Solid liver SOL

Solid space-occupying lesions in Liver- Concepts, diagnosis, and management

1. APPROACH TO SOLID LIVER SOL

2. Introduction Diagnosis of Liver SOL increased with ever increasing use of various diagnostic modalities. Clinical suspicion with clinical background and various ancillary markers helps in shortlisting the most likely diagnosis Lesions can range from cystic to solid, from benign to malignant. We will be discussing various solid lesions of liver today.

3. Benign Liver Lesions

4. Main differentials are: Hepatocellular --- Focal nodular hyperplasia, Hepatocellular adenoma, Nodular regenerative hyperplasia, Dysplastic nodule Cholangiocellular --- Bile duct adenoma (biliary hamartoma/ von Meyenburg complex), Intraductal papillary neoplasm of bile duct. Mesenchyma l--- Cavernous hemangioma , Lipoma, Angiolipoma Others --- Mesenchymal hamartoma, Focal fatty infiltration, Hepatic pseudotumor

5. Focal Nodular Hyperplasia 2 nd M/C solid benign liver lesion with 0.2% incidence. Common in young female– association not proven yet. FNH is thought to be originating due to portal injury leading to development of tortuous artery and vein to compensate with hyperplasia of hepatocytes with inflammatory changes giving rise to vascular tumor with a central scar.

6. On CT scan, it is iso-attenuating to parenchyma before contrast and enhancing in arterial phase, as it is a hypervascular lesion with hypodense central scar. Scar shows enhancement in delayed portal phase when rest of FNH becomes isointense again. MRI is more sensitive and specific (70% and 98% respectively), with FNH being Hypo- to iso-intense on T1 and Iso- to hyperintense on T2 weighted films with hyperintense central scar on T2. Enhancement to contrast is similar to CECT 1 . According to ACG guidelines FNH is to be followed every 2-3 years if a young female wants to continue OCP or else no follow up is recommended at present.

7. Hepatocellular Adenoma (HCA ) Rare liver SOL– Incidence- 0.04%. Young female with high potency OCP’s, other are steroids, anabolic hormones. 25% present with intra-abdominal haemorrhage. Pathology wise it’s a fatty lesion ranges from microscopic size to up to 20cm in diameter. There is intra-tumoral congestion/necrosis/haemorrhage/fibrosis.

8. Usually detected with USG abdomen as a hyperechoic lesion, due to high lipid content, with heterogenous appearance due to necrosis/haemorrhage/lipid content. Further characterization can be done on Multi-phase helical CT. Findings depend on character of liver parenchyma as HCA is a fatty tumor . In a non fatty liver HCA is hypo- to isointense on plain/portal/delayed phase and can be Hyperintense if liver background is fatty. In contrast phase, tumor shows peripheral enhancement with centripetal pattern as large peripheral subcapsular vessels feed the tumor . Contrast is not retained as there is arteriovenous shunting. On MRI, HCA is heterogenous in appearance with bright T1 and Hyperintense T2 images. Recently, 18F-Fluoromethylcholin PET scan has been used to differentiate FNH and HCA but not yet proven. 2

9. More recently, molecular classification has revealed four major subtypes of HCA (the Bordeaux classification): HNF1A (coding hepatocyte nuclear factor 1a) inactivating mutations (30–40%), inflammatory adenomas (40–50%), β-catenin mutated HCAs (β-HCA; 10–15%) and unclassified HCAs (10%).16 Inflammatory HCAs can also be β-catenin activated (10%). It is important to differentiate between these subclasses, as β-catenin mutations appear to be associated with a higher risk of malignant transformation. 3 Some groups suggested that β-catenin activated and inflammatory adenoma are more prone for malignant degeneration and should be considered for resection. Management of HCA depends on various factors like size, sex, baseline liver and use of hormonal therapy. In male sex threshold of resection should be low, while in female if <5cm can be observed. Arterial embolization is a option when presents with bleed. OLT has been described , specially in case of adenomatosis or in background of Glycogen storage disease.

