Establishing vitreous glucose and beta-hydroxybutyrate thresholds to assist in the diagnosis of hypothermia.

The post-mortem diagnosis of hypothermia is challenging to establish due to the lack of pathognomonic findings and the confounding problem that any comorbidity may account for death. A 4-year retrospective case-control study was performed to compare the vitreous glucose and beta-hydroxybutyrate (BHB) concentrations between hypothermia deaths and controls. Over the study period 34 cases of hypothermia and 39 controls were analyzed. Hypothermia deaths versus controls had higher mean vitreous glucose (2.93 mmol/L vs. 1.14 mmol/L; p < 0.0001), BHB (1.89 mmol/L vs. 1.35 mmol/L; p = 0.01), and combined glucose+BHB (4.83 mmol/L vs. 2.46 mmol/L; p < 0.0001). Receiver operating characteristic (ROC) curves showed that the best model for predicting hypothermia in all cases was a combined vitreous glucose+BHB threshold of 2.03 mmol/L (sensitivity 88.2 %; specificity 56.4 %). A sub-group analysis broken down by detectable levels of blood ethanol showed that cases of hypothermia with and without ethanol maintained higher median vitreous glucose relative to the controls (2.05 vs. 0.35 mmol/L and 2.70 vs. 0.65 mmol/L; p = 0.02), however median BHB was only significantly elevated when ethanol was absent (1.88 vs. 1.42 mmol/L; p < 0.0001). Subsequent ROC curve analysis demonstrated that a better model for predicting hypothermia was in cases when blood ethanol was absent. In those deaths vitreous BHB alone had the best area under the curve, with an optimum threshold of 1.83 mmol/L (sensitivity 83.3 %; specificity 96.3 %). This study shows that post-mortem vitreous glucose and BHB are useful ancillary studies to assist in the diagnosis of hypothermia. Ethanol however is a confounder and can alter the utility of vitreous BHB when diagnosing hypothermia in those who have consumed alcohol prior to death.

Updates in Pathology for Retroperitoneal Soft Tissue Sarcoma.

Retroperitoneal tumors are extremely rare. More than 70% of primary retroperitoneal soft tissue tumors are malignant. The most common sarcomas in the retroperitoneum include liposarcomas and leiomyosarcoma, however other sarcomas, along with benign mesenchymal tumors, can occur. Sarcomas are a heterogenous group of tumors with overlapping microscopic features, posing a diagnostic challenge for the pathologist. Correct tumor classification has become important for prognostication and the evolving targeted therapies for sarcoma subtypes. In this review, the pathology of retroperitoneal soft tissue sarcomas is discussed, which is important to the surgical oncologist. In addition, less common sarcomas and benign mesenchymal tumors of the retroperitoneum, which may mimic sarcoma clinically and pathologically, are also discussed.

Single-Cell Analysis and Next-Generation Immuno-Sequencing Show That Multiple Clones Persist in Patients with Chronic Lymphocytic Leukemia.

The immunoglobulin heavy chain (IGH) gene rearrangement in chronic lymphocytic leukemia (CLL) provides a unique molecular signature; however, we demonstrate that 26/198 CLL patients (13%) had more than one IGH rearrangement, indicating the power of molecular technology over phenotypic analysis. Single-cell PCR analysis and next-generation immuno-sequencing identified IGH-defined clones. In 23% (18/79) of cases whose clones carried unmutated immunoglobulin heavy chain variable (IGHV) genes (U-CLL), IGH rearrangements were bialleic with one productive (P) and one non-productive (NP) allele. Two U-CLL were biclonal, each clone being monoallelic (P). In 119 IGHV-mutated (M-CLL) cases, one had biallelic rearrangements in their CLL (P/NP) and five had 2-4 distinct clones. Allelic exclusion was maintained in all B-clones analyzed. Based on single-cell PCR analysis, 5/11 partner clones (45%) reached levels of >5x10(9) cells/L, suggesting second CLL clones. Partner clones persisted over years. Conventional IGH characterization and next-generation sequencing of 13 CLL, 3 multiple myeloma, 2 Waldenstrom's macroglobulinemia and 3 age-matched healthy donors consistently identified the same rearranged IGH sequences. Most multiple clones occurred in M-CLL, perhaps indicative of weak clonal dominance, thereby associating with a good prognosis. In contrast, biallelic CLL occurred primarily in U-CLL thus being associated with poor prognosis. Extending beyond intra-clonal diversity, molecular analysis of clonal evolution and apparent subclones in CLL may also reflect inter-clonal diversity.