REVIEWS Diagnosis and management of solid benign liver lesions Jacques Belghiti, François Cauchy, Valérie Paradis & Valérie Vilgrain Abstract | More and more asymptomatic benign liver tumours are discovered incidentally and can be divided into regenerative lesions and true neoplastic lesions. The most common regenerative lesions include hemangioma, focal nodular hyperplasia and inflammatory pseudotumours of the liver. Neoplastic lesions include hepatocellular adenomas and angiomyolipomas. Regenerative lesions rarely increase in volume, do not yield a higher risk of complications and usually do not require treatment. By contrast, hepatocellular adenomas and angiomyolipomas can increase in volume and are associated with a risk of complications. Large hepatocellular adenomas (>5 cm in diameter) are undoubtedly associated with a risk of bleeding and malignant transformation, particularly the inflammatory (also known as telangiectatic) and β‑catenin mutated subtypes. Accurate diagnosis needs to be obtained to select patients eligible for surgical resection. MRI has markedly improved diagnosis and can identify the major hepatocellular adenomas subtypes. The use of biopsy results to inform the indication for resection remains questionable. However, when diagnosis remains uncertain after imaging, percutaneous biopsy could help improve diagnostic accuracy. Belghiti, J. et al. Nat. Rev. Gastroenterol. Hepatol. advance online publication 2 September 2014; doi:10.1038/nrgastro.2014.151
Introduction
Department of Hepatobiliary Surgery and Liver Transplantation (J.B., F.C.), Department of Pathology (V.P.) and Department of Radiology (V.V.), Beaujon Hospital, University Paris-Diderot, 100 Boulevard du General Leclerc, 92110 Clichy, France.
The widespread use of medical imaging has led to an increase in the incidental discovery of asymptomatic tumours, particularly benign liver lesions. The most frequent solid benign lesions of epithelium origin are focal nodular hyperplasia (FNH) and hepatocellular adenoma and of mesenchymal origin are haemangioma and angiomyolipoma. Clonal analysis shows that these benign lesions contain a spectrum of regenerative and neoplastic characteristics (Table 1). Tumour-like lesions, which include haemangioma, FNH and hepatic inflammatory pseudotumours rarely increase in volume and therefore do not require any treatment. 1,2 Although hepatocellular adenomas and angiomyolipomas are true neoplastic lesions that carry a risk of complication, better knowledge of their natural history and improved understanding of their radiological and pathological characteristics has resulted in a marked decrease in the use of resection for diagnosis.3–5 The trend towards a more conservative approach of resisting surgery requires an accurate diagnosis in order to reassure both the medical team and patient of the type of lesion and its associated natural history. Radiological diagnosis often includes MRI, thus reducing the use of percutaneous biopsy and restricting the number of resections for final diagnosis to patients in exceptional circumstances. This Review describes the solid benign liver lesions that are encountered in adults from the most frequent to the least frequent, with key differential diagnosis
Correspondence to: J.B. jacques.belghiti@ bjn.aphp.fr
Competing interests The authors declare no competing interests.
criteria for each tumour and a stepwise approach for the treatment of tumours with a risk of complication. As cystic liver lesions do not share a similar clinical background and require specific diagnostic and therapeutic approaches they are not discussed in this Review.