10. Nodular regenerative hyperplasia Thought to be caused due to portal venous obstruction which leads to ischemic changes leading to hyperplasia of hepatic acini to compensate for atrophied acini leading to micro-nodular transformation of liver. Have non-specific imaging character and diagnosis is based on clinical manifestation of portal vein with biopsy of liver. For treatment, manifestations of portal hypertension should be taken care of; liver failure is a complication for which LT should be considered.

11. Dysplastic Nodule (DN ) Defined as focal nodular region >1mm without any definite evidence of malignancy. With incidence of 14% to 37%, it is associated with liver cirrhosis. USG in these cases along with cirrhotic background might show hypo- to hyperechoic picture depends on fat content of lesion but often misses Dysplastic nodule. Multiphasic CT may show hypoattenuating lesion with early contrast enhancement without washout in delayed phase. On MRI, DN shows T1 hyperintense and T2 hypo- to isointense image without any diffusion restriction on DWI. As DN is considered to be pre-malignant, hence follow up is required. Percutaneous ablation is a viable option for management.

12. Bile duct adenoma Bile duct adenoma, bile duct hamartomas or Von Meyenberg complex are benign bile duct malformations. Pathology--- D ilated bile duct embedded in fibrous stroma usually <10mm. If found intra-operatively, it should be biopsied to distinguish from cholangiocarcinomas or metastasis. No treatment is required otherwise.

13. Intraductal papillary neoplasm of bile duct IPNB along with biliary intraepithelial neoplasia are rare lesions and considered to be precursor to Cholangiocarcinoma. They are biliary counterpart of pancreatic IPMN. Main presentation is with repeated episodes of abdominal pain, jaundice and cholangitis. Most common imaging findings are diffuse ductal ectasia with focal dilatation with intraductal mass. Patients are considered for surgical resection with negative margin if no metastasis is present.

14. Hemangioma Most common benign liver SOL--- with 3% incidence. Associated with female hormones but not yet proven. A rare presentation in patients with a giant haemangioma is thrombocytopenia and hypo-fibrinogenaemia caused by consumption coagulation factors, also known as Kasabach – Merritt syndrome. This is a serious complication and mortality ranges between 10% and 37%. Pathology wise it is supplied by hepatic artery with thin fibrous stroma with multiple small vessels lined by single layer of endothelial cells. Macroscopically it is purple coloured well defined compressible lesion. Needle biopsy is not recommended due to risk of haemorrhage.

15. As an initial diagnostic modality USG shows Hemangioma as well defined, lobulated, hyper-echoic lesion with hypoechoic internal shadow due to haemorrhage, necrosis and fibrosis. With Contrast Enhanced Ultrasound (CEUS) sensitivity of USG can be increased up to 90%. Haemangiomata on plain CT is well demarcated, hypodense mass, after contrast there is peripheral nodular enhancement with progressive centripetal filling in (Fig.3) MRI is the best modality with >90% sensitivity and specificity. It is best modality for hemangiomata specially <3cm, close to heart, close to intrahepatic vessels. Bright T2 weighted lesion with bright enhanced T1 weighted images with similar pattern of enhancement pattern as CT. SPECT has been shown to be useful in large hemangiomata but not used widely.

16. >10 cm Hemangioma are consider for enucleation or resection when symptomatic . Other options– RFA/Rarely transplant.

17. Primary malignant lesions of liver

18. HCC HCC is the most common primary hepatic malignancy worldwide. Imaging plays an essential role in the clinical management of HCC with MDCT and MR imaging as the most commonly used imaging modality in the diagnosis, staging, and surveillance of the disease. The typical CT appearance of HCC during a multiphasic scan is an early enhancing mass with rapid washout. A capsule, if present, demonstrates late enhancement. MDCT is also highly accurate in staging HCC. MDCT can detect the number of lesions, segments involved, regional adenopathy, vascular tumor invasion, and metastases.

