Histopathological Changes in Liver in Autopsies

Abstract

Histopathological examination is one of the important ancillary investigations to be done in medicolegal autopsies, particularly in sudden and natural deaths. Some of the liver diseases are silent that can contribute to fatal events in the later stages. Liver is one of the common viscera received in the pathology laboratory for histopathological examination. The findings in the liver vary from nonspecific to specific, which may or may not contribute to the cause of death. The important prerequisite for the histopathological examination is preservation. A well-preserved specimen gives detailed morphological details when compared to the poorly preserved specimen.

1. Introduction

The liver is vulnerable to a number of injuries, which may be metabolic, microbial, toxic, or traumatic. Although liver is known for its vast regenerative capacity, many serious injuries cause permanent damage, which is beyond its regenerative ability. Most hepatic injuries can be diagnosed on histopathology using liver biopsy but many fatal conditions remain undiagnosed and are studied at autopsy. Hepatic injuries may be acute or chronic. The disease condition lasting more than six months is labeled as chronic [1]. Thus, liver autopsy serves as an eminent tool in helping pathologists reach a definitive diagnosis and forensic experts to specify the cause of death and to plan medical intervention [2]. Gross and microscopic examination of the autopsy specimen of liver gives clues about the underlying diseased conditions. Abnormal liver biopsies on histopathology often reveal—liver cirrhosis, infarcts, fatty change, glycogen storage disease, tuberculosis, acute poisoning, hemosiderosis, hyperemia, amyloidosis, abscess, syphilis, actinomycosis, hydatid cyst, and malignancy [3]. Alcohol abuse is one of the major causes of pathological liver diseases such as fatty liver, alcoholic cirrhosis, and hepatitis. These disease conditions may all be seen concomitantly in one patient [4].

Abnormal findings in liver autopsy can be fatty change, hepar lobatum, glycogen storage disease, acute phosphorus poisoning, hemosiderosis, syphilis, actinomycosis, infarcts, cloudy swelling, tuberculosis, acute passive hyperemia, chronic passive hyperemia, amyloidosis, abscess, hydatid cyst, malignancy, cirrhosis, and acute yellow atrophy [3].

Autopsy is usually performed in cases of road trauma accidents, railway accidents, burns, drowning, poisoning, tuberculosis, etc. A careful autopsy examination both gross and microscopic is required to study in depth the disease etiology and the site of origin to differentiate between primary and secondary liver diseases and to reach a definitive diagnosis. After conducting the gross study, the sections taken for microscopy are stained with hematoxylin and eosin (H&E), evaluated and then, appropriate special stains are applied, as the need may arise.

The morphological findings of the liver or part of a liver received after the post-mortem in the Department of Pathology are discussed in detail as under:

2. Hepatic cirrhosis

Hepatic cirrhosis is diagnosed on histopathology. The histopathological findings include the loss of normal architecture with loss of normal central-portal relationships [5]. The specimen examined must be large with several intact portal and central areas. Grossly and microscopically, it is characterized by the formation of nodules, as depicted in Figures 1–3.

Figure 1.

Mixed nodular cirrhosis of liver at autopsy. Cut section of the liver shows nodular appearance, size of each nodule varying from 1 mm to 10 mm. The normal architecture of the liver parenchyma has been distorted by these nodular formations.

Figure 2.

Micropictograph of a section of a liver depicting the cirrhosis characterized by loss of architecture and presence of regenerating nodules separated by bands of fibrosis (hematoxylin and eosin (H&E), 40×).

Figure 3.

The reticulin stain for reticular fibers depicting the connective tissue septa surrounding the regenerating nodules and the general increase in connective tissue fibers (fibrosis) (hematoxylin and eosin (H&E), 40×).

