Diagnosis and Management of Benign Liver Tumors

• Common Benign Liver Tumors
• Solid Lesions
• Hemangioma
• Focal Nodular Hyperplasia
• Hepatocellular Adenoma
• Less Common Solid Benign Liver Tumors
• Cystic Lesions
• Hepatic Cyst
• Hepatobiliary Cystadenoma
• Diagnosis of Benign Liver Tumors
• Clinical Features
• Symptomatic Patients
• Asymptomatic Patient
• Diagnostic Tools
• Approach
• Management of Benign Tumors
• Indications for Surgery
• Bleeding Tumors
• Solitary Symptomatic Tumors
• Solitary Asymptomatic Tumor
• Multiple Lesions
• Principles of Surgery
• Which Approach Should Be Used?
• Which Procedure Should Be Employed?
• The Role of Liver Transplantation
• Conclusion
• References

Abstract

The widespread use of imaging modalities and the continuous improvement in their sensitivity have lead to an increasing number of incidental findings of focal liver masses, either solitary or multiple. Most of these so-called incidentalomas are benign and are discovered in healthy, asymptomatic patients. The main issue is to ensure the proper diagnosis, so that clear management recommendations can be provided. Surgery is rarely indicated in these circumstances. Infrequently, benign liver tumors are diagnosed because of symptoms or complications, and require urgent management including surgery as a major role in the cure. Due to better understanding of the clinical and pathological features of benign liver tumors, the increased accuracy of imaging tools, and improvement in surgical techniques (including laparoscopy), the management of these lesions has evolved. Here the clinical and biological features of the most common solid and cystic benign liver tumors are reviewed, and the key points of management focusing on the role of surgery, preventive or diagnostic, are addressed.

Benign liver tumors (BLT) are extremely frequent, varied, and mostly asymptomatic. Each cellular component of the liver (e.g., hepatocyte, biliary, endothelial, or other mesenchymal cells) can undergo benign proliferation, but only four lesions have common clinical relevance: hemangioma, focal nodular hyperplasia, hepatocellular adenoma, and hepatic cysts. The affected population usually consists of young women. Clinical management should take into account the symptoms, history, hormonal status (present and future), nature of the tumor, and psychological aspects.

The widespread use of highly sensitive imaging has led to an increasing incidence of focal liver masses, either solitary or multiple. In these so-called incidentalomas, the patient is healthy and asymptomatic; therefore, the major goal is to ensure the diagnosis so that clear management recommendations, including rare and strictly justified surgical options, may be provided. Infrequently, BLTs are diagnosed because of symptoms or complications, and surgery may play a major role in cure under these circumstances.

Nonetheless, for practitioners treating BLT, the initial step is to establish an accurate diagnosis. The next step is to decide on the proper management of the patient, based first on the symptoms, and second, on the nature of the tumor. To reach these goals, it is mandatory to (1) know the natural history of the various tumors and be familiar with their radiological behavior, and (2) consider the surgery guidelines for the particular indication. The operative procedures must be justified, be safe (with no mortality and minimal morbidity), involve no blood transfusions, be as minimally invasive as possible, and have no long-term aftereffects. Some useful considerations to keep in mind with regard to diagnosis and management of BLT are given in [Table 1].

Common Benign Liver Tumors

Solid Lesions

Hemangioma

Cavernous hemangiomas ([Fig. 1]) are the most common BLT, with an incidence of up to 20% in the general population, depending on the ultrasound studies[1] or autopsy series.[2] This usually small lesion is a congenital hamartomatous proliferation of vascular endothelial cells and may be multiple in 10% of cases.[3] The term “giant hemangioma” is used for any lesion over 5 cm, although this does not have any particular significance.

Hemangiomas are rarely symptomatic (pain due to necrosis, infarction, or thrombosis), except in cases involving large tumors (> 10 cm). Hemangiomas may increase in size during pregnancy[4] and shrink after menopause. Although estrogen receptors have been identified in certain tumors,[5] oral contraceptive (OC) intake is not a risk factor associated with the growth of hemangiomas.[6] Complications consist of spontaneous or posttraumatic rupture causing acute hemorrhagic shock in very rare circumstances; Kassabach-Meritt syndrome, including bleeding, thrombocytopenia, and coagulopathy; and Blumgart-Bornman-Terblanche syndrome, including fever and abdominal pain. Sclerosing hemangioma represents an involutive change in a cavernous hemangioma; its diagnosis by imaging can be difficult, requiring confirmatory pathological examination.[7] Angiomatosis is an extremely rare condition with multiple hemangiomas, which is commonly asymptomatic and associated with hemangiomas in the skin or other organs.

