2362 A Case of BRAF V600E Intrahepatic Cholangiocarcinoma

Abstract

INTRODUCTION: Intrahepatic cholangiocarcinoma is an uncommon hepatic malignancy and accounts for 3% of all gastrointestinal malignancies. Patients with this disease have a poor prognosis, with an average 5-year survival rate of 5 to 10%. Herein we describe a case of BRAF-related cholangiocarcinoma. CASE DESCRIPTION/METHODS: A 26 year-old female presented with right-upper quadrant pain and worsening nausea, vomiting for four months. On exam the abdomen was soft, non-tender and non-distended. A right upper quadrant ultra sound revealed a 7 cm mass in the inferior right hepatic lobe and ensuing magnetic resonance imaging of the liver should an 8 cm lesion with numerous satellite lesions. She underwent laparoscopic wedge excision of the liver mass which revealed poorly differentiated adenocarcinoma with features concerning for cholangiocarcinoma (See Images). PET revealed also portal hepatic lymph node metastasis, and metastatic lytic lesions at the clavicle and scapula. CEA and AFP were elevated. Comprehensive genetic analysis with next generation sequencing genomic panel was performed on her initial biopsy and confirmed BRAF V600E mutation. She was initiated on a phase II trial with trametinib and dabrafenib at a referral center. Despite this, repeat CT imaging revealed she had progression of metastatic cholangiocarcinoma. She was switched to FOLFIRI and vemurafineb. However, the patient developed worsening abdominal distension, hyperbilirubinemia and pancytopenia. At that point, the family elected for hospice care whereupon after a few weeks, the patient expired at home. DISCUSSION: Currently the only curative therapy is surgical resection or transplant. However there has been research in molecular targeted therapies to treat BRAF cholangiocarcinoma with optimal response. BRAF V600 mutation results in activation of down-stream signaling though MAPK pathway and can contribute to malignancies such as melanoma, hairy cell leukemia, or non-small cell lung cancer. The frequency of BRAF V600E mutation has been reported to be 0-22% in intrahepatic cholangiocarcinoma. Inhibitors of BRAF V600 kinase such as vemurafenib and dabrafenib can be used to target these aberrations. Although this patient failed treatment with molecular targeting, precision medicine may change the trajectory in management of intrahepatic cholangiocarcinoma. The implementation of these therapies will require multi-team and institutional collaborations and will positively impact these patients.