There are three main forms of hepatic cirrhosis according to the pathomorphological classification which classifies cirrhosis based on the diameter of the connective tissue nodes:

1. Micronodular form of hepatic cirrhosis (MNHC), where the diameter of connective tissue nodes is less than 3 millimeters (nodule size in the range of 1–3 mm);

2. Coarse nodular form of hepatic cirrhosis (CNHC) where the diameter of nodules is more than 3 mm; and

3. Mixed hepatic cirrhosis (MHC), which involves both small and large nodules in the liver parenchyma [3].

Morphological changes taking into consideration the severity of destructive and dystrophic changes in structure are used to classify the stage of liver failure. As per this concept, all deaths by hepatic cirrhosis can be divided into three groups, each of which corresponded to a certain stage of liver failure as follows:

1. Compensated stage of liver failure (CSLF) with initial morphological changes, where changes are seen only in the hepatoportal sections of the hepatic acini.

2. Decompensated stage of liver failure (DSLF) or a stage of pronounced changes, when destructive and dystrophic changes are detected throughout both the hepatoportal sections and hepatic tubules of the hepatic acini.

3. The end-stage of liver failure (ESLF), when during histological examination changes are seen in all three sections of the hepatic acini: hepatoportal, tubular, and the central vein area.

3. Hepatitis

It can be acute or chronic. In acute hepatitis, there may be focal/multifocal necrosis that does not follow a zonal pattern but involves random, individual clusters of hepatocytes. Acute hepatitis also includes ballooning degeneration of hepatocytes, lobular and sinusoidal inflammation, Kupffer cell hyperplasia, increased apoptotic bodies, and cholestasis. If this process lasts longer than six months, it is deemed chronic and often presents progressive fibrosis [6].

3.1 Chronic hepatitis

It is defined as a liver disease with persistent necro-inflammatory activity lasting more than six months. The most common causes of chronic hepatitis are viral, autoimmune, and drug-induced.

3.1.1 Gross findings

Liver may appear grossly normal in the early stages of chronic hepatitis. In later stages, the hepatic parenchyma is firm because of increased fibrosis. Cirrhosis due to viral hepatitis is generally macronodular.

3.1.2 Microscopic findings

In chronic hepatitis, there is focal necrosis of hepatocytes at the limiting plate between the portal tract connective tissue and the beginning of hepatic parenchyma with an associated lymphocytic infiltrate—called piecemeal necrosis or interface hepatitis, necrosis and fibrosis are seen in later stages.

In most cases of chronic hepatitis, there is portal inflammation characterized by the presence of a prominent inflammatory infiltrate consisting of lymphocytes with a variable number of plasma cells involving the portal tracts. Scattered macrophages, neutrophils, and eosinophils are typically a minor component of the infiltrate. Lymphoid follicles and germinal centers may be seen. Bile duct reaction may be seen at the periphery of the portal tract. Interface hepatitis, also known as piecemeal necrosis or periportal necrosis, is an important feature of chronic hepatitis. The lymphocytes and plasma cells of the inflammatory periportal infiltrate are closely associated with degenerating hepatocytes at the limiting plate. Hepatocytes, in areas of piecemeal necrosis, often undergo ballooning degeneration and appear pale and swollen with clumping of cytoplasm. Apoptotic bodies may also be seen in areas of active interface hepatitis. The periportal parenchyma is gradually destroyed and replaced by fibrosis. Hepatocyte necrosis in chronic hepatitis is variable in severity but usually spotty. Apoptotic hepatocytes (acidophil bodies) are scattered throughout the lobule. Mononuclear inflammatory cells cluster around injured hepatocytes and may obscure focal hepatocyte necrosis. Kupffer cells in these areas of spotty hepatocyte necrosis may contain phagocytosed cellular debris. Ballooning degeneration may be seen in the exacerbation of chronic viral hepatitis and may be associated with zone 3 cholestasis. Regeneration of hepatocytes is recognizable by the formation of liver cell plates that are two cells thick and by the formation of regenerating rosettes.

3.1.3 Fibrosis

Progressive fibrosis at the limiting plate as the result of continued necro-inflammatory activity leads to stellate enlargement of the portal tract. Portal-portal fibrous septa are the result of the linkage of adjacent fibrotic portal tracts. Portal central fibrous bridging can also develop generally from superimposed episodes of severe lobular necro-inflammatory activity involving zone 3. The end result of bridging fibrosis is cirrhosis, which is usually macronodular or mixed micro- and macronodular. Other hepatocyte changes seen in chronic hepatitis include steatosis, iron deposition, and oncocyte change. The scoring system based on the inflammation and lobular activity is used for grading chronic hepatitis, whereas staging depends upon the fibrosis as depicted in Table 1.