Focal Nodular Hyperplasia

Focal nodular hyperplasia (FNH) is the second most common solid BLT, occurring in up to 3% of the population.[8] FNH is considered to be a nonneoplastic lesion that is caused by a hyperplastic response to a congenital vascular malformation or a disruption in blood supply.[9] On pathology, FNH usually forms a firm, lobulated, and well-circumscribed lesion.[10] Macroscopically, the main feature is the presence of a central stellate scar from which fibrous septa emanate and divide the lesion into many nodules or pseudonodules ([Fig. 2]).

Focal nodular hyperplasia has a higher prevalence in women from their second to fourth decades.[9] [11] In 10 to 20% of cases, the lesions are multifocal, and up to 20% of FNH coexist with hemangiomas.[12] Oral contraceptive use is not involved in FNH formation, but its effects on FNH progression still remain controversial. According to World Health Organization (WHO) guidelines, OC intake should not be interrupted in women with FNH.[13] A history of treatment of pediatric cancers with chemotherapy or hematopoietic stem cell transplantation has also been reported as a risk factor for the development of FNH in children, among whom one third of the cases exhibit multifocal FNH.[14] [15]

Focal nodular hyperplasia has no malignant potential and usually remains stable or decreases in size over time. Less than 20% of patients with FNH develop symptoms. Spontaneous rupture and hemorrhage most likely do not exist, and most of the reports concerning bleeding are old case reports that involve misdiagnoses of telangiectatic FNH, which has been recently reclassified as inflammatory hepatic adenoma.[16]

Focal nodular hyperplasia occur mainly in normal liver and should be distinguished from FNH-like lesions, which occur in livers affected by alcoholic cirrhosis or vascular diseases, such as portal venous thrombosis, Budd-Chiari syndrome, and Rendu-Osler disease, in which FNH-like lesions are often multiple. In these cases, the major issue is to distinguish FNH-like nodules from hepatocellular carcinoma (HCC).

Nodular regenerative hyperplasia (NRH) corresponds to a diffuse transformation of normal hepatic parenchyma into small regenerative nodules, which are distinct from the nodules of cirrhosis or FNH.[17] One of the pathogenic hypotheses is that obliteration of the portal vein causes ischemia followed by hyperplasia of hepatic acini in response to the atrophy of hepatocytes in the central area.[18] [19] Numerous diseases and drugs have been reported to be associated with NRH, such as myeloproliferative or lymphoproliferative disorders, chronic vascular disorders, rheumatologic disorders, and use of steroids or chemotherapeutic agents.[20] Usually, NRH is discovered incidentally. However, patients may experience hepatomegaly, cholestatic symptoms, and symptoms of portal hypertension, such as ascites, splenomegaly, or esophageal varices.[20] [21] [22]

Hepatocellular Adenoma

Hepatocellular adenoma (HCA) is a very rare, benign hepatic neoplasia (incidence: 1/10⁶) that is usually identified as a well-defined, solitary lesion ([Fig. 3]). Hepatocellular adenoma occurs predominantly in childbearing women (M:F 1:8–15)[23] [24] and is related to endogenous or exogenous estrogen levels. High doses and long duration of OC, as well as pregnancy, are associated with a higher incidence of HCA,[25] whereas discontinuation of OC is associated with regression of HCA.[26] [27] [28] [29] The use of anabolic androgen steroids,[30] glycogen storage diseases (type I and III), and galactosemia also promote HCA, with a male preponderance.[31] Furthermore, HCAs associated with type I and type III glycogen storage diseases are more likely to be multifocal and to become malignant.[32]

The two main complications are spontaneous rupture with subsequent subcapsular or intraperitoneal bleeding and malignant transformation into HCC.[33] [34] Growth (∼20%) and rupture have been reported in pregnant women for a tumor size > 6.5 cm, occurring even during the postpartum course, although not all adenomas are hormone sensitive.[35] [36] The incidence of malignant transformation is estimated to be 5% (varies from 4–10%).[24] [37] [38] [39] [40] Several risk factors for this transformation have been identified: size > 5 cm, male gender, glycogen storage disease, androgen or steroid use, and β-catenin mutations.[33] [34] [39] [41]

