title: Use of molecular studies for treatment of metastatic pleomorphic large cell pancreatic cancers-a novel strategy.
abstract: Pleomorphic large cell pancreatic cancer is a rare and more aggressive variant with no proven treatment in the metastatic setting. It constitutes about 1% of the total pancreatic cancer cases. In the absence of any standard of care, we aim to increase awareness amongst clinical practitioners that molecular level testing, using immunohistochemistry, next-generation sequencing and chromogenic in-situ hybridization can help in making chemotherapeutic decisions for this variant of pancreatic cancer. We present a 50-year-old male who presented to our hospital complaining of persistent abdominal pain. CT scan revealed a pancreatic tail mass that was invading the splenic flexure causing high-grade obstruction. There was evidence of peritoneal studding. He underwent exploratory laparotomy with biopsy of the pancreatic mass and omentum which revealed metastatic undifferentiated pleomorphic large cell pancreatic cancer. Since there is no proven treatment for this particular entity, his specimen was sent for molecular testing. The molecular studies revealed positive mutations of TLE3 gene, EGFR, KRAS, PD1 gene, TP53 and TOP2A gene. The tumor was found to be sensitive to gemcitabine, paclitaxel, docetaxel, temozolamide, dacarbazine and doxorubicin. He was initiated on gemcitabine and nab-paclitaxel. The patient was treated based on these recommendations. The patient completed 5 cycles of gemcitabine and nab-paclitaxel. Treatment had to be held because of gemcitabine induced hemolytic uremic syndrome. Serial CT scans have shown stable disease and currently it has been 10 months since his diagnosis. Molecular level testing can be an important instrument in not only diagnosing but also be an important aid in deciding about the chemotherapeutic agents to be used in cases of metastatic pleomorphic large cell pancreatic cancer. Availability a knowledge of the novel tools like immunohistochemistry, next-generation sequencing and chromogenic in-situ hybridization can be prudent and treating some rare forms of pancreatic cancer as in this patient.
authors.affiliation: 1 Department of Hematology/Oncology, 2 Department of Internal Medicine, 3 Department of Pathology, Allegheny Health Network, Pittsburgh, PA, USA.
authors.forename: Parikshit
authors.initials: P
authors.lastname: Padhi
authors.affiliation: 1 Department of Hematology/Oncology, 2 Department of Internal Medicine, 3 Department of Pathology, Allegheny Health Network, Pittsburgh, PA, USA.
authors.forename: Arshjyot
authors.initials: A
authors.lastname: Narula
authors.affiliation: 1 Department of Hematology/Oncology, 2 Department of Internal Medicine, 3 Department of Pathology, Allegheny Health Network, Pittsburgh, PA, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Balog
authors.affiliation: 1 Department of Hematology/Oncology, 2 Department of Internal Medicine, 3 Department of Pathology, Allegheny Health Network, Pittsburgh, PA, USA.
authors.forename: Antonios
authors.initials: A
authors.lastname: Christou
keywords: Next-generation sequencing; gemcitabine; molecular testing; pleomorphic large cell pancreatic cancer