Grade
A. Portal inflammation and interface hepatitis
0	Absent or minimal
1	Portal inflammation only
2	Mild or localized interface hepatitis
3	Moderate or more extensive interface hepatitis
4	Severe and widespread interface hepatitis
B. Lobular activity
0	None
1	Inflammatory cells but no hepatocellular damage
2	Focal necrosis or apoptosis
3	Severe hepatocellular damage
4	Damage includes bridging confluent necrosis
Stage
0	No fibrosis
1	Fibrosis confined to portal tracts
2	Periportal or portal-portal septa but intact vascular relationships
3	Fibrosis with distorted structure but no obvious cirrhosis
4	Probable or definite cirrhosis

Table 1.

A simple scoring system for chronic hepatitis.

4. Chronic venous congestion

The hepatic manifestations due to circulatory compromise lead to venous congestion. Chronic venous congestion and centrilobular necrosis are commonly seen at autopsy because there is an element of preterminal circulatory failure with virtually every death [7]. Right-sided cardiac decompensation leads to passive congestion of the liver. The liver is slightly enlarged, tense, and cyanotic with round edges. The liver takes on a variegated mottled appearance, known traditionally as the ‘Nutmeg’ Liver. Microscopically, there is congestion of centrilobular sinusoids (Figure 4) [8]. Left-sided cardiac failure or shock may lead to hepatic hypoperfusion and hypoxia. The hepatocytes in the central region of the lobule undergo ischemic necrosis and centrilobular necrosis is visible microscopically as a slight depression of necrotic lobular centers. By microscopy, there is a sharp demarcation of viable hepatocytes in the periportal region versus necrotic hepatocytes in the centrilobular region of the parenchyma. Congestion alone, no matter how severe or prolonged, seems to do little if any damage to the liver. Centrilobular necrosis or ischemic hepatitis appears to result from hepatic hypoperfusion and mimics viral hepatitis [7].

Figure 4.

Light micrograph of a section through the liver with chronic venous congestion depicting red blood cells (RBCs) are phagocytosed by macrophages, which are called siderophages (depicted with arrows in A) and central vein and sinusoids are distended with RBCs along with the presence of fatty change (depicted with star in B).

5. Granulomatous lesions of liver

Granulomatous lesions of liver are seen in 2–10% liver biopsies [9]. These are seen in various systemic conditions or may be noticed as incidental findings in an otherwise normal liver biopsy. The structural liver damage is rarely caused by the granulomas themselves, but their detection can be the first indication of an underlying systemic disease.

5.1 Causes of hepatic granuloma

Granulomatous lesions of liver are associated with various disorders (Table 2). In the West, most common causes are sarcoidosis, drug-induced, tuberculosis, neoplastic disease, and primary biliary cholangitis [10].

Causes of granulomatous lesions in liver
Autoimmune diseases	Sarcoidosis; Primary biliary cirrhosis
Infections	Bacterial	Tuberculosis; Brucellosis; Secondary syphilis; Listeriosis; Mycobacterium avium complex; Lepromatous leprosy; Cat scratch fever; Leishmaniasis
	Viral	Cytomegalovirus; Hepatitis A, B, and C; Epstein-Barr virus
	Fungal	Histoplasmosis; Cryptococcus; Candidiasis; Nocardiosis; Coccidioidomycosis
	Parasitic	Schistosomiasis; Toxoplasmosis
Vasculitides	Polyarteritis nodosa; Churg-Strauss syndrome; Granulomatosis with polyangiitis
Drugs	Nitrofurantoin; Allopurinol; Phenytoin
Malignancy	Hodgkin’s lymphoma and non-Hodgkin’s lymphoma; Renal cell carcinoma; Hepatic metastases
Inherited	Chronic granulomatous diseases
Ingestion of foreign body	Mineral oil, talc, or starch
Metal toxicity	Copper toxicity; Berylliosis
Chronic gastrointestinal disease	Crohn’s disease
Idiopathic

Table 2.

