Liver Tumors and Transplantation: Liver Tumors and Transplantation: Benign Lesions

0:00Welcome to Board Pearls. This is episode one of four of the Liver Tumors and Transplantation chapter, in the Liver Disease module. This episode is the benign liver lesion found by chance. A young woman whose ultrasound for gallstones found a mass in her liver shows how magnetic resonance imaging, MRI, tells the three common benign lesions apart, why one keeps contrast in the late phase and another doesn't, which can be left alone and which have to come out, and what her contraceptive pill and her plans for pregnancy change. A man who uses anabolic steroids shows why the same lesion is treated differently in a man, and what else his steroids can do to the liver. And a woman on azathioprine whose liver looks cirrhotic but isn't shows the lesion that hides from a routine biopsy.

0:44Here's the patient. A thirty-two-year-old woman had an ultrasound for right upper quadrant pain after meals. It found gallstones, and also a six-centimeter solid lesion in the right lobe of her liver. Her liver tests are normal. She has no history of liver disease, and she doesn't drink. She's taken an estrogen-containing oral contraceptive for eleven years. She and her husband plan to try for a baby next year.

1:11A solid lesion found by chance in a young woman with a normal liver and years on the pill is most likely one of three benign lesions: a hemangioma, focal nodular hyperplasia, or an adenoma. Imaging usually decides which, because in a liver without cirrhosis most benign lesions have imaging signatures, and only the atypical ones need a biopsy. So her next test is a contrast-enhanced MRI. A patient with cirrhosis is different, because there a new lesion is cancer until proven otherwise, as episode two explains. She doesn't have cirrhosis, so the benign possibilities come first.

1:47The first possibility is the most common. Cavernous hemangioma is the most common benign liver tumor, found in about seven percent of autopsies. It's more common in women, and it's multiple in up to thirty percent. Its MRI signature is peripheral nodular enhancement in the arterial phase, followed by centripetal fill-in during the venous phase. That pattern comes from its structure. A hemangioma is a network of slow-flow vascular spaces separated by thin fibrous walls, so contrast enters the wide channels at the edge first, pools there, and gradually fills toward the center. A lesion with that pattern is a hemangioma, and the patient is reassured without a biopsy or follow-up imaging.

2:28A hemangioma is treated only when it causes trouble. Treatment is reserved for symptomatic giant lesions, for the rare case of high-output heart failure from large arteriovenous shunting, which is treated by resection or arterial embolization, and for Kasabach-Merritt syndrome. In Kasabach-Merritt syndrome, a giant or rapidly enlarging hemangioma traps platelets and consumes fibrinogen, causing thrombocytopenia, disseminated intravascular coagulation, and microangiopathic hemolysis, as platelets and red cells are damaged in the abnormal vessels.

3:01The second possibility is the lesion most often confused with an adenoma, focal nodular hyperplasia, FNH. FNH is a benign hyperplastic reaction to a congenital arterial malformation. It's more common in women, it's multiple in ten to twenty percent, and it coexists with hemangiomas in about twenty percent. Its classic feature is a stellate central scar that contains the malformed feeding artery, surrounded by normal, polyclonal hepatocytes and working bile ductules.

3:29Those ductules are why the gadoxetate MRI helps. Gadoxetate is taken up by functioning hepatocytes and excreted into bile, so FNH, with working hepatocytes and intact ductules, stays bright in the hepatobiliary phase, while an adenoma, which lacks bile ducts, is dark. FNH has no malignant potential and no consistent link to oral contraceptives, and the twenty twenty-four American College of Gastroenterology, ACG, guidance doesn't recommend stopping them or managing FNH differently by sex. With classic imaging, FNH needs no surveillance.

4:07Her MRI settles it. Her six-centimeter lesion enhances in the arterial phase but has no central scar, and it's dark in the hepatobiliary phase on gadoxetate. A lesion that doesn't retain the contrast lacks functioning bile ducts, so it isn't FNH. In a young woman who's taken an oral contraceptive for eleven years, it's a hepatic adenoma.

4:28Her history fits. Hepatic adenoma occurs mostly in women of reproductive age and is strongly associated with oral contraceptives, with a risk that climbs with duration to roughly twenty-five to forty times baseline after nine or more years of use. Other associations are maturity-onset diabetes of the young, MODY, the glycogen storage diseases, especially types one-a and three, polycystic ovary syndrome, obesity, and anabolic androgen use in men. On histology, an adenoma is made of monoclonal hepatocytes with prominent unaccompanied arteries, meaning arteries without the portal tracts or bile ducts that normally travel with them, and the missing bile ducts are also why it's dark in the hepatobiliary phase.

5:12Her adenoma's subtype predicts its risk. Inflammatory adenomas are the most common, about forty to fifty percent, and were once called telangiectatic FNH. HNF1A-inactivated adenomas make up about thirty to forty percent. Beta-catenin-activated adenomas make up about ten to fifteen percent and carry the highest malignant potential, and they're identified by nuclear beta-catenin and glutamine synthetase staining. The rest are unclassified. Overall, about five percent of adenomas undergo malignant transformation.