Cavernous haemangioma
Hepatic cavernous haemangiomas account for up to 70% of all benign liver lesions and have an estimated prevalence of 3–20%, which makes them the most common liver lesion.1,6 They can occur at all ages but are predominantly found in adult females, in whom the incidence reaches up to 10%.7,8 The vast majority of haemangiomas are 10 cm in diameter) can contain extensive fibrous changes, thrombosis and calcifications. Haemangiomas are usually found incidentally during routine imaging work-up of the abdomen or for unrelated reasons.10 Liver function tests, including those for alkaline phosphatase and γ‑glutamyl transferase, yield normal results. 11 In patients with giant haem angiomas, complications such as abdominal pain or fullness and biological abnormalities such as coagulation disorders, low platelet count or inflammatory syndrome might be observed.12,13 In a rare number of instances,
NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY © 2014 Macmillan Publishers Limited. All rights reserved
ADVANCE ONLINE PUBLICATION | 1
REVIEWS Key points ■■ Haemangioma and focal nodular hyperplasia are the two most frequent benign liver lesions and only exceptionally require treatment, specific advice or follow-up ■■ Hepatocellular adenoma, which now frequently occurs in obese females, is a heterogeneous liver lesion at risk of bleeding and malignant transformation according to the patients’ gender and the pathological subtype and size of the tumour ■■ In women, the low risk of complications associated with hepatocellular adenomas of
Introduction
Department of Hepatobiliary Surgery and Liver Transplantation (J.B., F.C.), Department of Pathology (V.P.) and Department of Radiology (V.V.), Beaujon Hospital, University Paris-Diderot, 100 Boulevard du General Leclerc, 92110 Clichy, France.
The widespread use of medical imaging has led to an increase in the incidental discovery of asymptomatic tumours, particularly benign liver lesions. The most frequent solid benign lesions of epithelium origin are focal nodular hyperplasia (FNH) and hepatocellular adenoma and of mesenchymal origin are haemangioma and angiomyolipoma. Clonal analysis shows that these benign lesions contain a spectrum of regenerative and neoplastic characteristics (Table 1). Tumour-like lesions, which include haemangioma, FNH and hepatic inflammatory pseudotumours rarely increase in volume and therefore do not require any treatment. 1,2 Although hepatocellular adenomas and angiomyolipomas are true neoplastic lesions that carry a risk of complication, better knowledge of their natural history and improved understanding of their radiological and pathological characteristics has resulted in a marked decrease in the use of resection for diagnosis.3–5 The trend towards a more conservative approach of resisting surgery requires an accurate diagnosis in order to reassure both the medical team and patient of the type of lesion and its associated natural history. Radiological diagnosis often includes MRI, thus reducing the use of percutaneous biopsy and restricting the number of resections for final diagnosis to patients in exceptional circumstances. This Review describes the solid benign liver lesions that are encountered in adults from the most frequent to the least frequent, with key differential diagnosis
Correspondence to: J.B. jacques.belghiti@ bjn.aphp.fr
Competing interests The authors declare no competing interests.
criteria for each tumour and a stepwise approach for the treatment of tumours with a risk of complication. As cystic liver lesions do not share a similar clinical background and require specific diagnostic and therapeutic approaches they are not discussed in this Review.
Cavernous haemangioma
Hepatic cavernous haemangiomas account for up to 70% of all benign liver lesions and have an estimated prevalence of 3–20%, which makes them the most common liver lesion.1,6 They can occur at all ages but are predominantly found in adult females, in whom the incidence reaches up to 10%.7,8 The vast majority of haemangiomas are 10 cm in diameter) can contain extensive fibrous changes, thrombosis and calcifications. Haemangiomas are usually found incidentally during routine imaging work-up of the abdomen or for unrelated reasons.10 Liver function tests, including those for alkaline phosphatase and γ‑glutamyl transferase, yield normal results. 11 In patients with giant haem angiomas, complications such as abdominal pain or fullness and biological abnormalities such as coagulation disorders, low platelet count or inflammatory syndrome might be observed.12,13 In a rare number of instances,
NATURE REVIEWS | GASTROENTEROLOGY & HEPATOLOGY © 2014 Macmillan Publishers Limited. All rights reserved
ADVANCE ONLINE PUBLICATION | 1
REVIEWS Key points ■■ Haemangioma and focal nodular hyperplasia are the two most frequent benign liver lesions and only exceptionally require treatment, specific advice or follow-up ■■ Hepatocellular adenoma, which now frequently occurs in obese females, is a heterogeneous liver lesion at risk of bleeding and malignant transformation according to the patients’ gender and the pathological subtype and size of the tumour ■■ In women, the low risk of complications associated with hepatocellular adenomas of
