Leptomeningeal disease in BRIP1-mutated pancreatic adenocarcinoma

Abstract

Leptomeningeal disease is rare in pancreatic cancer and prognosis remains poor. Mutation profiles are now directing therapy to improve survival. We describe a case of leptomeningeal and brain metastasis in BRCA1 interacting protein 1, or BRIP1-mutated pancreatic adenocarcinoma with progression through several lines of chemotherapy and immunotherapy. A woman in her late 50s presented with metastatic pancreatic adenocarcinoma on liver biopsy. She achieved complete response after modified FOLFIRINOX and started a poly (ADP-ribose) polymerase (PARP) inhibitor for a BRIP1 mutation. She had recurrence at 9 months and started pembrolizumab (programmed cell death protein 1, or PD-1receptor antibody) for tumour mutational burden of 10 muts/Mb. At 10 months, she presented with lower extremity weakness and back pain. MRI revealed leptomeningeal metastases from T11 to cauda equina roots and right occipital metastasis. Cerebrospinal fluid studies revealed elevated pressure (290 mm H₂O) and protein (73 mg/dL) with negative cytology. Leptomeningeal carcinomatosis was diagnosed. She began palliative radiation but died at 11 months from initial diagnosis.

Keywords: CNS cancer; Genetics; Neurooncology; Pancreatic cancer.

Figure 1

(A, B) MRI of the total spine with numerous metastatic lesions throughout the spine (C5, T1, T2, T3, T4, T7, T8, T11, T12, L1, L4, L5 and S1 vertebral bodies). (B) There is leptomeningeal enhancement involving the distal cord from the T11 level and diffuse enhancement and loss of definition of the cauda equina nerve roots.

Figure 2

MRI of the brain with (A, B) 0.3 cm focus of enhancement within the right occipital lobe with (C) mild associated T2/FLAIR signal. There was no obvious leptomeningeal enhancement.

Figure 3

CT abdomen/pelvis showing innumerable hepatic metastases, atrophic pancreas with infiltrative soft tissue and multiple retroperitoneal lymph nodes.