Based on recent molecular[42] and immunohistochemical studies[43] and international guidelines,[44] HCA are now categorized into four subtypes based on genetic and pathological criteria: hepatocyte nuclear factor-1 α (HNF1-α) inactivated HCA (35–40%), β-catenin mutated HCA (10–15%), inflammatory HCA (> 50%) of which ∼ 10% have a β-catenin mutation, and unclassified HCAs (< 10%) lacking specific phenotypical markers. HNF1-α mutated adenomas are mostly found in women and are often histologically associated with intratumoral steatosis. Beta-catenin mutated adenomas are more often found in male patients, and are more frequently associated with the development of hepatocellular carcinoma.[45] Inflammatory HCAs are more often found in patients with a body mass index > 25 kg/m[2] [46] and with chronic alcohol consumption.[43] These tumors present a higher risk of hemorrhage and a slight risk of malignant transformation.[37] [46]

Hepatocellular carcinoma can be solitary or multiple, including vast numbers called adenomatosis (> 10 nodules of various sizes). Liver adenomatosis is a rare entity that was first described in 1985.[47] It is more frequently encountered in the HNF1-α-inactivated subgroup, but also presents in the inflammatory HCA subgroup, has a higher incidence in women (including 52% with a history of OC), and is associated with hepatic steatosis in 80% of the cases.[48] The complications are similar to those resulting from solitary adenomas and are not influenced by the number of lesions ([Fig. 4]).[37] [49]

Less Common Solid Benign Liver Tumors

An angiomyolipoma is a very rare hepatic tumor consisting of fat, epithelioid, and smooth muscle cells with thick-walled blood vessels. An association with tuberous sclerosis and renal angiolipomas are found in 10% of cases with a female preponderance.[50] The complications of this rare tumor include compressive effects due to its growth potential, and malignant transformation though this is much rarer than in the kidney.[51]

Hepatic lipoma is a homogeneous and well-defined lesion that is less common than angiomyolipoma. Background hepatic steatosis may be associated with hepatic lipoma in 50% of the cases.[52] These rare lesions must be distinguished from more frequent nontumor lesions, which are focal fatty lesions resulting from heterogeneous distribution of fat often located adjacent to the falciform ligament or in subcapsular areas.[53] The lesions may be associated with obesity, diabetes, alcoholism, steroids, total parental nutrition, chemotherapy, and antiretroviral therapy.

A mesenchymal hamartoma is another uncommon benign lesion, which is composed of bile ducts, immature mesenchymal cells, and hepatocytes and is usually diagnosed during childhood.[54] Benign biliary hamartomas, such as bile duct adenomas (also called peribiliary gland hamartoma), biliary adenofibromas and Von Meyenburg complexes are small, often subcapsular nodules. If the hamartomas are fortuitously discovered by surgeons, then pathologists must distinguish these tumors from adenocarcinoma metastases.

Cystic Lesions

Hepatic Cyst

Simple hepatic cysts (SHCs) are congenital biliary hepatic lesions that are thought to result from progressive dilatation of biliary microhamartomas. They do not communicate with the biliary tree. Based on recent data from imaging studies, the prevalence of these lesions is between 1.6 and 18%.[55] [56] [57] They are mostly found in women between 50 and 60 years of age.[58] [59] Rare complications, usually in very large cysts, include intracystic hemorrhage, compression of the biliary tree, vascular compression, visceral compression, rupture, secondary infection, and rarely cholangiocarcinoma.[60] [61] [62] [63] [64]

Multiple cysts are quite common, typically less than five small or medium cysts. This is distinct from polycystic liver disease (PCLD), which is an autosomal dominant genetic disease with a prevalence of less than 0.1%[65] characterized by the development of multiple macroscopic and microscopic cysts throughout the hepatic parenchyma ([Fig. 5]). These cysts are histopathologically similar to SHC, so PCLD is defined by the gross number of cysts. The most common form of PCLD is associated with autosomal-dominant polycystic kidney disease due to mutations of at least one of the following genes: PKD1 or PKD2.[66] The prevalence of combined disease ranges from 1 in 400 to 1 in 1,000 and represents ∼10% of all cases of end-stage renal failure.[67] Several factors are correlated with more extensive liver involvement: increasing age, female gender, and the severity of renal disease and renal dysfunction.[68] The second form is much rarer and occurs with liver-only involvement; in one third of cases, the disease is caused by mutations occurring in two other genes (PRKCSH and SEC63).[69] Repeat pregnancies and OC intake are associated with faster development of hepatic cysts,[68] [70] which could explain why massive hepatomegaly rarely occurs before the fourth decade[71] and why the prevalence and size of cysts are greater in women compared with men.[69] Approximately 80% of patients with PCLD are asymptomatic.[72]

