A 32-year-old woman on combined oral contraceptive pills for 10 years presents with acute right upper quadrant pain and hypotension. CT imaging shows a 7 cm well-circumscribed right hepatic mass with intratumoral hemorrhage. Resection specimen shows sheets and cords of bland hepatocytes with low nuclear-to-cytoplasmic ratio, eosinophilic cytoplasm with steatosis, and thin-walled arteries coursing through the lesion unaccompanied by portal veins or bile ducts. The structure marked **A** is most consistent with which diagnosis, and what is the PRIMARY pathophysiologic mechanism underlying its development in this patient?

Explanation

## Why option 1 is correct The clinical presentation (OCP use >5 years, acute hemorrhage in a 7 cm mass), histopathology (sheets of bland hepatocytes with marked steatosis, absence of portal tracts/bile ducts/central veins, thin-walled "naked" arteries), and imaging findings are pathognomonic for **hepatocellular adenoma (HCA), specifically the HNF1α-inactivated (H-HCA) subtype**. The Bordeaux molecular classification identifies H-HCA (~35% of HCAs) by biallelic HNF1A mutations, marked steatosis, strong female/OCP association, and loss of liver-fatty acid binding protein (LFABP) on immunohistochemistry. The PRIMARY pathophysiologic mechanism is **benign monoclonal proliferation of hepatocytes driven by prolonged estrogen exposure** — OCPs (especially use >5 years) confer a 30-fold increased risk. This is a benign lesion with low malignant potential (<5% transformation overall), but rupture with hemoperitoneum is a life-threatening complication in lesions >5 cm, as occurred in this patient. [Robbins 10e — Liver Tumors; Bordeaux HCA Molecular Classification] ## Why each distractor is wrong - **Option 2 (Focal nodular hyperplasia)**: FNH is a polyclonal hyperplastic response to a vascular anomaly, NOT a monoclonal neoplasm. Critically, FNH retains Kupffer cells and takes up sulfur colloid on imaging, whereas HCA lacks Kupffer cells. FNH has a characteristic central scar with delayed enhancement — absent in this case. The histology of bland hepatocytes without portal tracts is consistent with HCA, not FNH. - **Option 3 (Well-differentiated HCC)**: While the tumor is well-differentiated, the absence of cytologic atypia, mitoses, and trabecular thickening >3 cells explicitly excludes malignancy. HCC would show these features. The bland morphology and lack of atypia are hallmarks of benign HCA, not HCC. - **Option 4 (Inflammatory HCA with β-catenin activation)**: This conflates two distinct molecular subtypes. Inflammatory HCA (I-HCA, ~50%) is driven by IL6ST/STAT3 mutations and shows telangiectatic appearance with sinusoidal dilation and inflammatory infiltrates — not the marked steatosis seen here. β-catenin-activated HCA (b-HCA, ~10%) is strongly associated with male sex and androgens, NOT OCPs. The marked steatosis and OCP history point to H-HCA, not I-HCA or b-HCA. **High-Yield:** HNF1α-inactivated HCA = marked steatosis + OCP use + low malignant potential; β-catenin-activated HCA = male/androgen association + high malignant potential (40% HCC transformation risk). [Robbins 10e — Liver Tumors; Bordeaux HCA Molecular Classification]