Clinical Sequencing Contributes to a BRCA-Associated Cancer Rediagnosis That Guides an Effective Therapeutic Course

NCCN: open access

Abstract
Cancer is currently classified and treated using an approach based on tissue of origin. Ambiguous or incorrect diagnoses, however, are common and often go unnoticed......

Case and Results

A 54-year-old woman presented to a community hospital with jaundice, anorexia, and 20-pound weight loss. An abdominal and pelvic CT showed a 5-cm mass at the head of the pancreas with intrahepatic and extrahepatic biliary dilatation and involvement of the celiac plexus with extensive retroperitoneal lymphadenopathy (Figure 1A and B). Results of a CT-guided biopsy of the pancreatic mass showed a poorly differentiated adenocarcinoma. Initial review of the specimen with immunohistochemistry indicated that it was positive for CK7 and CK19 and negative for CK20, TTF-1, ER, CGA, and synaptophysin, with these results interpreted as PDA (pancreatic). On external review, a tertiary medical center pathologist concurred with this diagnosis. The patient underwent decompressive bile duct stenting and was referred to our institution with a diagnosis of stage IV PDA.

On presentation, because of the patient's relatively young age at diagnosis of advanced-stage cancer, she was referred for genetic counseling, which revealed no family history of hereditable cancer. Plasma was sent for cell-free DNA (cfDNA) sequencing.⁷ A baseline staging CT scan was obtained before the planned initiation of gemcitabine and nanoparticle albumin-bound paclitaxel therapy.⁸ Results of this CT showed evolving findings, including ascites with peritoneal thickening, a complex 6.1-cm right adnexal lesion, and the absence of a discrete pancreatic mass, which was reinterpreted as a lymph node conglomerate (Figure 1B and C). Extensive celiac plexus retroperitoneal lymphadenopathy with bile duct compression remained. An examination of a repeat biopsy again showed poorly differentiated adenocarcinoma. However, immunohistochemistry staining at our institution suggested a pelvic serous carcinoma (Figure 1C, inset). These new CT results and disparate pathologic conclusions suggested the possibility that this patient was incorrectly diagnosed with PDA and instead had advanced serous ovarian cancer. However,.....