Causes of granulomatous lesions in liver.

5.2 Histopathology

Granulomas are well-circumscribed lesions that are formed as a result of an inflammatory reaction. They have a central core of macrophages, with a surrounding rim that consists of lymphocytes, plasma cells, giant cells, and fibroblasts, as depicted in Figure 5. There are four main histological types of hepatic granulomas, which are described in Table 3.

Figure 5.

Photomicrograph of liver biopsy from a patient at autopsy showing epithelioid cell (A) and giant cell granulomas (B) (hematoxylin and eosin (H&E), 40×).

Histological variants of hepatic granulomas
S. no.	Variant	Histological feature	Causes
1.	Noncaseating	They do not have necrosis	Sarcoidosis
2.	Caseating	They have central core of caseous necrosis	Tuberculosis; Granulomatosis with polyangitis
3.	Fibrin-ring	The epithelioid cells surround a vacuole within an encircling fibrin ring	Hodgkin’s lymphoma, Leishmaniasis, Q fever, giant cell arteritis, allopurinol
4.	Lipogranulomas	These granulomas contain a central lipid vacuole	Ingestion of mineral oil, hepatic steatosis

Table 3.

The different histological variants of hepatic granulomas.

The granulomas are mostly located in the hepatic parenchyma but in certain conditions like primary biliary cholangitis, they are located in the portal tracts.

Special stains like acid-fast and fungal staining can be used for visualization of the concerned microorganisms in the liver biopsy, which can aid in reaching the diagnosis.

6. Liver abscess

Liver abscess is a pus-filled cavity in the liver which can develop due to any injury to the liver or any intra-abdominal infection which is disseminated through the portal circulation [11]. They can be categorized into pyogenic or amoebic, although a few of them can also be caused by parasites and fungi. Entamoeba histolytica is the main offending agent observed in amoebic liver abscess. Pyogenic abscess is most commonly caused by Escherichia coli (E.coli), Klebsiella, Streptococcus, Staphylococcus, and anaerobes.

Around 40–50 million people are annually infected with amoebic abscesses and the majority of infections occur in developing countries [12, 13]. The prevalence of infection in endemic areas is higher than 10% and in certain areas, it is reported to be as high as 55%. Amoebic liver abscesses are the most common extraintestinal manifestation of Entamoeba histolytica infection. The incidence of Pyogenic liver abscess in the USA is 2.3 per 1,00,000 [14]. Streptococcus milleri is the most common pathogen followed by Klebsiella pneumoniae found in Pyogenic liver abscess.

The abscess is formed mostly due to leakage from the bowel in the abdomen, which travels through the portal vein to the liver. Biliary tract infection, which has direct contact with liver, can also cause abscess.

The classification of liver abscesses can be done by various methods: One of the methods is by its location in the liver. Liver abscess is seen more commonly in the right lobe of the liver because of its blood supply as compared to the left liver lobe or caudate lobe. Another method is the cause of liver abscess. If it is infectious, then most of them can be classified into bacterial (amoebic) and parasitic (hydatiform cyst).

6.1 Pathogenesis

Pyogenic abscess is defined as a collection of pus which consists of many inflammatory cells, mainly neutrophils and tissue debris [15]. Necrosis is also associated with the infection. In amoebic liver abscess, hepatocyte cell death occurs either by apoptosis or by necrosis [16]. The inflammatory cells are absent due to the lysis of neutrophils by the protozoan, thus forming the nonpurulent ‘anchovy paste’ abscess [17]. Expansion of the abscess with cell death continues until the treatment of the patient starts.

7. Steatohepatitis

Nonalcoholic fatty liver disease (NAFLD) is one of the most common liver diseases in developed countries. It is defined as the accumulation of fat within liver cells in individuals who do not have a history of alcohol ingestion [18]. Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are diagnosed on the basis of histological findings of either fat alone, fat along with inflammation, fat with ballooning degeneration, or fat along with fibrosis and cirrhosis [19]. The prevalence and clinical outcome of these vary according to the histological category [20].

