Malignant Solid Pseudopapillary Neoplasm of the Pancreas: An Orthogonal Analysis.

BACKGROUND: Pancreatic solid pseudopapillary neoplasms (SPN) are generally indolent; however, some patients present with "malignant" SPN. An orthogonal analysis of multiple datasets was performed to investigate the utility of complete surgical resection (CSR) for malignant SPN. METHODS: A systematic review was performed for cases of malignant SPN, defined as T4, N1, and/or M1. Malignant SPN was analyzed within the National Cancer Database (NCDB) and compared with T1-3N0M0 SPN. Predictors of malignant SPN were assessed, and treatments were analyzed by using survival analysis. RESULTS: The systematic review yielded 164 cases of malignant SPN. Of 31 children, only one died due to malignant SPN. Among adults, CSR was associated with improved disease-specific survival (DSS) (P = 0.0002). Chemotherapy did not improve malignant SPN DSS, whether resected (P = 0.8485) or not (P = 0.2219). Of 692 adults with SPN within the NCDB, 93 (13.4%) had malignant SPN. Pancreatic head location (odds ratio [OR] 2.174; 95% confidence interval [CI] 1.136-4.166; P = 0.0186) and tumor size (OR 1.154; 95% CI 1.079-1.235; P < 0.0001) associated with the malignant phenotype. Malignant SPN predicted decreased overall survival (OS) compared with T1-3N0M0 disease (P < 0.0001). Resected malignant SPN demonstrated improved OS (P < 0.0001), including resected stage IV malignant SPN (P = 0.0003). Chemotherapy did not improve OS for malignant SPN, whether resected (P = 0.8633) or not (P = 0.5734). Within a multivariable model, resection was associated with decreased hazard of death (hazard ratio 0.090; 95% CI 0.030-0.261; P < 0.0001). CONCLUSIONS: Approximately 13% of patients with SPN present with a malignant phenotype. Pediatric cases may be less aggressive. Resection may improve survival for malignant SPN, which does not appear chemosensitive.

CTNNB1 exon 3 mutations in metastatic solid pseudopapillary neoplasm of the pancreas.

BACKGROUND AND OBJECTIVES: Solid pseudopapillary neoplasm (SPN) of the pancreas demonstrates an indolent disease course; however, some patients present with a "malignant" phenotype, including distant metastases resistant to chemotherapy. This analysis identifies molecular drivers of metastatic SPN using the world's largest clinicogenomics database. METHODS: The American Association for Cancer Research Project Genomics Evidence Neoplasia Information Exchange was queried for primary and metastatic SPN samples. Sample-level genomic alterations were compared. A pan-pancreatic cancer analysis assessed relevant mutations among all metastatic pancreatic malignancies. RESULTS: Among 28 SPN samples identified (n = 17 primary, n = 11 metastatic), the most commonly mutated gene was CTNNB1, (24/28 samples; 85.7%). Most mutations were missense (21/24; 87.5%) or in-frame deletions (3/24; 12.5%). The most common CTNNB1 mutations in primary SPN were exon 3 S37F/C missense mutations (6/16 profiled patients, 37.5%), contrasting exon 3 D32N/Y/H missense mutations in metastatic samples (6/11 profiled patients, 54.5%). Metastatic SPN had higher rates of CTNNB1 mutations than metastases from pancreatic ductal adenocarcinoma (72.7% vs. 1.1%; q < 0.0001), pancreatic neuroendocrine tumor (72.7% vs. 2.5%; q < 0.0001), and pancreatic acinar cell carcinoma (72.7% vs. 11.5%; q = 0.0254). CONCLUSIONS: Missense mutations along exon 3 of CTNNB1 predominate metastatic SPN, differentiating these patients from those with metastases from analogous pancreatic malignancies.

Lithium-associated primary hyperparathyroidism:: An evaluation of screening and referral patterns in a southeastern veteran population.

BACKGROUND: Long-term lithium therapy has a well-established but under-recognized association with primary hyperparathyroidism. Rates of hypercalcemia, screening for primary hyperparathyroidism, and referral for parathyroidectomy were evaluated among United States veterans on long-term lithium therapy. METHODS: Patients undergoing chronic long-term lithium therapy (>12 months) were identified from 1999 to 2022. Demographics, long-term lithium therapy duration, post-treatment calcium, parathyroid hormone, creatinine, and vitamin D levels were abstracted. Rates of screening for hypercalcemia (calcium ≥10.2 mg/dL), primary hyperparathyroidism (parathyroid hormone ≥30 pg/mL in the setting of hypercalcemia), referral for parathyroidectomy, and outcomes were evaluated. RESULTS: A total of 1,356 patients underwent long-term lithium therapy, 514 of whom received chronic long-term lithium therapy. Baseline characteristics of patients with and without post-treatment hypercalcemia were compared. Of 148 patients with post-treatment hypercalcemia, 112 (74.7%) underwent no further evaluation for primary hyperparathyroidism, while 36 (25.3%) patients had a parathyroid hormone level recorded. Although 33 (91.7%) hypercalcemic patients screened positive for primary hyperparathyroidism, only 5 (13%) were referred for parathyroidectomy. Of the 4 patients who underwent parathyroidectomy, mean calcium was 11.2 mg/dL (range 11.1-11.4), and mean parathyroid hormone was 272 pg/mL (range 108-622). Three patients were localized on preoperative imaging, 2 of whom underwent unilateral exploration with cure, with 1 experiencing recurrence at 31 months. The remaining patient who localized preoperatively underwent bilateral exploration and had 2 ipsilateral glands resected and persistence. The patient who did not localize preoperatively underwent bilateral exploration with 3 gland resection and cure. CONCLUSIONS: Screening for primary hyperparathyroidism and referral for parathyroidectomy are underutilized in United States veterans undergoing chronic long-term lithium therapy. Institutional protocols to standardize screening, surveillance, and referrals to endocrinology/endocrine surgery could benefit this population at increased risk for primary hyperparathyroidism.