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study.
Mod Pathol 22: 1218-27



. Amelanotic melanoma is easily identified by positive immunolabelling for S100 protein and HMB45
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Oien KA (2009)
Pathologic evaluation of unknown primary cancer.
Semin Oncol 36: 8-37



.
The distinction between cholangiocarcinoma and metastatic adenocarcinomas is much more difficult, if not impossible

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Leong AS, Sormunen RT, Tsui WM, Liew CT (1998)
Hep Par 1 and selected antibodies in the immunohistological distinction of hepatocellular carcinoma from cholangiocarcinoma, combined tumours and metastatic carcinoma.
Histopathology 33: 318-24




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Oien KA (2009)
Pathologic evaluation of unknown primary cancer.
Semin Oncol 36: 8-37



. The presence of high-grade intraepithelial neoplasia within intrahepatic bile ducts near an adenocarcinoma is strong evidence that the neoplasm is a primary cholangiocarcinoma; without this finding, panels of immunohistochemical stains are required.
Cholangiocarcinoma may assume any of the histological patterns of a metastatic adenocarcinoma; it is usually tubular but may be mucinous, signet-ring, papillary, cystic, or undifferentiated. Some metastases form reproducible patterns that may provide clues to their primary origin, e.g. small tubular or tubulo-papillary glands frequently derive from the pancreaticobiliary system, while a signet ring-cell appearance suggests a gastric or breast primary.
Perhaps the easiest pattern to recognize as metastatic in origin is that exhibited by adenocarcinomas of the colon and rectum, which nearly always show glands of variable size and shape, lined by tall columnar cells, with lumina containing abundant necrotic debris. Metastases from the colorectum frequently have welldefined edges whereas those from other glandular sites tend to be more diffuse. Of note, some metastatic colonic adenocarcinomas are associated with prominent intrabiliary ductal growth that mimics high-grade intraepithelial neoplasia of intrahepatic bile ducts

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Riopel MA, Klimstra DS, Godellas CV, Blumgart LH, Westra WH (1997)
Intrabiliary growth of metastatic colonic adenocarcinoma: a pattern of intrahepatic spread easily confused with primary neoplasia of the biliary tract.
Am J Surg Pathol 21: 1030-6



. Cholangiocarcinomas typically express keratins 7 and 19 but not 20, while colorectal carcinomas are typically negative for keratins 7 and 19 and positive for keratin 20
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Maeda T, Kajiyama K, Adachi E, Takenaka K, Sugimachi K, Tsuneyoshi M (1996)
The expression of cytokeratins 7, 19, and 20 in primary and metastatic carcinomas of the liver.
Mod Pathol 9: 901-9




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Rullier A, Le Bail B, Fawaz R, Blanc JF, Saric J, Bioulac-Sage P (2000)
Cytokeratin 7 and 20 expression in cholangiocarcinomas varies along the biliary tract but still differs from that in colorectal carcinoma metastasis.
Am J Surg Pathol 24: 870-6



. Nuclear positivity for CDX2 is also a marker for gastrointestinal origin
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Werling RW, Yaziji H, Bacchi CE, Gown AM (2003)
CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas.
Am J Surg Pathol 27: 303-10



. Metastases from the breast may be identified by immunostains for gross cystic disease fluid protein 15, estrogen and progesterone receptors
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O'Connell FP, Wang HH, Odze RD (2005)
Utility of immunohistochemistry in distinguishing primary adenocarcinomas from metastatic breast carcinomas in the gastrointestinal tract.
Arch Pathol Lab Med 129: 338-47



. Metastatic adenocarcinoma from the lung is typically positive for TTF1; however, occult breast or lung carcinoma with hepatic metastases as the initial presentation is rare. The same applies to squamous cell carcinomas of the oesophagus and cervix. In patients presenting with hepatic metastasis, the most common primary is a small cell carcinoma of the lung, characteristically producing an enlarged liver caused by diffuse infiltration
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Rajvanshi P, Kowdley KV, Hirota WK, Meyers JB, Keeffe EB (2005)
Fulminant hepatic failure secondary to neoplastic infiltration of the liver.
J Clin Gastroenterol 39: 339-43



