Germline BRCA2 variants in advanced pancreatic acinar cell carcinoma: A case report and review of literature

Abstract

BACKGROUND Pancreatic acinar cell carcinoma (PACC) is a rare tumor. Up to 45% of PACCs have alterations in the DNA damage repair pathway and 23% harbor rearrangements in the BRAF or RAF1 genes. We present a PACC case with a germline BRCA2 likely pathogenic variant (LPV) to highlight the impact of genomic testing on treatment decisions and patient outcomes. In our larger case series, we provide clinic-based information on additional 10 PACC patients treated in our center. CASE SUMMARY A 70-year-old male was diagnosed with advanced PACC. At presentation, he was cachectic with severe arthralgia despite prednisolone and a skin rash that was later confirmed to be panniculitis. He was treated with modified FOLFIRINOX (mFFX) with the knowledge of the germline BRCA2 LPV. Following 11 cycles of mFFX, a computed tomography (CT) scan demonstrated significant tumor response in the pancreatic primary and hepatic metastases, totaling 70% from baseline as per Response Evaluation Criteria in Solid Tumors. Resolution of the skin panniculitis was also noted. We identified two additional PACCs with druggable targets in our case series. Our data contribute to practical evidence for the value of germline and somatic profiling in the management of rare diseases like PACC. CONCLUSION This patient and others in our larger case series highlight the importance of genomic testing in PACC with potential utility in personalized treatment.

Diverse avenues of research support the transmethylation theory of psychosis: implications for neuroprotection

“…There have been numerous case reports of one particular class chemotherapy drugs, Folfirinox and its predecessor Folfiri, eliciting psychotic features in patients [159][160][161][162][163][164], including mania with delusions [162] or, in some cases, triggering only visual or auditory hallucinations [165,166]. Folfirinox is a combination of folinic acid, 5-fluorouracil (5-FU), irinotecan and oxaliplatin.…”

“…In the case reports of Folfirinox causing psychotic symptoms, if there was attribution of the cause of the cases of psychosis, the authors have pointed towards 5-FU alone [160,165], to steroid psychosis from coadministered steroids [163] or to the cancer mechanism itself [162] without evaluating what might happen if excess folate is administered when the normal destination of methyl groups towards DNA synthesis is blocked. Rustum [174] demonstrated that modest increases in what he termed "reduced folates" occurred with 5-FU infusion alone in an animal model (Table 2 of Rustum, [174]), likely because their consumption by the DNA synthetic pathway was blocked, but massive increases in 5-methyl-THF (which is indeed one form of "reduced folate") specifically occurred with co-infusion of 5-FU and high-dose folinic acid (Table 3 of Rustum, [174]).…”

Roseate and merest-acinar cell carcinoma-pancreas

“…Acinar cell carcinoma pancreas configures ~ 2% of adult pancreatic neoplasms and ~15% of paediatric pancreatic tumours. 1,2 Acinar cell carcinoma pancreas exhibits a mild male predilection with male to female proportion of 2.1:1. Average age of disease emergence is 60 years.…”

“…Head of pancreas configures as a frequent site of disease emergence. 1,2 Acinar cell carcinoma pancreas is posited to occur due to cellular accumulation of genetic alterations or occurrence of chromosomal instability a Acinar cell carcinoma nd frequent allelic copy number variation. 3,4 Additionally, acinar cell carcinoma is postulated to arise from factors such as tobacco consumption or cigarette smoking and defective repair of deoxy ribonucleic acid (DNA) (Table 1).…”

Laparoscopic radical distal pancreatectomy with portal venous tumor thrombectomy for the treatment of pancreatic acinar cell carcinoma after neoadjuvant chemotherapy

“…A literature review found that up to 22% of ACC patients have BRCA1/2 gene defects ( 4 ). In patients with ACC harboring BRCA2 gene mutations, platinum-based chemotherapy drugs have shown particular sensitivity, and regimens such as FOLFIRINOX have achieved good results ( 3 , 5 , 6 ). In this case, thanks to the targeted therapy based on the BRCA2 germline mutation detected through genetic testing, platinum-based chemotherapy was used as neoadjuvant chemotherapy, and satisfactory results were achieved before surgery, converting the previously unresectable tumor into a potentially resectable one.…”