Based on the number and size of the remnant liver parenchyma, Gigot et al described a classification of three types of PCLD, which is useful to guide the therapeutic approach: type I, large cysts; type II, localized disease; and type III, diffuse disease with small- and medium- size cysts.[73] A more recent classification added the symptoms that are related to PCLD.[74]

Hepatobiliary Cystadenoma

Hepatobiliary cystadenomas are uncommon, benign cystic neoplasms of the biliary system, and comprise less than 5% of all hepatobiliary cystic masses.[75] These arise more often within the liver (80%), but can affect the extrahepatic bile duct, and rarely, the gallbladder.[76] [77] [78] They can be serious, or more commonly, mucinous (called mucinous cystic neoplasms as of the last WHO classification), characterized by the presence of an ovarian-like stroma under the mucin-secreting epithelium.[79] These tumors are premalignant, and transformations into cystadenocarcinomas are not uncommon.[79] [80] [81]

Mucinous cystic neoplasms occur predominantly in women of middle age (40–60 years) and are usually discovered based on symptoms at a large size (> 10 cm).[79] Complications may occur due to mass effect and include obstructive jaundice, chronic cholecystitis, and cholelithiasis.[80] The serum CEA and CA19–9 concentrations are usually normal, but elevated levels should alert the physician to possible malignant transformation.

Diagnosis of Benign Liver Tumors

Clinical symptoms and patient history are crucial in determining the extent of the diagnostic workup. The diagnostic challenge is to distinguish between three types of lesions: tumors that must be removed, tumors that should be monitored, and tumors that may be ignored.

Clinical Features

Symptomatic Patients

In cases of pain or severe discomfort, the first step is to ensure these symptoms are related to the liver mass and to evaluate the severity of these symptoms, considering the psychological effect of the diagnosis of a liver tumor. Symptoms are usually related to large cysts, or necrotic/hemorrhagic adenomas. It is an exceptional case when focal nodular hyperplasia or hemangiomas cause symptoms. If the tumor is indeed symptomatic, surgical resection is most likely indicated, so that the preoperative diagnostic workup can be shortened—as histology will unlikely influence the decision. In cases of hemorrhagic or ruptured tumors, imaging investigations are less diagnostic than strategic, the goal being to plan the surgical procedure.

Asymptomatic Patient

Incidentalomas are increasingly frequent because of the development of imaging modalities. A common clinical discovery involves one or several focal lesions on an ultrasound (US) or computed tomography (CT) scan performed for reasons unrelated to the liver. Usually, the patient is a young woman, and the focal lesion is small. In other cases, the presentation is different; the tumor is large and multiple, and sometimes, different types of focal lesions are described.

The clinical interview should address the personal or familial history of malignancy and age-appropriate screening, past history of hepatitis or blood transfusions or intravenous drug use, and estrogen or progesterone use. Liver biochemistry (usually normal in cases of benign, uncomplicated tumors), viral serologies, and tumor markers are useful for excluding liver disease or with atypical presentations.

Diagnostic Tools

The diagnostic tools in this field principally involve US, contrast-enhanced CT scan, and magnetic resonance imaging (MRI).

Ultrasound is usually the first investigation that detects the focal mass. It is a simple and noninvasive technique to differentiate solid from cystic lesions and may be sufficient to establish the diagnosis of small hemangiomas or hepatic cysts. However, the diagnostic specificity for solid lesions is low even when improved by the use of color-flow Doppler or contrast US, which may add dynamic information regarding the lesions. Tripe-phase CT is an excellent modality for characterizing lesions, yielding specific signs in cases of large hemangiomas or FNH, but in many cases, this single modality is not sufficient for establishing the correct diagnosis. Magnetic resonance imaging is the best imaging modality in terms of specificity for diagnosing hepatic lesions, particularly when liver-specific contrast agents are utilized.[82] Usually, a combination of these exams provides sufficient clues to establish a definitive diagnosis. Positron emission tomography (PET), sulfur colloid, tagged red blood cells, and other modalities have been infrequently used, and their role requires further evaluation.