Nonalcoholic fatty liver disease (NAFLD) is commonly noted in obese individuals. Around 74–90% of liver biopsies of such individuals show fatty change [21]. Ludwig et al. coined the term NASH [22]. It is less aggressive as compared to alcoholic hepatitis but can progress through necro-inflammatory change and early fibrosis to cirrhosis [23].

8. Fatty liver

One of the common findings seen in the liver both in the autopsy and clinical settings is fatty liver or steatosis. It is frequently associated with alcohol abuse and also seen in nonalcoholic fatty liver disease (NAFLD), resulting in end-stage hepatic failure. Abnormal retention of fat vacuoles or triglycerides in hepatocytes leads to fatty change, which in turn constitutes liver disease. Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation in hepatic parenchyma (≥ 5%) in the absence of excessive alcohol intake (< 20 g/day). As per the World Health Organization (WHO), mortality related to alcohol consumption is 3.8% globally and the prevalence of nonalcoholic steatohepatitis in India ranges from 5 to 28% [24]. It is one of the frequent findings at autopsy, seen in all age groups [25]. The main etiological factors that constitute chronic liver disease worldwide are chronic alcohol abuse followed by virus-induced hepatitis and NAFLD [26]. The prevalence of fatty liver among the population depends upon the technique being used for the diagnosis, which can range from imaging to biopsy, each having different accuracy levels in different settings. It is considered a marker of other disorders that can be one of the causes of death. The twelfth leading cause of death in the USA is attributed to chronic liver diseases and cirrhosis, with NAFLD being rapidly increasing in the USA as well as in other developed worlds within this subcategory [27].

Steatosis is one of the most common findings seen microscopically and it can be microvesicular or macrovesicular, the latter being more common. Macrovesicular steatosis is characterized by the presence of a single fat vacuole in the hepatocyte that displaces the nucleus toward the edge, whereas in microvesicular steatosis, there are multiple small vacuoles in the cytoplasm with a centrally placed nucleus. The histological findings in fatty liver include the presence of steatosis that can range from mild to more severe forms along with lobular and/or portal inflammation, hepatocyte ballooning, and fibrosis that may vary in distribution, as shown in Figures 6 and 7.

Figure 6.

Gross photograph of the liver tissue illustrates the yellowish color of the liver parenchyma. The yellow color indicates high fat content in this tissue.

Figure 7.

Micropictograph of fatty change in hepatocytes with lipid vacuoles. In many cells, the nucleus is displaced to the periphery of the cell and the entire cytoplasm is taken up by the giant lipid vacuole (shown with arrow). (hematoxylin and eosin (H&E), 40×).

9. Structural abnormalities

Many chronic liver diseases may remain silent and may undergo undiagnosed during their lifetime. These diseases may be found as incidental findings during routine body checkup or investigations for other diseases or at autopsy. Liver abnormalities can be structural, congenital, or vascular or abnormalities of the bile duct [28].

The major congenital abnormalities of liver are listed in Table 4.

(A) Structural abnormalities of liver
S. no	Abnormality	Features
a.	Agenesis/absence of liver	Autopsy finding in stillbirths
b.	Agenesis of lobe of liver
c.	Hypoplasia of right lobe	Is a rare condition, can be seen associated with suprahepatic or retrohepatic gallbladder
d.	Situs inversus totalis or abdominalis	Characterized by abnormal position of the liver in left hypochondrium
e.	Riedel lobe	Accessory hepatic lobe seen as a tongue-like projection from the right lobe
f.	Ectopic hepatic tissue	Found in suspensory ligaments of the liver, lung, wall of the gallbladder, splenic capsule, greater omentum, etc.
(B) Vascular anomalies that can involve portal vein or hepatic artery are:
a.	Preduodenal portal vein	Can result in duodenal obstruction, causing gastric outlet obstruction in adults
b.	Aberrant hepatic arteries	Can be present in association with biliary atresia
(B) Vascular anomalies that can involve portal vein or hepatic artery are:
S. No	Abnormality	Features
c.	Presence of obstructing valves within splenic vein or portal vein	Is a rare cause of portal hypertension in children
d.	Duplication of portal vein
e.	Atresia/hypoplasia of portal vein	It may involve the entire length or part of a vessel
f.	Congenital absence of portal vein	Is a rare entity in children, with a few cases also having been reported in adults
g.	Portal cavernoma	Also known as cavernous transformation of portal vein characterized by the replacement of vein by trabeculated venous lake that are spongy and extend to gastroduodenal ligament
h.	Congenital shunts	Can be portohepatic, portocaval, or between left portal vein and internal mammary veins
(C) Anomalies involving bile duct are listed
S. No	Abnormality	Features
a.	Agenesis of the common bile duct	Is a rare entity
b.	Agenesis of the common hepatic duct	Obstructive jaundice is a common presenting complaint
c.	Anomalous insertion of the right hepatic duct	Is also a rare entity
d.	Anomalous (‘accessory’) bile ducts
e.	Duplication of the bile ducts	One duct may empty into the pylorus or both may drain into the duodenum
f.	Ciliated hepatic foregut cyst	Is a rare entity, more common in men, involving the medial segment of the left hepatic lobe.

