Diagnostic Approach for Double-Hit and Triple-Hit Lymphoma Based on Immunophenotypic and Cytogenetic Characteristics of Bone Marrow Specimens

Background@#High-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6 (BCL2/BCL6), also known as double-hit lymphoma (DHL) and/or triple-hit lymphoma (THL), is a new entity of B-cell lymphoma in the 2017 WHO Classification. We retrospectively investigated D/THL and their clinico-laboratory features among cases of large B-cell lymphoma involving the bone marrow (BM), including diffuse large B-cell lymphoma, Burkitt lymphoma, and B-cell lymphomas with medium to large lymphoid cells, by additional FISH analysis of BM aspirates. @*Methods@#A total of 111 patients diagnosed with aggressive B-cell lymphomas or B-cell lymphoma involving the BM with medium to large-sized malignant lymphocytes were reviewed from January 2000 to January 2018. Patients with available BM aspirates were evaluated by immunophenotyping by flow cytometry, chromosome, and FISH analysis for MYC and/or BCL2/BCL6 rearrangements. @*Results@#In total, 23/111 (20.7%) showed MYC rearrangement, and eight (7.2%) were reclassified as D/THL on BM after FISH analysis for MYC and BCL2/BCL6. The detection of CD5(-)/CD10(+) based on flow cytometry was strongly associated with D/THL. A complex karyotype with aberrations related to regions in MYC and BCL2/BCL6 was significantly associated with D/THL. When the MYC FISH results of 28 BM aspirates and formalin-fixed paraffin-embedded tissue specimens were compared, 14% were discrepant. @*Conclusions@#Immunophenotypic and cytogenetic characteristics facilitate the diagnosis of D/THL in the cases with BM-involving aggressive B-cell lymphomas.

Evaluation of Intact Parathyroid Hormone Levels in Plasma Samples: A Comparative Study Using Serum Samples

Background@#Intraoperative measurement of intact parathyroid hormone (iPTH) levels is crucial for confirming complete removal of hyperfunctioning parathyroid glands during parathyroidectomy and for detecting parathyroid gland damage during thyroidectomy. The use of plasma samples can shorten the turnaround time (TAT) for iPTH. The present study explored the effectiveness of using plasma samples for iPTH quantitation by comparison with the corresponding serum samples. We also evaluated the analytical performance of iPTH. @*Methods@#The TAT of plasma and serum samples analyzed in March 2019 was compared. In addition, comparative evaluation of the iPTH levels in 100 paired plasma and serum samples were performed. Analytical performances including within-run and within-laboratory precision, and linearity were evaluated in plasma samples using the ADVIA Centaur iPTH assay (Siemens Healthineers, Germany). The reference range was verified with plasma samples collected from 20 healthy adults. @*Results@#Plasma iPTH tests showed shorter TAT values (P<0.001) and higher iPTH levels (P<0.001) than serum. Correlation analysis between plasma and serum iPTH levels showed a strong positive correlation (r=0.925). The within-run and within-laboratory precision values were within the manufacturer's recommendation. iPTH showed linearity from 5.1 to 1,670.0 pg/mL (R2=0.999). The plasma iPTH levels from 20 healthy adults were within the reference range, thus validating our method. @*Conclusions@#The plasma iPTH levels were higher than the serum levels, with a strong positive correlation. The TAT of plasma samples was considerably shorter than that of serum. iPTH quantitation from plasma samples is preferable when rapid results are required.

First Case of Plasma Cell Myeloma With Brown Tumor Features Unrelated to Hyperparathyroidism

No abstract available.

Korean Society for Genetic Diagnostics Guidelines for Validation of Next-Generation Sequencing-Based Somatic Variant Detection in Hematologic Malignancies

Next-generation sequencing (NGS) is currently used in the clinical setting for targeted therapies and diagnosis of hematologic malignancies. Accurate detection of somatic variants is challenging because of tumor purity, heterogeneity, and the complexity of genetic alterations, with various issues ranging from high detection design to test implementation. This article presents guidelines developed through consensus among a panel of experts from the Korean Society for Genetic Diagnostics. They are based on experiences with the validation processes of NGS-based somatic panels for hematologic malignancies, with reference to previous international recommendations. These guidelines describe basic parameters with emphasis on the design of a validation protocol for NGS-based somatic panels to be used in practice. In addition, they suggest thresholds of key metrics, including minimum coverage, mean coverage with uniformity index, and minimum variant allele frequency, for the initial diagnosis of hematologic malignancies.

A Rare Case of Pediatric T Lymphoblastic Leukemia With t(11;17)(q23;q21) Involving Mixed-Lineage Leukemia Gene Rearrangement

No abstract available.

Usefulness of Serum Thymidine Kinase 1 as a Biomarker for Aggressive Clinical Behavior in B-cell Lymphoma

BACKGROUND: The cell cycle-dependent enzyme thymidine kinase 1 (TK1) is known to increase during cancer cell proliferation and has been reported as a prognostic marker for various hematologic malignancies and solid tumors. This study aimed to determine the reference interval in Korean healthy controls and to evaluate the usefulness of TK1 as a biomarker for aggressive clinical behavior in B-cell lymphoma patients. METHODS: We enrolled 72 previously untreated patients with B-cell lymphoma and 143 healthy controls. Serum TK1 levels were measured by chemiluminescence immunoassay (Liaison(R), DiaSorin, USA). We established the reference intervals in healthy controls. The diagnostic performance of serum TK1 was studied using receiver operating characteristic (ROC) analysis, and the correlation between the cutoff level for serum TK1 and clinical characteristics of B-cell lymphoma was evaluated. RESULTS: The reference range (95th percentile) of serum TK1 in healthy controls was 5.4-21.8 U/L. There was a clear difference in TK1 levels between patients with B-cell lymphoma and healthy controls (40.6+/-68.5 vs. 11.8+/-4.4 U/L, P or =15.2 U/L) correlated with the advanced clinical stage (P<0.001), bone marrow involvement (P=0.013), international prognostic index score (P=0.001), lactate dehydrogenase level (P=0.001), low Hb level (<12 g/dL) (P=0.028), and lymphocyte count (P=0.023). CONCLUSIONS: The serum TK1 level could serve as a useful biomarker for aggressive clinical behavior in B-cell lymphoma patients.

A Case of Hereditary Spherocytosis Coexisting with Gilbert's Syndrome / 대한소화기학회지

We recently encountered a case of hereditary spherocytosis coexisting with Gilbert's syndrome. Patient was initially diagnosed with Gilbert's syndrome and observed, but other findings suggestive of concurrent hemolysis, such as splenomegaly and gallstones were noted during the follow-up period. Therefore, further evaluations, including a peripheral blood smear, osmotic fragility test, autohemolysis test, and red blood cell membrane protein test were performed, and coexisting hereditary spherocytosis was diagnosed. Genotyping of the conjugation enzyme uridine diphosphate-glucuronosyltransferase was used to confirm Gilbert's syndrome. Because of the high prevalence rates and similar symptoms of these 2 diseases, hereditary spherocytosis can be masked in patients with Gilbert's syndrome. In review of a case and other article, the possibility of the coexistence of these 2 diseases should be considered, especially in patients with unconjugated hyperbilirubinemia who also have splenomegaly and gallstones.