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Liver and intrahepatic bile ducts - Tumor

Benign tumors

Hepatocellular adenoma


Reviewers: Deepali Jain, M.D. (see Reviewers page)
Revised: 9 January 2013, last major update February 2012
Copyright: (c) 2004-2013, PathologyOutlines.com, Inc.

General
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● Also called liver cell adenoma
● Arises in normal or nearly normal liver in patients with abnormal hormonal or metabolic condition
● 95% women, usually child-bearing age (very rare in children), history of 5+ years of oral contraceptives in 85% (occasionally regress after discontinuation)
● Also associated with anabolic steroids (in men), anti-estrogens, Klinefelter’s syndrome or other abnormal secretion of sex steroids
● Also associated with glycogen storage disease types Ia and III, Fanconi’s anemia, thalassemia, familial adenomatous polyposis, familial diabetes mellitus, Hurler’s disease, galactosemia or tyrosinemia; also spontaneous
● 2-4% of hepatic tumors in children
● Subcapsular tumors may rupture, particularly during pregnancy
● Benign, but may contain hepatocellular carcinoma or cause severe hemorrhage
● 10% or lower risk of hepatocellular carcinoma if not resected; definite risk in young men with glycogen storage disease type Ia
● Must sample generously to rule out coexisting hepatocellular carcinoma
● Risk of malignancy is not related to number of adenomas but to size and pathological subtype (lower risk for steatotic subtype)
● May contain hepatic progenitor cells (Am J Surg Pathol 2001;25:1388)

Laboratory
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● Normal liver function tests, may have elevated alpha fetoprotein
Hepatocellular adenomatosis: 10+ tumors, both in man and woman, genetic mutation of HNF1α no association with oral contraceptives

Treatment
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● Excision

Case reports
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● 9 year old girl with hepatic adenoma and subsequent fibrolamellar carcinoma (Arch Pathol Lab Med 2004;128:222)

Gross description
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● Solitary (70%, anabolic steroid related more often multiple), pale, yellow-tan (different from surrounding liver), frequently bile-stained nodules, often subcapsular, 10-30 cm, sharply demarcated or encapsulated
● Usually right lobe, may be pedunculated (10%)
● May have hemorrhagic, necrotic or infarcted foci
● Usually no fibrous septa or central scar; adjacent liver is noncirrhotic

Micro description
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● Sheets and cords 1-3 cells thick of normal appearing hepatocytes with variable glycogen
● Prominent “free floating” arterial vessels and draining veins are present throughout tumor; intact reticulin framework
● Pseudoglands may be present
● May have cytoplasmic globules (PAS+, diastase resistant, alpha-1-antitrypsin+, AFP-), 10% have multinucleation
● Degenerative changes include dilated sinusoids, blood filled (pelioid) spaces, myxoid stroma, focal necrosis, infarction, hematoma
● Rarely contains abundant fat, oncocytic changes, Mallory’s hyaline, granulomatous inflammation
● No atypia, no prominent nucleoli, no intranuclear vacuoles
● No angiolymphatic invasion, no/rare extramedullary hematopoiesis, no epithelioid granulomas, no decreased reticulin framework
● No/rare mitotic figures; no portal tracts; no central veins or connection with biliary system

Three major subtypes: (a) inflammatory/telangiectatic; (b) steatotic; with HNF-1α gene mutation; (c) with β-catenin activation; (d) also an additional unclassified/miscellaneous subgroup (Hepatology 2009;50:481)

(a) inflammatory: previously misclassified as telangiectatic focal nodular hyperplasia; 40-55% of hepatocellular adenomas; increased risk of bleeding but small risk of malignant transformation
● Due to mutations involving interleukin-6
● Strong expression of serum amyloid associated protein A2 (SAA-2) and CRP on IHC
● Inflammation and peliosis at histology

(b) steatotic: 35%-50% of hepatocellular adenomas; no risk of malignant transformation
● Develop familial adenomatosis and MODY-3 diabetes mellitus
● Lack of expression of liver fatty acid binding protein (LFABP) on immunohistochemistry

(c) with β-catenin activation: 10%-18% of hepatocellular adenomas
● Affects men and women; increased risk of malignancy; associated with androgen therapy and glycogen storage disease
● Strong diffuse overexpression of glutamine synthetase and nuclear β catenin staining (Hum Pathol 2002;33:852)

Micro images
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14 year old with subsequent fibrolamellar carcinoma (Figures A-D)


ER and PR staining

Positive stains
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● ER, PR

Negative stains
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● p53

Differential diagnosis
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● Hepatocellular carcinoma: mitotic activity, atypia, trabecular growth, cell plates > 2 cells thick, vascular invasion, infiltrative, often different clinical features
Focal nodular hyperplasia: central stellate scar and radiating fibrous septa


Atypical hepatocellular adenoma

General
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● Androgen related tumors that regress with androgen withdrawal
● Only rarely metastasize

Micro description
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● Marked pleomorphism with prominent nucleoli and extensive pseudoglands resembling hepatocellular carcinoma, but no trabecular pattern, low N/C ratio, no vascular invasion

Differential diagnosis
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● Hepatocellular carcinoma: elevated serum AFP, cirrhosis, vascular invasion, high N/C ratio, trabecular pattern
Focal nodular hyperplasia: central scar
● Hepatoblastoma: elevated serum AFP, age < 3 years, no metabolic disease, light and dark cytoplasmic pattern, small cell size


Pigmented liver cell adenoma

General
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● <25 cases reported (Am J Surg Pathol 2011;35:927, Surg Today 2011;41:881)
● Due to phenobarbitol, long-term oral contraceptives, obesity
● Male predominance
● Black pigment present

Case reports
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● 2 men without Dubin-Johnson syndrome (Am J Surg Pathol 2000;24:1429)

Gross description
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● Solitary and multiple; 2.5-16 cm

Micro description
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● Pigment granules are larger and darker than lipofuscin; no portal tracts, bile ducts or ductules within the tumor

Positive stains
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● Masson-Fontana (for melanin and Dubin-Johnson pigment)

Differential diagnosis
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● Well-differentiated hepatocellular carcinoma

End of Liver and intrahepatic bile ducts - Tumor > Benign tumors > Hepatocellular adenoma


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