Table 4.

The major congenital abnormalities of liver.

10. Nodules

Nodules in the liver can be found as an incidental finding at autopsy. These nodules may vary in size and may occur singly or as multiple lesions. The nodular lesions in liver may be benign or malignant. The differential diagnosis of benign nodules includes hepatic hemangioma, hepatocellular adenoma, regenerative nodules, hepatic cyst, focal nodular hyperplasia, liver abscess, compensatory hyperplasia, focal fatty change, whereas the malignant lesions include hepatocellular carcinoma, dysplastic nodules, cholangiocarcinoma, liver metastasis, and rarely lymphoma.

11. Alcoholic liver disease and nonalcoholic fatty liver disease

Alcohol-associated liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) are significant global health issues. These two conditions share similar pathological characteristics, encompassing a spectrum from simple hepatic steatosis to steatohepatitis, liver cirrhosis, and hepatocellular carcinoma [29]. Alcohol-associated liver disease (ALD) alone accounts for 5.1% of all worldwide disease and injury burdens, often resulting in earlier mortality and disability compared to other chronic liver injuries [30]. Nonalcoholic fatty liver disease (NAFLD) is diagnosed clinically and is characterized by the presence of 5% or more hepatic steatosis, as determined by liver imaging or biopsy, in the absence of secondary causes of hepatic fat accumulation (such as alcohol, hepatitis C virus (HCV), Wilson’s disease, medications, etc.). It is a metabolic disorder influenced by hormonal, nutritional, and genetic factors [31].

Gross features of ALD:

• Early stage: enlarged, soft, greasy, yellow liver

• Late stage: shrunken, mottled, red-brown liver with bile staining

• End-stage: cirrhosis

Histopathological findings:

• Steatosis (accumulation of fat)

• Zone 3 injury pattern

• Ballooning degeneration

• Lobular inflammatory infiltrates, particularly rich in neutrophils

• Mallory hyaline

• Perivenular fibrosis

• Pericellular fibrosis

• Bile ductular reaction [32]

The fatty degeneration of liver cells occurs to a greater degree in NAFLD than in ALD. In contrast, inflammatory cell infiltration is more pronounced in ALD than in NAFLD. Furthermore, venous or perivenular fibrosis, phlebosclerosis, and (less commonly) lymphocytic phlebitis are more common in ALD than in NAFLD [29].

12. Leukemic infiltrates

Hematopoietic tumors of the liver are infrequently encountered by practicing pathologists due to the rarity of primary hepatic lesions and the fact that many cases of leukemia and lymphoma involving the liver are not biopsied [33]. While hepatic involvement in acute leukemia is typically mild and asymptomatic during diagnosis, a post-mortem study revealed liver infiltration in over 95% of acute lymphoblastic leukemia (ALL) cases and up to 75% of acute myeloid leukemia (AML) cases. Massive infiltration of leukemic cells in the liver can manifest as fulminant hepatic failure [34].