Approach

In symptomatic patients exhibiting acute signs due to hemorrhage, tumor necrosis, or experiencing discomfort caused by mass effects and compressive phenomena, a diagnostic workup is useful less for the decision to go to surgery than to determine the strategy that will allow for an adequate and safe surgical approach. In these cases, a CT scan is the standard. Generally, the combination of the clinical presentation, medical history, and CT scan renders the diagnosis obvious. For example, a young woman who presents with hemorrhagic solid lesions like suffers from adenoma, whereas a large cyst with dense, layering components has hemorrhaged into a simple cyst. If the clinical or radiological presentation is unusual,[83] the differential diagnosis includes different considerations. For solid lesions, HCC, fibrolamellar carcinoma, choriocarcinoma, or rare metastatic hypervascularized tumors (endocrine, breast metastasis, etc.) should be considered. For cystic lesions, hydatid cysts, cystadenocarcinoma, or cystic metastasis (gastrointestinal stromal tumors, endocrine tumors, etc.) should be considered. Male sex, severe pain, systemic symptoms, or abnormal liver biochemistry should increase the suspicion of malignancy and lead to further investigation.

For asymptomatic tumors, a combination of two to three imaging modalities usually makes the diagnosis: in greater than 70% of cases, a diagnosis of hemangioma, FNH, or hepatic cyst may be achieved with these noninvasive modalities ([Table 2]). Otherwise, a radiologist may suggest an atypical FNH or adenoma, or rare tumors such as angiomyolipomas, focal fatty nodules, pseudotumors, or granulomas because of nonspecific signs or because the suspected tumor is exceedingly rare.

In cases with an uncertain diagnosis or a neoplastic history, histological analysis is mandatory; thus, image-guided or laparoscopic biopsy, or operative resection should be considered.

Management of Benign Tumors

The management of BLT is still evolving because of several advances: (1) the improvement in diagnostic radiological imaging, which should reduce the prevalence of unnecessary liver resections; (2) recent histopathological and biomolecular findings, particularly concerning adenomas; (3) the widespread use and safety of laparoscopic surgery; and (4) improved identification and knowledge of the multiple lesions. The main challenge is to determine the indications for surgery, considering as usual, the risk–benefit ratio.

In fact, four types of surgery can be identified: life-saving surgery for emergency situations, symptomatic surgery for patients with pain or discomfort, preventive surgery for tumors presenting a high probability of complications, and diagnostic surgery for when the diagnostic workup fails to distinguish benign from malignant tumors. In the first two situations, the discussion concerns the modality of surgery; in the last two situations, the discussion focuses on clear indications.

Indications for Surgery

Bleeding Tumors

This clinical feature consists of an acute onset of abdominal pain related to a subcapsular giant hematoma and/or hemoperitoneum with hemorrhagic shock, generally caused by spontaneous rupture of an adenoma, or in exceptional cases, a hemangioma.

The first step is appropriate resuscitation in a monitored setting. Usually, the patient can be stabilized and a CT scan performed to make the diagnosis. If there is no evidence of continued bleeding on imaging or based on clinical improvement, the indication for selective arterial embolization is controversial. Bleeding may sometimes spontaneously stop, and delayed surgery may be performed under nonacute conditions after resorption of the hemoperitoneum or the subcapsular hematoma. If the patient remains hemodynamically unstable, arterial embolization is the initial treatment of choice as emergent operative exploration is highly morbid with high rates of mortality. In cases of misdiagnosis or clinical instability, a laparotomy may be emergently performed and the ruptured tumor intraoperatively discovered. In this situation, surgical resection should be performed only if a minor hepatectomy can be performed such as a left lateral sectionectomy or resection of a pedunculated tumor. Otherwise, perihepatic packing may be performed, followed by arterial embolization, as a major hepatectomy is not recommended because of a mortality rate of near 8%.

Some authors recommend embolization to support the delayed surgery because embolization reduces the size of the adenoma so that hepatectomy may be minimized in extent, or avoided altogether because of major or complete regression of the tumor.

Solitary Symptomatic Tumors

The symptomatic tumors are usually large lesions. The indications for surgery, which include complete removal of the solid lesion, should be discussed based on the severity of symptoms and the risks of surgery.

