Intracranial metastasis in fibrolamellar hepatocellular carcinoma

Abstract

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare liver malignancy in adolescents and young adults. Surgery is the mainstay of therapy for primary and metastatic disease. Most patients relapse, with development of both local and distant metastases. Brain metastases from solid tumors are rare in the pediatric and young adult population. Here, we document three patients with brain metastases from FLHCC, confirmed by histology and molecular characterization of the chimeric fusion DNAJB1-PRKACA, each necessitating neurosurgical intervention. These observations highlight the ability of FLHCC to metastasize to the brain and suggest the need for surveillance neuroimaging for patients with advanced-stage disease.

Keywords: adolescent and young adult tumors; brain; fibrolamellar; liver; rare tumors; tumor biology; tumors.

Figure 1

Patient 1: Axial (A) T1-weighted contrast-enhanced and sagittal (B) T1-weighted pre-contrast, demonstrate a cystic and solid metastasis within the left frontal lobe resulting in mid line shift. The metastasis contains T1 iso to hyperintense material that are iso to hyperintense on the T2-weighted images consistent with blood products (arrows). Sagittal contrast enhanced T1-weighted images depict the solid enhancing components surrounded by cystic parts of the metastasis. Patient 2: Axial (C) and sagittal (D) reformatted CT images demonstrate a hyperdense hemorrhagic metastasis within the left temporal lobe. Rupture into ventricular system with blood extending into temporal horn of the lateral ventricle [white arrow image (C)]. Edema surrounding the metastasis dark shade of gray designated by black arrows on image (D). Patient 3: Axial (E) and sagittal (F) T1-weighted contrast enhanced images reveal several enhancing metastases (white arrows).

Figure 2

H&E of resected brain metastasis at 10x (A,C,E) and 60x (B,D,F) magnification from Patient 1 (A,B) and Patient 2 (C,D) and Patient 3 (E,F), demonstrating well-differentiated tumor cells with abundant eosinophilic cytoplasm and prominent nucleoli. Fibrous bands, classic for FLHCC are demonstrated in Patient 2 (D, top right corner) and were absent in Patients 1 and 3. Scale bars 100 microns (A,C,E) and 20 microns (B,D,F). RT-PCR agarose gel electrophoresis for the DNAJB1-PRKACA fusion mRNA, is positive for a 148bp amplicon in brain metastases from Patient 1 (lane 2), Patient 2 (lane 3), Patient 3 (lane 4), positive control for DNAJB1-PRKACA (lane 5) and a negative control (lane 6). Lanes are shown from left to right with a 10Kb ladder (lane 1) (G).