A Molecular Diagnosis of Cholangiocarcinoma suggested using Cell-free DNA following Multiple Unsuccessful Attempts at Obtaining a Tissue Diagnosis.

Abstract

A tissue diagnosis is fundamental for the evaluation and care for most malignancies. However, for malignancies arising from certain tissues, obtaining a tissue diagnosis can occasionally be problematic. Here a patient is described where multiple attempts failed to confirm a tissue diagnosis, despite clinical, radiographic and biochemical evidence of localized cholangiocarcinoma. Circulating cell-free DNA next generation sequencing (cfDNA NGS) testing was suggestive of an underlying cholangiocarcinoma.Although cfDNA NGS testing is not validated or approved as a method to diagnose cholangiocarcinoma, this case illustrates the potential utility of cfDNA NGS testing in order to suggest a genomic diagnosis of cholangiocarcinoma when attempts at a tissue diagnosis are not feasible or were not successful.

Circulating cell-free DNA use for diagnosing cholangiocarcinoma

“…Aside from therapeutically relevant ctDNA alterations, they also noted that one or a number of other molecular alterations could be identified in the circulating DNA of these patients and Andersen and Jakobsen demonstrated that driver mutations in RAS and RAF seen in the tumors can typically be identified in cfDNA [3, 4]. Also, a patient with a molecularly diagnosed cholangiocarcinoma based on clinical suspicion and after multiple failed attempts at a tissue diagnosis has been described [5]. Identifying cfDNA with any of the oncogenic molecular abnormalities seen in the tumors of patients with known cholangiocarcinomas would be unexpected in patients without known underlying malignancies [6].…”