For cystic tumors, percutaneous aspiration may serve as a “diagnostic tool” proving that the symptoms are commensurate with the cyst; however, this procedure is not a valid treatment. Laparoscopic fenestration or deroofing of the cyst is the gold standard. This technique involves wide excision of the roof of the cystic wall so that the cyst is opened into the peritoneum. Omentoplasty is useful to avoid closure of the cyst. Resection might be indicated in selected cases such as the atrophy of a lobe or the doubtful diagnosis of cystadenoma. Histological examination of the cystic wall is mandatory for excluding the presence of a rare cystadenoma. Alternative surgical treatment consists of aspiration-sclerotherapy with alcohol under US guidance. After removal and analysis of the fluid, excluding bile staining and (for some authors) a contrast cystogram, instillation of ∼30% of the cyst volume with alcohol is performed, and kept in place for 2 hours. For medium-large cysts, this procedure appears to be efficient and minimally invasive; however, not as effective as laparoscopic deroofing.

Solitary Asymptomatic Tumor

Hemangioma, FNH, and cysts, if diagnosed with certainty by imaging, must be managed conservatively regardless of their size. No follow-up is recommended because even if the tumor size increases, surgery will not be indicated if the patient remains asymptomatic. Unwarranted and prolonged follow-up may induce anxiety and symptoms in the patient. No change in lifestyle is necessary for any of these lesions, such as refraining from contact sports or terminating OC use. The only condition to be discussed is the desire for pregnancy in a woman presenting with a large subcapsular hemangioma. Some investigators advocate preventive surgical resection because of the rare risk of rupture during pregnancy.

For asymptomatic adenomas, surgery must be discussed in terms of a preventive strategy because of the risks of bleeding and malignancy. Indeed, routine surgery for adenomas is controversial, and conservative management may be recommended in many cases. Much data are currently available concerning the genetic and pathological characterization of these BLT and the real risk of complications. It has been shown that the risk of hemorrhage (20–40%) is greater than the risk of malignancy (10%).[84] [85] There is a clear relationship between these risks and two types of data: the size of the tumor and the genetic and pathological type of HCA. The latter may be determined by MRI or diagnosed by biopsy.[86] The risk of hemorrhage is higher for HCA > 5 cm and inflammatory HAs, and the probability of malignancy is higher in HCA > 5 cm, and linked to the β-catenin mutation.

Nonetheless, it should be stressed that some small adenomas bleed (12%), and it may be difficult to distinguish between adenoma and HCC on imaging and even in histological specimens. Therefore, treatment recommendations can be summarized as follows: (1) For small adenomas (< 5 cm) in females, discontinue OP and attempt to characterize the tumor (as steatotic or inflammatory) based on MRI. If the tumor is steatotic, then follow-up is justified (every 6 months, by US). If the tumor is inflammatory or if it increases in size, then discuss surgery with the patient. Otherwise, observation appears to be justified. If pregnancy is planned, discuss surgery or radiofrequency ablation. (2) For patients with large adenomas (> 5 cm), surgery should be scheduled. (3) For adenomas of any size in males, surgery should be proposed.

Multiple Lesions

Management of the multiple forms of benign tumors is difficult because surgical clearance is often impossible and because no clear recommendations are available.

In cases of hemangiomatosis, the same rules as for solitary hemangiomas are applied: only symptomatic forms require surgery and follow-up is unnecessary. Multiple FNHs are usually asymptomatic and also require no follow-up. The most delicate issue is the management of adenomatosis. Surgical management depends on the type of adenomatosis (large adenomas or diffuse adenomatosis presenting as multiple small nodules), the histological subtype, the symptoms, and the patient.[87] Resection of the largest or most complicated adenomas may be performed, with or without intraoperative radiofrequency ablation, while small, uncomplicated lesions may be surveyed. Arterial embolization has been applied to progressive adenomatosis with good results.[88] In the rare cases of iterative complications or proven malignant transformation, liver transplantation should be discussed.

In PCLD patients, the indications for surgery depend only on the severity of symptoms. The surgical options consist of fenestration, liver resection, and liver transplantation. The procedure depends on the type of the disease based on the Gigot classification and the presence of renal dysfunction. Before considering resection or transplantation, which are potentially morbid procedures, alternative medical management should also be discussed for Gigot type II and III disease (e.g., somatostatin, mTOR inhibitors, or hepatic embolization). Despite the absence of liver dysfunction, transplantation is often the cure especially for patients with end-stage renal disease.

