Case Presentation: A 28-year-old woman with Turner syndrome, hypertension, hyperlipidemia, and a history of congenital portal hypertension treated with TIPS as an infant for gastrointestinal bleeding presented to the emergency room in June 2025 with new-onset painless jaundice, early satiety, and nausea. Laboratory results on admission showed a total bilirubin of 13.7 mg/dL, AST 538 U/L, ALT 168 U/L, alkaline phosphatase 179 U/L, albumin 2.4 g/dL, INR 1.3, platelets 137 K/µL, and AFP > 3000 ng/mL.CT four-phase imaging revealed a 17.2 cm heterogeneous hepatic mass occupying most of the liver with regions of fat and calcification, compressing the hepatic veins without evidence of biliary obstruction. A transjugular liver biopsy confirmed well-differentiated hepatocellular carcinoma (HCC). Tumor board review determined she was not a candidate for transplant or surgical resection. Despite initiation on palliative 5-fluorouracil and whole liver radiation, her disease progressed and she was transitioned to hospice care.
Discussion: This case highlights the diagnostic and clinical challenges of hepatocellular carcinoma (HCC) arising in a young, non-cirrhotic woman with Turner syndrome. Hepatic involvement in Turner syndrome is diverse, ranging from mild enzyme elevations to vascular and structural abnormalities such as nodular regenerative hyperplasia and, in rare cases, HCC [3]. The literature on hepatic neoplasia in this population remains limited to isolated case reports, underscoring the rarity of this presentation [2].The absence of pain and the predominance of cholestatic symptoms in this patient initially shifted attention toward autoimmune or obstructive etiologies. However, imaging and biopsy confirmed HCC, challenging traditional assumptions about age-related prevalence and risk factors. Proposed mechanisms of hepatocarcinogenesis in Turner syndrome include chronic estrogen exposure, vascular malformations, and metabolic injury, all of which may contribute to chronic hepatic inflammation and dysplasia.This case is particularly notable for childhood-onset portal hypertension and TIPS placement suggesting early vascular liver pathology; an anatomically large HCC in a non-viral, non-alcoholic liver with underlying steatohepatitis and secondary iron overload, and rapid progression to hepatic and renal failure that precluded curative therapy. It emphasizes the importance of maintaining a broad differential diagnosis for liver dysfunction in Turner syndrome and supports the role of routine hepatic surveillance, particularly in patients with known vascular or structural liver abnormalities.
Conclusions: Turner syndrome is a chromosomal disorder characterized by complete or partial monosomy of the X chromosome, associated with short stature and multiple organ abnormalities, including hepatic structural and vascular lesions [1]. While benign hepatic abnormalities are relatively common, the development of hepatocellular carcinoma (HCC) is exceedingly rare, with the few case reports presenting in childhood rather than adulthood [2]. This case report describes a young woman with Turner syndrome, long-standing portal hypertension, and prior transjugular intrahepatic portosystemic shunt (TIPS) who presented with painless jaundice and was found to have HCC leading, to rapid hepatic and renal failure, underscoring the need for heightened clinical suspicion in atypical presentations within genetic syndromes with multisystem involvement.