The Use of Glucagon-like Peptide-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus Does Not Increase the Risk of Pancreatic Cancer: A U.S.-Based Cohort Study.

BACKGROUND: GLP-1 RAs are widely used for T2DM treatment due to their cardiorenal and metabolic benefits. This study examines the risk of pancreatic cancer with GLP-1 RA use in patients with T2DM. METHODS: We analyzed TriNetX's deidentified research database using the U.S. Collaborative Network comprising 62 healthcare organizations across the U.S.A. Patients with T2DM were split into two cohorts: one receiving GLP-1 RAs, and one not receiving GLP-1 RAs. We excluded patients with known risk factors for pancreatic cancer, including pancreatic cysts, a personal or family history of BRCA1, BRCA2, CDKN2A, KRAS, MEN1, MLH1, MSH2, NOTCH1, PALB2, PMS2, and PRSS1S genes, family history of pancreatic cancer, and VHL syndrome. Using a 1:1 propensity score-matching model based on baseline characteristics and comorbidities, we created comparable cohorts. We then compared the rate of pancreatic cancer between the two cohorts at a 7-year interval. RESULTS: Out of 7,146,015 identified patients with T2DM, 10.3% were on a GLP-1 RA and 89.7% were not. Post-PSM, 721,110 patients were in each group. Patients on GLP-1 RAs had a 0.1% risk compared to a 0.2% risk of pancreatic cancer in the 7-year timeframe. CONCLUSION: The use of GLP-1 RAs in patients with type 2 diabetes mellitus (T2DM) does not appear to substantially elevate the risk of pancreatic cancer; in fact, it may potentially exert a protective effect.

Atypical Localization of Malignant Plasma Cells in Non-Viable Cell Area on Flow Cytometry Light-Scatter Dot Plot.

BACKGROUND Multi-parameter (multicolor) flow cytometric study of the bone marrow aspirate is a very useful tool for diagnosis of plasma cell dyscrasia and for evaluation of post-therapy bone marrow for minimal residual disease. CASE REPORT We present a case of a 50-year-old man with multiple myeloma, whose plasma cells on a bone marrow aspirate flow cytometric study showed atypical placement on a light-scatter dot plot, both on forward and side scatter. The bone marrow aspirate sample was 33 hours and 11 minutes old, and the light-scatter dot plot demonstrated that plasma cells, detected by their expression of CD138, CD38, and CD56, occupied an area otherwise characteristic for dead cells and cell detritus. Expressions of CD138 and CD56 were dim (down-regulated). CONCLUSIONS Morphologically atypical plasma cells with irregular nuclear contours/polylobated nuclei from non-fresh samples can present with atypical localization in the area of dead cells. Our study of the multiple myeloma patient with normal localization of plasma cells on a light-scatter dot plot showed a fraction of plasma cells in the dead cell area with dim expression of CD138 and CD56, suggesting that plasma cells may deteriorate (age) rather rapidly, losing surface markers even in less than 24-hour-old specimens. We suggest that the non-viable cell/dead cell area should be checked for expression of CD138 so as not to miss plasma cell dyscrasia, especially if the specimen was run 24 hours after bone marrow sampling.

Nodal Marginal Zone Large B-Cell Lymphoma with Burkitt Translocation and Complex Chromosomal Changes Associated with Overexpression of BCL2, MYC, and BCL6.

We report the first case of a nodal marginal zone large B-cell lymphoma and the first with MYC rearrangement. This high proliferation rate lymphoma (40% of cells) occurred in the bilateral cervical, axillary, and para-aortic lymph nodes of an 82 year old woman. It involved extensively her bone marrow, and was lethal. Malignant B-cells were CD10 negative, harbored Burkitt translocation, and multiple chromosomal changes including trisomies of chromosomes 3 and 18, and three copies of 8q with an intact q24 cytoband (in addition to MYC rearrangement), associated with overexpression of BCL6, BCL2, and MYC respectively. We suggest that in aggressive nodular marginal zone lymphomas (clinical picture or high proliferation rate of lymphoma cells), fluorescence in situ hybridization analysis for MYC rearrangement, with break-apart probe, and for MYC/IGH translocation, in addition to chromosome analysis, should be performed. MYC rearrangement associated with a more rapid progression of the neoplasia, might warrant a more aggressive treatment.

Hematogones in the peripheral blood of a 5½-month-old boy with cyclic neutropenia due to heterozygous, novel ELANE gene mutation p.Q97P, c.290 A>C.

We have identified a novel point mutation in the ELANE gene of a 5.5-month-old boy with severe cyclic neutropenia, and we are reporting for the first time, to our knowledge, the presence of hematogones in the peripheral blood of an infant. The novel point mutation occurred at base number 290 in codon 97, where adenine was replaced with cytosine. The mutation caused the replacement of amino acid glutamine with amino acid proline in the activation domain of the elastase 2 enzyme. The heterozygous mutation generated severe cyclic neutropenia, granulocytic maturation arrest, an increased number of hematogones (26% of marrow cells) in the bone marrow, an absence of neutrophils, and the presence of stage 3 (mature) hematogones in the peripheral blood. The percentage of hematogones in the peripheral blood was inversely proportional to the absolute number of neutrophils. Leukemic number of blast-like cells (hematogones) in the bone marrow, blast-like cells in the peripheral blood, marked neutropenia, and the arrest of granulopoiesis might suggest an acute leukemia. However, the finding of characteristic flow cytometric features of hematogones should help to avoid a wrong diagnosis.