.
Neuroendocrine/islet cell/carcinoid tumours are easily identified by their organoid nesting pattern, uniform cytology and vascularity, and positive immunostaining for chromogranin, synaptophysin and neuron-specific enolase. Islet cell tumours also produce specific hormones, e.g. insulin, glucagon, gastrin, vasoactive intestinal peptide and somatostatin, which either give rise to clinical syndromes or can be detected in the blood or tumour tissue. In some instances, the site of origin of the neuroendocrine neoplasm (e.g. gastrointestinal vs pulmonary) can be identified by nuclear positivity for CDX2 or TTF1, respectively

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Saqi A, Alexis D, Remotti F, Bhagat G (2005)
Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids.
Am J Clin Pathol 123: 394-404



.
Although uncommon, most sarcomas that metastasize to the liver are gastrointestinal stromal tumours (typically positive for CD34 and KIT) or uterine leiomyosarcomas (that may be positive for desmin or muscle-specific actin)

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Stavrou GA, Flemming P, Oldhafer KJ (2006)
Liver resection for metastasis due to malignant mesenchymal tumours.
HPB (Oxford) 8: 110-3



. Some carcinomas, notably of the kidney, may be sarcomatoid in their morphology. Sarcomatoid renal cell carcinomas nonetheless retain PAX8 expression
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Tong GX, Yu WM, Beaubier NT, Weeden EM, Hamele-Bena D, Mansukhani MM, O'Toole KM (2009)
Expression of PAX8 in normal and neoplastic renal tissues: an immunohistochemical study.
Mod Pathol 22: 1218-27



.
Leukaemias, myeloproliferative disorders, Hodgkin and non-Hodgkin lymphomas may involve the liver at advanced stages of disease. Leukaemias tend to produce diffuse sinusoidal infiltrates. Hodgkin and high-grade non-Hodgkin lymphomas produce tumour-like masses, while low-grade nonHodgkin lymphomas produce diffuse portal infiltrates

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Jaffe ES (1987)
Malignant lymphomas: pathology of hepatic involvement.
Semin Liver Dis 7: 257-68



.
Rarely, carcinomas of the thyroid, prostate and testis may metastasize to the liver. In these cases, the diagnosis can be confirmed by immunohistochemical detection of thyroglobulin, prostate-specific antigen and AFP and bHCG, respectively. Squamous cell carcinomas of the head and neck seldom involve the liver. The presence of a characteristic histological triad of features – proliferating bile ducts, leukocytes and focal sinusoidal dilatation – in a core biopsy suggests that a metastatic deposit (a space-occupying lesion) has been missed by the biopsy needle. Three lesions – bile duct adenoma, sclerosed haemangioma, and larval granuloma – may resemble metastatic tumours at laparotomy

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Yachida S, Iacobuzio-Donahue CA (2009)
The pathology and genetics of metastatic pancreatic cancer.
Arch Pathol Lab Med 133: 413-22



.

Prognosis
In most patients, the presence of hepatic metastasis indicates an advanced and disseminated stage of disease that precludes surgical intervention. However, for patients with colorectal carcinoma and low-burden metastatic disease, 5-year survival can be as high as 40%. Without surgical therapy, median survivals of < 12 months should be expected

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Bosman FT, Carneiro F, Hruban RH, Theise ND (Eds.)
WHO Classification of Tumours of the Digestive System.
4th Edition
International Agency for Research on Cancer: Lyon 2010



.







Christine Iacobuzio-Donahue
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Christine Iacobuzio-Donahue
Department of Pathology
The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions
Baltimore
USA




Linda Ferrell
Click to contact editor
Linda Ferrell
Department of Anatomic Pathology
University of California
San Francisco
USA





Frequency of metastasis to the liver according to site of the primary neoplasm.
Frequency of metastasis to the liver according to site of the primary neoplasm.

Metastatic colon carcinoma showing umbilication and hyperaemic borders.
Metastatic colon carcinoma showing umbilication and hyperaemic borders.

Metastatic small cell carcinoma of the lung forming innumerable small nodules.
Metastatic small cell carcinoma of the lung forming innumerable small nodules.

Metastatic large-intestinal carcinoma, cut surface.
Metastatic large-intestinal carcinoma, cut surface.

Metastatic large-intestinal carcinoma, cut surface.
Metastatic large-intestinal carcinoma, cut surface.

Metastatic colorectal carcinoma.
Metastatic colorectal carcinoma.