2 Histopathologic Classification of Liver Pathologies CONTENTS 2.8.3 Fatty Liver 2.8.4 Wilson’s Disease 2.1 Benign and Malignant Nodular Hepatocellular 2.8.5 Primary Sclerosing Cholangitis Lesions 2.8.6 Cirrhosis 2.1.1 Regenerative Lesions 2.8.7 Primary Biliary Cirrhosis 2.1.2 Dysplastic or Neoplastic Lesions 2.8.8 Secondary Biliary Cirrhosis 2.2 Benign and Malignant Tumors of the Biliary 2.8.9 Reye’s Syndrome Tract 2.8.10 Caroli’s Syndrome 2.2.1 Bile Duct Adenoma 2.8.11 Liver Disease in Patients with Cystic Kidneys 2.2.2 Bile Duct Cystadenoma 2.8.12 Langerhans Cell Histiocytosis 2.2.3 Biliary Papillomatosis 2.8.13 Storage Diseases 2.2.4 Bile Duct Carcinoma (Cholangiocarcinoma) 2.8.14 Viral Hepatitis 2.2.5 Bile Duct Cystadenocarcinoma 2.8.15 Liver Disease in Congestive Heart Disease 2.2.6 Gallbladder Carcinoma 2.9 Vascular Changes 2.3 Benign Non-Epithelial Tumors 2.9.1 Thrombosis of the Portal Vein 2.3.1 Hemangioma 2.9.2 Obstruction of Smaller Portal Branches 2.3.2 Infantile Hemangioendothelioma 2.9.3 Budd-Chiari Syndrome 2.3.3 Lymphangioma 2.9.4 Veno-Occlusive Disease 2.3.4 Angiomyolipoma 2.9.5 Lobular or Segmental Atrophy 2.4 Malignant Non-Epithelial Tumors 2.9.6 Infarction / Ischemia 2.4.1 Angiosarcoma 2.1 0 HIV-associated Liver Diseases 2.4.2 Malignant Epitheloid Hemangioendothelioma 2.10.1 Kaposi’s Sarcoma 2.4.3 Undifferentiated (Embryonal) Sarcoma 2.10.2 Primary Lymphoma of the Liver 2.4.4 Rhabdomyosarcoma (Sarcoma Botryoides) 2.10.3 Cholangitis 2.4.5 Other Primary Sarcomas 2.10.4 Fungal Infections 2.4.6 Primary Lymphoma of the Liver 2.10.5 Protozoal Infections 2.5 Hepatoblastoma 2.10.6 Bacterial Infections 2.6 Tumor-like Lesions 2.1 1 Hepatic Trauma 2.6.1 Cysts 2.1 2 Metastases 2.6.2 Mesenchymal Hamartoma 2.12.1 Metastases of Colorectal Adenocarcinoma 2.6.3 Biliary Hamartoma 2.12.2 Metastases of Breast Carcinoma 2.6.4 Inflammatory Pseudotumor 2.12.3 Carcinoid Metastases 2.6.5 Other Tumor-like Lesions: Peliosis Hepatis 2.1 3 Infiltration of the Liver in Hematologic 2.7 Infectious Diseases of the Liver Diseases 2.7.1 Liver Abscess 2.13.1 Non-Hodgkin’s Lymphoma 2.7.2 Helminthic Infections 2.13.2 Hepatic Hodgkin’s Lymphoma 2.8 Parenchymal Disease 2.8.1 Hemochromatosis 2.8.2 Transfusional Iron Overload (Hemosiderosis) 18 MRI of the Liver 2.1 Benign and Malignant Nodular Hepatocellular Lesions 2.1.1 Regenerative Lesions Generally, a regenerative nodule is a well-circum- scribed area of parenchyma showing enlargement as a response to necrosis, altered circulation or other stimuli. Fig. 1. Cut surface of a nodular regenerative hyperplasia (NRH) 2.1.1.1 Monoacinar Regenerative Nodule A monoacinar regenerative nodule is a regenera- tive nodule limited to one portal tract. Usually, multiple nodules are found involving most of the liver. This is referred to as diffuse nodular hyper- plasia [184]. Diffuse Nodular Hyperplasia without Fibrous Septa (Nodular Regenerative Hyperplasia, NRH) Diffuse nodular hyperplasia can be subdivided in- to nodular regenerative hyperplasia in which no fi- brous septa can be found, or diffuse nodular hy- perplasia containing fibrous septa or occuring in coexisting cirrhosis. Nodular hyperplasia is defined by the presence Fig. 2. Nodular regenerative hyperplasia demonstrating a non- of non-neoplastic nodules that are not limited by neoplastic nodule with hyperplastic liver cells surrounded by at- fibrous septa (Fig. 1). The cells of the surrounding rophic parenchyma parenchyma are atrophic (Fig. 2). Nodular hyper- plasia is usually a regenerative response occurring after circulatory stress. Portal vein obstruction may be responsible for widespread hepatocellular atrophy and secondary hepatic arterial dilatation (Fig. 3). Increased arterial flow and possible hepa- totropic factors cause hepatocellular hyperplasia and nodule formation. Monoacinar regenerative nodules may also occur in cases of disturbed circulation, such as hepatic vein obstruction and circulation disor- ders of the sinusoids. However, the resulting nodules are less uniformly distributed and are accompanied by more congestion and fibrous septa. The term NRH was originally applied to livers with minimal or no parenchymal fibrosis. NRH can be found in up to 5% of the older population. A higher prevalence occurs in patients with con- comitant systemic diseases associated with vascu- Fig. 3. Histology of diffuse nodular regenerative hyperplasia with lopathy, such as polycythemia, rheumatoid arthri- demonstration of multiple nodules (arrows) surrounded by atro- tis and polyarteritis nodosa. phy in adjacent liver tissue caused by Budd-Chiari syndrome 2 • Histopathologic Classification of Liver Pathologies 19 Clinical symptoms, which aid the diagnosis in affected patients, include esophageal varices, splenomegaly, moderate increased alkaline phos- phatase and ascites [118, 176]. Diffuse Nodular Hyperplasia with Fibrous Septa or in Cirrhosis As described above, this lesion corresponds to nodular regenerative hyperplasia with concomi- tant