19. On MR, the T1 appearance of HCC ranges from hypointense to slightly hyperintense, depending on fat content, copper deposition within the tumor , and the degree of differentiation. On T2 images, most HCC demonstrate increased signal compared to the surrounding liver, although the tumours tend to be inhomogeneous. Raised AFP strongly corroborates malignancy.

20. Fibrolamellar carcinoma FLC is a rare variant of HCC, defined as well differentiated polygonal hepatic tumour cells with an eosinophilic granular cytoplasm surrounded by a fibrous lamellar stroma. Usually these present late as palpable mass and pain, often in younger female with normal AFP. On imaging, FLC presents as a large solitary hyper-vascular heterogeneous liver mass with a central hypodense region due to central necrosis or fibrosis. On MRI, the central scar has low attenuation on T2 images, whereas the central scar of focal nodular hyperplasia has high attenuation. They have well defined margins and calcification is present 2/3rd of cases 4 . Histology demonstrates deeply eosinophilic, polygonal neoplastic cells surrounded by a dense, layered fibrous stroma .

21. Intrahepatic cholangiocarcinoma Cholangiocarcinoma is the second most common primary hepatobiliary malignancy, after HCC. Peripheral cholangiocarcinomas are usually large because they are rarely symptomatic early in their course. Cholangiocarcinomas have normal AFP but Ca 19-9 could be raised.

22. The most common CT appearance of cholangiocarcinoma is that of a low-attenuation mass with irregular margins with mild peripheral enhancement on the delayed phase of imaging. This delayed enhancement is a result of slow diffusion of contrast into the interstitial space and results in prolonged enhancement. Satellite nodules, regional lymph nodes, and capsule retraction may be present. In contrast to HCC, these tumors usually do not invade adjacent vessels but encase them. Contrast enhanced T1 films are helpful in differentiating dilated bile ducts from enhancing cholangioCA .

23. Hepatic Metastasis Liver is the most common site for metastasis from other primary malignancy. Most of the liver metastasis are hypo-vascular, frequently with peripheral rim enhancement on CT/MRI (Fig.5). Contrast uptake in the arterial phase on CT or MRI suggests neuroendocrine tumour, melanoma, sarcoma, hypernephroma, or thyroid neoplasia. Isotopic studies using labelled somatostatin analogues can identify neuroendocrine tumours. Management depends on presentation, liver status, status of primary and probability of R0 resection with adequate FLR and is guided mainly by tumour biology.

24. Other Imagings Radio-isotope Scanning is useful for many lesions. Thus, Sulphur colloid scan can differentiate FNH and regenerative nodule. PET Scan may be useful for metastasis as well as detecting primary lesions. PET scan may not detect <1cm tumours or mucinous tumours. It may also miss neuroendocrine and other tumours with especially necrotic components.

25. Current Approach to SOL liver

26. Liver SOL on USG Solid/Indeterminate <1 cm >1 cm Present Absent Further evaluation with alternate imaging Follow up Suspicious imaging features Equivocal findings Benign Imaging feature LR 4/5/M/TIV LR 3 LR 1/2 Risk - Cirrhosis/ HBsAg etc Nonrim Arterial phase Hyperenhancement Enhancing capsule Non peripheral washout Threshold growth Return to surveillance /6 months Repeat/Alternate Imaging in 3-6 months Treat accordingly

27. References 1. Cogley JR, Miller FH. MR imaging of benign focal liver lesions. Radiol Clin North Am. 2014;52:657-82. 2. Kwee TC, Kwee RM. Combined FDG-PET/CT for the detection of unknown primary tumors: systematic review and meta-analysis. Eur Radiol . 2009;19:731Y744. 3. Blanc JF, Frulio N, Chiche L, et al. Hepatocellular adenoma management: call for shared guidelines and multidisciplinary approach. Clin Res Hepatol Gastroenterol 2015;39:180–7 4. Aytekin O, Tamm EP, Szklaruk J. Multidetector Row CT of the Liver. Radiol Clin N Am 43 (2005) 827 - 48.

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