D-dimer in Adolescent Pulmonary Embolism.

BACKGROUND: D-dimer is used to aid in diagnosing adult pulmonary embolism (PE). D-dimer has not been validated in adolescents. Clinicians must balance the risk of overtesting with that of a missed PE. D-dimer may be useful in this context. This study evaluates D-dimer in PE-positive and PE-negative adolescents. METHODS: PE-positive patients < 22 years were diagnosed with PE by computed tomography (CT) or high-probability ventilation/perfusion, seen at emergency departments (EDs)/hospitals within a 16-hospital system across two states, January 1998 through December 2016. Of the 189 PE-positive patients, 88 (46.5%) had a D-dimer and were matched 1:1 by age, sex, and race to patients suspected of PE but confirmed negative by CT angiogram. RESULTS: Ages of PE-positive patients ranged from 13 to 21 years, 64 (73%) were female, and 52 (60%) were Caucasian. Mean D-dimer was significantly higher (3,256 ng/mL, 95% confidence interval [CI] = 2,505-4,006 ng/mL) in PE-positive versus PE-negative patients (1,244 ng/mL, 95% CI = 493-1,995 ng/mL; p < 0.001). Mean D-dimer was higher in patients with massive or submassive PE (8,742 ng/mL, 95% CI = 5,994-11,491 ng/mL), followed by PE in central (4,795 ng/mL [95% CI = 3,465-6,125 ng/mL), lobar (3,758 ng/mL [95% CI = 1,841-5,676), and distal (2,327 ng/mL [95% CI = 1,273-3,381 ng/mL]) arteries. When comparing thresholds of positive D-dimer (≥500, ≥750, and ≥1,000 ng/mL), D-dimer had sensitivities of 90, 82, and 67% and specificities of 16, 53, and 67%, respectively. Negative predictive values were 61, 75, and 71% while positive likelihood ratios were 1.1, 1.8, and 2.2, respectively. CONCLUSIONS: This study represents the largest available cohort of adolescent patients examining the diagnostic value of D-dimer for PE. Our results indicate that depending on the threshold selected, D-dimer can be a sensitive test for PE in adolescents and that discriminative value is higher for a cutoff of 750 ng/mL than that for 500 ng/mL. Prospective studies investigating the diagnostic value of D-dimer and a clinical decision rule for PE in pediatrics are needed.

Filter Paper-based Nucleic Acid Storage in High-throughput Solid Tumor Genotyping.

Molecular testing of tumors from formalin-fixed paraffin-embedded (FFPE) tissue blocks is central to clinical practice; however, it requires histology support and increases test turnaround time. Prospective fresh frozen tissue collection requires special handling, additional storage space, and may not be feasible for small specimens. Filter paper-based collection of tumor DNA reduces the need for histology support, requires little storage space, and preserves high-quality nucleic acid. We investigated the performance of tumor smears on filter paper in solid tumor genotyping, as compared with paired FFPE samples. Whatman FTA Micro Card (FTA preps) smears were prepared from 21 fresh tumor samples. A corresponding cytology smear was used to assess tumor cellularity and necrosis. DNA was isolated from FTA preps and FFPE core samples using automated methods and quantified using SYBR green dsDNA detection. Samples were genotyped for 471 mutations on a mass spectrophotometry-based platform (Sequenom). DNA concentrations from FTA preps and FFPE correlated for untreated carcinomas but not for mesenchymal tumors (Spearman σ=0.39 and σ=-0.1, respectively). Average DNA concentrations were lower from FTA preps as compared with FFPE, but DNA quality was higher with less fragmentation. Seventy-six percent of FTA preps and 86% of FFPE samples generated adequate DNA for genotyping. FTA preps tended to perform poorly for collection of DNA from pretreated carcinomas and mesenchymal neoplasms. Of the 16 paired DNA samples that were genotyped, 15 (94%) gave entirely concordant results. Filter paper-based sample preservation is a feasible alternative to FFPE for use in automated, high-throughput genotyping of carcinomas.

Prospective enterprise-level molecular genotyping of a cohort of cancer patients.

Ongoing cancer genome characterization studies continue to elucidate the spectrum of genomic abnormalities that drive many cancers, and in the clinical arena assessment of the driver genetic alterations in patients is playing an increasingly important diagnostic and/or prognostic role for many cancer types. However, the landscape of genomic abnormalities is still unknown for less common cancers, and the influence of specific genotypes on clinical behavior is often still unclear. To address some of these deficiencies, we developed Profile, a prospective cohort study to obtain genomic information on all patients at a large tertiary care medical center for cancer-related care. We enrolled patients with any cancer diagnosis, and, for each patient (unselected for cancer site or type) we applied mass spectrometric genotyping (OncoMap) of 471 common recurrent mutations in 41 cancer-related genes. We report the results of the first 5000 patients, of which 26% exhibited potentially actionable somatic mutations. These observations indicate the utility of genotyping in advancing the field of precision oncology.

Relapsing polymyositis in chronic graft versus host disease.

Chronic graft versus host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplantation, which contributes to the morbidity and mortality of transplant patients. A polymyositis pattern of injury is a rare manifestation of chronic GVHD in skeletal muscle after hematopoietic stem cell transplantation. We report a 54-year-old man with acute myeloid lymphoma who underwent an allogeneic bone marrow transplantation and subsequently developed acute gastrointestinal GVHD 2 months post-transplantation and polymyositis 14 months post-transplantation. Upon tapering of steroids, the patient experienced a relapse of polymyositis. The literature on polymyositis in chronic GVHD is briefly reviewed.

Primary Hodgkin lymphoma of the central nervous system.

Primary involvement of the central nervous system by Hodgkin lymphoma is rare; most cases represent metastases. We report a primary Hodgkin lymphoma presenting in the cerebellum of a 77-year-old man and review the literature on primary Hodgkin lymphoma of the central nervous system.