fibrous septa, or which is superimposed on a previous hepatic cirrhosis [177, 184]. Fig. 4 . Nodular regenerative hyperplasia with a diffuse micro- nodular pattern 2.1.1.2 Multiacinar Regenerative Nodule 2.1.1.4 Cirrhotic Nodule (Monoacinar Cirrhotic Nodule/ A regenerative nodule involving more than one Multiacinar Cirrhotic Nodule) solitary portal tract is called a multiacinar regen- erative nodule. Normally, it presents in livers with Generally, a cirrhotic nodule is defined as a regen- pre-existing pathology such as cirrhosis, or in cas- erative nodule in which hepatocytes are partially es of severe disease of the portal veins, hepatic or completely surrounded by fibrous septa. It can veins, or sinusoids. Usually, multiple nodules oc- be subdivided according to its expansion. Thus, a cur within the liver and these can correspond to monoacinar cirrhotic nodule contains no more cirrhotic nodules if they are surrounded by fibrous than one terminal portal tract, whereas a multiaci- septa. If larger than most cirrhotic nodules of the nar cirrhotic nodule is composed of two or more same liver or measuring at least 5 mm in diameter, portal tracts. However, this definition is not in ac- multiacinar regenerative nodules are also called cordance with the classifications micronodule and large regenerative nodules or macroregenerative macronodule that exist in cirrhosis. This is usually nodules [172] (Fig. 4). defined by size with a division point at 3 mm in di- ameter [14]. 2.1.1.3 2.1.1.5 Lobar or Segmental Hyperplasia Focal Nodular Hyperplasia (FNH) Lobar or segmental hyperplasia is defined as the Focal nodular hyperplasia is defined as a nodule enlargement of an entire lobe or the major part of that consists of benign-appearing hepatocytes a lobe in one or several liver segments, while other which are accompanied by fibrous stroma and parts of the liver show atrophy, necrosis or fibrosis. which may contain ductules that form a character- This pathologic pattern has also been described as istic central stellate scar. It usually occurs in an atrophy-hypertrophy complex [71]. otherwise histologically normal or nearly normal Lobar or segmental hyperplasia may occur in liver. Budd-Chiari syndrome or in primary sclerosing Similar to adenoma (2.1.2.1), FNH is predomi- cholangitis involving the hepatic veins or bile nantly found in female patients. Although oral ducts. It introduces both a hyperplasia and an contraception does not seem to be causal, continu- atrophy or fibrosis into the liver parenchyma. As ous enlargement of lesions has been reported con- hyperplasia typically arises in regions with in- comitant with the taking of birth-control pills and creased blood flow in Budd-Chiari syndrome, during pregnancy [182]. the caudate lobe often presents as hyperplastic Multiple FNH occur in 10-20% of all cases because the drainage of this part of the liver is while an association with hemangioma occurs in usually independent of the main hepatic veins. 5-10% of cases [78, 107]. Normally lobar or segmental hyperplasia meas- Macroscopically, FNH shows septations and, in ures at least several centimeters in diameter but classical cases, a central scar. However, in up to consists of histologically normal liver cells 30% of all cases a central scar is not present. In [164]. contrast to fibrolamellar carcinoma (2.1.2.5), the 20 MRI of the Liver Fig. 5. Focal nodular hyperplasia consists of liver nodules which Fig. 6. Histology of focal nodular hyperplasia demonstrating are separated by fibrous septa (arrows). Bile ducts, sometimes nu- Kupffer cells (arrows) merous, are always present at the interface between liver nodules and septa. scar is not a true one, but rather congeries of blood often resembles adenoma. The teleangiectatic type vessels and bile ducts and sometimes a focal area presents with atrophic hepatic plates separated by of cirrhosis.An elevated fat- and glycogen-content dilated sinusoids. Short fibrous septa and bile-duct can often be demonstrated. FNH is thought to de- proliferation is always found in teleangiectatic FNH. rive from an initial regional vascular arterio- FNH with cytologic atypia typically exhibit the venous (AV) malformation which undergoes con- appearance of classic FNH, but contain areas of secutive localized overgrowth of all liver con- cell dysplasia. stituents. Thus, histologically, FNH consists of ab- Mixed hyperplastic and adenomatous FNH normally arranged normal liver cells (Fig. 5). In presents features of the teleangiectatic type as well contrast to adenoma, small bile ductules that do as a resemblance to adenoma. not communicate with larger bile ducts are found. A so-called FNH syndrome is present if more Kupffer cells are also present although their func- than two FNH co-exist with intracerebral vascular tion is frequently deficient (Fig. 6). malformations, meningioma or astrocytoma. If FNH is currently divided into a classic and a any of the associated lesions are found in the pres- non-classic type.