In almost all cases, myeloid tumors of the liver indicate hepatic involvement by myeloid leukemias, although rare instances of hepatic myeloid sarcomas have been reported. In the chronic phase, approximately 50% of chronic myeloid leukemia (CML) patients show mild to moderate hepatomegaly at presentation, without liver function abnormalities. However, during blastic crisis, sinusoidal infiltration of immature cells may lead to liver enlargement and elevated serum alkaline phosphatase (ALP) levels.

Primary hepatic lymphoma is a rare form of liver malignancy. The most common subtype is diffuse large B-cell lymphoma, a type of non-Hodgkin’s lymphoma that frequently occurs outside of lymph nodes. Hepatic involvement with lymphoma cells and hepatomegaly is more common in non-Hodgkin’s lymphoma (NHL) compared to Hodgkin’s lymphoma (HL), with 16–43% of NHL cases showing liver involvement. Extrahepatic obstruction is also more prevalent in NHL compared to HL. Liver infiltration by malignant cells has been reported in 14% of HL patients. Hepatomegaly is found in 9% of patients with stage I-II disease and in 45% of patients with stage III-I disease [34].

Another rare subtype is hepatosplenic T-cell lymphoma, which primarily affects young adult males.

Patterns of hepatic involvement in important leukemic infiltrates include:

• Acute myeloid leukemia-Sinusoids, portal tracts, and even individual hepatocytes. If the infiltrate forms a distinct mass that disrupts the hepatic architecture, it is termed a myeloid sarcoma.

• Acute lymphoblastic leukemia-Portal tracts.

• Chronic myelogenous leukemia-Distension of hepatic sinusoids by neoplastic cells, although variable-sized infiltrates in the portal tracts can also be present.

• Hepatosplenic T-cell lymphoma is characterized by sinusoidal infiltration by uniform medium-sized lymphocytes [33].

13. Metastasis

The liver is a common site for cancer metastasis, accounting for approximately 25% of all cases. Metastatic carcinomas are more frequently encountered than primary liver tumors. The presence of hepatic metastases increases the morbidity and mortality of patients with primary tumors in other sites, including the colon, breast, pancreas, lung, kidney, and stomach. The dual blood supply of the liver makes it susceptible to metastasis from gastrointestinal cancers and allows for interventional therapies. However, metastases are relatively uncommon in cirrhotic livers [35].

They typically appear as discrete and well-demarcated lesions, both grossly and histologically, separate from the surrounding liver tissue often with a hyperemic rim and can be single or multiple. In some cases, they may display infiltrative growth, resembling intrahepatic cholangiocarcinoma or hepatocellular carcinoma (HCC). Diffuse infiltrative patterns can also resemble primary liver tumors [32].

14. Carcinoma

Hepatocellular carcinoma (HCC) is the primary tumor that originates in the liver and accounts for over 90% of all primary liver tumors. It is currently the fifth most common cancer worldwide. Among men, HCC is the second leading cause of cancer-related deaths following lung cancer. The major risk factors for hepatocellular carcinoma include viral hepatitis (hepatitis B and hepatitis C), alcoholic liver disease, and nonalcoholic fatty liver disease (NAFLD) or steatohepatitis [36].

Gross pathology:

• Nodules that are soft, yellow-green, or reddish in color

• Variable sizes, ranging from small to large

• Different types, including solitary, multinodular, and diffuse

Histopathology:

Three classic patterns: trabecular, acinar, and solid

• Trabecular pattern: thick cords lined by flat endothelial cells, lacking Kupffer cells

• Acinar pattern: central degeneration of solid trabeculae, leading to pseudoglandular spaces containing colloid-like material or bile; may also involve dilated canaliculi

• Solid pattern: resulting from compression artifacts or scarring; the least common of the three patterns

The cytological features of HCC depend on the level of hepatocyte differentiation, ranging from well differentiated to poorly differentiated.

15. Conclusion

The liver is a common site for various diseases, of which many are symptomatic, whereas others may remain silent or asymptomatic and a few are found only at autopsy. Having a vast reserve, many liver diseases remain silent most of the time. Thus, the histopathological study of liver specimens at post-mortem examination is an important learning modality for both pathologists and clinicians to study silent liver diseases, to further improve the clinical and diagnostic approach toward diseases of the liver.