Principles of Surgery

Which Approach Should Be Used?

The development of laparoscopic surgery has changed the approach to treatment of benign liver tumors. Currently, laparoscopic liver resection is feasible and safe when performed by experienced surgeons. The trend is moving from limited hepatectomy involving the anterior segments to major hepatectomy and resection of any segments of the liver.[89]

The most beneficial aspect of laparoscopy is a reduction of the invasiveness of liver resection in terms of postoperative pain and cosmetic outcomes, which is important in the population that is usually affected. However, there is a dangerous and unjustifiable trend toward resecting an increasing number of BLT since the introduction of laparoscopy, and some series report a questionably high rate of diagnostic surgery or preventive surgery.[90] Nonetheless, the first rule of surgical management is the safety of the patient, regardless of the approach.

In appropriate hands, laparoscopy is the gold standard for the management of hepatic cysts, small benign tumors located in the left lobe, or in anterior segments of the liver (< 5 cm) or pedunculated masses. Laparoscopy is also an excellent approach for multiple benign lesions: it allows complete exploration of the parenchyma, and multiple biopsies of various nodules and of the nontumorous liver. In large tumors requiring major hepatectomies, some authors have demonstrated the feasibility of laparoscopy.[91] However, open surgery remains the gold standard, especially if the tumors are closely adherent or adjacent to major vessels. Major laparoscopic hepatectomy should be reserved for trained surgeons in specialized centers.

Which Procedure Should Be Employed?

Surgery for large, benign, solid tumors may be difficult because of the size of the tumor, the peripheral vascularization, or compression of the hepatic veins or vena cava. A right subcostal incision is usually appropriate, but for massive tumors located close to hepatic veins, there should not be any hesitation to perform a larger incision, including a right thoraco-abdominal approach. Intraoperative US is mandatory to detect small lesions and to study the limit of the tumor, thus guiding the surgical plan. The Pringle maneuver or selected devascularization of the tumor must be performed to reduce the blood inflow so that the tumor is more easily mobilized and enucleated—which is obvious in cases of large hemangiomas[92] or FNHs. Enucleation of adenomas may be hazardous because it can be difficult to identify the limits of the tumor; indeed, a margin is preferable in cases of focal malignant transformation. In some cases, total vascular exclusion is mandatory to control subhepatic bleeding. Nonetheless, in benign disease, removal of the normal liver parenchyma must be kept to a minimum.

The Role of Liver Transplantation

Benign liver tumors constitute a rare indication for liver transplantation, which is understandable given the usual excellent prognosis of these tumors compared with the complexities of transplantation. Moreover, liver function is always preserved. Therefore, transplantation should be discussed in terms of preventive or symptomatic surgery for extreme cases. Concerning solid tumors, the indications include (1) a solitary, giant, unresectable, solid tumor with severe symptoms[93] [94] or with underlying liver disease; and (2) multiple benign tumors with serious untreatable complications, such as iterative hemorrhage or the high suspicion or occurrence of malignant transformation in adenomatosis.[95] These indications are anecdotal and should remain so. For example, in Europe, less than 50 transplantations have been performed for adenomatosis (unpublished data). A larger body of experience exists regarding liver transplantation for polycystic liver disease because of the associated kidney disease. Approximately 45% of these patients undergo a combined liver kidney transplant with good—but not excellent—results: 5-year survival of 68.7% in LT and 75.5% in CLKT.

Transplantation is technically difficult in these cases, especially if the patient has undergone previous surgical procedures; therefore, some authors advocate early consideration of LT in a selected group of patients.[96]

Conclusion

Practitioners are increasingly presented with BLTs and the need to make clinical decisions as to their treatment. The diagnostic workup identifies the tumors that must be removed, the tumors that should be monitored, and the tumors that may be ignored, and this analysis requires extensive knowledge of the characteristics of the various tumors.[97] The goal of surgery depends on the symptoms and on the nature of the tumor. The clinical challenge is to perform safe symptomatic surgery, to justify preventive surgery, and to decrease the rate of diagnostic surgery.

Acknowledgments

We wish to thank Professor Paulette Bioulac-Sage (CHU Bordeaux, Department of Pathology, Hôpital Pellegrin) for the critical review of this manuscript.

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Address for correspondence

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