5:44At six centimeters, hers has to come out. Resection is recommended for any adenoma in a man, because men carry a higher risk of transformation regardless of size. It's recommended for any lesion of five centimeters or more, a growing lesion, a beta-catenin-activated lesion on biopsy or imaging, and a lesion that has bled. And it's recommended for any adenoma before a planned pregnancy, because hormonal stimulation enlarges adenomas and raises the risk of rupture and hemoperitoneum.

6:15She meets two of those criteria. Her lesion is six centimeters and she plans to conceive next year, so it should be resected before she tries. A biopsy for subtype wouldn't change that decision. The subtype matters most in a smaller lesion that would otherwise be watched, where beta-catenin activation turns observation into surgery. She stops her estrogen-containing contraceptive and switches to a non-estrogen method. Her gallstones, if they explain her pain, are covered in chapter twenty-seven.

6:44A smaller adenoma shows what observation looks like. A two-centimeter adenoma in a woman with no pregnancy planned and no bleeding falls outside the resection criteria. Her contraceptive stops, because some adenomas regress when estrogen is withdrawn, and she has surveillance MRI or computed tomography, CT, every six months for two years, then yearly. Growth means resection, and bleeding is an indication for resection whatever the size. More than ten adenomas is hepatic adenomatosis, and when it can't be resected it's a rare indication for liver transplant.

7:18The second patient shows how sex changes the rule. A thirty-eight-year-old man who uses anabolic steroids for bodybuilding has a three-centimeter liver lesion that's dark in the hepatobiliary phase, so it's an adenoma. Any adenoma in a man is resected regardless of size, so a lesion that would be watched in a woman is an indication for surgery in him. He stops the steroids and is referred for resection.

7:43His steroids can injure the liver in other ways too, so his liver tests and imaging deserve a careful look. Anabolic steroids taken for bodybuilding cause a striking cholestatic injury, with a very high bilirubin and only a mild rise in alanine aminotransferase, ALT, that can persist for months. They also cause peliosis hepatis, randomly distributed blood-filled cavities that arise from injury to the sinusoidal endothelium. Peliosis has other causes as well: azathioprine, oral contraceptives, tamoxifen, Bartonella henselae in human immunodeficiency virus, HIV, infection, Staphylococcus aureus, tuberculosis, end-stage renal disease, multiple myeloma, Hodgkin disease, histiocytosis X, and hepatic adenoma itself. If his liver ever needs a biopsy, peliosis is a reason to take it by the transjugular approach rather than through the skin.

8:41The third patient's liver looks cirrhotic but isn't. A fifty-four-year-old woman with Crohn disease has taken azathioprine for ten years. Her imaging looks cirrhotic, she has an enlarged spleen and varices, but her biopsy looks nearly normal on standard staining. That's nodular regenerative hyperplasia. Normal hepatocytes reorganize into small regenerative nodules without bridging fibrosis or inflammation, driven by injury to the small portal venules inside the liver, an obliterative portal venopathy now grouped under porto-sinusoidal vascular disease.

9:16It explains everything about her. Nodular regenerative hyperplasia causes non-cirrhotic portal hypertension, and it looks cirrhotic on imaging while routine histology looks normal. A reticulin stain is what reveals the nodular architecture without fibrosis. Its associations include connective tissue disease, common variable immunodeficiency, myeloproliferative disorders, Hodgkin lymphoma, multiple myeloma, Turner syndrome, ADAMTS13 deficiency, and drugs including azathioprine and oxaliplatin. Her azathioprine is the likely cause, and her portal hypertension is managed by the variceal rules of chapter twenty-three.

9:54Here are the traps the boards set in these patients. A lesion with classic imaging in a liver without cirrhosis doesn't need a biopsy. A classic hemangioma doesn't need follow-up. FNH isn't a reason to stop contraceptives. FNH is bright in the hepatobiliary phase and an adenoma is dark, and confusing the two changes everything.

10:15The adenoma traps are about who gets surgery. An adenoma in a man is resected, not observed. So is an adenoma of five centimeters or more, and any adenoma in a woman planning pregnancy. A woman with an adenoma stops estrogen. And nodular regenerative hyperplasia is missed when a normal routine biopsy is taken at face value, without a reticulin stain.

10:39So, start to finish. Let imaging decide benign liver lesions in a liver without cirrhosis, and biopsy only the atypical ones. A hemangioma shows peripheral nodular enhancement with centripetal fill-in and needs no follow-up. FNH has a central scar, retains gadoxetate in the hepatobiliary phase, needs no follow-up, and doesn't require stopping contraceptives.

11:01An adenoma is dark in the hepatobiliary phase. Stop estrogen, and resect any adenoma in a man, any lesion of five centimeters or more, a growing or bleeding one, a beta-catenin-activated one, and any adenoma before pregnancy. Otherwise image every six months for two years, then yearly. And nodular regenerative hyperplasia causes portal hypertension without cirrhosis and needs a reticulin stain.

11:28Episode two is hepatocellular carcinoma: surveillance, reading a nodule with the Liver Imaging Reporting and Data System, LI-RADS, and treatment by stage.

11:39For the full chapter, the practice vignettes, and the topic-tagged question bank, head to board pearls dot com. You'll find the rest of the series on Apple Podcasts, Spotify, or wherever you listen to podcasts. That brings us to the end of episode one of four of chapter twenty-four, and I'll see you in the next one.